fmriphys.bib

Heeger:2000
Spikes versus BOLD: what does neuroimaging tell us about neuronal activity?
D. J. Heeger and A. C. Huk and W. S. Geisler and D. G. Albrecht
Nat Neurosci  3  631--633  (2000 Jul)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=10862687
Rees:2000
A direct quantitative relationship between the functional properties of human and macaque V5.
G. Rees and K. Friston and C. Koch
Nat Neurosci  3  716--723  (2000 Jul)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=10862705
The nature of the quantitative relationship between single-neuron recordings in monkeys and functional magnetic resonance imaging (fMRI) measurements in humans is crucial to understanding how experiments in these different species are related, yet it remains undetermined. We measured brain activity in humans attending to moving visual stimuli, using blood oxygenation level-dependent (BOLD) fMRI. Responses in V5 showed a strong and highly linear dependence on increasing strength of motion signal (coherence). These population responses in human V5 had a remarkably simple mathematical relationship to previously observed single-cell responses in macaque V5. We provided an explicit quantitative estimate for the interspecies comparison of single-neuron activity and BOLD population responses. Our data show previously unknown dissociations between the functional properties of human V5 and other human motion-sensitive areas, thus predicting similar dissociations for the properties of single neurons in homologous areas of macaque cortex.
Smith:2002
Cerebral energetics and spiking frequency: the neurophysiological basis of fMRI.
A. J. Smith and H. Blumenfeld and K. L. Behar and D. L. Rothman and R. G. Shulman and F. Hyder
Proc Natl Acad Sci U S A  99  10765--10770  (2002 Aug 6)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=12134056
Functional MRI (fMRI) is widely assumed to measure neuronal activity, but no satisfactory mechanism for this linkage has been identified. Here we derived the changes in the energetic component from the blood oxygenation level-dependent (BOLD) fMRI signal and related it to changes in the neuronal spiking frequency in the activated voxels. Extracellular recordings were used to measure changes in cerebral spiking frequency (Deltanu/nu) of a neuronal ensemble during forepaw stimulation in the alpha-chloralose anesthetized rat. Under the same conditions localized changes in brain energy metabolism (DeltaCMR(O2)/CMR(O2)) were obtained from BOLD fMRI data in conjunction with measured changes in cerebral blood flow (DeltaCBF/CBF), cerebral blood volume (DeltaCBV/CBV), and transverse relaxation rates of tissue water (T(2)(*) and T(2)) by MRI methods at 7T. On stimulation from two different depths of anesthesia DeltaCMR(O2)/CMR(O2) approximately Deltanu/nu. Previous (13)C magnetic resonance spectroscopy studies, under similar conditions, had shown that DeltaCMR(O2)/CMR(O2) was proportional to changes in glutamatergic neurotransmitter flux (DeltaV(cyc)/V(cyc)). These combined results show that DeltaCMR(O2)/CMR(O2) approximately DeltaV(cyc)/V(cyc) approximately Deltanu/nu, thereby relating the energetic basis of brain activity to neuronal spiking frequency and neurotransmitter flux. Because DeltaCMR(O2)/CMR(O2) had the same high spatial and temporal resolutions of the fMRI signal, these results show how BOLD imaging, when converted to DeltaCMR(O2)/CMR(O2), responds to localized changes in neuronal spike frequency.
Hyder:2002
Total neuroenergetics support localized brain activity: implications for the interpretation of fMRI.
F. Hyder and D. L. Rothman and R. G. Shulman
Proc Natl Acad Sci U S A  99  10771--10776  (2002 Aug 6)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=12134057
In alpha-chloralose-anesthetized rats, changes in the blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal (DeltaS/S), and the relative spiking frequency of a neuronal ensemble (Deltanu/nu) were measured in the somatosensory cortex during forepaw stimulation from two different baselines. Changes in cerebral oxygen consumption (DeltaCMR(O2)/CMR(O2)) were derived from the BOLD signal (at 7T) by independent determinations in cerebral blood flow (DeltaCBF/CBF) and volume (DeltaCBV/CBV). The spiking frequency was measured by extracellular recordings in layer 4. Changes in all three parameters (CMR(O2), nu, and S) were greater from the lower baseline (i.e., deeper anesthesia). For both baselines, DeltaCMR(O2)/CMR(O2) and Deltanu/nu were approximately one order of magnitude larger than DeltaS/S. The final values of CMR(O2) and nu reached during stimulation were approximately the same from both baselines. If only increments were required to support functions then their magnitudes should be independent of the baseline. In contrast, if particular magnitudes of activity were required, then sizes of increments should inversely correlate with the baseline (being larger from a lower baseline). The results show that particular magnitudes of activity support neural function. The disregard of baseline activity in fMRI experiments by differencing removes a large and necessary component of the total activity. Implications of these results for understanding brain function and fMRI experiments are discussed.
Nersesyan:2004
Dynamic fMRI and EEG recordings during spike-wave seizures and generalized tonic-clonic seizures in WAG/Rij rats.
H. Nersesyan and F. Hyder and D. L. Rothman and H. Blumenfeld
J Cereb Blood Flow Metab  24  589--599  (2004 Jun)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=15181366
Generalized epileptic seizures produce widespread physiological changes in the brain. Recent studies suggest that "generalized" seizures may not involve the whole brain homogeneously. For example, electrophysiological recordings in WAG/Rij rats, an established model of human absence seizures, have shown that spike-and-wave discharges are most intense in the perioral somatosensory cortex and thalamus, but spare the occipital cortex. Is this heterogeneous increased neuronal activity matched by changes in local cerebral blood flow sufficient to meet or exceed cerebral oxygen consumption? To investigate this, we performed blood oxygen level-dependent functional magnetic resonance imaging (fMRI) measurements at 7T with simultaneous electroencephalogram recordings. During spontaneous spike-wave seizures in WAG/Rij rats under fentanylhaloperidol anesthesia, we found increased fMRI signals in focal regions including the perioral somatosensory cortex, known to be intensely involved during seizures, whereas the occipital cortex was spared. For comparison, we also studied bicuculline-induced generalized tonic-clonic seizures under the same conditions, and found fMRI increases to be larger and more widespread than during spike-and-wave seizures. These findings suggest that even in regions with intense neuronal activity during epileptic seizures, oxygen delivery exceeds metabolic needs, enabling fMRI to be used for investigation of dynamic cortical and subcortical network involvement in this disorder.
Schridde:2008
Negative BOLD with large increases in neuronal activity.
U. Schridde and M. Khubchandani and J. E. Motelow and B. G. Sanganahalli and F. Hyder and H. Blumenfeld
Cereb Cortex  18  1814--1827  (2008 Aug)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=18063563
Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used in neuroscience to study brain activity. However, BOLD fMRI does not measure neuronal activity directly but depends on cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO(2)) consumption. Using fMRI, CBV, CBF, neuronal recordings, and CMRO(2) modeling, we investigated how the signals are related during seizures in rats. We found that increases in hemodynamic, neuronal, and metabolic activity were associated with positive BOLD signals in the cortex, but with negative BOLD signals in hippocampus. Our data show that negative BOLD signals do not necessarily imply decreased neuronal activity or CBF, but can result from increased neuronal activity, depending on the interplay between hemodynamics and metabolism. Caution should be used in interpreting fMRI signals because the relationship between neuronal activity and BOLD signals may depend on brain region and state and can be different during normal and pathological conditions.
Shmuel:2008
Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: Implications for functional connectivity at rest.
A. Shmuel and D. A. Leopold
Hum Brain Mapp  29  751--761  (2008 Jul)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=18465799
Recent studies have demonstrated large amplitude spontaneous fluctuations in functional-MRI (fMRI) signals in humans in the resting state. Importantly, these spontaneous fluctuations in blood-oxygenation-level-dependent (BOLD) signal are often synchronized over distant parts of the brain, a phenomenon termed functional-connectivity. Functional-connectivity is widely assumed to reflect interregional coherence of fluctuations in activity of the underlying neuronal networks. Despite the large body of human imaging literature on spontaneous activity and functional-connectivity in the resting state, the link to underlying neural activity remains tenuous. Through simultaneous fMRI and intracortical neurophysiological recording, we demonstrate correlation between slow fluctuations in BOLD signals and concurrent fluctuations in the underlying locally measured neuronal activity. This correlation varied with time-lag of BOLD relative to neuronal activity, resembling a traditional hemodynamic response function with peaks at approximately 6 s lag of BOLD signal. The correlations were reliably detected when the neuronal signal consisted of either the spiking rate of a small group of neurons, or relative power changes in the multi-unit activity band, and particularly in the local field potential gamma band. Analysis of correlation between the voxel-by-voxel fMRI time-series and the neuronal activity measured within one cortical site showed patterns of correlation that slowly traversed cortex. BOLD fluctuations in widespread areas in visual cortex of both hemispheres were significantly correlated with neuronal activity from a single recording site in V1. To the extent that our V1 findings can be generalized to other cortical areas, fMRI-based functional-connectivity between remote regions in the resting state can be linked to synchronization of slow fluctuations in the underlying neuronal signals.
Maier:2008
Divergence of fMRI and neural signals in V1 during perceptual suppression in the awake monkey.
A. Maier and M. Wilke and C. Aura and C. Zhu and F. Ye and D. Leopold
Nat Neurosci      (2008 Aug 24)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=18711393
The role of primary visual cortex (V1) in determining the contents of perception is controversial. Human functional magnetic resonance imaging (fMRI) studies of perceptual suppression have revealed a robust drop in V1 activity when a stimulus is subjectively invisible. In contrast, monkey single-unit recordings have failed to demonstrate such perception-locked changes in V1. To investigate the basis of this discrepancy, we measured both the blood oxygen level-dependent (BOLD) response and several electrophysiological signals in two behaving monkeys. We found that all signals were in good agreement during conventional stimulus presentation, showing strong visual modulation to presentation and removal of a stimulus. During perceptual suppression, however, only the BOLD response and the low-frequency local field potential (LFP) power showed decreases, whereas the spiking and high-frequency LFP power were unaffected. These results demonstrate that the coupling between the BOLD and electrophysiological signals in V1 is context dependent, with a marked dissociation occurring during perceptual suppression.
RBH00
Activity in primary visual cortex predicts performance in a visual detection task.
D. Ress and B. Backus and D. Heeger
Nat Neurosci  3  940-5  (2000)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=10966626
Visual attention can affect both neural activity and behavior in humans. To quantify possible links between the two, we measured activity in early visual cortex (V1, V2 and V3) during a challenging pattern-detection task. Activity was dominated by a large response that was independent of the presence or absence of the stimulus pattern. The measured activity quantitatively predicted the subject's pattern-detection performance: when activity was greater, the subject was more likely to correctly discern the presence or absence of the pattern. This stimulus-independent activity had several characteristics of visual attention, suggesting that attentional mechanisms modulate activity in early visual cortex, and that this attention-related activity strongly influences performance.
Fox:2006
Coherent spontaneous activity accounts for trial-to-trial variability in human evoked brain responses.
M. D. Fox and A. Z. Snyder and J. M. Zacks and M. E. Raichle
Nat Neurosci  9  23--25  (2006 Jan)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=16341210
Trial-to-trial variability in the blood oxygen level-dependent (BOLD) response of functional magnetic resonance imaging has been shown to be relevant to human perception and behavior, but the sources of this variability remain unknown. We demonstrate that coherent spontaneous fluctuations in human brain activity account for a significant fraction of the variability in measured event-related BOLD responses and that spontaneous and task-related activity are linearly superimposed in the human brain.
Fox:2007
Intrinsic Fluctuations within Cortical Systems Account for Intertrial Variability in Human Behavior.
M. D. Fox and A. Z. Snyder and J. L. Vincent and M. E. Raichle
Neuron  56  171--184  (2007)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17920023
The resting brain is not silent, but exhibits organized fluctuations in neuronal activity even in the absence of tasks or stimuli. This intrinsic brain activity persists during task performance and contributes to variability in evoked brain responses. What is unknown is if this intrinsic activity also contributes to variability in behavior. In the current fMRI study, we identify a relationship between human brain activity in the left somatomotor cortex and spontaneous trial-to-trial variability in button press force. We then demonstrate that 74% of this brain-behavior relationship is attributable to ongoing fluctuations in intrinsic activity similar to those observed during resting fixation. In addition to establishing a functional and behavioral significance of intrinsic brain activity, these results lend new insight into the origins of variability in human behavior.
Vincent:2007
Intrinsic functional architecture in the anaesthetized monkey brain.
J. L. Vincent and G. H. Patel and M. D. Fox and A. Z. Snyder and J. T. Baker and D. C. Van Essen and J. M. Zempel and L. H. Snyder and M. Corbetta and M. E. Raichle
Nature  447  83--86  (2007)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17476267
The traditional approach to studying brain function is to measure physiological responses to controlled sensory, motor and cognitive paradigms. However, most of the brain's energy consumption is devoted to ongoing metabolic activity not clearly associated with any particular stimulus or behaviour. Functional magnetic resonance imaging studies in humans aimed at understanding this ongoing activity have shown that spontaneous fluctuations of the blood-oxygen-level-dependent signal occur continuously in the resting state. In humans, these fluctuations are temporally coherent within widely distributed cortical systems that recapitulate the functional architecture of responses evoked by experimentally administered tasks. Here, we show that the same phenomenon is present in anaesthetized monkeys even at anaesthetic levels known to induce profound loss of consciousness. We specifically demonstrate coherent spontaneous fluctuations within three well known systems (oculomotor, somatomotor and visual) and the 'default' system, a set of brain regions thought by some to support uniquely human capabilities. Our results indicate that coherent system fluctuations probably reflect an evolutionarily conserved aspect of brain functional organization that transcends levels of consciousness.
Viswanathan:2007
Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity.
A. Viswanathan and R. D. Freeman
Nat Neurosci  10  1308--1312  (2007 Oct)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17828254
In noninvasive neuroimaging, neural activity is inferred from local fluctuations in deoxyhemoglobin. A fundamental question of functional magnetic resonance imaging (fMRI) is whether the inferred neural activity is driven primarily by synaptic or spiking activity. The answer is critical for the interpretation of the blood oxygen level-dependent (BOLD) signal in fMRI. Here, we have used well-established visual-system circuitry to create a stimulus that elicits synaptic activity without associated spike discharge. In colocalized recordings of neural and metabolic activity in cat primary visual cortex, we observed strong coupling between local field potentials (LFPs) and changes in tissue oxygen concentration in the absence of spikes. These results imply that the BOLD signal is more closely coupled to synaptic activity.
Masamoto:2007
Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex.
K. Masamoto and T. Kim and M. Fukuda and P. Wang and S. Kim
Cereb Cortex  17  942--950  (2007 Apr)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=16731882
Functional magnetic resonance imaging (fMRI) in anesthetized rodents has been commonly performed with alpha-chloralose, which can be used only for terminal experiments. To develop a survival fMRI protocol, an isoflurane (ISO) -anesthetized rat model was systematically evaluated by simultaneous measurements of field potential (FP) and cerebral blood flow (CBF) in the somatosensory cortex. A conventional forepaw stimulation paradigm with 0.3 ms pulse width, 1.2 mA current, and 3 Hz frequency induced 54% less evoked FP and 84% less CBF response under ISO than alpha-chloralose. To improve stimulation-induced responses under ISO, 10-pulse stimulations were performed with variations of width, current, and frequency. For widths of 0.1-5.0 ms and currents of 0.4-2.0 mA, evoked FP and CBF increased similarly and reached a plateau. The evoked FP increased monotonically for intervals from 50 to 500 ms, but the CBF peaked at an interval of 83 ms (approximately 12 Hz frequency). These data suggest that different anesthetics profoundly affect FP and CBF responses in different ways, which requires optimizing stimulation parameters for each anesthetic. With the refined stimulation parameters, fMRI consistently detected a well-localized activation focus at the primary somatosensory cortex in ISO-anesthetized rats. Thus, the ISO-anesthetized rat model can be used for cerebrovascular activation studies, allowing repeated noninvasive survival experiments.
Fukuda:2006
Mapping iso-orientation columns by contrast agent-enhanced functional magnetic resonance imaging: reproducibility, specificity, and evaluation by optical imaging of intrinsic signal.
M. Fukuda and C. Moon and P. Wang and S. Kim
J Neurosci  26  11821--11832  (2006 Nov 15)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17108155
Activation resembling ocular dominance or orientation columns has been mapped with high-resolution functional magnetic resonance imaging (fMRI). However, the neuronal interpretation of these functional maps is unclear because of the poor sensitivity of fMRI, unknown point spread function (PSF), and lack of comparison with independent techniques. Here we show that cerebral blood volume (CBV)-weighted fMRI with a blood plasma contrast agent (monocrystalline iron oxide nanoparticles), in combination with continuous temporally encoded stimulation, can map columnar neuronal activity in the cat primary visual cortex with high sensitivity, selectivity, and reproducibility. We examined hemodynamic response PSF by comparing these CBV-based signals with oxygen metabolism-based negative blood oxygenation level-dependent signals. A significant positive correlation exists between CBV- and metabolism-based iso-orientation maps, suggesting that the hemodynamic PSF is narrower than intercolumn distances. We also compared CBV-based fMRI with optical intrinsic signal (OIS) imaging, a technique that identifies sites of increased neuronal activity, to investigate neuronal correlation. Iso-orientation maps obtained by fMRI and OIS were well matched, indicating that areas of the highest orientation-selective CBV signals correspond to sites of increased neural activity. Using CBV-based fMRI, we successfully mapped orientation-selective functional architecture in the medial bank of the visual cortex, an area inaccessible to OIS imaging. Thus, we conclude that contrast agent-based fMRI, in combination with continuous temporally encoded stimulation, is a highly sensitive technique capable of mapping neural activity at the resolution of functional columns without depth limitation.
TPF03
Single-neuron activity and tissue oxygenation in the cerebral cortex.
J. K. Thompson and M. R. Peterson and R. D. Freeman
Science  299  1070-2  (2003)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=12586942
Blood oxygen level-dependent functional magnetic resonance imaging uses alterations in brain hemodynamics to infer changes in neural activity. Are these hemodynamic changes regulated at a spatial scale capable of resolving functional columns within the cerebral cortex? To address this question, we made simultaneous measurements of tissue oxygenation and single-cell neural activity within the visual cortex. Results showed that increases in neuronal spike rate were accompanied by immediate decreases in tissue oxygenation. We used this decrease in tissue oxygenation to predict the orientation selectivity and ocular dominance of neighboring neurons. Our results establish a coupling between neural activity and oxidative metabolism and suggest that high-resolution functional magnetic resonance imaging may be used to localize neural activity at a columnar level.
Thompson:2005
Separate spatial scales determine neural activity-dependent changes in tissue oxygen within central visual pathways.
J. K. Thompson and M. R. Peterson and R. D. Freeman
J Neurosci  25  9046-58  (2005)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=16192396
The relationship between oxygen levels and neural activity in the brain is fundamental to functional neuroimaging techniques. We have examined this relationship on a fine spatial scale in the lateral geniculate nucleus (LGN) and visual cortex of the cat using a microelectrode sensor that provides simultaneous colocalized measurements of oxygen partial pressure in tissue (tissue oxygen) and multiunit neural activity. In previous work with this sensor, we found that changes in tissue oxygen depend strongly on the location and spatial extent of neural activation. Specifically, focal neural activity near the microelectrode elicited decreases in tissue oxygen, whereas spatially extended activation, outside the field of view of our sensor, yielded mainly increases. In the current study, we report an expanded set of measurements to quantify the spatiotemporal relationship between neural responses and changes in tissue oxygen. For the purpose of data analysis, we develop a quantitative model that assumes that changes in tissue oxygen are composed of two response components (one positive and one negative) with magnitudes determined by neural activity on separate spatial scales. Our measurements from visual cortex and the LGN are consistent with this model and suggest that the positive response spreads over a distance of 1-2 mm, whereas the negative component is confined to a few hundred micrometers. These results are directly relevant to the mechanisms that generate functional brain imaging signals and place limits on their spatial properties.
Thompson:2004
High-resolution neurometabolic coupling revealed by focal activation of visual neurons.
J. K. Thompson and M. R. Peterson and R. D. Freeman
Nat Neurosci  7  919-20  (2004)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=15322552
Functional magnetic resonance imaging is an important tool for measuring brain function noninvasively, but the vascular and metabolic changes on which its measurements are based are not fully understood. Here, we examined the relationship between these changes and neural activity on a fine spatial scale through simultaneous measurements of tissue oxygen and extracellular neural activity in the cat lateral geniculate nucleus. Our findings indicate that activity-dependent increases in cerebral blood flow and oxidative metabolism occur on different spatial scales, and that the ratio between the two depends on the size of the activated neural population.
Li:2007
High-resolution neurometabolic coupling in the lateral geniculate nucleus.
B. Li and R. D. Freeman
J Neurosci  27  10223--10229  (2007)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17881528
The relationships between neural and metabolic processes in activated brain regions are central to the interpretation of noninvasive imaging. To examine this relationship, we have used a specialized sensor to measure simultaneously tissue oxygen changes and neural activity in colocalized regions of the cat's lateral geniculate nucleus (LGN). Previous work with this sensor has shown that a decrease or increase in tissue oxygen can be elicited by selective control of the location and extent of neural activation in the LGN. In the current study, to evaluate the temporal integration and homogeneity of neurometabolic coupling, we have determined the relationship between multiunit extracellular neural activity and tissue oxygen responses to visual stimuli of various durations and contrasts. Our results show that the negative but not the positive oxygen response changes in an approximately linear manner with stimulus duration. The relationship between the negative oxygen response and neural activity is relatively constant with stimulus duration. Moreover, both negative and positive oxygen responses saturate at high stimulus contrast levels. Coupling between neural activity and negative oxygen responses is well described by a power law function. These results help elucidate differences between the initial negative and subsequent positive metabolic responses and may be directly relevant to questions concerning brain mapping with functional magnetic resonance imaging.
Masamoto:2008
Trial-by-trial relationship between neural activity, oxygen consumption, and blood flow responses.
K. Masamoto and A. Vazquez and P. Wang and S. Kim
Neuroimage  40  442--450  (2008 Apr 1)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=18234525
Trial-by-trial variability in local field potential (LFP), tissue partial pressure of oxygen (PO2), cerebral blood flow (CBF), and deoxyhemoglobin-weighted optical imaging of intrinsic signals (OIS) were tested in the rat somatosensory cortex while fixed electrical forepaw stimulation (1.0-ms pulses with amplitude of 1.2 mA at a frequency of 6 Hz) was repeatedly applied. The changes in the cerebral metabolic rate of oxygen (CMRO2) were also evaluated using a hypotension condition established by our group based on the administration of a vasodilator. Under normal conditions, CBF, PO2, and OIS showed positive signal changes (48%, 32%, and 0.42%, respectively) following stimulation. Over multiple trials, the CBF responses were well correlated with the integral of the LFP amplitudes (sigmaLFP) (Rmean=0.78), whereas a lower correlation was found between PO2 and sigmaLFP (Rmean=0.60) and between OIS and sigmaLFP (Rmean=0.54). Under the hypotension condition the LFP responses were preserved, but the CBF responses were suppressed and the PO2 and OIS changes were negative (-12% and -0.28%, respectively). In this condition, the trial-by-trial variations in PO2 and OIS were well correlated with the variability in sigmaLFPs (Rmean= -0.77 and -0.76, respectively), indicating a single trial coupling between CMRO2 changes and sigmaLFP. These findings show that CBF and CMRO2 signals are more directly correlated with neural activity compared to blood oxygen-sensitive methods such as OIS and BOLD fMRI.
Kim:2004
Spatial relationship between neuronal activity and BOLD functional MRI.
D. Kim and I. Ronen and C. Olman and S. Kim and K. Ugurbil and L. J. Toth
Neuroimage  21  876--885  (2004)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=15006654
Despite the ubiquitous use of functional magnetic resonance imaging (fMRI), the extent to which the magnitude and spatial scale of the fMRI signal correlates with neuronal activity is poorly understood. In this study, we directly compared single and multiunit neuronal activity with blood oxygenation level-dependent (BOLD) fMRI responses across a large area of the cat area 18. Our data suggest that at the scale of several millimeters, the BOLD contrast correlates linearly with the underlying neuronal activity. At the level of individual electrode recording sites, however, the correlation between the two signals varied substantially. We conclude from our study that T(2)*-based positive BOLD signals are a robust predictor for neuronal activity only at supra-millimeter spatial scales.
Moon:2007
Neural interpretation of blood oxygenation level-dependent fMRI maps at submillimeter columnar resolution.
C. Moon and M. Fukuda and S. Park and S. Kim
J Neurosci  27  6892--6902  (2007)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17596437
Whether conventional gradient-echo (GE) blood oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is able to map submillimeter-scale functional columns remains debatable mainly because of the spatially nonspecific large vessel contribution, poor sensitivity and reproducibility, and lack of independent evaluation. Furthermore, if the results from optical imaging of intrinsic signals are directly applicable, regions with the highest BOLD signals may indicate neurally inactive domains rather than active columns when multiple columns are activated. To examine these issues, we performed BOLD fMRI at a magnetic field of 9.4 tesla to map orientation-selective columns of isoflurane-anesthetized cats. We could not convincingly map orientation columns using conventional block-design stimulation and differential analysis method because of large fluctuations of signals. However, we successfully obtained GE BOLD iso-orientation maps with high reproducibility (r = 0.74) using temporally encoded continuous cyclic orientation stimulation with Fourier data analysis, which reduces orientation-nonselective signals such as draining artifacts and is less sensitive to signal fluctuations. We further reduced large vessel contribution using the improved spin-echo (SE) BOLD method but with overall decreased sensitivity. Both GE and SE BOLD iso-orientation maps excluding large pial vascular regions were significantly correlated to maps with a known neural interpretation, which were obtained in contrast agent-aided cerebral blood volume fMRI and total hemoglobin-based optical imaging of intrinsic signals at a hemoglobin iso-sbestic point (570 nm). These results suggest that, unlike the expectation from deoxyhemoglobin-based optical imaging studies, the highest BOLD signals are localized to the sites of increased neural activity when column-nonselective signals are suppressed.
BEG+96
Linear systems analysis of functional magnetic resonance imaging in human {V}1.
G. Boynton and S. Engel and G. Glover and D. Heeger
J Neurosci  16  4207-21  (1996)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=8753882
The linear transform model of functional magnetic resonance imaging (fMRI) hypothesizes that fMRI responses are proportional to local average neural activity averaged over a period of time. This work reports results from three empirical tests that support this hypothesis. First, fMRI responses in human primary visual cortex (V1) depend separably on stimulus timing and stimulus contrast. Second, responses to long-duration stimuli can be predicted from responses to shorter duration stimuli. Third, the noise in the fMRI data is independent of stimulus contrast and temporal period. Although these tests can not prove the correctness of the linear transform model, they might have been used to reject the model. Because the linear transform model is consistent with our data, we proceeded to estimate the temporal fMRI impulse-response function and the underlying (presumably neural) contrast-response function of human V1.
Buracas:2005
The relationship between task performance and functional magnetic resonance imaging response.
G. T. Buracas and I. Fine and G. M. Boynton
J Neurosci  25  3023-31  (2005)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=15788758
We compared psychophysical and functional magnetic resonance imaging (fMRI) responses within areas V1-V3 and MT+ during both a speed and a contrast discrimination task. We found that fMRI responses did not depend significantly on task in any of these areas. Moreover, responses in V1-V3 were larger than those in MT+ for both the speed and the contrast discrimination tasks across a wide range of contrasts. This pattern of results demonstrates that localizing function based on finding those regions of cortex that show greater activity to a given task-stimulus combination than to other tasks and stimuli may, under certain conditions, be misleading. However, a simple ideal observer model assuming that perceptual thresholds are dependent on neuronal population responses does successfully show that V1 has neuronal properties consistent with our subjects' contrast discrimination performance, and that MT+ has neuronal properties consistent with subjects' performance on a speed discrimination task.
LPA+01
Neurophysiological investigation of the basis of the f{MRI} signal.
N. Logothetis and J. Pauls and M. Augath and T. Trinath and A. Oeltermann
Nature  412  150-7  (2001)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=11449264
Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trial-by-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.
RAT+01
Nonmonotonic noise tuning of {BOLD} f{MRI} signal to natural images in the visual cortex of the anesthetized monkey.
G. Rainer and M. Augath and T. Trinath and N. Logothetis
Curr Biol  11  846-54  (2001)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=11516645
Background: The perceptual ability of humans and monkeys to identify objects in the presence of noise varies systematically and monotonically as a function of how much noise is introduced to the visual display. That is, it becomes more and more difficult to identify an object with increasing noise. Here we examine whether the blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) signal in anesthetized monkeys also shows such monotonic tuning. We employed parametric stimulus sets containing natural images and noise patterns matched for spatial frequency and intensity as well as intermediate images generated by interpolation between natural images and noise patterns. Anesthetized monkeys provide us with the unique opportunity to examine visual processing largely in the absence of top-down cognitive modulations and can thus provide an important baseline against which work with awake monkeys and humans can be compared.Results: We measured BOLD activity in occipital visual cortical areas as natural images and noise patterns, as well as intermediate interpolated patterns at three interpolation levels (25\%, 50\%, and 75\%) were presented to anesthetized monkeys in a block paradigm. We observed reliable visual activity in occipital visual areas including V1, V2, V3, V3A, and V4 as well as the fundus and anterior bank of the superior temporal sulcus (STS). Natural images consistently elicited higher BOLD levels than noise patterns. For intermediate images, however, we did not observe monotonic tuning. Instead, we observed a characteristic V-shaped noise-tuning function in primary and extrastriate visual areas. BOLD signals initially decreased as noise was added to the stimulus but then increased again as the pure noise pattern was approached. We present a simple model based on the number of activated neurons and the strength of activation per neuron that can account for these results.Conclusions: We show that, for our parametric stimulus set, BOLD activity varied nonmonotonically as a function of how much noise was added to the visual stimuli, unlike the perceptual ability of humans and monkeys to identify such stimuli. This raises important caveats for interpreting fMRI data and demonstrates the importance of assessing not only which neural populations are activated by contrasting conditions during an fMRI study, but also the strength of this activation. This becomes particularly important when using the BOLD signal to make inferences about the relationship between neural activity and behavior.
Shmuel:2006
Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1.
A. Shmuel and M. Augath and A. Oeltermann and N. K. Logothetis
Nat Neurosci  9  569--577  (2006)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=16547508
Most functional brain imaging studies use task-induced hemodynamic responses to infer underlying changes in neuronal activity. In addition to increases in cerebral blood flow and blood oxygenation level-dependent (BOLD) signals, sustained negative responses are pervasive in functional imaging. The origin of negative responses and their relationship to neural activity remain poorly understood. Through simultaneous functional magnetic resonance imaging and electrophysiological recording, we demonstrate a negative BOLD response (NBR) beyond the stimulated regions of visual cortex, associated with local decreases in neuronal activity below spontaneous activity, detected 7.15 +/- 3.14 mm away from the closest positively responding region in V1. Trial-by-trial amplitude fluctuations revealed tight coupling between the NBR and neuronal activity decreases. The NBR was associated with comparable decreases in local field potentials and multiunit activity. Our findings indicate that a significant component of the NBR originates in neuronal activity decreases.
Goense:2008
Neurophysiology of the BOLD fMRI signal in awake monkeys.
J. B. M. Goense and N. K. Logothetis
Curr Biol  18  631--640  (2008)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=18439825
BACKGROUND: Simultaneous intracortical recordings of neural activity and blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in primary visual cortex of anesthetized monkeys demonstrated varying degrees of correlation between fMRI signals and the different types of neural activity, such as local field potentials (LFPs), multiple-unit activity (MUA), and single-unit activity (SUA). One important question raised by the aforementioned investigation is whether the reported correlations also apply to alert subjects. RESULTS: Monkeys were trained to perform a fixation task while stimuli within the receptive field of each recording site were used to elicit neural responses followed by a BOLD response. We show -- also in alert behaving monkeys -- that although both LFP and MUA make significant contributions to the BOLD response, LFPs are better and more reliable predictors of the BOLD signal. Moreover, when MUA responses adapt but LFP remains unaffected, the BOLD signal remains unaltered. CONCLUSIONS: The persistent coupling of the BOLD signal to the field potential when LFP and MUA have different time evolutions suggests that BOLD is primarily determined by the local processing of inputs in a given cortical area. In the alert animal the largest portion of the BOLD signal's variance is explained by an LFP range (20-60 Hz) that is most likely related to neuromodulation. Finally, the similarity of the results in alert and anesthetized subjects indicates that at least in V1 anesthesia is not a confounding factor. This enables the comparison of human fMRI results with a plethora of electrophysiological results obtained in alert or anesthetized animals.