Myles Jones - Academia.edu (original) (raw)

Papers by Myles Jones

Research paper thumbnail of Increased peak gamma frequency in individuals with higher levels of autistic traits

The European journal of neuroscience, Jan 8, 2015

Individual differences in orientation discrimination threshold are related to both visually-induc... more Individual differences in orientation discrimination threshold are related to both visually-induced peak gamma frequency and the presence of autistic traits. The relationship between peak gamma frequency and orientation discrimination thresholds may be due to both of these factors being mediated by levels of neural inhibition. No study has previously measured the relationship between peak gamma frequency and levels of autistic traits. Thus, this was the aim of the present study. We measured orientation discrimination thresholds and autistic traits in a neurotypical human sample (N = 33), and separately recorded electroencephalography to measure visually induced gamma activity. In line with our prediction, we found a significant relationship between peak gamma frequency and level of autistic traits. Consistent with previous work we also found significant relationships between orientation discrimination thresholds and level of autistic traits and between orientation discrimination thr...

Research paper thumbnail of Long-Latency Reductions in Gamma Power Predict Hemodynamic Changes That Underlie the Negative BOLD Signal

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 18, 2015

Studies that use prolonged periods of sensory stimulation report associations between regional re... more Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to "negative" hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30-80 Hz) in the middle-superficial cor...

Research paper thumbnail of Inter-trial variability in sensory-evoked cortical hemodynamic responses: the role of the magnitude of pre-stimulus fluctuations

Frontiers in neuroenergetics, 2012

Brain imaging techniques utilize hemodynamic changes that accompany brain activation. However, st... more Brain imaging techniques utilize hemodynamic changes that accompany brain activation. However, stimulus-evoked hemodynamic responses display considerable inter-trial variability and the sources of this variability are poorly understood. One of the sources of this response variation could be ongoing spontaneous hemodynamic fluctuations. We recently investigated this issue by measuring cortical hemodynamics in response to sensory stimuli in anesthetized rodents using 2-dimensional optical imaging spectroscopy. We suggested that sensory-evoked cortical hemodynamics displayed distinctive response characteristics and magnitudes depending on the phase of ongoing fluctuations at stimulus onset due to a linear superposition of evoked and ongoing hemodynamics (Saka et al., 2010). However, the previous analysis neglected to examine the possible influence of variability of the size of ongoing fluctuations. Consequently, data were further analyzed to examine whether the size of pre-stimulus hem...

Research paper thumbnail of Oblique Orientation Discrimination Thresholds Are Superior in Those with a High Level of Autistic Traits

Journal of Autism and Developmental Disorders, 2014

Enhanced low-level perception, although present in individuals with autism, is not seen in indivi... more Enhanced low-level perception, although present in individuals with autism, is not seen in individuals with high, but non-clinical, levels of autistic traits (Brock et al.in Percept Lond 40(6):739. doi: 10.1068/p6953 , 2011). This is surprising, as many of the higher-level visual differences found in autism have been shown to correlate with autistic traits in non-clinical samples. Here we measure vertical-oblique and, more difficult, oblique-oblique orientation discrimination thresholds in a non-clinical sample. As predicted, oblique-oblique thresholds provided a more sensitive test of orientation discrimination, and were negatively related to autistic traits (N = 94, r = -.356, p < .0001). We conclude that individual differences in orientation discrimination and autistic traits are related, and suggest that both of these factors could be mediated by increased levels of the inhibitory neurotransmitter GABA.

Research paper thumbnail of Polarographic Electrode Measures of Cerebral Tissue Oxygenation: Implications for Functional Brain Imaging

Research paper thumbnail of Nonlinear coupling of neural activity and CBF in rodent barrel cortex

NeuroImage, 2004

The relationship between neural activity and accompanying changes in cerebral blood flow (CBF) an... more The relationship between neural activity and accompanying changes in cerebral blood flow (CBF) and oxygenation must be fully understood before data from brain imaging techniques can be correctly interpreted. Whether signals in fMRI reflect the neural input or output of an activated region is still unclear. Similarly, quantitative relationships between neural activity and changes in CBF are not well understood. The present study addresses these issues by using simultaneous laser Doppler flowmetry (LDF) to measure CBF and multichannel electrophysiology to record neural activity in the form of field potentials and multiunit spiking. We demonstrate that CBF-activation coupling is a nonlinear inverse sigmoid function. Comparing the data with previous work suggests that within a cortical model, CBF shows greatest spatial correlation with a current sink 500 Am below the surface corresponding to sensory input. These results show that care must be exercised when interpreting imaging data elicited by particularly strong or weak stimuli and that hemodynamic changes may better reflect the input to a region rather than its spiking output. D 2004 Elsevier Inc. All rights reserved.

Research paper thumbnail of A Model of the Hemodynamic Response and Oxygen Delivery to Brain

NeuroImage, 2002

NeuroImage 12: 466 -477) links the changes in BOLD response to changes in neural activity. The sy... more NeuroImage 12: 466 -477) links the changes in BOLD response to changes in neural activity. The system consists of five subsystems, linking: (1) neural activity to flow changes; (2) flow changes to oxygen delivery to tissue; (3) flow changes to changes in blood volume and venous outflow; (4) changes in flow, volume, and oxygen extraction fraction to deoxyhemoglobin changes; and finally (5) volume and deoxyhemoglobin changes to the BOLD response. Friston et al. exploit, in subsystem 2, a model by Buxton and Frank coupling flow changes to changes in oxygen metabolism which assumes tissue oxygen concentration to be close to zero. We describe below a model of the coupling between flow and oxygen delivery which takes into account the modulatory effect of changes in tissue oxygen concentration. The major development has been to extend the original Buxton and Frank model for oxygen transport to a full dynamic capillary model making the model applicable to both transient and steady state conditions. Furthermore our modification enables us to determine the time series of CMRO 2 changes under different conditions, including CO 2 challenges. We compare the differences in the performance of the "Friston system" using the original model of Buxton and Frank and that of our model. We also compare the data predicted by our model (with appropriate parameters) to data from a series of OIS studies. The qualitative differences in the behaviour of the models are exposed by different experimental simulations and by comparison with the results of OIS data from brief and extended stimulation protocols and from experiments using hypercapnia. © 2002 Elsevier Science (USA)

Research paper thumbnail of Increased Oxygen Consumption Following Activation of Brain: Theoretical Footnotes Using Spectroscopic Data from Barrel Cortex

NeuroImage, 2001

Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthet... more Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthetized rats were used to determine the relationship between changes in oxy-and deoxygenated hemoglobin concentration and changes in blood volume and flow in the presence and absence of stimulation. The data from Jones et al. (accompanying paper) were used to explore the differences between two theoretical models of flow activation coupling. The essential difference between the two models is the extension of the model of Buxton and Frank by Hyder et al. (1998, J. Appl. Physiol. 85: 554 -564) to incorporate change in capillary diffusivity coupled to flow. In both models activation-increased flow changes increase oxygen transport from the capillary; however, in Hyder et al.'s model the diffusivity of the capillary itself is increased. Hyder et al. proposed a parameter (⍀), a scaling "constant" linking increased blood flow and oxygen "diffusivity" in the capillary bed. Thus, in Buxton and Frank's theory, ⍀ ‫؍‬ 0; i.e., there are no changes in diffusivity. In Hyder et al.'s theory, 0 < ⍀ < 1, and changes in diffusivity are assumed to be linearly related to flow changes. We elaborate the theoretical position of both models to show that, in principle, the different predictions from the two theories can be evaluated using optical imaging spectroscopy data. We find that both theoretical positions have limitations when applied to data from brief stimulation and when applied to data from mild hypercapnia. In summary, the analysis showed that although Hyder et al.'s proposal that diffusivity increased during activation did occur; it was shown to arise from an implementation of Buxton and Frank's theory under episodes of brief stimulation. The results also showed that the scaling parameter ⍀ is not a constant as the Hyder et al. model entails but in fact varies over the time course of the flow changes. Data from experiments in which mild hypercapnia was administered also indicated changes in the diffusivity of the capillary bed, but in this case the changes were negative; i.e., oxygen transport from the capillary decreased relative to baseline under hypercapnia. Neither of the models could account for the differences between the hypercapnia and activation data when matched for equivalent flow changes. A modification to the models to allow non-null tissue oxygen concentrations that can be moderated by changes due to increased metabolic demand following increased neural activity is proposed. This modification would allow modulation of oxygen transport from the capillary bed (e.g., changes in diffusivity) by tissue oxygen tension and would allow a degree of decoupling of flow and oxygen delivery, which can encompass both the data from stimulation and from hypercapnia.

Research paper thumbnail of Pseudo-random procedures for rapid presentation rates using optical imaging and spectroscopy

NeuroReport, 2000

Optical imaging of rat barrel cortex has provided detailed spatio-temporal maps of functional cor... more Optical imaging of rat barrel cortex has provided detailed spatio-temporal maps of functional cortical architecture. We describe an event-related procedure (ERP) for optical imaging based on selective signal averaging as reported by Burock et al., using an anti-correlative pseudo-random event sequence. The sequence used 1s vibrissal stimulation at 5 Hz, with an interevent interval of 2 s. This rapid presentation rate allows for greater statistical power per unit time, and allows for direct comparison of event-related studies with other imaging modalities. The spatio-temporal characteristics of single wavelength and spectrographic results were found to be comparable with those obtained by standard techniques, although a general lessening of haemodynamic response function (HRF) was noted. We also describe a method of locating barrel activity by spectral analysis of summed event data. Using this technique, the power spectrum of remitted light from the barrel region was found to peak within AE 0.12 Hz of the inter-event interval frequency. NeuroReport 11:1±6 & 2000 Lippincott Williams & Wilkins.

Research paper thumbnail of Concurrent Optical Imaging Spectroscopy and Laser-Doppler Flowmetry: The Relationship between Blood Flow, Oxygenation, and Volume in Rodent Barrel Cortex

NeuroImage, 2001

Functional magnetic resonance imaging (fMRI) is based on the coupling between neural activity and... more Functional magnetic resonance imaging (fMRI) is based on the coupling between neural activity and changes in the concentration of the endogenous paramagnetic contrast agent deoxygenated hemoglobin. Changes in the blood oxygen level-dependent (BOLD) signal result from a complex interplay of blood volume, flow, and oxygen consumption. Optical imaging spectroscopy (OIS) has been used to measure changes in blood volume and saturation in response to increased neural activity, while laser Doppler Flowmetry (LDF) can be used to measure flow changes and is now commonplace in neurovascular research. Here, we use concurrent OIS and LDF to examine the hemodynamic response in rodent barrel cortex using electrical stimulation of the whisker pad at varying intensities. Spectroscopic analysis showed that stimulation produced a biphasic early increase in deoxygenated hemoglobin (Hbr), followed by a decrease below baseline, reaching minima at ϳ3.7 s. There was no evidence for a corresponding early decrease in oxygenated hemoglobin (HbO 2 ), which simply increased after stimulation, reaching maximum at ϳ3.2 s. The time courses of changes in blood volume (CBV) and blood flow (CBF) were similar. Both increased within a second of stimulation onset and peaked at ϳ2.7 s, after which CBV returned to baseline at a slower rate than CBF. The changes in Hbr, Hbt, and CBF were used to estimate changes in oxygen consumption (CMRO 2 ), which increased within a second of stimulation and peaked ϳ2.2 s after stimulus onset. Analysis of the relative magnitudes of CBV and CBF indicates that the fractional changes of CBV could be simply scaled to match those of CBF. We found the relationship to be well approximated by CBV ‫؍‬ CBF 0.29 . A similar relationship was found using the response to elevated fraction of inspired carbon dioxide (FICO 2 ).

Research paper thumbnail of Temporal coupling between stimulus-evoked neural activity and hemodynamic responses from individual cortical columns

Physics in Medicine and Biology, 2010

Using previously published data from the whisker barrel cortex of anesthetized rodents (Berwick e... more Using previously published data from the whisker barrel cortex of anesthetized rodents (Berwick et al 2008 J. Neurophysiol. 99 787-98) we investigated whether highly spatially localized stimulus-evoked cortical hemodynamics responses displayed a linear time-invariant (LTI) relationship with neural activity. Presentation of stimuli to individual whiskers of 2 s and 16 s durations produced hemodynamics and neural activity spatially localized to individual cortical columns. Two-dimensional optical imaging spectroscopy (2D-OIS) measured hemoglobin responses, while multi-laminar electrophysiology recorded neural activity. Hemoglobin responses to 2 s stimuli were deconvolved with underlying evoked neural activity to estimate impulse response functions which were then convolved with neural activity evoked by 16 s stimuli to generate predictions of hemodynamic responses. An LTI system more adequately described the temporal neuro-hemodynamics coupling relationship for these spatially localized sensory stimuli than in previous studies that activated the entire whisker cortex. An inability to predict the magnitude of an initial &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;peak&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; in the total and oxy- hemoglobin responses was alleviated when excluding responses influenced by overlying arterial components. However, this did not improve estimation of the hemodynamic responses return to baseline post-stimulus cessation.

Research paper thumbnail of Further nonlinearities in neurovascular coupling in rodent barrel cortex

NeuroImage, 2005

An essential prerequisite for the accurate interpretation of noninvasive functional brain imaging... more An essential prerequisite for the accurate interpretation of noninvasive functional brain imaging techniques, such as blood oxygen level dependent (BOLD) fMRI, is a thorough understanding of the coupling relationship between neural activity and the haemodynamic response. The current study investigates this relationship using rat barrel cortex as a model. Neural input was measured by applying current source density (CSD) analysis to multi-laminar field potentials to remove ambiguities regarding the origin of the signal inherent in single electrode recordings. Changes in cerebral blood flow (CBF) were recorded with a laser Doppler flowmetry probe. The magnitude of neural and CBF responses were modulated over a large range by altering both the intensity and frequency of electrical whisker pad stimulation. Consistent with previous findings [Devor, A., et al., 2003. Neuron 39, 353-359;. Neuron 42, 347-355] a power law function well described the relationship between neural activity and haemodynamics. Despite the nonlinearity of the coupling over the whole data set, the relationship was very well approximated by a linear function over mid-range stimuli. Altering the frequency of stimulation at 1.2 mA shifted the neural activity and corresponding haemodynamic response along this linear region, reconciling recent reports of a nonlinear relationship [Devor, A., et al., 2003. Neuron 39, 353-359; Jones, M., et al., 2004. NeuroImage 22, 956-965; Sheth, S.A., et al., 2004. Neuron 42, 347-355] with previous work that found a linear coupling relationship when altering stimulation frequency

Research paper thumbnail of The effect of hypercapnia on the neural and hemodynamic responses to somatosensory stimulation

NeuroImage, 2005

Modern non-invasive imaging techniques utilize the coupling between neural activity and changes i... more Modern non-invasive imaging techniques utilize the coupling between neural activity and changes in blood flow, volume and oxygenation to map the functional architecture of the human brain. An understanding of how the hemodynamic response is influenced by pre-stimulus baseline perfusion is important for the interpretation of imaging data. To address this issue, the present study measured hemodynamics with optical imaging spectroscopy and laser Doppler flowmetry, while multichannel electrophysiology was used to record local field potentials (LFP) and multi-unit activity (MUA). The response to whisker stimulation in rodent barrel cortex was recorded during baseline (normocapnia) and elevated perfusion rates produced by two levels of hypercapnia (5 and 10%). With the exception of the Fwashout_ of deoxyhemoglobin, which was attenuated, all aspects of the neural and hemodynamic response to whisker stimulation were similar during 5% hypercapnia to those evoked during normocapnia. In contrast, 10% hypercapnia produced cortical arousal and a reduction in both the current sink and MUA elicited by stimulation. Blood flow and volume responses were reduced by a similar magnitude to that observed in the current sink. The deoxyhemoglobin Fwashout_, however, was attenuated to a greater degree than could be expected from the neural activity. These data suggest that imaging techniques based on perfusion or blood volume changes may be more robust to shifts in baseline than those based on the dilution of deoxyhemoglobin, such as conventional BOLD fMRI. D

Research paper thumbnail of Changes in Blood Flow, Oxygenation, and Volume Following Extended Stimulation of Rodent Barrel Cortex

NeuroImage, 2002

Simultaneous optical imaging spectroscopy and laser-Doppler flowmetry were used in rodent barrel ... more Simultaneous optical imaging spectroscopy and laser-Doppler flowmetry were used in rodent barrel cortex to examine the hemodynamic response to extended electrical stimulation (20 s, 5 Hz) of the whisker pad. Stimulation results in a fast early increase in deoxyhemoglobin concentration (Hbr) followed by a later decrease to a "plateau" phase ϳ4 s after stimulation onset. There was no corresponding decrease in oxyhemoglobin (HbO 2 ), which simply increased after stimulation, reaching a plateau at ϳ5 s. The time series of flow and volume had similar onset times and did not differ significantly throughout the presentation of the stimuli. Following stimulation cessation all aspects of the hemodynamic response returned to baseline with a long decay constant (>20 s), CBV doing so at a slower rate than CBF. The time courses of CBF, CBV, Hbr, and HbO 2 were very similar to that produced by a brief stimulus up to peak. The relationship between the flow and the volume changes is well approximated by the expression CBV ‫؍‬ CBF . We find to be slightly lower under stimulation (0.26 ؎ 0.0152) than during hypercapnia (0.32 ؎ 0.0172). Saturation and flow data were used to estimate changes in CMRO 2 for a range of baseline oxygen extraction fractions (OEF). In the case of hypercapnia CMRO 2 was biphasic, increasing after onset and sharply decreasing below baseline following cessation. If it is assumed that there is no "net" increase in CMRO 2 (i.e., ¥⌬CMRO 2 ‫؍‬ 0) following the onset and offset of hypercapnia, then the corresponding estimate of baseline OEF is 0.45. Evidence for increased oxygen consumption was obtained for all stimulation intensities assuming a baseline OEF of 0.45.

Research paper thumbnail of “Spectroscopic Analysis of Neural Activity in Brain: Increased Oxygen Consumption Following Activation of Barrel Cortex”

NeuroImage, 2001

This research investigates the hemodynamic response to stimulation of the barrel cortex in anaest... more This research investigates the hemodynamic response to stimulation of the barrel cortex in anaesthetized rats using optical imaging and spectroscopy . A slit spectrograph was used to collect spectral image data sequences. These were analyzed using an algorithm that corrects for the wavelength dependency in the optical path lengths produced by the light scattering properties of tissue. The analysis produced the changes in the oxyand deoxygenation of hemoglobin following stimulation. Two methods of stimulation were used. One method mechanically vibrated a single whisker, the other electrically stimulated the whisker pad. The electrical stimulation intensity varied from 0.4 to 1.6 mA. The hemodynamic responses to stimulation increased as a function of intensity. At 0.4 mA they were commensurate with those from the mechanical stimulation; however, the responses at the higher levels were greater by a factor of ϳ10. For both methods of data collection, the results of the spectroscopic analysis showed an early increase in deoxygenated hemoglobin (Hbr) with no evidence for a corresponding decrease in oxygenated hemoglobin (HbO 2 ). Evidence for increased oxygen consumption (CMRO 2 ) was obtained by converting the fractional changes in blood volume (Hbt) into estimates of changes in blood flow and using the resulting time course to scale the fractional changes in Hbr. The results show an early increase CMRO 2 peaking ϳ2 s after stimulation onset. Using these methods, we find evidence for increased oxygen consumption following increased neural activity even at low levels of stimulation intensity.

Research paper thumbnail of The Hemodynamic Impulse Response to a Single Neural Event

Journal of Cerebral Blood Flow & Metabolism, 2003

This article investigates the relation between stimulus-evoked neural activity and cerebral hemod... more This article investigates the relation between stimulus-evoked neural activity and cerebral hemodynamics. Specifically, the hypothesis is tested that hemodynamic responses can be modeled as a linear convolution of experimentally obtained measures of neural activity with a suitable hemodynamic impulse response function. To obtain a range of neural and hemodynamic responses, rat whisker pad was stimulated using brief (Յ2 seconds) electrical stimuli consisting of single pulses (0.3 millisecond, 1.2 mA) combined both at different frequencies and in a paired-pulse design. Hemodynamic responses were measured using concurrent optical imaging spectroscopy and laser Doppler flowmetry, whereas neural re-sponses were assessed through current source density analysis of multielectrode recordings from a single barrel. General linear modeling was used to deconvolve the hemodynamic impulse response to a single "neural event" from the hemodynamic and neural responses to stimulation. The model provided an excellent fit to the empirical data. The implications of these results for modeling schemes and for physiologic systems coupling neural and hemodynamic activity are discussed.

Research paper thumbnail of Hemodynamic Response in the Unanesthetized Rat: Intrinsic Optical Imaging and Spectroscopy of the Barrel Cortex

Journal of Cerebral Blood Flow & Metabolism, 2002

Research paper thumbnail of Early and late stimulus-evoked cortical hemodynamic responses provide insight into the neurogenic nature of neurovascular coupling

Journal of Cerebral Blood Flow & Metabolism, 2012

Understanding neurovascular coupling is a prerequisite for the interpretation of results obtained... more Understanding neurovascular coupling is a prerequisite for the interpretation of results obtained from modern neuroimaging techniques. This study investigated the hemodynamic and neural responses in rat somatosensory cortex elicited by 16 seconds electrical whisker stimuli. Hemodynamics were measured by optical imaging spectroscopy and neural activity by multichannel electrophysiology. Previous studies have suggested that the whisker-evoked hemodynamic response contains two mechanisms, a transient 'backwards' dilation of the middle cerebral artery, followed by an increase in blood volume localized to the site of neural activity. To distinguish between the mechanisms responsible for these aspects of the response, we presented whisker stimuli during normocapnia ('control'), and during a high level of hypercapnia. Hypercapnia was used to 'predilate' arteries and thus possibly 'inhibit' aspects of the response related to the 'early' mechanism. Indeed, hemodynamic data suggested that the transient stimulus-evoked response was absent under hypercapnia. However, evoked neural responses were also altered during hypercapnia and convolution of the neural responses from both the normocapnic and hypercapnic conditions with a canonical impulse response function, suggested that neurovascular coupling was similar in both conditions. Although data did not clearly dissociate early and late vascular responses, they suggest that the neurovascular coupling relationship is neurogenic in origin.

Research paper thumbnail of A Model of the Dynamic Relationship Between Blood Flow and Volume Changes During Brain Activation

Journal of Cerebral Blood Flow & Metabolism, 2004

The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume ... more The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen leveldependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBVϰCBF ⌽ has been used extensively in the literature. Two similar models, the Balloon (Buxton et al., 1998) and the Windkessel (Mandeville et al., 1999), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

Research paper thumbnail of Altered neurovascular coupling during information-processing states

European Journal of Neuroscience, 2008

The user has requested enhancement of the downloaded file.

Research paper thumbnail of Increased peak gamma frequency in individuals with higher levels of autistic traits

The European journal of neuroscience, Jan 8, 2015

Individual differences in orientation discrimination threshold are related to both visually-induc... more Individual differences in orientation discrimination threshold are related to both visually-induced peak gamma frequency and the presence of autistic traits. The relationship between peak gamma frequency and orientation discrimination thresholds may be due to both of these factors being mediated by levels of neural inhibition. No study has previously measured the relationship between peak gamma frequency and levels of autistic traits. Thus, this was the aim of the present study. We measured orientation discrimination thresholds and autistic traits in a neurotypical human sample (N = 33), and separately recorded electroencephalography to measure visually induced gamma activity. In line with our prediction, we found a significant relationship between peak gamma frequency and level of autistic traits. Consistent with previous work we also found significant relationships between orientation discrimination thresholds and level of autistic traits and between orientation discrimination thr...

Research paper thumbnail of Long-Latency Reductions in Gamma Power Predict Hemodynamic Changes That Underlie the Negative BOLD Signal

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 18, 2015

Studies that use prolonged periods of sensory stimulation report associations between regional re... more Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to "negative" hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30-80 Hz) in the middle-superficial cor...

Research paper thumbnail of Inter-trial variability in sensory-evoked cortical hemodynamic responses: the role of the magnitude of pre-stimulus fluctuations

Frontiers in neuroenergetics, 2012

Brain imaging techniques utilize hemodynamic changes that accompany brain activation. However, st... more Brain imaging techniques utilize hemodynamic changes that accompany brain activation. However, stimulus-evoked hemodynamic responses display considerable inter-trial variability and the sources of this variability are poorly understood. One of the sources of this response variation could be ongoing spontaneous hemodynamic fluctuations. We recently investigated this issue by measuring cortical hemodynamics in response to sensory stimuli in anesthetized rodents using 2-dimensional optical imaging spectroscopy. We suggested that sensory-evoked cortical hemodynamics displayed distinctive response characteristics and magnitudes depending on the phase of ongoing fluctuations at stimulus onset due to a linear superposition of evoked and ongoing hemodynamics (Saka et al., 2010). However, the previous analysis neglected to examine the possible influence of variability of the size of ongoing fluctuations. Consequently, data were further analyzed to examine whether the size of pre-stimulus hem...

Research paper thumbnail of Oblique Orientation Discrimination Thresholds Are Superior in Those with a High Level of Autistic Traits

Journal of Autism and Developmental Disorders, 2014

Enhanced low-level perception, although present in individuals with autism, is not seen in indivi... more Enhanced low-level perception, although present in individuals with autism, is not seen in individuals with high, but non-clinical, levels of autistic traits (Brock et al.in Percept Lond 40(6):739. doi: 10.1068/p6953 , 2011). This is surprising, as many of the higher-level visual differences found in autism have been shown to correlate with autistic traits in non-clinical samples. Here we measure vertical-oblique and, more difficult, oblique-oblique orientation discrimination thresholds in a non-clinical sample. As predicted, oblique-oblique thresholds provided a more sensitive test of orientation discrimination, and were negatively related to autistic traits (N = 94, r = -.356, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). We conclude that individual differences in orientation discrimination and autistic traits are related, and suggest that both of these factors could be mediated by increased levels of the inhibitory neurotransmitter GABA.

Research paper thumbnail of Polarographic Electrode Measures of Cerebral Tissue Oxygenation: Implications for Functional Brain Imaging

Research paper thumbnail of Nonlinear coupling of neural activity and CBF in rodent barrel cortex

NeuroImage, 2004

The relationship between neural activity and accompanying changes in cerebral blood flow (CBF) an... more The relationship between neural activity and accompanying changes in cerebral blood flow (CBF) and oxygenation must be fully understood before data from brain imaging techniques can be correctly interpreted. Whether signals in fMRI reflect the neural input or output of an activated region is still unclear. Similarly, quantitative relationships between neural activity and changes in CBF are not well understood. The present study addresses these issues by using simultaneous laser Doppler flowmetry (LDF) to measure CBF and multichannel electrophysiology to record neural activity in the form of field potentials and multiunit spiking. We demonstrate that CBF-activation coupling is a nonlinear inverse sigmoid function. Comparing the data with previous work suggests that within a cortical model, CBF shows greatest spatial correlation with a current sink 500 Am below the surface corresponding to sensory input. These results show that care must be exercised when interpreting imaging data elicited by particularly strong or weak stimuli and that hemodynamic changes may better reflect the input to a region rather than its spiking output. D 2004 Elsevier Inc. All rights reserved.

Research paper thumbnail of A Model of the Hemodynamic Response and Oxygen Delivery to Brain

NeuroImage, 2002

NeuroImage 12: 466 -477) links the changes in BOLD response to changes in neural activity. The sy... more NeuroImage 12: 466 -477) links the changes in BOLD response to changes in neural activity. The system consists of five subsystems, linking: (1) neural activity to flow changes; (2) flow changes to oxygen delivery to tissue; (3) flow changes to changes in blood volume and venous outflow; (4) changes in flow, volume, and oxygen extraction fraction to deoxyhemoglobin changes; and finally (5) volume and deoxyhemoglobin changes to the BOLD response. Friston et al. exploit, in subsystem 2, a model by Buxton and Frank coupling flow changes to changes in oxygen metabolism which assumes tissue oxygen concentration to be close to zero. We describe below a model of the coupling between flow and oxygen delivery which takes into account the modulatory effect of changes in tissue oxygen concentration. The major development has been to extend the original Buxton and Frank model for oxygen transport to a full dynamic capillary model making the model applicable to both transient and steady state conditions. Furthermore our modification enables us to determine the time series of CMRO 2 changes under different conditions, including CO 2 challenges. We compare the differences in the performance of the "Friston system" using the original model of Buxton and Frank and that of our model. We also compare the data predicted by our model (with appropriate parameters) to data from a series of OIS studies. The qualitative differences in the behaviour of the models are exposed by different experimental simulations and by comparison with the results of OIS data from brief and extended stimulation protocols and from experiments using hypercapnia. © 2002 Elsevier Science (USA)

Research paper thumbnail of Increased Oxygen Consumption Following Activation of Brain: Theoretical Footnotes Using Spectroscopic Data from Barrel Cortex

NeuroImage, 2001

Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthet... more Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthetized rats were used to determine the relationship between changes in oxy-and deoxygenated hemoglobin concentration and changes in blood volume and flow in the presence and absence of stimulation. The data from Jones et al. (accompanying paper) were used to explore the differences between two theoretical models of flow activation coupling. The essential difference between the two models is the extension of the model of Buxton and Frank by Hyder et al. (1998, J. Appl. Physiol. 85: 554 -564) to incorporate change in capillary diffusivity coupled to flow. In both models activation-increased flow changes increase oxygen transport from the capillary; however, in Hyder et al.'s model the diffusivity of the capillary itself is increased. Hyder et al. proposed a parameter (⍀), a scaling "constant" linking increased blood flow and oxygen "diffusivity" in the capillary bed. Thus, in Buxton and Frank's theory, ⍀ ‫؍‬ 0; i.e., there are no changes in diffusivity. In Hyder et al.'s theory, 0 < ⍀ < 1, and changes in diffusivity are assumed to be linearly related to flow changes. We elaborate the theoretical position of both models to show that, in principle, the different predictions from the two theories can be evaluated using optical imaging spectroscopy data. We find that both theoretical positions have limitations when applied to data from brief stimulation and when applied to data from mild hypercapnia. In summary, the analysis showed that although Hyder et al.'s proposal that diffusivity increased during activation did occur; it was shown to arise from an implementation of Buxton and Frank's theory under episodes of brief stimulation. The results also showed that the scaling parameter ⍀ is not a constant as the Hyder et al. model entails but in fact varies over the time course of the flow changes. Data from experiments in which mild hypercapnia was administered also indicated changes in the diffusivity of the capillary bed, but in this case the changes were negative; i.e., oxygen transport from the capillary decreased relative to baseline under hypercapnia. Neither of the models could account for the differences between the hypercapnia and activation data when matched for equivalent flow changes. A modification to the models to allow non-null tissue oxygen concentrations that can be moderated by changes due to increased metabolic demand following increased neural activity is proposed. This modification would allow modulation of oxygen transport from the capillary bed (e.g., changes in diffusivity) by tissue oxygen tension and would allow a degree of decoupling of flow and oxygen delivery, which can encompass both the data from stimulation and from hypercapnia.

Research paper thumbnail of Pseudo-random procedures for rapid presentation rates using optical imaging and spectroscopy

NeuroReport, 2000

Optical imaging of rat barrel cortex has provided detailed spatio-temporal maps of functional cor... more Optical imaging of rat barrel cortex has provided detailed spatio-temporal maps of functional cortical architecture. We describe an event-related procedure (ERP) for optical imaging based on selective signal averaging as reported by Burock et al., using an anti-correlative pseudo-random event sequence. The sequence used 1s vibrissal stimulation at 5 Hz, with an interevent interval of 2 s. This rapid presentation rate allows for greater statistical power per unit time, and allows for direct comparison of event-related studies with other imaging modalities. The spatio-temporal characteristics of single wavelength and spectrographic results were found to be comparable with those obtained by standard techniques, although a general lessening of haemodynamic response function (HRF) was noted. We also describe a method of locating barrel activity by spectral analysis of summed event data. Using this technique, the power spectrum of remitted light from the barrel region was found to peak within AE 0.12 Hz of the inter-event interval frequency. NeuroReport 11:1±6 & 2000 Lippincott Williams & Wilkins.

Research paper thumbnail of Concurrent Optical Imaging Spectroscopy and Laser-Doppler Flowmetry: The Relationship between Blood Flow, Oxygenation, and Volume in Rodent Barrel Cortex

NeuroImage, 2001

Functional magnetic resonance imaging (fMRI) is based on the coupling between neural activity and... more Functional magnetic resonance imaging (fMRI) is based on the coupling between neural activity and changes in the concentration of the endogenous paramagnetic contrast agent deoxygenated hemoglobin. Changes in the blood oxygen level-dependent (BOLD) signal result from a complex interplay of blood volume, flow, and oxygen consumption. Optical imaging spectroscopy (OIS) has been used to measure changes in blood volume and saturation in response to increased neural activity, while laser Doppler Flowmetry (LDF) can be used to measure flow changes and is now commonplace in neurovascular research. Here, we use concurrent OIS and LDF to examine the hemodynamic response in rodent barrel cortex using electrical stimulation of the whisker pad at varying intensities. Spectroscopic analysis showed that stimulation produced a biphasic early increase in deoxygenated hemoglobin (Hbr), followed by a decrease below baseline, reaching minima at ϳ3.7 s. There was no evidence for a corresponding early decrease in oxygenated hemoglobin (HbO 2 ), which simply increased after stimulation, reaching maximum at ϳ3.2 s. The time courses of changes in blood volume (CBV) and blood flow (CBF) were similar. Both increased within a second of stimulation onset and peaked at ϳ2.7 s, after which CBV returned to baseline at a slower rate than CBF. The changes in Hbr, Hbt, and CBF were used to estimate changes in oxygen consumption (CMRO 2 ), which increased within a second of stimulation and peaked ϳ2.2 s after stimulus onset. Analysis of the relative magnitudes of CBV and CBF indicates that the fractional changes of CBV could be simply scaled to match those of CBF. We found the relationship to be well approximated by CBV ‫؍‬ CBF 0.29 . A similar relationship was found using the response to elevated fraction of inspired carbon dioxide (FICO 2 ).

Research paper thumbnail of Temporal coupling between stimulus-evoked neural activity and hemodynamic responses from individual cortical columns

Physics in Medicine and Biology, 2010

Using previously published data from the whisker barrel cortex of anesthetized rodents (Berwick e... more Using previously published data from the whisker barrel cortex of anesthetized rodents (Berwick et al 2008 J. Neurophysiol. 99 787-98) we investigated whether highly spatially localized stimulus-evoked cortical hemodynamics responses displayed a linear time-invariant (LTI) relationship with neural activity. Presentation of stimuli to individual whiskers of 2 s and 16 s durations produced hemodynamics and neural activity spatially localized to individual cortical columns. Two-dimensional optical imaging spectroscopy (2D-OIS) measured hemoglobin responses, while multi-laminar electrophysiology recorded neural activity. Hemoglobin responses to 2 s stimuli were deconvolved with underlying evoked neural activity to estimate impulse response functions which were then convolved with neural activity evoked by 16 s stimuli to generate predictions of hemodynamic responses. An LTI system more adequately described the temporal neuro-hemodynamics coupling relationship for these spatially localized sensory stimuli than in previous studies that activated the entire whisker cortex. An inability to predict the magnitude of an initial &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;peak&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; in the total and oxy- hemoglobin responses was alleviated when excluding responses influenced by overlying arterial components. However, this did not improve estimation of the hemodynamic responses return to baseline post-stimulus cessation.

Research paper thumbnail of Further nonlinearities in neurovascular coupling in rodent barrel cortex

NeuroImage, 2005

An essential prerequisite for the accurate interpretation of noninvasive functional brain imaging... more An essential prerequisite for the accurate interpretation of noninvasive functional brain imaging techniques, such as blood oxygen level dependent (BOLD) fMRI, is a thorough understanding of the coupling relationship between neural activity and the haemodynamic response. The current study investigates this relationship using rat barrel cortex as a model. Neural input was measured by applying current source density (CSD) analysis to multi-laminar field potentials to remove ambiguities regarding the origin of the signal inherent in single electrode recordings. Changes in cerebral blood flow (CBF) were recorded with a laser Doppler flowmetry probe. The magnitude of neural and CBF responses were modulated over a large range by altering both the intensity and frequency of electrical whisker pad stimulation. Consistent with previous findings [Devor, A., et al., 2003. Neuron 39, 353-359;. Neuron 42, 347-355] a power law function well described the relationship between neural activity and haemodynamics. Despite the nonlinearity of the coupling over the whole data set, the relationship was very well approximated by a linear function over mid-range stimuli. Altering the frequency of stimulation at 1.2 mA shifted the neural activity and corresponding haemodynamic response along this linear region, reconciling recent reports of a nonlinear relationship [Devor, A., et al., 2003. Neuron 39, 353-359; Jones, M., et al., 2004. NeuroImage 22, 956-965; Sheth, S.A., et al., 2004. Neuron 42, 347-355] with previous work that found a linear coupling relationship when altering stimulation frequency

Research paper thumbnail of The effect of hypercapnia on the neural and hemodynamic responses to somatosensory stimulation

NeuroImage, 2005

Modern non-invasive imaging techniques utilize the coupling between neural activity and changes i... more Modern non-invasive imaging techniques utilize the coupling between neural activity and changes in blood flow, volume and oxygenation to map the functional architecture of the human brain. An understanding of how the hemodynamic response is influenced by pre-stimulus baseline perfusion is important for the interpretation of imaging data. To address this issue, the present study measured hemodynamics with optical imaging spectroscopy and laser Doppler flowmetry, while multichannel electrophysiology was used to record local field potentials (LFP) and multi-unit activity (MUA). The response to whisker stimulation in rodent barrel cortex was recorded during baseline (normocapnia) and elevated perfusion rates produced by two levels of hypercapnia (5 and 10%). With the exception of the Fwashout_ of deoxyhemoglobin, which was attenuated, all aspects of the neural and hemodynamic response to whisker stimulation were similar during 5% hypercapnia to those evoked during normocapnia. In contrast, 10% hypercapnia produced cortical arousal and a reduction in both the current sink and MUA elicited by stimulation. Blood flow and volume responses were reduced by a similar magnitude to that observed in the current sink. The deoxyhemoglobin Fwashout_, however, was attenuated to a greater degree than could be expected from the neural activity. These data suggest that imaging techniques based on perfusion or blood volume changes may be more robust to shifts in baseline than those based on the dilution of deoxyhemoglobin, such as conventional BOLD fMRI. D

Research paper thumbnail of Changes in Blood Flow, Oxygenation, and Volume Following Extended Stimulation of Rodent Barrel Cortex

NeuroImage, 2002

Simultaneous optical imaging spectroscopy and laser-Doppler flowmetry were used in rodent barrel ... more Simultaneous optical imaging spectroscopy and laser-Doppler flowmetry were used in rodent barrel cortex to examine the hemodynamic response to extended electrical stimulation (20 s, 5 Hz) of the whisker pad. Stimulation results in a fast early increase in deoxyhemoglobin concentration (Hbr) followed by a later decrease to a "plateau" phase ϳ4 s after stimulation onset. There was no corresponding decrease in oxyhemoglobin (HbO 2 ), which simply increased after stimulation, reaching a plateau at ϳ5 s. The time series of flow and volume had similar onset times and did not differ significantly throughout the presentation of the stimuli. Following stimulation cessation all aspects of the hemodynamic response returned to baseline with a long decay constant (>20 s), CBV doing so at a slower rate than CBF. The time courses of CBF, CBV, Hbr, and HbO 2 were very similar to that produced by a brief stimulus up to peak. The relationship between the flow and the volume changes is well approximated by the expression CBV ‫؍‬ CBF . We find to be slightly lower under stimulation (0.26 ؎ 0.0152) than during hypercapnia (0.32 ؎ 0.0172). Saturation and flow data were used to estimate changes in CMRO 2 for a range of baseline oxygen extraction fractions (OEF). In the case of hypercapnia CMRO 2 was biphasic, increasing after onset and sharply decreasing below baseline following cessation. If it is assumed that there is no "net" increase in CMRO 2 (i.e., ¥⌬CMRO 2 ‫؍‬ 0) following the onset and offset of hypercapnia, then the corresponding estimate of baseline OEF is 0.45. Evidence for increased oxygen consumption was obtained for all stimulation intensities assuming a baseline OEF of 0.45.

Research paper thumbnail of “Spectroscopic Analysis of Neural Activity in Brain: Increased Oxygen Consumption Following Activation of Barrel Cortex”

NeuroImage, 2001

This research investigates the hemodynamic response to stimulation of the barrel cortex in anaest... more This research investigates the hemodynamic response to stimulation of the barrel cortex in anaesthetized rats using optical imaging and spectroscopy . A slit spectrograph was used to collect spectral image data sequences. These were analyzed using an algorithm that corrects for the wavelength dependency in the optical path lengths produced by the light scattering properties of tissue. The analysis produced the changes in the oxyand deoxygenation of hemoglobin following stimulation. Two methods of stimulation were used. One method mechanically vibrated a single whisker, the other electrically stimulated the whisker pad. The electrical stimulation intensity varied from 0.4 to 1.6 mA. The hemodynamic responses to stimulation increased as a function of intensity. At 0.4 mA they were commensurate with those from the mechanical stimulation; however, the responses at the higher levels were greater by a factor of ϳ10. For both methods of data collection, the results of the spectroscopic analysis showed an early increase in deoxygenated hemoglobin (Hbr) with no evidence for a corresponding decrease in oxygenated hemoglobin (HbO 2 ). Evidence for increased oxygen consumption (CMRO 2 ) was obtained by converting the fractional changes in blood volume (Hbt) into estimates of changes in blood flow and using the resulting time course to scale the fractional changes in Hbr. The results show an early increase CMRO 2 peaking ϳ2 s after stimulation onset. Using these methods, we find evidence for increased oxygen consumption following increased neural activity even at low levels of stimulation intensity.

Research paper thumbnail of The Hemodynamic Impulse Response to a Single Neural Event

Journal of Cerebral Blood Flow & Metabolism, 2003

This article investigates the relation between stimulus-evoked neural activity and cerebral hemod... more This article investigates the relation between stimulus-evoked neural activity and cerebral hemodynamics. Specifically, the hypothesis is tested that hemodynamic responses can be modeled as a linear convolution of experimentally obtained measures of neural activity with a suitable hemodynamic impulse response function. To obtain a range of neural and hemodynamic responses, rat whisker pad was stimulated using brief (Յ2 seconds) electrical stimuli consisting of single pulses (0.3 millisecond, 1.2 mA) combined both at different frequencies and in a paired-pulse design. Hemodynamic responses were measured using concurrent optical imaging spectroscopy and laser Doppler flowmetry, whereas neural re-sponses were assessed through current source density analysis of multielectrode recordings from a single barrel. General linear modeling was used to deconvolve the hemodynamic impulse response to a single "neural event" from the hemodynamic and neural responses to stimulation. The model provided an excellent fit to the empirical data. The implications of these results for modeling schemes and for physiologic systems coupling neural and hemodynamic activity are discussed.

Research paper thumbnail of Hemodynamic Response in the Unanesthetized Rat: Intrinsic Optical Imaging and Spectroscopy of the Barrel Cortex

Journal of Cerebral Blood Flow & Metabolism, 2002

Research paper thumbnail of Early and late stimulus-evoked cortical hemodynamic responses provide insight into the neurogenic nature of neurovascular coupling

Journal of Cerebral Blood Flow & Metabolism, 2012

Understanding neurovascular coupling is a prerequisite for the interpretation of results obtained... more Understanding neurovascular coupling is a prerequisite for the interpretation of results obtained from modern neuroimaging techniques. This study investigated the hemodynamic and neural responses in rat somatosensory cortex elicited by 16 seconds electrical whisker stimuli. Hemodynamics were measured by optical imaging spectroscopy and neural activity by multichannel electrophysiology. Previous studies have suggested that the whisker-evoked hemodynamic response contains two mechanisms, a transient 'backwards' dilation of the middle cerebral artery, followed by an increase in blood volume localized to the site of neural activity. To distinguish between the mechanisms responsible for these aspects of the response, we presented whisker stimuli during normocapnia ('control'), and during a high level of hypercapnia. Hypercapnia was used to 'predilate' arteries and thus possibly 'inhibit' aspects of the response related to the 'early' mechanism. Indeed, hemodynamic data suggested that the transient stimulus-evoked response was absent under hypercapnia. However, evoked neural responses were also altered during hypercapnia and convolution of the neural responses from both the normocapnic and hypercapnic conditions with a canonical impulse response function, suggested that neurovascular coupling was similar in both conditions. Although data did not clearly dissociate early and late vascular responses, they suggest that the neurovascular coupling relationship is neurogenic in origin.

Research paper thumbnail of A Model of the Dynamic Relationship Between Blood Flow and Volume Changes During Brain Activation

Journal of Cerebral Blood Flow & Metabolism, 2004

The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume ... more The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen leveldependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBVϰCBF ⌽ has been used extensively in the literature. Two similar models, the Balloon (Buxton et al., 1998) and the Windkessel (Mandeville et al., 1999), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

Research paper thumbnail of Altered neurovascular coupling during information-processing states

European Journal of Neuroscience, 2008

The user has requested enhancement of the downloaded file.