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Spatial dependence of the nonlinear BOLD response at short stimulus duration
Abstract
Most functional magnetic resonance imaging studies use linear models to predict the measured response by convolution of an impulse response with the stimulus profile. Using very short visual presentation times (<2 s), deviation from the linear model in the measured BOLD data from the human brain was found for the response integral, amplitude, and width. In this study, high temporal and spatial resolution were used to quantify nonlinear effects and investigate the spatial dependence. Data at 4 Tesla showed at short stimulus duration a nonlinearity, i.e., deviation from a linear model, with an index up to 400%, whereas data at 7 Tesla exhibited a nonlinearity index up to 40%. The effect was more pronounced for response amplitude than for response area. A reduced width and sharpening of responses at shorter stimulus duration was also found. A voxel-based analysis of 7 Tesla data with 1.2 x 1.2 x 2 mm(3) resolution revealed a correlation between response onset and nonlinearity index. This suggests that the nonlinearity effects are a tissue-specific phenomenon and are likely to be more localized to the site of neuronal activity. The observed magnetic field dependence and the demonstrated nonlinearity in the response width support the hypothesis that the source of the nonlinearity at short stimulus duration has a considerable hemodynamic contribution. The nonlinearity was modeled as a "switch"-type initial hemodynamic response onset. Understanding these nonlinearities in the BOLD response is important for design and the analysis of rapid event-related fMRI experiments with brief stimulus presentations.
... Par exemple, des non-linéarités ont été trouvées dans les réponses d'extraction d'oxygène (Rees et al., 1997), du débit sanguin cérébral (Miller et al., 2001) et de l'activité neuronale (Logothetis et al., 2001). En ce qui concerne l'activité neuronale, l'adaptation neuronale dans le système auditif (Smith, 1977 ;Picton et al., 1978 ;Smith, 1979) a été considérée comme un des arguments les plus forts pour expliquer cette non-linéarité (Miller et al., 2001 ;Pfeuffer et al., 2003). Les contributions multifactorielles à la non-linéarité peuvent conduire à une variation de la forme de la RHD, en particulier, de la latence du pic. ...
... Conversely, Glover demonstrated that the auditory response is linear for short-duration auditory stimuli but highly nonlinear for longer stimuli (Glover, 1999) . The authors demonstrated a higher degree of nonlinearity in the blood-oxygen-level-dependent (BOLD) response changes in the visual cortex for shorter-duration stimuli (Vazquez and Noll, 1998 ;Liu and Gao, 2000 ;Pfeuffer et al., 2003) . A nonlinearity response is also shown in the human somatosensory cortex (Nangini et al., 2002) . ...
... For example, nonlinearities were found in responses of oxygen extraction (Rees et al., 1997) , cerebral blood flow (Miller et al., 2001) , and neuronal activity (Logothetis et al., 2001) . In regard to neural activity, neural adaptation supported by strong evidence in the auditory system (Smith, 1977 ;Picton et al., 1978 ;Smith, 1979) has been considered an adequate way to account for this nonlinearity (Miller et al., 2001 ;Pfeuffer et al., 2003) . Multifactorial contributions to nonlinearity may lead to unpredictable variability in slopes, as we observed in Fig. 6. ...
Introduction La surdité unilatérale est une pathologie fréquente chez l'enfant. Les répercussions en sont importantes tant sur le plan de l'audition spatiale que sur l'aspect du développement psychosocial. À ce jour, très peu de données neurofonctionnelles ont été recueillies chez l'enfant. L'objectif de cette thèse est donc d'étudier, chez l'enfant, le lien entre l'atteinte auditive unilatérale et ses corrélats neuraux. Cet objectif repose sur deux études, lesquelles sont définies comme suit : 1) Procéder à l'identification des paramètres de stimulation optimaux utilisés en fNIRS afin d'obtenir un signal de qualité sur l'enfant et, 2) Mesurer la réorganisation corticale suite à la surdité unilatérale et corréler cette réorganisation aux performances psychoacoustiques, psychosociales. Matériels et méthodes S'agissant de la première étude, dix-sept sujets adultes normo-entendants ont été recrutés. Ils ont été soumis à quatre conditions de stimulation auditive en fNIRS. L'amplitude du signal fNIRS enregistré et la durée expérimentale ont été comparées, entre ces conditions. Concernant la seconde étude, quatre enfants porteurs de surdité unilatérale ont été inclus. Ils ont été évalués en psychoacoustique par les tests de localisation du son dans l'espace et de la compréhension de la parole dans le bruit, en neurofonctionnel par la fNIRS, et en développement psychosocial par les tests mesurant les habiletés linguistiques différentes. Ils ont enfin répondu aux questionnaires de qualité de vie. Résultats L'étude 1 a identifié la durée de stimulation de 15 s comme étant un choix optimal, lorsqu'elle est associée à une amplitude trois fois plus importante et à une durée plus courte de 105 s que les autres conditions de stimulation. L'étude 2 a démontré une grande variabilité des résultats en performances psychoacoustiques et psychosociales. De plus, la surdité unilatérale a induit une augmentation de l'activation corticale ipsilatérale à l'oreille saine. Cette augmentation est significativement corrélée aux performances binaurales. Conclusion La surdité unilatérale induit des phénomènes de réorganisation corticale associés à une forte variabilité des performances binaurales et psychosociales, suggérant l'existence de facteurs compensatoires. Ce travail souligne la nécessité de l'identification de ces facteurs compensatoires et d'une prise en charge des enfants vulnérables aux effets néfastes de la surdité unilatérale.
... The slow dynamics of the hemodynamic response function (HRF) result in strong attenuation of high-frequency neural activity (14). In addition, rapidly repeating neural stimuli typically result in smaller fMRI responses (15)(16)(17)(18)(19)(20), further limiting the detectability of neural oscillations. ...
... Although the magnitude of neural activity appeared similar across conditions, the duration of neural activity in the 0.5-Hz condition was substantially shorter (Fig. 3 D and E). fMRI responses are known to exhibit nonlinear dependence on stimulus duration, with briefer stimuli inducing larger responses than expected from a linear system (17,34,35). To test the role of stimulus duration explicitly, we presented stimuli with luminance contrast varying as the square of a sinusoidal function, yielding a narrower stimulus waveform than the sinusoidal case (Fig. 4A). ...
... The slow canonical hemodynamic response functions may reflect the slow experimental paradigms used to obtain them, whereas hemodynamic responses to rapidly fluctuating neural activity are, in fact, fast. This interpretation also could explain the observations of previous studies that have reported nonlinear fMRI responses to short-duration stimuli (17,25,34,42). We suggest that, rather than representing a problem for fMRI because of the failure of the canonical linear models, these fast responses in fact mean that fMRI has an unexpectedly strong ability to measure naturalistic, rapidly varying neural activity. ...
Significance
A major challenge in neuroscience is our limited ability to image neural signals noninvasively in humans. Oscillations in brain activity are important for perception, attention, and awareness, and progress in cognitive neuroscience depends on localizing these patterns. fMRI is thought to be too slow to measure brain oscillations because it depends on slow changes in blood flow. Here, we use recently developed imaging techniques to show that fMRI can measure faster neural oscillations than previously thought, and responses are 10 times larger than expected. With computational modeling and simultaneous electroencephalography we show that vascular responses are surprisingly fast when brain activity fluctuates rapidly. These results suggest that fMRI can be used to track oscillating brain activity directly during human cognition.
... This result suggests that any nonlinearity of the BOLD response may be due to nonlinearities in the neural response. Although one study (Birn et al., 2001) did not find any correlation between response latency and degree of nonlinearity, another study (Pfeuffer et al., 2003) did find such a correlation, suggesting that vessel size may be a contributing factor to nonlinearity. The exact origin of the nonlinear effect is still not clear. ...
... Two studies (Birn et al., 2001;Pfeuffer et al., 2003) have looked at the variation of nonlinearity on a spatial basis. Individual voxels were assigned indices of nonlinearity based on the response profiles for several stimulus or task durations. ...
... This study also found voxelwise variation of the nonlinearity index in the primary visual cortex, but no clear difference between the visual and motor cortices. Pfeuffer et al. (2003) looked at the spatial dependence of the nonlinearity only within the visual cortex. Therefore, further research is necessary to compare the nonlinearity across different cortices of the brain. ...
Hemodynamic responses to auditory and visual stimuli and motor tasks were assessed for the nonlinearity of response in each of the respective primary cortices. Five stimulus or task durations were used (1, 2, 4, 8, and 16 s), and five male subjects (aged 19 ± 1.9 years) were imaged. Two tests of linearity were conducted. The first test consisted of using BOLD responses to short stimuli to predict responses to longer stimuli. The second test consisted of fitting ideal impulse response functions to the observed responses for each event duration. Both methods show that the extent of the nonlinearity varies across cortices. Results for the second method indicate that the hemodynamic response is nonlinear for stimuli less than 10 s in the primary auditory cortex, nonlinear for tasks less than 7 s in the primary motor cortex, and nonlinear for stimuli less than 3 s in the primary visual cortex. In addition, neural adaptation functions were characterized that could model the observed nonlinearities.
... Therefore, the BOLD response in the primary visual cortex is nonlinear with respect to stimulus rate. Furthermore, the three modalities of Pfeuffer et al. 2003Birn et al. 2001Miller et al. 2001Liu and Gao 2000Vazquez and Noll 1998(Boynton et al. 1996) Singh et al. 2003Chawla et al. 1999Kwong et al. 1992Vazquez and Noll 1998 Motor Birn et al. 2001Miller et al. 2001Glover 1999J@ncke et al. 1998 Auditory Glover 1999Robson 1998Friston et al. 1998Rees et al. 1997Binder et al. 1994Somatosensory Nangini et al. 2002 Harrington One of the earliest papers to focus on the nonlinearity of the BOLD response looked at the effect of duration and contrast for a visual stimulus (Vazquez and Noll 1998). The researchers found that a nonlinear behavior exists for the BOLD response with respect to changes in both duration (1, 2, 4, and 8 seconds) and contrast (10%, 20%, 40%, and 80%), although the nonlinearity was stronger for changes in duration. ...
... A second paper looked at the spatial variation of the nonlinearity on a voxelwise basis in the visual cortex (Pfeuffer et al. 2003). Using very short stimuli (100, 200, 400, 800, and 1600 milliseconds for 4 T experiments and 250, 500, 1000, and 2000 milliseconds for 7 T experiments), the authors calculated nonlinearity indices for response area, amplitude, and width. ...
... Another paper has reported a linear relationship between local field potentials (LFP) of neurons and the BOLD response (Logethetis et al. 2001) and stated that both LFPs and the BOLD response were nonlinear functions of visual stimulus contrast. Although one paper (Birn et al. 2001) did not find any correlation between response latency and degree of nonlinearity, another paper (Pfeuffer et al. 2003) did find such a correlation, suggesting that vessel size may be a contributing factor to nonlinearity. The exact origin of the nonlinear effect is still not clear. ...
... This has been found for stimulus durations longer than approximately 3 s in the visual system [4][5][6][7] and may hold in the motor and auditory systems for even longer stimulus durations [5]. However, significant deviations from LTI properties have been reported for BOLD responses of the visual [5,6,[8][9][10][11][12][13][14][15][16], motor [5,9,10,17], auditory [5,17,18] and somatosensory systems [19,20] for stimulus durations less than approximately 3 s. Moreover, such deviations have also been found for cognitive tasks [21]. ...
... Moreover, such deviations have also been found for cognitive tasks [21]. Recognizing that the assumption of constant neural activity for a sustained stimulus is an oversimplification, a number of authors have suggested that neural transients or neural adaptation could explain, at least partially, such deviations from LTI properties [5,7,8,10,12,[19][20][21][22]. These reports primarily focus on transient stimulus onset responses. ...
... Therefore, we optimized the latency for each participant p and voxel v. The shape of h was defined by the "Cox special function" h Cox [n] (as implemented in AFNI) with the following parameter settings: a peak amplitude of one, a rise time rt=3.5 s, a fall time ft=5 s, an undershoot us=0.2 and a restore time ret=15 s: (8) where z(x) = 0.50212657·(tanh(tan(0.5π·(1.6x−0.8))) + 0.99576486). ...
Blood oxygenation level-dependent (BOLD) signal time courses in functional magnetic resonance imaging are estimated within the framework of general linear modeling by convolving an input function, that represents neural activity, with a canonical hemodynamic response function (HRF). Here we investigate the performance of different neural input functions and latency-optimized HRFs for modeling BOLD signals in response to vibrotactile somatosensory stimuli of variable durations (0.5, 1, 4, 7 s) in 14 young, healthy adults who were required to make button press responses at each stimulus cessation. Informed by electrophysiology and the behavioral task, three nested models with an increasing number of parameters were considered: a boxcar; boxcar and offset transient; and onset transient, boxcar and offset transient (TBT). The TBT model provided the best fit of the group-averaged BOLD time courses based on χ(2) and F statistics. Only the TBT model was capable of fitting the bimodal shape of the BOLD response to the 7-s stimulus and the relative peak amplitudes for all stimulus lengths in key somatosensory and motor areas. This suggests that the TBT model provides a more comprehensive description of brain sensorimotor responses in this experiment than provided by the simple boxcar model. Work comparing the activation maps obtained with the TBT model with magnetoencephalography data is under way.
... Unfortunately, a number of studies have demonstrated that significant nonlinearity exists in the BOLD signal (Birn and Bandettini, 2005;Birn et al., 2001;Boynton et al., 1996;Cannestra et al., 1998;Dale and Buckner, 1997;Friston et al., 1998;Friston et al., 2000;Glover, 1999;Huettel and McCarthy, 2000;Inan et al., 2004;Janz et al., 2001;Pfeuffer et al., 2003;Robson et al., 1998;Soon et al., 2003;Wager et al., 2005, Buxton, 1998#18, Vazquez, 1998. When subtracting the BOLD response to a single stimulus from the response to two identical sequential stimuli, the magnitude of the subtracted response is smaller compared to the singlestimulus response and the degree of this BOLD reduction depends on the delay between two sequential stimuli and stimulation duration (Boynton et al., 1996;Huettel and McCarthy, 2000;Inan et al., 2004;Pfeuffer et al., 2003;Robson et al., 1998;Wager et al., 2005). ...
... Unfortunately, a number of studies have demonstrated that significant nonlinearity exists in the BOLD signal (Birn and Bandettini, 2005;Birn et al., 2001;Boynton et al., 1996;Cannestra et al., 1998;Dale and Buckner, 1997;Friston et al., 1998;Friston et al., 2000;Glover, 1999;Huettel and McCarthy, 2000;Inan et al., 2004;Janz et al., 2001;Pfeuffer et al., 2003;Robson et al., 1998;Soon et al., 2003;Wager et al., 2005, Buxton, 1998#18, Vazquez, 1998. When subtracting the BOLD response to a single stimulus from the response to two identical sequential stimuli, the magnitude of the subtracted response is smaller compared to the singlestimulus response and the degree of this BOLD reduction depends on the delay between two sequential stimuli and stimulation duration (Boynton et al., 1996;Huettel and McCarthy, 2000;Inan et al., 2004;Pfeuffer et al., 2003;Robson et al., 1998;Wager et al., 2005). In addition, the onset latency of the BOLD response to the subsequent stimulus is longer compared to the single-stimulus BOLD response and this latency difference also depends on the delay between two sequential stimuli with longer latencies observed for shorter delays (Huettel and McCarthy, 2000;Pfeuffer et al., 2003). ...
... When subtracting the BOLD response to a single stimulus from the response to two identical sequential stimuli, the magnitude of the subtracted response is smaller compared to the singlestimulus response and the degree of this BOLD reduction depends on the delay between two sequential stimuli and stimulation duration (Boynton et al., 1996;Huettel and McCarthy, 2000;Inan et al., 2004;Pfeuffer et al., 2003;Robson et al., 1998;Wager et al., 2005). In addition, the onset latency of the BOLD response to the subsequent stimulus is longer compared to the single-stimulus BOLD response and this latency difference also depends on the delay between two sequential stimuli with longer latencies observed for shorter delays (Huettel and McCarthy, 2000;Pfeuffer et al., 2003). ...
Several studies have demonstrated significant nonlinearity in the blood-oxygenation-level-dependent (BOLD) signal. Completely understanding the nature of this nonlinear behavior is important in the interpretation of the BOLD signal. However, this task is hindered by the uncertainty of the source of BOLD nonlinearity which could come from neuronal and/or vascular origin. The obscurity of this issue not only impedes accurate modeling of BOLD nonlinearity, but also limits generalization of the conclusions regarding BOLD nonlinearity. To examine this issue, we eliminated nonlinear contributions from the neuronal response and selectively study BOLD nonlinearity under only the vascular effect by employing a paired-stimulus paradigm composed of two ultra-short visual stimuli separated by a variable inter-stimulus interval (ISI). ISIs chosen were long enough (> or = 1s) to ensure invariant neuronal activity to all stimuli. Under this circumstance, we still observed significant nonlinearity in the BOLD signal reflected by a progressive recovery of BOLD response to the second stimuli as ISI gets longer and delayed BOLD onset latency. These nonlinear behaviors identified in the BOLD signal originate entirely from the vascular responses as the neuronal responses to all stimuli are identical. More importantly, we found that BOLD nonlinearity became much less significant after we removed activated pixels from large vessels. These finds reveal that the dominant component, if not all, of the source of BOLD nonlinearity comes from large-vessel hemodynamic response. They also suggest a possible mechanism to improve the spatial specificity of gradient-echo BOLD signal for fMRI mapping based on the characteristics of vascular refractoriness.
... Due to the significant differences between the BOLD responses of humans and rats, application of the human HRF may not be appropriate for the analysis of small animal data. Furthermore, several studies indicate that experimental conditions like anesthesia (Masamoto et al., 2009;Schlegel et al., 2015;Schroeter et al., 2014;van Alst et al., 2019), as well as stimulation type (Albers et al., 2018) and stimulation duration (Huettel and McCarthy, 2000;Pfeuffer et al., 2003;Vazquez and Noll, 1998;Yeşilyurt et al., 2008) influence the BOLD response. Therefore, it is not clear whether a universal rat HRF is appropriate to analyze data obtained under different experimental conditions. ...
... The observed deviations from linearity of the BOLD response are consistent with several human studies (Huettel and McCarthy, 2000;Miller et al., 2001;Pfeuffer et al., 2003;Vazquez and Noll, 1998;Wager et al., 2005;Yeşilyurt et al., 2008), in which such deviations have partly been attributed to neuronal adaptation. However, several rodent studies showed that the BOLD response changed approximately linearly with neuronal activation (Brinker et al., 1999;Herman et al., 2009;Logothetis et al., 2001;Ogawa et al., 2000), suggesting a nonlinearity between stimulation and neuronal activity. ...
For a reliable estimation of neuronal activation based on BOLD fMRI measurements an accurate model of the hemodynamic response is essential. Since a large part of basic neuroscience research is based on small animal data, it is necessary to characterize a hemodynamic response function (HRF) which is optimized for small animals. Therefore, we have determined and investigated the HRFs of rats obtained under a variety of experimental conditions in the primary somatosensory cortex. Measurements were performed on animals of different sex and strain, under different anesthetics, with and without ventilation and using different stimulation modalities. All modalities of stimulation used in this study induced neuronal activity in the primary somatosensory cortex or in subcortical regions. Since the HRFs of the BOLD responses in the primary somatosensory cortex showed a close concordance for the different conditions, we were able to determine a cortical rat HRF. This HRF is based on 143 BOLD measurements of 76 rats and can be used for statistical parametric mapping. It showed substantially faster progression than the human HRF, with a maximum after (2.8) s, and a following undershoot after (6.1) s. If the rat HRF was used statistical analysis of rat data showed a significantly improved detection performance in the somatosensory cortex in comparison to the commonly used HRF based on measurements in humans.
... We observed saturation of both the peak amplitude and TTP of the BOLD HRF in all three regions for stimuli longer than 128 pulses (2 s). This saturation of the peak BOLD amplitude implies that a linear relationship between the BOLD response and the neural activity, [28][29][30] in which both the amplitude and the area under the BOLD response increase linearly with stimulus duration, can be supported for stimulus durations up to 64 pulses (1 s). For stimulus durations longer than 128 pulses (2 s), the BOLD peak amplitude becomes constant, whereas the area under the curve and FHWM increase linearly with stimulus duration. ...
... For stimulus durations longer than 128 pulses (2 s), the BOLD peak amplitude becomes constant, whereas the area under the curve and FHWM increase linearly with stimulus duration. 29 The location and size of the areas of activation in S1 and S2 agree well with previous histological and electrophysiological studies in marmosets mapping area 3b, the main homologous area of S1 of other mammals, 31 and area S2, respectively. 32,33 Area 3b extends 2 mm in the rostrocaudal direction, and spans 8 mm lateral to the midline before bending rostrally and extending 6 mm further. ...
Understanding the spatiotemporal features of the hemodynamic response function (HRF) to brain stimulation is essential for the correct application of neuroimaging methods to study brain function. Here, we investigated the spatiotemporal evolution of the blood oxygen level-dependent (BOLD) and cerebral blood volume (CBV) HRF in conscious, awake marmosets (Callithrix jacchus), a New World non-human primate with a lissencephalic brain and with growing use in biomedical research. The marmosets were acclimatized to head fixation and placed in a 7-T magnetic resonance imaging (MRI) scanner. Somatosensory stimulation (333-μs pulses; amplitude, 2 mA; 64 Hz) was delivered bilaterally via pairs of contact electrodes. A block design paradigm was used in which the stimulus duration increased in pseudo-random order from a single pulse up to 256 electrical pulses (4 s). For CBV measurements, 30 mg/kg of ultrasmall superparamagnetic ironoxide particles (USPIO) injected intravenously, were used. Robust BOLD and CBV HRFs were obtained in the primary somatosensory cortex (S1), secondary somatosensory cortex (S2) and caudate at all stimulus conditions. In particular, BOLD and CBV responses to a single 333-μs-long stimulus were reliably measured, and the CBV HRF presented shorter onset time and time to peak than the BOLD HRF. Both the size of the regions of activation and the peak amplitude of the HRFs grew quickly with increasing stimulus duration, and saturated for stimulus durations greater than 1 s. Onset times in S1 and S2 were faster than in caudate. Finally, the fine spatiotemporal features of the HRF in awake marmosets were similar to those obtained in humans, indicating that the continued refinement of awake non-human primate models is essential to maximize the applicability of animal functional MRI studies to the investigation of human brain function.
... Therefore, for simple sentences where each semantically rich word occurs only once per sentence (as in the study presented here), higher order brain regions involved in semantic processing should not be strongly impacted by this nonlinearity. Furthermore, use of higher field strength (e.g., 7T) also greatly reduces non-linearities in the BOLD response (Pfeuffer, McCullough, Van de Moortele, Ugurbil, & Hu, 2003), potentially due to the relatively larger contribution from the microvasculature at higher field. Thus, in addition to the gains in CNR expected from higher field strength Ugurbil, 2014;Vaughan et al., 2001), improvements in BOLD linearity should further enhance extraction of word timing information. ...
... Our results suggest that there is more temporal information available at higher field strength, even for the same sampling rate (500 ms) and similar CNR conditions. Much of the improvements in classification accuracy at 7T, in our study, may have come from the improved BOLD linearity (Pfeuffer et al., 2003) as well as the increased sensitivity to capillaries (Duong et al., 2003;Yacoub et al., 2001) found at higher field strengths. Given that capillaries respond faster (Hulvershorn et al., 2005) and more linearly (Zhang, Yacoub, Zhu, Ugurbil, & Chen, 2009) than large veins, it would make sense that increasing sensitivity to them by going to higher field strength would improve decodability of finegrained temporal information. ...
The blood-oxygen-level-dependent (BOLD) signal measured in functional magnetic resonance imaging (fMRI) experiments is generally regarded as sluggish and poorly suited for probing neural function at the rapid timescales involved in sentence comprehension. However, recent studies have shown the value of acquiring data with very short repetition times (TRs), not merely in terms of improvements in contrast to noise ratio (CNR) through averaging, but also in terms of additional fine-grained temporal information. Using multiband-accelerated fMRI, we achieved whole-brain scans at 3-mm resolution with a TR of just 500 ms at both 3T and 7T field strengths. By taking advantage of word timing information, we found that word decoding accuracy across two separate sets of scan sessions improved significantly, with better overall performance at 7T than at 3T. The effect of TR was also investigated; we found that substantial word timing information can be extracted using fast TRs, with diminishing benefits beyond TRs of 1000 ms.
... Third, our model provides a simpler and more linear interpretation of the HRF than balloon models, in which most non-linearity comes from non-linear venous inflation Buxton et al., 1998;Griffeth and Buxton, 2011). The absence of the putative venous inflation in the arterial impulse model results in an offset-linear relationship between CBF and CMRO 2 responses that is consistent with the observed non-linearity between the BOLD response and neural activity (Pfeuffer et al., 2003;Vazquez and Noll, 1998). Fourth, our model postulates independent CBF and CMRO 2 response kernels driven by the neural response. ...
... This offset in the linearity between CBF and CMRO 2 is consistent with non-linearities in the BOLD response that have been observed and characterized in a number of reports (Friston et al., 2000;Pfeuffer et al., 2003;Vazquez and Noll, 1998). Largest non-linearities were generally observed for very short stimulation durations, in response to which we expect very low metabolic demand and very small CMRO 2 response. ...
The blood oxygen level dependent (BOLD) signal evoked by brief neural stimulation, the hemodynamic response function (HRF), is a critical feature of neurovascular coupling. The HRF is directly related to local transient changes in oxygen supplied by cerebral blood flow (CBF) and oxygen demand, the cerebral metabolic rate of oxygen (CMRO2). Previous efforts to explain the HRF have relied upon the hypothesis that CBF produces a non-linear venous dilation within the cortical parenchyma. Instead, the observed dynamics correspond to prompt arterial dilation without venous volume change. This work develops an alternative biomechanical model for the BOLD response based on the hypothesis that prompt upstream dilation creates an arterial flow impulse amenable to linear description. This flow model is coupled to a continuum description of oxygen transport. Measurements using high-resolution fMRI demonstrate the efficacy of the model. The model predicts substantial spatial variations of the oxygen saturation along the length of capillaries and veins, and fits the varied gamut of measured HRFs by the combined effects of corresponding CBF and CMRO2 responses. Three interesting relationships among the hemodynamic parameters are predicted. First, there is an offset linear correlation with approximately unity slope between CBF and CMRO2 responses. Second, the HRF undershoot is strongly correlated to the corresponding CBF undershoot. Third, late-time-CMRO2 response can contribute to a slow recovery to baseline, lengthening the HRF undershoot. The model provides a powerful mathematical framework to understand the dynamics of neurovascular and neurometabolic responses that form the BOLD HRF.
... Altogether, the strong desynchronization at the 96-pulse stimulation resulted in low VPM and S1BF LFP response levels and weakened thalamo-cortical recurrent activities to recruit and synchronize neurons in remote regions 71,[74][75][76] . Note that BOLD activations decreased as expected when reducing stimulation length from 24-pulse to 8-and 16-pulse, which was primarily due to the relationship between BOLD responses and the length of stimulations 78 , not the mechanisms governing spindle termination and synchronization. Our results indicate that both oscillation length and frequency play important roles in driving the brainwide targeting of thalamo-cortical spindle activities through inherent neural mechanisms underlying spindle generation, synchronization, and termination. ...
As a key oscillatory activity in the brain, thalamic spindle activities are long believed to support memory consolidation. However, their propagation characteristics and causal actions at systems level remain unclear. Using functional MRI (fMRI) and electrophysiology recordings in male rats, we found that optogenetically-evoked somatosensory thalamic spindle-like activities targeted numerous sensorimotor (cortex, thalamus, brainstem and basal ganglia) and non-sensorimotor limbic regions (cortex, amygdala, and hippocampus) in a stimulation frequency- and length-dependent manner. Thalamic stimulation at slow spindle frequency (8 Hz) and long spindle length (3 s) evoked the most robust brain-wide cross-modal activities. Behaviorally, evoking these global cross-modal activities during memory consolidation improved visual-somatosensory associative memory performance. More importantly, parallel visual fMRI experiments uncovered response potentiation in brain-wide sensorimotor and limbic integrative regions, especially superior colliculus, periaqueductal gray, and insular, retrosplenial and frontal cortices. Our study directly reveals that thalamic spindle activities propagate in a spatiotemporally specific manner and that they consolidate associative memory by strengthening multi-target memory representation.
... Indeed, using multiple stringent dropouts resulted in no overfitting in our DNN model (Fig. 6). Finally, BOLD signals in a fast-event design, such as in movies, present nonlinear relationships between variables (Pfeuffer et al., 2003;Vazquez & Noll, 1998), which GLMs cannot model, due to their underlying assumption of linearity between variables. Since ...
For centuries, neuroscience has proposed models of the neurobiology of language processing that are static and localised to few temporal and inferior frontal regions. Although existing models have offered some insight into the processes underlying lower-level language features, they have largely overlooked how language operates in the real world. Here, we aimed at investigating the network organisation of the brain and how it supports language processing in a naturalistic setting. We hypothesised that the brain is organised in a multiple core-periphery and dynamic modular architecture, with canonical language regions forming high-connectivity hubs. Moreover, we predicted that language processing would be distributed to much of the rest of the brain, allowing it to perform more complex tasks and to share information with other cognitive domains. To test these hypotheses, we collected the Naturalistic Neuroimaging Database of people watching full length movies during functional magnetic resonance imaging. We computed network algorithms to capture the voxel-wise architecture of the brain in individual participants and inspected variations in activity distribution over different stimuli and over more complex language features. Our results confirmed the hypothesis that the brain is organised in a flexible multiple core-periphery architecture with large dynamic communities. Here, language processing was distributed to much of the rest of the brain, together forming multiple communities. Canonical language regions constituted hubs, explaining why they consistently appear in various other neurobiology of language models. Moreover, language processing was supported by other regions such as visual cortex and episodic memory regions, when processing more complex context-specific language features. Overall, our flexible and distributed model of language comprehension and the brain points to additional brain regions and pathways that could be exploited for novel and more individualised therapies for patients suffering from speech impairments.
... The decision to perform the study exclusively on males individuals was based on previous reports revealing consistent sex differences in brain structures activation (amygdala, thalamus, insula) when experiencing emotions (Newhoff et al., 2015;Whittle et al., 2011 for a review) and also to emotional distraction (prefrontal cortex) (Iordan et al., 2013). Therefore, including both sexes could have been a significant confusion variable added to the normal variability expected in an event-related fMRI design (Birn et al., 2001;Pfeuffer et al., 2003). Exclusion criteria were antecedents of neurological or psychiatric disease, diagnostic criteria of ADHD, substance abuse affecting the central nervous system, and any intrinsic situation that impeded a subject from entering the fMRI machine due to concerns over personal safety (such as any kind of metallic implants or psychological concerns, claustrophobia for example). ...
Modulation of reflex responses is crucial to adapt our behavior and cognition, and this is especially difficult when biological relevant stimuli are present such as emotional faces. The aim of this study was to identify the effect of peripherally presented happy and angry facial expressions in reflexive saccades and saccadic inhibition/re-orientation of attention. Behavior through eye-tracking technique and fMRI event-related BOLD signals activations were evaluated in adult males during the performance of an antisaccade task. fMRI signals obtained during task performance were compared to a baseline. Results showed that antisaccades had a lower percentage of correct responses and higher latency onsets than prosaccades. At the activation brain level, differences between both emotions and the baseline were found during stimuli presentation. Prosaccades for happy and angry faces recruited larger clusters with higher Z values mainly in occipito-parietal and temporal regions related to visual basic and integration processing, as well as regions of the oculomotor network. Meanwhile, when compared to the baseline, antisaccades recruited similar areas but a lower number of clusters with lower Z values as expected for peripheral processing of faces. At antisaccades, happy faces recruited parieto-occipital, temporal and cerebellar regions, while the angry faces added activation of orbital and ventrolateral prefrontal cortex related to emotional regulation. These results suggest that emotional facial expressions are being processed outside of the focus of attention. Particularly, angry expressions recruit a wider brain network in order to inhibit automatic behavior and re-orientate voluntary attention efficiently that may be due to its biological relevance.
... 0.2 to 0.8Hz) (Hathout et al., 1999;Janz et al., 2001). This is because neurovascular coupling is not entirely linear but depends on the frequency (Lewis et al., 2016;Liu et al., 2010;Zhang et al., 2008), amplitude, and duration of neural response (Pfeuffer et al., 2003;Yeşilyurt et al., 2008). If neural response is relatively weak or short (likely due to strong adaptation), its cumulative (over time) effect is less likely to saturate the vascular response, allowing the vasculature to remain sensitive to changes in neural activity and respond within its dynamic range and thus capable of following faster modulation in neural activity. ...
The stomach and the brain interact closely with each other. Their interactions are central to digestive functions and the “gut feeling”. The neural pathways that mediate the stomach-brain interactions include the vagus nerve and the thoracic nerve. Through these nerves, the stomach can relay neural signals to a number of brain regions that span a central gastric network. This gastric network allows the brain to monitor and regulate gastric physiology and allows the stomach to influence emotion and cognition. Impairment of this gastric network may lead to both gastric and neurological disorders, e.g., anxiety, gastroparesis, functional dyspepsia, and obesity. However, the structural constituents and functional roles of the central gastric network remain unclear. In my dissertation research, I leveraged complementary techniques to characterize the central gastric network in rats across a wide range of scales and different gastric states. I used functional magnetic resonance imaging (fMRI) to map blood-oxygen-level-dependent (BOLD) activity synchronized with gastric electrical activity and to map brain activations induced by electrical stimulation applied to the vagus nerve or its afferent terminals on the stomach. I also used neurophysiology to characterize gastric neurons in the brainstem in response to gastric electrical stimulation. My results suggest that gastric neurons in the brainstem are selective to the orientation of gastric electrical stimulation. This electrical stimulation can also evoke neural activity beyond the brainstem and drive fast blood oxygenation level dependent (BOLD) activity in the central gastric network, primarily covering the cingulate cortex, somatosensory cortex, motor cortex, and insular cortex. Stimulating the vagus nerve – the primary neural pathway between the stomach and the brain, can evoke BOLD responses across widespread brain regions partially overlapped with the brain network evoked by gastric electrical stimulation. BOLD activity within the gastric network is also coupled to intrinsic gastric activity. Specifically, gastric slow waves are synchronized with the BOLD activity in the central gastric network. The synchronization manifests itself as the phase-coupling between BOLD activity and gastric slow waves as well as the correlation between BOLD activity and power fluctuations of gastric slow waves. This synchronization is primarily supported by the vagus nerve and varies across the postprandial and fasting states. My dissertation research contributes to the foundation of mapping and characterizing the central and peripheral mechanisms of gastric interoception and sheds new light on where and how to stimulate the peripheral nerves to modulate stomach-brain interactions.
... Conversely, Glover demonstrated that the auditory response is linear for short-duration auditory stimuli but highly nonlinear for longer stimuli (Glover, 1999). The authors showed a higher degree of nonlinearity in the blood-oxygen-level-dependent (BOLD) response changes in the visual cortex for shorter-duration stimuli (Vazquez and Noll, 1998;Liu and Gao, 2000;Pfeuffer et al., 2003). A nonlinearity response is also shown in the human somatosensory cortex (Nangini et al., 2002). ...
Functional near-infrared spectroscopy (fNIRS) is an increasingly popular method in hearing research. However, few studies have considered efficient stimulation parameters for fNIRS auditory experimental design. The objectives of our study are (1) to characterize the auditory hemodynamic responses to trains of white noise with increasing stimulation durations (8s, 10s, 15s, 20s) in terms of amplitude and response linearity; (2) to identify the most-efficient stimulation duration using fNIRS; and (3) to generalize results to more ecological environmental stimuli. We found that cortical activity is augmented following the increments in stimulation durations and reaches a plateau after about 15s of stimulation. The linearity analysis showed that this augmentation due to stimulation duration is not linear in the auditory cortex, the non-linearity being more pronounced for longer durations (15s and 20s). The 15s block duration that we propose as optimal precludes signal saturation, is associated with a high response amplitude and a relatively short total experimental duration. Moreover, the 15s duration remains optimal independently of the nature of presented sounds. The sum of these findings suggests that 15s stimulation duration used in the appropriate experimental setup allows researchers to acquire optimal fNIRS signal quality.
... Subjects were first instructed about giving confidence after completing the Confidence-absent condition. www.nature.com/scientificreports/ each event is calculated after a convolution with the sluggish hemodynamic response function, longer events are easier to separate from shorter ones such that two short events in succession would not produce differentiable neural activations but two long events would [52][53][54][55] . Therefore, elongating the perceptual decision and confidence response periods helps separate the regressors associated with these two events. ...
The period of making a perceptual decision is often followed by a period of rating confidence where one evaluates the likely accuracy of the initial decision. However, it remains unclear whether the same or different neural circuits are engaged during periods of perceptual decision making and confidence report. To address this question, we conducted two functional MRI experiments in which we dissociated the periods related to perceptual decision making and confidence report by either separating their respective regressors or asking for confidence ratings only in the second half of the experiment. We found that perceptual decision making and confidence reports gave rise to activations in large and mostly overlapping brain circuits including frontal, parietal, posterior, and cingulate regions with the results being remarkably consistent across the two experiments. Further, the confidence report period activated a number of unique regions, whereas only early sensory areas were activated for the decision period across the two experiments. We discuss the possible reasons for this overlap and explore their implications about theories of perceptual decision making and visual metacognition.
... 13,[38][39][40][41][42] ; for nonlinearities, mostly found in event-related designs, see e.g. [43][44][45][46][47][48][49] . Based on these results at conventional resolutions, the assumptions for a linear system are expected to largely hold for responses across cortical depth. ...
A fundamental assumption of nearly all functional magnetic resonance imaging (fMRI) analyses is that the relationship between local neuronal activity and the blood oxygenation level dependent (BOLD) signal can be described as following linear systems theory. With the advent of ultra-high field (7T and higher) MRI scanners, it has become possible to perform sub-millimeter resolution fMRI in humans. A novel and promising application of sub-millimeter fMRI is measuring responses across cortical depth, i.e. laminar imaging. However, the cortical vasculature and associated directional blood pooling towards the pial surface strongly influence the cortical depth-dependent BOLD signal, particularly for gradient-echo BOLD. This directional pooling may potentially affect BOLD linearity across cortical depth. Here we assess whether the amplitude scaling assumption for linear systems theory holds across cortical depth. For this, we use stimuli with different luminance contrasts to elicit different BOLD response amplitudes. We find that BOLD amplitude across cortical depth scales with luminance contrast, and that this scaling is identical across cortical depth. Although nonlinearities may be present for different stimulus configurations and acquisition protocols, our results suggest that the amplitude scaling assumption for linear systems theory across cortical depth holds for luminance contrast manipulations in sub-millimeter laminar BOLD fMRI.
... 15,22 Most studies have attributed nonlinearities to sources of non-BOLD contrast, such as volume changes of the active population, metabolic exchange, or partialvolume effects associated with large voxel sizes that do not purely sample the gray matter parenchyma. 18,[23][24][25][26][27][28] A few studies proposed the use of multiple-compartment models to better explain functional contrast. Kang et al 24 proposed a pH-driven chemical exchange between multiple spin populations tentatively identified as venous blood and tissue. ...
Purpose
Functional MRI contrast has generally been associated with changes in transverse relaxivity caused by blood oxygen concentration, the so‐called blood oxygen level dependent contrast. However, this interpretation of fMRI contrast has been called into question by several recent experiments at high spatial resolution. Experiments were conducted to examine contrast dependencies that cannot be explained only by differences in relaxivity in a single‐spin population.
Methods
Measurements of functional signal and contrast were obtained in human early visual cortex during a high‐contrast visual stimulation over a large range of TEs and for several flip angles. Small voxels (1.5 mm) were used to restrict the measurements to cortical gray matter in early visual areas identified using retinotopic mapping procedures.
Results
Measurements were consistent with models that include 2 spin populations. The dominant population has a relatively short transverse lifetime that is strongly modulated by activation. However, functional contrast is also affected by volume changes between this short‐lived population and the longer‐lived population.
Conclusion
Some of the previously observed “nonclassical” behaviors of functional contrast can be explained by these interacting dual‐spin populations.
... However, we chose a 2-s stimulus duration to avoid the non-linear regime observed for very short stimuli. These non-linearities may be partly the consequence of the inefficiency of matching metabolic demands by increasing blood flow to enhance diffusive transmural oxygen transport ( (Buxton and Frank, 1997;Kim and Ress, 2016;Uludag et al., 2004)); task switching effects may also play a role (Pfeuffer et al., 2003). The strong, extensive, and fairly stereotypical HRF that we observed in these experiments suggests that the 2-s stimulus provides an optimal time scale for measurement of the hemodynamic response across cortex: short enough to avoid long-term cognitive and neural changes, but long enough to avoid non-linearity in the neurovascular coupling. ...
A brief (<4 s) period of neural activation evokes a stereotypical sequence of vascular and metabolic events to create the hemodynamic response function (HRF) measured using functional magnetic resonance imaging (fMRI). Linear analysis of fMRI data requires that the HRF be treated as an impulse response, so the character and temporal stability of the HRF are critical issues. Here, a simple audiovisual stimulus combined with a fast-paced task was used to evoke a strong HRF across a majority, ∼77%, of cortex during a single scanning session. High spatiotemporal resolution (2-mm voxels, 1.25-s acquisition time) was used to focus HRF measurements specifically on the gray matter for whole brain. The majority of activated cortex responds with positive HRFs, while ∼27% responds with negative (inverted) HRFs. Spatial patterns of the HRF response amplitudes were found to be similar across subjects. Timing of the initial positive lobe of the HRF was relatively stable across the cortical surface with a mean of 6.1 ± 0.6 s across subjects, yet small but significant timing variations were also evident in specific regions of cortex. The results provide guidance for linear analysis of fMRI data. More importantly, this method provides a means to quantify neurovascular function across most of the brain, with potential clinical utility for the diagnosis of brain pathologies such as traumatic brain injury.
... The magnitude of the slow responses of HbR in Figure 2, and many in Figure S2, appear to be more constant than the slow responses of HbO and HbT (though, in TA S1H S1FL S1HL S1B S1T RS MP PP V2M S1SH LP M2 M1 S1BL S1FL S1BM RS V1 A M2 M1 S1BL S1FL S1BM RS V1 A durations (Culver et al. 2005;Desai et al. 2011) (also see Ji et al. 2012). It has been suggested (Pfeuffer et al. 2003) that the early onset responses following stimulation originate in gray matter, while longer latency responses are of vascular origin. The role of the vasculature itself as part of the neurovascular coupling chain is becoming increasingly emphasized. ...
Brain connectomics has expanded from histological assessment of axonal projection connectivity (APC) to encompass resting state functional connectivity (RS-FC). RS-FC analyses are efficient for whole-brain mapping, but attempts to explain aspects of RS-FC (e.g., interhemispheric RS-FC) based on APC have been only partially successful. Neuroimaging with hemoglobin alone lacks specificity for determining how activity in a population of cells contributes to RS-FC. Wide-field mapping of optogenetically defined connectivity could provide insights into the brain's structure-function relationship. We combined optogenetics with optical intrinsic signal imaging to create an efficient, optogenetic effective connectivity (Opto-EC) mapping assay. We examined EC patterns of excitatory neurons in awake, Thy1-ChR2 transgenic mice. These Thy1-based EC (Thy1-EC) patterns were evaluated against RS-FC over the cortex. Compared to RS-FC, Thy1-EC exhibited increased spatial specificity, reduced interhemispheric connectivity in regions with strong RS-FC, and appreciable connection strength asymmetry. Comparing the topography of Thy1-EC and RS-FC patterns to maps of APC revealed that Thy1-EC more closely resembled APC than did RS-FC. The more general method of Opto-EC mapping with hemoglobin can be determined for 100 sites in single animals in under an hour, and is amenable to other neuroimaging modalities. Opto-EC mapping represents a powerful strategy for examining evolving connectivity-related circuit plasticity.
... Using a fast event-related fMRI design and short stimulation durations (0.25s), detailed characterization of the BOLD response was achieved within an acceptable scan time for human participants (10min). Here, short stimulation duration and appropriately chosen inter-stimulus intervals (ISI) (>2.5s) are advised to avoid nonlinearities and large passive blood accumulation in the venous vasculature (Hirano et al., 2011;Miezin et al., 2000;Pfeuffer et al., 2003). The findings by Siero et al. are largely in line with findings in animal work. ...
The rapid developments in functional MRI (fMRI) acquisition methods and hardware technologies in recent years, particularly at high field (≥7 T), have enabled unparalleled visualization of functional detail at a laminar or columnar level, bringing fMRI close to the intrinsic resolution of brain function. These advances highlight the potential of high resolution fMRI to be a valuable tool to study the fundamental processing performed in cortical micro-circuits, and their interactions such as feedforward and feedback processes. Notably, because fMRI measures neuronal activity via hemodynamics, the ultimate resolution it affords depends on the spatial specificity of hemodynamics to neuronal activity at a detailed spatial scale, and by the evolution of this specificity over time. Several laminar (≤1 mm spatial resolution) fMRI studies have examined spatial characteristics of the measured hemodynamic signals across cortical depth, in light of understanding or improving the spatial specificity of laminar fMRI. Few studies have examined temporal features of the hemodynamic response across cortical depth. Temporal features of the hemodynamic response offer an additional means to improve the specificity of fMRI, and could help target neuronal processes and neurovascular coupling relationships across laminae, for example by differences in the onset times of the response across cortical depth. In this review, we discuss factors that affect the timing of neuronal and hemodynamic responses across laminae, touching on the neuronal laminar organization, and focusing on the laminar vascular organization. We provide an overview of hemodynamics across the cortical vascular tree based on optical imaging studies, and review temporal aspects of hemodynamics that have been examined across cortical depth in high spatiotemporal resolution fMRI studies. Last, we discuss the limits and potential of high spatiotemporal resolution fMRI to study laminar neurovascular coupling and neuronal processes.
... The prediction was generate by linear convolution of the recorded LFP signal with a hemodynamic response function (see Logothetis, 2002, for details). flickering stimulation was inferred by Pfeuffer et al. (2003) from the pattern of variations in BOLD response amplitude as a function of stimulus duration. ...
... The prediction was generate by linear convolution of the recorded LFP signal with a hemodynamic response function (see Logothetis, 2002, for details). flickering stimulation was inferred by Pfeuffer et al. (2003) from the pattern of variations in BOLD response amplitude as a function of stimulus duration. ...
The coupling of the neuronal energetics to the blood-oxygen-level-dependent (BOLD) response is still incompletely understood. To address this issue, we compared the fits of four plausible models of neurometabolic coupling dynamics to available data for simultaneous recordings of the local field potential and the local BOLD response recorded from monkey primary visual cortex over a wide range of stimulus durations. The four models of the metabolic demand driving the BOLD response were: direct coupling with the overall LFP; rectified coupling to the LFP; coupling with a slow adaptive component of the implied neural population response; and coupling with the non-adaptive intracellular input signal defined by the stimulus time course. Taking all stimulus durations into account, the results imply that the BOLD response is most closely coupled with metabolic demand derived from the intracellular input waveform, without significant influence from the adaptive transients and nonlinearities exhibited by the LFP waveform.
... Secondly, whereas the duration was varied every 200 ms among the six intervals for the supra-second condition, it was varied only every 50 ms for the sub-second condition. Third, the overall duration of a trial was shorter for the sub-second than supra-second condition, thereby potentially reducing BOLD signal in this condition (Pfeuffer, et al. 2003). Together, these factors may have obscured the differential activity in response to the sub-second condition. ...
... Finally, fMRI does have a somewhat limited degree of time resolution, usually between 1 and 4 seconds, due to signal/noise problems that emerge. Additionally, higher temporal resolutions have revealed nonlinearities in the BOLD signal and the normalization of the BOLD signal takes between 16 and 20 seconds, creating similar temporal resolution problems (Pfeuffer et al., 2003). While other imaging techniques with better temporal resolution, such as event-related potential (ERP) measurements, can be used in conjunction with fMRI, a number of practical issues emerge due to the use of strong magnetic fields (Schreiber, personal conversation). ...
English
Political scientists have access to a number of competing methodologies that marshal different forms of evidence for their arguments about political phenomena. Recently a new form of evidence has appeared in political science research and, more frequently, economics: spatially explicit and time-varying neurological activity of human subjects engaged in political or economic decision-making. As with any of the more standard methodologies, this approach carries with it a set of orienting theories linking hypotheses with the types of data induced to support or falsify these theories. While this new form of evidence is exciting, especially for the empirically minded social scientist, it deserves the utmost scrutiny. I provide a review of how neurological imaging is being used in the social sciences and consider several problems and prospects of using neuroimaging data in political science.
French
Les sciences politiques ont recours à des méthodes de recherche et à des évidences empiriques diverses pour étudier les phénomènes politiques. Récemment, les chercheurs en sciences politiques et plus souvent encore en économie se sont tout particulièrement intéressés à l'activité cérébrale, objectivable dans l'espace et variant dans le temps, de sujets humains en situation de prise de décision politique ou économique. Comme toute autre méthode de recherche, cette approche s'appuie sur des orientations théoriques, qui font le lien entre les hypothèses de recherche et les données destinées à étayer ou invalider ces théories. Si cette approche nouvelle semble prometteuse, tout particulièrement pour les chercheurs à l'esprit empirique, elle mérite d'être examinée en profondeur. L'article fait le point sur l'utilisation des résultats de l'imagerie cérébrale fonctionnelle en sciences sociales et considère les différents problèmes qu'elle pose ainsi que les perspectives nouvelles qu'elle peut offrir en sciences politiques.
... In [8], the conclusion (based on visual and motor tasks) was that probably both the neural and the hemodynamic activity were non-linear. The results presented here seem rather to indicate that the non-linearity is first and foremost in the hemodynamics, yet again underlining the dependence of the results on the exact task and setup (see also [64]). ...
... BOLD signal responses to a visual stimuli with different stimuli duration times (250,500,1000 and 2000 ms). Longer stimuli duration times results in lower amplitude and duration of the signal response (redrawn from Pfeuffer et al 2003 ...
... As mentioned earlier, superposition is approximately satisfied if the intertrial interval exceeds one second and if brief stimulus exposure durations are avoided (Vazquez & Noll, 1998). However, if stimulus events quickly follow one another, or if brief stimulus exposure durations are used, then it is well documented that the BOLD signal exhibits significant nonlinearities (Hinrichs et al., 2000;Huettel & McCarthy, 2000;Ogawa et al., 2000;Pfeuffer et al., 2003). ...
... BOLD non-linearity has been demonstrated at short timescales (Miller et al., 2001;Pfeuffer, McCullough, Van de Moortele, Ugurbil, & Hu, 2003;Vazquez & Noll, 1998;Wager, Vazquez, Hernandez, & Noll, 2005). Transient hemodynamic effects may contribute to such a non-linearity (Friston, Josephs, Rees, & Turner, 1998;Friston, Mechelli, Turner, & Price, 2000;Gu et al., 2005). ...
Prolonged visual stimulation results in neurophysiologic and hemodynamic adaptation. However, the hemodynamic adaptation appears to be small compared to neural adaptation. It is not clear how the cerebral metabolic rate of oxygen (CMRO2) is affected by adaptation. We measured cerebral blood flow (CBF) and CMRO2 change in responses to peripheral stimulation either continuously, or intermittently (on/off cycles). A linear system's response to the continuous input should be equal to the sum of the original response to the intermittent input and a version of that response shifted by half a cycle. The CMRO2 response showed a large non-linearity consistent with adaptation, the CBF response adapted to a lesser degree, and the blood oxygenation level dependent (BOLD) response was nearly linear. The metabolic response was coupled with a larger flow in the continuous condition than in the intermittent condition. Our results suggest that contrast adaptation improves energy economy of visual processing. However BOLD modulations may not accurately represent the underlying metabolic nonlinearity due to modulation of the coupling of blood flow and oxygen metabolism changes.
... The stimulus onset was uniformly jittered relative to the TR, yielding a sub-TR temporal resolution of 220 ms. Short stimuli together with a minimal ISI of 2.9 s will yield a narrow HRF with minimal hemodynamic nonlinearities [15,25,26]. All conditions included a central red fixation point. ...
High-field gradient-echo (GE) BOLD fMRI enables very high resolution imaging, and has great potential for detailed investigations of brain function. However, as spatial resolution increases, confounds due to signal from non-capillary vessels increasingly impact the fidelity of GE BOLD fMRI signals. Here we report on an assessment of the microvascular weighting of the GE BOLD response across the cortical depth in human cortex using spin-echo fMRI which is thought to be dominated by microvasculature (albeit not completely). BOLD responses were measured with a hemodynamic impulse response (HRF) obtained from the spin-echo (SE) and gradient-echo (GE) BOLD contrast using very short stimuli (0.25 s) and a fast event-related functional paradigm. We show that the onset (∼1.25 s) and the rising slope of the GE and SE HRFs are strikingly similar for voxels in deep gray matter presumably containing the most metabolically demanding neurons (layers III-IV). This finding provides a strong indication that the onset of the GE HRF in deep gray matter is predominantly associated with microvasculature.
... Divergent conclusions have been made on the linearity of neurovascular coupling regarding the durations of stimuli. Considerable fMRI studies on humans showed that neurovascular coupling is nonlinear for short durations but linear for long durations [38,39,40]. However, opposite results were reported on animal models [37]. ...
While functional imaging is widely used in studies of the brain, how well the hemodynamic signal represents the underlying neural activity is still unclear. And there is a debate on whether hemodynamic signal is more tightly related to synaptic activity or action potentials. This study intends to address these questions by examining neurovascular coupling driven by pyramidal cells in the motor cortex of rats. Pyramidal cells in the motor cortex of rats were selectively transduced with the light sensitive cation channel channelrhodopsin-2 (ChR2). Electrophysiological recordings and optical intrinsic signal imaging were performed simultaneously and synchronously to capture the neural activity and hemodynamics induced by optical stimulation of ChR2-expressing pyramidal cells. Our results indicate that both synaptic activity (local field potential, LFP) and action potentials (multi-unit activity, MUA) are tightly related to hemodynamic signals. While LFPs in γ band are better in predicting hemodynamic signals elicited by short stimuli, MUA has better predictions to hemodynamic signals elicited by long stimuli. Our results also indicate that strong nonlinearity exists in neurovascular coupling.
... A voxel which did not exceed this threshold for every combination was excluded from the ROI. While there is spatial heterogeneity of BOLD responses within an ROI (Birn et al., 2001; Pfeuffer et al., 2003), we utilized a relatively large ROI (on average 159 voxels per ROI) for our fMRI analyses to mirror the large ROI used in our MEG analyses. Time courses of voxels in each subject's ROI were averaged for each combination of stimulus and ramp condition. ...
While recent analysis of functional magnetic resonance imaging (fMRI) data utilize a generalized nonlinear convolution model (e.g., dynamic causal modeling), most conventional analyses of local responses utilize a linear convolution model (e.g., the general linear model). These models assume a linear relationship between the blood oxygenated level dependent (BOLD) signal and the underlying neuronal response. While previous studies have shown that this “neurovascular coupling” process is approximately linear, short stimulus durations are known to produce a larger fMRI response than expected from a linear system. This divergence from linearity between the stimulus time-course and BOLD signal could be caused by neuronal onset and offset transients, rather than a nonlinearity in the hemodynamics related to BOLD contrast. We tested this hypothesis by measuring MEG and fMRI responses to stimuli with ramped contrast onsets and offsets in place of abrupt transitions. MEG results show that the ramp successfully reduced the transient onset of neural activity. However, the nonlinearity in the fMRI response, while also reduced, remained. Predictions of fMRI responses from MEG signals show a weaker nonlinearity than observed in the actual fMRI data. These results suggest that the fMRI BOLD nonlinearity seen with short duration stimuli is not solely due to transient neuronal activity. © 2008 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 18, 17–28, 2008
... The ability to map the areas of brain function with unprecendeted resolution was demonstrated through a series of functional studies of the visual cortex. 48 The spatial accuracy of the high-field, high-resolution images, 49 however, may be affected by magnetic field and image-to-image fluctuations. Functional mapping at 7 T demonstrated resolution at the level of orientation and ocular dominance columns in visual cortex. ...
As the race for increased magnetic field strength continues, ultra high field magnetic resonance systems are entering the
clinical arena. Human brain imaging at ultra high field (7, 8, and 9.4 Tesla) offers an unprecedented resolution for anatomical
imaging that approaches in-vivo microscopy. Results from healthy volunteers and from stroke and tumor studies have demonstrated
that high field MRI can visualize microvasculature, details of pathological conditions, and iron deposits with a resolution
not obtainable at lower fields. High-resolution maps of brain function and biochemical markers have been obtained at 7 Tesla.
Clinical brain imaging is feasible at ultra high magnetic field, but more studies need to be done to determine its diagnostic
potential.
... We dampened the impact of temporal nonlinearities in our experimental design by the use of a 4-s bin duration. This is because deviations from linearity are large only at short-stimulus durations [Birn et al., 2001;Boynton et al., 1996;Pfeuffer et al., 2003;Vazquez and Noll, 1998]. Whereas the response to a moderate-length stimulus (4 s) well predicts the response to a longer stimulus (8 s), the response to a short stimulus (1 s) poorly predicts the response to a longer stimulus (2 s). ...
Functional magnetic resonance imaging (fMRI) suffers from many problems that make signal estimation difficult. These include variation in the hemodynamic response across voxels and low signal-to-noise ratio (SNR). We evaluate several analysis techniques that address these problems for event-related fMRI. (1) Many fMRI analyses assume a canonical hemodynamic response function, but this assumption may lead to inaccurate data models. By adopting the finite impulse response model, we show that voxel-specific hemodynamic response functions can be estimated directly from the data. (2) There is a large amount of low-frequency noise fluctuation (LFF) in blood oxygenation level dependent (BOLD) time-series data. To compensate for this problem, we use polynomials as regressors for LFF. We show that this technique substantially improves SNR and is more accurate than high-pass filtering of the data. (3) Model overfitting is a problem for the finite impulse response model because of the low SNR of the BOLD response. To reduce overfitting, we estimate a hemodynamic response timecourse for each voxel and incorporate the constraint of time-event separability, the constraint that hemodynamic responses across event types are identical up to a scale factor. We show that this technique substantially improves the accuracy of hemodynamic response estimates and can be computed efficiently. For the analysis techniques we present, we evaluate improvement in modeling accuracy via 10-fold cross-validation.
Functional near-infrared spectroscopy (fNIRS) is an increasingly popular method in hearing research. However, few studies have considered efficient stimulation parameters for the auditory experimental design of fNIRS. The objectives of our study are (1) to identify the most effective paradigm for the stimulation blocks with increasing duration (8s, 10s, 15s, 20s) in terms of response amplitude, i.e., the most-efficient stimulation duration; (2) to assess the linearity/nonlinearity of the hemodynamic responses with respect to increasing block durations; and (3) to generalize results to more ecological environmental stimuli. We found that cortical activity is augmented following the increments in stimulation durations and reaches a plateau after about 15s of stimulation. The linearity analysis showed that this augmentation due to stimulation duration is not linear in the auditory cortex, non-linearity being more pronounced for longer durations (15s and 20s). The 15s block duration that we propose as the most suitable precludes signal saturation and is associated with a high response amplitude and a relatively short total experimental duration. Moreover, the distribution of stimuli among the 15s blocks remains the most effective for white noise stimulation and also provides a comparably strong response for environmental sounds. The sum of these findings suggests that 15s stimulation duration used in the appropriate experimental setup allows researchers to acquire optimal fNIRS signal quality.
Fast fMRI enables the detection of neural dynamics over timescales of hundreds of milliseconds, suggesting it may provide a new avenue for studying subsecond neural processes in the human brain. The magnitudes of these fast fMRI dynamics are far greater than predicted by canonical models of the hemodynamic response. Several studies have established nonlinear properties of the hemodynamic response that have significant implications for fast fMRI. We first review nonlinear properties of the hemodynamic response function that may underlie fast fMRI signals. We then illustrate the breakdown of canonical hemodynamic response models in the context of fast neural dynamics. We will then argue that the canonical hemodynamic response function is not likely to reflect the BOLD response to neuronal activity driven by sparse or naturalistic stimuli or perhaps to spontaneous neuronal fluctuations in the resting state. These properties suggest that fast fMRI is capable of tracking surprisingly fast neuronal dynamics, and we discuss the neuroscientific questions that could be addressed using this approach.
Functional magnetic resonance imaging (fMRI) is commonly thought to be too slow to capture any neural dynamics faster than 0.1 Hz. However, recent findings demonstrate the feasibility of detecting fMRI activity at higher frequencies beyond 0.2 Hz. The origin, reliability, and generalizability of fast fMRI responses are still under debate and await confirmation through animal experiments with fMRI and invasive electrophysiology. Here, we acquired single-echo and multi-echo fMRI, as well as local field potentials, from anesthetized rat brains given gastric electrical stimulation modulated at 0.2, 0.4 and 0.8 Hz. Such gastric stimuli could drive widespread fMRI responses at corresponding frequencies from the somatosensory and cingulate cortices. Such fast fMRI responses were linearly dependent on echo times and thus indicative of blood oxygenation level dependent nature (BOLD). Local field potentials recorded during the same gastric stimuli revealed transient and phase-locked broadband neural responses, preceding the fMRI responses by as short as 0.5 s. Taken together, these results suggest that gastric stimulation can drive widespread and rapid fMRI responses of BOLD and neural origin, lending support to the feasibility of using fMRI to detect rapid changes in neural activity up to 0.8 Hz under visceral stimulation.
Recent developments in fMRI acquisition techniques now enable fast sampling with whole-brain coverage, suggesting fMRI can be used to track changes in neural activity at increasingly rapid timescales. When images are acquired at fast rates, the limiting factor for fMRI temporal resolution is the speed of the hemodynamic response. Given that HRFs may vary substantially in subcortical structures, characterizing the speed of subcortical hemodynamic responses, and how the hemodynamic response shape changes with stimulus duration (i.e. the hemodynamic nonlinearity), is needed for designing and interpreting fast fMRI studies of these regions. We studied the temporal properties and nonlinearities of the hemodynamic response function (HRF) across the human subcortical visual system, imaging superior colliculus (SC), lateral geniculate nucleus of the thalamus (LGN) and primary visual cortex (V1) with high spatiotemporal resolution 7 Tesla fMRI. By presenting stimuli of varying durations, we mapped the timing and nonlinearity of hemodynamic responses in these structures at high spatiotemporal resolution. We found that the hemodynamic response is consistently faster and narrower in subcortical structures than in cortex. However, the nonlinearity in LGN is similar to that in cortex, with shorter duration stimuli eliciting larger and faster responses than would have been predicted by a linear model. Using oscillatory visual stimuli, we tested the frequency response in LGN and found that its BOLD response tracked high-frequency (0.5 Hz) oscillations. The LGN response magnitudes were comparable to V1, allowing oscillatory BOLD signals to be detected in LGN despite the small size of this structure. These results suggest that the increase in the speed and amplitude of the hemodynamic response when neural activity is brief may be the key physiological driver of fast fMRI signals, enabling detection of high-frequency oscillations with fMRI. We conclude that subcortical visual structures exhibit fast and nonlinear hemodynamic responses, and that these dynamics enable detection of fast BOLD signals even within small deep brain structures when imaging is performed at ultra-high field.
Receptive fields (RFs) in visual cortex are organized in antagonistic, center-surround, configurations. RF properties change systematically across eccentricity and between visual field maps. However, it is unknown how center-surround configurations are organized in human visual cortex across lamina. We use sub-millimeter resolution functional MRI at 7 Tesla and population receptive field (pRF) modeling to investigate the pRF properties in primary visual cortex (V1) across cortical depth. pRF size varies according to a U-shaped function, indicating smaller pRF center size in the middle compared to superficial and deeper intra-cortical portions of V1, consistent with non-human primate neurophysiological measurements. Moreover, a similar U-shaped function is also observed for pRF surround size. However, pRF center-surround ratio remains constant across cortical depth. Simulations suggest that this pattern of results can be directly linked to the flow of signals across cortical depth, with the visual input reaching the middle of cortical depth and then spreading towards superficial and deeper layers of V1. Conversely, blood-oxygenation-level-dependent (BOLD) signal amplitude increases monotonically towards the pial surface, in line with the known vascular organization across cortical depth. Independent estimates of the haemodynamic response function (HRF) across cortical depth show that the center-surround pRF size estimates across cortical depth cannot be explained by variations in the full-width half maximum (FWHM) of the HRF.
The last decade has seen an unprecedented increase in the use of functional magnetic resonance imaging (fMRI) to understand the neural basis of cognition and behavior. Being non-invasive and relatively easy to use, most studies relied on changes in the blood oxygenation level dependent (BOLD) contrast as an indirect marker of variations in brain activity. However, the fact that BOLD fMRI is dependent on the blood flow response that follows neural activity and does not measure neural activity per se is seen as an inherent cause for concern while interpreting data from these studies. In order to characterize the BOLD signal correctly, it is imperative that we have a better understanding of neural events that lead to the BOLD response. A review of recent studies that addressed several aspects of BOLD fMRI including events at the level of the synapse, the nature of the neurovascular coupling, and some parameters of the BOLD signal is provided. This is intended to serve as background information for the interpretation of fMRI data in normal Subjects and in patients with compromised neurovascular Coupling. One of the aims is also to encourage researchers to interpret the results of functional imaging studies in light of the dynamic interactions between different brain regions, something that often is neglected. (c) 2005 Elsevier B.V. All rights reserved.
There is a wide range of functional magnetic resonance imaging (fMRI) study designs available for the neuroscientist who wants to investigate cognition. In this manuscript we review some aspects of fMRI study design, including cognitive comparison strategies (factorial, parametric designs), and stimulus presentation possibilities (block, event-related, rapid event-related, mixed, and self-driven experiment designs) along with technical aspects, such as limitations of signal to noise ratio, spatial, and temporal resolution. We also discuss methods to deal with cases where scanning parameters become the limiting factor (parallel acquisitions, variable jittered designs, scanner acoustic noise strategies).
The functional magnetic resonance imaging (fMRI) based on blood oxygen level dependent (BOLD) contrast has emerged as one of the most potent noninvasive tools for mapping brain function and has been widely used to explore physiological, pathological changes and mental activity in the brain. Exploring the nature and property of BOLD signal has recently attracted more attentions. Despite that great progress has been made in investigation of the characteristics and neurophysiological basis, the exact nature of BOLD signal remains unclear. In this paper we discuss the characteristics of BOLD signals, the nonlinear BOLD response to external stimuli and the relation between BOLD signals and neural electrophysiological recordings. Furthermore, we develop our new opinions regarding nonlinear BOLD response and make some perspectives on future study.
In recent years, social scientists have begun exploring the neurological foundations of behavior in an attempt to gain a more complete understanding of decision-making in the realms of both politics and economics (see Cacioppo & Viser, 2003; Fowler & Schreiber, 2008; McDermott, 2009; Caplin & Schotter, 2008).
A widely held assumption is that spontaneous and task-evoked brain activity sum linearly, such that the recorded brain response in each single trial is the algebraic sum of the constantly changing ongoing activity and the stereotypical evoked activity. Using functional magnetic resonance imaging signals acquired from normal humans, we show that this assumption is invalid. Across widespread cortices, evoked activity interacts negatively with ongoing activity, such that higher prestimulus baseline results in less activation or more deactivation. As a consequence of this negative interaction, trial-to-trial variability of cortical activity decreases following stimulus onset. We further show that variability reduction follows overlapping but distinct spatial pattern from that of task-activation/deactivation and it contains behaviorally relevant information. These results favor an alternative perspective to the traditional dichotomous framework of ongoing and evoked activity. That is, to view the brain as a nonlinear dynamical system whose trajectory is tighter when performing a task. Further, incoming sensory stimuli modulate the brain's activity in a manner that depends on its initial state. We propose that across-trial variability may provide a new approach to brain mapping in the context of cognitive experiments.
The sensory evoked neuromagnetic response consists of superimposition of an immediately stimulus-driven component and induced changes in the autonomous brain activity, each having distinct functional relevance. Commonly, the strength of phase locking in neural activities has been used to differentiate the different responses. The steady-state response is a strong oscillatory neural activity, which is evoked with rhythmic stimulation, and provides an effective tool to investigate oscillatory brain networks. In this case, both the sensory response and intrinsic activity, representing higher order processes, are highly synchronized to the stimulus. In this study we hypothesized that temporal dynamics of oscillatory activities would characterize the differences between the two types of activities and that beta and gamma oscillations are differently involved in this distinction.
In the last two decades, magnetic resonance imaging (MRI) instruments operating at a magnetic field strength of 1.5 Tesla
have emerged as the most commonly employed high-end platform for clinical diagnosis. Despite the dominant position enjoyed
by this field strength, even its promotion as the “optimum” field to work for human applications, the late 1980s witnessed
the beginnings of an interest in substantially higher magnetic fields. After brief and cursory explorations, however, high
field strengths were virtually abandoned by industry leaders while their efforts were focused on further refinements of the
1.5T or even lower field platforms. Nevertheless, a handful of 3 and 4-Tesla instruments were established in academic research
laboratories by about 1990. Since these early beginnings, work conducted in these academic sites has demonstrated that magnetic
fields substantially beyond 1.5 Tesla provide numerous advantages in aspects of magnetic resonance imaging and spectroscopy
(MRS) applications in humans, even though such high fields also pose serious challenges. In considering these accomplishments,
however, it is imperative to recognize that, to date, virtually all of the research at high magnetic fields, especially at
field strengths greater than 3 Tesla, has been carried out only in a few laboratories and using instruments that are definitely
far less than optimized; as such, the amount of man-hours and talent dedicated to this effort has been minuscule compared
to the clinical uses of MR and, even then, this effort has been hampered by suboptimal instrumentation. Therefore, any positive
conclusions obtained thus far, and there are many, can only be interpreted as harbingers of potential gains and definitely
not as what can be ultimately achieved.
In this work, a nonlinear dynamics method, coupled map lattices, was applied to functional magnetic resonance imaging (fMRI) datasets to examine the spatiotemporal properties of resting state blood oxygen level-dependent (BOLD) fluctuations. Spatiotemporal Lyapunov Exponent (SPLE) was calculated to study the deterministic nonlinearity in resting state human brain of nine subjects based on fMRI datasets. The results show that there is nonlinearity and determinism in resting state human brain. Furthermore, the results demonstrate that there is a spatiotemporal chaos phenomenon in resting state brain, and suggest that fluctuations of fMRI data in resting state brain cannot be fully attributed to nuclear magnetic resonance noise. At the same time, the spatiotemporal chaos phenomenon suggests that the correlation between voxels varies with time and there is a dynamic functional connection or network in resting state human brain.
During the past 20 years, BOLD fMRI has developed towards a central and fundamental tool in neuroscience. It has been shown that the BOLD response provides an indicator of neuronal activity in the brain. Consequently, for an accurate interpretation of findings in BOLD MRI experiments and to draw meaningful conclusions about the temporal evolution of neural events, a deep understanding of the nature of the BOLD contrast has become of essential importance. Since the dynamics of the major direct determinants of the BOLD signal (CBF, CBV and CMRO(2)) range between seconds and minutes, long duration stimulation was an early key strategy needed to study and understand the BOLD characteristics. This paper summarizes and discusses the thoughts and rationales of the long duration stimulation studies.
The dysfunction in anxiety disease has been widely observed in clinics, but the underlying neural mechanism is not yet well understood. Function MRI data were collected conventionally 'imperfectly' with low frequency and short scans when participants were processing our experimental tasks. In order to find the nonlinear differences, we here propose the spatiotemporal Lyapunov exponent as a quantitative measure. Our result reveals that there are significant differences between the two groups. We conclude that: (1) spatiotemporal Lyapunov exponent could be used to explore nonlinear character of conventional 'imperfect' fMRI data; (2) the abnormal nonlinear dynamic behavior exists in bilateral temporal lobes when patients are taking our experimental tasks.
To evaluate whether hemodynamic refractory effects provoked by repeated visual stimulation can be detected and quantified at the single-subject level using a recently described hemodynamic response function (HRF) fitting algorithm.
Hemodynamic refractory effects were induced with an easily applicable functional MRI (fMRI) paradigm. A fitting method with inverse logit (IL) functions was applied to quantify net HRFs at the single-subject level with three interstimulus intervals (ISI; 1, 2, and 6 s). The model yielded amplitude, latencies, and width for each HRF.
HRF fitting was possible in 44 of 51 healthy volunteers, with excellent goodness-of-fit (R(2) = 0.9745 ± 0.0241). Refractory effects were most pronounced for the 1-s ISI (P < 0.001) and had nearly disappeared for the 6-s ISI.
Quantifying refractory effects in individuals was possible in 86.3% of normal subjects using the IL fitting algorithm. This setup may be suitable to explore such effects in individual patients.
Introduction Recently actively switched volume coil/ surface coil combinations have been developed for very high field systems such as 4 Tesla [1,2,3]. To improve patient comfort, task presentation, RF power requirements, and to perform high resolution imaging studies that required high penetration and relatively uniform excitation and inversion it was desirable to develop an actively switched quadrature half-volume transmit/ receive coil combination for 7 Tesla. Methods The quadrature transmit coil consisted of two 18x12 cm 2 coils built with 14 distributed capacitors [4]. The RF shield was incorporated into the resonance structure similar to coils previously described by Vaughan [5,6]. PIN diodes (M/A Com MA4PK2003) short-circuited each resonant loop structure in three locations to the RF shield for active transmitter detuning. The receive surface coils were detuned with a resonant trap circuit. All diodes were biased through RF chokes. We built linear and quadrature receive surface coils of 6 cm, 8 cm and 10 cm loop diameter using copper tape and high Q ceramic capacitors. The receiver coils were then mounted into a separate housing to allow for position adjustments relative to the transmit coil (Fig. 1). A Siemens PIN driver board (Erlangen, Germany) controlled by TTL signals from the console was used for all experiments. Experiments were performed on a 7 Tesla/ 90 cm magnet with a 38 cm i.d. head gradient coil (Magnex Scientific, UK) and a Siemens gradient amplifier interfaced to a Varian INOVA console (Palo Alto, CA). Results Coil decoupling of more than -30dB between the transmit coil and the receive coils with a phantom or a human head as a load was routinely achieved. The coil decoupling was independent of the relative receive coil position to the transmit coil, thus further indicating excellent isolation. Active PIN diode circuits switch the half-volume coil to one of three modes: transmit only, receive only, and transmit / receive. The receiver coils were similarly controlled. The transmit coil registered a 90 0 pulse power calibration in the human head of 57 W RF power for a 4ms sinc pulse. The combination coil yielded an increase in FOV compared to a T/R surface coil as observed in Figure 2. The transmit coil was able to provide complete inversion for the entire volume seen by the quadrature receive coils as observed in Figure 3. In the ROI we found that the combination coil improved the SNR up to 5-fold as compared to a half-volume coil in T/R mode. For regions up to 2 cm depth the SNR of the combination coil and a small T/R surface coil are comparable, however the SNR observed with the combination coil for regions deeper was found to be ~ 20% higher. Discussion An actively switched half-volume combination coil was found to improve the sensitivity significantly compared to T/R coils of the same size. Task presentation and patient comfort are improved because of the 'open face' appearance of the coil. The incorporation of the RF shield into the coil resonance structure was critical for coil homogenenity and RF perfomance at 300 MHz. Applications, which require homogeneous RF fields and inversion over large regions, such as CBF mapping and SE fMRI benefit in particular. Supported by NIH P41 RR08079, RO1 MH55346 and the W.M. Keck Foundation Fig. 1 The coil former is shown with a dielectric mirror for task presentation. The housing of the receive coils allows for +/-20 0 rotation in position relative from the center of the transmit coil. Fig. 2 Axial TurboFLASH images of a phantom (NMR tubes,14 cm diameter) and the human head acquired with the combination coil in different modes. The human head images were inversion prepared (FOV: 20x20cm 2 , 256x256, TI =1.5s). Fig. 3 Proton density image of a sagittal slice in the human head, acquired with the combination coil. A 2-cm wide slab is inverted perpendicular to the imaging plane, which edges can be seen as dark stripes. Any incomplete inversion would result in loss of signal within the slab.
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.
Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contrast has progressed rapidly and is commonly used to study function in many regions of the human brain. This paper introduces a method for characterizing the linear and nonlinear properties of the hemodynamic response. Such characterization is essential for accurate prediction of time-course behavior. Linearity of the BOLD response was examined in the primary visual cortex for manipulations of the stimulus amplitude and duration. Stimuli of 1, 2, 4, and 8 s duration (80% contrast) and 10, 20, 40, and 80% contrast (4 s duration) were used to test the hemodynamic response. Superposition of the obtained responses was performed to determine if the BOLD response is nonlinear. The nonlinear characteristics of the BOLD response were assessed using a Laplacian linear system model cascaded with a broadening function. Discrepancies between the model and the observed response provide an indirect measure of the nonlinearity of the response. The Laplacian linear system remained constant within subjects so the broadening function can be used to absorb nonlinearities in the response. The results show that visual stimulation under 4 s in duration and less than 40% contrast yield strong nonlinear responses.
The temporal characteristics of the BOLD response in sensorimotor and auditory cortices were measured in subjects performing finger tapping while listening to metronome pacing tones. A repeated trial paradigm was used with stimulus durations of 167 ms to 16 s and intertrial times of 30 s. Both cortical systems were found to be nonlinear in that the response to a long stimulus could not be predicted by convolving the 1-s response with a rectangular function. In the short-time regime, the amplitude of the response varied only slowly with stimulus duration. It was found that this character was predicted with a modification to Buxton's balloon model. Wiener deconvolution was used to deblur the response to concatenated short episodes of finger tapping at different temporal separations and at rates from 1 to 4 Hz. While the measured response curves were distorted by overlap between the individual episodes, the deconvolved response at each rate was found to agree well with separate scans at each of the individual rates. Thus, although the impulse response cannot predict the response to fully overlapping stimuli, linear deconvolution is effective when the stimuli are separated by at least 4 s. The deconvolution filter must be measured for each subject using a short-stimulus paradigm. It is concluded that deconvolution may be effective in diminishing the hemodynamically imposed temporal blurring and may have potential applications in quantitating responses in eventrelated fMRI.
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.
Recent developments towards event-related functional magnetic resonance imaging has greatly extended the range of experimental designs. If the events occur in rapid succession, the corresponding time-locked responses overlap significantly and need to be deconvolved in order to separate the contributions of different events. Here we present a deconvolution approach, which is especially aimed at the analysis of fMRI data where sequence- or context-related responses are expected. For this purpose, we make the assumption of a hemodynamic response function (HDR) with constant yet not predefined shape but with possibly variable amplitudes. This approach reduces the number of variables to be estimated but still keeps the solutions flexible with respect to the shape. Consequently, statistical efficiency is improved. Temporal variations of the HDR strength are directly indicated by the amplitudes derived by the algorithm. Both the estimation efficiency and statistical inference are further supported by an improved estimation of the noise covariance. Using synthesized data sets, both differently shaped HDRs and varying amplitude factors were correctly identified. The gain in statistical sensitivity led to improved ratios of false- and true-positive detection rates for synthetic activations in these data. In an event-related fMRI experiment with a human subject, different HDR amplitudes could be derived corresponding to stimulation at different visual stimulus contrasts. Finally, in a visual spatial attention experiment we obtained different fMRI response amplitudes depending on the sequences of attention conditions.
this article is to understand how the fMRI response relates to neural activity. The vascular source of the fMRI signal places important limits on the technique. Because the hemodynamic response is sluggish, perhaps the fMRI response is proportional to the local average neural activity, averaged over a small region of the brain and averaged over a period of time. We will refer to this as the "linear transform model" of fMRI response. The linear transform model, specialized for a visual area of the brain, is depicted in Figure 1. According to this model, neural activity is a nonlinear function of the contrast of a visual stimulus, but fMRI response is a linear transform (averaged over time) of the neural activity in V1. Noise might be introduced at each stage of the process, but the effects of these individual noises can be summarized by a single noise source that is added to the output.
In this paper, we demonstrate an approach by which some evoked neuronal events can be probed by functional MRI (fMRI) signal with temporal resolution at the time scale of tens of milliseconds. The approach is based on the close relationship between neuronal electrical events and fMRI signal that is experimentally demonstrated in concurrent fMRI and electroencephalographic (EEG) studies conducted in a rat model with forepaw electrical stimulation. We observed a refractory period of neuronal origin in a two-stimuli paradigm: the first stimulation pulse suppressed the evoked activity in both EEG and fMRI signal responding to the subsequent stimulus for a period of several hundred milliseconds. When there was an apparent site-site interaction detected in the evoked EEG signal induced by two stimuli that were primarily targeted to activate two different sites in the brain, fMRI also displayed signal amplitude modulation because of the interactive event. With visual stimulation using two short pulses in the human brain, a similar refractory phenomenon was observed in activated fMRI signals in the primary visual cortex. In addition, for interstimulus intervals shorter than the known latency time of the evoked potential induced by the first stimulus ( approximately 100 ms) in the primary visual cortex of the human brain, the suppression was not present. Thus, by controlling the temporal relation of input tasks, it is possible to study temporal evolution of certain neural events at the time scale of their evoked electrical activity by noninvasive fMRI methodology.
Improvements in B0 mapping and shimming were achieved by measuring the static field information in multiple subsequent echoes generated by an asymmetric echo-planar readout gradient train. With careful compensation, eddy current effects were shown to affect the adjustment of the shim coils minimally. In addition to reducing the time required for field mapping by two-fold, the sensitivity was simultaneously optimized irrespective of the prevalent T*2 present, thereby minimizing the error of the static field measurement to below 0.1 Hz. With adiabatic low flip-angle excitation, the time required for field mapping was below 1 second. Magn Reson Med 43:319–323, 2000. © 2000 Wiley-Liss, Inc.
A technique is described for discriminating blood-oxygen-level-dependent (BOLD) signal changes originating from large venous vessels and those that arise from the cortical parenchyma based on examining the temporal delay of each pixel's response. Photic stimulation experiments were performed with a conventional 1.5 T scanner and correlated each pixel's time-course with sine and cosine functions at the frequency of the stimulus. It was found that the signal in pixels anatomically associated with gray matter was delayed between 4 and 8 s compared with the stimulus, whereas the signal in pixels correlated with visible vessels and sulci was generally delayed from 8 to 14 s. This larger delay is consistent with the longer time required for blood to reach the larger vessels. Finally, stimulus-induced NMR phase changes were observed for the largest vessels, which are attributed to bulk susceptibility shifts.
Recent studies of blood oxygenation level dependent (BOLD) signal responses averaged over a region of interest have demonstrated that the response is nonlinear with respect to stimulus duration. Specifically, shorter duration stimuli produce signal changes larger than expected from a linear system. The focus of this study is to characterize the spatial heterogeneity of this nonlinear effect. A series of MR images of the visual and motor cortexes were acquired during visual stimulation and finger tapping, respectively, at five different stimulus durations (SD). The nonlinearity was assessed by fitting ideal linear responses to the responses at each SD. This amplitude, which is constant for different SD in a linear system, was normalized by the amplitude of the response to a blocked design, thus describing the amount by which the stimulus is larger than predicted from a linear extrapolation of the response to the long duration stimulus. The amplitude of the BOLD response showed a nonlinear behavior that varied considerably and consistently over space, ranging from almost linear to 10 times larger than a linear prediction at short SD. In the motor cortex different nonlinear behavior was found in the primary and supplementary motor cortexes.
A perfusion-based event-related functional MRI method for the study of brain activation is presented. In this method, cerebral blood flow (CBF) was measured using a recently developed multislice arterial spin-labeling (ASL) perfusion imaging method with rapid spiral scanning. Temporal resolution of the perfusion measurement was substantially improved by employing intertrial subtraction and stimulus-shifting schemes. Perfusion and blood oxygenation level-dependent (BOLD) signals were obtained simultaneously by subtracting or adding the control and labeled images, respectively, in the same data sets. The impulse response function (IRF) of perfusion during brain activation was characterized for multiple stimulus durations and compared to the simultaneously acquired BOLD response. The CBF response curve preceded the BOLD curve by 0.21 s in the rising phase and 0.64 s in the falling phase. Linear additivity of the CBF and BOLD responses was assessed with rapidly repeated stimulations within single trials, and departure from linearity was found in both responses, characterized as attenuated amplitude and delayed rising time. Event-related visual and sensorimotor activation experiments were successfully performed with the new perfusion technique.
Using a model of the functional MRI (fMRI) impulse response based on published data, we have demonstrated that the form of the fMRI response to stimuli of freely varied timing can be modeled well by convolution of the impulse response with the behavioral stimulus. The amplitudes of the responses as a function of parametrically varied behavioral conditions are fitted well using a piecewise linear approximation. Use of the combined model, in conjunction with correlation analysis, results in an increase in sensitivity for the MRI study. This approach, based on the well-established methods of linear systems analysis, also allows a quantitative comparison of the response amplitudes across subjects to a broad range of behavioral conditions. Fit parameters, derived from the amplitude data, are relatively insensitive to a variety of MRI-related artifacts and yield results that are compared readily across subjects.
Improvements in Bo mapping and shimming were achieved by measuring the static field information in multiple subsequent echoes generated by an asymmetric echo-planar readout gradient train. With careful compensation, eddy current effects were shown to affect the adjustment of the shim coils minimally. In addition to reducing the time required for field mapping by two-fold, the sensitivity was simultaneously optimized irrespective of the prevalent T2* present, thereby minimizing the error of the static field measurement to below 0.1 Hz. With adiabatic low flip-angle excitation, the time required for field mapping was below 1 second.
We investigated the effects of paired presentations of visual stimuli upon the evoked hemodynamic response of visual cortex measured by magnetic resonance imaging (MRI). Stimuli were identical 500-ms high-contrast checkerboard patterns, presented singly or with an interpair interval (IPI) of 1, 2, 4, or 6 s (onset-to-onset), followed by an intertrial interval of 16-20 s. Images were acquired at 1.5 Tesla using a gradient-echo echoplanar imaging sequence sensitive to blood-oxygenation-level dependent (BOLD) contrast. Single checkerboards evoked a hemodynamic response from visual cortex characterized by a rise at 3 s, peak activation at 5 s, and return to baseline by 10 s. We subtracted subjects' single-stimulus hemodynamic response from their paired-stimulus responses to isolate the contribution of the second stimulus. If the hemodynamic responses were fully additive, the residual should be a time-shifted replica of the single stimulus response. However, the amplitude of the hemodynamic response to the second checkerboard was smaller, and the peak latency was longer, than for the first. Furthermore, the amplitude decrement was dependent upon IPI, such that the response to the second stimulus at 1 s IPI was only 55% of that to a single stimulus, with recovery to 90% at a 6 s IPI. Peak latency was similarly dependent upon IPI with longer latencies observed for shorter IPIs. These results demonstrate an extended refractory period in the hemodynamic response to visual stimuli consistent with that shown previously for neuronal activity measured electrophysiologically.
Changes in cerebral blood flow (CBF) because of functional activation are used as a surrogate for neural activity in many functional neuroimaging studies. In these studies, it is often assumed that the CBF response is a linear-time invariant (LTI) transform of the underlying neural activity. By using a previously developed animal model system of electrical forepaw stimulation in rats (n = 11), laser Doppler measurements of CBF, and somatosensory evoked potentials, measurements of neural activity were obtained when the stimulus duration and intensity were separately varied. These two sets of time series data were used to assess the LTI assumption. The CBF data were modeled as a transform of neural activity (N1-P2 amplitude of the somatosensory evoked potential) by using first-order (linear) and second-order (nonlinear) components. Although a pure LTI model explained a large amount of the variance in the data for changes in stimulus duration, our results demonstrated that the second-order kernel (i.e., a nonlinear component) contributed an explanatory component that is both statistically significant and appreciable in magnitude. For variations in stimulus intensity, a pure LTI model explained almost all of the variance in the CBF data. In particular, the shape of the CBF response did not depend on intensity of neural activity when duration was held constant (time-intensity separability). These results have important implications for the analysis and interpretation of neuroimaging data.
There is a growing appreciation of the importance of nonlinearities in evoked responses in fMRI, particularly with the advent of event-related fMRI. These nonlinearities are commonly expressed as interactions among stimuli that can lead to the suppression and increased latency of responses to a stimulus that are incurred by a preceding stimulus. We have presented previously a model-free characterization of these effects using generic techniques from nonlinear system identification, namely a Volterra series formulation. At the same time Buxton et al. (1998) described a plausible and compelling dynamical model of hemodynamic signal transduction in fMRI. Subsequent work by Mandeville et al. (1999) provided important theoretical and empirical constraints on the form of the dynamic relationship between blood flow and volume that underpins the evolution of the fMRI signal. In this paper we combine these system identification and model-based approaches and ask whether the Balloon model is sufficient to account for the nonlinear behaviors observed in real time series. We conclude that it can, and furthermore the model parameters that ensue are biologically plausible. This conclusion is based on the observation that the Balloon model can produce Volterra kernels that emulate empirical kernels. To enable this evaluation we had to embed the Balloon model in a hemodynamic input-state-output model that included the dynamics of perfusion changes that are contingent on underlying synaptic activation. This paper presents (i) the full hemodynamic model (ii), how its associated Volterra kernels can be derived, and (iii) addresses the model's validity in relation to empirical nonlinear characterizations of evoked responses in fMRI and other neurophysiological constraints.
In this paper, we demonstrate an approach by which some evoked neuronal events can be probed by functional MRI (fMRI) signal with temporal resolution at the time scale of tens of milliseconds. The approach is based on the close relationship between neuronal electrical events and fMRI signal that is experimentally demonstrated in concurrent fMRI and electroencephalographic (EEG) studies conducted in a rat model with forepaw electrical stimulation. We observed a refractory period of neuronal origin in a two-stimuli paradigm: the first stimulation pulse suppressed the evoked activity in both EEG and fMRI signal responding to the subsequent stimulus for a period of several hundred milliseconds. When there was an apparent site-site interaction detected in the evoked EEG signal induced by two stimuli that were primarily targeted to activate two different sites in the brain, fMRI also displayed signal amplitude modulation because of the interactive event. With visual stimulation using two short pulses in the human brain, a similar refractory phenomenon was observed in activated fMRI signals in the primary visual cortex. In addition, for interstimulus intervals shorter than the known latency time of the evoked potential induced by the first stimulus ( approximately 100 ms) in the primary visual cortex of the human brain, the suppression was not present. Thus, by controlling the temporal relation of input tasks, it is possible to study temporal evolution of certain neural events at the time scale of their evoked electrical activity by noninvasive fMRI methodology.
The linearity of the cerebral perfusion response relative to stimulus duration is an important consideration in the characterization of the relationship between regional cerebral blood flow (CBF), cerebral metabolism, and the blood oxygenation level dependent (BOLD) signal. It is also a critical component in the design and analysis of functional neuroimaging studies. To study the linearity of the CBF response to different duration stimuli, the perfusion response in primary motor and visual cortices was measured during stimulation using an arterial spin labeling technique with magnetic resonance imaging (MRI) that allows simultaneous measurement of CBF and BOLD changes. In each study, the perfusion response was measured for stimuli lasting 2, 6, and 18 sec. The CBF response was found in general to be nonlinearly related to stimulus duration, although the strength of nonlinearity varied between the motor and visual cortices. In contrast, the BOLD response was found to be strongly nonlinear in both regions studied, in agreement with previous findings. The observed nonlinearities are consistent with a model with a nonlinear step from stimulus to neural activity, a linear step from neural activity to CBF change, and a nonlinear step from CBF change to BOLD signal change.
This article describes experimental studies performed to demonstrate the feasibility of BOLD fMRI using echo-planar imaging (EPI) at 7 T and to characterize the BOLD response in humans at this ultrahigh magnetic field. Visual stimulation studies were performed in normal subjects using high-resolution multishot EPI sequences. Changes in R(*)(2) arising from visual stimulation were experimentally determined using fMRI measurements obtained at multiple echo times. The results obtained at 7 T were compared to those at 4 T. Experimental data indicate that fMRI can be reliably performed at 7 T and that at this field strength both the sensitivity and spatial specificity of the BOLD response are increased. This study suggests that ultrahigh field MR systems are advantageous for functional mapping in humans. Magn Reson Med 45:588-594, 2001.
A technique is described for performing frequency-selective signal suppression with a high degree of tolerance to RF field inhomogeneity. The method is called B1-insensitive train to obliterate signal (BISTRO). BISTRO consists of multiple amplitude- and frequency-modulated (FM) pulses interleaved with spoiler gradients. BISTRO was developed for the purpose of accomplishing band-selective signal removal, as in water suppression and outer-volume suppression (OVS), in applications requiring the use of an inhomogeneous RF transmitter, such as a surface coil. In the present work, Bloch simulations were used to illustrate the principles and theoretical performance of BISTRO. Its performance for OVS was evaluated experimentally using MRI and spectroscopic imaging of phantoms and in vivo animal and human brain. By using FM pulses featuring offset-independent adiabaticity, BISTRO permitted high-quality, broadband suppression with one (or two) discrete borders demarcating the edge(s) of the suppression band. Simulations and experiments demonstrated the ability to operate BISTRO with reasonably attainable peak RF power levels and with average RF energy deposition similar to other multipulse OVS techniques.
Event-related BOLD fMRI data is modeled as a linear time-invariant system. Together with Bayesian inference techniques, a statistical test is developed for rigorously detecting linearity/nonlinearity in the BOLD response system. The test is applied to data collected from eight subjects using an event-related paradigm with a switching checkerboard as the visual stimulus. Analyzed as a group, the results clearly find the response to be nonlinear. When each subject is analyzed individually, however, the results are predominantly nonlinear, but there is some evidence to suggest that there may be a crossover from a linear to a nonlinear regime and vice versa. This could be important when estimating physiological parameters for individuals. Additionally, estimates of the hemodynamic response function and corresponding response were obtained, but there was no consistent appearance of a poststimulus undershoot in the event-related BOLD response.
Functional magnetic resonance imaging (fMRI) measures the correlation between the fMRI response and stimulus properties. A linear relationship between neural activity and fMRI response is commonly assumed. However, the response to repetitive stimulation cannot be explained by a simple superposition of single-event responses. This might be due to neural adaptation or the hemodynamic changes underlying the fMRI BOLD response. To assess the influence of adaptation, the BOLD responses and visual evoked potentials (VEPs) to identical stimuli were recorded. To achieve different adaptation levels, 2-s stimulus epochs alternated with different interstimulus intervals (ISI = 0.0, 0.4, 0.8, 2.0, and 12 s) were presented. Neural adaptation during the checkerboard reversal paradigm used for fMRI measurements is demonstrated. Even if the measured VEP amplitude is used as the weighting function for a linear model, the measured BOLD fMRI signal time-course is not adequately predicted.
The aim of this work was to investigate the dependence of BOLD responses on different patterns of stimulus input/neuronal changes. In an earlier report, we described an input-state-output model that combined (i) the Balloon/Windkessel model of nonlinear coupling between rCBF and BOLD signals, and (ii) a linear model of how regional flow changes with synaptic activity. In the present investigation, the input-state-output model was used to explore the dependence of simulated PET (rCBF) and fMRI (BOLD) signals on various parameters pertaining to experimental design. Biophysical simulations were used to estimate rCBF and BOLD responses as functions of (a) a prior stimulus, (b) epoch length (for a fixed SOA), (c) SOA (for a fixed number of events), and (d) stimulus amplitude. We also addressed the notion that a single neuronal response may differ, in terms of the relative contributions of early and late neural components, and investigated the effect of (e) the relative size of the late or "endogenous" neural component. We were interested in the estimated average rCBF and BOLD responses per stimulus or event, not in the statistical efficiency with which these responses are detected. The BOLD response was underestimated relative to rCBF with a preceding stimulus, increasing epoch length, and increasing SOA. Furthermore, the BOLD response showed some highly nonlinear behaviour when varying stimulus amplitude, suggesting some form of hemodynamic "rectification." Finally, the BOLD response was underestimated in the context of large late neuronal components. The difference between rCBF and BOLD is attributed to the nonlinear transduction of rCBF to BOLD signal. Our simulations support the idea that varying parameters that specify the experimental design may have differential effects in PET and fMRI. Moreover, they show that fMRI can be asymmetric in its ability to detect deactivations relative to activations when an absolute baseline is stipulated. Finally, our simulations suggest that relative insensitivity to BOLD signal in specific regions, such as the temporal lobe, may be partly explained by higher cognitive functions eliciting a relatively large late endogenous neuronal component.
In functional magnetic resonance imaging, a rapid method such as echo-planar (EPI) or spiral is used to collect a dynamic series of images. These techniques are sensitive to changes in resonance frequency which can arise from respiration and are more significant at high magnetic fields. To decrease the noise from respiration-induced phase and frequency fluctuations, a simple correction of the "dynamic off-resonance in k-space" (DORK) was developed. The correction uses phase information from the center of k-space and a navigator echo and is illustrated with dynamic scans of single-shot and segmented EPI and, for the first time, spiral imaging of the human brain at 7 T. Image noise in the respiratory spectrum was measured with an edge operator. The DORK correction significantly reduced respiration-induced noise (image shift for EPI, blurring for spiral, ghosting for segmented acquisition). While spiral imaging was found to exhibit less noise than EPI before correction, the residual noise after the DORK correction was comparable. The correction is simple to apply and can correct for other sources of frequency drift and fluctuations in dynamic imaging.
Functional neuroimaging in the human brain using noninvasive magnetic resonance methods has the potential of providing highly resolved maps of neuronal activation. Decreasing the voxel size and obtaining simultaneously high temporal resolution is a major challenge and is mainly limited by sensitivity. Here, signal-to-noise gains at high magnetic fields (7 Tesla) and an optimized surface coil setup are combined with a novel approach for zoomed functional imaging in the visual cortex. For echoplanar imaging, the acquisition time and segmentation was shortened fourfold by using a reduced field-of-view. An adiabatic outer-volume suppression method, BISTRO, was used to obliterate signal outside the area-of-interest achieving effective suppression even for inhomogeneous B1-fields. A single-shot acquisition was performed at submillimeter resolution in the human brain, while simultaneously maintaining a high temporal resolution of 125 ms. Functional studies with and without field-of-view reduction were performed. Activation and percent change maps were compared with respect to spatial extent, t values and percentage changes of the BOLD contrast. The detection of functional activation was found to be equal within the inter-series variability for the two acquisition schemes. Thus, single-trial BOLD responses were detected for the first time robustly at a 500 x 500 microm2 in plane and 250 ms temporal resolution, significantly expanding the possibilities of event-related functional imaging in the human brain. The magnetization transfer effect induced by the outer-volume suppression pulses was investigated and found to be increased during neuronal activity.
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