Science.gov

Sample records for bold fmri response

  1. Hemodynamic Nonlinearities Affect BOLD fMRI Response Timing and Amplitude

    PubMed Central

    de Zwart, Jacco A; van Gelderen, Peter; Jansma, J Martijn; Fukunaga, Masaki; Bianciardi, Marta; Duyn, Jeff H

    2009-01-01

    The interpretation of functional Magnetic Resonance Imaging (fMRI) studies based on Blood Oxygen-Level Dependent (BOLD) contrast generally relies on the assumption of a linear relationship between evoked neuronal activity and fMRI response. While nonlinearities in this relationship have been suggested by a number of studies, it remains unclear to what extent they relate to the neurovascular response and are therefore inherent to BOLD-fMRI. Full characterization of potential vascular nonlinearities is required for accurate inferences about the neuronal system under study. To investigate the extent of vascular nonlinearities, evoked activity was studied in humans with BOLD-fMRI (n=28) and Magnetoencephalography (MEG) (n=5). Brief (600-800 ms) rapidly repeated (1 Hz) visual stimuli were delivered using a stimulation paradigm that minimized neuronal nonlinearities. Nevertheless, BOLD-fMRI experiments showed substantial remaining nonlinearities. The smallest stimulus separation (200-400 ms) resulted in significant response broadening (15-20% amplitude decrease; 10-12% latency increase; 6-14% duration increase) with respect to a linear prediction. The substantial slowing and widening of the response in the presence of preceding stimuli suggests a vascular rather than neuronal origin to the observed non-linearity. This was confirmed by the MEG data, which showed no significant neuro-electric nonlinear interactions between stimuli as little as 200 ms apart. The presence of substantial vascular nonlinearities has important implications for rapid event-related studies by fMRI and other imaging modalities that infer neuronal activity from hemodynamic parameters. PMID:19520175

  2. Coupling of fMRI and NIRS measurements in the study of negative BOLD response to intermittent photic stimulation.

    PubMed

    Maggioni, E; Molteni, E; Arrigoni, F; Zucca, C; Reni, G; Triulzi, F M; Bianchi, A M

    2013-01-01

    Functional Magnetic Resonance Imaging (fMRI) in combination with Near Infrared Spectroscopy (NIRS) is finding widespread use in the analysis of brain function. While most of the studies deal with the detection of positive responses, here we focus on negative responses to visual stimulation. In a group fMRI study on Intermittent Photic Stimulation (IPS) we detected a sustained Negative BOLD Response (NBR) in the extrastriate visual cortex. To confirm and better characterize NBR, we repeated the same protocol during NIRS recordings. In this paper we show fMRI results and demonstrate the NBR on the basis of NIRS findings. PMID:24109953

  3. Global signal modulation of single-trial fMRI response variability: Effect on positive vs negative BOLD response relationship.

    PubMed

    Mayhew, S D; Mullinger, K J; Ostwald, D; Porcaro, C; Bowtell, R; Bagshaw, A P; Francis, S T

    2016-06-01

    In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR-NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of

  4. Increased sensitivity of fast BOLD fMRI with a subject-specific hemodynamic response function and application to epilepsy.

    PubMed

    Proulx, Sébastien; Safi-Harb, Mouna; Levan, Pierre; An, Dongmei; Watanabe, Satsuki; Gotman, Jean

    2014-06-01

    Activation detection in functional Magnetic Resonance Imaging (fMRI) typically assumes the hemodynamic response to neuronal activity to be invariant across brain regions and subjects. Reports of substantial variability of the morphology of blood-oxygenation-level-dependent (BOLD) responses are accumulating, suggesting that the use of a single generic model of the expected response in general linear model (GLM) analyses does not provide optimal sensitivity due to model misspecification. Relaxing assumptions of the model can limit the impact of hemodynamic response function (HRF) variability, but at a cost on model parsimony. Alternatively, better specification of the model could be obtained from a priori knowledge of the HRF of a given subject, but the effectiveness of this approach has only been tested on simulation data. Using fast BOLD fMRI, we characterized the variability of hemodynamic responses to a simple event-related auditory-motor task, as well as its effect on activation detection with GLM analyses. We show the variability to be higher between subjects than between regions and variation in different regions to correlate from one subject to the other. Accounting for subject-related variability by deriving subject-specific models from responses to the task in some regions lead to more sensitive detection of responses in other regions. We applied the approach to epilepsy patients, where task-derived patient-specific models provided additional information compared to the use of a generic model for the detection of BOLD responses to epileptiform activity identified on scalp electro-encephalogram (EEG). This work highlights the importance of improving the accuracy of the model for detecting neuronal activation with fMRI, and the fact that it can be done at no cost to model parsimony through the acquisition of independent a priori information about the hemodynamic response. PMID:24582920

  5. Study of the spatial correlation between neuronal activity and BOLD fMRI responses evoked by sensory and channelrhodopsin-2 stimulation in the rat somatosensory cortex

    PubMed Central

    Li, Nan; van Zijl, Peter; Thakor, Nitish; Pelled, Galit

    2014-01-01

    In this work we combined optogenetics tools with high-resolution blood oxygenation level dependent functional MRI (BOLD fMRI), electrophysiology, and optical imaging of cerebral blood flow (CBF), to study the spatial correlation between the hemodynamic responses and neuronal activity. We first investigated the spatial and temporal characteristics of BOLD fMRI and the underlying neuronal responses evoked by sensory stimulations at different frequencies. The results demonstrated that under dexmedetomidine anesthesia, BOLD fMRI and neuronal activity in the rat primary somatosensory cortex (S1) have different frequency - dependency and distinct laminar activation profiles. We the found that localized activation of channelrhodopsin-2 (ChR2) expressed in neurons throughout the cortex induced neuronal responses that were confined to the light stimulation S1 region (<500 μm) with distinct laminar activation profile. However, the spatial extent of the hemodynamic responses measured by CBF and BOLD fMRI induced by both ChR2 and sensory stimulation were greater than 3 mm. These results suggest that due to the complex neurovascular coupling it is challenging to determine specific characteristics of the underlying neuronal activity exclusively from the BOLD fMRI signals. PMID:24443233

  6. The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults.

    PubMed

    Cortese, Bernadette M; Uhde, Thomas W; Brady, Kathleen T; McClernon, F Joseph; Yang, Qing X; Collins, Heather R; LeMatty, Todd; Hartwell, Karen J

    2015-12-30

    Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. PMID:26475784

  7. Linear Discriminant Analysis Achieves High Classification Accuracy for the BOLD fMRI Response to Naturalistic Movie Stimuli.

    PubMed

    Mandelkow, Hendrik; de Zwart, Jacco A; Duyn, Jeff H

    2016-01-01

    Naturalistic stimuli like movies evoke complex perceptual processes, which are of great interest in the study of human cognition by functional MRI (fMRI). However, conventional fMRI analysis based on statistical parametric mapping (SPM) and the general linear model (GLM) is hampered by a lack of accurate parametric models of the BOLD response to complex stimuli. In this situation, statistical machine-learning methods, a.k.a. multivariate pattern analysis (MVPA), have received growing attention for their ability to generate stimulus response models in a data-driven fashion. However, machine-learning methods typically require large amounts of training data as well as computational resources. In the past, this has largely limited their application to fMRI experiments involving small sets of stimulus categories and small regions of interest in the brain. By contrast, the present study compares several classification algorithms known as Nearest Neighbor (NN), Gaussian Naïve Bayes (GNB), and (regularized) Linear Discriminant Analysis (LDA) in terms of their classification accuracy in discriminating the global fMRI response patterns evoked by a large number of naturalistic visual stimuli presented as a movie. Results show that LDA regularized by principal component analysis (PCA) achieved high classification accuracies, above 90% on average for single fMRI volumes acquired 2 s apart during a 300 s movie (chance level 0.7% = 2 s/300 s). The largest source of classification errors were autocorrelations in the BOLD signal compounded by the similarity of consecutive stimuli. All classifiers performed best when given input features from a large region of interest comprising around 25% of the voxels that responded significantly to the visual stimulus. Consistent with this, the most informative principal components represented widespread distributions of co-activated brain regions that were similar between subjects and may represent functional networks. In light of these

  8. Linear Discriminant Analysis Achieves High Classification Accuracy for the BOLD fMRI Response to Naturalistic Movie Stimuli

    PubMed Central

    Mandelkow, Hendrik; de Zwart, Jacco A.; Duyn, Jeff H.

    2016-01-01

    Naturalistic stimuli like movies evoke complex perceptual processes, which are of great interest in the study of human cognition by functional MRI (fMRI). However, conventional fMRI analysis based on statistical parametric mapping (SPM) and the general linear model (GLM) is hampered by a lack of accurate parametric models of the BOLD response to complex stimuli. In this situation, statistical machine-learning methods, a.k.a. multivariate pattern analysis (MVPA), have received growing attention for their ability to generate stimulus response models in a data-driven fashion. However, machine-learning methods typically require large amounts of training data as well as computational resources. In the past, this has largely limited their application to fMRI experiments involving small sets of stimulus categories and small regions of interest in the brain. By contrast, the present study compares several classification algorithms known as Nearest Neighbor (NN), Gaussian Naïve Bayes (GNB), and (regularized) Linear Discriminant Analysis (LDA) in terms of their classification accuracy in discriminating the global fMRI response patterns evoked by a large number of naturalistic visual stimuli presented as a movie. Results show that LDA regularized by principal component analysis (PCA) achieved high classification accuracies, above 90% on average for single fMRI volumes acquired 2 s apart during a 300 s movie (chance level 0.7% = 2 s/300 s). The largest source of classification errors were autocorrelations in the BOLD signal compounded by the similarity of consecutive stimuli. All classifiers performed best when given input features from a large region of interest comprising around 25% of the voxels that responded significantly to the visual stimulus. Consistent with this, the most informative principal components represented widespread distributions of co-activated brain regions that were similar between subjects and may represent functional networks. In light of these

  9. Using an achiasmic human visual system to quantify the relationship between the fMRI BOLD signal and neural response

    PubMed Central

    Bao, Pinglei; Purington, Christopher J; Tjan, Bosco S

    2015-01-01

    Achiasma in humans causes gross mis-wiring of the retinal-fugal projection, resulting in overlapped cortical representations of left and right visual hemifields. We show that in areas V1-V3 this overlap is due to two co-located but non-interacting populations of neurons, each with a receptive field serving only one hemifield. Importantly, the two populations share the same local vascular control, resulting in a unique organization useful for quantifying the relationship between neural and fMRI BOLD responses without direct measurement of neural activity. Specifically, we can non-invasively double local neural responses by stimulating both neuronal populations with identical stimuli presented symmetrically across the vertical meridian to both visual hemifields, versus one population by stimulating in one hemifield. Measurements from a series of such doubling experiments show that the amplitude of BOLD response is proportional to approximately 0.5 power of the underlying neural response. Reanalyzing published data shows that this inferred relationship is general. DOI: http://dx.doi.org/10.7554/eLife.09600.001 PMID:26613411

  10. Sustained Negative BOLD Response in Human fMRI Finger Tapping Task

    PubMed Central

    Liu, Yadong; Shen, Hui; Zhou, Zongtan; Hu, Dewen

    2011-01-01

    In this work, we investigated the sustained negative blood oxygen level-dependent (BOLD) response (sNBR) using functional magnetic resonance imaging during a finger tapping task. We observed that the sNBR for this task was more extensive than has previously been reported. The cortical regions involved in sNBR are divided into the following three groups: frontal, somatosensory and occipital. By investigating the spatial structure, area, amplitude, and dynamics of the sNBR in comparison with those of its positive BOLD response (PBR) counterpart, we made the following observations. First, among the three groups, the somatosensory group contained the greatest number of activated voxels and the fewest deactivated voxels. In addition, the amplitude of the sNBR in this group was the smallest among the three groups. Second, the onset and peak time of the sNBR are both larger than those of the PBR, whereas the falling edge time of the sNBR is less than that of the PBR. Third, the long distance between most sNBR foci and their corresponding PBR foci makes it unlikely that they share the same blood supply artery. Fourth, the couplings between the sNBR and its PBR counterpart are distinct among different regions and thus should be investigated separately. These findings imply that the origin of most sNBR foci in the finger-tapping task is much more likely to be neuronal activity suppression rather than “blood steal.” PMID:21887329

  11. Sustained negative BOLD response in human fMRI finger tapping task.

    PubMed

    Liu, Yadong; Shen, Hui; Zhou, Zongtan; Hu, Dewen

    2011-01-01

    In this work, we investigated the sustained negative blood oxygen level-dependent (BOLD) response (sNBR) using functional magnetic resonance imaging during a finger tapping task. We observed that the sNBR for this task was more extensive than has previously been reported. The cortical regions involved in sNBR are divided into the following three groups: frontal, somatosensory and occipital. By investigating the spatial structure, area, amplitude, and dynamics of the sNBR in comparison with those of its positive BOLD response (PBR) counterpart, we made the following observations. First, among the three groups, the somatosensory group contained the greatest number of activated voxels and the fewest deactivated voxels. In addition, the amplitude of the sNBR in this group was the smallest among the three groups. Second, the onset and peak time of the sNBR are both larger than those of the PBR, whereas the falling edge time of the sNBR is less than that of the PBR. Third, the long distance between most sNBR foci and their corresponding PBR foci makes it unlikely that they share the same blood supply artery. Fourth, the couplings between the sNBR and its PBR counterpart are distinct among different regions and thus should be investigated separately. These findings imply that the origin of most sNBR foci in the finger-tapping task is much more likely to be neuronal activity suppression rather than "blood steal." PMID:21887329

  12. High-resolution BOLD fMRI measurements of local orientation-dependent contextual modulation show a mismatch between predicted V1 output and local BOLD response

    PubMed Central

    Schumacher, Jennifer F.; Olman, Cheryl A.

    2010-01-01

    The blood oxygenation level-dependent (BOLD) functional MRI response to suppressive neural activity has not been tested on a fine spatial scale. Using Gabor patches placed in the near periphery, we precisely localized individual regions of interest in primary visual cortex and measured the response at a range of contrasts in two different contexts: with parallel and with orthogonal flanking Gabor patches. Psychophysical measurements confirmed strong suppression of the target Gabor response when flanked by parallel Gabors. However, the BOLD response to the target with parallel flankers decreased as the target contrast increased, which contradicts psychophysical estimates of local neural activity. PMID:20382175

  13. The association between cortisol and the BOLD response in male adolescents undergoing fMRI.

    PubMed

    Keulers, Esther H H; Stiers, Peter; Nicolson, Nancy A; Jolles, Jelle

    2015-02-19

    MRI participation has been shown to induce subjective and neuroendocrine stress reactions. A recent aging study showed that cortisol levels during fMRI have an age-dependent effect on cognitive performance and brain functioning. The present study examined whether this age-specific influence of cortisol on behavioral and brain activation levels also applies to adolescence. Salivary cortisol as well as subjective experienced anxiety were assessed during the practice session, at home, and before, during and after the fMRI session in young versus old male adolescents. Cortisol levels were enhanced pre-imaging relative to during and post-imaging in both age groups, suggesting anticipatory stress and anxiety. Overall, a negative correlation was found between cortisol output during the fMRI experiment and brain activation magnitude during performance of a gambling task. In young but not in old adolescents, higher cortisol output was related to stronger deactivation of clusters in the anterior and posterior cingulate cortex. In old but not in young adolescents, a negative correlation was found between cortisol and activation in the inferior parietal and in the superior frontal cortex. In sum, cortisol increased the deactivation of several brain areas, although the location of the affected areas in the brain was age-dependent. The present findings suggest that cortisol output during fMRI should be considered as confounder and integrated in analyzing developmental changes in brain activation during adolescence. PMID:25514334

  14. Modeling of region-specific fMRI BOLD neurovascular response functions in rat brain reveals residual differences that correlate with the differences in regional evoked potentials.

    PubMed

    Pawela, Christopher P; Hudetz, Anthony G; Ward, B Douglas; Schulte, Marie L; Li, Rupeng; Kao, Dennis S; Mauck, Matthew C; Cho, Younghoon R; Neitz, Jay; Hyde, James S

    2008-06-01

    The response of the rat visual system to flashes of blue light has been studied by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The BOLD temporal response is dependent on the number of flashes presented and demonstrates a refractory period that depends on flash frequency. Activated brain regions included the primary and secondary visual cortex, superior colliculus (SC), dorsal lateral geniculate (DLG), and lateral posterior nucleus (LP), which were found to exhibit differing temporal responses. To explain these differences, the BOLD neurovascular response function was modeled. A second-order differential equation was developed and solved numerically to arrive at region-specific response functions. Included in the model are the light input from the diode (duty cycle), a refractory period, a transient response following onset and cessation of stimulus, and a slow adjustment to changes in the average level of the signal. Constants in the differential equation were evaluated for each region by fitting the model to the experimental BOLD response from a single flash, and the equation was then solved for multiple flashes. The simulation mimics the major features of the data; however, remaining differences in the frequency dependence of the response between the cortical and subcortical regions were unexplained. We hypothesized that these discrepancies were due to regional-specific differences in neuronal response to flash frequency. To test this hypothesis, cortical visual evoked potentials (VEPs) were recorded using the same stimulation protocol as the fMRI. Cortical VEPs were more suppressed than subcortical VEPs as flash frequency increased, supporting our hypothesis. This is the first report that regional differences in neuronal activation to the same stimulus lead to differential BOLD activation. PMID:18406628

  15. BOLD effect: new aspects of the hemodynamic response through combination of fMRI and optical recording in the barrel cortex of the gerbil

    NASA Astrophysics Data System (ADS)

    Hess, Andreas; Stiller, Detelf; Scheich, Henning

    2000-04-01

    Functional MRI (fMRI) is a non-invasive technique widely used to map brain-functions. Nevertheless, its hemodynamic basis and spatial precision with which fMRI reflects sites of neuronal activity are not completely understood. We therefore combined fMRI, based on the blood oxygenation level dependent (BOLD) effect, with optical recording of intrinsic signals (ORIS), a technique, which has a better spatial and temporal resolution. Furthermore, ORIS can distinguish between localized changes in deoxyhemoglobin, and more widespread changes in cerebral blood volume/flow. In gerbils hemodynamic responses over the contralateral barrel cortex were studied with both methods, using identical stimulation of a single vibrissae and identical integration and correlation analysis strategies. Analysis of integration maps and of the spatial distribution and temporal correlation with the block-design of vibrissal stimulation revealed that the BOLD signal, at the site of neuronal activation, does not reflect a depletion of deoxyhemoglobin, as generally assumed. Instead, its positive polarity is likely due to an increase in cerebral blood volume (CBV) whose highly dynamic effect on the BOLD signal exceeds that of the increase in deoxyhemoglobin remaining elevated during prolonged stimulation. This is so, because we show, that blood flow does wash out deoxyhemoglobin but at a rate which is to decrease the deoxyhemoglobin concentration in the voxel below resting level. The wash out causes an accumulation of deoxyhemoglobin in the draining venous side, but at a time window which can be clearly distinguished from the specific activity by applying an analysis strategy based on correlation functions. Therefore, draining veins do not appear as confounding problem. This knowledge could be useful to model the BOLD effect more accurately and improve the spatial resolution of fMRI.

  16. BOLD fMRI of C-Fiber Mediated Nociceptive Processing in Mouse Brain in Response to Thermal Stimulation of the Forepaws

    PubMed Central

    Bosshard, Simone C.; Stuker, Florian; von Deuster, Constantin; Schroeter, Aileen; Rudin, Markus

    2015-01-01

    Functional magnetic resonance imaging (fMRI) in rodents enables non-invasive studies of brain function in response to peripheral input or at rest. In this study we describe a thermal stimulation paradigm using infrared laser diodes to apply noxious heat to the forepaw of mice in order to study nociceptive processing. Stimulation at 45 and 46°C led to robust BOLD signal changes in various brain structures including the somatosensory cortices and the thalamus. The BOLD signal amplitude scaled with the temperature applied but not with the area irradiated by the laser beam. To demonstrate the specificity of the paradigm for assessing nociceptive signaling we administered the quaternary lidocaine derivative QX-314 to the forepaws, which due to its positive charge cannot readily cross biological membranes. However, upon activation of TRPV1 channels following the administration of capsaicin the BOLD signal was largely abolished, indicative of a selective block of the C-fiber nociceptors due to QX-314 having entered the cells via the now open TRPV1 channels. This demonstrates that the cerebral BOLD response to thermal noxious paw stimulation is specifically mediated by C-fibers. PMID:25950440

  17. Characterization of the blood-oxygen level-dependent (BOLD) response in cat auditory cortex using high-field fMRI.

    PubMed

    Brown, Trecia A; Joanisse, Marc F; Gati, Joseph S; Hughes, Sarah M; Nixon, Pam L; Menon, Ravi S; Lomber, Stephen G

    2013-01-01

    Much of what is known about the cortical organization for audition in humans draws from studies of auditory cortex in the cat. However, these data build largely on electrophysiological recordings that are both highly invasive and provide less evidence concerning macroscopic patterns of brain activation. Optical imaging, using intrinsic signals or dyes, allows visualization of surface-based activity but is also quite invasive. Functional magnetic resonance imaging (fMRI) overcomes these limitations by providing a large-scale perspective of distributed activity across the brain in a non-invasive manner. The present study used fMRI to characterize stimulus-evoked activity in auditory cortex of an anesthetized (ketamine/isoflurane) cat, focusing specifically on the blood-oxygen-level-dependent (BOLD) signal time course. Functional images were acquired for adult cats in a 7 T MRI scanner. To determine the BOLD signal time course, we presented 1s broadband noise bursts between widely spaced scan acquisitions at randomized delays (1-12 s in 1s increments) prior to each scan. Baseline trials in which no stimulus was presented were also acquired. Our results indicate that the BOLD response peaks at about 3.5s in primary auditory cortex (AI) and at about 4.5 s in non-primary areas (AII, PAF) of cat auditory cortex. The observed peak latency is within the range reported for humans and non-human primates (3-4 s). The time course of hemodynamic activity in cat auditory cortex also occurs on a comparatively shorter scale than in cat visual cortex. The results of this study will provide a foundation for future auditory fMRI studies in the cat to incorporate these hemodynamic response properties into appropriate analyses of cat auditory cortex. PMID:23000258

  18. P300 amplitude variation is related to ventral striatum BOLD response during gain and loss anticipation: An EEG and fMRI experiment

    PubMed Central

    Pfabigan, Daniela M.; Seidel, Eva-Maria; Sladky, Ronald; Hahn, Andreas; Paul, Katharina; Grahl, Arvina; Küblböck, Martin; Kraus, Christoph; Hummer, Allan; Kranz, Georg S.; Windischberger, Christian; Lanzenberger, Rupert; Lamm, Claus

    2014-01-01

    The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation. PMID:24718288

  19. Biophysical Modeling of Phase Changes in BOLD fMRI

    PubMed Central

    Feng, Zhaomei; Caprihan, Arvind; Blagoev, Krastan B.; Calhoun, Vince D

    2009-01-01

    In BOLD fMRI, stimulus related phase changes have been repeatedly observed in humans. However, virtually all fMRI processing utilizes the magnitude information only, while ignoring the phase. This results in an unnecessary loss of physiological information and signal-to-noise efficiency. A widely held view is that the BOLD phase change is zero for a voxel containing randomly orientated blood vessels and that phase changes are only due to the presence of large vessels. Based on a previously developed theoretical model, we show through simulations and experimental human BOLD fMRI data that a non-zero phase change can be present in a region with randomly oriented vessels. Using simulations of the model, we first demonstrate that a spatially distributed susceptibility results in a non-zero phase distribution. Next, experimental data in a finger-tapping experiment show consistent bipolar phase distribution across multiple subjects. This model is then used to show that in theory a bipolar phase distribution can also be produced by the model. Finally, we show that the model can produce a bipolar phase pattern consistent with that observed in the experimental data. Understanding of the mechanisms behind the experimentally observed phase changes in BOLD fMRI would be an important step forward and will enable biophysical model based methods for integrating the phase and magnitude information in BOLD fMRI experiments. PMID:19426815

  20. fMRI at High Spatial Resolution: Implications for BOLD-Models

    PubMed Central

    Goense, Jozien; Bohraus, Yvette; Logothetis, Nikos K.

    2016-01-01

    As high-resolution functional magnetic resonance imaging (fMRI) and fMRI of cortical layers become more widely used, the question how well high-resolution fMRI signals reflect the underlying neural processing, and how to interpret laminar fMRI data becomes more and more relevant. High-resolution fMRI has shown laminar differences in cerebral blood flow (CBF), volume (CBV), and neurovascular coupling. Features and processes that were previously lumped into a single voxel become spatially distinct at high resolution. These features can be vascular compartments such as veins, arteries, and capillaries, or cortical layers and columns, which can have differences in metabolism. Mesoscopic models of the blood oxygenation level dependent (BOLD) response therefore need to be expanded, for instance, to incorporate laminar differences in the coupling between neural activity, metabolism and the hemodynamic response. Here we discuss biological and methodological factors that affect the modeling and interpretation of high-resolution fMRI data. We also illustrate with examples from neuropharmacology and the negative BOLD response how combining BOLD with CBF- and CBV-based fMRI methods can provide additional information about neurovascular coupling, and can aid modeling and interpretation of high-resolution fMRI. PMID:27445782

  1. fMRI at High Spatial Resolution: Implications for BOLD-Models.

    PubMed

    Goense, Jozien; Bohraus, Yvette; Logothetis, Nikos K

    2016-01-01

    As high-resolution functional magnetic resonance imaging (fMRI) and fMRI of cortical layers become more widely used, the question how well high-resolution fMRI signals reflect the underlying neural processing, and how to interpret laminar fMRI data becomes more and more relevant. High-resolution fMRI has shown laminar differences in cerebral blood flow (CBF), volume (CBV), and neurovascular coupling. Features and processes that were previously lumped into a single voxel become spatially distinct at high resolution. These features can be vascular compartments such as veins, arteries, and capillaries, or cortical layers and columns, which can have differences in metabolism. Mesoscopic models of the blood oxygenation level dependent (BOLD) response therefore need to be expanded, for instance, to incorporate laminar differences in the coupling between neural activity, metabolism and the hemodynamic response. Here we discuss biological and methodological factors that affect the modeling and interpretation of high-resolution fMRI data. We also illustrate with examples from neuropharmacology and the negative BOLD response how combining BOLD with CBF- and CBV-based fMRI methods can provide additional information about neurovascular coupling, and can aid modeling and interpretation of high-resolution fMRI. PMID:27445782

  2. Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates

    PubMed Central

    Asad, Abu Bakar Ali; Seah, Stephanie; Baumgartner, Richard; Feng, Dai; Jensen, Andres; Manigbas, Elaine; Henry, Brian; Houghton, Andrea; Evelhoch, Jeffrey L.; Derbyshire, Stuart W. G.; Chin, Chih-Liang

    2016-01-01

    Background Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored. Methodology Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm) application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail). Principal Findings Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the ‘pain matrix’, including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8), while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures. Conclusions These findings provide insights into the specific brain regions involved with aversive, ‘pain-like’, responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain

  3. Visual Mapping Using BOLD fMRI

    PubMed Central

    DeYoe, Edgar A.; Raut, Ryan V.

    2014-01-01

    Synopsis Functional magnetic resonance imaging (fMRI) is used clinically to map visual cortex prior to brain surgery or other invasive treatments in order to achieve an optimal balance between therapeutic effect and the avoidance of post-operative vision deficits. Clinically optimized stimuli, behavioral task, analysis and displays permit identification of cortical subregions supporting high acuity central vision that is critical for reading and other essential visual functions. A novel data display permits instant appreciation of the functional relationship between the pattern of fMRI brain activation and the pattern of vision loss and preservation within the patient’s field of view. Neurovascular uncoupling and its detection in visual cortex are key issues for the interpretation of fMRI results in patients with existing brain pathology. Emerging techniques such as resting state fMRI may facilitate the use of fMRI-based vision mapping with a broader range of patients. PMID:25441501

  4. Matched-filter acquisition for BOLD fMRI.

    PubMed

    Kasper, Lars; Haeberlin, Maximilian; Dietrich, Benjamin E; Gross, Simon; Barmet, Christoph; Wilm, Bertram J; Vannesjo, S Johanna; Brunner, David O; Ruff, Christian C; Stephan, Klaas E; Pruessmann, Klaas P

    2014-10-15

    We introduce matched-filter fMRI, which improves BOLD (blood oxygen level dependent) sensitivity by variable-density image acquisition tailored to subsequent image smoothing. Image smoothing is an established post-processing technique used in the vast majority of fMRI studies. Here we show that the signal-to-noise ratio of the resulting smoothed data can be substantially increased by acquisition weighting with a weighting function that matches the k-space filter imposed by the smoothing operation. We derive the theoretical SNR advantage of this strategy and propose a practical implementation of 2D echo-planar acquisition matched to common Gaussian smoothing. To reliably perform the involved variable-speed trajectories, concurrent magnetic field monitoring with NMR probes is used. Using this technique, phantom and in vivo measurements confirm reliable SNR improvement in the order of 30% in a "resting-state" condition and prove robust in different regimes of physiological noise. Furthermore, a preliminary task-based visual fMRI experiment equally suggests a consistent BOLD sensitivity increase in terms of statistical sensitivity (average t-value increase of about 35%). In summary, our study suggests that matched-filter acquisition is an effective means of improving BOLD SNR in studies that rely on image smoothing at the post-processing level. PMID:24844745

  5. Linear and Nonlinear Relationships between Visual Stimuli, EEG and BOLD fMRI Signals

    PubMed Central

    Liu, Zhongming; Rios, Cristina; Zhang, Nanyin; Yang, Lin; Chen, Wei; He, Bin

    2010-01-01

    In the present study, the cascaded interactions between stimuli and neural and hemodynamic responses were modeled using linear systems. These models provided the theoretical hypotheses that were tested against the electroencephalography (EEG) and blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data recorded from human subjects during prolonged periods of repeated visual stimuli with a variable setting of the inter-stimulus-interval (ISI) and visual contrast. Our results suggest that 1) neural response is nonlinear only when ISI<0.2 s, 2) BOLD response is nonlinear with an exclusively vascular origin when 0.25response nonlinearity reflects a refractory effect, rather than a ceiling effect, and 4) there is a strong linear relationship between the BOLD effect size and the integrated power of event-related synaptic current activity, after modeling and taking into account the vascular refractory effect. These conclusions offer important insights into the origins of BOLD nonlinearity and the nature of neurovascular coupling, and suggest an effective means to quantitatively interpret the BOLD signal in terms of neural activity. The validated cross-modal relationship between fMRI and EEG may provide a theoretical basis for the integration of these two modalities. PMID:20079854

  6. Functional MRI during hyperbaric oxygen: Effects of oxygen on neurovascular coupling and BOLD fMRI signals.

    PubMed

    Cardenas, Damon P; Muir, Eric R; Huang, Shiliang; Boley, Angela; Lodge, Daniel; Duong, Timothy Q

    2015-10-01

    Hyperbaric oxygen (HBO) therapy is used to treat a number of ailments. Improved understanding of how HBO affects neuronal activity, cerebral blood flow (CBF) and blood-oxygenation-level dependent (BOLD) changes could shed light on the role of oxygen in neurovascular coupling and help guide HBO treatments. The goal of this study was to test two hypotheses: i) activation-induced CBF fMRI response is not dependent on hemoglobin deoxygenation, and ii) activation-induced BOLD fMRI is markedly attenuated under HBO. CBF and BOLD fMRI of forepaw stimulation in anesthetized rats under HBO at 3 atmospheres absolute (ATA) were compared with normobaric air. Robust BOLD and CBF fMRI were detected under HBO. Inflow effects and spin-density changes did not contribute significantly to the BOLD fMRI signal under HBO. Analysis of the T2(⁎)-weighted signal at normobaric air and 1, 2 and 3ATA oxygen in the tissue and the superior sagittal sinus showed a strong dependence on increasing inhaled [O2]. Spontaneous electrophysiological activity and evoked local-field potentials were reduced under HBO. The differences between normobaric air and HBO in basal and evoked electrical activity could not fully account for the strong BOLD responses under HBO. We concluded that activation-induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism and that stimulus-evoked BOLD responses and the venous T2(⁎)-weighted signals still have room to increase under 3ATA HBO. To our knowledge, this is the first fMRI study under HBO, providing insights into the effects of HBO on neural activity, neurovascular coupling, tissue oxygenation, and the BOLD signal. PMID:26143203

  7. Cortex-based inter-subject analysis of iEEG and fMRI data sets: application to sustained task-related BOLD and gamma responses.

    PubMed

    Esposito, Fabrizio; Singer, Neomi; Podlipsky, Ilana; Fried, Itzhak; Hendler, Talma; Goebel, Rainer

    2013-02-01

    Linking regional metabolic changes with fluctuations in the local electromagnetic fields directly on the surface of the human cerebral cortex is of tremendous importance for a better understanding of detailed brain processes. Functional magnetic resonance imaging (fMRI) and intra-cranial electro-encephalography (iEEG) measure two technically unrelated but spatially and temporally complementary sets of functional descriptions of human brain activity. In order to allow fine-grained spatio-temporal human brain mapping at the population-level, an effective comparative framework for the cortex-based inter-subject analysis of iEEG and fMRI data sets is needed. We combined fMRI and iEEG recordings of the same patients with epilepsy during alternated intervals of passive movie viewing and music listening to explore the degree of local spatial correspondence and temporal coupling between blood oxygen level dependent (BOLD) fMRI changes and iEEG spectral power modulations across the cortical surface after cortex-based inter-subject alignment. To this purpose, we applied a simple model of the iEEG activity spread around each electrode location and the cortex-based inter-subject alignment procedure to transform discrete iEEG measurements into cortically distributed group patterns by establishing a fine anatomic correspondence of many iEEG cortical sites across multiple subjects. Our results demonstrate the feasibility of a multi-modal inter-subject cortex-based distributed analysis for combining iEEG and fMRI data sets acquired from multiple subjects with the same experimental paradigm but with different iEEG electrode coverage. The proposed iEEG-fMRI framework allows for improved group statistics in a common anatomical space and preserves the dynamic link between the temporal features of the two modalities. PMID:23138047

  8. Comparison of fMRI BOLD response patterns by electrical stimulation of the ventroposterior complex and medial thalamus of the rat.

    PubMed

    Yang, Pai-Feng; Chen, You-Yin; Chen, Der-Yow; Hu, James W; Chen, Jyh-Horng; Yen, Chen-Tung

    2013-01-01

    The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD) activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP) and medial (MT) thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA) and frequencies (1 Hz to 12 Hz). BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL) after VP stimulation and in the ipsilateral cingulate cortex (iCC) after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu). Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways. PMID:23826146

  9. Comparison of fMRI BOLD Response Patterns by Electrical Stimulation of the Ventroposterior Complex and Medial Thalamus of the Rat

    PubMed Central

    Yang, Pai-Feng; Chen, You-Yin; Chen, Der-Yow; Hu, James W.; Chen, Jyh-Horng; Yen, Chen-Tung

    2013-01-01

    The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD) activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP) and medial (MT) thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA) and frequencies (1 Hz to 12 Hz). BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL) after VP stimulation and in the ipsilateral cingulate cortex (iCC) after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu). Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways. PMID:23826146

  10. Test-retest reliability of evoked heat stimulation BOLD fMRI.

    PubMed

    Upadhyay, Jaymin; Lemme, Jordan; Anderson, Julie; Bleakman, David; Large, Thomas; Evelhoch, Jeffrey L; Hargreaves, Richard; Borsook, David; Becerra, Lino

    2015-09-30

    To date, the blood oxygenated-level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique has enabled an objective and deeper understanding of pain processing mechanisms embedded within the human central nervous system (CNS). In order to further comprehend the benefits and limitations of BOLD fMRI in the context of pain as well as the corresponding subjective pain ratings, we evaluated the univariate response, test-retest reliability and confidence intervals (CIs) at the 95% level of both data types collected during evoked stimulation of 40°C (non-noxious), 44°C (mildly noxious) and a subject-specific temperature eliciting a 7/10 pain rating. The test-retest reliability between two scanning sessions was determined by calculating group-level interclass correlation coefficients (ICCs) and at the single-subject level. Across the three stimuli, we initially observed a graded response of increasing magnitude for both VAS (visual analog score) pain ratings and fMRI data. Test-retest reliability was observed to be highest for VAS pain ratings obtained during the 7/10 pain stimulation (ICC=0.938), while ICC values of pain fMRI data for a distribution of CNS structures ranged from 0.5 to 0.859 (p<0.05). Importantly, the upper and lower confidence interval CI bounds reported herein could be utilized in subsequent trials involving healthy volunteers to hypothesize the magnitude of effect required to overcome inherent variability of either VAS pain ratings or BOLD responses evoked during innocuous or noxious thermal stimulation. PMID:26072245

  11. Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex

    PubMed Central

    Walter, Susanna A.; Forsgren, Mikael; Lundengård, Karin; Simon, Rozalyn; Torkildsen Nilsson, Maritha; Söderfeldt, Birgitta; Lundberg, Peter; Engström, Maria

    2016-01-01

    Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms. PMID:26930498

  12. Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex.

    PubMed

    Walter, Susanna A; Forsgren, Mikael; Lundengård, Karin; Simon, Rozalyn; Torkildsen Nilsson, Maritha; Söderfeldt, Birgitta; Lundberg, Peter; Engström, Maria

    2016-01-01

    Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms. PMID:26930498

  13. Using High Spatial Resolution to Improve BOLD fMRI Detection at 3T

    PubMed Central

    Claise, Béatrice; Jean, Betty

    2015-01-01

    For different functional magnetic resonance imaging experiments using blood oxygenation level-dependent (BOLD) contrast, the acquisition of T2*-weighted scans at a high spatial resolution may be advantageous in terms of time-course signal-to-noise ratio and of BOLD sensitivity when the regions are prone to susceptibility artifacts. In this study, we explore this solution by examining how spatial resolution influences activations elicited when appetizing food pictures are viewed. Twenty subjects were imaged at 3 T with two different voxel volumes, 3.4 μl and 27 μl. Despite the diminution of brain coverage, we found that high-resolution acquisition led to a better detection of activations. Though known to suffer to different degrees from susceptibility artifacts, the activations detected by high spatial resolution were notably consistent with those reported in published activation likelihood estimation meta-analyses, corresponding to taste-responsive regions. Furthermore, these regions were found activated bilaterally, in contrast with previous findings. Both the reduction of partial volume effect, which improves BOLD contrast, and the mitigation of susceptibility artifact, which boosts the signal to noise ratio in certain regions, explained the better detection noted with high resolution. The present study provides further evidences that high spatial resolution is a valuable solution for human BOLD fMRI, especially for studying food-related stimuli. PMID:26550990

  14. Vascular Origins of BOLD and CBV fMRI Signals: Statistical Mapping and Histological Sections Compared.

    PubMed

    Kennerley, Aneurin J; Mayhew, John E; Redgrave, Peter; Berwick, Jason

    2010-01-01

    Comparison of 3T blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) activation maps to histological sections enables the spatial discrimination of functional magnetic resonance imaging (fMRI) signal changes into different vascular compartments. We use a standard gradient echo-echo planar imaging technique to measure BOLD signal changes in the somatosensory cortex in response to whisker stimulation. Corresponding changes in CBV were estimated following the infusion of a super-paramagnetic contrast agent. We imaged in a tangential imaging plane that covered the cortical surface. Images were associated with post mortem histological sections showing both the surface vasculature and cytochrome oxidase stained whisker barrel cortex. We found a significant BOLD signal change in the large draining veins which occurred in the absence of a corresponding CBV change. Results suggest that in the venous drainage system, ~3mm distant from the area of activity, there is a robust change in blood oxygen saturation with little or no volume change. CBV changes are localised over the somatosensory barrel cortex and overlying arterial supply, supporting the theory that CBV changes are greater in the arterial than in the venous vasculature. This work investigating BOLD signal and underlying hemodynamics provides more information on the vascular origins of these important neuroimaging signals. PMID:20563253

  15. BOLD fMRI Correlation Reflects Frequency-Specific Neuronal Correlation.

    PubMed

    Hipp, Joerg F; Siegel, Markus

    2015-05-18

    The brain-wide correlation of hemodynamic signals as measured with BOLD fMRI is widely studied as a proxy for integrative brain processes. However, the relationship between hemodynamic correlation structure and neuronal correlation structure remains elusive. We investigated this relation using BOLD fMRI and spatially co-registered, source-localized MEG in resting humans. We found that across the entire cortex BOLD correlation reflected the co-variation of frequency-specific neuronal activity. Resolving the relation between electrophysiological and hemodynamic correlation structures locally in cortico-cortical connection space, we found that this relation was subject specific and even persisted on the centimeter scale. At first sight, this relation was strongest in the alpha to beta frequency range (8-32 Hz). However, correcting for differences in signal-to-noise ratios across electrophysiological frequencies, we found that the relation extended over a broad frequency range from 2 to 128 Hz. Moreover, we found that the frequency with the tightest link to BOLD correlation varied across cortico-cortical space. For every cortico-cortical connection, we show which specific correlated oscillations were most related to BOLD correlations. Our work provides direct evidence for the neuronal origin of BOLD correlation structure. Moreover, our work suggests that, across the brain, BOLD correlation reflects correlation of different types of neuronal network processes and that frequency-specific electrophysiological correlation provides information about large-scale neuronal interactions complementary to BOLD fMRI. PMID:25936551

  16. Spikes, BOLD, Attention and Awareness: A comparison of electrophysiology and fMRI signals in V1

    PubMed Central

    Boynton, Geoffrey M.

    2014-01-01

    Early fMRI studies comparing results from fMRI and electrophysiology experiments supports the notion that the blood oxygen level dependent (BOLD) signal reliably follows the spiking activity of an underlying neuronal population averaged across a small region in space and a brief period in time. However, more recent studies focusing on higher-level cognitive factors such as attention and visual awareness report striking discrepancies between the fMRI response in humans and electrophysiological signals in macaque early visual areas. Four hypotheses are discussed that can explain the discrepancies between the two methods: (1) the BOLD signal follows local field potential (LFP) signals closer than spikes, and the only the LFP is modulated by top-down factors, (2) the BOLD signal is reflecting electrophysiological signals that are occurring later in time due to feedback delay, (3) the BOLD signal is more sensitive than traditional electrophysiological methods due to massive pooling by the hemodynamic coupling process, and finally (4) there is no real discrepancy, and instead weak but reliable effects on firing rates may be obscured by to differences in experimental design and interpretation of results across methods. PMID:22199162

  17. BOLD fMRI study of ultrahigh frequency encoding in the inferior colliculus.

    PubMed

    Gao, Patrick P; Zhang, Jevin W; Chan, Russell W; Leong, Alex T L; Wu, Ed X

    2015-07-01

    Many vertebrates communicate with ultrahigh frequency (UHF) vocalizations to limit auditory detection by predators. The mechanisms underlying the neural encoding of such UHF sounds may provide important insights for understanding neural processing of other complex sounds (e.g. human speeches). In the auditory system, sound frequency is normally encoded topographically as tonotopy, which, however, contains very limited representation of UHFs in many species. Instead, electrophysiological studies suggested that two neural mechanisms, both exploiting the interactions between frequencies, may contribute to UHF processing. Neurons can exhibit excitatory or inhibitory responses to a tone when another UHF tone is presented simultaneously (combination sensitivity). They can also respond to such stimulation if they are tuned to the frequency of the cochlear-generated distortion products of the two tones, e.g. their difference frequency (cochlear distortion). Both mechanisms are present in an early station of the auditory pathway, the midbrain inferior colliculus (IC). Currently, it is unclear how prevalent the two mechanisms are and how they are functionally integrated in encoding UHFs. This study investigated these issues with large-view BOLD fMRI in rat auditory system, particularly the IC. UHF vocalizations (above 40kHz), but not pure tones at similar frequencies (45, 55, 65, 75kHz), evoked robust BOLD responses in multiple auditory nuclei, including the IC, reinforcing the sensitivity of the auditory system to UHFs despite limited representation in tonotopy. Furthermore, BOLD responses were detected in the IC when a pair of UHF pure tones was presented simultaneously (45 & 55kHz, 55 & 65kHz, 45 & 65kHz, 45 & 75kHz). For all four pairs, a cluster of voxels in the ventromedial side always showed the strongest responses, displaying combination sensitivity. Meanwhile, voxels in the dorsolateral side that showed strongest secondary responses to each pair of UHF pure tones

  18. BOLD fMRI in awake prairie voles: A platform for translational social and affective neuroscience.

    PubMed

    Yee, J R; Kenkel, W M; Kulkarni, P; Moore, K; Perkeybile, A M; Toddes, S; Amacker, J A; Carter, C S; Ferris, C F

    2016-09-01

    The advancement of neuroscience depends on continued improvement in methods and models. Here, we present novel techniques for the use of awake functional magnetic resonance imaging (fMRI) in the prairie vole (Microtus ochrogaster) - an important step forward in minimally-invasive measurement of neural activity in a non-traditional animal model. Imaging neural responses in prairie voles, a species studied for its propensity to form strong and selective social bonds, is expected to greatly advance our mechanistic understanding of complex social and affective processes. The use of ultra-high-field fMRI allows for recording changes in region-specific activity throughout the entire brain simultaneously and with high temporal and spatial resolutions. By imaging neural responses in awake animals, with minimal invasiveness, we are able to avoid the confound of anesthesia, broaden the scope of possible stimuli, and potentially make use of repeated scans from the same animals. These methods are made possible by the development of an annotated and segmented 3D vole brain atlas and software for image analysis. The use of these methods in the prairie vole provides an opportunity to broaden neuroscientific investigation of behavior via a comparative approach, which highlights the ethological relevance of pro-social behaviors shared between voles and humans, such as communal breeding, selective social bonds, social buffering of stress, and caregiving behaviors. Results using these methods show that fMRI in the prairie vole is capable of yielding robust blood oxygen level dependent (BOLD) signal changes in response to hypercapnic challenge (inhaled 5% CO2), region-specific physical challenge (unilateral whisker stimulation), and presentation of a set of novel odors. Complementary analyses of repeated restraint sessions in the imaging hardware suggest that voles do not require acclimation to this procedure. Taken together, awake vole fMRI represents a new arena of neurobiological

  19. MEG and fMRI Fusion for Non-Linear Estimation of Neural and BOLD Signal Changes.

    PubMed

    Plis, Sergey M; Calhoun, Vince D; Weisend, Michael P; Eichele, Tom; Lane, Terran

    2010-01-01

    The combined analysis of magnetoencephalography (MEG)/electroencephalography and functional magnetic resonance imaging (fMRI) measurements can lead to improvement in the description of the dynamical and spatial properties of brain activity. In this paper we empirically demonstrate this improvement using simulated and recorded task related MEG and fMRI activity. Neural activity estimates were derived using a dynamic Bayesian network with continuous real valued parameters by means of a sequential Monte Carlo technique. In synthetic data, we show that MEG and fMRI fusion improves estimation of the indirectly observed neural activity and smooths tracking of the blood oxygenation level dependent (BOLD) response. In recordings of task related neural activity the combination of MEG and fMRI produces a result with greater signal-to-noise ratio, that confirms the expectation arising from the nature of the experiment. The highly non-linear model of the BOLD response poses a difficult inference problem for neural activity estimation; computational requirements are also high due to the time and space complexity. We show that joint analysis of the data improves the system's behavior by stabilizing the differential equations system and by requiring fewer computational resources. PMID:21120141

  20. MEG and fMRI Fusion for Non-Linear Estimation of Neural and BOLD Signal Changes

    PubMed Central

    Plis, Sergey M.; Calhoun, Vince D.; Weisend, Michael P.; Eichele, Tom; Lane, Terran

    2010-01-01

    The combined analysis of magnetoencephalography (MEG)/electroencephalography and functional magnetic resonance imaging (fMRI) measurements can lead to improvement in the description of the dynamical and spatial properties of brain activity. In this paper we empirically demonstrate this improvement using simulated and recorded task related MEG and fMRI activity. Neural activity estimates were derived using a dynamic Bayesian network with continuous real valued parameters by means of a sequential Monte Carlo technique. In synthetic data, we show that MEG and fMRI fusion improves estimation of the indirectly observed neural activity and smooths tracking of the blood oxygenation level dependent (BOLD) response. In recordings of task related neural activity the combination of MEG and fMRI produces a result with greater signal-to-noise ratio, that confirms the expectation arising from the nature of the experiment. The highly non-linear model of the BOLD response poses a difficult inference problem for neural activity estimation; computational requirements are also high due to the time and space complexity. We show that joint analysis of the data improves the system's behavior by stabilizing the differential equations system and by requiring fewer computational resources. PMID:21120141

  1. Electrophysiological correlates of the BOLD signal for EEG-informed fMRI

    PubMed Central

    Murta, Teresa; Leite, Marco; Carmichael, David W; Figueiredo, Patrícia; Lemieux, Louis

    2015-01-01

    Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG–fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level-dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological–haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG–fMRI mapping), or exploring a range of EEG-derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG–fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG–fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations. PMID:25277370

  2. Decoding neural events from fMRI BOLD signal: A comparison of existing approaches and development of a new algorithm

    PubMed Central

    Bush, Keith; Cisler, Josh

    2013-01-01

    Neuroimaging methodology predominantly relies on the blood oxygenation level dependent (BOLD) signal. While the BOLD signal is a valid measure of neuronal activity, variance in fluctuations of the BOLD signal are not only due to fluctuations in neural activity. Thus, a remaining problem in neuroimaging analyses is developing methods that ensure specific inferences about neural activity that are not confounded by unrelated sources of noise in the BOLD signal. Here, we develop and test a new algorithm for performing semi-blind (i.e., no knowledge of stimulus timings) deconvolution of the BOLD signal that treats the neural event as an observable, but intermediate, probabilistic representation of the system’s state. We test and compare this new algorithm against three other recent deconvolution algorithms under varied levels of autocorrelated and Gaussian noise, hemodynamic response function (HRF) misspecification, and observation sampling rate (i.e., TR). Further, we compare the algorithms’ performance using two models to simulate BOLD data: a convolution of neural events with a known (or misspecified) HRF versus a biophysically accurate balloon model of hemodynamics. We also examine the algorithms’ performance on real task data. The results demonstrated good performance of all algorithms, though the new algorithm generally outperformed the others (3.0% improvement) under simulated resting state experimental conditions exhibiting multiple, realistic confounding factors (as well as 10.3% improvement on a real Stroop task). The simulations also demonstrate that the greatest negative influence on deconvolution accuracy is observation sampling rate. Practical and theoretical implications of these results for improving inferences about neural activity from fMRI BOLD signal are discussed. PMID:23602664

  3. BMI Not WHR Modulates BOLD fMRI Responses in a Sub-Cortical Reward Network When Participants Judge the Attractiveness of Human Female Bodies

    PubMed Central

    Holliday, Ian E.; Longe, Olivia A.; Thai, N. Jade; Hancock, Peter J. B.; Tovée, Martin J.

    2011-01-01

    In perceptual terms, the human body is a complex 3d shape which has to be interpreted by the observer to judge its attractiveness. Both body mass and shape have been suggested as strong predictors of female attractiveness. Normally body mass and shape co-vary, and it is difficult to differentiate their separate effects. A recent study suggested that altering body mass does not modulate activity in the reward mechanisms of the brain, but shape does. However, using computer generated female body-shaped greyscale images, based on a Principal Component Analysis of female bodies, we were able to construct images which covary with real female body mass (indexed with BMI) and not with body shape (indexed with WHR), and vice versa. Twelve observers (6 male and 6 female) rated these images for attractiveness during an fMRI study. The attractiveness ratings were correlated with changes in BMI and not WHR. Our primary fMRI results demonstrated that in addition to activation in higher visual areas (such as the extrastriate body area), changing BMI also modulated activity in the caudate nucleus, and other parts of the brain reward system. This shows that BMI, not WHR, modulates reward mechanisms in the brain and we infer that this may have important implications for judgements of ideal body size in eating disordered individuals. PMID:22102883

  4. Arterial spin tagging fMRI in continuous overt speech production compared to BOLD technique

    NASA Astrophysics Data System (ADS)

    Kemeny, Stefan; Ye, Frank; Braun, Allen

    2003-05-01

    Conventional BOLD fMRI has limited use in overt speech paradigms, due to movement and susceptibility artifacts. Our study used an arterial spin-tagging (AST) sequence to quantify focal brain activation in a continuous speech task. Furthermore, we compared the results to conventional BOLD fMRI. The ASSIST sequence was used to obtain transverse perfusion images of the brain, acquired on a 1.5T GE-Signa scanner. Three conditions were alternated in a block design: generation of complete sentences, nonsense syllables and rest with continuous and overt speech production. For 4 normal volunteers, task-related perfusion maps with quantified rCBF and rCBV values were calculated and activations were mapped to the MNI brain. The same paradigm was scanned with BOLD contrast fMRI in separate, independent scans and data from 6 subjects were analyzed using SPM99. Using the AST sequence, we could reliably identify focal brain activation in an overt continuous speech paradigm, and the activations observed were consistent with previous PET studies. We found differential activation at increasing levels of speech production with a focus in the left insula and opercular IFG related to the production of sentences at a syntactic level as opposed to nonsense syllable production. The BOLD technique failed to identify some of these activation foci, possibly due to decreased SNR and artifacts.

  5. Investigating the source of BOLD nonlinearity in human visual cortex in response to paired visual stimuli.

    PubMed

    Zhang, Nanyin; Zhu, Xiao-Hong; Chen, Wei

    2008-11-01

    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. PMID:18657623

  6. The relationship between time to peak of fMRI-BOLD responses and difficulty of a task suggests neuronal origins to the BOLD contrast

    NASA Astrophysics Data System (ADS)

    Alonso, Benito De Celis

    2012-10-01

    Functional magnetic resonance imaging (fMRI) and its blood oxygen level contrast (BOLD) was used to study the response of the vibrissa system of rodents to different combinations of bilateral stimulations. We found that difficult tasks to perform, associated with longer neuronal periods, were correlated with larger times to peak (ttp) for the BOLD signal. This delay depended on number of vibrissa stimulated and the region of brain studied. By contrast, delay was not affected by which hemisphere was stimulated.

  7. Improving the precision of fMRI BOLD signal deconvolution with implications for connectivity analysis.

    PubMed

    Bush, Keith; Cisler, Josh; Bian, Jiang; Hazaroglu, Gokce; Hazaroglu, Onder; Kilts, Clint

    2015-12-01

    An important, open problem in neuroimaging analyses is developing analytical methods that ensure precise inferences about neural activity underlying fMRI BOLD signal despite the known presence of confounds. Here, we develop and test a new meta-algorithm for conducting semi-blind (i.e., no knowledge of stimulus timings) deconvolution of the BOLD signal that estimates, via bootstrapping, both the underlying neural events driving BOLD as well as the confidence of these estimates. Our approach includes two improvements over the current best performing deconvolution approach; 1) we optimize the parametric form of the deconvolution feature space; and, 2) we pre-classify neural event estimates into two subgroups, either known or unknown, based on the confidence of the estimates prior to conducting neural event classification. This knows-what-it-knows approach significantly improves neural event classification over the current best performing algorithm, as tested in a detailed computer simulation of highly-confounded fMRI BOLD signal. We then implemented a massively parallelized version of the bootstrapping-based deconvolution algorithm and executed it on a high-performance computer to conduct large scale (i.e., voxelwise) estimation of the neural events for a group of 17 human subjects. We show that by restricting the computation of inter-regional correlation to include only those neural events estimated with high-confidence the method appeared to have higher sensitivity for identifying the default mode network compared to a standard BOLD signal correlation analysis when compared across subjects. PMID:26226647

  8. Whole brain 3D T2-weighted BOLD fMRI at 7T

    PubMed Central

    Hua, Jun; Qin, Qin; van Zijl, Peter C. M.; Pekar, James J.; Jones, Craig K.

    2014-01-01

    Purpose A new acquisition scheme for T2-weighted spin-echo BOLD fMRI is introduced. Methods It employs a T2-preparation module to induce BOLD contrast, followed by a single-shot 3D fast gradient-echo readout with short TE. It differs from most spin-echo BOLD sequences in that BOLD contrast is generated before the readout, which eliminates the “dead time” due to long TE required for T2 contrast, and substantially improves acquisition efficiency. This approach, termed “3D T2prep-GRE”, was implemented at 7T with a typical spatial (2.5×2.5×2.5mm3) and temporal (TR=2.3s) resolution for fMRI and whole-brain coverage (55 slices), and compared with the widely used 2D spin-echo EPI sequence. Results In fMRI experiments of simultaneous visual/motor activities, 3D T2prep-GRE showed minimal distortion and little signal dropout across the whole brain. Its lower power deposition allowed greater spatial coverage (55 versus 17 slices with identical TR, resolution and power level), temporal SNR (60% higher) and CNR (35% higher) efficiency than 2D spin-echo EPI. It also showed smaller T2* contamination. Conclusion This approach is expected to be useful for ultra-high field fMRI, especially for regions near air cavities. The concept of using T2-preparation to generate BOLD contrast can be combined with many other sequences at any field strength. PMID:24338901

  9. Evidence that the negative BOLD response is neuronal in origin: a simultaneous EEG-BOLD-CBF study in humans.

    PubMed

    Mullinger, K J; Mayhew, S D; Bagshaw, A P; Bowtell, R; Francis, S T

    2014-07-01

    Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO2) in this NBR region. The ∆CMRO2/∆CBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n=0.91±0.04, M=10.45%) than in the contralateral S1/M1 (n=0.65±0.03, M=10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8-13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR. PMID:24632092

  10. A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation

    NASA Technical Reports Server (NTRS)

    Strangman, Gary; Culver, Joseph P.; Thompson, John H.; Boas, David A.; Sutton, J. P. (Principal Investigator)

    2002-01-01

    Near-infrared spectroscopy (NIRS) has been used to noninvasively monitor adult human brain function in a wide variety of tasks. While rough spatial correspondences with maps generated from functional magnetic resonance imaging (fMRI) have been found in such experiments, the amplitude correspondences between the two recording modalities have not been fully characterized. To do so, we simultaneously acquired NIRS and blood-oxygenation level-dependent (BOLD) fMRI data and compared Delta(1/BOLD) (approximately R(2)(*)) to changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations derived from the NIRS data from subjects performing a simple motor task. We expected the correlation with deoxyhemoglobin to be strongest, due to the causal relation between changes in deoxyhemoglobin concentrations and BOLD signal. Instead we found highly variable correlations, suggesting the need to account for individual subject differences in our NIRS calculations. We argue that the variability resulted from systematic errors associated with each of the signals, including: (1) partial volume errors due to focal concentration changes, (2) wavelength dependence of this partial volume effect, (3) tissue model errors, and (4) possible spatial incongruence between oxy- and deoxyhemoglobin concentration changes. After such effects were accounted for, strong correlations were found between fMRI changes and all optical measures, with oxyhemoglobin providing the strongest correlation. Importantly, this finding held even when including scalp, skull, and inactive brain tissue in the average BOLD signal. This may reflect, at least in part, the superior contrast-to-noise ratio for oxyhemoglobin relative to deoxyhemoglobin (from optical measurements), rather than physiology related to BOLD signal interpretation.

  11. Pitfalls in Fractal Time Series Analysis: fMRI BOLD as an Exemplary Case

    PubMed Central

    Eke, Andras; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Mukli, Peter; Nagy, Zoltan

    2012-01-01

    This article will be positioned on our previous work demonstrating the importance of adhering to a carefully selected set of criteria when choosing the suitable method from those available ensuring its adequate performance when applied to real temporal signals, such as fMRI BOLD, to evaluate one important facet of their behavior, fractality. Earlier, we have reviewed on a range of monofractal tools and evaluated their performance. Given the advance in the fractal field, in this article we will discuss the most widely used implementations of multifractal analyses, too. Our recommended flowchart for the fractal characterization of spontaneous, low frequency fluctuations in fMRI BOLD will be used as the framework for this article to make certain that it will provide a hands-on experience for the reader in handling the perplexed issues of fractal analysis. The reason why this particular signal modality and its fractal analysis has been chosen was due to its high impact on today’s neuroscience given it had powerfully emerged as a new way of interpreting the complex functioning of the brain (see “intrinsic activity”). The reader will first be presented with the basic concepts of mono and multifractal time series analyses, followed by some of the most relevant implementations, characterization by numerical approaches. The notion of the dichotomy of fractional Gaussian noise and fractional Brownian motion signal classes and their impact on fractal time series analyses will be thoroughly discussed as the central theme of our application strategy. Sources of pitfalls and way how to avoid them will be identified followed by a demonstration on fractal studies of fMRI BOLD taken from the literature and that of our own in an attempt to consolidate the best practice in fractal analysis of empirical fMRI BOLD signals mapped throughout the brain as an exemplary case of potentially wide interest. PMID:23227008

  12. BOLD fMRI and DTI in strabismic amblyopes following occlusion therapy.

    PubMed

    Gupta, Shikha; Kumaran, Senthil S; Saxena, Rohit; Gudwani, Sunita; Menon, Vimala; Sharma, Pradeep

    2016-08-01

    Evaluation of brain cluster activation using the functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) was sought in strabismic amblyopes. In this hospital-based case-control cross-sectional study, fMRI and DTI were conducted in strabismic amblyopes before initiation of any therapy and after visual recovery following the administration of occlusion therapy. FMRI was performed in 10 strabismic amblyopic subjects (baseline group) and in 5 left strabismic amblyopic children post-occlusion therapy after two-line visual improvement. Ten age-matched healthy children with right ocular dominance formed control group. Structural and functional MRI was carried out on 1.5T MR scanner. The visual task consisted of 8 Hz flickering checkerboard with red dot and occasional green dot. Blood-oxygen-level-dependent (BOLD) fMRI was analyzed using statistical parametric mapping and DTI on NordicIce (NordicNeuroLab) softwares. Reduced occipital activation was elicited when viewing with the amblyopic eye in amblyopes. An 'ipsilateral to viewing eye' pattern of calcarine BOLD activation was observed in controls and left amblyopes. Activation of cortical areas associated with visual processing differed in relation to the viewing eye. Following visual recovery on occlusion therapy, enhanced activity in bilateral hemispheres in striate as well as extrastriate regions when viewing with either eye was seen. Improvement in visual acuity following occlusion therapy correlates with hemodynamic activity in amblyopes. PMID:26659010

  13. Influence of EEG electrodes on the BOLD fMRI signal.

    PubMed

    Bonmassar, G; Hadjikhani, N; Ives, J R; Hinton, D; Belliveau, J W

    2001-10-01

    Measurement of the EEG during fMRI scanning can give rise to image distortions due to magnetic susceptibility, eddy currents or chemical shift artifacts caused by certain types of EEG electrodes, cream, leads, or amplifiers. Two different creams were tested using MRS and T2* measurements, and we found that the one with higher water content was superior. This study introduces an index that quantifies the influence of EEG equipment on the BOLD fMRI signal. This index can also be used more generally to measure the changes in the fMRI signal due to the presence of any type of device inside (or outside) of the field of view (e.g., with fMRI and diffuse optical tomography, infrared imaging, transcranial magnetic stimulation, ultrasound imaging, etc.). Quantitative noise measurements are hampered by the normal variability of functional activation within the same subject and by the different slice profiles obtained when inserting a subject multiple times inside a MR imaging system. Our measurements account for these problems by using a matched filtering of cortical surface maps of functional activations. The results demonstrate that the BOLD signal is not influenced by the presence of EEG electrodes when using a properly constructed MRI compatible recording cap. PMID:11500994

  14. Development of BOLD signal hemodynamic responses in the human brain

    PubMed Central

    Arichi, Tomoki; Fagiolo, Gianlorenzo; Varela, Marta; Melendez-Calderon, Alejandro; Allievi, Alessandro; Merchant, Nazakat; Tusor, Nora; Counsell, Serena J.; Burdet, Etienne; Beckmann, Christian F.; Edwards, A. David

    2012-01-01

    In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing populations. We aimed to characterize HRF in human infants before and after the normal time of birth using rapid sampling of the Blood Oxygen Level Dependent (BOLD) signal. A somatosensory stimulus and an event related experimental design were used to collect data from 10 healthy adults, 15 sedated infants at term corrected post menstrual age (PMA) (median 41 + 1 weeks), and 10 preterm infants (median PMA 34 + 4 weeks). A positive amplitude HRF waveform was identified across all subject groups, with a systematic maturational trend in terms of decreasing time-to-peak and increasing positive peak amplitude associated with increasing age. Application of the age-appropriate HRF models to fMRI data significantly improved the precision of the fMRI analysis. These findings support the notion of a structured development in the brain's response to stimuli across the last trimester of gestation and beyond. PMID:22776460

  15. Linear aspects of transformation from interictal epileptic discharges to BOLD fMRI signals in an animal model of occipital epilepsy.

    PubMed

    Mirsattari, Seyed M; Wang, Zheng; Ives, John R; Bihari, Frank; Leung, L Stan; Bartha, Robert; Menon, Ravi S

    2006-05-01

    Epileptic disorders manifest with seizures and interictal epileptic discharges (IEDs). The hemodynamic changes that accompany IEDs are poorly understood and may be critical for understanding epileptogenesis. Despite a known linear coupling of the neurovascular elements in normal brain tissues, previous simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies have shown variable correlations between epileptic discharges and blood oxygenation level-dependent (BOLD) response, partly because most previous studies assumed particular hemodynamic properties in normal brain tissue. The occurrence of IEDs in human subjects is unpredictable. Therefore, an animal model with reproducible stereotyped IEDs was developed by the focal injection of penicillin into the right occipital cortex of rats anesthetized with isoflurane. Simultaneous EEG-fMRI was used to study the hemodynamic changes during IEDs. A hybrid of temporal independent component analysis (ICA) of EEG and spatial ICA of fMRI data was used to correlate BOLD fMRI signals with IEDs. A linear autoregression with exogenous input (ARX) model was used to estimate the hemodynamic impulse response function (HIRF) based on the data from simultaneous EEG-fMRI measurement. Changes in the measured BOLD signal from the right primary visual cortex and bilateral visual association cortices were consistently coupled to IEDs. The linear ARX model was applied here to confirm that a linear transform can be used to study the correlation between BOLD signal and its corresponding neural activity in this animal model of occipital epilepsy. PMID:16414283

  16. Prospective active marker motion correction improves statistical power in BOLD fMRI

    PubMed Central

    Ooi, Melvyn B.; Goldman, Robin I.; Krueger, Sascha; Thomas, William J.; Sajda, Paul; Brown, Truman R.

    2013-01-01

    Group level statistical maps of blood oxygenation level dependent (BOLD) signals acquired using functional magnetic resonance imaging (fMRI) have become a basic measurement for much of systems, cognitive and social neuroscience. A challenge in making inferences from these statistical maps is the noise and potential confounds that arise from the head motion that occurs within and between acquisition volumes. This motion results in the scan plane being misaligned during acquisition, ultimately leading to reduced statistical power when maps are constructed at the group level. In most cases, an attempt is made to correct for this motion through the use of retrospective analysis methods. In this paper, we use a prospective active marker motion correction (PRAMMO) system that uses radio frequency markers for real-time tracking of motion, enabling on-line slice plane correction. We show that the statistical power of the activation maps is substantially increased using PRAMMO compared to conventional retrospective correction. Analysis of our results indicates that the PRAMMO acquisition reduces the variance without decreasing the signal component of the BOLD (beta). Using PRAMMO could thus improve the overall statistical power of fMRI based BOLD measurements, leading to stronger inferences of the nature of processing in the human brain. PMID:23220430

  17. Clinical utility of BOLD fMRI in preoperative work-up of epilepsy

    PubMed Central

    Ganesan, Karthik; Ursekar, Meher

    2014-01-01

    Surgical techniques have emerged as a viable therapeutic option in patients with drug refractory epilepsy. Pre-surgical evaluation of epilepsy requires a comprehensive, multiparametric, and multimodal approach for precise localization of the epileptogenic focus. Various non-invasive techniques are available at the disposal of the treating physician to detect the epileptogenic focus, which include electroencephalography (EEG), video-EEG, magnetic resonance imaging (MRI), functional MRI including blood oxygen level dependent (BOLD) techniques, single photon emission tomography (SPECT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Currently, non-invasive high-resolution MR imaging techniques play pivotal roles in the preoperative detection of the seizure focus, and represent the foundation for successful epilepsy surgery. BOLD functional magnetic resonance imaging (fMRI) maps allow for precise localization of the eloquent cortex in relation to the seizure focus. This review article focuses on the clinical utility of BOLD (fMRI) in the pre-surgical work-up of epilepsy patients. PMID:24851002

  18. A Novel Method for Integrating MEG and BOLD fMRI Signals With the Linear Convolution Model in Human Primary Somatosensory Cortex

    PubMed Central

    Nangini, Cathy; Tam, Fred; Graham, Simon J.

    2016-01-01

    Characterizing the neurovascular coupling between hemodynamic signals and their neural origins is crucial to functional neuroimaging research, even more so as new methods become available for integrating results from different functional neuroimaging modalities. We present a novel method to relate magnetoencephalography (MEG) and BOLD fMRI data from primary somatosensory cortex within the context of the linear convolution model. This model, which relates neural activity to BOLD signal change, has been widely used to predict BOLD signals but typically lacks experimentally derived measurements of neural activity. In this study, an fMRI experiment is performed using variable-duration (≤1 s) vibrotactile stimuli applied at 22 Hz, analogous to a previously published MEG study (Nangini et al., [2006]: Neuroimage 33:252–262), testing whether MEG source waveforms from the previous study can inform the convolution model and improve BOLD signal estimates across all stimulus durations. The typical formulation of the convolution model in which the input is given by the stimulus profile is referred to as Model 1. Model 2 is based on an energy argument relating metabolic demand to the postsynaptic currents largely responsible for the MEG current dipoles, and uses the energy density of the estimated MEG source waveforms as input to the convolution model. It is shown that Model 2 improves the BOLD signal estimates compared to Model 1 under the experimental conditions implemented, suggesting that MEG energy density can be a useful index of hemodynamic activity. PMID:17290370

  19. Spiral-in/out BOLD fMRI for increased SNR and reduced susceptibility artifacts.

    PubMed

    Glover, G H; Law, C S

    2001-09-01

    BOLD fMRI is hampered by dropout of signal in the orbitofrontal and parietal brain regions due to magnetic field gradients near air-tissue interfaces. This work reports the use of spiral-in trajectories that begin at the edge of k-space and end at the origin, and spiral in/out trajectories in which a spiral-in readout is followed by a conventional spiral-out trajectory. The spiral-in trajectory reduces the dropout and increases the BOLD contrast. The spiral-in and spiral-out images can be combined in several ways to simultaneously achieve increased signal-to-noise ratio (SNR) and reduced dropout artifacts. Activation experiments employing an olfaction task demonstrate significantly increased activation volumes due to reduced dropout, and overall increased SNR in all regions. PMID:11550244

  20. Resting state BOLD fMRI for pre-surgical planning

    PubMed Central

    Kamran, Mudassar; Hacker, Carl D; Allen, Monica G; Mitchell, Timothy J; Leuthardt, Eric C; Snyder, Abraham Z; Shimony, Joshua S

    2014-01-01

    SYNOPSIS Resting state functional MRI (rsfMRI) measures spontaneous fluctuations in the BOLD signal and can be used to elucidate the brain’s functional organization. It can be used to simultaneously assess multiple distributed resting state networks. Unlike task fMRI, rsfMRI does not require task performance and thus can be performed in any subject that can obtain an MRI scan. In this article we present a brief introduction of rsfMRI processing methods followed by a detailed discussion on the use of rsfMRI in pre-surgical planning. Example cases are provided to highlight the strengths and limitations of the technique. PMID:25441506

  1. Repeated BOLD-fMRI imaging of deep brain stimulation responses in rats.

    PubMed

    Chao, Tzu-Hao Harry; Chen, Jyh-Horng; Yen, Chen-Tung

    2014-01-01

    Functional magnetic resonance imaging (fMRI) provides a picture of the global spatial activation pattern of the brain. Interest is growing regarding the application of fMRI to rodent models to investigate adult brain plasticity. To date, most rodent studies used an electrical forepaw stimulation model to acquire fMRI data, with α-chloralose as the anesthetic. However, α-chloralose is harmful to animals, and not suitable for longitudinal studies. Moreover, peripheral stimulation models enable only a limited number of brain regions to be studied. Processing between peripheral regions and the brain is multisynaptic, and renders interpretation difficult and uncertain. In the present study, we combined the medetomidine-based fMRI protocol (a noninvasive rodent fMRI protocol) with chronic implantation of an MRI-compatible stimulation electrode in the ventroposterior (VP) thalamus to repetitively sample thalamocortical responses in the rat brain. Using this model, we scanned the forebrain responses evoked by the VP stimulation repeatedly of individual rats over 1 week. Cortical BOLD responses were compared between the 2 profiles obtained at day1 and day8. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral somatosensory cortex (S1). The S1 BOLD responses during the 2 sessions were conserved in maximal response amplitude, area size (size ratio from 0.88 to 0.91), and location (overlap ratio from 0.61 to 0.67). The present study provides a long-term chronic brain stimulation protocol for studying the plasticity of specific neural circuits in the rodent brain by BOLD-fMRI. PMID:24825464

  2. Repeated BOLD-fMRI Imaging of Deep Brain Stimulation Responses in Rats

    PubMed Central

    Chao, Tzu-Hao Harry; Chen, Jyh-Horng; Yen, Chen-Tung

    2014-01-01

    Functional magnetic resonance imaging (fMRI) provides a picture of the global spatial activation pattern of the brain. Interest is growing regarding the application of fMRI to rodent models to investigate adult brain plasticity. To date, most rodent studies used an electrical forepaw stimulation model to acquire fMRI data, with α-chloralose as the anesthetic. However, α-chloralose is harmful to animals, and not suitable for longitudinal studies. Moreover, peripheral stimulation models enable only a limited number of brain regions to be studied. Processing between peripheral regions and the brain is multisynaptic, and renders interpretation difficult and uncertain. In the present study, we combined the medetomidine-based fMRI protocol (a noninvasive rodent fMRI protocol) with chronic implantation of an MRI-compatible stimulation electrode in the ventroposterior (VP) thalamus to repetitively sample thalamocortical responses in the rat brain. Using this model, we scanned the forebrain responses evoked by the VP stimulation repeatedly of individual rats over 1 week. Cortical BOLD responses were compared between the 2 profiles obtained at day1 and day8. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral somatosensory cortex (S1). The S1 BOLD responses during the 2 sessions were conserved in maximal response amplitude, area size (size ratio from 0.88 to 0.91), and location (overlap ratio from 0.61 to 0.67). The present study provides a long-term chronic brain stimulation protocol for studying the plasticity of specific neural circuits in the rodent brain by BOLD-fMRI. PMID:24825464

  3. Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults.

    PubMed

    Golestani, Ali M; Wei, Luxi L; Chen, J Jean

    2016-09-01

    In conventional neuroimaging, cerebrovascular reactivity (CVR) is quantified primarily using the blood-oxygenation level-dependent (BOLD) functional MRI (fMRI) signal, specifically, as the BOLD response to intravascular carbon dioxide (CO2) modulations, in units of [%ΔBOLD/mmHg]. While this method has achieved wide appeal and clinical translation, the tolerability of CO2-related tasks amongst patients and the elderly remains a challenge in more routine and large-scale applications. In this work, we propose an improved method to quantify CVR by exploiting intrinsic fluctuations in CO2 and corresponding changes in the resting-state BOLD signal (rs-qCVR). Our rs-qCVR approach requires simultaneous monitoring of PETCO2, cardiac pulsation and respiratory volume. In 16 healthy adults, we compare our quantitative CVR estimation technique to the prospective CO2-targeting based CVR quantification approach (qCVR, the "standard"). We also compare our rs-CVR to non-quantitative alternatives including the resting-state fluctuation amplitude (RSFA), amplitude of low-frequency fluctuation (ALFF) and global-signal regression. When all subjects were pooled, only RSFA and ALFF were significantly associated with qCVR. However, for characterizing regional CVR variations within each subject, only the PETCO2-based rs-qCVR measure is strongly associated with standard qCVR in 100% of the subjects (p≤0.1). In contrast, for the more qualitative CVR measures, significant within-subject association with qCVR was only achieved in 50-70% of the subjects. Our work establishes the feasibility of extracting quantitative CVR maps using rs-fMRI, opening the possibility of mapping functional connectivity and qCVR simultaneously. PMID:27177763

  4. Influence of BOLD Contributions to Diffusion fMRI Activation of the Visual Cortex

    PubMed Central

    Williams, Rebecca J.; Reutens, David C.; Hocking, Julia

    2016-01-01

    Reliance on the hemodynamic response as a surrogate marker of neural activity imposes an intrinsic limit on the spatial specificity of functional MRI. An alternative approach based on diffusion-weighted functional MRI (DfMRI) has been reported as a contrast less reliant on hemodynamic effects, however current evidence suggests that both hemodynamic and unique neural sources contribute to the diffusion signal. Here we compare activation patterns obtained with the standard blood oxygenation level-dependent (BOLD) contrast to DfMRI in order to gain a deeper understanding of how the BOLD proportion contributes to the observable diffusion signal. Both individual and group-level activation patterns obtained with DfMRI and BOLD to a visual field stimulation paradigm were analyzed. At the individual level, the DfMRI contrast showed a strong, positive relationship between the volumes of cortex activated in response to quadrant- and hemi-field visual stimulation. This was not observed in the corresponding BOLD experiment. Overall, the DfMRI response indicated less between-subject variability, with random effects analyses demonstrating higher statistical values at the peak voxel for DfMRI. Furthermore, the spatial extent of the activation was more restricted to the primary visual region for DfMRI than BOLD. However, the diffusion signal was sensitive to the hemodynamic response in a manner dependent on experimental manipulation. It was also limited by its low signal-to-noise ratio (SNR), demonstrating lower sensitivity than BOLD. Together these findings both support DfMRI as a contrast that bears a closer spatial relationship to the underlying neural activity than BOLD, and raise important caveats regarding its utilization. Models explaining the DfMRI signal change need to consider the dynamic vascular contributions that may vary with neural activity. PMID:27445654

  5. Characterization of regional heterogeneity in cerebrovascular reactivity dynamics using novel hypocapnia task and BOLD fMRI.

    PubMed

    Bright, Molly G; Bulte, Daniel P; Jezzard, Peter; Duyn, Jeff H

    2009-10-15

    We offer a new method for characterizing the magnitude and dynamics of the vascular response to changes in arterial gas tensions using non-invasive blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) and paradigms appropriate for clinical settings. A novel respiratory task, "Cued Deep Breathing" (CDB), consisting of two consecutive cycles of cued breaths, has been developed to cause transient hypocapnia, and consequently a strong, short-lived BOLD signal decrease. Data from CDB hypocapnia paradigms and traditional breath-holding hypercapnia paradigms were analyzed on a voxel-wise basis to map regional heterogeneity in magnitude and timing parameters. The tasks caused comparable absolute BOLD percent signal changes (approximately 0.5-3.0% in gray matter) and both datasets suggested consistent regional heterogeneity in the response timing: parts of the basal ganglia, particularly the putamen, and bilateral areas of medial cortex reached their maximum signal change several seconds earlier than remaining cortical gray matter voxels. This phenomenon and a slightly delayed response in posterior cortical regions were present in group-maps of ten healthy subjects. An auxiliary experiment in different subjects measured end-tidal CO2 changes associated with the new CDB task and quantitatively compared the resulting reactivity maps with those acquired using a traditional hypercapnia challenge of 4% CO2 gas inspiration. The CDB task caused average end-tidal CO2 decreases between 6.0+/-1.1 and 10.5+/-2.6 mm Hg, with levels returning to baseline after approximately three breaths, giving evidence that the task indeed causes transient mild hypocapnia. Similarity between resulting reactivity maps suggest CDB offers an alternative method for mapping cerebrovascular reactivity. PMID:19450694

  6. MDMA (Ecstasy) association with impaired fMRI BOLD thalamic coherence and functional connectivity*

    PubMed Central

    Salomon, Ronald M.; Karageorgiou, John; Dietrich, Mary S.; McLellan, Jessica Y.; Charboneau, Evonne J.; Blackford, Jennifer U.; Cowan, Ronald L.

    2011-01-01

    Background MDMA exposure is associated with chronic serotonergic dysfunction in preclinical and clinical studies. A recent functional magnetic resonance imaging (fMRI) comparison of past MDMA users to non-MDMA-using controls revealed increased spatial extent and amplitude of activation in the supplementary motor area during motor tasks (Karageorgiou et al., 2009). Blood oxygenation level dependent (BOLD) data from that study were reanalyzed for intraregional coherence and for inter-regional temporal correlations between time series, as functional connectivity. Methods Fourteen MDMA users and ten controls reporting similar non-MDMA abuse performed finger taps during fMRI. Fourteen motor pathway regions plus a pontine raphé region were examined. Coherence was expressed as percent of voxels positively correlated with an intraregional index voxel. Functional connectivity was determined using wavelet correlations. Results Intraregional thalamic coherence was significantly diminished at low frequencies in MDMA users compared to controls (p=0.009). Inter-regional functional connectivity was significantly weaker for right thalamo - left caudate (p=0.002), right thalamo - left thalamus (p=0.007), right caudate - right postcentral (p=0.007) and right supplementary motor area - right precentral gyrus (p=0.011) region pairs compared to controls. When stratified by lifetime exposure, significant negative associations were observed between cumulative MDMA use and functional connectivity in seven other region-pairs, while only one region-pair showed a positive association. Conclusions Reported prior MDMA use was associated with deficits in BOLD intraregional coherence and inter-regional functional connectivity, even among functionally robust pathways involving motor regions. This suggests that MDMA use is associated with long-lasting effects on brain neurophysiology beyond the cognitive domain. PMID:21807471

  7. Transient and sustained BOLD signal time courses affect the detection of emotion-related brain activation in fMRI.

    PubMed

    Paret, Christian; Kluetsch, Rosemarie; Ruf, Matthias; Demirakca, Traute; Kalisch, Raffael; Schmahl, Christian; Ende, Gabriele

    2014-12-01

    A tremendous amount of effort has been dedicated to unravel the functional neuroanatomy of the processing and regulation of emotion, resulting in a well-described picture of limbic, para-limbic and prefrontal regions involved. Studies applying functional magnetic resonance imaging (fMRI) often use the block-wise presentation of stimuli with affective content, and conventionally model brain activation as a function of stimulus or task duration. However, there is increasing evidence that regional brain responses may not always translate to task duration and rather show stimulus onset-related transient time courses. We assume that brain regions showing transient responses cannot be detected in block designs using a conventional fMRI analysis approach. At the same time, the probability of detecting these regions with conventional analyses may be increased when shorter stimulus timing or a more intense stimulation during a block is used. In a within-subject fMRI study, we presented aversive pictures to 20 healthy subjects and investigated the effect of experimental design (i.e. event-related and block design) on the detection of brain activation in limbic and para-limbic regions of interest of emotion processing. In addition to conventional modeling of sustained activation during blocks of stimulus presentation, we included a second response function into the general linear model (GLM), suited to detect transient time courses at block onset. In the conventional analysis, several regions like the amygdala, thalamus and periaqueductal gray were activated irrespective of design. However, we found a positive BOLD response in the anterior insula (AI) in event-related but not in block-design analyses. GLM analyses suggest that this difference may result from a transient response pattern which cannot be captured by the conventional fMRI analysis approach. Our results indicate that regions with a transient response profile like the AI can be missed in block designs if analyses

  8. Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain.

    PubMed

    Liang, Christine L; Ances, Beau M; Perthen, Joanna E; Moradi, Farshad; Liau, Joy; Buracas, Giedrius T; Hopkins, Susan R; Buxton, Richard B

    2013-01-01

    The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO(2) coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction-independent of details of the model-that if the CBF/CMRO(2) coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/weakest response ratio) of the CMRO(2) response (~1.7-fold) compared to that of the CBF response (~2.4-fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes. PMID:22963855

  9. Visual, Auditory, and Cross Modal Sensory Processing in Adults with Autism: An EEG Power and BOLD fMRI Investigation

    PubMed Central

    Hames, Elizabeth’ C.; Murphy, Brandi; Rajmohan, Ravi; Anderson, Ronald C.; Baker, Mary; Zupancic, Stephen; O’Boyle, Michael; Richman, David

    2016-01-01

    Electroencephalography (EEG) and blood oxygen level dependent functional magnetic resonance imagining (BOLD fMRI) assessed the neurocorrelates of sensory processing of visual and auditory stimuli in 11 adults with autism (ASD) and 10 neurotypical (NT) controls between the ages of 20–28. We hypothesized that ASD performance on combined audiovisual trials would be less accurate with observable decreased EEG power across frontal, temporal, and occipital channels and decreased BOLD fMRI activity in these same regions; reflecting deficits in key sensory processing areas. Analysis focused on EEG power, BOLD fMRI, and accuracy. Lower EEG beta power and lower left auditory cortex fMRI activity were seen in ASD compared to NT when they were presented with auditory stimuli as demonstrated by contrasting the activity from the second presentation of an auditory stimulus in an all auditory block vs. the second presentation of a visual stimulus in an all visual block (AA2-VV2).We conclude that in ASD, combined audiovisual processing is more similar than unimodal processing to NTs. PMID:27148020

  10. Visual, Auditory, and Cross Modal Sensory Processing in Adults with Autism: An EEG Power and BOLD fMRI Investigation.

    PubMed

    Hames, Elizabeth' C; Murphy, Brandi; Rajmohan, Ravi; Anderson, Ronald C; Baker, Mary; Zupancic, Stephen; O'Boyle, Michael; Richman, David

    2016-01-01

    Electroencephalography (EEG) and blood oxygen level dependent functional magnetic resonance imagining (BOLD fMRI) assessed the neurocorrelates of sensory processing of visual and auditory stimuli in 11 adults with autism (ASD) and 10 neurotypical (NT) controls between the ages of 20-28. We hypothesized that ASD performance on combined audiovisual trials would be less accurate with observable decreased EEG power across frontal, temporal, and occipital channels and decreased BOLD fMRI activity in these same regions; reflecting deficits in key sensory processing areas. Analysis focused on EEG power, BOLD fMRI, and accuracy. Lower EEG beta power and lower left auditory cortex fMRI activity were seen in ASD compared to NT when they were presented with auditory stimuli as demonstrated by contrasting the activity from the second presentation of an auditory stimulus in an all auditory block vs. the second presentation of a visual stimulus in an all visual block (AA2-VV2).We conclude that in ASD, combined audiovisual processing is more similar than unimodal processing to NTs. PMID:27148020

  11. A physiologically-based spatiotemporal model of fMRI hemodynamic responses.

    NASA Astrophysics Data System (ADS)

    Huber, Jackie; Drysdale, Peter; Robinson, Peter

    2006-03-01

    A 3D cerebrovascular model is developed to describe the spatiotemporal Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI) response. Modelling spatial effects is particularly important as technology improves, shrinking image voxels and thereby increasing voxel interdependence. Specifically, poroelastic theory, originally developed in geophysics, is used to model the brain tissue and vasculature as a porous continuum. The model yields equations describing conservation of mass, momentum, and deoxyhemoglobin, plus the effect of neuronal activity on blood flow. The equations reproduce existing, non-spatial, hemodynamic models in the relevant limit. Imposition of continuity of flow between adjacent points enables potential investigation of spatial phenomena such as `blood steal' which has been proposed to account for negative BOLD signals abutting sites of positive BOLD responses. This model will enable future study of spatiotemporal relationships between stimuli and experimental fMRI BOLD responses.

  12. A statistical approach for segregating cognitive task stages from multivariate fMRI BOLD time series.

    PubMed

    Demanuele, Charmaine; Bähner, Florian; Plichta, Michael M; Kirsch, Peter; Tost, Heike; Meyer-Lindenberg, Andreas; Durstewitz, Daniel

    2015-01-01

    Multivariate pattern analysis can reveal new information from neuroimaging data to illuminate human cognition and its disturbances. Here, we develop a methodological approach, based on multivariate statistical/machine learning and time series analysis, to discern cognitive processing stages from functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) time series. We apply this method to data recorded from a group of healthy adults whilst performing a virtual reality version of the delayed win-shift radial arm maze (RAM) task. This task has been frequently used to study working memory and decision making in rodents. Using linear classifiers and multivariate test statistics in conjunction with time series bootstraps, we show that different cognitive stages of the task, as defined by the experimenter, namely, the encoding/retrieval, choice, reward and delay stages, can be statistically discriminated from the BOLD time series in brain areas relevant for decision making and working memory. Discrimination of these task stages was significantly reduced during poor behavioral performance in dorsolateral prefrontal cortex (DLPFC), but not in the primary visual cortex (V1). Experimenter-defined dissection of time series into class labels based on task structure was confirmed by an unsupervised, bottom-up approach based on Hidden Markov Models. Furthermore, we show that different groupings of recorded time points into cognitive event classes can be used to test hypotheses about the specific cognitive role of a given brain region during task execution. We found that whilst the DLPFC strongly differentiated between task stages associated with different memory loads, but not between different visual-spatial aspects, the reverse was true for V1. Our methodology illustrates how different aspects of cognitive information processing during one and the same task can be separated and attributed to specific brain regions based on information contained in

  13. A statistical approach for segregating cognitive task stages from multivariate fMRI BOLD time series

    PubMed Central

    Demanuele, Charmaine; Bähner, Florian; Plichta, Michael M.; Kirsch, Peter; Tost, Heike; Meyer-Lindenberg, Andreas; Durstewitz, Daniel

    2015-01-01

    Multivariate pattern analysis can reveal new information from neuroimaging data to illuminate human cognition and its disturbances. Here, we develop a methodological approach, based on multivariate statistical/machine learning and time series analysis, to discern cognitive processing stages from functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) time series. We apply this method to data recorded from a group of healthy adults whilst performing a virtual reality version of the delayed win-shift radial arm maze (RAM) task. This task has been frequently used to study working memory and decision making in rodents. Using linear classifiers and multivariate test statistics in conjunction with time series bootstraps, we show that different cognitive stages of the task, as defined by the experimenter, namely, the encoding/retrieval, choice, reward and delay stages, can be statistically discriminated from the BOLD time series in brain areas relevant for decision making and working memory. Discrimination of these task stages was significantly reduced during poor behavioral performance in dorsolateral prefrontal cortex (DLPFC), but not in the primary visual cortex (V1). Experimenter-defined dissection of time series into class labels based on task structure was confirmed by an unsupervised, bottom-up approach based on Hidden Markov Models. Furthermore, we show that different groupings of recorded time points into cognitive event classes can be used to test hypotheses about the specific cognitive role of a given brain region during task execution. We found that whilst the DLPFC strongly differentiated between task stages associated with different memory loads, but not between different visual-spatial aspects, the reverse was true for V1. Our methodology illustrates how different aspects of cognitive information processing during one and the same task can be separated and attributed to specific brain regions based on information contained in

  14. Test-retest Stability Analysis of Resting Brain Activity Revealed by BOLD fMRI

    PubMed Central

    Li, Zhengjun; Kadivar, Aniseh; Pluta, John; Dunlop, John; Wang, Ze

    2012-01-01

    Purpose To assess test-retest stability of four fMRI-derived resting brain activity metrics: the seed-region-based functional connectivity (SRFC), independent component analysis (ICA)-derived network-based FC (NTFC), regional homogeneity (ReHo), and the amplitude of low frequency fluctuation (ALFF). Methods Simulations were used to assess the sensitivity of SRFC, ReHo, and ALFF to noise interference. Repeat resting blood-oxygen-level-dependent (BOLD) fMRI were acquired from 32 healthy subjects. The intra-class correlation coefficient (ICC) was used to assess the stability of the 4 metrics. Results Random noise yielded small random SRFC, small but consistent ReHo and ALFF. A neighborhood size greater than 20 voxels should be used for calculating ReHo in order to reduce the noise interference. Both the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC)-based SRFC were reproducible in more spatially extended regions than ICA NTFC. The two regional spontaneous brain activity (SBA) measures, ReHo and ALFF, showed test-retest reproducibility in almost the whole grey matter. Conclusion SRFC, ReHo, and ALFF are robust to random noise interference. The neighborhood size for calculating ReHo should be larger than 20 voxels. ICC>0.5 and cluster size>11 should be used to assess the ICC maps for ACC/PCC SRFC, ReHo and ALFF. BOLD fMRI-based SBA can be reliably measured using ACC/PCC SRFC, ReHo and ALFF after two months. PMID:22535702

  15. Spatio-Temporal Information Analysis of Event-Related BOLD Responses

    PubMed Central

    Alpert, Galit Fuhrmann; Handwerker, Dan; Sun, Felice T.; D’Esposito, Mark; Knight, Robert T.

    2009-01-01

    A new approach for analysis of event related fMRI (BOLD) signals is proposed. The technique is based on measures from information theory and is used both for spatial localization of task related activity, as well as for extracting temporal information regarding the task dependent propagation of activation across different brain regions. This approach enables whole brain visualization of voxels (areas) most involved in coding of a specific task condition, the time at which they are most informative about the condition, as well as their average amplitude at that preferred time. The approach does not require prior assumptions about the shape of the hemodynamic response function (HRF), nor about linear relations between BOLD response and presented stimuli (or task conditions). We show that relative delays between different brain regions can also be computed without prior knowledge of the experimental design, suggesting a general method that could be applied for analysis of differential time delays that occur during natural, uncontrolled conditions. Here we analyze BOLD signals recorded during performance of a motor learning task. We show that during motor learning, the BOLD response of unimodal motor cortical areas precedes the response in higher-order multimodal association areas, including posterior parietal cortex. Brain areas found to be associated with reduced activity during motor learning, predominantly in prefrontal brain regions, are informative about the task typically at significantly later times. PMID:17188515

  16. Early suppressive mechanisms and the negative BOLD response in human visual cortex

    PubMed Central

    Wade, Alex R.; Rowland, Jess

    2010-01-01

    Functional magnetic resonance imaging (fMRI) studies of early sensory cortex often measure stimulus-driven increases in the blood oxygenation level-dependent (BOLD) signal. However, these positive responses are frequently accompanied by reductions in the BOLD signal in adjacent regions of cortex. Although this negative BOLD response (NBR) is thought to result from neuronal suppression, the precise relationship between local activity, suppression and perception remains unknown. By measuring BOLD signals in human primary visual cortex while varying the baseline contrast levels in the region affected by the NBR, we tested three physiologically-plausible computational models of neuronal modulation which could explain this phenomenon: a subtractive model, a response gain model and a contrast gain model. We also measured the ability of isoluminant contrast to generate an NBR. We show that the NBR can be modeled as a pathway-specific contrast gain modulation that is strongest outside the fovea. We found a similar spatial bias in a psychophysical study using identical stimuli, although these data indicated a response- rather than a contrast-gain mechanism. We reconcile these findings by proposing 1) that the NBR is associated with a long-range suppressive mechanism that hyperpolarizes a subset of magnocellularly-driven neurons at the input to V1; 2) that this suppression is broadly-tuned to match the spatial features of the mask region; 3) that increasing the baseline contrast in the suppressed region drives all neurons in the input layer, reducing the relative contribution of the suppressing subpopulation in the fMRI signal. PMID:20371821

  17. Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

    PubMed Central

    Furukawa, Emi; Bado, Patricia; Tripp, Gail; Mattos, Paulo; Wickens, Jeff R.; Bramati, Ivanei E.; Alsop, Brent; Ferreira, Fernanda Meireles; Lima, Debora; Tovar-Moll, Fernanda; Sergeant, Joseph A.; Moll, Jorge

    2014-01-01

    Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD. PMID:24586543

  18. Enhancement of temporal resolution and BOLD sensitivity in real-time fMRI using multi-slab echo-volumar imaging.

    PubMed

    Posse, Stefan; Ackley, Elena; Mutihac, Radu; Rick, Jochen; Shane, Matthew; Murray-Krezan, Cristina; Zaitsev, Maxim; Speck, Oliver

    2012-05-15

    In this study, a new approach to high-speed fMRI using multi-slab echo-volumar imaging (EVI) is developed that minimizes geometrical image distortion and spatial blurring, and enables nonaliased sampling of physiological signal fluctuation to increase BOLD sensitivity compared to conventional echo-planar imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286 ms temporal resolution (4mm isotropic voxel size) and partial brain 2-slab EVI with 136 ms temporal resolution (4×4×6 mm(3) voxel size) was performed on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain moving average filtering (2s width) to suppress physiological noise from cardiac and respiratory fluctuations further improved mean (visual: 196%, motor: 140%) and maximum (visual: 384%, motor: 200%) t-scores and increased extents of activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity enhancement, which is attributed to high sampling rate at only moderately reduced temporal signal-to-noise ratio (mean: -52%) and longer sampling of the BOLD effect in the echo-time domain compared to EPI, was measured in auditory cortex. Two-slab EVI further improved temporal resolution for measuring task-related activation and enabled mapping of five major resting state networks (RSNs) in individual subjects in 5 min scans. The bilateral sensorimotor, the default mode and the occipital RSNs were detectable in time frames as short as 75 s. In conclusion, the high sampling rate of real-time multi-slab EVI significantly improves sensitivity for studying the temporal dynamics of hemodynamic responses and for characterizing functional networks at high field strength in short measurement times. PMID:22398395

  19. Enhancement of Temporal Resolution and BOLD Sensitivity in Real-Time fMRI using Multi-Slab Echo-Volumar Imaging

    PubMed Central

    Posse, Stefan; Ackley, Elena; Mutihac, Radu; Rick, Jochen; Shane, Matthew; Murray-Krezan, Cristina; Zaitsev, Maxim; Speck, Oliver

    2012-01-01

    In this study, a new approach to high-speed fMRI using multi-slab echo-volumar imaging (EVI) is developed that minimizes geometrical image distortion and spatial blurring, and enables nonaliased sampling of physiological signal fluctuation to increase BOLD sensitivity compared to conventional echo-planar imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286 ms temporal resolution (4 mm isotropic voxel size) and partial brain 2-slab EVI with 136 ms temporal resolution (4×4×6 mm3 voxel size) was performed on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain moving average filtering (2 s width) to suppress physiological noise from cardiac and respiratory fluctuations further improved mean (visual: 196%, motor: 140%) and maximum (visual: 384%, motor: 200%) t-scores and increased extents of activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity enhancement, which is attributed to high sampling rate at only moderately reduced temporal signal-to-noise ratio (mean: − 52%) and longer sampling of the BOLD effect in the echo-time domain compared to EPI, was measured in auditory cortex. Two-slab EVI further improved temporal resolution for measuring task-related activation and enabled mapping of five major resting state networks (RSNs) in individual subjects in 5 min scans. The bilateral sensorimotor, the default mode and the occipital RSNs were detectable in time frames as short as 75 s. In conclusion, the high sampling rate of real-time multi-slab EVI significantly improves sensitivity for studying the temporal dynamics of hemodynamic responses and for characterizing functional networks at high field strength in short measurement times. PMID:22398395

  20. Investigation of the electrophysiological correlates of negative BOLD response during intermittent photic stimulation: An EEG-fMRI study.

    PubMed

    Maggioni, Eleonora; Zucca, Claudio; Reni, Gianluigi; Cerutti, Sergio; Triulzi, Fabio M; Bianchi, Anna M; Arrigoni, Filippo

    2016-06-01

    Although the occurrence of concomitant positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to visual stimuli is increasingly investigated in neuroscience, it still lacks a definite explanation. Multimodal imaging represents a powerful tool to study the determinants of negative BOLD responses: the integration of functional Magnetic Resonance Imaging (fMRI) and electroencephalographic (EEG) recordings is especially useful, since it can give information on the neurovascular coupling underlying this complex phenomenon. In the present study, the brain response to intermittent photic stimulation (IPS) was investigated in a group of healthy subjects using simultaneous EEG-fMRI, with the main objective to study the electrophysiological mechanisms associated with the intense NBRs elicited by IPS in extra-striate visual cortex. The EEG analysis showed that IPS induced a desynchronization of the basal rhythm, followed by the instauration of a novel rhythm driven by the visual stimulation. The most interesting results emerged from the EEG-informed fMRI analysis, which suggested a relationship between the neuronal rhythms at 10 and 12 Hz and the BOLD dynamics in extra-striate visual cortex. These findings support the hypothesis that NBRs to visual stimuli may be neuronal in origin rather than reflecting pure vascular phenomena. Hum Brain Mapp 37:2247-2262, 2016. © 2016 Wiley Periodicals, Inc. PMID:26987932

  1. Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 Tesla.

    PubMed

    Bednařík, Petr; Tkáč, Ivan; Giove, Federico; DiNuzzo, Mauro; Deelchand, Dinesh K; Emir, Uzay E; Eberly, Lynn E; Mangia, Silvia

    2015-04-01

    Several laboratories have consistently reported small concentration changes in lactate, glutamate, aspartate, and glucose in the human cortex during prolonged stimuli. However, whether such changes correlate with blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been determined. The present study aimed at characterizing the relationship between metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI data were acquired from 12 volunteers. A short echo-time semi-LASER localization sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS data. The group analysis confirmed that during stimulation lactate and glutamate increased by 0.26 ± 0.06 μmol/g (~30%) and 0.28 ± 0.03 μmol/g (~3%), respectively, while aspartate and glucose decreased by 0.20 ± 0.04 μmol/g (~5%) and 0.19 ± 0.03 μmol/g (~16%), respectively. The single-subject analysis revealed that BOLD-fMRI signals were positively correlated with glutamate and lactate concentration changes. The results show a linear relationship between metabolic and BOLD responses in the presence of strong excitatory sensory inputs, and support the notion that increased functional energy demands are sustained by oxidative metabolism. In addition, BOLD signals were inversely correlated with baseline γ-aminobutyric acid concentration. Finally, we discussed the critical importance of taking into account linewidth effects on metabolite quantification in fMRS paradigms. PMID:25564236

  2. Fourier modeling of the BOLD response to a breath-hold task: Optimization and reproducibility.

    PubMed

    Pinto, Joana; Jorge, João; Sousa, Inês; Vilela, Pedro; Figueiredo, Patrícia

    2016-07-15

    Cerebrovascular reactivity (CVR) reflects the capacity of blood vessels to adjust their caliber in order to maintain a steady supply of brain perfusion, and it may provide a sensitive disease biomarker. Measurement of the blood oxygen level dependent (BOLD) response to a hypercapnia-inducing breath-hold (BH) task has been frequently used to map CVR noninvasively using functional magnetic resonance imaging (fMRI). However, the best modeling approach for the accurate quantification of CVR maps remains an open issue. Here, we compare and optimize Fourier models of the BOLD response to a BH task with a preparatory inspiration, and assess the test-retest reproducibility of the associated CVR measurements, in a group of 10 healthy volunteers studied over two fMRI sessions. Linear combinations of sine-cosine pairs at the BH task frequency and its successive harmonics were added sequentially in a nested models approach, and were compared in terms of the adjusted coefficient of determination and corresponding variance explained (VE) of the BOLD signal, as well as the number of voxels exhibiting significant BOLD responses, the estimated CVR values, and their test-retest reproducibility. The brain average VE increased significantly with the Fourier model order, up to the 3rd order. However, the number of responsive voxels increased significantly only up to the 2nd order, and started to decrease from the 3rd order onwards. Moreover, no significant relative underestimation of CVR values was observed beyond the 2nd order. Hence, the 2nd order model was concluded to be the optimal choice for the studied paradigm. This model also yielded the best test-retest reproducibility results, with intra-subject coefficients of variation of 12 and 16% and an intra-class correlation coefficient of 0.74. In conclusion, our results indicate that a Fourier series set consisting of a sine-cosine pair at the BH task frequency and its two harmonics is a suitable model for BOLD-fMRI CVR measurements

  3. Individual differences in EEG theta and alpha dynamics during working memory correlate with fMRI responses across subjects

    PubMed Central

    Meltzer, Jed A.; Negishi, Michiro; Mayes, Linda C.; Constable, R. Todd

    2007-01-01

    Objective Theta and alpha range EEG oscillations are commonly induced in cognitive tasks, but their possible relationship to the BOLD signal of fMRI is not well understood, and individual variability is high. We explored individual differences in EEG reactivity to determine whether it is positively or negatively correlated with BOLD across subjects. Methods A Sternberg working memory task with 2, 4, or 6 digits was administered to 18 subjects in separate fMRI and EEG sessions. Memory load dependent theta and alpha reactivity was quantified and used as a regressor to reveal brain areas exhibiting EEG-fMRI correlation across subjects. Results Theta increases localized to medial prefrontal cortex, and correlated negatively with BOLD in that region and in other “default mode” areas. Alpha modulation localized to parietal-occipital midline cortex and also correlated negatively with BOLD. Conclusions Individual tendencies to exhibit memory-load dependent oscillations are associated with negative BOLD responses certain brain regions. Significance Positive BOLD responses and increased EEG oscillations do not necessarily arise in the same regions. Negative BOLD responses may also relate to cognitive activity, as traditionally indexed by increased EEG power in the theta band. PMID:17900976

  4. Rapid three-dimensional functional magnetic resonance imaging of the initial negative BOLD response

    NASA Astrophysics Data System (ADS)

    Lindquist, Martin A.; Zhang, Cun-Hui; Glover, Gary; Shepp, Lawrence

    2008-03-01

    Functional MRI is most commonly used to study the local changes in blood flow that accompanies neuronal activity. In this work we introduce a new approach towards acquiring and analyzing fMRI data that instead provides the potential to study the initial oxygen consumption in the brain that accompanies activation. As the oxygen consumption is closer in timing to the underlying neuronal activity than the subsequent blood flow, this approach promises to provide more precise information about the location and timing of activity. Our approach is based on using a new single shot 3D echo-volumar imaging sequence which samples a small central region of 3D k-space every 100 ms, thereby giving a low spatial resolution snapshot of the brain with extremely high temporal resolution. Explicit and simple rules for implementing the trajectory are provided, together with a straightforward reconstruction algorithm. Using our approach allows us to effectively study the behavior of the brain in the time immediately following activation through the initial negative BOLD response, and we discuss new techniques for detecting the presence of the negative response across the brain. The feasibility and efficiency of the approach is confirmed using data from a visual-motor task and an auditory-motor-visual task. The results of these experiments provide a proof of concept of our methodology, and indicate that rapid imaging of the initial negative BOLD response can serve an important role in studying cognition tasks involving rapid mental processing in more than one region.

  5. Thirty minute transcutaneous electric acupoint stimulation modulates resting state brain activities: a perfusion and BOLD fMRI study.

    PubMed

    Jiang, Yin; Hao, Ying; Zhang, Yue; Liu, Jing; Wang, Xiaoying; Han, Jisheng; Fang, Jing; Zhang, Jue; Cui, Cailian

    2012-05-31

    Increasing neuroimaging studies have focused on the sustained after effects of acupuncture, especially for the changes of brain activities in rest. However, short-period stimuli have mostly been chosen in these works. The present study aimed to investigate how the resting state brain activities in healthy subjects were modulated by relatively long-period (30 min) acupuncture, a widely used modality in clinical practice. Transcutaneous electric acupoint stimulation (TEAS) or intermittent minimal TEAS (MTEAS) were given for 30 min to 40 subjects. Functional MRI (fMRI) data were collected including the pre-stimulation resting state and the post-stimulation resting state, using dual-echo arterial spin labeling (ASL) techniques, representing both cerebral blood flow (CBF) signals and blood oxygen-dependent level (BOLD) signals simultaneously. Following 30 min TEAS, but not MTEAS, the mean global CBF decreased, and a significant decrease of regional CBF was observed in SI, insula, STG, MOG and IFG. Functional connectivity analysis showed more secure and spatially extended connectivity of both the DMN and SMN after 30 min TEAS. Our results implied that modulation of the regional brain activities and network connectivity induced by thirty minute TEAS may associate with the acupuncture-related therapeutic effects. Furthermore, the resting state regional CBF quantified by ASL perfusion fMRI may serve as a potential biomarker in future acupuncture studies. PMID:22541167

  6. BOLD sensitivity and SNR characteristics of parallel imaging-accelerated single-shot multi-echo EPI for fMRI.

    PubMed

    Bhavsar, Saurabh; Zvyagintsev, Mikhail; Mathiak, Klaus

    2014-01-01

    Echo-planar imaging (EPI) is a standard procedure in functional magnetic resonance imaging (fMRI) for measuring changes in the blood oxygen level-dependent (BOLD) signal associated with neuronal activity. The images obtained from fMRI with EPI, however, exhibit signal dropouts and geometric distortions. Parallel imaging (PI), due to its short readout, accelerates image acquisition and might reduce dephasing in phase-encoding direction. The concomitant loss of signal-to-noise ratio (SNR) might be compensated through single-shot multi-echo EPI (mEPI). We systematically compared the temporal SNR and BOLD sensitivity of single echoes (TE=15, 45, and 75ms) and contrast-optimized mEPI with and without PI and mEPI-based denoising. Audio-visual stimulation under natural viewing conditions activated distributed neural networks. Heterogeneous SNR, noise gain, and sensitivity maps emerged. In single echoes, SNR and BOLD sensitivity followed the predicted dependency on echo time (TE) and were reduced under PI. However, the combination of echoes with mEPI recovered the quality parameters and increased BOLD signal changes at circumscribed fronto-polar and deep brain structures. We suggest applying PI only in combination with mEPI to reduce imaging artifacts and conserve BOLD sensitivity. PMID:23954488

  7. BOLD Response to Semantic and Syntactic Processing during Hypoglycemia Is Load-Dependent

    ERIC Educational Resources Information Center

    Schafer, Robin J.; Page, Kathleen A.; Arora, Jagriti; Sherwin, Robert; Constable, R. Todd

    2012-01-01

    This study investigates how syntactic and semantic load factors impact sentence comprehension and BOLD signal under moderate hypoglycemia. A dual session, whole brain fMRI study was conducted on 16 healthy participants using the glucose clamp technique. In one session, they experienced insulin-induced hypoglycemia (plasma glucose at [image…

  8. Dynamic Retrospective Filtering of Physiological Noise in BOLD fMRI: DRIFTER

    PubMed Central

    Särkkä, Simo; Solin, Arno; Nummenmaa, Aapo; Vehtari, Aki; Auranen, Toni; Vanni, Simo; Lin, Fa-Hsuan

    2012-01-01

    In this article we introduce the DRIFTER algorithm, which is a new model based Bayesian method for retrospective elimination of physiological noise from functional magnetic resonance imaging (fMRI) data. In the method, we first estimate the frequency trajectories of the physiological signals with the interacting multiple models (IMM) filter algorithm. The frequency trajectories can be estimated from external reference signals, or if the temporal resolution is high enough, from the fMRI data. The estimated frequency trajectories are then used in a state space model in combination of a Kalman filter (KF) and Rauch-Tung-Striebel (RTS) smoother, which separates the signal into an activation related cleaned signal, physiological noise, and white measurement noise components. Using experimental data, we show that the method outperforms the RETROICOR algorithm if the shape and amplitude of the physiological signals change over time. PMID:22281675

  9. Acute Alcohol Effects on Contextual Memory BOLD Response: Differences Based on Fragmentary Blackout History

    PubMed Central

    Wetherill, Reagan R.; Schnyer, David M.; Fromme, Kim

    2011-01-01

    Background Contextual memory, or memory for source details, is an important aspect of episodic memory and has been implicated in alcohol-induced fragmentary blackouts (FB). Little is known, however, about how neural functioning during contextual memory processes may differ between individuals with and without a history of fragmentary blackouts. This study examined whether neural activation during a contextual memory task differed by history of fragmentary blackout and acute alcohol consumption. Methods Twenty-four matched individuals with (FB+; n = 12) and without (FB−; n = 12) a history of FBs were recruited from a longitudinal study of alcohol use and behavioral risks and completed a laboratory beverage challenge followed by two functional magnetic resonance imaging (fMRI) sessions under no alcohol and alcohol [breath alcohol concentration (BrAC) = 0.08%] conditions. Task performance and brain hemodynamic activity during a block design contextual memory task were examined across 48 fMRI sessions. Results Groups demonstrated no differences in performance on the contextual memory task, yet exhibited different brain response patterns after alcohol intoxication. A significant FB group by beverage interaction emerged in bilateral dorsolateral prefrontal cortex and posterior parietal cortex with FB− individuals showing greater BOLD response after alcohol exposure (p < .05). Conclusions Alcohol had differential effects on neural activity for FB+ and FB− individuals during recollection of contextual information, perhaps suggesting a neurobiological mechanism associated with alcohol-induced fragmentary blackouts. PMID:22420742

  10. Deep brain stimulation induces BOLD activation in motor and non-motor networks: An fMRI comparison study of STN and EN/GPi DBS in large animals

    PubMed Central

    Min, Hoon-Ki; Hwang, Sun-Chul; Marsh, Michael P.; Kim, Inyong; Knight, Emily; Striemer, Bryan; Felmlee, Joel P.; Welker, Kirk M.; Blaha, Charles D.; Chang, Su-Youne; Bennet, Kevin E.; Lee, Kendall H.

    2012-01-01

    The combination of deep brain stimulation (DBS) and functional MRI (fMRI) is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. The goal of this study was to trace DBS-induced global neuronal network activation in a large animal model by monitoring the blood oxygenation level-dependent (BOLD) response on fMRI. We conducted DBS in normal anesthetized pigs, targeting the subthalamic nucleus (STN) (n=7) and the entopeduncular nucleus (EN), the non-primate analogue of the primate globus pallidus interna (n=4). Using a normalized functional activation map for group analysis and the application of general linear modeling across subjects, we found that both STN and EN DBS significantly increased BOLD activation in the ipsilateral sensorimotor network (FDR < 0.001). In addition, we found differential, target-specific, non-motor network effects. In each group the activated brain areas showed a distinctive correlation pattern forming a group of network connections. Results suggest that the scope of DBS extends beyond an ablation-like effect and that it may have modulatory effects not only on circuits that facilitate motor function but also on those involved in higher cognitive and emotional processing. Taken together, our results show that the swine model for DBS fMRI, which conforms to human implanted DBS electrode configurations and human neuroanatomy, may be a useful platform for translational studies investigating the global neuromodulatory effects of DBS. PMID:22967832

  11. Ketamine and fMRI BOLD signal: distinguishing between effects mediated by change in blood flow versus change in cognitive state.

    PubMed

    Abel, Kathryn M; Allin, Matthew P G; Kucharska-Pietura, Katarzyna; Andrew, Chris; Williams, Steve; David, Anthony S; Phillips, Mary L

    2003-02-01

    No human fMRI studies have examined ketamine effects on the BOLD signal change associated with cognitive task performance. We wished to distinguish between effects on 1) cerebral blood flow, with resultant change in BOLD signal; and 2) cognition and neural mechanisms underlying BOLD signal change associated with task performance. Eight right-handed men (mean age 28.75 years) received ketamine or saline i.v. in a randomized, double-blind manner (bolus 0.23 mg/kg; 0.5 mg/kg over 45 min to a maximum 1 hr). Subjects viewed 10 alternating 30-sec blocks of faces with neutral expressions and a fixation cross and discriminated gender of faces. Gradient echo echoplanar images were acquired on a GE Signa 1.5 T Neurovascular system. One hundred T2-weighted images depicting BOLD contrast were acquired over 5 min (for each task) at each of 14 near-axial noncontiguous 7-mm thick planes. Ketamine significantly increased dissociative phenomena and negative symptoms, but did not affect performance of the gender discrimination task. Significant BOLD signal change was demonstrated predominantly in occipitotemporal cortex with both ketamine and placebo. Only two clusters in middle occipital gyrus (BA 18) and precentral gyrus (BA 4) showed significantly decreased BOLD signal change during ketamine compared to placebo. BOLD signal change was not significantly greater in any region during ketamine. Our findings demonstrate subtle rather than major differences between the effects of ketamine and placebo upon the BOLD signal change during perception of face-non face contrast. We suggest that they represent task-dependent effects of the drug/placebo, rather than task-independent effects of the drug per se, and indicate that the effects of ketamine on cerebral blood flow are predominantly focal and task-dependent, rather than global and task-independent. PMID:12518293

  12. Using a novel source-localized phase regressor technique for evaluation of the vascular contribution to semantic category area localization in BOLD fMRI

    PubMed Central

    Vu, An T.; Gallant, Jack L.

    2015-01-01

    Numerous studies have shown that gradient-echo blood oxygen level dependent (BOLD) fMRI is biased toward large draining veins. However, the impact of this large vein bias on the localization and characterization of semantic category areas has not been examined. Here we address this issue by comparing standard magnitude measures of BOLD activity in the Fusiform Face Area (FFA) and Parahippocampal Place Area (PPA) to those obtained using a novel method that suppresses the contribution of large draining veins: source-localized phase regressor (sPR). Unlike previous suppression methods that utilize the phase component of the BOLD signal, sPR yields robust and unbiased suppression of large draining veins even in voxels with no task-related phase changes. This is confirmed in ideal simulated data as well as in FFA/PPA localization data from four subjects. It was found that approximately 38% of right PPA, 14% of left PPA, 16% of right FFA, and 6% of left FFA voxels predominantly reflect signal from large draining veins. Surprisingly, with the contributions from large veins suppressed, semantic category representation in PPA actually tends to be lateralized to the left rather than the right hemisphere. Furthermore, semantic category areas larger in volume and higher in fSNR were found to have more contributions from large veins. These results suggest that previous studies using gradient-echo BOLD fMRI were biased toward semantic category areas that receive relatively greater contributions from large veins. PMID:26578868

  13. Category-specific semantic memory: converging evidence from bold fMRI and Alzheimer's disease.

    PubMed

    Grossman, Murray; Peelle, Jonathan E; Smith, Edward E; McMillan, Corey T; Cook, Philip; Powers, John; Dreyfuss, Michael; Bonner, Michael F; Richmond, Lauren; Boller, Ashley; Camp, Emily; Burkholder, Lisa

    2013-03-01

    Patients with Alzheimer's disease have category-specific semantic memory difficulty for natural relative to manufactured objects. We assessed the basis for this deficit by asking healthy adults and patients to judge whether pairs of words share a feature (e.g. "banana:lemon-COLOR"). In an fMRI study, healthy adults showed gray matter (GM) activation of temporal-occipital cortex (TOC) where visual-perceptual features may be represented, and prefrontal cortex (PFC) which may contribute to feature selection. Tractography revealed dorsal and ventral stream white matter (WM) projections between PFC and TOC. Patients had greater difficulty with natural than manufactured objects. This was associated with greater overlap between diseased GM areas correlated with natural kinds in patients and fMRI activation in healthy adults for natural kinds. The dorsal WM projection between PFC and TOC in patients correlated only with judgments of natural kinds. Patients thus remained dependent on the same neural network as controls during judgments of natural kinds, despite disease in these areas. For manufactured objects, patients' judgments showed limited correlations with PFC and TOC GM areas activated by controls, and did not correlate with the PFC-TOC dorsal WM tract. Regions outside of the PFC-TOC network thus may help support patients' judgments of manufactured objects. We conclude that a large-scale neural network for semantic memory implicates both feature knowledge representations in modality-specific association cortex and heteromodal regions important for accessing this knowledge, and that patients' relative deficit for natural kinds is due in part to their dependence on this network despite disease in these areas. PMID:23220494

  14. Data-driven optimization and evaluation of 2D EPI and 3D PRESTO for BOLD fMRI at 7 Tesla: I. Focal coverage.

    PubMed

    Barry, Robert L; Strother, Stephen C; Gatenby, J Christopher; Gore, John C

    2011-04-01

    Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is commonly performed using 2D single-shot echo-planar imaging (EPI). However, single-shot EPI at 7 Tesla (T) often suffers from significant geometric distortions (due to low bandwidth (BW) in the phase-encode (PE) direction) and amplified physiological noise. Recent studies have suggested that 3D multi-shot sequences such as PRESTO may offer comparable BOLD contrast-to-noise ratio with increased volume coverage and decreased geometric distortions. Thus, a four-way group-level comparison was performed between 2D and 3D acquisition sequences at two in-plane resolutions. The quality of fMRI data was evaluated via metrics of prediction and reproducibility using NPAIRS (Non-parametric Prediction, Activation, Influence and Reproducibility re-Sampling). Group activation maps were optimized for each acquisition strategy by selecting the number of principal components that jointly maximized prediction and reproducibility, and showed good agreement in sensitivity and specificity for positive BOLD changes. High-resolution EPI exhibited the highest z-scores of the four acquisition sequences; however, it suffered from the lowest BW in the PE direction (resulting in the worst geometric distortions) and limited spatial coverage, and also caused some subject discomfort through peripheral nerve stimulation (PNS). In comparison, PRESTO also had high z-scores (higher than EPI for a matched in-plane resolution), the highest BW in the PE direction (producing images with superior geometric fidelity), the potential for whole-brain coverage, and no reported PNS. This study provides evidence to support the use of 3D multi-shot acquisition sequences in lieu of single-shot EPI for ultra high field BOLD fMRI at 7T. PMID:21232613

  15. The valuation system: A coordinate-based meta-analysis of BOLD fMRI experiments examining neural correlates of subjective value

    PubMed Central

    Bartra, Oscar; McGuire, Joseph T.; Kable, Joseph W.

    2013-01-01

    Numerous experiments have recently sought to identify neural signals associated with the subjective value (SV) of choice alternatives. Theoretically, SV assessment is an intermediate computational step during decision making, in which alternatives are placed on a common scale to facilitate value-maximizing choice. Here we present a quantitative, coordinate-based meta-analysis of 206 published fMRI studies investigating neural correlates of SV. Our results identify two general patterns of SV-correlated brain responses. In one set of regions, both positive and negative effects of SV on BOLD are reported at above-chance rates across the literature. Areas exhibiting this pattern include anterior insula, dorsomedial prefrontal cortex, dorsal and posterior striatum, and thalamus. The mixture of positive and negative effects potentially reflects an underlying U-shaped function, indicative of signal related to arousal or salience. In a second set of areas, including ventromedial prefrontal cortex and anterior ventral striatum, positive effects predominate. Positive effects in the latter regions are seen both when a decision is confronted and when an outcome is delivered, as well as for both monetary and primary rewards. These regions appear to constitute a "valuation system," carrying a domain-general SV signal and potentially contributing to value-based decision making. PMID:23507394

  16. Layer-Specific fMRI Responses to Excitatory and Inhibitory Neuronal Activities in the Olfactory Bulb

    PubMed Central

    Poplawsky, Alexander John; Fukuda, Mitsuhiro; Murphy, Matthew

    2015-01-01

    High-resolution functional magnetic resonance imaging (fMRI) detects localized neuronal activity via the hemodynamic response, but it is unclear whether it accurately identifies neuronal activity specific to individual layers. To address this issue, we preferentially evoked neuronal activity in superficial, middle, and deep layers of the rat olfactory bulb: the glomerular layer by odor (5% amyl acetate), the external plexiform layer by electrical stimulation of the lateral olfactory tract (LOT), and the granule cell layer by electrical stimulation of the anterior commissure (AC), respectively. Electrophysiology, laser-Doppler flowmetry of cerebral blood flow (CBF), and blood oxygenation level-dependent (BOLD) and cerebral blood volume-weighted (CBV) fMRI at 9.4 T were performed independently. We found that excitation of inhibitory granule cells by stimulating LOT and AC decreased the spontaneous multi-unit activities of excitatory mitral cells and subsequently increased CBF, CBV, and BOLD signals. Odor stimulation also increased the hemodynamic responses. Furthermore, the greatest CBV fMRI responses were discretely separated into the same layers as the evoked neuronal activities for all three stimuli, whereas BOLD was poorly localized with some exception to the poststimulus undershoot. In addition, the temporal dynamics of the fMRI responses varied depending on the stimulation pathway, even within the same layer. These results indicate that the vasculature is regulated within individual layers and CBV fMRI has a higher fidelity to the evoked neuronal activity compared with BOLD. Our findings are significant for understanding the neuronal origin and spatial specificity of hemodynamic responses, especially for the interpretation of laminar-resolution fMRI. SIGNIFICANCE STATEMENT Functional magnetic resonance imaging (fMRI) is a noninvasive, in vivo technique widely used to map function of the entire brain, including deep structures, in animals and humans. However, it

  17. Internal representations for face detection: an application of noise-based image classification to BOLD responses.

    PubMed

    Nestor, Adrian; Vettel, Jean M; Tarr, Michael J

    2013-11-01

    What basic visual structures underlie human face detection and how can we extract such structures directly from the amplitude of neural responses elicited by face processing? Here, we address these issues by investigating an extension of noise-based image classification to BOLD responses recorded in high-level visual areas. First, we assess the applicability of this classification method to such data and, second, we explore its results in connection with the neural processing of faces. To this end, we construct luminance templates from white noise fields based on the response of face-selective areas in the human ventral cortex. Using behaviorally and neurally-derived classification images, our results reveal a family of simple but robust image structures subserving face representation and detection. Thus, we confirm the role played by classical face selective regions in face detection and we help clarify the representational basis of this perceptual function. From a theory standpoint, our findings support the idea of simple but highly diagnostic neurally-coded features for face detection. At the same time, from a methodological perspective, our work demonstrates the ability of noise-based image classification in conjunction with fMRI to help uncover the structure of high-level perceptual representations. PMID:22711230

  18. Dishabituation of the BOLD response to speech sounds

    PubMed Central

    Zevin, Jason D; McCandliss, Bruce D

    2005-01-01

    Background Neural systems show habituation responses at multiple levels, including relatively abstract language categories. Dishabituation – responses to non-habituated stimuli – can provide a window into the structure of these categories, without requiring an overt task. Methods We used an event-related fMRI design with short interval habituation trials, in which trains of stimuli were presented passively during 1.5 second intervals of relative silence between clustered scans. Trains of four identical stimuli (standard trials) and trains of three identical stimuli followed by a stimulus from a different phonetic category (deviant trials) were presented. This paradigm allowed us to measure and compare the time course of overall responses to speech, and responses to phonetic change. Results Comparisons between responses to speech and silence revealed strong responses throughout the extent of superior temporal gyrus (STG) bilaterally. Comparisons between deviant and standard trials revealed dishabituation responses in a restricted region of left posterior STG, near the border with supramarginal gyrus (SMG). Novelty responses to deviant trials were also observed in right frontal regions and hippocampus. Conclusion A passive, dishabituation paradigm provides results similar to studies requiring overt responses. This paradigm can readily be extended for the study of pre-attentive processing of speech in populations such as children and second-language learners whose overt behavior is often difficult to interpret because of ancillary task demands. PMID:15953396

  19. fMRI response to negative words and SSRI treatment outcome in major depressive disorder: a preliminary study

    PubMed Central

    Miller, Jeffrey Morris; Schneck, Noam; Siegle, Greg J.; Chen, Yakuan; Ogden, R. Todd; Kikuchi, Toshiaki; Oquendo, Maria A.; Mann, J. John; Parsey, Ramin V.

    2013-01-01

    Clinically useful predictors of treatment outcome in major depressive disorder (MDD) remain elusive. We examined associations between functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal during active negative word processing and subsequent selective serotonin reuptake inhibitor (SSRI) treatment outcome in MDD. Unmedicated MDD subjects (n=17) performed an emotional word processing fMRI task, and then received eight weeks of standardized antidepressant treatment with escitalopram. Lower pre-treatment BOLD responses to negative words in midbrain, dorsolateral prefrontal cortex, paracingulate, anterior cingulate, thalamus and caudate nuclei correlated significantly with greater improvement following escitalopram treatment. Activation of these regions in response to negative words correlated significantly with reaction time for rating word relevance. Maximally predictive clusters of voxels identified using a cross-validation approach predicted 48% of the variance in response to treatment. This study provides preliminary evidence that SSRIs may be most beneficial in patients who are less able to engage cognitive control networks while processing negative stimuli. Differences between these findings and previous fMRI studies of SSRI treatment outcome may relate to differences in task design. Regional BOLD responses to negative words predictive of SSRI outcome in this study were both overlapping and distinct from those predictive of outcome with cognitive behavioral therapy (CBT) in previous studies using the same task. Future studies may examine prediction of differential outcome across treatments in the context of a randomized controlled trial. PMID:24446548

  20. BOLD response analysis by iterated local multigrid priors.

    PubMed

    da Rocha Amaral, Selene; Rabbani, Said R; Caticha, Nestor

    2007-06-01

    We present a non parametric Bayesian multiscale method to characterize the Hemodynamic Response HR as function of time. This is done by extending and adapting the Multigrid Priors (MGP) method proposed in (S.D.R. Amaral, S.R. Rabbani, N. Caticha, Multigrid prior for a Bayesian approach to fMRI, NeuroImage 23 (2004) 654-662; N. Caticha, S.D.R. Amaral, S.R. Rabbani, Multigrid Priors for fMRI time series analysis, AIP Conf. Proc. 735 (2004) 27-34). We choose an initial HR model and apply the MGP method to assign a posterior probability of activity for every pixel. This can be used to construct the map of activity. But it can also be used to construct the posterior averaged time series activity for different regions. This permits defining a new model which is only data-dependent. Now in turn it can be used as the model behind a new application of the MGP method to obtain another posterior probability of activity. The method converges in just a few iterations and is quite independent of the original HR model, as long as it contains some information of the activity/rest state of the patient. We apply this method of HR inference both to simulated and real data of blocks and event-related experiments. Receiver operating characteristic (ROC) curves are used to measure the number of errors with respect to a few hyperparameters. We also study the deterioration of the results for real data, under information loss. This is done by decreasing the signal to noise ratio and also by decreasing the number of images available for analysis and compare the robustness to other methods. PMID:17258909

  1. Acute Nicotine Administration Increases BOLD fMRI Signal in Brain Regions Involved in Reward Signaling and Compulsive Drug Intake in Rats

    PubMed Central

    Alexander, Jon C.; Perez, Pablo D.; Bauzo-Rodriguez, Rayna; Hall, Gabrielle; Klausner, Rachel; Guerra, Valerie; Zeng, Huadong; Igari, Moe; Febo, Marcelo

    2015-01-01

    Background: Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine. Methods: Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03–0.6mg/kg) on the BOLD signal was investigated for 10min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated. Results: A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal. Conclusions: These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function. PMID:25552431

  2. Modeling the Hemodynamic Response Function in fMRI: Efficiency, Bias and Mis-modeling

    PubMed Central

    Lindquist, Martin A.; Loh, Ji Meng; Atlas, Lauren Y.; Wager, Tor D.

    2012-01-01

    Most brain research to date has focused on studying the amplitude of evoked fMRI responses, though there has recently been an increased interest in measuring onset, peak latency and duration of the responses as well. A number of modeling procedures provide measures of the latency and duration of fMRI responses. In this work we compare several techniques that vary in their assumptions, model complexity, and interpretation. For each method, we introduce methods for estimating amplitude, peak latency, and duration and for performing inference in a multi-subject fMRI setting. We then assess the techniques’ relative sensitivity and their propensity for mis-attributing task effects on one parameter (e.g., duration) to another (e.g., amplitude). Finally, we introduce methods for quantifying model misspecification and assessing bias and power-loss related to the choice of model. Overall, the results show that it is surprisingly difficult to accurately recover true task-evoked changes in BOLD signal and that there are substantial differences among models in terms of power, bias and parameter confusability. Because virtually all fMRI studies in cognitive and affective neuroscience employ these models, the results bear on the interpretation of hemodynamic response estimates across a wide variety of psychological and neuroscientific studies. PMID:19084070

  3. Correlation between baseline blood pressure and the brainstem FMRI response to isometric forearm contraction in human volunteers: a pilot study.

    PubMed

    Coulson, J M; Murphy, K; Harris, A D; Fjodorova, M; Cockcroft, J R; Wise, R G

    2015-07-01

    It has been shown previously that changes in brainstem neural activity correlate with changes in both mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) during static handgrip (SHG). However, the relationship between baseline MAP and brainstem neural activity is unclear. We investigated changes in blood oxygen level-dependent (BOLD) signal induced by SHG in 12 young adults using BOLD functional magnetic resonance imaging (FMRI). An estimation of the blood pressure response to SHG was obtained in seven subjects during a session outside the MRI scanner and was used to model the blood pressure response to SHG inside the scanner. SHG at 40% of maximum grip increased MAP (mean ± s.d.) at the end of the 180-s squeeze from 85 ± 6 mm Hg to 108 ± 15 mm Hg, P = 0.0001. The brainstem BOLD signal change associated with SHG was localised to the ventrolateral medulla. This regional BOLD signal change negatively correlated with baseline MAP, r = -0.61, P = 0.01. This relationship between baseline MAP and brainstem FMRI responses to forearm contraction is suggestive of a possible role for brainstem activity in the control of MAP and may provide mechanistic insights into neurogenic hypertension. PMID:25391759

  4. The Relationship between Fearfulness, GABA+, and Fear-Related BOLD Responses in the Insula

    PubMed Central

    Lipp, Ilona; Evans, C. John; Lewis, Caroline; Murphy, Kevin; Wise, Richard G.; Caseras, Xavier

    2015-01-01

    The inhibitory neurotransmitter GABA plays a crucial role in anxiety and fear, but its relationship to brain activation during fear reactions is not clear. Previous studies suggest that GABA agonists lead to an attenuation of emotion-processing related BOLD signals in the insula. The aim of this study was to investigate the relationship between GABA concentration and fear-related BOLD responses in this region. In 44 female participants with different levels of fearfulness, GABA concentration in the left insula was measured using a GABA+ MRS acquisition during rest; additionally, BOLD signals were obtained during performance of a fear provocation paradigm. Fearfulness was not associated with GABA+ in the left insula, but could predict fear-related BOLD responses in a cluster in the left anterior insula. The BOLD signal change in this cluster did not correlate with GABA+ concentration. However, we found a significant positive correlation between GABA+ concentration and fear-related BOLD responses in a different cluster that included parts of the left insula, amygdala and putamen. Our findings indicate that low insular GABA concentration is not a predisposition for fearfulness, and that several factors influence whether a correlation between GABA and BOLD can be found. PMID:25811453

  5. Correlation between amygdala BOLD activity and frontal EEG asymmetry during real-time fMRI neurofeedback training in patients with depression.

    PubMed

    Zotev, Vadim; Yuan, Han; Misaki, Masaya; Phillips, Raquel; Young, Kymberly D; Feldner, Matthew T; Bodurka, Jerzy

    2016-01-01

    Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging approach for studies and novel treatments of major depressive disorder (MDD). EEG performed simultaneously with an rtfMRI-nf procedure allows an independent evaluation of rtfMRI-nf brain modulation effects. Frontal EEG asymmetry in the alpha band is a widely used measure of emotion and motivation that shows profound changes in depression. However, it has never been directly related to simultaneously acquired fMRI data. We report the first study investigating electrophysiological correlates of the rtfMRI-nf procedure, by combining the rtfMRI-nf with simultaneous and passive EEG recordings. In this pilot study, MDD patients in the experimental group (n = 13) learned to upregulate BOLD activity of the left amygdala using an rtfMRI-nf during a happy emotion induction task. MDD patients in the control group (n = 11) were provided with a sham rtfMRI-nf. Correlations between frontal EEG asymmetry in the upper alpha band and BOLD activity across the brain were examined. Average individual changes in frontal EEG asymmetry during the rtfMRI-nf task for the experimental group showed a significant positive correlation with the MDD patients' depression severity ratings, consistent with an inverse correlation between the depression severity and frontal EEG asymmetry at rest. The average asymmetry changes also significantly correlated with the amygdala BOLD laterality. Temporal correlations between frontal EEG asymmetry and BOLD activity were significantly enhanced, during the rtfMRI-nf task, for the amygdala and many regions associated with emotion regulation. Our findings demonstrate an important link between amygdala BOLD activity and frontal EEG asymmetry during emotion regulation. Our EEG asymmetry results indicate that the rtfMRI-nf training targeting the amygdala is beneficial to MDD patients. They further suggest that EEG-nf based on frontal EEG asymmetry in the alpha band would be compatible with the amygdala

  6. Correlation between amygdala BOLD activity and frontal EEG asymmetry during real-time fMRI neurofeedback training in patients with depression

    PubMed Central

    Zotev, Vadim; Yuan, Han; Misaki, Masaya; Phillips, Raquel; Young, Kymberly D.; Feldner, Matthew T.; Bodurka, Jerzy

    2016-01-01

    Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging approach for studies and novel treatments of major depressive disorder (MDD). EEG performed simultaneously with an rtfMRI-nf procedure allows an independent evaluation of rtfMRI-nf brain modulation effects. Frontal EEG asymmetry in the alpha band is a widely used measure of emotion and motivation that shows profound changes in depression. However, it has never been directly related to simultaneously acquired fMRI data. We report the first study investigating electrophysiological correlates of the rtfMRI-nf procedure, by combining the rtfMRI-nf with simultaneous and passive EEG recordings. In this pilot study, MDD patients in the experimental group (n = 13) learned to upregulate BOLD activity of the left amygdala using an rtfMRI-nf during a happy emotion induction task. MDD patients in the control group (n = 11) were provided with a sham rtfMRI-nf. Correlations between frontal EEG asymmetry in the upper alpha band and BOLD activity across the brain were examined. Average individual changes in frontal EEG asymmetry during the rtfMRI-nf task for the experimental group showed a significant positive correlation with the MDD patients' depression severity ratings, consistent with an inverse correlation between the depression severity and frontal EEG asymmetry at rest. The average asymmetry changes also significantly correlated with the amygdala BOLD laterality. Temporal correlations between frontal EEG asymmetry and BOLD activity were significantly enhanced, during the rtfMRI-nf task, for the amygdala and many regions associated with emotion regulation. Our findings demonstrate an important link between amygdala BOLD activity and frontal EEG asymmetry during emotion regulation. Our EEG asymmetry results indicate that the rtfMRI-nf training targeting the amygdala is beneficial to MDD patients. They further suggest that EEG-nf based on frontal EEG asymmetry in the alpha band would be compatible with the amygdala

  7. BOLD responses in the superior colliculus and lateral geniculate nucleus of the rat viewing an apparent motion stimulus.

    PubMed

    Lau, Condon; Zhang, Jevin W; Xing, Kyle K; Zhou, Iris Y; Cheung, Matthew M; Chan, Kevin C; Wu, Ed X

    2011-10-01

    In rats, the superior colliculus (SC) is a main destination for retinal ganglion cells and is an important subcortical structure for vision. Electrophysiology studies have observed that many SC neurons are highly sensitive to moving objects, but complementary non-invasive functional imaging studies with larger fields of view have been rarely conducted. In this study, BOLD fMRI is used to measure the SC and nearby lateral geniculate nucleus' (LGN) hemodynamic responses, in normal adult Sprague Dawley (SD) rats, during a dynamic visual stimulus similar to those used in long-range apparent motion studies. The stimulation paradigm consists of four light spots arranged in a linear array and turned on and off sequentially at different rates to create five effective speeds of motion (7, 14, 41, 82, and 164°/s across the visual field). Stationary periods (same light spot always on) are interleaved between the moving periods. The speed response function (SRF), the hemodynamic response amplitude at each speed tested, is measured. Significant responses are observed in the SC and LGN at all speeds. In the SC, the SRF increases monotonically from 7 to 82°/s. The minimum response amplitude occurs at 164°/s. The results suggest that the SC is sensitive to slow moving visual stimuli but the hemodynamic response is reduced at higher speeds. In the LGN, the SRF exhibits a similar trend to that of the SC, but response amplitude during 7°/s stimulation is comparable to that during 164°/s stimulation. These findings are in good agreement with previous electrophysiology studies conducted on albino rats like the SD strain. This work represents the first fMRI study of stimulus speed dependence in the SC and is also the first fMRI study of motion responsiveness in the rat. PMID:21741483

  8. Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation

    PubMed Central

    Hougaard, Anders; Jensen, Bettina Hagström; Amin, Faisal Mohammad; Rostrup, Egill; Hoffmann, Michael B.; Ashina, Messoud

    2015-01-01

    Hemispheric asymmetry of a wide range of functions is a hallmark of the human brain. The visual system has traditionally been thought of as symmetrically distributed in the brain, but a growing body of evidence has challenged this view. Some highly specific visual tasks have been shown to depend on hemispheric specialization. However, the possible lateralization of cerebral responses to a simple checkerboard visual stimulation has not been a focus of previous studies. To investigate this, we performed two sessions of blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in 54 healthy subjects during stimulation with a black and white checkerboard visual stimulus. While carefully excluding possible non-physiological causes of left-to-right bias, we compared the activation of the left and the right cerebral hemispheres and related this to grey matter volume, handedness, age, gender, ocular dominance, interocular difference in visual acuity, as well as line-bisection performance. We found a general lateralization of cerebral activation towards the right hemisphere of early visual cortical areas and areas of higher-level visual processing, involved in visuospatial attention, especially in top-down (i.e., goal-oriented) attentional processing. This right hemisphere lateralization was partly, but not completely, explained by an increased grey matter volume in the right hemisphere of the early visual areas. Difference in activation of the superior parietal lobule was correlated with subject age, suggesting a shift towards the left hemisphere with increasing age. Our findings suggest a right-hemispheric dominance of these areas, which could lend support to the generally observed leftward visual attentional bias and to the left hemifield advantage for some visual perception tasks. PMID:25985078

  9. Probing neuronal activation by functional quantitative susceptibility mapping under a visual paradigm: A group level comparison with BOLD fMRI and PET.

    PubMed

    Özbay, Pinar Senay; Warnock, Geoffrey; Rossi, Cristina; Kuhn, Felix; Akin, Burak; Pruessmann, Klaas Paul; Nanz, Daniel

    2016-08-15

    Dynamic changes of brain-tissue magnetic susceptibility provide the basis for functional MR imaging (fMRI) via T2*-weighted signal-intensity modulations. Promising initial work on a detection of neuronal activity via quantitative susceptibility mapping (fQSM) has been published but consistently reported on ill-understood positive and negative activation patterns (Balla et al., 2014; Chen and Calhoun, 2015a). We set out to (i) demonstrate that fQSM can exploit established fMRI data acquisition and processing methods and to (ii) better describe aspects of the apparent activation patterns using fMRI and PET as standards of reference. Under a standardized visual-stimulation paradigm PET and 3-T gradient-echo EPI-based fQSM, fMRI data from 9 healthy volunteers were acquired and analyzed by means of Independent Component Analysis (ICA) at subject level and, for the first time, at group level. Numbers of activated (z-score>2.0) voxels were counted and their mean z-scores calculated in volumes of interest (occipital lobe (Nocc_lobe), segmented occipital gray-matter (NGM_occ_lobe), large veins (Nveins)), and in occipital-lobe voxels commonly activated in fQSM and fMRI component maps. Common but not entirely congruent regions of apparent activation were found in the occipital lobe in z-score maps from all modalities, fQSM, fMRI and PET, with distinct BOLD-negatively correlated regions in fQSM data. At subject-level, Nocc_lobe, NGM_occ_lobe and their mean z-scores were significantly smaller in fQSM than in fMRI, but their ratio, NGM_occ_lobe/Nocc_lobe, was comparable. Nveins did not statistically differ and the ratio Nveins/NGM_occ_lobe as well as the mean z-scores were higher for fQSM than for fMRI. In veins and immediate vicinity, z-score maps derived from both phase and fQSM-data showed positive and negative lobes resembling dipole shapes in simulated field and phase maps with no correlate in fMRI or PET data. Our results show that standard fMRI tools can directly be used

  10. Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers

    PubMed Central

    Versace, Francesco; Engelmann, Jeffrey M.; Jackson, Edward F.; Costa, Vincent D.; Robinson, Jason D.; Lam, Cho Y.; Minnix, Jennifer A.; Brown, Victoria L.; Cinciripini, Paul M.

    2011-01-01

    Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing 1) would be more active during exposure to cigarette-related than neutral pictures, and 2) would be less active to pleasant compared to cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole brain blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli. PMID:22097928

  11. Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients

    PubMed Central

    Garza-Villarreal, Eduardo A.; Jiang, Zhiguo; Vuust, Peter; Alcauter, Sarael; Vase, Lene; Pasaye, Erick H.; Cavazos-Rodriguez, Roberto; Brattico, Elvira; Jensen, Troels S.; Barrios, Fernando A.

    2015-01-01

    Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (rACC), right supplementary motor area (rSMA), precuneus and right precentral gyrus (rPreG). Pain intensity (PI) analgesia was correlated (r = 0.61) to the connectivity of the lAnG with the rPreG. Our results show that MIA in FM is related to top-down regulation of the pain modulatory network by the default mode network (DMN). PMID:26257695

  12. The hemodynamic response to somatosensory stimulation in mice depends on the anesthetic used: Implications on analysis of mouse fMRI data.

    PubMed

    Schlegel, Felix; Schroeter, Aileen; Rudin, Markus

    2015-08-01

    In recent years, the number of functional MRI (fMRI) studies in mice has been rapidly increasing. Technological improvements provide the sensitivity required to match the high demands on spatial and temporal resolution and to analyze fast and small signal components of the fMRI response. Yet, the interpretation of mouse fMRI data largely relies on assumptions that were uncritically adopted from previous research in humans or rats. Here, we show based on a large dataset employing an innocuous electrical stimulation paradigm, that (1) the shape of the HRF shapes comprises significant transient signal components; correspondingly analysis procedures have to account for this dynamic nature and allow for variable response functions. (2) The effects of the anesthetics are crucial in determining the shape of the hemodynamic response function (HRF) and also influence the spatial specificity of BOLD signal. (3) The dominant systemic confounding contributions elicited by stimulus-evoked cardiovascular responses observed in mouse fMRI when applying block stimuli may be largely avoided by a milder event-related design applying a randomly spaced single pulse train (RSSPT). Thereby the spatial specificity of the fMRI response is largely retained. We conclude that the sensitivity, specificity and interpretability of stimulus-evoked BOLD signals in mice can be improved by combining appropriate stimulation paradigms with analysis procedures that include adapted HRFs. PMID:25979665

  13. Cortical Network Models of Firing Rates in the Resting and Active States Predict BOLD Responses

    PubMed Central

    Bennett, Maxwell R.; Farnell, Les; Gibson, William G.; Lagopoulos, Jim

    2015-01-01

    Measurements of blood oxygenation level dependent (BOLD) signals have produced some surprising observations. One is that their amplitude is proportional to the entire activity in a region of interest and not just the fluctuations in this activity. Another is that during sleep and anesthesia the average BOLD correlations between regions of interest decline as the activity declines. Mechanistic explanations of these phenomena are described here using a cortical network model consisting of modules with excitatory and inhibitory neurons, taken as regions of cortical interest, each receiving excitatory inputs from outside the network, taken as subcortical driving inputs in addition to extrinsic (intermodular) connections, such as provided by associational fibers. The model shows that the standard deviation of the firing rate is proportional to the mean frequency of the firing when the extrinsic connections are decreased, so that the mean BOLD signal is proportional to both as is observed experimentally. The model also shows that if these extrinsic connections are decreased or the frequency of firing reaching the network from the subcortical driving inputs is decreased, or both decline, there is a decrease in the mean firing rate in the modules accompanied by decreases in the mean BOLD correlations between the modules, consistent with the observed changes during NREM sleep and under anesthesia. Finally, the model explains why a transient increase in the BOLD signal in a cortical area, due to a transient subcortical input, gives rises to responses throughout the cortex as observed, with these responses mediated by the extrinsic (intermodular) connections. PMID:26659399

  14. High spatial resolution increases the specificity of block-design BOLD fMRI studies of overt vowel production.

    PubMed

    Soltysik, David A; Hyde, James S

    2008-06-01

    Functional MRI (fMRI) studies of tasks involving orofacial motion, such as speech, are prone to problems related to motion-induced magnetic field variations. Orofacial motion perturbs the static magnetic field, leading to signal changes that correlate with the task and corrupt activation maps with false positives or signal loss. These motion-induced signal changes represent a contraindication for the implementation of fMRI to study the neurophysiology of orofacial motion. An fMRI experiment of a structured, non-semantic vowel production task was performed using four different voxel volumes and three different slice orientations in an attempt to find a set of acquisition parameters leading to activation maps with maximum specificity. Results indicate that the use of small voxel volumes (2 x 2 x 3 mm(3)) yielded a significantly higher percentage of true positive activation compared to the use of larger voxel volumes. Slice orientation did not have as great an impact as spatial resolution, although coronal slices appeared superior at high spatial resolutions. Furthermore, it was found that combining the strategy of high spatial resolution with an optimum task duration and post-processing methods for separating true and false positives greatly improved the specificity of single-subject, block-design fMRI studies of structured, overt vowel production. PMID:18387825

  15. An fMRI study of behavioral response inhibition in adolescents with and without histories of heavy prenatal alcohol exposure

    PubMed Central

    Ware, Ashley L.; Infante, M. Alejandra; O’Brien, Jessica W.; Tapert, Susan F.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

    2014-01-01

    Heavy prenatal alcohol exposure results in a range of deficits, including both volumetric and functional changes in brain regions involved in response inhibition such as the prefrontal cortex and striatum. The current study examined blood oxygen level-dependent (BOLD) response during a stop signal task in adolescents (ages 13–16 y) with histories of heavy prenatal alcohol exposure (AE, n = 21) and controls (CON, n = 21). Task performance was measured using percent correct inhibits during three difficulty conditions: easy, medium, and hard. Group differences in BOLD response relative to baseline motor responding were examined across all inhibition trials and for each difficulty condition separately. The contrast between hard and easy trials was analyzed to determine whether increasing task difficulty affected BOLD response. Groups had similar task performance and demographic characteristics, except for full scale IQ scores (AE < CON). The AE group demonstrated greater BOLD response in frontal, sensorimotor, striatal, and cingulate regions relative to controls, especially as task difficulty increased. When contrasting hard vs. easy inhibition trials, the AE group showed greater medial/superior frontal and cuneus BOLD response than controls. Results were unchanged after demographics and FAS diagnosis were statistically controlled. This was the first fMRI study to utilize a stop signal task, isolating fronto-striatal functioning, to assess response inhibition and the effects task difficulty in adolescents with prenatal alcohol exposure. Results suggest that heavy prenatal alcohol exposure disrupts neural function of this circuitry, resulting in immature cognitive processing and motor-association learning and neural compensation during response inhibition. PMID:25281280

  16. An fMRI study of behavioral response inhibition in adolescents with and without histories of heavy prenatal alcohol exposure.

    PubMed

    Ware, Ashley L; Infante, M Alejandra; O'Brien, Jessica W; Tapert, Susan F; Jones, Kenneth Lyons; Riley, Edward P; Mattson, Sarah N

    2015-02-01

    Heavy prenatal alcohol exposure results in a range of deficits, including both volumetric and functional changes in brain regions involved in response inhibition such as the prefrontal cortex and striatum. The current study examined blood oxygen level-dependent (BOLD) response during a stop signal task in adolescents (ages 13-16 y) with histories of heavy prenatal alcohol exposure (AE, n=21) and controls (CON, n=21). Task performance was measured using percent correct inhibits during three difficulty conditions: easy, medium, and hard. Group differences in BOLD response relative to baseline motor responding were examined across all inhibition trials and for each difficulty condition separately. The contrast between hard and easy trials was analyzed to determine whether increasing task difficulty affected BOLD response. Groups had similar task performance and demographic characteristics, except for full scale IQ scores (AEBOLD response in frontal, sensorimotor, striatal, and cingulate regions relative to controls, especially as task difficulty increased. When contrasting hard vs. easy inhibition trials, the AE group showed greater medial/superior frontal and cuneus BOLD response than controls. Results were unchanged after demographics and FAS diagnosis were statistically controlled. This was the first fMRI study to utilize a stop signal task, isolating fronto-striatal functioning, to assess response inhibition and the effects task difficulty in adolescents with prenatal alcohol exposure. Results suggest that heavy prenatal alcohol exposure disrupts neural function of this circuitry, resulting in immature cognitive processing and motor-association learning and neural compensation during response inhibition. PMID:25281280

  17. Relative changes of cerebral arterial and venous blood volumes during increased cerebral blood flow: implications for BOLD fMRI.

    PubMed

    Lee, S P; Duong, T Q; Yang, G; Iadecola, C; Kim, S G

    2001-05-01

    Measurement of cerebral arterial and venous blood volumes during increased cerebral blood flow can provide important information regarding hemodynamic regulation under normal, pathological, and neuronally active conditions. In particular, the change in venous blood volume induced by neural activity is one critical component of the blood oxygenation level-dependent (BOLD) signal because BOLD contrast is dependent only on venous blood, not arterial blood. Thus, relative venous and arterial blood volume (rCBV) and cerebral blood flow (rCBF) in alpha-chlorolase-anesthetized rats under hypercapnia were measured by novel diffusion-weighted (19)F NMR following an i.v. administration of intravascular tracer, perfluorocarbons, and continuous arterial spin labeling methods, respectively. The relationship between rCBF and total rCBV during hypercapnia was rCBV(total) = rCBF(0.40), which is consistent with previous PET measurement in monkeys. This relationship can be linearized in a CBF range of 50-130 ml/100 g/min as DeltarCBV(total)/ DeltarCBF = 0.31 where DeltarCBV and DeltarCBF represent rCBV and rCBF changes. The average arterial volume fraction was 0.25 at a basal condition with CBF of approximately 60 ml/100 g/min and increased up to 0.4 during hypercapnia. The change in venous rCBV was 2-fold smaller than that of total rCBV (DeltarCBV(vein)/DeltarCBF = 0.15), while the arterial rCBV change was 2.5 times larger than that of total rCBV (DeltarCBV(artery)/DeltarCBF = 0.79). These NMR results were confirmed by vessel diameter measurements with in vivo videomicroscopy. The absolute venous blood volume change contributes up to 36% of the total blood volume change during hypercapnia. Our findings provide a quantitative physiological model of BOLD contrast. PMID:11323805

  18. Reproducing the Hemoglobin Saturation Profile, a Marker of the Blood Oxygenation Level Dependent (BOLD) fMRI Effect, at the Microscopic Level.

    PubMed

    Hadjistassou, Constantinos; Moyle, Keri; Ventikos, Yiannis

    2016-01-01

    The advent of functional MRI in the mid-1990s has catalyzed progress pertaining to scientific discoveries in neuroscience. With the prospect of elucidating the physiological aspect of the Blood Oxygenation Level Dependent (BOLD) effect we present a computational capillary-tissue system capable of mapping venous hemoglobin saturation- a marker of the BOLD hemodynamic response. Free and facilitated diffusion and convection for hemoglobin and oxygen are considered in the radial and axial directions. Hemoglobin reaction kinetics are governed by the oxyhemoglobin dissociation curve. Brain activation, mimicked by dynamic transitions in cerebral blood velocity (CBv) and oxidative metabolism (CMRO2), is simulated by normalized changes in m = (ΔCBv/CBv)/(ΔCMRO2/CMRO2) of values 2, 3 and 4. Venous hemoglobin saturation profiles and peak oxygenation results, for m = 2, based upon a 50% and a 25% increase in CBv and CMRO2, respectively, lie within physiological limits exhibiting excellent correlation with the BOLD signal, for short-duration stimuli. Our analysis suggests basal CBv and CMRO2 values of 0.6 mm/s and 200 μmol/100g/min. Coupled CBv and CMRO2 responses, for m = 3 and m = 4, overestimate peak hemoglobin saturation, confirming the system's responsiveness to changes in hematocrit, CBv and CMRO2. Finally, factoring in neurovascular effects, we show that no initial dip will be observed unless there is a time delay in the onset of increased CBv relative to CMRO2. PMID:26939128

  19. Reproducing the Hemoglobin Saturation Profile, a Marker of the Blood Oxygenation Level Dependent (BOLD) fMRI Effect, at the Microscopic Level

    PubMed Central

    Hadjistassou, Constantinos; Moyle, Keri; Ventikos, Yiannis

    2016-01-01

    The advent of functional MRI in the mid-1990s has catalyzed progress pertaining to scientific discoveries in neuroscience. With the prospect of elucidating the physiological aspect of the Blood Oxygenation Level Dependent (BOLD) effect we present a computational capillary-tissue system capable of mapping venous hemoglobin saturation— a marker of the BOLD hemodynamic response. Free and facilitated diffusion and convection for hemoglobin and oxygen are considered in the radial and axial directions. Hemoglobin reaction kinetics are governed by the oxyhemoglobin dissociation curve. Brain activation, mimicked by dynamic transitions in cerebral blood velocity (CBv) and oxidative metabolism (CMRO2), is simulated by normalized changes in m = (ΔCBv/CBv)/(ΔCMRO2/CMRO2) of values 2, 3 and 4. Venous hemoglobin saturation profiles and peak oxygenation results, for m = 2, based upon a 50% and a 25% increase in CBv and CMRO2, respectively, lie within physiological limits exhibiting excellent correlation with the BOLD signal, for short-duration stimuli. Our analysis suggests basal CBv and CMRO2 values of 0.6 mm/s and 200 μmol/100g/min. Coupled CBv and CMRO2 responses, for m = 3 and m = 4, overestimate peak hemoglobin saturation, confirming the system’s responsiveness to changes in hematocrit, CBv and CMRO2. Finally, factoring in neurovascular effects, we show that no initial dip will be observed unless there is a time delay in the onset of increased CBv relative to CMRO2. PMID:26939128

  20. BOLD Responses in Human Primary Visual Cortex are Insensitive to Substantial Changes in Neural Activity.

    PubMed

    Swettenham, J B; Muthukumaraswamy, S D; Singh, K D

    2013-01-01

    The relationship between blood oxygenation level dependent-functional magnetic resonance imaging (BOLD-fMRI) and magnetoencephalography (MEG) metrics were explored using low-level visual stimuli known to elicit a rich variety of neural responses. Stimuli were either perceptually isoluminant red/green or luminance-modulated black/yellow square-wave gratings with spatial frequencies of 0.5, 3, and 6 cycles per degree. Neural responses were measured with BOLD-fMRI (3-tesla) and whole head MEG. For all stimuli, the BOLD response showed bilateral activation of early visual cortex that was greater in the contralateral hemisphere. There was variation between individuals but weak, or no evidence, of amplitude dependence on either spatial frequency or the presence of luminance contrast. In contrast, beamformer analysis of MEG data showed activation in contralateral early visual cortex and revealed: (i) evoked responses with stimulus-dependent amplitude and latency; (ii) gamma and high-beta oscillations, with spatial frequency dependent peaks at approximately 30 and 50 Hz, but only for luminance-modulated gratings; (iii) The gamma and beta oscillations appeared to show different spatial frequency tuning profiles; (iv) much weaker gamma and beta responses, and at higher oscillation frequencies, for isoluminant compared to luminance-modulated gratings. The results provide further evidence that the relationship between the fMRI-BOLD response and cortical neural activity is complex, with BOLD-fMRI being insensitive to substantial changes in neural activity. All stimuli were clearly visible to participants and so the paucity of gamma oscillations to isoluminant stimuli is inconsistent with theories of their role in conscious visual perception. PMID:23482840

  1. Fourier power, subjective distance, and object categories all provide plausible models of BOLD responses in scene-selective visual areas

    PubMed Central

    Lescroart, Mark D.; Stansbury, Dustin E.; Gallant, Jack L.

    2015-01-01

    Perception of natural visual scenes activates several functional areas in the human brain, including the Parahippocampal Place Area (PPA), Retrosplenial Complex (RSC), and the Occipital Place Area (OPA). It is currently unclear what specific scene-related features are represented in these areas. Previous studies have suggested that PPA, RSC, and/or OPA might represent at least three qualitatively different classes of features: (1) 2D features related to Fourier power; (2) 3D spatial features such as the distance to objects in a scene; or (3) abstract features such as the categories of objects in a scene. To determine which of these hypotheses best describes the visual representation in scene-selective areas, we applied voxel-wise modeling (VM) to BOLD fMRI responses elicited by a set of 1386 images of natural scenes. VM provides an efficient method for testing competing hypotheses by comparing predictions of brain activity based on encoding models that instantiate each hypothesis. Here we evaluated three different encoding models that instantiate each of the three hypotheses listed above. We used linear regression to fit each encoding model to the fMRI data recorded from each voxel, and we evaluated each fit model by estimating the amount of variance it predicted in a withheld portion of the data set. We found that voxel-wise models based on Fourier power or the subjective distance to objects in each scene predicted much of the variance predicted by a model based on object categories. Furthermore, the response variance explained by these three models is largely shared, and the individual models explain little unique variance in responses. Based on an evaluation of previous studies and the data we present here, we conclude that there is currently no good basis to favor any one of the three alternative hypotheses about visual representation in scene-selective areas. We offer suggestions for further studies that may help resolve this issue. PMID:26594164

  2. Neural signatures of experimentally induced flow experiences identified in a typical fMRI block design with BOLD imaging.

    PubMed

    Ulrich, Martin; Keller, Johannes; Grön, Georg

    2016-03-01

    Previously, experimentally induced flow experiences have been demonstrated with perfusion imaging during activation blocks of 3 min length to accommodate with the putatively slowly evolving "mood" characteristics of flow. Here, we used functional magnetic resonance imaging (fMRI) in a sample of 23 healthy, male participants to investigate flow in the context of a typical fMRI block design with block lengths as short as 30 s. To induce flow, demands of arithmetic tasks were automatically and continuously adjusted to the individual skill level. Compared against conditions of boredom and overload, experience of flow was evident from individuals' reported subjective experiences and changes in electrodermal activity. Neural activation was relatively increased during flow, particularly in the anterior insula, inferior frontal gyri, basal ganglia and midbrain. Relative activation decreases during flow were observed in medial prefrontal and posterior cingulate cortex, and in the medial temporal lobe including the amygdala. Present findings suggest that even in the context of comparably short activation blocks flow can be reliably experienced and is associated with changes in neural activation of brain regions previously described. Possible mechanisms of interacting brain regions are outlined, awaiting further investigation which should now be possible given the greater temporal resolution compared with previous perfusion imaging. PMID:26508774

  3. A NO way to BOLD? Dietary nitrate alters the hemodynamic response to visual stimulation.

    PubMed

    Aamand, Rasmus; Dalsgaard, Thomas; Ho, Yi-Ching Lynn; Møller, Arne; Roepstorff, Andreas; Lund, Torben E

    2013-12-01

    Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway. On this basis, we hypothesized that dietary nitrate (NO3-) could influence the brain's hemodynamic response to neuronal stimulation. In the present study, 20 healthy male participants were given either sodium nitrate (NaNO3) or sodium chloride (NaCl) (saline placebo) in a crossover study and were shown visual stimuli based on the retinotopic characteristics of the visual cortex. Our primary measure of the hemodynamic response was the blood oxygenation level dependent (BOLD) response measured with high-resolution functional magnetic resonance imaging (0.64×0.64×1.8 mm) in the visual cortex. From this response, we made a direct estimate of key parameters characterizing the shape of the BOLD response (i.e. lag and amplitude). During elevated nitrate intake, corresponding to the nitrate content of a large plate of salad, both the hemodynamic lag and the BOLD amplitude decreased significantly (7.0±2% and 7.9±4%, respectively), and the variation across activated voxels of both measures decreased (12.3±4% and 15.3±7%, respectively). The baseline cerebral blood flow was not affected by nitrate. Our experiments demonstrate, for the first time, that dietary nitrate may modulate the local cerebral hemodynamic response to stimuli. A faster and smaller BOLD response, with less variation across local cortex, is consistent with an enhanced hemodynamic coupling during elevated nitrate intake. These findings suggest that dietary patterns, via the nitrate-nitrite-NO pathway, may be a potential way to affect key properties of neurovascular coupling. This could have major clinical implications, which remain to be explored. PMID:23827330

  4. Application of fMRI to obesity research: differences in reward pathway activation measured with fMRI BOLD during visual presentation of high and low calorie foods

    NASA Astrophysics Data System (ADS)

    Tsao, Sinchai; Adam, Tanja C.; Goran, Michael I.; Singh, Manbir

    2012-03-01

    The factors behind the neural mechanisms that motivate food choice and obesity are not well known. Furthermore, it is not known when these neural mechanisms develop and how they are influenced by both genetic and environmental factors. This study uses fMRI together with clinical data to shed light on the aforementioned questions by investigating how appetite-related activation in the brain changes with low versus high caloric foods in pre-pubescent girls. Previous studies have shown that obese adults have less striatal D2 receptors and thus reduced Dopamine (DA) signaling leading to the reward-deficit theory of obesity. However, overeating in itself reduces D2 receptor density, D2 sensitivity and thus reward sensitivity. The results of this study will show how early these neural mechanisms develop and what effect the drastic endocrinological changes during puberty has on these mechanisms. Our preliminary results showed increased activations in the Putamen, Insula, Thalamus and Hippocampus when looking at activations where High Calorie > Low Calorie. When comparing High Calorie > Control and Low Calorie > Control, the High > Control test showed increased significant activation in the frontal lobe. The Low > Control also yielded significant activation in the Left and Right Fusiform Gyrus, which did not appear in the High > Control test. These results indicate that the reward pathway activations previously shown in post-puberty and adults are present in pre-pubescent teens. These results may suggest that some of the preferential neural mechanisms of reward are already present pre-puberty.

  5. Dopamine-induced dissociation of BOLD and neural activity in macaque visual cortex.

    PubMed

    Zaldivar, Daniel; Rauch, Alexander; Whittingstall, Kevin; Logothetis, Nikos K; Goense, Jozien

    2014-12-01

    Neuromodulators determine how neural circuits process information during cognitive states such as wakefulness, attention, learning, and memory. fMRI can provide insight into their function and dynamics, but their exact effect on BOLD responses remains unclear, limiting our ability to interpret the effects of changes in behavioral state using fMRI. Here, we investigated the effects of dopamine (DA) injections on neural responses and haemodynamic signals in macaque primary visual cortex (V1) using fMRI (7T) and intracortical electrophysiology. Aside from DA's involvement in diseases such as Parkinson's and schizophrenia, it also plays a role in visual perception. We mimicked DAergic neuromodulation by systemic injection of L-DOPA and Carbidopa (LDC) or by local application of DA in V1 and found that systemic application of LDC increased the signal-to-noise ratio (SNR) and amplitude of the visually evoked neural responses in V1. However, visually induced BOLD responses decreased, whereas cerebral blood flow (CBF) responses increased. This dissociation of BOLD and CBF suggests that dopamine increases energy metabolism by a disproportionate amount relative to the CBF response, causing the reduced BOLD response. Local application of DA in V1 had no effect on neural activity, suggesting that the dopaminergic effects are mediated by long-range interactions. The combination of BOLD-based and CBF-based fMRI can provide a signature of dopaminergic neuromodulation, indicating that the application of multimodal methods can improve our ability to distinguish sensory processing from neuromodulatory effects. PMID:25456449

  6. Joint maximum likelihood estimation of activation and Hemodynamic Response Function for fMRI.

    PubMed

    Bazargani, Negar; Nosratinia, Aria

    2014-07-01

    Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) maps the brain activity by measuring blood oxygenation level, which is related to brain activity via a temporal impulse response function known as the Hemodynamic Response Function (HRF). The HRF varies from subject to subject and within areas of the brain, therefore a knowledge of HRF is necessary for accurately computing voxel activations. Conversely a knowledge of active voxels is highly beneficial for estimating the HRF. This work presents a joint maximum likelihood estimation of HRF and activation based on low-rank matrix approximations operating on regions of interest (ROI). Since each ROI has limited data, a smoothing constraint on the HRF is employed via Tikhonov regularization. The method is analyzed under both white noise and colored noise. Experiments with synthetic data show that accurate estimation of the HRF is possible with this method without prior assumptions on the exact shape of the HRF. Further experiments involving real fMRI experiments with auditory stimuli are used to validate the proposed method. PMID:24835179

  7. Moderating Effect of Working Memory Capacity on Acute Alcohol Effects on BOLD Response During Inhibition and Error Monitoring in Male Heavy Drinkers

    PubMed Central

    Claus, Eric D.; Hendershot, Christian S.

    2014-01-01

    Rationale While alcohol intoxication is known to increase disinhibited behavior, the degree to which disinhibition occurs appears to depend on a number of factors including executive functioning ability. However, the neural mechanisms by which individual differences in executive functioning lead to variable degrees of disinhibition remain unclear. Objectives The aim of the current study was to examine the neural mechanisms by which individual differences in WM capacity moderate alcohol-induced disinhibition. Methods Seventeen heavy drinking males participated in a within-subjects design in which two sessions were completed: an alcohol session (.82g/kg) and a control session. Participants completed a Go/No-go task while undergoing functional magnetic resonance imaging (fMRI) after ingestion of the control or alcohol beverage. WM capacity was measured using an operation span task. Results Significant interactions of session and WM capacity emerged in contrasts examining successful response inhibition within superior temporal gyrus and unsuccessful inhibition in regions within the default mode network. In all cases, individuals with low WM capacity demonstrated a relative decrease in blood oxygen level dependent (BOLD) response during the alcohol compared to control session whereas the high WM capacity group demonstrated relative increases in BOLD response in the alcohol compared to control session. Conclusions Low WM capacity appears to be associated with decreased neural response to signals indicating a need for behavioral control, an effect that may lead to increased difficulty with inhibiting responses and increased negative consequences from alcohol intoxication. PMID:25127927

  8. Citicoline Treatment Improves Measures of Impulsivity and Task Performance in Chronic Marijuana Smokers: A Pilot BOLD fMRI Study

    PubMed Central

    Gruber, Staci A.; Sagar, Kelly A.; Dahlgren, Mary Kathryn; Gonenç, Atilla; Conn, Nina A.; Winer, Jeffrey P.; Penetar, David; Lukas, Scott E.

    2015-01-01

    Objective Citicoline is an endogenous nucleotide that has historically been used to treat stroke, traumatic brain injury, and cognitive dysfunction. Research has also shown that citicoline treatment is associated with improved cognitive performance in substance-abusing populations. We hypothesized that marijuana (MJ) smokers who received citicoline would demonstrate improvement in cognitive performance as well as increased neural efficiency during tasks of cognitive control relative to those who received placebo. Method The current study tested this hypothesis by examining the effects of citicoline in treatment-seeking chronic MJ smokers. In an 8-week double-blind, placebo-controlled study, 19 MJ smokers were randomly assigned via a double-blind procedure to the citicoline (8 Males, 2 Females) or placebo group (9 Males, 0 Females). All participants completed fMRI scanning at baseline and after 8 weeks of treatment during two cognitive measures of inhibitory processing, the Multi Source Interference Test (MSIT) and Stroop Color Word Test, and also completed the Barratt Impulsiveness Scale (BIS-11), a self-report measure of impulsivity. Results Following the 8 week trial, MJ smokers treated with citicoline demonstrated significantly lower levels of behavioral impulsivity, improved task accuracy on both the MSIT and Stroop tasks, and exhibited significantly different patterns of brain activation relative to baseline levels and relative to those who received placebo. Conclusions Findings suggest that citicoline may facilitate the treatment of MJ use disorders by improving the cognitive skills necessary to fully engage in comprehensive treatment programs. PMID:26658924

  9. Dependence of chromatic responses in V1 on visual field eccentricity and spatial frequency: an fMRI study.

    PubMed

    D'Souza, Dany V; Auer, Tibor; Frahm, Jens; Strasburger, Hans; Lee, Barry B

    2016-03-01

    Psychophysical sensitivity to red-green chromatic modulation decreases with visual eccentricity, compared to sensitivity to luminance modulation, even after appropriate stimulus scaling. This is likely to occur at a central, rather than a retinal, site. Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to stimuli designed to separately stimulate different afferent channels' [red-green, luminance, and short-wavelength (S)-cone] circular gratings were recorded as a function of visual eccentricity (±10  deg) and spatial frequency (SF) in human primary visual cortex (V1) and further visual areas (V2v, V3v). In V1, the SF tuning of BOLD fMRI responses became coarser with eccentricity. For red-green and luminance gratings, similar SF tuning curves were found at all eccentricities. The pattern for S-cone modulation differed, with SF tuning changing more slowly with eccentricity than for the other two modalities. This may be due to the different retinal distribution with eccentricity of this receptor type. A similar pattern held in V2v and V3v. This would suggest that transformation or spatial filtering of the chromatic (red-green) signal occurs beyond these areas. PMID:26974942

  10. Comparing consistency of R2* and T2*-weighted BOLD analysis of resting state fetal fMRI

    NASA Astrophysics Data System (ADS)

    Seshamani, Sharmishtaa; Blazejewska, Anna I.; Gatenby, Christopher; Mckown, Susan; Caucutt, Jason; Dighe, Manjiri; Studholme, Colin

    2015-03-01

    Understanding when and how resting state brain functional activity begins in the human brain is an increasing area of interest in both basic neuroscience and in the clinical evaluation of the brain during pregnancy and after premature birth. Although fMRI studies have been carried out on pregnant women since the 1990's, reliable mapping of brain function in utero is an extremely challenging problem due to the unconstrained fetal head motion. Recent studies have employed scrubbing to exclude parts of the time series and whole subjects from studies in order to control the confounds of motion. Fundamentally, even after correction of the location of signals due to motion, signal intensity variations are a fundamental limitation, due to coil sensitivity and spin history effects. An alternative technique is to use a more parametric MRI signal derived from multiple echoes that provides a level of independence from basic MRI signal variation. Here we examine the use of R2* mapping combined with slice based multi echo geometric distortion correction for in-utero studies. The challenges for R2* mapping arise from the relatively low signal strength of in-utero data. In this paper we focus on comparing activation detection in-utero using T2W and R2* approaches. We make use a subset of studies with relatively limited motion to compare the activation patterns without the additional confound of significant motion. Results at different gestational ages indicate comparable agreement in many activation patterns when limited motion is present, and the detection of some additional networks in the R2* data, not seen in the T2W results.

  11. One pair of hands is not like another: caudate BOLD response in dogs depends on signal source and canine temperament

    PubMed Central

    Cook, Peter F.; Spivak, Mark

    2014-01-01

    Having previously used functional MRI to map the response to a reward signal in the ventral caudate in awake unrestrained dogs, here we examined the importance of signal source to canine caudate activation. Hand signals representing either incipient reward or no reward were presented by a familiar human (each dog’s respective handler), an unfamiliar human, and via illustrated images of hands on a computer screen to 13 dogs undergoing voluntary fMRI. All dogs had received extensive training with the reward and no-reward signals from their handlers and with the computer images and had minimal exposure to the signals from strangers. All dogs showed differentially higher BOLD response in the ventral caudate to the reward versus no reward signals, and there was a robust effect at the group level. Further, differential response to the signal source had a highly significant interaction with a dog’s general aggressivity as measured by the C-BARQ canine personality assessment. Dogs with greater aggressivity showed a higher differential response to the reward signal versus no-reward signal presented by the unfamiliar human and computer, while dogs with lower aggressivity showed a higher differential response to the reward signal versus no-reward signal from their handler. This suggests that specific facets of canine temperament bear more strongly on the perceived reward value of relevant communication signals than does reinforcement history, as each of the dogs were reinforced similarly for each signal, regardless of the source (familiar human, unfamiliar human, or computer). A group-level psychophysiological interaction (PPI) connectivity analysis showed increased functional coupling between the caudate and a region of cortex associated with visual discrimination and learning on reward versus no-reward trials. Our findings emphasize the sensitivity of the domestic dog to human social interaction, and may have other implications and applications pertinent to the training

  12. Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects.

    PubMed

    Bogdanov, Volodymyr B; Viganò, Alessandro; Noirhomme, Quentin; Bogdanova, Olena V; Guy, Nathalie; Laureys, Steven; Renshaw, Perry F; Dallel, Radhouane; Phillips, Christophe; Schoenen, Jean

    2015-03-15

    The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n=7), increased (n=10) or stayed unchanged (n=7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety. PMID:25461267

  13. Spatially Extended fMRI Signal Response to Stimulus in Non-Functionally Relevant Regions of the Human Brain: Preliminary Results

    PubMed Central

    Kornak, John; Hall, Deborah A; Haggard, Mark P

    2011-01-01

    The blood-oxygenation level dependent (BOLD) haemodynamic response function (HDR) in functional magnetic resonance imaging (fMRI) is a delayed and indirect marker of brain activity. In this single case study a small BOLD response synchronised with the stimulus paradigm is found globally, i.e. in all areas outside those of expected activation in a single subject study. The nature of the global response has similar shape properties to the archetypal BOLD HDR, with an early positive signal and a late negative response typical of the negative overshoot. Fitting Poisson curves to these responses showed that voxels were potentially split into two sets: one with dominantly positive signal and the other predominantly negative. A description, quantification and mapping of the global BOLD response is provided along with a 2 × 2 classification table test to demonstrate existence with very high statistical confidence. Potential explanations of the global response are proposed in terms of 1) global HDR balancing; 2) resting state network modulation; and 3) biological systems synchronised with the stimulus cycle. Whilst these widespread and low-level patterns seem unlikely to provide additional information for determining activation in functional neuroimaging studies as conceived in the last 15 years, knowledge of their properties may assist more comprehensive accounts of brain connectivity in the future. PMID:21760873

  14. Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3.

    PubMed

    Duarte, João Valente; Faustino, Ricardo; Lobo, Mercês; Cunha, Gil; Nunes, César; Ferreira, Carlos; Januário, Cristina; Castelo-Branco, Miguel

    2016-10-01

    Machado-Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole-brain functional biomarkers, based on parametric performance-level-dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel-based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio-paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance-level-based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency-dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate-dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger-tapping task significantly often reached >80% sensitivity and specificity in single regions-of-interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656-3668, 2016. © 2016 Wiley

  15. Modulation of cognitive control levels via manipulation of saccade trial-type probability assessed with event-related BOLD fMRI.

    PubMed

    Pierce, Jordan E; McDowell, Jennifer E

    2016-02-01

    Cognitive control supports flexible behavior adapted to meet current goals and can be modeled through investigation of saccade tasks with varying cognitive demands. Basic prosaccades (rapid glances toward a newly appearing stimulus) are supported by neural circuitry, including occipital and posterior parietal cortex, frontal and supplementary eye fields, and basal ganglia. These trials can be contrasted with complex antisaccades (glances toward the mirror image location of a stimulus), which are characterized by greater functional magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) signal in the aforementioned regions and recruitment of additional regions such as dorsolateral prefrontal cortex. The current study manipulated the cognitive demands of these saccade tasks by presenting three rapid event-related runs of mixed saccades with a varying probability of antisaccade vs. prosaccade trials (25, 50, or 75%). Behavioral results showed an effect of trial-type probability on reaction time, with slower responses in runs with a high antisaccade probability. Imaging results exhibited an effect of probability in bilateral pre- and postcentral gyrus, bilateral superior temporal gyrus, and medial frontal gyrus. Additionally, the interaction between saccade trial type and probability revealed a strong probability effect for prosaccade trials, showing a linear increase in activation parallel to antisaccade probability in bilateral temporal/occipital, posterior parietal, medial frontal, and lateral prefrontal cortex. In contrast, antisaccade trials showed elevated activation across all runs. Overall, this study demonstrated that improbable performance of a typically simple prosaccade task led to augmented BOLD signal to support changing cognitive control demands, resulting in activation levels similar to the more complex antisaccade task. PMID:26609113

  16. Concurrent fMRI and optical measures for the investigation of the hemodynamic response function.

    PubMed

    Kennerley, Aneurin J; Berwick, Jason; Martindale, John; Johnston, David; Papadakis, Nikos; Mayhew, John E

    2005-08-01

    Functional magnetic resonance imaging (fMRI) signal variations are based on a combination of changes in cerebral blood flow (CBF) and volume (CBV), and blood oxygenation. We investigated the relationship between these hemodynamic parameters in the rodent barrel cortex by performing fMRI concurrently with laser Doppler flowmetry (LDF) or optical imaging spectroscopy (OIS), following whisker stimulation and hypercapnic challenge. A difference between the positions of the maximum blood oxygenation level-dependent (BOLD) and CBV changes was observed in coronal fMRI maps, with the BOLD region being more superficial. A 6.5% baseline blood volume fraction in this superficial region dropped to 4% in deeper cortical layers (corresponding to total hemoglobin baseline volumes Hbt0 = 110 microM and 67 microM, respectively), as inferred from maps of deltaR2*. Baseline volume profiles were used to parameterize the Monte Carlo simulations (MCS) to interpret the 2D OIS. From this it was found that the optical blood volume measurements (i.e., changes in total hemoglobin) equated with CBV-MRI measurements when the MRI data were taken from superficial cortical layers. Optical measures of activation showed a good spatial overlap with fMRI measurements taken in the same plane (covering the right hemisphere surface). Changes in CBV and CBF followed the scaling relationship CBV = CBF(alpha), with mean alpha = 0.38 +/- 0.06. PMID:16032695

  17. Complex relationship between BOLD signal and synchronization/desynchronization of human brain MEG oscillations.

    PubMed

    Winterer, Georg; Carver, Frederick W; Musso, Francesco; Mattay, Venkata; Weinberger, Daniel R; Coppola, Richard

    2007-09-01

    Functional magnetic resonance imaging (fMRI) depends on the coupling of cerebral blood flow, energy demand, and neural activity. The precise nature of this interaction, however, is poorly understood. A positive correlation between BOLD-response and cortically generated local field potentials, which reflect the weighted average of synchronized dentrosomatic components of pyramidal synaptic signals, has been demonstrated. Likewise, positive BOLD-responses have been reported in conjunction with scalp-recorded synchronized electromagnetic activity by a number of groups. However, it is not yet clear how the opposite electromagnetic pattern, i.e. cortical desynchronization, is related to the BOLD signal. To address this question, we conducted a combined event-related fMRI and 275 sensor whole-head MEG study during identical visual two-choice reaction time task conditions in 10 human subjects. We found complex sequences of MEG-synchronization and desynchronization across a wide frequency range in the visual and motor area in close correspondence with "locales" of positive BOLD-responses. These results indicate that a correspondence of positive BOLD-responses is not exclusively found for cortical synchronization but also for desynchronization, suggesting that the relationship between BOLD signals and electromagnetic activity might be more complex than previously thought. PMID:17133396

  18. Variability of the Relationship between Electrophysiology and BOLD-fMRI across Cortical Regions in Humans

    PubMed Central

    Conner, Christopher R.; Ellmore, Timothy M.; Pieters, Thomas A.; DiSano, Michael A.; Tandon, Nitin

    2012-01-01

    The relationship between blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal and the underlying neural electrical activity in humans is a topic of intense interest to systems neuroscience. This relationship has generally been assumed to be invariant regardless of the brain region and the cognitive task being studied. We critically evaluated these assumptions by comparing the BOLD-fMRI response with local field potential (LFP) measurements during visually cued common noun and verb generation in 11 humans in whom 1210 subdural electrodes were implanted. As expected, power in the mid-gamma band (60 –120 Hz) correlated positively (r2 = 0.16, p < 10−16) and power in the beta band (13–30 Hz) correlated negatively (r2 = 0.09, p < 10−16) with the BOLD signal change. Beta and mid-gamma band activity independently explain different components of the observed BOLD signal. Importantly, we found that the location (i.e., lobe) of the recording site modulates the relationship between the electrocorticographic (ECoG) signal and the observed fMRI response (p < 10−16, F21,1830 = 52.7), while the type of language task does not. Across all brain regions, ECoG activity in the gamma and beta bands explains 22% of the fMRI response, but if the lobar location is considered, 28% of the variance can be explained. Further evaluation of this relationship at the level of individual gyri provides additional evidence of differences in the BOLD-LFP relationship by cortical locus. This spatial variability in the relationship between the fMRI signal and neural activity carries implications for modeling of the hemodynamic response function, an essential step for interregional fMRI comparisons. PMID:21900564

  19. Functional MRI during sleep: BOLD signal decreases and their electrophysiological correlates.

    PubMed

    Czisch, Michael; Wehrle, Renate; Kaufmann, Christian; Wetter, Thomas C; Holsboer, Florian; Pollmächer, Thomas; Auer, Dorothee P

    2004-07-01

    Prominent local decreases in blood oxygenation level (BOLD) can be observed by functional magnetic resonance imaging (fMRI) upon acoustic stimulation during sleep. The goal of this study was to further characterize this BOLD signal decrease with respect to corresponding neurophysiological phenomena using a simultaneous electroencephalography (EEG)/fMRI approach in sleeping human subjects. Healthy volunteers were subjected to acoustic stimulation during non-rapid eye movement (NREM) sleep. On the basis of statistical parametric maps, the correlations between the fMRI response (both amplitude and extent of the BOLD response) and the concomittant changes in the EEG (delta power and K-complexes) were calculated. Amplitude and extent of the stimulus-induced negative BOLD effect correlated positively with measures of EEG synchronization, namely an increase in the number of K-complexes and EEG delta power. Stimulus-induced BOLD decreases were most prominent during light (stage 2) NREM sleep and disappeared during slow wave sleep, indicating an influence of the baseline degree of hyperpolarization. Our observations provide first evidence that 'negative' BOLD signal changes during human sleep are associated with electrophysiological indicators of altered neuronal activity. Increased number of K-complexes and delta power reflecting hyperpolarization suggests true cortical deactivation upon stimulus presentation. This sleep stage-dependent deactivation might serve to protect the brain from arousing stimuli, particularly during the light phases of sleep shortly after sleep onset. PMID:15233766

  20. Using fMRI to Test Models of Complex Cognition

    ERIC Educational Resources Information Center

    Anderson, John R.; Carter, Cameron S.; Fincham, Jon M.; Qin, Yulin; Ravizza, Susan M.; Rosenberg-Lee, Miriam

    2008-01-01

    This article investigates the potential of fMRI to test assumptions about different components in models of complex cognitive tasks. If the components of a model can be associated with specific brain regions, one can make predictions for the temporal course of the BOLD response in these regions. An event-locked procedure is described for dealing…

  1. Patterns of Cortical Oscillations Organize Neural Activity into Whole-Brain Functional Networks Evident in the fMRI BOLD Signal

    PubMed Central

    Whitman, Jennifer C.; Ward, Lawrence M.; Woodward, Todd S.

    2013-01-01

    Recent findings from electrophysiology and multimodal neuroimaging have elucidated the relationship between patterns of cortical oscillations evident in EEG/MEG and the functional brain networks evident in the BOLD signal. Much of the existing literature emphasized how high-frequency cortical oscillations are thought to coordinate neural activity locally, while low-frequency oscillations play a role in coordinating activity between more distant brain regions. However, the assignment of different frequencies to different spatial scales is an oversimplification. A more informative approach is to explore the arrangements by which these low- and high-frequency oscillations work in concert, coordinating neural activity into whole-brain functional networks. When relating such networks to the BOLD signal, we must consider how the patterns of cortical oscillations change at the same speed as cognitive states, which often last less than a second. Consequently, the slower BOLD signal may often reflect the summed neural activity of several transient network configurations. This temporal mismatch can be circumvented if we use spatial maps to assess correspondence between oscillatory networks and BOLD networks. PMID:23504590

  2. Patterns of Cortical Oscillations Organize Neural Activity into Whole-Brain Functional Networks Evident in the fMRI BOLD Signal.

    PubMed

    Whitman, Jennifer C; Ward, Lawrence M; Woodward, Todd S

    2013-01-01

    Recent findings from electrophysiology and multimodal neuroimaging have elucidated the relationship between patterns of cortical oscillations evident in EEG/MEG and the functional brain networks evident in the BOLD signal. Much of the existing literature emphasized how high-frequency cortical oscillations are thought to coordinate neural activity locally, while low-frequency oscillations play a role in coordinating activity between more distant brain regions. However, the assignment of different frequencies to different spatial scales is an oversimplification. A more informative approach is to explore the arrangements by which these low- and high-frequency oscillations work in concert, coordinating neural activity into whole-brain functional networks. When relating such networks to the BOLD signal, we must consider how the patterns of cortical oscillations change at the same speed as cognitive states, which often last less than a second. Consequently, the slower BOLD signal may often reflect the summed neural activity of several transient network configurations. This temporal mismatch can be circumvented if we use spatial maps to assess correspondence between oscillatory networks and BOLD networks. PMID:23504590

  3. Quantitative comparisons on hand motor functional areas determined by resting state and task BOLD fMRI and anatomical MRI for pre-surgical planning of patients with brain tumors

    PubMed Central

    Hou, Bob L.; Bhatia, Sanjay; Carpenter, Jeffrey S.

    2016-01-01

    For pre-surgical planning we present quantitative comparison of the location of the hand motor functional area determined by right hand finger tapping BOLD fMRI, resting state BOLD fMRI, and anatomically using high resolution T1 weighted images. Data were obtained on 10 healthy subjects and 25 patients with left sided brain tumors. Our results show that there are important differences in the locations (i.e., > 20 mm) of the determined hand motor voxels by these three MR imaging methods. This can have significant effect on the pre-surgical planning of these patients depending on the modality used. In 13 of the 25 cases (i.e., 52%) the distances between the task-determined and the rs-fMRI determined hand areas were more than 20 mm; in 13 of 25 cases (i.e., 52%) the distances between the task-determined and anatomically determined hand areas were > 20 mm; and in 16 of 25 cases (i.e., 64%) the distances between the rs-fMRI determined and anatomically determined hand areas were more than 20 mm. In just three cases, the distances determined by all three modalities were within 20 mm of each other. The differences in the location or fingerprint of the hand motor areas, as determined by these three MR methods result from the different underlying mechanisms of these three modalities and possibly the effects of tumors on these modalities. PMID:27069871

  4. A hemodynamic model for layered BOLD signals.

    PubMed

    Heinzle, Jakob; Koopmans, Peter J; den Ouden, Hanneke E M; Raman, Sudhir; Stephan, Klaas Enno

    2016-01-15

    High-resolution blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at the sub-millimeter scale has become feasible with recent advances in MR technology. In principle, this would enable the study of layered cortical circuits, one of the fundaments of cortical computation. However, the spatial layout of cortical blood supply may become an important confound at such high resolution. In particular, venous blood draining back to the cortical surface perpendicularly to the layered structure is expected to influence the measured responses in different layers. Here, we present an extension of a hemodynamic model commonly used for analyzing fMRI data (in dynamic causal models or biophysical network models) that accounts for such blood draining effects by coupling local hemodynamics across layers. We illustrate the properties of the model and its inversion by a series of simulations and show that it successfully captures layered fMRI data obtained during a simple visual experiment. We conclude that for future studies of the dynamics of layered neuronal circuits with high-resolution fMRI, it will be pivotal to include effects of blood draining, particularly when trying to infer on the layer-specific connections in cortex--a theme of key relevance for brain disorders like schizophrenia and for theories of brain function such as predictive coding. PMID:26484827

  5. Effects of anesthesia on BOLD signal and neuronal activity in the somatosensory cortex.

    PubMed

    Aksenov, Daniil P; Li, Limin; Miller, Michael J; Iordanescu, Gheorghe; Wyrwicz, Alice M

    2015-11-01

    Most functional magnetic resonance imaging (fMRI) animal studies rely on anesthesia, which can induce a variety of drug-dependent physiological changes, including depression of neuronal activity and cerebral metabolism as well as direct effects on the vasculature. The goal of this study was to characterize the effects of anesthesia on the BOLD signal and neuronal activity. Simultaneous fMRI and electrophysiology were used to measure changes in single units (SU), multi-unit activity (MUA), local field potentials (LFP), and the blood oxygenation level-dependent (BOLD) response in the somatosensory cortex during whisker stimulation of rabbits before, during and after anesthesia with fentanyl or isoflurane. Our results indicate that anesthesia modulates the BOLD signal as well as both baseline and stimulus-evoked neuronal activity, and, most significantly, that the relationship between the BOLD and electrophysiological signals depends on the type of anesthetic. Specifically, the behavior of LFP observed under isoflurane did not parallel the behavior of BOLD, SU, or MUA. These findings suggest that the relationship between these signals may not be straightforward. BOLD may scale more closely with the best measure of the excitatory subcomponents of the underlying neuronal activity, which may vary according to experimental conditions that alter the excitatory/inhibitory balance in the cortex. PMID:26104288

  6. Steady-state BOLD Response to Higher-order Cognition Modulates Low-Frequency Neural Oscillations.

    PubMed

    Wang, Yi-Feng; Dai, Gang-Shu; Liu, Feng; Long, Zhi-Liang; Yan, Jin H; Chen, Hua-Fu

    2015-12-01

    Steady-state responses (SSRs) reflect the synchronous neural oscillations evoked by noninvasive and consistently repeated stimuli at the fundamental or harmonic frequencies. The steady-state evoked potentials (SSEPs; the representative form of the SSRs) have been widely used in the cognitive and clinical neurosciences and brain-computer interface research. However, the steady-state evoked potentials have limitations in examining high-frequency neural oscillations and basic cognition. In addition, synchronous neural oscillations in the low frequency range (<1 Hz) and in higher-order cognition have received a little attention. Therefore, we examined the SSRs in the low frequency range using a new index, the steady-state BOLD responses (SSBRs) evoked by semantic stimuli. Our results revealed that the significant SSBRs were induced at the fundamental frequency of stimuli and the first harmonic in task-related regions, suggesting the enhanced variability of neural oscillations entrained by exogenous stimuli. The SSBRs were independent of neurovascular coupling and characterized by sensorimotor bias, an indication of regional-dependent neuroplasticity. Furthermore, the amplitude of SSBRs may predict behavioral performance and show the psychophysiological relevance. Our findings provide valuable insights into the understanding of the SSRs evoked by higher-order cognition and how the SSRs modulate low-frequency neural oscillations. PMID:26284992

  7. fMRI responses to words repeated in a congruous semantic context are abnormal in mild Alzheimer’s disease

    PubMed Central

    Olichney, John M.; Taylor, Jason R.; Chan, Shiaohui; Yang, Jin-Chen; Stringfellow, Andrew; Hillert, Dieter G.; Simmons, Amanda L.; Salmon, David P.; Iragui-Madoz, Vicente; Kutas, Marta

    2010-01-01

    Background We adapted an event-related brain potential word repetition paradigm, sensitive to early Alzheimer’s disease (AD), for functional MRI (fMRI). We hypothesized that AD would be associated with reduced differential response to new/old congruous words. Methods Fifteen mild AD patients (mean age = 72.9) and 15 normal elderly underwent 1.5T fMRI during a semantic category decision task. Results We found robust between-groups differences in BOLD response to congruous words. In controls, the New > Old contrast demonstrated larger responses in much of the left-hemisphere (including putative P600 generators: parahippocampal, cingulate, fusiform, perirhinal, middle temporal (MTG) and inferior frontal gyri (IFG)); the Old > New contrast showed modest activation, mainly in right parietal and prefrontal cortex. By contrast, there were relatively few regions of significant New > Old responses in AD patients, mainly in the right-hemisphere, and their Old > New contrast did not demonstrate a right-hemisphere predominance. Across subjects, the spatial extent of New > Old responses in left medial temporal lobe (MTL) correlated with subsequent recall and recognition (r’s ≥ 0.60). In controls, the magnitude of New - Old response in left MTL, fusiform, IFG, MTG, superior temporal and cingulate gyrus correlated with subsequent cued recall and/or recognition (0.51 ≤ r’s ≤ 0.78). Conclusions A distributed network of mostly left-hemisphere structures, which are putative P600 generators, appears important for successful verbal encoding (with New > Old responses to congruous words in normal elderly). This network appears dysfunctional in mild AD patients, as reflected in decreased word repetition effects particularly in left association cortex, paralimbic and MTL structures. PMID:20433856

  8. Hippocampal BOLD response during category learning predicts subsequent performance on transfer generalization.

    PubMed

    Fera, Francesco; Passamonti, Luca; Herzallah, Mohammad M; Myers, Catherine E; Veltri, Pierangelo; Morganti, Giuseppina; Quattrone, Aldo; Gluck, Mark A

    2014-07-01

    To test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands. PMID:24142480

  9. BOLD Response Selective to Flow-Motion in Very Young Infants

    PubMed Central

    Tosetti, Michela; Morrone, Maria Concetta

    2015-01-01

    In adults, motion perception is mediated by an extensive network of occipital, parietal, temporal, and insular cortical areas. Little is known about the neural substrate of visual motion in infants, although behavioural studies suggest that motion perception is rudimentary at birth and matures steadily over the first few years. Here, by measuring Blood Oxygenated Level Dependent (BOLD) responses to flow versus random-motion stimuli, we demonstrate that the major cortical areas serving motion processing in adults are operative by 7 wk of age. Resting-state correlations demonstrate adult-like functional connectivity between the motion-selective associative areas, but not between primary cortex and temporo-occipital and posterior-insular cortices. Taken together, the results suggest that the development of motion perception may be limited by slow maturation of the subcortical input and of the cortico-cortical connections. In addition they support the existence of independent input to primary (V1) and temporo-occipital (V5/MT+) cortices very early in life. PMID:26418729

  10. Influences of High-Level Features, Gaze, and Scene Transitions on the Reliability of BOLD Responses to Natural Movie Stimuli.

    PubMed

    Lu, Kun-Han; Hung, Shao-Chin; Wen, Haiguang; Marussich, Lauren; Liu, Zhongming

    2016-01-01

    Complex, sustained, dynamic, and naturalistic visual stimulation can evoke distributed brain activities that are highly reproducible within and across individuals. However, the precise origins of such reproducible responses remain incompletely understood. Here, we employed concurrent functional magnetic resonance imaging (fMRI) and eye tracking to investigate the experimental and behavioral factors that influence fMRI activity and its intra- and inter-subject reproducibility during repeated movie stimuli. We found that widely distributed and highly reproducible fMRI responses were attributed primarily to the high-level natural content in the movie. In the absence of such natural content, low-level visual features alone in a spatiotemporally scrambled control stimulus evoked significantly reduced degree and extent of reproducible responses, which were mostly confined to the primary visual cortex (V1). We also found that the varying gaze behavior affected the cortical response at the peripheral part of V1 and in the oculomotor network, with minor effects on the response reproducibility over the extrastriate visual areas. Lastly, scene transitions in the movie stimulus due to film editing partly caused the reproducible fMRI responses at widespread cortical areas, especially along the ventral visual pathway. Therefore, the naturalistic nature of a movie stimulus is necessary for driving highly reliable visual activations. In a movie-stimulation paradigm, scene transitions and individuals' gaze behavior should be taken as potential confounding factors in order to properly interpret cortical activity that supports natural vision. PMID:27564573

  11. Influences of High-Level Features, Gaze, and Scene Transitions on the Reliability of BOLD Responses to Natural Movie Stimuli

    PubMed Central

    Lu, Kun-Han; Hung, Shao-Chin; Wen, Haiguang; Marussich, Lauren; Liu, Zhongming

    2016-01-01

    Complex, sustained, dynamic, and naturalistic visual stimulation can evoke distributed brain activities that are highly reproducible within and across individuals. However, the precise origins of such reproducible responses remain incompletely understood. Here, we employed concurrent functional magnetic resonance imaging (fMRI) and eye tracking to investigate the experimental and behavioral factors that influence fMRI activity and its intra- and inter-subject reproducibility during repeated movie stimuli. We found that widely distributed and highly reproducible fMRI responses were attributed primarily to the high-level natural content in the movie. In the absence of such natural content, low-level visual features alone in a spatiotemporally scrambled control stimulus evoked significantly reduced degree and extent of reproducible responses, which were mostly confined to the primary visual cortex (V1). We also found that the varying gaze behavior affected the cortical response at the peripheral part of V1 and in the oculomotor network, with minor effects on the response reproducibility over the extrastriate visual areas. Lastly, scene transitions in the movie stimulus due to film editing partly caused the reproducible fMRI responses at widespread cortical areas, especially along the ventral visual pathway. Therefore, the naturalistic nature of a movie stimulus is necessary for driving highly reliable visual activations. In a movie-stimulation paradigm, scene transitions and individuals’ gaze behavior should be taken as potential confounding factors in order to properly interpret cortical activity that supports natural vision. PMID:27564573

  12. Toddler Inhibitory Control, Bold Response to Novelty, and Positive Affect Predict Externalizing Symptoms in Kindergarten

    PubMed Central

    Buss, Kristin A.; Kiel, Elizabeth J.; Morales, Santiago; Robinson, Emily

    2013-01-01

    Poor inhibitory control and bold-approach have been found to predict the development of externalizing behavior problems in young children. Less research has examined how positive affect may influence the development of externalizing behavior in the context of low inhibitory control and high approach. We used a multimethod approach to examine how observed toddler inhibitory control, bold-approach, and positive affect predicted externalizing outcomes (observed, adult- and self-reported) in additive and interactive ways at the beginning of kindergarten. 24-month-olds (N = 110) participated in a laboratory visit and 84 were followed up in kindergarten for externalizing behaviors. Overall, children who were low in inhibitory control, high in bold-approach, and low in positive affect at 24-months of age were at greater risk for externalizing behaviors during kindergarten. PMID:25018589

  13. Concordance of Epileptic Networks Associated with Epileptic Spikes Measured by High-Density EEG and Fast fMRI

    PubMed Central

    Jäger, Vera; Dümpelmann, Matthias; LeVan, Pierre; Ramantani, Georgia; Mader, Irina; Schulze-Bonhage, Andreas; Jacobs, Julia

    2015-01-01

    Objective The present study aims to investigate whether a newly developed fast fMRI called MREG (magnetic resonance encephalography) measures metabolic changes related to interictal epileptic discharges (IED). For this purpose BOLD changes are correlated with the IED distribution and variability. Methods Patients with focal epilepsy underwent EEG-MREG using a 64 channel cap. IED voltage maps were generated using 32 and 64 channels and compared regarding their correspondence to the BOLD response. The extents of IEDs (defined as number of channels with >50% of maximum IED negativity) were correlated with the extents of positive and negative BOLD responses. Differences in inter-spike variability were investigated between interictal epileptic discharges (IED) sets with and without concordant positive or negative BOLD responses. Results 17 patients showed 32 separate IED types. In 50% of IED types the BOLD changes could be confirmed by another independent imaging method. The IED extent significantly correlated with the positive BOLD extent (p = 0.04). In 6 patients the 64-channel EEG voltage maps better reflected the positive or negative BOLD response than the 32-channel EEG; in all others no difference was seen. Inter-spike variability was significantly lower in IED sets with than without concordant positive or negative BOLD responses (with p = 0.04). Significance Higher density EEG and fast fMRI seem to improve the value of EEG-fMRI in epilepsy. The correlation of positive BOLD and IED extent could suggest that widespread BOLD responses reflect the IED network. Inter-spike variability influences the likelihood to find IED concordant positive or negative BOLD responses, which is why single IED analysis may be promising. PMID:26496480

  14. Discerning Professional Identity and Becoming Bold, Socially Responsible Teacher-Leaders

    ERIC Educational Resources Information Center

    Collay, Michelle

    2006-01-01

    This essay reviews the powerful influence of professional identity in shaping how school leaders perceive their work. I review factors that mold teacher professional identity, implications for educational leadership pedagogy, and supports and barriers for teacher leaders to consider in their quest to more fully enact bold, socially responsible…

  15. Co-localization between the BOLD response and epileptiform discharges recorded by simultaneous intracranial EEG-fMRI at 3 T

    PubMed Central

    Aghakhani, Yahya; Beers, Craig A.; Pittman, Daniel J.; Gaxiola-Valdez, Ismael; Goodyear, Bradley G.; Federico, Paolo

    2015-01-01

    Objectives Simultaneous scalp EEG-fMRI can identify hemodynamic changes associated with the generation of interictal epileptiform discharges (IEDs), and it has the potential of becoming a standard, non-invasive technique for pre-surgical assessment of patients with medically intractable epilepsy. This study was designed to assess the BOLD response to focal IEDs recorded via simultaneous intracranial EEG-functional MRI (iEEG-fMRI). Methods Twelve consecutive patients undergoing intracranial video EEG monitoring were recruited for iEEG-fMRI studies at 3 T. Depth, subdural strip, or grid electrodes were implanted according to our standard clinical protocol. Subjects underwent 10–60 min of continuous iEEG-fMRI scanning. IEDs were marked, and the most statistically significant clusters of BOLD signal were identified (Z-score 2.3, p value < 0.05). We assessed the concordance between the locations of the BOLD response and the IED. Concordance was defined as a distance <1.0 cm between the IED and BOLD response location. Negative BOLD responses were not studied in this project. Results Nine patients (7 females) with a mean age of 31 years (range 22–56) had 11 different types of IEDs during fMR scanning. The IEDs were divided based on the location of the active electrode contact into mesial temporal, lateral temporal, and extra-temporal. Seven (5 left) mesial temporal IED types were recorded in 5 patients (110–2092 IEDs per spike location). Six of these IEDs had concordant BOLD response in the ipsilateral mesial temporal structures, <1 cm from the most active contact. One of the two subjects with left lateral temporal IEDs had BOLD responses concordant with the location of the most active contact, as well other ipsilateral and contralateral sites. Notably, the remaining two subjects with extratemporal discharges showed no BOLD signal near the active electrode contact. Conclusions iEEG-fMRI is a feasible and low-risk method for assessment of hemodynamic changes

  16. Fitting Computational Models to fMRI Data

    PubMed Central

    Ashby, F. Gregory; Waldschmidt, Jennifer G.

    2008-01-01

    Many computational models in psychology predict how neural activation in specific brain regions should change during certain cognitive tasks. The emergence of fMRI as a research tool provides an ideal vehicle to test these predictions. Before such tests are possible, however, significant methodological problems must be solved. These problems include transforming the neural activations predicted by the model into predicted BOLD responses, identifying the voxels within each region of interest against which to test the model, and comparing the observed and predicted BOLD responses in each of these regions. Methods are described for solving each of these problems. PMID:18697666

  17. Negative BOLD response and serotonin concentration within rostral subgenual portion of the anterior cingulate cortex for long-allele carriers during perceptual processing of emotional tasks

    NASA Astrophysics Data System (ADS)

    Hadi, Shamil M.; Siadat, Mohamad R.; Babajani-Feremi, Abbas

    2012-03-01

    We investigated the effect of synaptic serotonin concentration on hemodynamic responses. The stimuli paradigm involved the presentation of fearful and threatening facial expressions to a set of 24 subjects who were either5HTTLPR long- or short-allele carriers (12 of each type in each group). The BOLD signals of the rACC from subjects of each group were averaged to increase the signal-to-noise ratio. We used a Bayesian approach to estimate the parameters of the underlying hemodynamic model. Our results, during this perceptual processing of emotional task, showed a negative BOLD signal in the rACC in the subjects with long-alleles. In contrast, the subjects with short-alleles showed positive BOLD signals in the rACC. These results suggest that high synaptic serotonin concentration in the rACC inhibits neuronal activity in a fashion similar to GABA, and a consequent negative BOLD signal ensues.

  18. Opposing relationships of BMI with BOLD and dopamine D2/3 receptor binding potential in the dorsal striatum

    PubMed Central

    Cosgrove, Kelly P.; Veldhuizen, Maria G.; Sandiego, Christine M.; Morris, Evan D.; Small, Dana M.

    2015-01-01

    Findings from clinical and preclinical studies converge to suggest that increased adiposity and/or exposure to a high fat diet are associated with alterations in dorsal striatal (DS) circuitry. In humans there is a reliable inverse relationship between body mass index (BMI) and response to palatable food consumption in the dorsal striatum (DS). Positron emission tomography (PET) studies also suggest altered DS dopamine type 2/3 receptor (D2R/D3R) availability in obesity; however, the direction of the association is unclear. It is also not clear whether dopamine receptor levels contribute to the lower blood oxygen level dependent (BOLD) response because PET studies have targeted the morbidly obese and, functional magnetic resonance imaging (fMRI) studies rarely include individuals with BMIs in this range. Therefore we examined whether the fMRI BOLD response in the DS to milkshake is associated with D2R/D3R availability measured with [11C]PHNO and PET in individuals with BMI ranging from healthy weight to moderately obese. Twenty-nine subjects participated in the fMRI study, twelve in the [11C]PHNO PET study, eight of whom also completed the fMRI study. As predicted there was a significant negative association between DS BOLD response to milkshake and BMI. In contrast, BMI was positively associated with D2R/D3R availability. Dorsal striatal BOLD response was unrelated to D2R/D3R availability. Considered in the context of the larger literature our results suggest the existence of a non-linear relationship between D2R/D3R availability and BMI. Additionally, the altered BOLD responses to palatable food consumption observed in obesity are not clearly related to D2R/D3R receptor availability. PMID:25664726

  19. Sex-based fMRI differences in obese humans in response to high vs. low energy food cues.

    PubMed

    Geliebter, Allan; Pantazatos, Spiro P; McOuatt, Haley; Puma, Lauren; Gibson, Charlisa D; Atalayer, Deniz

    2013-04-15

    Gender specific effects on human eating have been previously reported. Here we investigated sex-based differences in neural activation via whole-brain blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in response to high energy-dense (high-ED) vs. low-ED visual and auditory food cues in obese men vs. women in both fed and fasted states. The results show that in response to high vs. low ED foods in the fed state, obese men (vs. women) had greater activation in brain areas associated with motor control regions (e.g. supplementary motor areas) whereas women showed greater activation in cognitive-related regions. In the fasted state, obese men had greater activation in a visual-attention region whereas obese women showed greater activation in affective and reward related processing regions (e.g. caudate). Overall the results support our a priori hypothesis that obese women (vs. men) have greater neural activation in regions associated with cognition and emotion-related brain regions. These findings may improve our understanding of sex specific differences among obese individuals in eating behavior. PMID:23261871

  20. Sex-Based fMRI Differences in Obese Humans in Response to High vs. Low Energy Food Cues

    PubMed Central

    Geliebter, Allan; Pantazatos, Spiro P.; McOuatt, Haley; Puma, Lauren; Gibson, Charlisa D.; Atalayer, Deniz

    2013-01-01

    Gender specific effects on human eating have been previously reported. Here we investigated sex-based differences in neural activation via whole-brain blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in response to high energy-dense (high-ED) vs. low-ED visual and auditory food cues in obese men vs. women in both fed and fasted states. The results show that in response to high vs. low ED foods in the fed state, obese men (vs. women), had greater activation in brain areas associated with motor control regions (e.g. supplementary motor areas) whereas women showed greater activation in cognitive-related regions. When fasted, obese men had greater activation in a visual-attention region whereas obese women showed greater activation in affective and reward related processing regions (e.g. caudate). Overall the results support our a priori hypothesis that obese women (vs. men) have greater neural activation in regions associated with cognition and emotion-related brain regions. These findings may improve our understanding of sex specific differences among obese individuals in eating behavior. PMID:23261871

  1. Blood pressure changes induced by arterial blood withdrawal influence bold signal in anesthesized rats at 7 Tesla: implications for pharmacologic mri.

    PubMed

    Kalisch, R; Elbel, G K; Gössl, C; Czisch, M; Auer, D P

    2001-10-01

    Functional magnetic resonance imaging (fMRI) using the blood oxygenation level-dependent (BOLD) contrast is now increasingly applied for measuring drug effects on brain activity. A possible confound in pharmacologic fMRI (phMRI) is that the BOLD signal may be sensitive to systemic cardiovascular or respiratory parameters, which can themselves be modulated by a drug. To assess whether abrupt changes in arterial blood pressure (BP) as may be observed in phMRI experiments influence the BOLD signal, a hemorrhage model was studied in anesthesized rats at 7 T using spin-echo EPI. BP and BOLD signal time courses were found to be significantly correlated (P < 0.01). This effect was detected under the three different anesthetic regimens employed (isoflurane, halothane, and propofol). The regional pattern of BP-BOLD correlations was heterogeneous and may reflect vascular density. In physiological terms, a BOLD decrease during a decrease in BP may result from an increase in mostly venous cerebral blood volume (CBV) as an autoregulatory response to maintain cerebral blood flow (CBF) during decreased perfusion pressure. The observed influence of BP on BOLD may complicate qualitative and quantitative description of drug effects. PMID:11554808

  2. Area-Specific Information Processing in Prefrontal Cortex during a Probabilistic Inference Task: A Multivariate fMRI BOLD Time Series Analysis

    PubMed Central

    Demanuele, Charmaine; Kirsch, Peter; Esslinger, Christine; Zink, Mathias; Meyer-Lindenberg, Andreas; Durstewitz, Daniel

    2015-01-01

    Introduction Discriminating spatiotemporal stages of information processing involved in complex cognitive processes remains a challenge for neuroscience. This is especially so in prefrontal cortex whose subregions, such as the dorsolateral prefrontal (DLPFC), anterior cingulate (ACC) and orbitofrontal (OFC) cortices are known to have differentiable roles in cognition. Yet it is much less clear how these subregions contribute to different cognitive processes required by a given task. To investigate this, we use functional MRI data recorded from a group of healthy adults during a “Jumping to Conclusions” probabilistic reasoning task. Methods We used a novel approach combining multivariate test statistics with bootstrap-based procedures to discriminate between different task stages reflected in the fMRI blood oxygenation level dependent signal pattern and to unravel differences in task-related information encoded by these regions. Furthermore, we implemented a new feature extraction algorithm that selects voxels from any set of brain regions that are jointly maximally predictive about specific task stages. Results Using both the multivariate statistics approach and the algorithm that searches for maximally informative voxels we show that during the Jumping to Conclusions task, the DLPFC and ACC contribute more to the decision making phase comprising the accumulation of evidence and probabilistic reasoning, while the OFC is more involved in choice evaluation and uncertainty feedback. Moreover, we show that in presumably non-task-related regions (temporal cortices) all information there was about task processing could be extracted from just one voxel (indicating the unspecific nature of that information), while for prefrontal areas a wider multivariate pattern of activity was maximally informative. Conclusions/Significance We present a new approach to reveal the different roles of brain regions during the processing of one task from multivariate activity patterns

  3. Women with borderline personality disorder do not show altered BOLD responses during response inhibition.

    PubMed

    van Eijk, Julia; Sebastian, Alexandra; Krause-Utz, Annegret; Cackowski, Sylvia; Demirakca, Traute; Biedermann, Sarah V; Lieb, Klaus; Bohus, Martin; Schmahl, Christian; Ende, Gabriele; Tüscher, Oliver

    2015-12-30

    Impulsivity is central to borderline personality disorder (BPD). Response inhibition, addressing the ability to suppress or stop actions, is one aspect of behavioral impulse control which is frequently used to assess impulsivity. BPD patients display deficits in response inhibition under stress condition or negative emotions. We assessed whether response inhibition and its neural underpinnings are impaired in BPD when tested in an emotionally neutral setting and when co-morbid attention-deficit/hyperactivity disorder (ADHD) is excluded. To this end, we studied response inhibition in unmedicated BPD patients and healthy controls (HC) in two independent samples using functional magnetic resonance imaging during Simon-, Go/nogo-, and Stopsignal tasks. BPD patients and HC did not differ significantly in their performance in the Go/nogo and the Stopsignal tasks. Response interference in the Simon task was increased in BPD patients in one sample, but this could not be replicated in the second sample. In both samples, no significant differences in brain activation patterns during any of the tasks were present while the neural impulse control network was robustly activated during the inhibition tasks in both groups. Our results provide evidence that under emotionally neutral conditions response inhibition is not impaired in patients with BPD without co-occurring ADHD. PMID:26483213

  4. Optogenetic drive of neocortical pyramidal neurons generates fMRI signals that are correlated with spiking activity

    PubMed Central

    Kahn, I.; Knoblich, U.; Desai, M.; Bernstein, J.; Graybiel, A.M.; Boyden, E.S.; Buckner, R.L.; Moore, C.I.

    2013-01-01

    Local fluctuations in the blood oxygenation level-dependent (BOLD) signal serve as the basis of functional magnetic resonance imaging (fMRI). Understanding the correlation between distinct aspects of neural activity and the BOLD response is fundamental to the interpretation of this widely used mapping signal. Analysis of this question requires the ability to precisely manipulate the activity of defined neurons. To achieve such control, we combined optogenetic drive of neocortical neurons with high-resolution (9.4 T) rodent fMRI and detailed analysis of neurophysiological data. Light-driven activation of pyramidal neurons resulted in a positive BOLD response at the stimulated site. To help differentiate the neurophysiological correlate(s) of the BOLD response, we employed light trains of the same average frequency, but with periodic and Poisson distributed pulse times. These different types of pulse trains generated dissociable patterns of single-unit, multi-unit and local field potential (LFP) activity, and of BOLD signals. The BOLD activity exhibited the strongest correlation to spiking activity with increasing rates of stimulation, and, to a first approximation, was linear with pulse delivery rate, while LFP activity showed a weaker correlation. These data provide an example of a strong correlation between spike rate and the BOLD response. PMID:23523914

  5. Another kind of 'BOLD Response': answering multiple-choice questions via online decoded single-trial brain signals.

    PubMed

    Sorger, Bettina; Dahmen, Brigitte; Reithler, Joel; Gosseries, Olivia; Maudoux, Audrey; Laureys, Steven; Goebel, Rainer

    2009-01-01

    The term 'locked-in'syndrome (LIS) describes a medical condition in which persons concerned are severely paralyzed and at the same time fully conscious and awake. The resulting anarthria makes it impossible for these patients to naturally communicate, which results in diagnostic as well as serious practical and ethical problems. Therefore, developing alternative, muscle-independent communication means is of prime importance. Such communication means can be realized via brain-computer interfaces (BCIs) circumventing the muscular system by using brain signals associated with preserved cognitive, sensory, and emotional brain functions. Primarily, BCIs based on electrophysiological measures have been developed and applied with remarkable success. Recently, also blood flow-based neuroimaging methods, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), have been explored in this context. After reviewing recent literature on the development of especially hemodynamically based BCIs, we introduce a highly reliable and easy-to-apply communication procedure that enables untrained participants to motor-independently and relatively effortlessly answer multiple-choice questions based on intentionally generated single-trial fMRI signals that can be decoded online. Our technique takes advantage of the participants' capability to voluntarily influence certain spatio-temporal aspects of the blood oxygenation level-dependent (BOLD) signal: source location (by using different mental tasks), signal onset and offset. We show that healthy participants are capable of hemodynamically encoding at least four distinct information units on a single-trial level without extensive pretraining and with little effort. Moreover, real-time data analysis based on simple multi-filter correlations allows for automated answer decoding with a high accuracy (94.9%) demonstrating the robustness of the presented method. Following our 'proof of concept', the

  6. Modeling of the hemodynamic responses in block design fMRI studies

    PubMed Central

    Shan, Zuyao Y; Wright, Margaret J; Thompson, Paul M; McMahon, Katie L; Blokland, Gabriella G A M; de Zubicaray, Greig I; Martin, Nicholas G; Vinkhuyzen, Anna A E; Reutens, David C

    2014-01-01

    The hemodynamic response function (HRF) describes the local response of brain vasculature to functional activation. Accurate HRF modeling enables the investigation of cerebral blood flow regulation and improves our ability to interpret fMRI results. Block designs have been used extensively as fMRI paradigms because detection power is maximized; however, block designs are not optimal for HRF parameter estimation. Here we assessed the utility of block design fMRI data for HRF modeling. The trueness (relative deviation), precision (relative uncertainty), and identifiability (goodness-of-fit) of different HRF models were examined and test–retest reproducibility of HRF parameter estimates was assessed using computer simulations and fMRI data from 82 healthy young adult twins acquired on two occasions 3 to 4 months apart. The effects of systematically varying attributes of the block design paradigm were also examined. In our comparison of five HRF models, the model comprising the sum of two gamma functions with six free parameters had greatest parameter accuracy and identifiability. Hemodynamic response function height and time to peak were highly reproducible between studies and width was moderately reproducible but the reproducibility of onset time was low. This study established the feasibility and test–retest reliability of estimating HRF parameters using data from block design fMRI studies. PMID:24252847

  7. Opposing relationships of BMI with BOLD and dopamine D2/3 receptor binding potential in the dorsal striatum.

    PubMed

    Cosgrove, Kelly P; Veldhuizen, Maria G; Sandiego, Christine M; Morris, Evan D; Small, Dana M

    2015-04-01

    Findings from clinical and preclinical studies converge to suggest that increased adiposity and/or exposure to a high fat diet are associated with alterations in dorsal striatal (DS) circuitry. In humans there is a reliable inverse relationship between body mass index (BMI) and response to palatable food consumption in the dorsal striatum (DS). Positron emission tomography (PET) studies also suggest altered DS dopamine type 2/3 receptor (D2R/D3R) availability in obesity; however, the direction of the association is unclear. It is also not clear whether dopamine receptor levels contribute to the lower blood oxygen level dependent (BOLD) response because PET studies have targeted the morbidly obese and, functional magnetic resonance imaging (fMRI) studies rarely include individuals with BMIs in this range. Therefore we examined whether the fMRI BOLD response in the DS to milkshake is associated with D2R/D3R availability measured with [(11) C]PHNO and PET in individuals with BMI ranging from healthy weight to moderately obese. Twenty-nine subjects participated in the fMRI study, 12 in the [(11) C]PHNO PET study, 8 of whom also completed the fMRI study. As predicted there was a significant negative association between DS BOLD response to milkshake and BMI. In contrast, BMI was positively associated with D2R/D3R availability. Dorsal striatal BOLD response was unrelated to D2R/D3R availability. Considered in the context of the larger literature our results suggest the existence of a non-linear relationship between D2R/D3R availability and BMI. Additionally, the altered BOLD responses to palatable food consumption observed in obesity are not clearly related to D2R/D3R receptor availability. Using [(11) C]PHNO and PET brain imaging techniques we show that body mass index was positively associated with D2R/D3R availability in the dorsal striatum, but that functional MR BOLD response was unrelated to D2R/D3R availability. These results suggest the existence of a nonlinear

  8. Hypnotic depth and response to suggestion under standardized conditions and during FMRI scanning.

    PubMed

    Oakley, David A; Deeley, Quinton; Halligan, Peter W

    2007-01-01

    Hypnosis is a potentially valuable cognitive tool for neuroimaging studies. However, understandable concern that Magnetic Resonance Imaging (MRI) in particular may adversely affect hypnotic procedures remains. Measurements of hypnotic depth and responsiveness to suggestions were taken using a standardized procedure that met all the requirements for functional MRI (fMRI). Testing outside the scanning environment showed reliable and stable changes in subjective hypnotic depth, with no carryover once the hypnosis had been terminated. Within-subject comparisons showed that the magnitude and pattern of these changes and the degree of responsiveness to hypnotic suggestion were not discernibly affected by the fMRI environment. It is concluded that hypnosis can be employed as a discrete and reliable cognitive tool within fMRI neuroimaging settings. PMID:17135062

  9. Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience.

    PubMed

    Hall, Catherine N; Howarth, Clare; Kurth-Nelson, Zebulun; Mishra, Anusha

    2016-10-01

    Cognitive neuroscience depends on the use of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to probe brain function. Although commonly used as a surrogate measure of neuronal activity, BOLD signals actually reflect changes in brain blood oxygenation. Understanding the mechanisms linking neuronal activity to vascular perfusion is, therefore, critical in interpreting BOLD. Advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD. Meanwhile, within cognitive neuroscience, the increasing use of high magnetic field strengths and the development of model-based tasks and analyses have broadened the capability of BOLD signals to inform us about the underlying neuronal activity, but these methods are less well understood by cellular neuroscientists. In 2016, a Royal Society Theo Murphy Meeting brought scientists from the two communities together to discuss these issues. Here, we consolidate the main conclusions arising from that meeting. We discuss areas of consensus about what BOLD fMRI can tell us about underlying neuronal activity, and how advanced modelling techniques have improved our ability to use and interpret BOLD. We also highlight areas of controversy in understanding BOLD and suggest research directions required to resolve these issues.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574302

  10. Comparison between end-tidal CO2 and respiration volume per time for detecting BOLD signal fluctuations during paced hyperventilation

    PubMed Central

    Vogt, Keith M.; Ibinson, James W.; Schmalbrock, Petra; Small, Robert H.

    2011-01-01

    Respiratory motion and capnometry monitoring were performed during blood oxygen level dependent (BOLD) functional magnetic resonance imaging (FMRI) of the brain while a series of paced hyperventilation tasks were performed that caused significant hypocapnia. Respiration volume per time (RVT) and end-tidal carbon dioxide (ETCO2) were determined and compared for their ability to explain BOLD contrast changes in the data. A 35% decrease in ETCO2 was observed along with corresponding changes in RVT. A best-fit ETCO2 response function, with an average initial peak delay time of 12 s, was empirically determined. ETCO2 data convolved with this response function was more strongly and prevalently correlated to BOLD signal changes than RVT data convolved with the corresponding respiration response function. The results suggest that ETCO2 better models BOLD signal fluctuations in FMRI experiments with significant transient hypocapnia. This is due to hysteresis in the ETCO2 response when moving from hypocapnia to normocapnia, compared to moving from normocapnia to hypocapnia. PMID:21908130

  11. Serotonergic modulation of neuronal responses to behavioural inhibition and reinforcing stimuli: an fMRI study in healthy volunteers.

    PubMed

    Völlm, Birgit; Richardson, Paul; McKie, Shane; Elliott, Rebecca; Deakin, J F W; Anderson, Ian M

    2006-01-01

    Serotonin (5-HT) has been implicated in the aetiology of a number of psychiatric conditions, including depression, anxiety and antisocial personality disorder. The development of these disorders may arise from alterations in underlying motivational and cognitive processes such as emotional recognition, reinforcement processing and central inhibitory control. This study aimed to localize where in the brain 5-HT modulates neuropsychological processes relevant to putative 5-HT disorders, using functional magnetic resonance imaging. We examined the effect of the antidepressant mirtazapine on brain activations associated with behavioural inhibition and reinforcement processing in healthy subjects. Forty-five men were randomly allocated to receiving mirtazapine or placebo in a double-blind fashion. A Go/No-Go, Reward/No-Reward and Loss/No-loss task were performed during functional magnetic resonance imaging using a 1.5 Tesla Philips Gyroscan scanner. Blood oxygenation level dependent (BOLD) responses were analysed using SPM2. Task activations were largely consistent with previous findings. Mirtazapine modulated brain activations in the Go/No-Go and Reward/No-Reward task. During behavioural inhibition, enhanced activations were observed in the right orbitofrontal cortex (BA47). Increased activations in bilateral parietal cortex were found during the Reward task while no significant interaction was observed in the Loss task. Our results support the suggestion of an important role of serotonin in modulating basic processes involved in psychiatric disorders. Combining drug challenge with fMRI (pharmacoMRI; pMRI) is a promising tool for investigating these processes in healthy as well as patient groups. PMID:16420462

  12. Altered BOLD Response during Inhibitory and Error Processing in Adolescents with Anorexia Nervosa

    PubMed Central

    Wierenga, Christina; Bischoff-Grethe, Amanda; Melrose, A. James; Grenesko-Stevens, Emily; Irvine, Zoë; Wagner, Angela; Simmons, Alan; Matthews, Scott; Yau, Wai-Ying Wendy; Fennema-Notestine, Christine; Kaye, Walter H.

    2014-01-01

    Background Individuals with anorexia nervosa (AN) are often cognitively rigid and behaviorally over-controlled. We previously showed that adult females recovered from AN relative to healthy comparison females had less prefrontal activation during an inhibition task, which suggested a functional brain correlate of altered inhibitory processing in individuals recovered from AN. However, the degree to which these functional brain alterations are related to disease state and whether error processing is altered in AN individuals is unknown. Methodology/Principal Findings In the current study, ill adolescent AN females (n = 11) and matched healthy comparison adolescents (CA) with no history of an eating disorder (n = 12) performed a validated stop signal task (SST) during functional magnetic resonance imaging (fMRI) to explore differences in error and inhibitory processing. The groups did not differ on sociodemographic variables or on SST performance. During inhibitory processing, a significant group x difficulty (hard, easy) interaction was detected in the right dorsal anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left posterior cingulate cortex (PCC), which was characterized by less activation in AN compared to CA participants during hard trials. During error processing, a significant group x accuracy (successful inhibit, failed inhibit) interaction in bilateral MFG and right PCC was observed, which was characterized by less activation in AN compared to CA participants during error (i.e., failed inhibit) trials. Conclusion/Significance Consistent with our prior findings in recovered AN, ill AN adolescents, relative to CA, showed less inhibition-related activation within the dorsal ACC, MFG and PCC as inhibitory demand increased. In addition, ill AN adolescents, relative to CA, also showed reduced activation to errors in the bilateral MFG and left PCC. These findings suggest that altered prefrontal and cingulate activation during

  13. The way to her heart? Response to romantic cues is dependent on hunger state and dieting history: An fMRI pilot study.

    PubMed

    Ely, Alice V; Childress, Anna Rose; Jagannathan, Kanchana; Lowe, Michael R

    2015-12-01

    Normal weight historical dieters (HDs) are prone to future weight gain, and show higher levels of brain activation in reward-related regions after having eaten than nondieters (NDs) in response to food stimuli (Ely, Childress, Jagannathan, & Lowe, 2014), a similar pattern to that seen in obesity. We hypothesized that HDs are differentially sensitive after eating to rewards in general, and thus extended prior findings by comparing the same groups' brain activation when viewing romantic pictures compared to neutral stimuli while being scanned in a blood oxygenation level-dependent (BOLD) fMRI paradigm in a fasted and fed state. Results show that 1) in fed relative to fasted conditions, both HDs and NDs were more responsive in areas related to reward and 2) in HDs, greater fed versus fasted activation extended to areas linked to perception and goal-directed behavior. HDs relative to NDs were more responsive to romantic cues in the superior frontal gyrus when fasted and the middle temporal gyrus when fed. This pattern of response is similar to HDs' activation when viewing highly palatable food cues, and is consistent with research showing overlapping brain-based responses to sex, drugs and food. PMID:26145276

  14. Replicability and Heterogeneity of Awake Unrestrained Canine fMRI Responses

    PubMed Central

    Berns, Gregory S.; Brooks, Andrew; Spivak, Mark

    2013-01-01

    Previously, we demonstrated the possibility of fMRI in two awake and unrestrained dogs. Here, we determined the replicability and heterogeneity of these results in an additional 11 dogs for a total of 13 subjects. Based on an anatomically placed region-of-interest, we compared the caudate response to a hand signal indicating the imminent availability of a food reward to a hand signal indicating no reward. 8 of 13 dogs had a positive differential caudate response to the signal indicating reward. The mean differential caudate response was 0.09%, which was similar to a comparable human study. These results show that canine fMRI is reliable and can be done with minimal stress to the dogs. PMID:24324719

  15. Investigations on spinal cord fMRI of cats under ketamine.

    PubMed

    Cohen-Adad, J; Hoge, R D; Leblond, H; Xie, G; Beaudoin, G; Song, A W; Krueger, G; Doyon, J; Benali, H; Rossignol, S

    2009-01-15

    Functional magnetic resonance imaging (fMRI) of the spinal cord has been the subject of intense research for the last ten years. An important motivation for this technique is its ability to detect non-invasively neuronal activity in the spinal cord related to sensorimotor functions in various conditions, such as after spinal cord lesions. Although promising results of spinal cord fMRI have arisen from previous studies, the poor reproducibility of BOLD activations and their characteristics remain a major drawback. In the present study we investigated the reproducibility of BOLD fMRI in the spinal cord of cats (N=9) by repeating the same stimulation protocol over a long period (approximately 2 h). Cats were anaesthetized with ketamine, and spinal cord activity was induced by electrical stimulation of cutaneous nerves of the hind limbs. As a result, task-related signals were detected in most cats with relatively good spatial specificity. However, BOLD response significantly varied within and between cats. This variability was notably attributed to the moderate intensity of the stimulus producing a low amplitude haemodynamic response, variation in end-tidal CO(2) during the session, low signal-to-noise ratio (SNR) in spinal fMRI time series and animal-specific vascular anatomy. Original contributions of the present study are: (i) first spinal fMRI experiment in ketamine-anaesthetized animals, (ii) extensive study of intra- and inter-subject variability of activation, (iii) characterisation of static and temporal SNR in the spinal cord and (iv) investigation on the impact of CO(2) end-tidal level on the amplitude of BOLD response. PMID:18938251

  16. Left fusiform BOLD responses are inversely related to word-likeness in a one-back task

    PubMed Central

    Wang, Xiaojuan; Yang, Jianfeng; Shu, Hua; Zevin, Jason D.

    2011-01-01

    Although its precise functional contribution to reading remains unclear, there is broad consensus that activity in the left mid-fusiform gyrus is highly sensitive to written words and word-like stimuli. In the current study, we take advantage of a particularity of the Chinese writing system in order to manipulate word-likeness parametrically, from real characters, to pseudo-characters that vary in whether they contain phonological and semantic cues, to artificial stimuli with varying surface similarity to real characters. In a one-back task, BOLD activity in the left mid-fusiform was inversely related to word-likeness, such that the least activity was observed in response to real characters, and the greatest to artificial stimuli that violate the orthotactic constraints of the writing system. One possible explanation for this surprising result is that the short-term memory demands of the one-back task put more pressure on the visual system when other sources of information cannot be used to aid in detecting repeated stimuli. For real characters and, to a lesser extent for pseudo-characters, information about meaning and pronunciation can contribute to performance, whereas artificial stimuli are entirely dependent on visual information. Consistent with this view, functional connectivity analyses revealed a strong positive relationship between left mid-fusiform and other visual areas, whereas areas typically involved in phonological and semantic processing for text were negatively correlated with this region. PMID:21216293

  17. Developmental changes of BOLD signal correlations with global human EEG power and synchronization during working memory.

    PubMed

    Michels, Lars; Lüchinger, Rafael; Koenig, Thomas; Martin, Ernst; Brandeis, Daniel

    2012-01-01

    In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding working memory (WM) tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent) signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-)dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was--in contrast to EEG power--positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and synchronization and that

  18. Sexually dimorphic functional connectivity in response to high vs. low energy-dense food cues in obese humans: An fMRI study

    PubMed Central

    Atalayer, Deniz; Pantazatos, Spiro P.; Gibson, Charlisa D.; McOuatt, Haley; Puma, Lauren; Astbury, Nerys M.; Geliebter, Allan

    2014-01-01

    Sexually-dimorphic behavioral and biological aspects of human eating have been described. Using psychophysiological interactions (PPI) analysis, we investigated sex-based differences in functional connectivity with a key emotion-processing region (amygdala, AMG) and a key reward-processing area (ventral striatum, VS) in response to high vs. low energy-dense (ED) food images using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in obese persons in fasted and fed states. When fed, in response to high vs. low-ED food cues, obese men (vs. women) had greater functional connectivity with AMG in right subgenual anterior cingulate, whereas obese women had greater functional connectivity with AMG in left angular gyrus and right primary motor areas. In addition, when fed, AMG functional connectivity with pre/post-central gyrus was more associated with BMI in women (vs. men). When fasted, obese men (vs. women) had greater functional connectivity with AMG in bilateral supplementary frontal and primary motor areas, left precuneus, and right cuneus, whereas obese women had greater functional connectivity with AMG in left inferior frontal gyrus, right thalamus, and dorsomedial prefrontal cortex. When fed, greater functional connectivity with VS was observed in men in bilateral supplementary and primary motor areas, left postcentral gyrus, and left precuneus. These sex-based differences in functional connectivity in response to visual food cues may help partly explain differential eating behavior, pathology prevalence, and outcomes in men and women. PMID:24862077

  19. Improving fMRI sensitivity by normalization of basal physiologic state

    PubMed Central

    Lu, Hanzhang; Yezhuvath, Uma S.; Xiao, Guanghua

    2009-01-01

    The power of fMRI in assessing neural activities is hampered by inter-subject variations in basal physiologic parameters, which may not be related to neural activation but has a modulatory effect on fMRI signals. Therefore, normalization of fMRI signals with these parameters is useful in reducing variations and improving sensitivity of this important technique. Recently, we have shown that basal venous oxygenation is a significant modulator of fMRI signals and individuals with higher venous oxygenation tend to have lower fMRI signals. In this study, we aim to test the utility of venous oxygenation normalization in distinguishing subject groups. A “model” condition was used in which two visual stimuli with different flashing frequencies were used to stimulate two subject groups, respectively, thereby simulating the situation of control and patient groups. It was found that visual-evoked BOLD signal is significantly correlated with baseline venous T2 (p=0.0003) and inclusion of physiologic modulator in the regression analysis can substantially reduce p values of group-level statistical tests. When applied to voxel-wise analysis, the normalization process can allow the detection of more significant voxels. The utility of other basal parameters, including blood pressure, heart rate, arterial oxygenation and end-tidal CO2, in BOLD normalization was also assessed and it was found that the improvement was less significant. Time-to-peak of the BOLD responses was also studied and it was found that subjects with higher basal venous oxygenation tend to have slower BOLD responses. PMID:19585589

  20. Regional differences in neurovascular coupling in rat brain as determined by fMRI and electrophysiology.

    PubMed

    Sloan, H L; Austin, V C; Blamire, A M; Schnupp, J W H; Lowe, A S; Allers, K A; Matthews, P M; Sibson, N R

    2010-11-01

    Increases in neuronal activity induce local increases in cerebral perfusion. However, our understanding of the processes underlying this neurovascular coupling remains incomplete and, particularly, how these vary across the brain. Recent work supports an important role for astrocytes in neurovascular coupling, in large part via activation of their metabotropic glutamate receptors (mGluR). Here, using a combination of functional magnetic resonance imaging (fMRI) and electrophysiology we demonstrate regional heterogeneity in the mechanisms underlying neurovascular coupling. Direct electrical stimulation of the rat hindpaw sensorimotor cortex induces blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) fMRI responses in several anatomically distinct cortical and subcortical structures. Following intraperitoneal administration of the type 5 mGluR antagonist, MPEP, both BOLD and CBV responses to cortical stimulation were significantly reduced, whilst the local field potential (LFP) responses remained largely constant. Spatially, the degree of reduction in fMRI responses varied between cortical and subcortical regions (primary cortex approximately 18% vs. striatum approximately 66%), and also between primary and secondary cortical areas ( approximately 18% vs. approximately 55%). Similarly, greater decreases in response amplitude were seen in the contralateral secondary cortex ( approximately 91%) and ipsilateral striatum (approximately 70%), compared to the primary cortex (approximately 44%). Following MPEP, a negative component of the BOLD and CBV responses became more apparent, suggesting that different mechanisms mediate vasodilatory and vasoconstrictory responses. Interestingly, under baseline conditions the quantitative relationship between fMRI and LFP responses in cortical and subcortical regions was markedly different. Our data indicate that coupling between neuronal and fMRI responses is neither empirically nor mechanistically consistent

  1. Neurophysiological investigation of spontaneous correlated and anticorrelated fluctuations of the BOLD signal

    PubMed Central

    Keller, Corey J.; Bickel, Stephan; Honey, Christopher J.; Groppe, David M.; Entz, Laszlo; Craddock, R. Cameron; Lado, Fred A.; Kelly, Clare; Milham, Michael; Mehta, Ashesh D.

    2013-01-01

    Analyses of intrinsic fMRI BOLD signal fluctuations reliably reveal correlated and anticorrelated functional networks in the brain. Since the BOLD signal is an indirect measure of neuronal activity, and anticorrelations can be introduced by preprocessing steps such as global signal regression (GSR), the neurophysiological significance of correlated and anticorrelated BOLD fluctuations is a source of debate. Here, we address this question by examining the correspondence between the spatial organization of correlated BOLD fluctuations and correlated fluctuations in electrophysiological high gamma power (HGP) signals recorded directly from the cortical surface of 5 patients. We demonstrate that both positive and negative BOLD correlations have neurophysiological correlates reflected in fluctuations of spontaneous neuronal activity. Although applying GSR to BOLD signals results in some BOLD anticorrelations that are not apparent in the ECoG data, it enhances the neuronal-hemodynamic correspondence overall. Together, these findings provide support for the neurophysiological fidelity of BOLD correlations and anticorrelations. PMID:23575832

  2. Brain region and activity-dependent properties of M for calibrated fMRI.

    PubMed

    Shu, Christina Y; Herman, Peter; Coman, Daniel; Sanganahalli, Basavaraju G; Wang, Helen; Juchem, Christoph; Rothman, Douglas L; de Graaf, Robin A; Hyder, Fahmeed

    2016-01-15

    Calibrated fMRI extracts changes in oxidative energy demanded by neural activity based on hemodynamic and metabolic dependencies of the blood oxygenation level-dependent (BOLD) response. This procedure requires the parameter M, which is determined from the dynamic range of the BOLD signal between deoxyhemoglobin (paramagnetic) and oxyhemoglobin (diamagnetic). Since it is unclear if the range of M-values in human calibrated fMRI is due to regional/state differences, we conducted a 9.4T study to measure M-values across brain regions in deep (α-chloralose) and light (medetomidine) anesthetized rats, as verified by electrophysiology. Because BOLD signal is captured differentially by gradient-echo (R2*) and spin-echo (R2) relaxation rates, we measured M-values by the product of the fMRI echo time and R2' (i.e., the reversible magnetic susceptibility component), which is given by the absolute difference between R2* and R2. While R2' mapping was shown to be dependent on the k-space sampling method used, at nominal spatial resolutions achieved at high magnetic field of 9.4T the M-values were quite homogenous across cortical gray matter. However cortical M-values varied in relation to neural activity between brain states. The findings from this study could improve precision of future calibrated fMRI studies by focusing on the global uniformity of M-values in gray matter across different resting activity levels. PMID:26529646

  3. Load Modulation of BOLD Response and Connectivity Predicts Working Memory Performance in Younger and Older Adults

    ERIC Educational Resources Information Center

    Nagel, Irene E.; Preuschhof, Claudia; Li, Shu-Chen; Nyberg, Lars; Backman, Lars; Lindenberger, Ulman; Heekeren, Hauke R.

    2011-01-01

    Individual differences in working memory (WM) performance have rarely been related to individual differences in the functional responsivity of the WM brain network. By neglecting person-to-person variation, comparisons of network activity between younger and older adults using functional imaging techniques often confound differences in activity…

  4. The importance of the negative blood-oxygenation-level-dependent (BOLD) response in the somatosensory cortex.

    PubMed

    Klingner, Carsten M; Brodoehl, Stefan; Witte, Otto W

    2015-01-01

    In recent years, multiple studies have shown task-induced negative blood-oxygenation-level-dependent responses (NBRs) in multiple brain regions in humans and animals. Converging evidence suggests that task-induced NBRs can be interpreted in terms of decreased neuronal activity. However, the vascular and metabolic dynamics and functional importance of the NBR are highly debated. Here, we review studies investigating the origin and functional importance of the NBR, with special attention to the somatosensory cortex. PMID:26057216

  5. Shape-independent object category responses revealed by MEG and fMRI decoding.

    PubMed

    Kaiser, Daniel; Azzalini, Damiano C; Peelen, Marius V

    2016-04-01

    Neuroimaging research has identified category-specific neural response patterns to a limited set of object categories. For example, faces, bodies, and scenes evoke activity patterns in visual cortex that are uniquely traceable in space and time. It is currently debated whether these apparently categorical responses truly reflect selectivity for categories or instead reflect selectivity for category-associated shape properties. In the present study, we used a cross-classification approach on functional MRI (fMRI) and magnetoencephalographic (MEG) data to reveal both category-independent shape responses and shape-independent category responses. Participants viewed human body parts (hands and torsos) and pieces of clothing that were closely shape-matched to the body parts (gloves and shirts). Category-independent shape responses were revealed by training multivariate classifiers on discriminating shape within one category (e.g., hands versus torsos) and testing these classifiers on discriminating shape within the other category (e.g., gloves versus shirts). This analysis revealed significant decoding in large clusters in visual cortex (fMRI) starting from 90 ms after stimulus onset (MEG). Shape-independent category responses were revealed by training classifiers on discriminating object category (bodies and clothes) within one shape (e.g., hands versus gloves) and testing these classifiers on discriminating category within the other shape (e.g., torsos versus shirts). This analysis revealed significant decoding in bilateral occipitotemporal cortex (fMRI) and from 130 to 200 ms after stimulus onset (MEG). Together, these findings provide evidence for concurrent shape and category selectivity in high-level visual cortex, including category-level responses that are not fully explicable by two-dimensional shape properties. PMID:26740535

  6. Coupling Mechanism and Significance of the BOLD Signal: A Status Report

    PubMed Central

    Hillman, Elizabeth M.C.

    2014-01-01

    Functional magnetic resonance imaging (fMRI) provides a unique view of the working human mind. The blood-oxygen-level-dependent (BOLD) signal, detected in fMRI, reflects changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation, which are coupled to underlying neuronal activity by a process termed neurovascular coupling. Over the past 10 years, a range of cellular mechanisms, including astrocytes, pericytes, and interneurons, have been proposed to play a role in functional neurovascular coupling. However, the field remains conflicted over the relative importance of each process, while key spatiotemporal features of BOLD response remain unexplained. Here, we review current candidate neurovascular coupling mechanisms and propose that previously overlooked involvement of the vascular endothelium may provide a more complete picture of how blood flow is controlled in the brain. We also explore the possibility and consequences of conditions in which neurovascular coupling may be altered, including during postnatal development, pathological states, and aging, noting relevance to both stimulus-evoked and resting-state fMRI studies. PMID:25032494

  7. Differences in BOLD responses to intragastrically infused glucose and saccharin in rats.

    PubMed

    Tsurugizawa, Tomokazu; Uneyama, Hisayuki

    2014-10-01

    The postingestive effect is different between caloric and noncaloric sweeteners. The gut administration of glucose induces a preference for flavored water which is paired with the intragastric infusion of glucose. However, a comparison of the brain response to the gut glucose and saccharin stimuli still remains to be demonstrated. Here, using functional magnetic resonance imaging, we investigated the blood oxygenation level-dependent signal response to gut glucose and saccharin in the brain of conscious rats. Glucose induced a positive signal increase in the amygdala and nucleus accumben, both of which receive dopaminergic input from the ventral tegmental area. In contrast, saccharin administration did not activate these areas. Both glucose and saccharin increased the blood oxygenation level-dependent signal intensity in the insular cortex and the nucleus of the solitary tract. These results show that there were significant differences between postingestive glucose and saccharin-induced increases in the blood oxygenation level-dependent signal in rats. Together with previous findings, these results suggest distinct activation patterns in the brain for both glucose and saccharin, which is partially due to different changes of internal signals, including the blood glucose and insulin levels. PMID:25179231

  8. Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers.

    PubMed

    Versace, Francesco; Engelmann, Jeffrey M; Jackson, Edward F; Costa, Vincent D; Robinson, Jason D; Lam, Cho Y; Minnix, Jennifer A; Brown, Victoria L; Wetter, David W; Cinciripini, Paul M

    2011-12-01

    Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing: (i) would be more active during exposure to cigarette-related than neutral pictures; and (ii) would be less active to pleasant compared with cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole-brain blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole-brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli. PMID:22097928

  9. Oxytocin modulates fMRI responses to facial expression in macaques

    PubMed Central

    Liu, Ning; Hadj-Bouziane, Fadila; Jones, Katherine B.; Turchi, Janita N.; Averbeck, Bruno B.; Ungerleider, Leslie G.

    2015-01-01

    Increasing evidence has shown that oxytocin (OT), a mammalian hormone, modifies the way social stimuli are perceived and the way they affect behavior. Thus, OT may serve as a treatment for psychiatric disorders, many of which are characterized by dysfunctional social behavior. To explore the neural mechanisms mediating the effects of OT in macaque monkeys, we investigated whether OT would modulate functional magnetic resonance imaging (fMRI) responses in face-responsive regions (faces vs. blank screen) evoked by the perception of various facial expressions (neutral, fearful, aggressive, and appeasing). In the placebo condition, we found significantly increased activation for emotional (mainly fearful and appeasing) faces compared with neutral faces across the face-responsive regions. OT selectively, and differentially, altered fMRI responses to emotional expressions, significantly reducing responses to both fearful and aggressive faces in face-responsive regions while leaving responses to appeasing as well as neutral faces unchanged. We also found that OT administration selectively reduced functional coupling between the amygdala and areas in the occipital and inferior temporal cortex during the viewing of fearful and aggressive faces, but not during the viewing of neutral or appeasing faces. Taken together, our results indicate homologies between monkeys and humans in the neural circuits mediating the effects of OT. Thus, the monkey may be an ideal animal model to explore the development of OT-based pharmacological strategies for treating patients with dysfunctional social behavior. PMID:26015576

  10. Oxytocin modulates fMRI responses to facial expression in macaques.

    PubMed

    Liu, Ning; Hadj-Bouziane, Fadila; Jones, Katherine B; Turchi, Janita N; Averbeck, Bruno B; Ungerleider, Leslie G

    2015-06-16

    Increasing evidence has shown that oxytocin (OT), a mammalian hormone, modifies the way social stimuli are perceived and the way they affect behavior. Thus, OT may serve as a treatment for psychiatric disorders, many of which are characterized by dysfunctional social behavior. To explore the neural mechanisms mediating the effects of OT in macaque monkeys, we investigated whether OT would modulate functional magnetic resonance imaging (fMRI) responses in face-responsive regions (faces vs. blank screen) evoked by the perception of various facial expressions (neutral, fearful, aggressive, and appeasing). In the placebo condition, we found significantly increased activation for emotional (mainly fearful and appeasing) faces compared with neutral faces across the face-responsive regions. OT selectively, and differentially, altered fMRI responses to emotional expressions, significantly reducing responses to both fearful and aggressive faces in face-responsive regions while leaving responses to appeasing as well as neutral faces unchanged. We also found that OT administration selectively reduced functional coupling between the amygdala and areas in the occipital and inferior temporal cortex during the viewing of fearful and aggressive faces, but not during the viewing of neutral or appeasing faces. Taken together, our results indicate homologies between monkeys and humans in the neural circuits mediating the effects of OT. Thus, the monkey may be an ideal animal model to explore the development of OT-based pharmacological strategies for treating patients with dysfunctional social behavior. PMID:26015576

  11. An application of item response theory to fMRI data: Prospects and pitfalls

    PubMed Central

    Thomas, Michael L.; Brown, Gregory G.; Thompson, Wesley K.; Voyvodic, James; Greve, Douglas N.; Turner, Jessica A.; Mathalon, Daniel H.; Ford, Judith; Wible, Cynthia G.; Potkin, Steven G.

    2013-01-01

    When using functional brain imaging to study neuropsychiatric patients an important challenge is determining whether the imaging task assesses individual differences with equal precision in healthy control and impaired patient groups. Classical test theory (CTT) requires separate reliability studies of patients and controls to determine equivalent measurement precision with additional studies to determine measurement precision for different levels of disease severity. Unlike CTT, item response theory (IRT) provides estimates of measurement error for different levels of ability, without the need for separate studies, and can determine if different tests are equivalently difficult when investigating differential deficits between groups. To determine the potential value of IRT in functional brain imaging, IRT was applied to behavioral data obtained during a multi-center functional MRI (fMRI) study of working memory (WM). Average item difficulty was approximately one standard deviation below the ability scale mean, supporting the task’s sensitivity to individual differences within the ability range of patients with WM impairment, but not within the range of most controls. The correlation of IRT estimated ability with fMRI activation during the task recognition period supported the linkage of the latent IRT scale to brain activation data. IRT can meaningfully contribute to the design of fMRI tasks. PMID:23642468

  12. A signal subspace approach for modeling the hemodynamic response function in fMRI.

    PubMed

    Hossein-Zadeh, Gholam-Ali; Ardekani, Babak A; Soltanian-Zadeh, Hamid

    2003-10-01

    Many fMRI analysis methods use a model for the hemodynamic response function (HRF). Common models of the HRF, such as the Gaussian or Gamma functions, have parameters that are usually selected a priori by the data analyst. A new method is presented that characterizes the HRF over a wide range of parameters via three basis signals derived using principal component analysis (PCA). Covering the HRF variability, these three basis signals together with the stimulation pattern define signal subspaces which are applicable to both linear and nonlinear modeling and identification of the HRF and for various activation detection strategies. Analysis of simulated fMRI data using the proposed signal subspace showed increased detection sensitivity compared to the case of using a previously proposed trigonometric subspace. The methodology was also applied to activation detection in both event-related and block design experimental fMRI data using both linear and nonlinear modeling of the HRF. The activated regions were consistent with previous studies, indicating the ability of the proposed approach in detecting brain activation without a priori assumptions about the shape parameters of the HRF. The utility of the proposed basis functions in identifying the HRF is demonstrated by estimating the HRF in different activated regions. PMID:14599533

  13. Intentional social distance regulation alters affective responses towards victims of violence: an FMRI study.

    PubMed

    Leiberg, Susanne; Eippert, Falk; Veit, Ralf; Anders, Silke

    2012-10-01

    We used functional magnetic resonance imaging (fMRI) to investigate brain processes underlying control of emotional responses towards a person in distress by cognitive social distance modulation. fMRI and peripheral physiological responses (startle response and electrodermal activity) were recorded from 24 women while they watched victim-offender scenes and modulated their social distance to the victim by cognitive reappraisal. We found that emotional responses, including startle eyeblink and amygdala responses, can effectively be modulated by social distance modulation. Furthermore, our data provide evidence that activity in the dorsomedial prefrontal cortex (dmPFC) and the anterior paracingulate cortex (aPCC), two brain regions that have previously been associated with brain processes related to distant and close others, is differentially modulated by intentional social distance modulation: activity in the dmPFC increased with increasing disengagement from the victim and activity in the aPCC increased with increasing engagement with the victim. We suggest that these two regions play opposing roles in cognitive modulation of social distance and affective responses towards persons in distress that enable the adaptive and flexible social behavior observed in humans. PMID:21998031

  14. Vascular autorescaling of fMRI (VasA fMRI) improves sensitivity of population studies: A pilot study

    PubMed Central

    Kazan, Samira M.; Mohammadi, Siawoosh; Callaghan, Martina F.; Flandin, Guillaume; Huber, Laurentius; Leech, Robert; Kennerley, Aneurin; Windischberger, Christian; Weiskopf, Nikolaus

    2016-01-01

    The blood oxygenation level-dependent (BOLD) signal is widely used for functional magnetic resonance imaging (fMRI) of brain function in health and disease. The statistical power of fMRI group studies is significantly hampered by high inter-subject variance due to differences in baseline vascular physiology. Several methods have been proposed to account for physiological vascularization differences between subjects and hence improve the sensitivity in group studies. However, these methods require the acquisition of additional reference scans (such as a full resting-state fMRI session or ASL-based calibrated BOLD). We present a vascular autorescaling (VasA) method, which does not require any additional reference scans. VasA is based on the observation that slow oscillations (< 0.1 Hz) in arterial blood CO2 levels occur naturally due to changes in respiration patterns. These oscillations yield fMRI signal changes whose amplitudes reflect the blood oxygenation levels and underlying local vascularization and vascular responsivity. VasA estimates proxies of the amplitude of these CO2-driven oscillations directly from the residuals of task-related fMRI data without the need for reference scans. The estimates are used to scale the amplitude of task-related fMRI responses, to account for vascular differences. The VasA maps compared well to cerebrovascular reactivity (CVR) maps and cerebral blood volume maps based on vascular space occupancy (VASO) measurements in four volunteers, speaking to the physiological vascular basis of VasA. VasA was validated in a wide variety of tasks in 138 volunteers. VasA increased t-scores by up to 30% in specific brain areas such as the visual cortex. The number of activated voxels was increased by up to 200% in brain areas such as the orbital frontal cortex while still controlling the nominal false-positive rate. VasA fMRI outperformed previously proposed rescaling approaches based on resting-state fMRI data and can be readily applied to

  15. Vascular autorescaling of fMRI (VasA fMRI) improves sensitivity of population studies: A pilot study.

    PubMed

    Kazan, Samira M; Mohammadi, Siawoosh; Callaghan, Martina F; Flandin, Guillaume; Huber, Laurentius; Leech, Robert; Kennerley, Aneurin; Windischberger, Christian; Weiskopf, Nikolaus

    2016-01-01

    The blood oxygenation level-dependent (BOLD) signal is widely used for functional magnetic resonance imaging (fMRI) of brain function in health and disease. The statistical power of fMRI group studies is significantly hampered by high inter-subject variance due to differences in baseline vascular physiology. Several methods have been proposed to account for physiological vascularization differences between subjects and hence improve the sensitivity in group studies. However, these methods require the acquisition of additional reference scans (such as a full resting-state fMRI session or ASL-based calibrated BOLD). We present a vascular autorescaling (VasA) method, which does not require any additional reference scans. VasA is based on the observation that slow oscillations (<0.1Hz) in arterial blood CO2 levels occur naturally due to changes in respiration patterns. These oscillations yield fMRI signal changes whose amplitudes reflect the blood oxygenation levels and underlying local vascularization and vascular responsivity. VasA estimates proxies of the amplitude of these CO2-driven oscillations directly from the residuals of task-related fMRI data without the need for reference scans. The estimates are used to scale the amplitude of task-related fMRI responses, to account for vascular differences. The VasA maps compared well to cerebrovascular reactivity (CVR) maps and cerebral blood volume maps based on vascular space occupancy (VASO) measurements in four volunteers, speaking to the physiological vascular basis of VasA. VasA was validated in a wide variety of tasks in 138 volunteers. VasA increased t-scores by up to 30% in specific brain areas such as the visual cortex. The number of activated voxels was increased by up to 200% in brain areas such as the orbital frontal cortex while still controlling the nominal false-positive rate. VasA fMRI outperformed previously proposed rescaling approaches based on resting-state fMRI data and can be readily applied to any

  16. Transferring cognitive tasks between brain imaging modalities: implications for task design and results interpretation in FMRI studies.

    PubMed

    Warbrick, Tracy; Reske, Martina; Shah, N Jon

    2014-01-01

    As cognitive neuroscience methods develop, established experimental tasks are used with emerging brain imaging modalities. Here transferring a paradigm (the visual oddball task) with a long history of behavioral and electroencephalography (EEG) experiments to a functional magnetic resonance imaging (fMRI) experiment is considered. The aims of this paper are to briefly describe fMRI and when its use is appropriate in cognitive neuroscience; illustrate how task design can influence the results of an fMRI experiment, particularly when that task is borrowed from another imaging modality; explain the practical aspects of performing an fMRI experiment. It is demonstrated that manipulating the task demands in the visual oddball task results in different patterns of blood oxygen level dependent (BOLD) activation. The nature of the fMRI BOLD measure means that many brain regions are found to be active in a particular task. Determining the functions of these areas of activation is very much dependent on task design and analysis. The complex nature of many fMRI tasks means that the details of the task and its requirements need careful consideration when interpreting data. The data show that this is particularly important in those tasks relying on a motor response as well as cognitive elements and that covert and overt responses should be considered where possible. Furthermore, the data show that transferring an EEG paradigm to an fMRI experiment needs careful consideration and it cannot be assumed that the same paradigm will work equally well across imaging modalities. It is therefore recommended that the design of an fMRI study is pilot tested behaviorally to establish the effects of interest and then pilot tested in the fMRI environment to ensure appropriate design, implementation and analysis for the effects of interest. PMID:25285453

  17. Retrieving the Hemodynamic Response Function in resting state fMRI: Methodology and application.

    PubMed

    Wu, Guo-Rong; Deshpande, Gopikhrishna; Laureys, Steven; Marinazzo, Daniele

    2015-08-01

    In this paper we present a procedure to retrieve the hemodynamic response function (HRF) from resting state functional magnetic resonance imaging (fMRI) data. The fundamentals of the procedures are further validated by considering simultaneous electroencephalographic (EEG) recordings. The typical HRF shape at rest for a group of healthy subject is presented. Then we present the modifications to the shape of the HRF at rest following two physiological modulations: eyes open versus eyes closed and propofol-induced modulations of consciousness. PMID:26737671

  18. Selective responses to specular surfaces in the macaque visual cortex revealed by fMRI.

    PubMed

    Okazawa, Gouki; Goda, Naokazu; Komatsu, Hidehiko

    2012-11-15

    The surface properties of objects, such as gloss, transparency and texture, provide important information about the material characteristics of objects in our visual environment. However, because there have been few reports on the neuronal responses to surface properties in primates, we still lack information about where and how surface properties are processed in the primate visual cortex. In this study, we used functional magnetic resonance imaging (fMRI) to examine the cortical responses to specular surfaces in the macaque visual cortex. Using computer graphics, we generated images of specular and matte objects and prepared scrambled images by locally randomizing the luminance phases of the images with specular and matte objects. In experiment 1, we contrasted the responses to specular images with those to matte and scrambled images. Activation was observed along the ventral visual pathway, including V1, V2, V3, V4 and the posterior inferior temporal (IT) cortex. In experiment 2, we manipulated the contrasts of images and found that the activation observed in these regions could not be explained solely by the global or local contrasts. These results suggest that image features related to specular surface are processed along the ventral visual pathway from V1 to specific regions in the IT cortex. This is consistent with previous human fMRI experiments that showed surface properties are processed in the ventral visual pathway. PMID:22885246

  19. Working memory fMRI activation in cocaine-dependent subjects: association with treatment response.

    PubMed

    Moeller, F Gerard; Steinberg, Joel L; Schmitz, Joy M; Ma, Liangsuo; Liu, Shijing; Kjome, Kimberly L; Rathnayaka, Nuvan; Kramer, Larry A; Narayana, Ponnada A

    2010-03-30

    Functional magnetic resonance imaging (fMRI) studies of early abstinence cocaine users offer information about the state of the brain when most cocaine users seek treatment. This study examined the relationship between pretreatment brain function and subsequent treatment response in 19 treatment-seeking early abstinence cocaine-dependent (CD) subjects. These subjects and 14 non-drug-using control subjects underwent fMRI while performing a working memory task with three levels of difficulty. CD subjects were then randomized to treatment studies. Results showed CD subjects had significantly lower (random effects, corrected for multiple comparisons) brain activation in caudate, putamen, cingulate gyrus, middle and superior frontal gyri, inferior frontal gyrus pars triangularis and pars opercularis, precentral gyrus, and thalamus compared with non-drug-using controls. Within CD subjects, thalamic activation significantly correlated with treatment response. This study shows CD subjects in early abstinence have alterations of brain function in frontal, striatal, and thalamic brain regions known to be part of a circuit associated with motor control, reward, and cognition. Subjects with pretreatment thalamic deactivation showed the poorest treatment response, possibly related to thalamic involvement in mesocortical and mesolimbic dopamine projections. PMID:20153142

  20. Improving the spatial accuracy in functional magnetic resonance imaging (fMRI) based on the blood oxygenation level dependent (BOLD) effect: benefits from parallel imaging and a 32-channel head array coil at 1.5 Tesla.

    PubMed

    Fellner, C; Doenitz, C; Finkenzeller, T; Jung, E M; Rennert, J; Schlaier, J

    2009-01-01

    Geometric distortions and low spatial resolution are current limitations in functional magnetic resonance imaging (fMRI). The aim of this study was to evaluate if application of parallel imaging or significant reduction of voxel size in combination with a new 32-channel head array coil can reduce those drawbacks at 1.5 T for a simple hand motor task. Therefore, maximum t-values (tmax) in different regions of activation, time-dependent signal-to-noise ratios (SNR(t)) as well as distortions within the precentral gyrus were evaluated. Comparing fMRI with and without parallel imaging in 17 healthy subjects revealed significantly reduced geometric distortions in anterior-posterior direction. Using parallel imaging, tmax only showed a mild reduction (7-11%) although SNR(t) was significantly diminished (25%). In 7 healthy subjects high-resolution (2 x 2 x 2 mm3) fMRI was compared with standard fMRI (3 x 3 x 3 mm3) in a 32-channel coil and with high-resolution fMRI in a 12-channel coil. The new coil yielded a clear improvement for tmax (21-32%) and SNR(t) (51%) in comparison with the 12-channel coil. Geometric distortions were smaller due to the smaller voxel size. Therefore, the reduction in tmax (8-16%) and SNR(t) (52%) in the high-resolution experiment seems to be tolerable with this coil. In conclusion, parallel imaging is an alternative to reduce geometric distortions in fMRI at 1.5 T. Using a 32-channel coil, reduction of the voxel size might be the preferable way to improve spatial accuracy. PMID:19713602

  1. Altered Dynamics of the fMRI Response to Faces in Individuals with Autism

    ERIC Educational Resources Information Center

    Kleinhans, Natalia M.; Richards, Todd; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

    2016-01-01

    Abnormal fMRI habituation in autism spectrum disorders (ASDs) has been proposed as a critical component in social impairment. This study investigated habituation to fearful faces and houses in ASD and whether fMRI measures of brain activity discriminate between ASD and typically developing (TD) controls. Two identical fMRI runs presenting masked…

  2. Relationship between BOLD amplitude and pattern classification of orientation-selective activity in the human visual cortex.

    PubMed

    Tong, Frank; Harrison, Stephenie A; Dewey, John A; Kamitani, Yukiyasu

    2012-11-15

    Orientation-selective responses can be decoded from fMRI activity patterns in the human visual cortex, using multivariate pattern analysis (MVPA). To what extent do these feature-selective activity patterns depend on the strength and quality of the sensory input, and might the reliability of these activity patterns be predicted by the gross amplitude of the stimulus-driven BOLD response? Observers viewed oriented gratings that varied in luminance contrast (4, 20 or 100%) or spatial frequency (0.25, 1.0 or 4.0 cpd). As predicted, activity patterns in early visual areas led to better discrimination of orientations presented at high than low contrast, with greater effects of contrast found in area V1 than in V3. A second experiment revealed generally better decoding of orientations at low or moderate as compared to high spatial frequencies. Interestingly however, V1 exhibited a relative advantage at discriminating high spatial frequency orientations, consistent with the finer scale of representation in the primary visual cortex. In both experiments, the reliability of these orientation-selective activity patterns was well predicted by the average BOLD amplitude in each region of interest, as indicated by correlation analyses, as well as decoding applied to a simple model of voxel responses to simulated orientation columns. Moreover, individual differences in decoding accuracy could be predicted by the signal-to-noise ratio of an individual's BOLD response. Our results indicate that decoding accuracy can be well predicted by incorporating the amplitude of the BOLD response into simple simulation models of cortical selectivity; such models could prove useful in future applications of fMRI pattern classification. PMID:22917989

  3. Response inhibition among early adolescents prenatally exposed to tobacco: An fMRI study

    PubMed Central

    Bennett, David S.; Mohamed, Feroze B.; Carmody, Dennis P.; Bendersky, Margaret; Patel, Sunil; Khorrami, Maryam; Faro, Scott H.; Lewis, Michael

    2009-01-01

    Children prenatally exposed to tobacco have been found to exhibit increased rates of behavior problems related to response inhibition deficits. The present study compared the brain function of tobacco-exposed (n = 7) and unexposed (n = 11) 12-year-olds during a Go/No-Go response inhibition task using an event-related functional MRI (fMRI) design. Prenatal alcohol exposure, neonatal medical problems, environmental risk, IQ, current environmental smoke exposure, and handedness were statistically controlled. Tobacco-exposed children showed greater activation in a relatively large and diverse set of regions, including left frontal, right occipital, and bilateral temporal, and parietal regions. In contrast, unexposed but not exposed children showed activation in the cerebellum, which prior research has indicated is important for attention and motor preparation. The diversity of regions showing greater activation among tobacco-exposed children suggests that their brain function is characterized by an inefficient recruitment of regions required for response inhibition. PMID:19351556

  4. Identifying Core Affect in Individuals from fMRI Responses to Dynamic Naturalistic Audiovisual Stimuli.

    PubMed

    Kim, Jongwan; Wang, Jing; Wedell, Douglas H; Shinkareva, Svetlana V

    2016-01-01

    Recent research has demonstrated that affective states elicited by viewing pictures varying in valence and arousal are identifiable from whole brain activation patterns observed with functional magnetic resonance imaging (fMRI). Identification of affective states from more naturalistic stimuli has clinical relevance, but the feasibility of identifying these states on an individual trial basis from fMRI data elicited by dynamic multimodal stimuli is unclear. The goal of this study was to determine whether affective states can be similarly identified when participants view dynamic naturalistic audiovisual stimuli. Eleven participants viewed 5s audiovisual clips in a passive viewing task in the scanner. Valence and arousal for individual trials were identified both within and across participants based on distributed patterns of activity in areas selectively responsive to audiovisual naturalistic stimuli while controlling for lower level features of the stimuli. In addition, the brain regions identified by searchlight analyses to represent valence and arousal were consistent with previously identified regions associated with emotion processing. These findings extend previous results on the distributed representation of affect to multimodal dynamic stimuli. PMID:27598534

  5. The Influence of Recency of Use on fMRI Response During Spatial Working Memory in Adolescent Marijuana Users

    PubMed Central

    Schweinsburg, Alecia D.; Schweinsburg, Brian C.; Medina, Krista Lisdahl; McQueeny, Tim; Brown, Sandra A.; Tapert, Susan F.

    2010-01-01

    Some neurocognitive recovery occurs within a month of abstinence from heavy marijuana use, yet functional magnetic resonance imaging (fMRI) has revealed altered activation among recent and abstinent adult users. Here, we compared fMRI response during a spatial working memory (SWM) task between adolescent marijuana users with brief and sustained durations of abstinence. Participants were 13 recent users (2 – 7 days abstinent), 13 abstinent users (27 – 60 days abstinent), and 18 non-using controls, all ages 15 – 18. Groups were similar on demographics, had no psychiatric or medical disorders, and user groups were similar on substance histories. Teens performed a 2-back SWM task during fMRI. Groups performed similarly on the task, but recent users showed greater fMRI response in medial and left superior prefrontal cortices, as well as bilateral insula. Abstinent users had increased response in the right precentral gyrus (clusters ≥1328 μl, p<.05). This cross-sectional study did not examine changes in brain response among the same participants over time. Yet results suggests that adolescents who recently used marijuana show increased brain activity in regions associated with working memory updating and inhibition, compared to users with weeks to months of abstinence. This study preliminarily suggests that (1) recent marijuana use may disrupt neural connections associated with SWM and result in compensatory brain response, and (2) sustained abstinence from marijuana may be associated with improvements in SWM response among adolescents. PMID:21053763

  6. Brain activations in response to vibrotactile tooth stimulation: a psychophysical and fMRI study.

    PubMed

    Trulsson, Mats; Francis, Susan T; Bowtell, Richard; McGlone, Francis

    2010-10-01

    The tactile sensitivity of the teeth, and associated periodontium, serves important sensory and motor functions. Microneurographic recordings from human periodontal ligament mechanoreceptor (PDLM) nerves, in response to tooth loading, reveal discharge patterns with sole slowly adapting (SA) II-type characteristics, highlighting the unique role of PDLMs in oral sensory processes. Here we investigate these receptors' properties, psychophysically and with neuroimaging (fMRI), in response to varying frequencies of dynamic (vibrotactile) stimulation. The finding of increased activity in primary (SI) and secondary (SII) somatosensory cortices (SI and SII) at low frequencies of stimulation (20 Hz) as compared with higher frequencies (50 and 100 Hz), shows an increased entrainment of the PDLMs at this lower frequency in line with expected SA II-type response properties. At the highest frequency (100 Hz), no significant activity was found in SI or SII, suggesting this frequency is outside the range of activity of PDLMs. An activation matrix is mapped that includes SI, SII, insular, inferior frontal gyrus, inferior parietal lobe and supplementary motor area as well as middle frontal gyrus and cerebellum. We compared the responses to tooth stimulation with those produced by identical vibrotactile stimulation of the finger. The results strongly suggest that the PDLMs play a significant role in the specification of the forces used to hold and manipulate food between teeth, and in these respects, the masticatory system appears analogous to fine finger-control mechanisms used during precision manipulation of small objects. Because fMRI reveals activations in posterior insular cortex, we also speculate that PDLMs, and SA II-type receptors in general, may be involved in one aspect of the feeling of body ownership. PMID:20668275

  7. Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI

    PubMed Central

    Lundengård, Karin; Cedersund, Gunnar; Sten, Sebastian; Leong, Felix; Smedberg, Alexander; Elinder, Fredrik

    2016-01-01

    Functional magnetic resonance imaging (fMRI) measures brain activity by detecting the blood-oxygen-level dependent (BOLD) response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new, independent validation data

  8. Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI.

    PubMed

    Lundengård, Karin; Cedersund, Gunnar; Sten, Sebastian; Leong, Felix; Smedberg, Alexander; Elinder, Fredrik; Engström, Maria

    2016-06-01

    Functional magnetic resonance imaging (fMRI) measures brain activity by detecting the blood-oxygen-level dependent (BOLD) response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new, independent validation data

  9. Task modulation of brain responses in visual word recognition as studied using EEG/MEG and fMRI

    PubMed Central

    Chen, Y.; Davis, M. H.; Pulvermüller, F.; Hauk, O.

    2013-01-01

    Do task demands change the way we extract information from a stimulus, or only how we use this information for decision making? In order to answer this question for visual word recognition, we used EEG/MEG as well as fMRI to determine the latency ranges and spatial areas in which brain activation to words is modulated by task demands. We presented letter strings in three tasks (lexical decision, semantic decision, silent reading), and measured combined EEG/MEG as well as fMRI responses in two separate experiments. EEG/MEG sensor statistics revealed the earliest reliable task effects at around 150 ms, which were localized, using minimum norm estimates (MNE), to left inferior temporal, right anterior temporal and left precentral gyri. Later task effects (250 and 480 ms) occurred in left middle and inferior temporal gyri. Our fMRI data showed task effects in left inferior frontal, posterior superior temporal and precentral cortices. Although there was some correspondence between fMRI and EEG/MEG localizations, discrepancies predominated. We suggest that fMRI may be less sensitive to the early short-lived processes revealed in our EEG/MEG data. Our results indicate that task-specific processes start to penetrate word recognition already at 150 ms, suggesting that early word processing is flexible and intertwined with decision making. PMID:23888133

  10. Altered neural response of the appetitive emotional system in cocaine addiction: an fMRI Study.

    PubMed

    Asensio, Samuel; Romero, Maria J; Palau, Carmina; Sanchez, Amparo; Senabre, Isabel; Morales, Julia L; Carcelen, Raquel; Romero, Francisco J

    2010-10-01

    Research on addiction suggests that emotional alterations play an essential role in the development, maintenance, relapse and treatment outcome of substance abuse disorders. Although many neuroimaging studies focussed on the neural response to conditioned stimuli, much less is known about the neural response to natural affective stimuli in this pathological population. Previous research has demonstrated an altered emotional experience and autonomic response to emotional stimuli using the International Affective Picture System (IAPS) in drug abusers. Here we aimed, using functional magnetic resonance imaging (fMRI), to study the alterations in the neural responsitivity to pleasant (erotic), unpleasant and neutral IAPS stimuli in cocaine addiction. Thirty-two cocaine-dependent subjects and 26 matched controls completed an fMRI session during the presentation of a set of IAPS pictures as background, while performing a letter discrimination task. Consistent with previous studies, emotional pictures activated an emotional network including amygdala, medial prefrontal cortex, orbitofrontal cortex and occipito-temporal areas in both groups. However, compared with controls, the cocaine group showed a significant hypoactivation of the dorsal and ventral striatum (including the nucleus accumbens), thalamus, parietal cortex and dorso-medial prefrontal cortex (dmPFC) when processing pleasant pictures. The analysis of pleasant versus unpleasant stimuli suggested that between-group differences in the dmPFC and striatal activation may be attributed to arousal processing rather than valence. These results could reflect the neural basis for the reduced ability of cocaine-dependent subjects to experience pleasure by daily natural reinforcers, suggesting that these alterations in the emotion processing may play an important role in drug dependence, treatment and relapse. PMID:20579005

  11. Magnitude and phase behavior of multiresolution BOLD signal

    PubMed Central

    Chen, Zikuan; Calhoun, Vince D.

    2010-01-01

    High spatial resolution fMRI provides a more precise estimate of brain activity than low resolution fMRI. The magnitude and phase parts of the BOLD signals are impacted differently by changes in the scan resolution. In this paper, we report on a numerical simulation to show the impact of spatial resolution upon the complex-valued BOLD signal in terms of magnitude and phase variation. We generate realistic capillary networks in cortex voxels, calculate the BOLD-induced magnetic field disturbance and the complex BOLD signals for the voxel and its subvoxels, and thereby characterize the magnitude and phase behaviors across multiple grid resolutions. Our results show that: 1) at higher spatial resolution there is greater spatial variation in the phase of the BOLD signal as compared to its magnitude; 2) the spatial variation of the phase signal monotonically increases with respect to spatial resolution while for the magnitude the spatial variation may reach a maximum at some resolution level; 3) voxels containing large capillaries have higher phase spatial variation than those with smaller capillaries; 4) the amplitude spatial variation at a resolution level increases with respect to relaxation time whereas the phase variation is generally unaffected. PMID:20890375

  12. Nicotine effects on brain function during a visual oddball task: a comparison between conventional and EEG-informed fMRI analysis.

    PubMed

    Warbrick, Tracy; Mobascher, Arian; Brinkmeyer, Jürgen; Musso, Francesco; Stoecker, Tony; Shah, N Jon; Fink, Gereon R; Winterer, Georg

    2012-08-01

    In a previous oddball task study, it was shown that the inclusion of electrophysiology (EEG), that is, single-trial P3 ERP parameters, in the analysis of fMRI responses can detect activation that is not apparent with conventional fMRI data modeling strategies [Warbrick, T., Mobascher, A., Brinkmeyer, J., Musso, F., Richter, N., Stoecker, T., et al. Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task. Neuroimage, 47, 1532-1544, 2009]. Given that P3 is modulated by nicotine, including P3 parameters in the fMRI analysis might provide additional information about nicotine effects on brain function. A 1-mg nasal nicotine spray (0.5 mg each nostril) or placebo (pepper) spray was administered in a double-blind, placebo-controlled, within-subject, randomized, cross-over design. Simultaneous EEG-fMRI and behavioral data were recorded from 19 current smokers in response to an oddball-type visual choice RT task. Conventional general linear model analysis and single-trial P3 amplitude informed general linear model analysis of the fMRI data were performed. Comparing the nicotine with the placebo condition, reduced RTs in the nicotine condition were related to decreased BOLD responses in the conventional analysis encompassing the superior parietal lobule, the precuneus, and the lateral occipital cortex. On the other hand, reduced RTs were related to increased BOLD responses in the precentral and postcentral gyri, and ACC in the EEG-informed fMRI analysis. Our results show how integrated analyses of simultaneous EEG-fMRI data can be used to detect nicotine effects that would not have been revealed through conventional analysis of either measure in isolation. This emphasizes the significance of applying multimodal imaging methods to pharmacoimaging. PMID:22452559

  13. Quantifying the microvascular origin of BOLD-fMRI from first principles with two-photon microscopy and an oxygen-sensitive nanoprobe.

    PubMed

    Gagnon, Louis; Sakadžić, Sava; Lesage, Frédéric; Musacchia, Joseph J; Lefebvre, Joël; Fang, Qianqian; Yücel, Meryem A; Evans, Karleyton C; Mandeville, Emiri T; Cohen-Adad, Jülien; Polimeni, Jonathan R; Yaseen, Mohammad A; Lo, Eng H; Greve, Douglas N; Buxton, Richard B; Dale, Anders M; Devor, Anna; Boas, David A

    2015-02-25

    The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences. PMID:25716864

  14. Role of 3T multiparametric-MRI with BOLD hypoxia imaging for diagnosis and post therapy response evaluation of postoperative recurrent cervical cancers

    PubMed Central

    Mahajan, Abhishek; Engineer, Reena; Chopra, Supriya; Mahanshetty, Umesh; Juvekar, S.L.; Shrivastava, S.K.; Desekar, Naresh; Thakur, M.H.

    2015-01-01

    Objectives To assess the diagnostic value of multiparametric-MRI (MPMRI) with hypoxia imaging as a functional marker for characterizing and detecting vaginal vault/local recurrence following primary surgery for cervical cancer. Methods With institutional review board approval and written informed consent 30 women (median age: 45 years) from October 2009 to March 2010 with previous operated carcinoma cervix and suspected clinical vaginal vault/local recurrence were examined with 3.0T-MRI. MRI imaging included conventional and MPMRI sequences [dynamic contrast enhanced (DCE), diffusion weighted (DW), 1H-MR spectroscopy (1HMRS), blood oxygen level dependent hypoxia imaging (BOLD)]. Two radiologists, blinded to pathologic findings, independently assessed the pretherapy MRI findings and then correlated it with histopathology findings. Sensitivity, specificity, positive predictive value, negative predictive value and their confidence intervals were calculated. The pre and post therapy conventional and MPMRI parameters were analyzed and correlated with response to therapy. Results Of the 30 patients, there were 24 recurrent tumors and 6 benign lesions. The accuracy of diagnosing recurrent vault lesions was highest at combined MPMRI and conventional MRI (100%) than at conventional-MRI (70%) or MPMRI (96.7%) alone. Significant correlation was seen between percentage tumor regression and pre-treatment parameters such as negative enhancement integral (NEI) (p = 0.02), the maximum slope (p = 0.04), mADC value (p = 0.001) and amount of hypoxic fraction on the pretherapy MRI (p = 0.01). Conclusion Conventional-MR with MPMRI significantly increases the diagnostic accuracy for suspected vaginal vault/local recurrence. Post therapy serial MPMRI with hypoxia imaging follow-up objectively documents the response. MPMRI and BOLD hypoxia imaging provide information regarding tumor biology at the molecular, subcellular, cellular and tissue levels and this information may be used

  15. The power of using functional fMRI on small rodents to study brain pharmacology and disease

    PubMed Central

    Jonckers, Elisabeth; Shah, Disha; Hamaide, Julie; Verhoye, Marleen; Van der Linden, Annemie

    2015-01-01

    Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anesthesia and the animal’s physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest. In addition, fMRI techniques allow one to dissect how specific modifications (e.g., treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological

  16. An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders

    PubMed Central

    Masten, Carrie L.; Colich, Natalie L.; Rudie, Jeffrey D.; Bookheimer, Susan Y.; Eisenberger, Naomi I.; Dapretto, Mirella

    2011-01-01

    Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives. PMID:22318914

  17. Monitoring of the tumor response to nano-graphene oxide-mediated photothermal/photodynamic therapy by diffusion-weighted and BOLD MRI.

    PubMed

    Cao, Jianbo; An, Hengqing; Huang, Xinglu; Fu, Guifeng; Zhuang, Rongqiang; Zhu, Lei; Xie, Jin; Zhang, Fan

    2016-05-21

    Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities. Because each modality has its own set of advantages and limitations, there has been interest in developing methods that can co-deliver the two regimens for enhanced tumor treatment. Among the efforts, nano-graphene oxide-mediated phototherapies have recently attracted much attention. Nano-graphene oxide has a broad absorbance spectrum and can be loaded with photosensitizers, such as chlorin e6, with high efficiency. Chlorin e6-loaded and PEGylated nano-graphene (GO-PEG-Ce6) can be excited at 660 nm, 808 nm, or both, to induce PDT, PTT, or PDT/PTT combination. Despite the potential of the treatments, there is a lack of a diagnostic tool which can monitor their therapeutic response in a non-invasive and prognostic manner; such an ability is urgently needed for the transformation and translation of the technologies. In this study, we performed diffusion-weighted and blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) after GO-PEG-Ce6-mediated PTT, PDT, or PTT/PDT. We found that after efficient PTT, there is a significant increase of the tumor apparent diffusion coefficient (ADC) value in diffusion-weighted imaging (DWI) maps; meanwhile, an efficient PDT led to an increase of in BOLD images. In both the cases, the amplitude of the increase was correlated with the treatment outcomes. More interestingly, a synergistic treatment efficacy was observed when the PTT/PDT combination was applied, and the combination was associated with a greater ADC and increase than when either modality was used alone. In particular, the PTT/PDT condition that induced the most dramatic short-term increase of the ADC value (>70%) caused the most effective tumor control in the long-run, with 60% of the treated animals being tumor-free after 60 days. These results suggest the great promise of the combination of DWI and BOLD MRI as a tool for accurate monitoring and prognosis

  18. Monitoring of the tumor response to nano-graphene oxide-mediated photothermal/photodynamic therapy by diffusion-weighted and BOLD MRI

    NASA Astrophysics Data System (ADS)

    Cao, Jianbo; An, Hengqing; Huang, Xinglu; Fu, Guifeng; Zhuang, Rongqiang; Zhu, Lei; Xie, Jin; Zhang, Fan

    2016-05-01

    Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities. Because each modality has its own set of advantages and limitations, there has been interest in developing methods that can co-deliver the two regimens for enhanced tumor treatment. Among the efforts, nano-graphene oxide-mediated phototherapies have recently attracted much attention. Nano-graphene oxide has a broad absorbance spectrum and can be loaded with photosensitizers, such as chlorin e6, with high efficiency. Chlorin e6-loaded and PEGylated nano-graphene (GO-PEG-Ce6) can be excited at 660 nm, 808 nm, or both, to induce PDT, PTT, or PDT/PTT combination. Despite the potential of the treatments, there is a lack of a diagnostic tool which can monitor their therapeutic response in a non-invasive and prognostic manner; such an ability is urgently needed for the transformation and translation of the technologies. In this study, we performed diffusion-weighted and blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) after GO-PEG-Ce6-mediated PTT, PDT, or PTT/PDT. We found that after efficient PTT, there is a significant increase of the tumor apparent diffusion coefficient (ADC) value in diffusion-weighted imaging (DWI) maps; meanwhile, an efficient PDT led to an increase of in BOLD images. In both the cases, the amplitude of the increase was correlated with the treatment outcomes. More interestingly, a synergistic treatment efficacy was observed when the PTT/PDT combination was applied, and the combination was associated with a greater ADC and increase than when either modality was used alone. In particular, the PTT/PDT condition that induced the most dramatic short-term increase of the ADC value (>70%) caused the most effective tumor control in the long-run, with 60% of the treated animals being tumor-free after 60 days. These results suggest the great promise of the combination of DWI and BOLD MRI as a tool for accurate monitoring and prognosis

  19. The contribution of surprise to the prediction based modulation of fMRI responses.

    PubMed

    Amado, Catarina; Hermann, Petra; Kovács, Petra; Grotheer, Mareike; Vidnyánszky, Zoltán; Kovács, Gyula

    2016-04-01

    In recent years, several functional magnetic resonance imaging (fMRI) studies showed that correct stimulus predictions reduce the neural responses when compared to surprising events (Egner et al., 2010). Further, it has been shown that such fulfilled expectations enhance the magnitude of repetition suppression (RS, i.e. a decreased neuronal response after the repetition of a given stimulus) in face selective visual cortex as well (Summerfield et al., 2008). Current MEG and neuroimaging studies suggest that the underlying mechanisms of expectation effects are independent from these of RS (Grotheer and Kovács, 2015; Todorovic and Lange, 2012). However, it is not clear as of today how perceptual expectations modulate the neural responses: is the difference between correctly predicted and surprising stimuli due to a genuine response reduction for correctly predicted stimuli or is it due to an increased response for surprising stimuli? Therefore, here we used a modified version of the paradigm of Grotheer and Kovács (2015) to induce predictions independently from repetition probability by presenting pairs of faces (female, male or infant) that were either repeated or alternating. Orthogonally to this, predictions were manipulated by the gender of the first face within each pair so that it signaled high, low or equal probability of repetitions. An unpredicted, neutral condition with equal probabilities for alternating and repeated trials was used to identify the role of surprising and enhancing modulations. Similarly, to Grotheer and Kovács (2015), we found significant RS and significant expectation effect in the FFA. Importantly, we observed larger response for surprising events in comparison to the neutral and correctly predicted conditions for alternating trials. Altogether, these results emphasize the role of surprise in prediction effects. PMID:26873275

  20. [fMRI study of deliberate deception].

    PubMed

    Kireev, M V; Korotkov, A D; Medvedev, C V

    2012-01-01

    The aim of the present research was to study the deliberate deception. Event related functional magnetic resonance (fMRI) imaging technique was used to assess the changes in functional brain activity by virtue of recording blood oxygen level dependant signal (BOLD-signal). 12 right-handed healthy volunteers aged 19-44 participated in the study. BOLD images were acquired in three different experimental trials. There were deliberate deception, manipulative honest and control truthful trials (catch trials). The main finding of the present study is that the deliberate deception and manipulative honest actions in comparison with instructed truthful responding was characterized by BOLD signal increase within the anterior cingulated cortex (ACC), frontal and parietal areas as well. Comparison of present fMRI data with results demonstrated in our previous research implemented with event related potentials technique points to the involvement of the brain mechanism of error detection to brain processing of deliberate deception. PMID:22567835

  1. Abnormal Social Reward Responses in Anorexia Nervosa: An fMRI Study

    PubMed Central

    Via, Esther; Soriano-Mas, Carles; Sánchez, Isabel; Forcano, Laura; Harrison, Ben J.; Davey, Christopher G.; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Menchón, José M.; Fernández-Aranda, Fernando; Cardoner, Narcís

    2015-01-01

    Patients with anorexia nervosa (AN) display impaired social interactions, implicated in the development and prognosis of the disorder. Importantly, social behavior is modulated by reward-based processes, and dysfunctional at-brain-level reward responses have been involved in AN neurobiological models. However, no prior evidence exists of whether these neural alterations would be equally present in social contexts. In this study, we conducted a cross-sectional social-judgment functional magnetic resonance imaging (fMRI) study of 20 restrictive-subtype AN patients and 20 matched healthy controls. Brain activity during acceptance and rejection was investigated and correlated with severity measures (Eating Disorder Inventory -EDI-2) and with personality traits of interest known to modulate social behavior (The Sensitivity to Punishment and Sensitivity to Reward Questionnaire). Patients showed hypoactivation of the dorsomedial prefrontal cortex (DMPFC) during social acceptance and hyperactivation of visual areas during social rejection. Ventral striatum activation during rejection was positively correlated in patients with clinical severity scores. During acceptance, activation of the frontal opercula-anterior insula and dorsomedial/dorsolateral prefrontal cortices was differentially associated with reward sensitivity between groups. These results suggest an abnormal motivational drive for social stimuli, and involve overlapping social cognition and reward systems leading to a disruption of adaptive responses in the processing of social reward. The specific association of reward-related regions with clinical and psychometric measures suggests the putative involvement of reward structures in the maintenance of pathological behaviors in AN. PMID:26197051

  2. Bold Books for Teenagers

    ERIC Educational Resources Information Center

    Gallo, Don

    2005-01-01

    "Bold Books for Teenagers" provides dynamic, informative viewpoints on important issues in publishing and teaching contemporary literature, especially literature for adolescents. Reviews of young adult literature also appear in this column. This article examines how English teachers can help students explore their interests without promoting any…

  3. Laminar analysis of 7 T BOLD using an imposed spatial activation pattern in human V1

    PubMed Central

    Polimeni, Jonathan R.; Fischl, Bruce; Greve, Douglas N.; Wald, Lawrence L.

    2010-01-01

    With sufficient image encoding, high-resolution fMRI studies are limited by the biological point-spread of the hemodynamic signal. The extent of this spread is determined by the local vascular distribution and by the spatial specificity of blood flow regulation, as well as by measurement parameters that (i) alter the relative sensitivity of the acquisition to activation-induced hemodynamic changes and (ii) determine the image contrast as a function of vessel size. In particular, large draining vessels on the cortical surface are a major contributor to both the BOLD signal change and to the spatial bias of the BOLD activation away from the site of neuronal activity. In this work, we introduce a laminar surface-based analysis method and study the relationship between spatial localization and activation strength as a function of laminar depth by acquiring 1 mm isotropic, single-shot EPI at 7 T and sampling the BOLD signal exclusively from the superficial, middle, or deep cortical laminae. We show that highly-accelerated EPI can limit image distortions to the point where a boundary-based registration algorithm accurately aligns the EPI data to the surface reconstruction. The spatial spread of the BOLD response tangential to the cortical surface was analyzed as a function of cortical depth using our surface-based analysis. Although sampling near the pial surface provided the highest signal strength, it also introduced the most spatial error. Thus, avoiding surface laminae improved spatial localization by about 40% at a cost of 36% in z-statistic, implying that optimal spatial resolution in functional imaging of the cortex can be achieved using anatomically-informed spatial sampling to avoid large pial vessels. PMID:20460157

  4. Resting-state FMRI confounds and cleanup

    PubMed Central

    Murphy, Kevin; Birn, Rasmus M.; Bandettini, Peter A.

    2013-01-01

    The goal of resting-state functional magnetic resonance imaging (FMRI) is to investigate the brain’s functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of FMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state FMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state FMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state FMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline. PMID:23571418

  5. Fast fMRI provides high statistical power in the analysis of epileptic networks.

    PubMed

    Jacobs, Julia; Stich, Julia; Zahneisen, Benjamin; Assländer, Jakob; Ramantani, Georgia; Schulze-Bonhage, Andreas; Korinthenberg, Rudolph; Hennig, Jürgen; LeVan, Pierre

    2014-03-01

    EEG-fMRI is a unique method to combine the high temporal resolution of EEG with the high spatial resolution of MRI to study generators of intrinsic brain signals such as sleep grapho-elements or epileptic spikes. While the standard EPI sequence in fMRI experiments has a temporal resolution of around 2.5-3s a newly established fast fMRI sequence called MREG (Magnetic-Resonance-Encephalography) provides a temporal resolution of around 100ms. This technical novelty promises to improve statistics, facilitate correction of physiological artifacts and improve the understanding of epileptic networks in fMRI. The present study compares simultaneous EEG-EPI and EEG-MREG analyzing epileptic spikes to determine the yield of fast MRI in the analysis of intrinsic brain signals. Patients with frequent interictal spikes (>3/20min) underwent EEG-MREG and EEG-EPI (3T, 20min each, voxel size 3×3×3mm, EPI TR=2.61s, MREG TR=0.1s). Timings of the spikes were used in an event-related analysis to generate activation maps of t-statistics. (FMRISTAT, |t|>3.5, cluster size: 7 voxels, p<0.05 corrected). For both sequences, the amplitude and location of significant BOLD activations were compared with the spike topography. 13 patients were recorded and 33 different spike types could be analyzed. Peak T-values were significantly higher in MREG than in EPI (p<0.0001). Positive BOLD effects correlating with the spike topography were found in 8/29 spike types using the EPI and in 22/33 spikes types using the MREG sequence. Negative BOLD responses in the default mode network could be observed in 3/29 spike types with the EPI and in 19/33 with the MREG sequence. With the latter method, BOLD changes were observed even when few spikes occurred during the investigation. Simultaneous EEG-MREG thus is possible with good EEG quality and shows higher sensitivity in regard to the localization of spike-related BOLD responses than EEG-EPI. The development of new methods of analysis for this sequence such as

  6. Negligible fronto-parietal BOLD activity accompanying unreportable switches in bistable perception

    PubMed Central

    Brascamp, Jan; Blake, Randolph; Knapen, Tomas

    2015-01-01

    The human brain's executive systems play a vital role in deciding and selecting among actions. Selection among alternatives also occurs in the perceptual domain, for instance when perception switches between interpretations during perceptual bistability. Whether executive systems also underlie this functionality remains debated, with known fronto-parietal concomitants of perceptual switches being variously interpreted as reflecting the switches' cause, or as reflecting their consequences. We developed a paradigm where the two eyes receive different inputs and perception demonstrably switches between these inputs, yet where switches themselves are so inconspicuous as to become unreportable, minimizing their executive consequences. Fronto-parietal fMRI BOLD responses that accompany perceptual switches were similarly minimized in this paradigm, indicating that these reflect the switches' consequences rather than their cause. We conclude that perceptual switches do not always rely on executive brain areas, and that processes responsible for selection among alternatives may operate outside of the brain's executive systems. PMID:26436901

  7. Simultaneous fMRI and local field potential measurements during epileptic seizures in medetomidine sedated rats using RASER pulse sequence

    PubMed Central

    Airaksinen, Antti M; Niskanen, Juha-Pekka; Chamberlain, Ryan; Huttunen, Joanna K; Nissinen, Jari; Garwood, Michael; Pitkänen, Asla; Gröhn, Olli

    2010-01-01

    Simultaneous electrophysiological and functional magnetic resonance imaging (fMRI) measurements of animal models of epilepsy are methodologically challenging, but essential to better understand abnormal brain activity and hemodynamics during seizures. In the present study, fMRI of medetomidine sedated rats was performed using novel Rapid Acquisition by Sequential Excitation and Refocusing (RASER) fast imaging pulse sequence and simultaneous local field potential (LFP) measurements during kainic acid (KA) induced seizures. The image distortion caused by the hippocampal measuring electrode was clearly seen in echo planar imaging (EPI) images, whereas no artifact was seen in RASER images. Robust blood oxygenation level dependent (BOLD) responses were observed in the hippocampus during KA induced seizures. The recurrent epileptic seizures were detected in the LFP signal after KA injection. The presented combination of deep electrode LFP measurements and fMRI under medetomidine anesthesia, that does not significantly suppress KA induced seizures, provides a unique tool for studying abnormal brain activity in rats. PMID:20725933

  8. Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats

    PubMed Central

    Ferris, Craig F.; Yee, Jason R.; Kenkel, William M.; Dumais, Kelly Marie; Moore, Kelsey; Veenema, Alexa H.; Kulkarni, Praveen; Perkybile, Allison M.; Carter, C. Sue

    2015-01-01

    A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood–brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose–response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity. PMID:26441574

  9. LH-RH agonists modulate amygdala response to visual sexual stimulation: a single case fMRI study in pedophilia.

    PubMed

    Habermeyer, Benedikt; Händel, Nadja; Lemoine, Patrick; Klarhöfer, Markus; Seifritz, Erich; Dittmann, Volker; Graf, Marc

    2012-01-01

    Pedophilia is characterized by a persistent sexual attraction to prepubescent children. Treatment with anti-androgen agents, such as luteinizing hormone-releasing hormone (LH-RH) agonists, reduces testosterone levels and thereby sexual drive and arousal. We used functional magnetic resonance imaging (fMRI) to compare visual erotic stimulation pre- and on-treatment with the LH-RH agonist leuprolide acetate in the case of homosexual pedophilia. The pre-treatment contrasts of the erotic pictures against the respective neutral pictures showed an activation of the right amygdala and adjacent parahippocampal gyrus that decreased significantly under treatment with leuprolide acetate. Our single case fMRI study supports the notion that anti-androgens may modify amygdala response to visual erotic stimulation, a hypothesis that should be further examined in larger studies. PMID:22136615

  10. Assessment of temporal state-dependent interactions between auditory fMRI responses to desired and undesired acoustic sources.

    PubMed

    Olulade, O; Hu, S; Gonzalez-Castillo, J; Tamer, G G; Luh, W-M; Ulmer, J L; Talavage, T M

    2011-07-01

    A confounding factor in auditory functional magnetic resonance imaging (fMRI) experiments is the presence of the acoustic noise inherently associated with the echo planar imaging acquisition technique. Previous studies have demonstrated that this noise can induce unwanted neuronal responses that can mask stimulus-induced responses. Similarly, activation accumulated over multiple stimuli has been demonstrated to elevate the baseline, thus reducing the dynamic range available for subsequent responses. To best evaluate responses to auditory stimuli, it is necessary to account for the presence of all recent acoustic stimulation, beginning with an understanding of the attenuating effects brought about by interaction between and among induced unwanted neuronal responses, and responses to desired auditory stimuli. This study focuses on the characterization of the duration of this temporal memory and qualitative assessment of the associated response attenuation. Two experimental parameters--inter-stimulus interval (ISI) and repetition time (TR)--were varied during an fMRI experiment in which participants were asked to passively attend to an auditory stimulus. Results present evidence of a state-dependent interaction between induced responses. As expected, attenuating effects of these interactions become less significant as TR and ISI increase and in contrast to previous work, persist up to 18s after a stimulus presentation. PMID:21426929

  11. Incongruent Abstract Stimulus–Response Bindings Result in Response Interference: fMRI and EEG Evidence from Visual Object Classification Priming

    PubMed Central

    Horner, Aidan J.; Henson, Richard N.

    2013-01-01

    Stimulus repetition often leads to facilitated processing, resulting in neural decreases (repetition suppression) and faster RTs (repetition priming). Such repetition-related effects have been attributed to the facilitation of repeated cognitive processes and/or the retrieval of previously encoded stimulus–response (S-R) bindings. Although previous research has dissociated these two forms of learning, their interaction in the brain is not fully understood. Utilizing the spatial and temporal resolutions of fMRI and EEG, respectively, we examined a long-lag classification priming paradigm that required response repetitions or reversals at multiple levels of response representation. We found a repetition effect in occipital/temporal cortex (fMRI) that was time-locked to stimulus onset (EEG) and robust to switches in response, together with a repetition effect in inferior pFC (fMRI) that was time-locked to response onset (EEG) and sensitive to switches in response. The response-sensitive effect occurred even when changing from object names (words) to object pictures between repetitions, suggesting that S-R bindings can code abstract representations of stimuli. Most importantly, we found evidence for interference effects when incongruent S-R bindings were retrieved, with increased neural activity in inferior pFC, demonstrating that retrieval of S-R bindings can result in facilitation or interference, depending on the congruency of response between repetitions. PMID:22066586

  12. FMRI Signal Analysis Using Empirical Mean Curve Decomposition

    PubMed Central

    Deng, Fan; Zhu, Dajiang; Lv, Jinglei; Guo, Lei; Liu, Tianming

    2013-01-01

    Functional magnetic resonance imaging (fMRI) time series is non-linear and composed of components at multiple temporal scales, which presents significant challenges to its analysis. In the literature, significant effort has been devoted into model-based fMRI signal analysis, while much less attention has been directed to data-driven fMRI signal analysis. In this paper, we present a novel data-driven multi-scale signal decomposition framework named Empirical Mean Curve Decomposition (EMCD). Targeted on functional brain mapping, the EMCD optimizes mean envelopes from fMRI signals and iteratively extracts coarser-to-finer scale signal components. The EMCD framework was applied to infer meaningful low-frequency information from Blood Oxygenation Level Dependent (BOLD) signals from resting state fMRI, task-based fMRI, and natural stimulus fMRI, and promising results are obtained. PMID:23047856

  13. Longitudinal Changes in Cerebral Response to Proprioceptive Input in Individual Patients after Stroke: An fMRI Study

    PubMed Central

    Ward, Nick S.; Brown, Martin M.; Thompson, Alan J.; Frackowiak, Richard S. J.

    2013-01-01

    Objective Functional magnetic resonance imaging (fMRI) provides an opportunity to study the relationship between cerebral reorganization and functional recovery after stroke. The authors set out to demonstrate the feasibility of using fMRI to investigate mechanisms of recovery in individual patients presenting with severe motor impairment. Methods fMRI was performed during passive movement at both affected and unaffected wrists separately in 2 patients with pure motor stroke. Six scanning sessions were performed in each patient over the first 4 months after stroke. Seven control subjects were also studied, 1 of them over 6 sessions. The authors examined for longitudinal changes in cerebral responses to proprioceptive afferent input that correlated with motor recovery. Results In control subjects, passive movement of either wrist led to relative increases in brain activation in the contralateral sensorimotor cortex and supplementary motor area, the bilateral inferior parietal cortex and secondary somatosensory areas, and the ipsilateral cerebellum. Increases in brain activation correlating with motor recovery were observed in both the ipsilesional primary sensory and primary motor cortex in 1 patient with good motor recovery but not in another patient with poor recovery. No longitudinal changes were seen in the control subject. Conclusions These 2 case reports demonstrate that functionally relevant changes in cerebral organization can be identified in individual patients. PMID:16885426

  14. Comparison of Psychophysical, Electrophysiological, and fMRI Assessment of Visual Contrast Responses in Patients with Schizophrenia

    PubMed Central

    Calderone, Daniel J.; Martinez, Antígona; Zemon, Vance; Hoptman, Matthew J.; Hu, George; Watkins, Jade E.; Javitt, Daniel C.; Butler, Pamela D.

    2012-01-01

    Perception has been identified by the NIMH-sponsored Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) group as a useful domain for assessing cognitive deficits in patients with schizophrenia. Specific measures of contrast gain derived from recordings of steady-state visual evoked potentials (ssVEP) have demonstrated neural deficits within the visual pathways of patients with schizophrenia. Psychophysical measures of contrast sensitivity have also shown functional loss in these patients. In the current study, functional magnetic resonance imaging (fMRI) was used in conjunction with ssVEP and contrast sensitivity testing to elucidate the neural underpinnings of these deficits. During fMRI scanning, participants viewed 1) the same low and higher spatial frequency stimuli used in the psychophysical contrast sensitivity task, at both individual detection threshold contrast and at a high contrast; and 2) the same stimuli used in the ssVEP paradigm, which were designed to be biased toward either the magnocellular or parvocellular visual pathway. Patients showed significant impairment in contrast sensitivity at both spatial frequencies in the psychophysical task, but showed reduced occipital activation volume for low, but not higher, spatial frequency at the low and high contrasts tested in the magnet. As expected, patients exhibited selective deficits under the magnocellular-biased ssVEP condition. However, occipital lobe fMRI responses demonstrated the same general pattern for magnocellular- and parvocellular-biased stimuli across groups. These results indicate dissociation between the fMRI measures and the psychophysical/ssVEP measures. These latter measures appear to have greater value for the functional assessment of the contrast deficits explored here. PMID:23194815

  15. Hand gestures as visual prosody: BOLD responses to audio-visual alignment are modulated by the communicative nature of the stimuli.

    PubMed

    Biau, Emmanuel; Morís Fernández, Luis; Holle, Henning; Avila, César; Soto-Faraco, Salvador

    2016-05-15

    During public addresses, speakers accompany their discourse with spontaneous hand gestures (beats) that are tightly synchronized with the prosodic contour of the discourse. It has been proposed that speech and beat gestures originate from a common underlying linguistic process whereby both speech prosody and beats serve to emphasize relevant information. We hypothesized that breaking the consistency between beats and prosody by temporal desynchronization, would modulate activity of brain areas sensitive to speech-gesture integration. To this aim, we measured BOLD responses as participants watched a natural discourse where the speaker used beat gestures. In order to identify brain areas specifically involved in processing hand gestures with communicative intention, beat synchrony was evaluated against arbitrary visual cues bearing equivalent rhythmic and spatial properties as the gestures. Our results revealed that left MTG and IFG were specifically sensitive to speech synchronized with beats, compared to the arbitrary vision-speech pairing. Our results suggest that listeners confer beats a function of visual prosody, complementary to the prosodic structure of speech. We conclude that the emphasizing function of beat gestures in speech perception is instantiated through a specialized brain network sensitive to the communicative intent conveyed by a speaker with his/her hands. PMID:26892858

  16. Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture.

    PubMed

    Napadow, Vitaly; Dhond, Rupali; Park, Kyungmo; Kim, Jieun; Makris, Nikos; Kwong, Kenneth K; Harris, Richard E; Purdon, Patrick L; Kettner, Norman; Hui, Kathleen K S

    2009-08-01

    Acupuncture modulation of activity in the human brainstem is not well known. This structure is plagued by physiological artifact in neuroimaging experiments. In addition, most studies have used short (<15 min) block designs, which miss delayed responses following longer duration stimulation. We used brainstem-focused cardiac-gated fMRI and evaluated time-variant brain response to longer duration (>30 min) stimulation with verum (VA, electro-stimulation at acupoint ST-36) or sham point (SPA, non-acupoint electro-stimulation) acupuncture. Our results provide evidence that acupuncture modulates brainstem nuclei important to endogenous monoaminergic and opioidergic systems. Specifically, VA modulated activity in the substantia nigra (SN), nucleus raphe magnus, locus ceruleus, nucleus cuneiformis, and periaqueductal gray (PAG). Activation in the ventrolateral PAG was greater for VA compared to SPA. Linearly decreasing time-variant activation, suggesting classical habituation, was found in response to both VA and SPA in sensorimotor (SII, posterior insula, premotor cortex) brain regions. However, VA also produced linearly time-variant activity in limbic regions (amygdala, hippocampus, and SN), which was bimodal and not likely habituation--consisting of activation in early blocks, and deactivation by the end of the run. Thus, acupuncture induces different brain response early, compared to 20-30 min after stimulation. We attribute the fMRI differences between VA and SPA to more varied and stronger psychophysical response induced by VA. Our study demonstrates that acupuncture modulation of brainstem structures can be studied non-invasively in humans, allowing for comparison to animal studies. Our protocol also demonstrates a fMRI approach to study habituation and other time-variant phenomena over longer time durations. PMID:19345268

  17. The long-term effects of prenatal nicotine exposure on response inhibition: an fMRI study of young adults.

    PubMed

    Longo, Carmelinda A; Fried, Peter A; Cameron, Ian; Smith, Andra M

    2013-01-01

    The long-term effects of prenatal nicotine exposure on response inhibition were investigated in young adults using functional magnetic resonance imaging (fMRI). Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood, which allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana and alcohol exposure and current marijuana, nicotine and alcohol use. Twelve young adults with prenatal nicotine exposure and 13 non-exposed controls performed a Go/No-Go task while fMRI blood oxygen level-dependent responses were examined. Despite similar task performance, participants prenatally exposed to nicotine demonstrated significantly greater activity in several regions of the brain that typically subserve response inhibition including the inferior frontal gyrus, the inferior parietal lobe, the thalamus and the basal ganglia. In addition, prenatally exposed participants showed greater activity in relatively large posterior regions of the cerebellum. These results suggest that prenatal nicotine exposure leads to altered neural functioning during response inhibition that continues into adulthood. This alteration is compensated for by recruitment of greater neural resources within regions of the brain that subserve response inhibition and the recruitment of additional brain regions to successfully perform the task. Response inhibition is an important executive functioning skill and impairments can impede functioning in much of everyday life. Thus, awareness of the continued long-term neural physiological effects of prenatal nicotine exposure is critical. PMID:23743331

  18. The BOLD Response during Stroop Task-Like Inhibition Paradigms: Effects of Task Difficulty and Task-Relevant Modality

    ERIC Educational Resources Information Center

    Mitchell, Rachel L. C.

    2005-01-01

    Previous studies of the Stroop task propose two key mediators: the prefrontal and cingulate cortices but hints exist of functional specialization within these regions. This study aimed to examine the effect of task modality upon the prefrontal and cingulate response by examining the response to colour, number, and shape Stroop tasks whilst BOLD…

  19. Are Errors Differentiable from Deceptive Responses when Feigning Memory Impairment? An fMRI Study

    ERIC Educational Resources Information Center

    Lee, Tatia M. C.; Au, Ricky K. C.; Liu, Ho-Ling; Ting, K. H.; Huang, Chih-Mao; Chan, Chetwyn C. H.

    2009-01-01

    Previous neuroimaging studies have suggested that the neural activity associated with truthful recall, with false memory, and with feigned memory impairment are different from one another. Here, we report a functional magnetic resonance imaging (fMRI) study that addressed an important but yet unanswered question: Is the neural activity associated…

  20. Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: A pharmacological fMRI study.

    PubMed

    Bolstad, Ingeborg; Andreassen, Ole A; Groote, Inge; Server, Andres; Sjaastad, Ivar; Kapur, Shitij; Jensen, Jimmy

    2015-12-01

    The atypical antipsychotic drug aripiprazole is a partial dopamine (DA) D2 receptor agonist, which differentiates it from most other antipsychotics. This study compares the brain activation characteristic produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist. Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo, and then performed an active aversive conditioning task with aversive and neutral events presented as sounds, while blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out. The fMRI task, targeting the mesolimbic motivational system that is thought to be disturbed in psychosis, was based on the conditioned avoidance response (CAR) animal model - a widely used test of therapeutic potential of antipsychotic drugs. In line with the CAR animal model, the present results show that subjects given haloperidol were not able to avoid more aversive than neutral task trials, even though the response times were shorter during aversive events. In the aripiprazole and placebo groups more aversive than neutral events were avoided. Accordingly, the task-related BOLD-fMRI response in the mesolimbic motivational system was diminished in the haloperidol group compared to the placebo group, particularly in the ventral striatum, whereas the aripiprazole group showed task-related activations intermediate of the placebo and haloperidol groups. The current results show differential effects on brain function by aripiprazole and haloperidol, probably related to altered DA transmission. This supports the use of pharmacological fMRI to study antipsychotic properties in humans. PMID:26476705

  1. Systemic Low-Frequency Oscillations in BOLD Signal Vary with Tissue Type

    PubMed Central

    Tong, Yunjie; Hocke, Lia M.; Lindsey, Kimberly P.; Erdoğan, Sinem B.; Vitaliano, Gordana; Caine, Carolyn E.; Frederick, Blaise deB.

    2016-01-01

    Blood-oxygen-level dependent (BOLD) signals are widely used in functional magnetic resonance imaging (fMRI) as a proxy measure of brain activation. However, because these signals are blood-related, they are also influenced by other physiological processes. This is especially true in resting state fMRI, during which no experimental stimulation occurs. Previous studies have found that the amplitude of resting state BOLD is closely related to regional vascular density. In this study, we investigated how some of the temporal fluctuations of the BOLD signal also possibly relate to regional vascular density. We began by identifying the blood-bound systemic low-frequency oscillation (sLFO). We then assessed the distribution of all voxels based on their correlations with this sLFO. We found that sLFO signals are widely present in resting state BOLD signals and that the proportion of these sLFOs in each voxel correlates with different tissue types, which vary significantly in underlying vascular density. These results deepen our understanding of the BOLD signal and suggest new imaging biomarkers based on fMRI data, such as amplitude of low-frequency fluctuation (ALFF) and sLFO, a combination of both, for assessing vascular density. PMID:27445680

  2. Functional MRI and neural responses in a rat model of Alzheimer’s disease

    PubMed Central

    Sanganahalli, Basavaraju G.; Herman, Peter; Behar, Kevin L.; Blumenfeld, Hal; Rothman, Douglas L.; Hyder, Fahmeed

    2013-01-01

    Based on the hypothesis that brain plaques and tangles can affect cortical functions in Alzheimer's disease (AD) and thus modify functional activity, we investigated functional responses in an AD rat model (called the Samaritan Alzheimer’s rat achieved by ventricular infusion of amyloid peptide) and age-matched healthy control. High-field functional magnetic resonance imaging (fMRI) and extracellular neural activity measurements were applied to characterize sensory-evoked responses. Electrical stimulation of the forepaw led to BOLD and neural responses in the contralateral somatosensory cortex and thalamus. In AD brain we noted much smaller BOLD activation patterns in the somatosensory cortex (i.e., about 50% less activated voxels compared to normal brain). While magnitudes of BOLD and neural responses in the cerebral cortex were markedly attenuated in AD rats compared to normal rats (by about 50%), the dynamic coupling between the BOLD and neural responses in the cerebral cortex, as assessed by transfer function analysis, remained unaltered between the groups. However thalamic BOLD and neural responses were unaltered in AD brain compared to controls. Thus cortical responses in the AD model were indeed diminished compared to controls, but the thalamic responses in the AD and control rats were quite similar. Therefore these results suggest that Alzheimer’s disease may affect cortical function more than subcortical function, which may have implications for interpreting altered human brain functional responses in fMRI studies of Alzheimer’s disease. PMID:23648961

  3. The relationship between oscillatory EEG activity and the laminar-specific BOLD signal.

    PubMed

    Scheeringa, René; Koopmans, Peter J; van Mourik, Tim; Jensen, Ole; Norris, David G

    2016-06-14

    Electrophysiological recordings in animals have indicated that visual cortex γ-band oscillatory activity is predominantly observed in superficial cortical layers, whereas α- and β-band activity is stronger in deep layers. These rhythms, as well as the different cortical layers, have also been closely related to feedforward and feedback streams of information. Recently, it has become possible to measure laminar activity in humans with high-resolution functional MRI (fMRI). In this study, we investigated whether these different frequency bands show a differential relation with the laminar-resolved blood-oxygen level-dependent (BOLD) signal by combining data from simultaneously recorded EEG and fMRI from the early visual cortex. Our visual attention paradigm allowed us to investigate how variations in strength over trials and variations in the attention effect over subjects relate to each other in both modalities. We demonstrate that γ-band EEG power correlates positively with the superficial layers' BOLD signal and that β-power is negatively correlated to deep layer BOLD and α-power to both deep and superficial layer BOLD. These results provide a neurophysiological basis for human laminar fMRI and link human EEG and high-resolution fMRI to systems-level neuroscience in animals. PMID:27247416

  4. Mapping brain networks in awake mice using combined optical neural control and fMRI.

    PubMed

    Desai, M; Kahn, I; Knoblich, U; Bernstein, J; Atallah, H; Yang, A; Kopell, N; Buckner, R L; Graybiel, A M; Moore, C I; Boyden, E S

    2011-03-01

    Behaviors and brain disorders involve neural circuits that are widely distributed in the brain. The ability to map the functional connectivity of distributed circuits, and to assess how this connectivity evolves over time, will be facilitated by methods for characterizing the network impact of activating a specific subcircuit, cell type, or projection pathway. We describe here an approach using high-resolution blood oxygenation level-dependent (BOLD) functional MRI (fMRI) of the awake mouse brain-to measure the distributed BOLD response evoked by optical activation of a local, defined cell class expressing the light-gated ion channel channelrhodopsin-2 (ChR2). The utility of this opto-fMRI approach was explored by identifying known cortical and subcortical targets of pyramidal cells of the primary somatosensory cortex (SI) and by analyzing how the set of regions recruited by optogenetically driven SI activity differs between the awake and anesthetized states. Results showed positive BOLD responses in a distributed network that included secondary somatosensory cortex (SII), primary motor cortex (MI), caudoputamen (CP), and contralateral SI (c-SI). Measures in awake compared with anesthetized mice (0.7% isoflurane) showed significantly increased BOLD response in the local region (SI) and indirectly stimulated regions (SII, MI, CP, and c-SI), as well as increased BOLD signal temporal correlations between pairs of regions. These collective results suggest opto-fMRI can provide a controlled means for characterizing the distributed network downstream of a defined cell class in the awake brain. Opto-fMRI may find use in examining causal links between defined circuit elements in diverse behaviors and pathologies. PMID:21160013

  5. Hypothalamic BOLD response to glucose intake and hypothalamic volume are similar in anorexia nervosa and healthy control subjects

    PubMed Central

    van Opstal, Anna M.; Westerink, Anna M.; Teeuwisse, Wouter M.; van der Geest, Mirjam A. M.; van Furth, Eric F.; van der Grond, Jeroen

    2015-01-01

    Background: Inconsistent findings about the neurobiology of Anorexia Nervosa (AN) hinder the development of effective treatments for this severe mental disorder. Therefore, the need arises for elucidation of neurobiological factors involved in the pathophysiology of AN. The hypothalamus plays a key role in the neurobiological processes that govern food intake and energy homeostasis, processes that are disturbed in anorexia nervosa (AN). The present study will assess the hypothalamic response to energy intake and the hypothalamic structure in patients with AN and healthy controls. Methods: Ten women aged 18–30 years diagnosed with AN and 11 healthy, lean (BMI < 23 kg/m2) women in the same age range were recruited. We used functional magnetic resonance imaging (MRI) to determine function of the hypothalamus in response to glucose. Structural MRI was used to determine differences in hypothalamic volume and local gray matter volume using manual segmentation and voxel-based morphometry. Results: No differences were found in hypothalamic volume and neuronal activity in response to a glucose load between the patients and controls. Whole brain structural analysis showed a significant decrease in gray matter volume in the cingulate cortex in the AN patients, bilaterally. Conclusions: We argue that in spite of various known changes in the hypothalamus the direct hypothalamic response to glucose intake is similar in AN patients and healthy controls. PMID:25999808

  6. Automated real-time behavioral and physiological data acquisition and display integrated with stimulus presentation for FMRI.

    PubMed

    Voyvodic, James T; Glover, Gary H; Greve, Douglas; Gadde, Syam

    2011-01-01

    Functional magnetic resonance imaging (fMRI) is based on correlating blood oxygen-level dependent (BOLD) signal fluctuations in the brain with other time-varying signals. Although the most common reference for correlation is the timing of a behavioral task performed during the scan, many other behavioral and physiological variables can also influence fMRI signals. Variations in cardiac and respiratory functions in particular are known to contribute significant BOLD signal fluctuations. Variables such as skin conduction, eye movements, and other measures that may be relevant to task performance can also be correlated with BOLD signals and can therefore be used in image analysis to differentiate multiple components in complex brain activity signals. Combining real-time recording and data management of multiple behavioral and physiological signals in a way that can be routinely used with any task stimulus paradigm is a non-trivial software design problem. Here we discuss software methods that allow users control of paradigm-specific audio-visual or other task stimuli combined with automated simultaneous recording of multi-channel behavioral and physiological response variables, all synchronized with sub-millisecond temporal accuracy. We also discuss the implementation and importance of real-time display feedback to ensure data quality of all recorded variables. Finally, we discuss standards and formats for storage of temporal covariate data and its integration into fMRI image analysis. These neuroinformatics methods have been adopted for behavioral task control at all sites in the Functional Biomedical Informatics Research Network (FBIRN) multi-center fMRI study. PMID:22232596

  7. Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women.

    PubMed

    Borg, Charmaine; de Jong, Peter J; Georgiadis, Janniko R

    2014-02-01

    Lifetime experiences shape people's attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile-vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-'hot' vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-'hot') associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli. PMID:23051899

  8. Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women

    PubMed Central

    de Jong, Peter J.; Georgiadis, Janniko R.

    2014-01-01

    Lifetime experiences shape people’s attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile–vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-‘hot’ vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-‘hot’) associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli. PMID:23051899

  9. fMRI activation patterns in an analytic reasoning task: consistency with EEG source localization

    NASA Astrophysics Data System (ADS)

    Li, Bian; Vasanta, Kalyana C.; O'Boyle, Michael; Baker, Mary C.; Nutter, Brian; Mitra, Sunanda

    2010-03-01

    Functional magnetic resonance imaging (fMRI) is used to model brain activation patterns associated with various perceptual and cognitive processes as reflected by the hemodynamic (BOLD) response. While many sensory and motor tasks are associated with relatively simple activation patterns in localized regions, higher-order cognitive tasks may produce activity in many different brain areas involving complex neural circuitry. We applied a recently proposed probabilistic independent component analysis technique (PICA) to determine the true dimensionality of the fMRI data and used EEG localization to identify the common activated patterns (mapped as Brodmann areas) associated with a complex cognitive task like analytic reasoning. Our preliminary study suggests that a hybrid GLM/PICA analysis may reveal additional regions of activation (beyond simple GLM) that are consistent with electroencephalography (EEG) source localization patterns.

  10. Eye dominance predicts fMRI signals in human retinotopic cortex.

    PubMed

    Mendola, Janine D; Conner, Ian P

    2007-02-27

    There have been many attempts to define eye dominance in normal subjects, but limited consensus exists, and relevant physiological data is scarce. In this study, we consider two different behavioral methods for assignment of eye dominance, and how well they predict fMRI signals evoked by monocular stimulation. Sighting eye dominance was assessed with two standard tests, the Porta Test, and a 'hole in hand' variation of the Miles Test. Acuity dominance was tested with a standard eye chart and with a computerized test of grating acuity. We found limited agreement between the sighting and acuity methods for assigning dominance in our individual subjects. We then compared the fMRI response generated by dominant eye stimulation to that generated by non-dominant eye, according to both methods, in 7 normal subjects. The stimulus consisted of a high contrast hemifield stimulus alternating with no stimulus in a blocked paradigm. In separate scans, we used standard techniques to label the borders of visual areas V1, V2, V3, VP, V4v, V3A, and MT. These regions of interest (ROIs) were used to analyze each visual area separately. We found that percent change in fMRI BOLD signal was stronger for the dominant eye as defined by the acuity method, and this effect was significant for areas located in the ventral occipital territory (V1v, V2v, VP, V4v). In contrast, assigning dominance based on sighting produced no significant interocular BOLD differences. We conclude that interocular BOLD differences in normal subjects exist, and may be predicted by acuity measures. PMID:17194544