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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. Subject specific BOLD fMRI respiratory and cardiac response functions obtained from global signal.

    PubMed

    Falahpour, Maryam; Refai, Hazem; Bodurka, Jerzy

    2013-05-15

    Subtle changes in either breathing pattern or cardiac pulse rate alter blood oxygen level dependent functional magnetic resonance imaging signal (BOLD fMRI). This is problematic because such fluctuations could possibly not be related to underlying neuronal activations of interest but instead the source of physiological noise. Several methods have been proposed to eliminate physiological noise in BOLD fMRI data. One such method is to derive a template based on average multi-subject data for respiratory response function (RRF) and cardiac response function (CRF) by simultaneously utilizing an external recording of cardiac and respiratory waveforms with the fMRI. Standard templates can then be used to model, map, and remove respiration and cardiac fluctuations from fMRI data. Utilizing these does not, however, account for intra-subject variations in physiological response. Thus, performing a more individualized approach for single subject physiological noise correction becomes more desirable, especially for clinical purposes. Here we propose a novel approach that employs subject-specific RRF and CRF response functions obtained from the whole brain or brain tissue-specific global signals (GS). Averaging multiple voxels in global signal computation ensures physiological noise dominance over thermal and system noise in even high-spatial-resolution fMRI data, making the GS suitable for deriving robust estimations of both RRF and CRF for individual subjects. Using these individualized response functions instead of standard templates based on multi-subject averages judiciously removes physiological noise from the data, assuming that there is minimal neuronal contribution in the derived individualized filters. Subject-specific physiological response functions obtained from the GS better maps individuals' physiological characteristics.

  3. 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

  4. A critical role for purinergic signalling in the mechanisms underlying generation of BOLD fMRI responses.

    PubMed

    Wells, Jack A; Christie, Isabel N; Hosford, Patrick S; Huckstepp, Robert T R; Angelova, Plamena R; Vihko, Pirkko; Cork, Simon C; Abramov, Andrey Y; Teschemacher, Anja G; Kasparov, Sergey; Lythgoe, Mark F; Gourine, Alexander V

    2015-04-01

    The mechanisms of neurovascular coupling underlying generation of BOLD fMRI signals remain incompletely understood. It has been proposed that release of vasoactive substances by astrocytes couples neuronal activity to changes in cerebrovascular blood flow. However, the role of astrocytes in fMRI responses remains controversial. Astrocytes communicate via release of ATP, and here we tested the hypothesis that purinergic signaling plays a role in the mechanisms underlying fMRI. An established fMRI paradigm was used to trigger BOLD responses in the forepaw region of the somatosensory cortex (SSFP) of an anesthetized rat. Forepaw stimulation induced release of ATP in the SSFP region. To interfere with purinergic signaling by promoting rapid breakdown of the vesicular and/or released ATP, a lentiviral vector was used to express a potent ectonucleotidase, transmembrane prostatic acid phosphatase (TMPAP), in the SSFP region. TMPAP expression had no effect on resting cerebral blood flow, cerebrovascular reactivity, and neuronal responses to sensory stimulation. However, TMPAP catalytic activity markedly reduced the magnitude of BOLD fMRI responses triggered in the SSFP region by forepaw stimulation. Facilitated ATP breakdown could result in accumulation of adenosine. However, blockade of A1 receptors had no effect on BOLD responses and did not reverse the effect of TMPAP. These results suggest that purinergic signaling plays a significant role in generation of BOLD fMRI signals. We hypothesize that astrocytes activated during periods of enhanced neuronal activity release ATP, which propagates astrocytic activation, stimulates release of vasoactive substances and dilation of cerebral vasculature.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

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

    PubMed

    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.

  12. Prestimulus EEG Alpha Oscillations Modulate Task-Related fMRI BOLD Responses to Auditory Stimuli

    PubMed Central

    Walz, Jennifer M.; Goldman, Robin I.; Carapezza, Michael; Muraskin, Jordan; Brown, Truman R.; Sajda, Paul

    2015-01-01

    EEG alpha-band activity is generally thought to represent an inhibitory state related to decreased attention and play a role in suppression of task-irrelevant stimulus processing, but a competing hypothesis suggests an active role in processing task-relevant information – one in which phase dynamics are involved. Here we used simultaneous EEG-fMRI and a whole-brain analysis to investigate the effects of prestimulus alpha activity on the event-related BOLD response during an auditory oddball task. We separately investigated the effects of the posterior alpha rhythm’s power and phase on activity related to task-relevant stimulus processing and also investigated higher-level decision-related processing. We found stronger decision-related BOLD activity in areas late in the processing stream when subjects were in the high alpha power state prior to stimulus onset, but did not detect any effect in primary sensory regions. Our phase analysis revealed correlates in bilateral thalamus, providing support for a thalamo-cortical loop in attentional modulations and suggesting that the cortical alpha rhythm acts as a cyclic modulator of task-related responses very early in the processing stream. Our results help to reconcile the competing inhibition and active-processing hypotheses for ongoing alpha oscillations and begin to tease apart the distinct roles and mechanisms underlying their power and phase. PMID:25797833

  13. 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

  14. 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.

  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. Ghrelin Modulates the fMRI BOLD Response of Homeostatic and Hedonic Brain Centers Regulating Energy Balance in the Rat

    PubMed Central

    Deli, Levente; Gajári, Dávid; Dávid, Szabolcs; Pozsgay, Zsófia; Hegedűs, Nikolett; Tihanyi, Károly; Liposits, Zsolt

    2014-01-01

    The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the estradiol milieu does

  17. 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

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

    PubMed

    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.

  19. 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

  20. Separating slow BOLD from non-BOLD baseline drifts using multi-echo fMRI.

    PubMed

    Evans, Jennifer W; Kundu, Prantik; Horovitz, Silvina G; Bandettini, Peter A

    2015-01-15

    The functional magnetic resonance (fMRI) baseline is known to drift over the course of an experiment and is often attributed to hardware instability. These ultraslow fMRI fluctuations are inseparable from blood oxygenation level dependent (BOLD) changes in standard single echo fMRI and they are therefore typically removed before further analysis in both resting-state and task paradigms. However, some part of these fluctuations may be of neuronal origin, as neural activity can indeed fluctuate at the scale of several minutes or even longer, such as after the administration of drugs or during the ultradian rhythms. Here, we show that it is possible to separate the slow BOLD and non-BOLD drifts automatically using multi-echo fMRI and multi-echo independent components analysis (ME-ICA) denoising by demonstrating the detection of a visual signal evoked from a flickering checkerboard with slowly changing contrast.

  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.

  2. 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

  3. 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

  4. 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

  5. Perforant pathway stimulation as a conditioned stimulus for active avoidance learning triggers BOLD responses in various target regions of the hippocampus: a combined fMRI and electrophysiological study.

    PubMed

    Angenstein, Frank; Krautwald, Karla; Wetzel, Wolfram; Scheich, Henning

    2013-07-15

    Functional magnetic resonance imaging and electrophysiology were combined to monitor blood oxygen level dependent (BOLD) signals in the entire rat brain and neuronal activities in the dentate gyrus during electrical stimulation of the right perforant pathway. In naïve, medetomidine sedated animals, stimulation of the fiber bundle with 15 trains (i.e. 8 bursts of 20 pulses given with 10 ms intervals, one burst per second, pulse width 0.2 ms) generated significant BOLD responses in the right hippocampal formation and the left entorhinal cortex. The stimulation condition also caused changes in the synaptic efficacy of perforant pathway granular cell synapses that lasted for at least one day. Rerun of the same experiment one day later resulted in a significantly increased electrophysiological response in the dentate gyrus and an increase of the BOLD response in the entire hippocampal formation. Consequently, long-lasting changes in synaptic efficacy go along with changes in the generated BOLD response. Additional electrical stimulations of the perforant pathway in the awake animal between the two fMRI experiments caused in the second fMRI measurement an increased BOLD response in the hippocampal formation and an appearance of significant BOLD responses in target regions of the hippocampus, such as the septum, nucleus accumbens (NAcc), and anterior cingulate cortex/medial prefrontal cortex/motor cortex (ACC/mPFC/MC) regions. Consequently, the efficacy of signal processing in and propagation through the hippocampus can be monitored by variations of the BOLD response in target regions of the hippocampus. Using the electrical perforant pathway stimulations as conditioned stimulus for an active avoidance task (shuttle box) caused a further spreading of the BOLD response in the hippocampus formation, septum and ACC/mPFC/MC but not in the NAcc. In addition, the magnitude of the BOLD response in the trained animals was further increased in the right and left hippocampus and

  6. Functional MRI during Hyperbaric Oxygen: Effects of Oxygen on Neurovascular Coupling and BOLD fMRI signals

    PubMed Central

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

    2015-01-01

    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) was 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. 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.

  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. 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

  10. Age-related differences in cerebral blood flow underlie the BOLD fMRI signal in childhood

    PubMed Central

    Moses, Pamela; Hernandez, Leanna M.; Orient, Elizabeth

    2014-01-01

    Functional magnetic resonance imaging (fMRI) has become a premiere technique for studying the development and neural mediation of a wide range of typical and atypical behaviors in children. While the mechanism of the blood oxygen level-dependent (BOLD) fMRI signal has been a focus of investigation in the mature brain, it has been largely unexamined in the developing brain. One critical component of the BOLD signal that has been noted to change with age is cerebral blood flow (CBF). Reports of CBF in children based on clinical radioactive tracing methods have found elevated CBF in childhood relative to adulthood, which could affect the BOLD response. This study used non-invasive arterial spin labeling magnetic resonance imaging to study resting state and activity-driven CBF in conjunction with the functional BOLD response in healthy children 8 and 12 years of age and in adults. Participants performed a finger-tapping task to generate robust activation measured in the motor cortex. Quantification of resting state CBF demonstrated higher CBF in 8 year olds and in 12 year olds relative to adults. The absolute increase in CBF between baseline rest and peak response during the motor task was also higher in both child groups compared to adults. In contrast, the relative increase of CBF above baseline, expressed as percent of CBF change, was comparable across groups. The percent of BOLD signal change was also stable across age groups. This set of findings suggests that along with elevated CBF in childhood, other component processes of the BOLD response are also in an elevated state such that together they yield a net BOLD effect that resembles adults. These findings coincide with our previous examination of hemodynamics in primary sensory cortex. Although the magnitude of the BOLD response appears consistent between childhood and adulthood, the underlying physiology and cerebrovascular dynamics that give rise to the BOLD effect differ between immature and mature neural

  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.

  13. 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

  14. 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

  15. BOLD fMRI of visual and somatosensory-motor stimulations in baboons.

    PubMed

    Wey, Hsiao-Ying; Li, Jinqi; Szabó, C Akos; Fox, Peter T; Leland, M Michelle; Jones, Lisa; Duong, Timothy Q

    2010-10-01

    Baboon, with its large brain size and extensive cortical folding compared to other non-human primates, serves as a good model for neuroscience research. This study reports the implementation of a baboon model for blood oxygenation level-dependent (BOLD) fMRI studies (1.5 x 1.5 x 4 mm resolution) on a clinical 3T-MRI scanner. BOLD fMRI responses to hypercapnic (5% CO(2)) challenge, 10 Hz flicker visual, and vibrotactile somatosensory-motor stimulations were investigated in baboons anesthetized sequentially with isoflurane and ketamine. Hypercapnia evoked robust BOLD increases. Paralysis was determined to be necessary to achieve reproducible functional activations within and between subjects under our experimental conditions. With optimized anesthetic doses (0.8-1.0% isoflurane or 6-8 mg/kg/h ketamine) and adequate paralysis (vecuronium, 0.2 mg/kg), robust activations were detected in the visual (V), primary (S1) and secondary (S2) somatosensory, primary motor (M cortices), supplementary motor area (SMA), lateral geniculate nucleus (LGN) and thalamus (Th). Data were tabulated for 11 trials under isoflurane and 10 trials under ketamine on 5 baboons. S1, S2, M, and V activations were detected in essentially all trials (90-100% of the time, except 82% for S2 under isoflurane and 70% for M under ketamine). LGN activations were detected 64-70% of the time under both anesthetics. SMA and Th activations were detected 36-45% of the time under isoflurane and 60% of the time under ketamine. BOLD percent changes among different structures were slightly higher under ketamine than isoflurane (0.75% versus 0.58% averaging all structures), but none was statistically different (P>0.05). This baboon model offers an opportunity to non-invasively image brain functions and dysfunctions in large non-human primates.

  16. 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.

  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. Volumetric BOLD fMRI simulation: from neurovascular coupling to multivoxel imaging

    PubMed Central

    2012-01-01

    Background The blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) modality has been numerically simulated by calculating single voxel signals. However, the observation on single voxel signals cannot provide information regarding the spatial distribution of the signals. Specifically, a single BOLD voxel signal simulation cannot answer the fundamental question: is the magnetic resonance (MR) image a replica of its underling magnetic susceptibility source? In this paper, we address this problem by proposing a multivoxel volumetric BOLD fMRI simulation model and a susceptibility expression formula for linear neurovascular coupling process, that allow us to examine the BOLD fMRI procedure from neurovascular coupling to MR image formation. Methods Since MRI technology only senses the magnetism property, we represent a linear neurovascular-coupled BOLD state by a magnetic susceptibility expression formula, which accounts for the parameters of cortical vasculature, intravascular blood oxygenation level, and local neuroactivity. Upon the susceptibility expression of a BOLD state, we carry out volumetric BOLD fMRI simulation by calculating the fieldmap (established by susceptibility magnetization) and the complex multivoxel MR image (by intravoxel dephasing). Given the predefined susceptibility source and the calculated complex MR image, we compare the MR magnitude (phase, respectively) image with the predefined susceptibility source (the calculated fieldmap) by spatial correlation. Results The spatial correlation between the MR magnitude image and the magnetic susceptibility source is about 0.90 for the settings of TE = 30 ms, B0 = 3 T, voxel size = 100 micron, vessel radius = 3 micron, and blood volume fraction = 2%. Using these parameters value, the spatial correlation between the MR phase image and the susceptibility-induced fieldmap is close to 1.00. Conclusion Our simulation results show that the MR magnitude image is not an exact

  20. 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

  1. fMRI BOLD Response in High-risk College Students (Part 1): During Exposure to Alcohol, Marijuana, Polydrug and Emotional Picture Cues†

    PubMed Central

    Ray, Suchismita; Hanson, Catherine; Hanson, Stephen J.; Bates, Marsha E.

    2010-01-01

    Aim: This functional magnetic resonance imaging (fMRI) study examined reactivity to alcohol, polydrug, marijuana and emotional picture cues in students who were referred to a college alcohol and drug assistance program. Methods: The fMRI data of 10 participants (5 females; 5 males) were collected while they viewed standardized emotional and appetitive cues. Results: Positive and negative emotional cues produced greater activity than neutral cues in the expected brain areas. Compared with neutral cues, alcohol cues produced greater brain activation in the right insula, left anterior cingulate, left caudate and left prefrontal cortex (Z = 2.01, 1.86, 1.82, 1.81, respectively; P < 0.05). Drug cues produced significantly greater left prefrontal activity compared with neutral cues, with polydrug cues activating the right insula and marijuana cues activating left anterior cingulate. Conclusions: Students at-risk for alcohol abuse showed neural reactivity to alcohol cues in four brain regions, which is consistent with their greater use of alcohol. Insula activation to appetitive cues may be an early marker of risk for progression to alcohol/drug abuse. PMID:20729530

  2. BMI not WHR modulates BOLD fMRI responses in a sub-cortical reward network when participants judge the attractiveness of human female bodies.

    PubMed

    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

  3. 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

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

    PubMed

    Bush, Keith; Cisler, Josh

    2013-07-01

    Neuroimaging methodology predominantly relies on the blood oxygenation level dependent (BOLD) signal. While the BOLD signal is a valid measure of neuronal activity, variances 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 semiblind (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. 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.

  5. Differentiating BOLD and non-BOLD signals in fMRI time series from anesthetized rats using multi-echo EPI at 11.7 T.

    PubMed

    Kundu, Prantik; Santin, Mathieu D; Bandettini, Peter A; Bullmore, Edward T; Petiet, Alexandra

    2014-11-15

    The study of spontaneous brain activity using fMRI is central to mapping brain networks. However, current fMRI methodology has limitations in the study of small animal brain organization using ultra-high field fMRI experiments, as imaging artifacts are difficult to control and the relationship between classical neuroanatomy and spontaneous functional BOLD activity is not fully established. Challenges are especially prevalent during the fMRI study of individual rodent brains, which could be instrumental to studies of disease progression and pharmacology. A recent advance in fMRI methodology enables unbiased, accurate, and comprehensive identification of functional BOLD signals by interfacing multi-echo (ME) fMRI acquisition, NMR signal decay analysis, and independent components analysis (ICA), in a procedure called ME-ICA. Here we present a pilot study on the suitability of ME-ICA for ultra high field animal fMRI studies of spontaneous brain activity under anesthesia. ME-ICA applied to 11.7 T fMRI data of rats first showed robust performance in automatic high dimensionality estimation and ICA decomposition, similar to that previously reported for 3.0 T human data. ME sequence optimization for 11.7 T indicated that 3 echoes, 0.5mm isotropic voxel size and TR=3s was adequate for sensitive and specific BOLD signal acquisition. Next, in seeking optimal inhaled isoflurane anesthesia dosage, we report that progressive increase in anesthesia goes with concomitant decrease in statistical complexity of "global" functional activity, as measured by the number of BOLD components, or degrees of freedom (DOF). Finally, BOLD functional connectivity maps for individual rodents at the component level show that spontaneous BOLD activity follows classical neuroanatomy, and seed-based analysis shows plausible cortical-cortical and cortical-subcortical functional interactions.

  6. 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.

  7. 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

  8. Studying the Spatial Distribution of Physiological Effects on BOLD Signals Using Ultrafast fMRI

    PubMed Central

    Tong, Yunjie; Frederick, Blaise deB.

    2014-01-01

    The blood-oxygen-level dependent (BOLD) signal in functional MRI (fMRI) reflects both neuronal activations and global physiological fluctuations. These physiological fluctuations can be attributed to physiological low frequency oscillations (pLFOs), respiration, and cardiac pulsation. With typical TR values, i.e., 2 s or longer, the high frequency physiological signals (i.e., from respiration and cardiac pulsation) are aliased into the low frequency band, making it hard to study the individual effect of these physiological processes on BOLD. Recently developed multiband EPI sequences, which offer full brain coverage with extremely short TR values (400 ms or less) allow these physiological signals to be spectrally separated. In this study, we applied multiband resting state scans on nine healthy participants with TR = 0.4 s. The spatial distribution of each physiological process on BOLD fMRI was explored using their spectral features and independent component analysis (ICA). We found that the spatial distributions of different physiological processes are distinct. First, cardiac pulsation affects mostly the base of the brain, where high density of arteries exists. Second, respiration affects prefrontal and occipital areas, suggesting the motion associated with breathing might contribute to the noise. Finally, and most importantly, we found that the effects of pLFOs dominated many prominent ICA components, which suggests that, contrary to the popular belief that aliased cardiac and respiration signals are the main physiological noise source in BOLD fMRI, pLFOs may be the most influential physiological signals. Understanding and measuring these pLFOs are important for denoising and accurately modeling BOLD signals. PMID:24744722

  9. 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.

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

    PubMed

    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

  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. Refinement of Optical Imaging Spectroscopy Algorithms using concurrent BOLD and CBV fMRI

    PubMed Central

    Kennerley, Aneurin J; Berwick, Jason; Martindale, John; Johnston, David; Zheng, Ying; Mayhew, John E

    2009-01-01

    We describe the use of the three dimensional characteristics of the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) MRI signal changes to refine a two dimensional optical imaging spectroscopy (OIS) algorithm. The cortical depth profiles of the BOLD and CBV changes following neural activation were used to parameterise a 5-layer heterogeneous tissue model used in the Monte Carlo simulations (MCS) of light transport through tissue in the OIS analysis algorithm. To transform the fMRI BOLD and CBV measurements into deoxy-haemoglobin (Hbr) profiles we inverted an MCS of extravascular MR signal attenuation under the assumption that the extra-/intravascular ratio is 2:1 at a magnetic field strength of 3T. The significant improvement in the quantitative accuracy of haemodynamic measurements using the new heterogeneous tissue model over the original homogeneous tissue model OIS algorithm was demonstrated on new concurrent OIS and fMRI data covering a range of stimulus durations. PMID:19505581

  13. BOLD responses reflecting dopaminergic signals in the human ventral tegmental area.

    PubMed

    D'Ardenne, Kimberlee; McClure, Samuel M; Nystrom, Leigh E; Cohen, Jonathan D

    2008-02-29

    Current theories hypothesize that dopamine neuronal firing encodes reward prediction errors. Although studies in nonhuman species provide direct support for this theory, functional magnetic resonance imaging (fMRI) studies in humans have focused on brain areas targeted by dopamine neurons [ventral striatum (VStr)] rather than on brainstem dopaminergic nuclei [ventral tegmental area (VTA) and substantia nigra]. We used fMRI tailored to directly image the brainstem. When primary rewards were used in an experiment, the VTA blood oxygen level-dependent (BOLD) response reflected a positive reward prediction error, whereas the VStr encoded positive and negative reward prediction errors. When monetary gains and losses were used, VTA BOLD responses reflected positive reward prediction errors modulated by the probability of winning. We detected no significant VTA BOLD response to nonrewarding events.

  14. Investigation of negative BOLD responses in human brain through NIRS technique. A visual stimulation study.

    PubMed

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

    2015-03-01

    Despite negative blood oxygenation level dependent (BOLD) responses to visual stimuli have recently gained considerable interest, the explanation for their underlying neuronal and vascular mechanisms is still controversial. In the present study, a multimodal experimental approach is presented to shed light on the negative BOLD phenomenon in the human brain. In particular, information from functional magnetic resonance imaging (fMRI) and near infrared spectroscopy (NIRS) was integrated to confirm and gain insight into the phenomenon of negative BOLD responses (NBRs) to unpatterned intermittent photic stimulation (IPS) in healthy subjects. Eight healthy subjects participated in the study. Consistent findings emerged from the activation analysis of fMRI and NIRS data and the comparison of BOLD and hemoglobin responses at the single channel level showed that NBRs are related to a decrease in oxyhemoglobin (HbO) combined with a lower increase in deoxyhemoglobin (HHb), corresponding to a decrease in total hemoglobin (THb) and estimated cerebral blood volume (CBV). The HbO and HHb variations were significant in at least one channel in six subjects out of eight (p<0.05). The NIRS technique allowed obtaining valuable information on the vascular determinants of the NBRs, since the discrimination between HbO, HHb and THb information provided a more comprehensive view of the negative BOLD phenomenon. The within and between subject heterogeneous BOLD-Hb temporal relations pave the way to further investigations into the neurovascular properties of NBRs.

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

    PubMed

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

    2013-03-01

    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.

  16. 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

  17. Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7 T.

    PubMed

    Huber, Laurentius; Goense, Jozien; Kennerley, Aneurin J; Ivanov, Dimo; Krieger, Steffen N; Lepsien, Jöran; Trampel, Robert; Turner, Robert; Möller, Harald E

    2014-08-15

    Decreases in stimulus-dependent blood oxygenation level dependent (BOLD) signal and their underlying neurovascular origins have recently gained considerable interest. In this study a multi-echo, BOLD-corrected vascular space occupancy (VASO) functional magnetic resonance imaging (fMRI) technique was used to investigate neurovascular responses during stimuli that elicit positive and negative BOLD responses in human brain at 7 T. Stimulus-induced BOLD, cerebral blood volume (CBV), and cerebral blood flow (CBF) changes were measured and analyzed in 'arterial' and 'venous' blood compartments in macro- and microvasculature. We found that the overall interplay of mean CBV, CBF and BOLD responses is similar for tasks inducing positive and negative BOLD responses. Some aspects of the neurovascular coupling however, such as the temporal response, cortical depth dependence, and the weighting between 'arterial' and 'venous' contributions, are significantly different for the different task conditions. Namely, while for excitatory tasks the BOLD response peaks at the cortical surface, and the CBV change is similar in cortex and pial vasculature, inhibitory tasks are associated with a maximum negative BOLD response in deeper layers, with CBV showing strong constriction of surface arteries and a faster return to baseline. The different interplays of CBV, CBF and BOLD during excitatory and inhibitory responses suggests different underlying hemodynamic mechanisms.

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

    PubMed

    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

  19. 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

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

    PubMed

    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.

  1. 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

  2. Diffusion modulation of the fMRI signal: early investigations on the origin of the BOLD signal.

    PubMed

    Song, Allen W

    2012-08-15

    The early 1990s was a very special period for functional MRI (fMRI). Many original concepts were formed during that period which helped set up the foundations for modern neuroimaging development. I was fortunate to be in graduate school at the time. I was even more fortunate to be enrolled in one of the pioneer groups in fMRI at the Medical College of Wisconsin, and witnessed some of the early fMRI experiments taking place in the lab. Under the daily influence and steady guidance by the extraordinarily talented researchers there, I also began my own work on the contrast mechanisms of fMRI. In particular, I was developing diffusion weighted strategies to investigate the origin of the functional signal using blood oxygenation level dependent (BOLD) contrast. Our results, that there was significant BOLD signal in large veins and their vicinities at low field strengths (e.g. 1.5T), played an immediate role in moving fMRI applications to higher fields (3T and above) where small vessels (e.g. capillaries) contribute more significantly to improve the neuronal specificity of the BOLD signal. This manuscript gathers some of my own recollections concerning this particular development.

  3. Rhythmic 3–4 Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures

    PubMed Central

    Youngblood, Mark W.; Chen, William C.; Mishra, Asht M.; Enamandram, Sheila; Sanganahalli, Basavaraju G.; Motelow, Joshua E.; Bai, Harrison X.; Frohlich, Flavio; Gribizis, Alexandra; Lighten, Alexis; Hyder, Fahmeed; Blumenfeld, Hal

    2015-01-01

    Absence seizures are transient episodes of impaired consciousness accompanied by 3–4 Hz spike-wave discharge on electroencephalography (EEG). Human functional magnetic resonance imaging (fMRI) studies have demonstrated widespread cortical decreases in the blood oxygen-level dependent (BOLD) signal that may play an important role in the pathophysiology of these seizures. Animal models could provide an opportunity to investigate the fundamental mechanisms of these changes, however they have so far failed to consistently replicate the cortical fMRI decreases observed in human patients. This may be due to important differences between human seizures and animal models, including a lack of cortical development in rodents or differences in the frequency of rodent (7–8 Hz) and human (3–4 Hz) spike-wave discharge. To examine the possible contributions of these differences, we developed a ferret model that exhibits 3–4 Hz spike-wave seizures in the presence of a sulcated cortex. Measurements of BOLD fMRI and simultaneous EEG demonstrated cortical fMRI increases during and following spike-wave seizures in ferrets. However unlike human patients, significant fMRI decreases were not observed. The lack of fMRI decreases was consistent across seizures of different durations, discharge frequencies, and anesthetic regimes, and using fMRI analysis models similar to human patients. In contrast, generalized tonic-clonic seizures under the same conditions elicited sustained postictal fMRI decreases, verifying that the lack of fMRI decreases with spike-wave was not due to technical factors. These findings demonstrate that 3–4 Hz spike-wave discharge in a sulcated animal model does not necessarily produce fMRI decreases, leaving the mechanism for this phenomenon open for further investigation. PMID:25562830

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. The current functional state of local neuronal circuits controls the magnitude of a BOLD response to incoming stimuli.

    PubMed

    Angenstein, Frank; Krautwald, Karla; Scheich, Henning

    2010-05-01

    The purpose of this study was to determine how the history-dependent activation state of neuronal networks controls fMRI signals to incoming stimuli. Simultaneous electrophysiological and blood oxygen level-dependent (BOLD) responses were monitored during stimulation of the perforant pathway with low, high, and again low intensity but, otherwise identical pulse trains. Under three different anesthetics (alpha-chloralose, medetomidine, isoflurane) consecutive low intensity stimulation trains, set just below the threshold for population spike generation to single pulses, yielded a stable BOLD response, although at different magnitudes. The first high intensity train increased the BOLD response under all anesthetics and generated population spikes, with varying amplitudes and latencies (alpha-chloralose, metedomidine) or in a regular pattern (isoflurane). Concurrent to the second high intensity train, the BOLD response became minimal, then slowly increasing with subsequent trains (alpha-chloralose, metedomidine), or immediately rising to a stable level (isoflurane). Second train population spikes became regularized, but at low amplitudes and long latencies that were slowly reversed across trains (alpha-chloralose, medetomidine); while under isoflurane, amplitude and latencies became stabilized with the second train. In comparison to initial stimulation, the final low intensity stimulation trains failed to produce BOLD responses (alpha-chloralose, medetomidine), or left the response unchanged (isoflurane), only reaching stable potentiation of population spikes when under isoflurane. Therefore, the fate of BOLD responses depends on whether a new stable functional state of the intrinsic network can be reached after high intensity stimulation. PMID:20114080

  12. 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

  13. Opposing BOLD responses to reciprocated and unreciprocated altruism in putative reward pathways.

    PubMed

    Rilling, James K; Sanfey, Alan G; Aronson, Jessica A; Nystrom, Leigh E; Cohen, Jonathan D

    2004-11-15

    Mesencephalic dopamine neurons are believed to facilitate reward-dependent learning by computing errors in reward predictions. We used fMRI to test whether this system was activated as expected in response to errors in predictions about whether a social partner would reciprocate an act of altruism. Nineteen subjects received fMRI scans as they played a series of single-shot Prisoner's Dilemma games with partners who were outside the scanner. In both ventromedial prefrontal cortex and ventral striatum, reciprocated and unreciprocated cooperation were associated with positive and negative BOLD responses, respectively. Our results are consistent with the hypothesis that mesencephalic dopamine projection sites carry information about errors in reward prediction that allow us to learn who can and cannot be trusted to reciprocate favors.

  14. PHYCAA+: an optimized, adaptive procedure for measuring and controlling physiological noise in BOLD fMRI.

    PubMed

    Churchill, Nathan W; Strother, Stephen C

    2013-11-15

    The presence of physiological noise in functional MRI can greatly limit the sensitivity and accuracy of BOLD signal measurements, and produce significant false positives. There are two main types of physiological confounds: (1) high-variance signal in non-neuronal tissues of the brain including vascular tracts, sinuses and ventricles, and (2) physiological noise components which extend into gray matter tissue. These physiological effects may also be partially coupled with stimuli (and thus the BOLD response). To address these issues, we have developed PHYCAA+, a significantly improved version of the PHYCAA algorithm (Churchill et al., 2011) that (1) down-weights the variance of voxels in probable non-neuronal tissue, and (2) identifies the multivariate physiological noise subspace in gray matter that is linked to non-neuronal tissue. This model estimates physiological noise directly from EPI data, without requiring external measures of heartbeat and respiration, or manual selection of physiological components. The PHYCAA+ model significantly improves the prediction accuracy and reproducibility of single-subject analyses, compared to PHYCAA and a number of commonly-used physiological correction algorithms. Individual subject denoising with PHYCAA+ is independently validated by showing that it consistently increased between-subject activation overlap, and minimized false-positive signal in non gray-matter loci. The results are demonstrated for both block and fast single-event task designs, applied to standard univariate and adaptive multivariate analysis models.

  15. 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.

  16. 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.

  17. BOLD matches neuronal activity at the mm scale: a combined 7T fMRI and ECoG study in human sensorimotor cortex.

    PubMed

    Siero, Jeroen C W; Hermes, Dora; Hoogduin, Hans; Luijten, Peter R; Ramsey, Nick F; Petridou, Natalia

    2014-11-01

    High resolution BOLD fMRI has the potential to map activation patterns of small neuronal populations at the scale of cortical columns. However, BOLD fMRI does not measure neuronal activity, but only a correlate thereof, since it measures blood dynamics. To confirm that BOLD activation maps reflect neuronal population activity patterns, a direct comparison with neuro-electrophysiological data from the same cortical patch is necessary. Here, we compare BOLD activation patterns obtained with fMRI at 7 T to electrophysiological patterns obtained with implanted high density electrocorticography (ECoG) grids in the same patch of human sensorimotor cortex, and with similar resolution (1.5mm). We used high spatially sampled high-frequency broadband (HFB) power from ECoG, which reflects local neuronal population activity. The spatial distribution of 7 T BOLD activation matched the spatial distribution of ECoG HFB-power changes in the covered patch of sensorimotor cortex. BOLD fMRI activation foci were located within 1-3mm of the HFB-power ECoG foci. Both methods distinguished individual finger movement activation within a 1cm cortical patch, revealing a topographical medial to lateral layout for the little finger to index to thumb. These findings demonstrate that the BOLD signal at 7 T is strongly correlated with the underlying electrophysiology, and is capable of discriminating patterns of neuronal population activity at a millimeter scale. The results further indicate the utility of 7 T fMRI for investigation of intra-area organization of function and network dynamics.

  18. Caffeine attenuates practice effects in word stem completion as measured by fMRI BOLD signal.

    PubMed

    Bendlin, Barbara B; Trouard, Theodore P; Ryan, Lee

    2007-07-01

    Caffeine ingestion results in increased brain cell metabolism (Nehlig et al. [1992] Brain Res Brain Res Rev 17:139-170) and decreased cerebral blood flow (Field et al. [2003] Radiology 227:129-135; Mulderink et al. [2002] Neuroimage 15:37-44). The current study investigated the effect of caffeine in a word stem completion task using only novel word stems (no repeated stimuli). Resting perfusion was measured with arterial spin labeled perfusion MRI, along with blood oxygenation level-dependent (BOLD) signal before and after ingestion of regular coffee, decaffeinated coffee, and water. Based on previous research (Laurienti et al. [2002] Neuroimage 17:751-757; Mulderink et al. [2002] Neuroimage 15:37-44), we hypothesized that caffeine would result in increased BOLD signal intensity and extent of BOLD activation. As expected, caffeine resulted in a significant decrease in cerebral perfusion. However, both the control and caffeine groups showed an increase in BOLD signal amplitude across two sets of novel word stems. Additionally, the control group showed a 50% reduction in the extent of BOLD activation, while the caffeine group showed no change in activation extent. Neither group showed changes in BOLD baseline signal over time, which had been suggested to mediate caffeine-related BOLD signal changes. The results suggest that caffeine may attenuate general task practice effects that have been described in recent functional MRI studies of word stem completion (Buckner et al. [2000] Brain 123:620-640).

  19. Detecting static and dynamic differences between eyes-closed and eyes-open resting states using ASL and BOLD fMRI.

    PubMed

    Zou, Qihong; Yuan, Bin-Ke; Gu, Hong; Liu, Dongqiang; Wang, Danny J J; Gao, Jia-Hong; Yang, Yihong; Zang, Yu-Feng

    2015-01-01

    Resting-state fMRI studies have increasingly focused on multi-contrast techniques, such as BOLD and ASL imaging. However, these techniques may reveal different aspects of brain activity (e.g., static vs. dynamic), and little is known about the similarity or disparity of these techniques in detecting resting-state brain activity. It is therefore important to assess the static and dynamic characteristics of these fMRI techniques to guide future applications. Here we acquired fMRI data while subjects were in eyes-closed (EC) and eyes-open (EO) states, using both ASL and BOLD techniques, at two research centers (NIDA and HNU). Static brain activity was calculated as voxel-wise mean cerebral blood flow (CBF) using ASL, i.e., CBF-mean, while dynamic activity was measured by the amplitude of low frequency fluctuations (ALFF) of BOLD, i.e., BOLD-ALFF, at both NIDA and HNU, and CBF, i.e., CBF-ALFF, at NIDA. We showed that mean CBF was lower under EC than EO in the primary visual cortex, while BOLD-ALFF was higher under EC in the primary somatosensory cortices extending to the primary auditory cortices and lower in the lateral occipital area. Interestingly, mean CBF and BOLD-ALFF results overlapped at the visual cortex to a very small degree. Importantly, these findings were largely replicated by the HNU dataset. State differences found by CBF-ALFF were located in the primary auditory cortices, which were generally a subset of BOLD-ALFF and showed no spatial overlap with CBF-mean. In conclusion, static brain activity measured by mean CBF and dynamic brain activity measured by BOLD- and CBF-ALFF may reflect different aspects of resting-state brain activity and a combination of ASL and BOLD may provide complementary information on the biophysical and physiological processes of the brain.

  20. 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

  1. Lamina-dependent calibrated BOLD response in human primary motor cortex.

    PubMed

    Guidi, Maria; Huber, Laurentius; Lampe, Leonie; Gauthier, Claudine J; Möller, Harald E

    2016-11-01

    Disentangling neural activity at different cortical depths during a functional task has recently generated growing interest, since this would allow to separate feedforward and feedback activity. The majority of layer-dependent studies have, so far, relied on gradient-recalled echo (GRE) blood-oxygenation-level dependent (BOLD) acquisitions, which are weighted towards the large draining veins at the cortical surface. The current study aims to obtain quantitative brain activity responses in the primary motor cortex on a laminar scale without the contamination due to accompanying secondary vascular effects. Evoked oxidative metabolism was evaluated using the Davis model, to investigate its applicability, advantages, and limits in lamina-dependent fMRI. Average values for the calibration parameter, M, and for changes in the cerebral metabolic rate of oxygen consumption (CMRO2) during a unilateral finger-tapping task were (11±2)% and (30±7)%, respectively, with distinct variation features across the cortical depth. The results presented here showed an uncoupling between BOLD-based functional magnetic resonance imaging (fMRI) and metabolic changes across cortical depth, while the tight coupling between CMRO2 and CBV was conserved across cortical layers. We conclude that the Davis model can help to obtain estimates of lamina-dependent metabolic changes without contamination from large draining veins, with high consistency and reproducibility across participants.

  2. Lamina-dependent calibrated BOLD response in human primary motor cortex.

    PubMed

    Guidi, Maria; Huber, Laurentius; Lampe, Leonie; Gauthier, Claudine J; Möller, Harald E

    2016-11-01

    Disentangling neural activity at different cortical depths during a functional task has recently generated growing interest, since this would allow to separate feedforward and feedback activity. The majority of layer-dependent studies have, so far, relied on gradient-recalled echo (GRE) blood-oxygenation-level dependent (BOLD) acquisitions, which are weighted towards the large draining veins at the cortical surface. The current study aims to obtain quantitative brain activity responses in the primary motor cortex on a laminar scale without the contamination due to accompanying secondary vascular effects. Evoked oxidative metabolism was evaluated using the Davis model, to investigate its applicability, advantages, and limits in lamina-dependent fMRI. Average values for the calibration parameter, M, and for changes in the cerebral metabolic rate of oxygen consumption (CMRO2) during a unilateral finger-tapping task were (11±2)% and (30±7)%, respectively, with distinct variation features across the cortical depth. The results presented here showed an uncoupling between BOLD-based functional magnetic resonance imaging (fMRI) and metabolic changes across cortical depth, while the tight coupling between CMRO2 and CBV was conserved across cortical layers. We conclude that the Davis model can help to obtain estimates of lamina-dependent metabolic changes without contamination from large draining veins, with high consistency and reproducibility across participants. PMID:27364473

  3. Low frequency stimulation of the perforant pathway generates anesthesia-specific variations in neural activity and BOLD responses in the rat dentate gyrus

    PubMed Central

    Krautwald, Karla; Angenstein, Frank

    2012-01-01

    To study how various anesthetics affect the relationship between stimulus frequency and generated functional magnetic resonance imaging (fMRI) signals in the rat dentate gyrus, the perforant pathway was electrically stimulated with repetitive low frequency (i.e., 0.625, 1.25, 2.5, 5, and 10 Hz) stimulation trains under isoflurane/N2O, isoflurane, medetomidine, and α-chloralose. During stimulation, the blood oxygen level-dependent signal intensity (BOLD response) and local field potentials in the dentate gyrus were simultaneously recorded to prove whether the present anesthetic controls the generation of a BOLD response via targeting general hemodynamic parameters, by affecting mechanisms of neurovascular coupling, or by disrupting local signal processing. Using this combined electrophysiological/fMRI approach, we found that the threshold frequency (i.e., the minimal frequency required to trigger significant BOLD responses), the optimal frequency (i.e., the frequency that elicit the strongest BOLD response), and the spatial distribution of generated BOLD responses are specific for each anesthetic used. Concurrent with anesthetic-dependent characteristics of the BOLD response, we found the pattern of stimulus-induced neuronal activity in the dentate gyrus is also specific for each anesthetic. Consequently, the anesthetic-specific influence on local signaling processes is the underlying cause for the observation that an identical stimulus elicits different BOLD responses under various anesthetics. PMID:21863039

  4. Low frequency stimulation of the perforant pathway generates anesthesia-specific variations in neural activity and BOLD responses in the rat dentate gyrus.

    PubMed

    Krautwald, Karla; Angenstein, Frank

    2012-02-01

    To study how various anesthetics affect the relationship between stimulus frequency and generated functional magnetic resonance imaging (fMRI) signals in the rat dentate gyrus, the perforant pathway was electrically stimulated with repetitive low frequency (i.e., 0.625, 1.25, 2.5, 5, and 10 Hz) stimulation trains under isoflurane/N(2)O, isoflurane, medetomidine, and α-chloralose. During stimulation, the blood oxygen level-dependent signal intensity (BOLD response) and local field potentials in the dentate gyrus were simultaneously recorded to prove whether the present anesthetic controls the generation of a BOLD response via targeting general hemodynamic parameters, by affecting mechanisms of neurovascular coupling, or by disrupting local signal processing. Using this combined electrophysiological/fMRI approach, we found that the threshold frequency (i.e., the minimal frequency required to trigger significant BOLD responses), the optimal frequency (i.e., the frequency that elicit the strongest BOLD response), and the spatial distribution of generated BOLD responses are specific for each anesthetic used. Concurrent with anesthetic-dependent characteristics of the BOLD response, we found the pattern of stimulus-induced neuronal activity in the dentate gyrus is also specific for each anesthetic. Consequently, the anesthetic-specific influence on local signaling processes is the underlying cause for the observation that an identical stimulus elicits different BOLD responses under various anesthetics. PMID:21863039

  5. 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

  6. Influence of gradient acoustic noise on fMRI response in the human visual cortex.

    PubMed

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

    2005-08-01

    A paired-stimuli paradigm combined with fMRI was utilized to study the effect of gradient acoustic noise on fMRI response in the human primary visual cortex (V1) in terms of the auditory-visual cross-modal neural interaction. The gradient noise generated during the fMRI acquisition was used as the primary stimulus, and a single flashing light was used as the secondary stimulus. An interstimulus interval (ISI) separated the two. Six tasks were designed with different ISIs ranging from 50 to 700 ms. Both BOLD signal intensity and the number of activated pixels in V1 were analyzed and examined, and they showed a significant reduction when the gradient noise preceded the flashing light by approximately 300 ms. These results indicate that the gradient acoustic noise generated during fMRI acquisitions does interfere with neural behavior and the BOLD signal in the human visual cortex. This interference is modulated by the delay between the gradient noise and visual stimulation, and it can be studied quantitatively when the stimulation paradigm is designed appropriately. This study provides evidence of the auditory-visual interaction during fMRI studies, and the results should have an impact on fMRI applications.

  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. Visual BOLD Response in Late Blind Subjects with Argus II Retinal Prosthesis

    PubMed Central

    Castaldi, E.; Cicchini, G. M.; Cinelli, L.; Rizzo, S.; Morrone, M. C.

    2016-01-01

    Retinal prosthesis technologies require that the visual system downstream of the retinal circuitry be capable of transmitting and elaborating visual signals. We studied the capability of plastic remodeling in late blind subjects implanted with the Argus II Retinal Prosthesis with psychophysics and functional MRI (fMRI). After surgery, six out of seven retinitis pigmentosa (RP) blind subjects were able to detect high-contrast stimuli using the prosthetic implant. However, direction discrimination to contrast modulated stimuli remained at chance level in all of them. No subject showed any improvement of contrast sensitivity in either eye when not using the Argus II. Before the implant, the Blood Oxygenation Level Dependent (BOLD) activity in V1 and the lateral geniculate nucleus (LGN) was very weak or absent. Surprisingly, after prolonged use of Argus II, BOLD responses to visual input were enhanced. This is, to our knowledge, the first study tracking the neural changes of visual areas in patients after retinal implant, revealing a capacity to respond to restored visual input even after years of deprivation. PMID:27780207

  9. 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

  10. Task-related BOLD responses and resting-state functional connectivity during physiological clamping of end-tidal CO(2).

    PubMed

    Madjar, C; Gauthier, C J; Bellec, P; Birn, R M; Brooks, J C W; Hoge, R D

    2012-05-15

    Carbon dioxide (CO(2)), a potent vasodilator, is known to have a significant impact on the blood-oxygen level dependent (BOLD) signal. With the growing interest in studying synchronized BOLD fluctuations during the resting state, the extent to which the apparent synchrony is due to variations in the end-tidal pressure of CO(2) (PETCO(2)) is an important consideration. CO(2)-related fluctuations in BOLD signal may also represent a potential confound when studying task-related responses, especially if breathing depth and rate are affected by the task. While previous studies of the above issues have explored retrospective correction of BOLD fluctuations related to arterial PCO(2), here we demonstrate an alternative approach based on physiological clamping of the arterial CO(2) level to a near-constant value. We present data comparing resting-state functional connectivity within the default-mode-network (DMN), as well as task-related BOLD responses, acquired in two conditions in each subject: 1) while subject's PETCO(2) was allowed to vary spontaneously; and 2) while controlling subject's PETCO(2) within a narrow range. Strong task-related responses and areas of maximal signal correlation in the DMN were not significantly altered by suppressing fluctuations in PETCO(2). Controlling PETCO(2) did, however, improve the performance of retrospective physiological noise correction techniques, allowing detection of additional regions of task-related response and resting-state connectivity in highly vascularized regions such as occipital cortex. While these results serve to further rule out systemic physiological fluctuations as a significant source of apparent resting-state network connectivity, they also demonstrate that fluctuations in arterial CO(2) are one of the factors limiting sensitivity in task-based and resting-state fMRI, particularly in regions of high vascular density. This must be considered when comparing subject groups who might exhibit differences in

  11. Oxygen Level and LFP in Task-Positive and Task-Negative Areas: Bridging BOLD fMRI and Electrophysiology.

    PubMed

    Bentley, William J; Li, Jingfeng M; Snyder, Abraham Z; Raichle, Marcus E; Snyder, Lawrence H

    2016-01-01

    The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these "task-negative" BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process.

  12. BOLD contrast fMRI of whole rodent tumour during air or carbogen breathing using echo-planar imaging at 1.5 T.

    PubMed

    Landuyt, W; Hermans, R; Bosmans, H; Sunaert, S; Béatse, E; Farina, D; Meijerink, M; Zhang, H; Van Den Bogaert, W; Lambin, P; Marchal, G

    2001-01-01

    The aim of this study was to evaluate the feasibility of functional MR imaging (fMRI) at 1.5 T, exploiting blood oxygenation level-dependent (BOLD) contrast, for detecting changes in whole-tumour oxygenation induced by carbogen (5% CO2+95% O2) inhalation of the host. Adult WAG/Rij rats with rhabdomyosarcomas growing subcutaneously in the lower flank were imaged when tumours reached sizes between 1 and 11 cm3 (n=12). Air and carbogen were alternatively supplied at 2 l/min using a snout mask. Imaging was done on a 1.5-T MR scanner using a T2*-weighted gradient-echo, echo-planar imaging (GE-EPI) sequence. Analysis of the whole-tumour EPI images was based on statistical parametric maps. Voxels with and without signal intensity changes (SIC) were recorded. Significance thresholds were set at p<0.05, corrected for multiple comparisons. In continuous air breathing condition, 3 of 12 tumours showed significant negative SIC and 1 tumour had a clear-cut positive SIC. The remaining tumours showed very little or no change. When switching to carbogen breathing, the SIC were significantly positive in 10 of 12 tumours. Negative SIC were present in 4 tumours, of which three were simultaneously characterised by positive SIC. The overall analysis indicated that 6 of the 12 tumours could be considered as strong positive responders to carbogen. Our research demonstrates the applicability of fMRI GE-EPI at 1.5 T to study whole-tumour oxygenation non-invasively. The observed negative SIC during air condition may reflect the presence of transient hypoxia during these measurements. Selection of tumours on the basis of their individual response to carbogen is possible, indicating a role of such non-invasive measurements for using tailor-made treatments. PMID:11702181

  13. 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

  14. Synchronized electrical stimulation of the rat medial forebrain bundle and perforant pathway generates an additive BOLD response in the nucleus accumbens and prefrontal cortex.

    PubMed

    Krautwald, Karla; Min, Hoon-Ki; Lee, Kendall H; Angenstein, Frank

    2013-08-15

    To study how a synchronized activation of two independent pathways affects the fMRI response in a common targeted brain region, blood oxygen dependent (BOLD) signals were measured during electrical stimulation of the right medial forebrain bundle (MFB), the right perforant pathway (PP) and concurrent stimulation of the two fiber systems. Repetitive electrical stimulations of the MFB triggered significant positive BOLD responses in the nucleus accumbens (NAcc), septum, anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), ventral tegmental area/substantia nigra (VTA/SN), right entorhinal cortex (EC) and colliculus superior, which, in general, declined during later stimulation trains. At the same time, negative BOLD responses were observed in the striatum. Thus, the same stimulus caused region-specific hemodynamic responses. An identical electrical stimulation of the PP generated positive BOLD responses in the right dentate gyrus/hippocampus proper/subiculum (DG/HC), the right entorhinal cortex and the left entorhinal cortex, which remained almost stable during consecutive stimulation trains. Co-stimulation of the two fiber systems resulted in an additive activation pattern, i.e., the BOLD responses were stronger during the stimulation of the two pathways than during the stimulation of only one pathway. However, during the simultaneous stimulation of the two pathways, the development of the BOLD responses to consecutive trains changed. The BOLD responses in regions that were predominantly activated by MFB stimulation (i.e., NAcc, septum and ACC/mPFC) did not decline as fast as during pure MFB stimulation, thus an additive BOLD response was only observed during later trains. In contrast, in the brain regions that were predominantly activated by PP stimulation (i.e., right EC, DG/HC), co-stimulation of the MFB only resulted in an additive effect during early trains but not later trains. Consequently, the development of the BOLD responses during consecutive

  15. Measuring vascular reactivity with breath-holds after stroke: a method to aid interpretation of group-level BOLD signal changes in longitudinal fMRI studies.

    PubMed

    Geranmayeh, Fatemeh; Wise, Richard J S; Leech, Robert; Murphy, Kevin

    2015-05-01

    Blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath-hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task-related BOLD signal changes. Three methods of analyzing the breath-hold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue and the peri-infarct tissue, both sub-acutely (∼2 weeks) and chronically (∼4 months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri-infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared with the controls may be confounded by a reduced CVR, longitudinal group-level BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath-hold-based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity.

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

    PubMed

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

    2013-12-30

    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.

  17. 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

  18. 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

  19. 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

  20. BOLD-contrast functional MRI signal changes related to intermittent rhythmic delta activity in EEG during voluntary hyperventilation-simultaneous EEG and fMRI study.

    PubMed

    Mäkiranta, Minna J; Ruohonen, Jyrki; Suominen, Kalervo; Sonkajärvi, Eila; Salomäki, Timo; Kiviniemi, Vesa; Seppänen, Tapio; Alahuhta, Seppo; Jäntti, Ville; Tervonen, Osmo

    2004-05-01

    Differences in the blood oxygen level dependent (BOLD) signal changes were studied during voluntary hyperventilation (HV) between young healthy volunteer groups, (1) with intermittent rhythmic delta activity (IRDA) (N = 4) and (2) controls (N = 4) with only diffuse arrhythmic slowing in EEG (normal response). Subjects hyperventilated (3 min) during an 8-min functional MRI in a 1.5-T scanner, with simultaneous recording of EEG (successful with N = 3 in both groups) and physiological parameters. IRDA power and average BOLD signal intensities (of selected brain regions) were calculated. Hypocapnia showed a tendency to be slightly lighter in the controls than in the IRDA group. IRDA power increased during the last minute of HV and ended 10-15 s after HV. The BOLD signal decreased in white and gray matter after the onset of HV and returned to the baseline within 2 min after HV. The BOLD signal in gray matter decreased approximately 30% more in subjects with IRDA than in controls, during the first 2 min of HV. This difference disappeared (in three subjects out of four) during IRDA in EEG. BOLD signal changes seem to depict changes, which precede IRDA. IRDA due to HV in healthy volunteers represent a model with a clearly defined EEG pattern and an observable BOLD signal change.

  1. Imaging of prolonged BOLD response in the somatosensory cortex of the rat.

    PubMed

    Sonnay, Sarah; Just, Nathalie; Duarte, João M N; Gruetter, Rolf

    2015-03-01

    Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience, although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods, it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long-term modifications induced by these functional challenges. While different types of sustained stimulation paradigm have been explored in human studies, the BOLD response is typically limited to a few minutes in animal models, due to fatigue, anesthesia effects and physiological instability. In the present study, the rat forepaw was electrically stimulated for 2 h, which resulted in a prolonged and localized cortical BOLD response over that period. The stimulation paradigm, including an inter-stimulus interval (ISI) of 10 s, that is 25% of the total time, was applied at constant or variable frequency over 2 h. The steady-state level of the BOLD response was reached after 15-20 min of stimulation and was maintained until the end of the stimulation. On average, no substantial loss in activated volume was observed at the end of the stimulation, but less variability in the fraction of remaining activated volume and higher steady-state BOLD amplitude were observed when stimulation frequency was varied between 2 and 3 Hz every 5 min. We conclude that the combination of ISI and variable stimulus frequency reproducibly results in robust, prolonged and localized BOLD activation.

  2. The relationship between fearfulness, GABA+, and fear-related BOLD responses in the insula.

    PubMed

    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.

  3. 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

  4. 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

  5. Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early and late IC-ERP amplitudes during face recognition.

    PubMed

    Wirsich, Jonathan; Bénar, Christian; Ranjeva, Jean-Philippe; Descoins, Médéric; Soulier, Elisabeth; Le Troter, Arnaud; Confort-Gouny, Sylviane; Liégeois-Chauvel, Catherine; Guye, Maxime

    2014-10-15

    Simultaneous EEG-fMRI has opened up new avenues for improving the spatio-temporal resolution of functional brain studies. However, this method usually suffers from poor EEG quality, especially for evoked potentials (ERPs), due to specific artifacts. As such, the use of EEG-informed fMRI analysis in the context of cognitive studies has particularly focused on optimizing narrow ERP time windows of interest, which ignores the rich diverse temporal information of the EEG signal. Here, we propose to use simultaneous EEG-fMRI to investigate the neural cascade occurring during face recognition in 14 healthy volunteers by using the successive ERP peaks recorded during the cognitive part of this process. N170, N400 and P600 peaks, commonly associated with face recognition, were successfully and reproducibly identified for each trial and each subject by using a group independent component analysis (ICA). For the first time we use this group ICA to extract several independent components (IC) corresponding to the sequence of activation and used single-trial peaks as modulation parameters in a general linear model (GLM) of fMRI data. We obtained an occipital-temporal-frontal stream of BOLD signal modulation, in accordance with the three successive IC-ERPs providing an unprecedented spatio-temporal characterization of the whole cognitive process as defined by BOLD signal modulation. By using this approach, the pattern of EEG-informed BOLD modulation provided improved characterization of the network involved than the fMRI-only analysis or the source reconstruction of the three ERPs; the latter techniques showing only two regions in common localized in the occipital lobe.

  6. Placental oxygen transport estimated by the hyperoxic placental BOLD MRI response.

    PubMed

    Sørensen, Anne; Sinding, Marianne; Peters, David A; Petersen, Astrid; Frøkjær, Jens B; Christiansen, Ole B; Uldbjerg, Niels

    2015-10-01

    Estimating placental oxygen transport capacity is highly desirable, as impaired placental function is associated with fetal growth restriction (FGR) and poor neonatal outcome. In clinical obstetrics, a noninvasive method to estimate the placental oxygen transport is not available, and the current methods focus on fetal well-being rather than on direct assessment of placental function. In this article, we aim to estimate the placental oxygen transport using the hyperoxic placental blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) response. In 21 normal pregnancies and in four cases of severe early onset FGR, placental BOLD MRI was performed in a 1.5 Tesla MRI system (TR:8000 msec, TE:50 msec, Flip angle:90). Placental histological examination was performed in the FGR cases. In normal pregnancies, the average hyperoxic placental BOLD response was 12.6 ± 5.4% (mean ± SD). In the FGR cases, the hyperoxic BOLD response was abnormal only in cases with histological signs of maternal hypoperfusion of the placenta. The hyperoxic placental BOLD response is mainly derived from an increase in the saturation of maternal venous blood. In the normal placenta, the pO2 of the umbilical vein is closely related to the pO2 of the uterine vein. Therefore, the hyperoxic placental BOLD response may reflect the placental oxygen supply to the fetus. In early onset FGR, the placental oxygen transport is reduced mainly because of the maternal hypoperfusion, and in these cases the placental BOLD response might be altered. Thus, the placental BOLD MRI might provide direct noninvasive assessment of placental oxygen transport. PMID:26471757

  7. Placental oxygen transport estimated by the hyperoxic placental BOLD MRI response.

    PubMed

    Sørensen, Anne; Sinding, Marianne; Peters, David A; Petersen, Astrid; Frøkjær, Jens B; Christiansen, Ole B; Uldbjerg, Niels

    2015-10-01

    Estimating placental oxygen transport capacity is highly desirable, as impaired placental function is associated with fetal growth restriction (FGR) and poor neonatal outcome. In clinical obstetrics, a noninvasive method to estimate the placental oxygen transport is not available, and the current methods focus on fetal well-being rather than on direct assessment of placental function. In this article, we aim to estimate the placental oxygen transport using the hyperoxic placental blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) response. In 21 normal pregnancies and in four cases of severe early onset FGR, placental BOLD MRI was performed in a 1.5 Tesla MRI system (TR:8000 msec, TE:50 msec, Flip angle:90). Placental histological examination was performed in the FGR cases. In normal pregnancies, the average hyperoxic placental BOLD response was 12.6 ± 5.4% (mean ± SD). In the FGR cases, the hyperoxic BOLD response was abnormal only in cases with histological signs of maternal hypoperfusion of the placenta. The hyperoxic placental BOLD response is mainly derived from an increase in the saturation of maternal venous blood. In the normal placenta, the pO2 of the umbilical vein is closely related to the pO2 of the uterine vein. Therefore, the hyperoxic placental BOLD response may reflect the placental oxygen supply to the fetus. In early onset FGR, the placental oxygen transport is reduced mainly because of the maternal hypoperfusion, and in these cases the placental BOLD response might be altered. Thus, the placental BOLD MRI might provide direct noninvasive assessment of placental oxygen transport.

  8. Placental oxygen transport estimated by the hyperoxic placental BOLD MRI response

    PubMed Central

    Sørensen, Anne; Sinding, Marianne; Peters, David A; Petersen, Astrid; Frøkjær, Jens B; Christiansen, Ole B; Uldbjerg, Niels

    2015-01-01

    Estimating placental oxygen transport capacity is highly desirable, as impaired placental function is associated with fetal growth restriction (FGR) and poor neonatal outcome. In clinical obstetrics, a noninvasive method to estimate the placental oxygen transport is not available, and the current methods focus on fetal well-being rather than on direct assessment of placental function. In this article, we aim to estimate the placental oxygen transport using the hyperoxic placental blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) response. In 21 normal pregnancies and in four cases of severe early onset FGR, placental BOLD MRI was performed in a 1.5 Tesla MRI system (TR:8000 msec, TE:50 msec, Flip angle:90). Placental histological examination was performed in the FGR cases. In normal pregnancies, the average hyperoxic placental BOLD response was 12.6 ± 5.4% (mean ± SD). In the FGR cases, the hyperoxic BOLD response was abnormal only in cases with histological signs of maternal hypoperfusion of the placenta. The hyperoxic placental BOLD response is mainly derived from an increase in the saturation of maternal venous blood. In the normal placenta, the pO2 of the umbilical vein is closely related to the pO2 of the uterine vein. Therefore, the hyperoxic placental BOLD response may reflect the placental oxygen supply to the fetus. In early onset FGR, the placental oxygen transport is reduced mainly because of the maternal hypoperfusion, and in these cases the placental BOLD response might be altered. Thus, the placental BOLD MRI might provide direct noninvasive assessment of placental oxygen transport. PMID:26471757

  9. Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity.

    PubMed

    Liu, Peiying; Hebrank, Andrew C; Rodrigue, Karen M; Kennedy, Kristen M; Section, Jarren; Park, Denise C; Lu, Hanzhang

    2013-09-01

    BOLD fMRI has provided a wealth of information about the aging brain. A common finding is that posterior regions of the brain manifest an age-related decrease in activation while the anterior regions show an age-related increase. Several neurocognitive models have been proposed to interpret these findings. However, one issue that has not been sufficiently considered to date is that the BOLD signal is based on vascular responses secondary to neural activity. Thus the above findings could be in part due to a vascular change, especially in view of the expected decline of vascular health with age. In the present study, we aim to examine age-related differences in memory-encoding fMRI response in the context of vascular aging. One hundred and thirty healthy subjects ranging from 20 to 89 years old underwent a scene-viewing fMRI task and, in the same session, cerebrovascular reactivity (CVR) was measured in each subject using a CO2-inhalation task. Without accounting for the influence of vascular changes, the task-activated fMRI signal showed the typical age-related decrease in visual cortex and medial temporal lobe (MTL), but manifested an increase in the right inferior frontal gyrus (IFG). In the same individuals, an age-related CVR reduction was observed in all of these regions. We then used a previously proposed normalization approach to calculate a CVR-corrected fMRI signal, which was defined as the uncorrected signal divided by CVR. Based on the CVR-corrected fMRI signal, an age-related increase is now seen in both the left and right sides of IFG; and no brain regions showed a signal decrease with age. We additionally used a model-based approach to examine the fMRI data in the context of CVR, which again suggested an age-related change in the two frontal regions, but not in the visual and MTL regions.

  10. BOLD Frequency Power Indexes Working Memory Performance.

    PubMed

    Balsters, Joshua Henk; Robertson, Ian H; Calhoun, Vince D

    2013-01-01

    Electrophysiology studies routinely investigate the relationship between neural oscillations and task performance. However, the sluggish nature of the BOLD response means that few researchers have investigated the spectral properties of the BOLD signal in a similar manner. For the first time we have applied group ICA to fMRI data collected during a standard working memory task (delayed match-to-sample) and using a multivariate analysis, we investigate the relationship between working memory performance (accuracy and reaction time) and BOLD spectral power within functional networks. Our results indicate that BOLD spectral power within specific networks (visual, temporal-parietal, posterior default-mode network, salience network, basal ganglia) correlated with task accuracy. Multivariate analyses show that the relationship between task accuracy and BOLD spectral power is stronger than the relationship between BOLD spectral power and other variables (age, gender, head movement, and neuropsychological measures). A traditional General Linear Model (GLM) analysis found no significant group differences, or regions that covaried in signal intensity with task accuracy, suggesting that BOLD spectral power holds unique information that is lost in a standard GLM approach. We suggest that the combination of ICA and BOLD spectral power is a useful novel index of cognitive performance that may be more sensitive to brain-behavior relationships than traditional approaches.

  11. Early anti-correlated BOLD signal changes of physiologic origin.

    PubMed

    Bright, Molly G; Bianciardi, Marta; de Zwart, Jacco A; Murphy, Kevin; Duyn, Jeff H

    2014-02-15

    Negative BOLD signals that are synchronous with resting state fluctuations have been observed in large vessels in the cortical sulci and surrounding the ventricles. In this study, we investigated the origin of these negative BOLD signals by applying a Cued Deep Breathing (CDB) task to create transient hypocapnia and a resultant global fMRI signal decrease. We hypothesized that a global stimulus would amplify the effect in large vessels and that using a global negative (vasoconstrictive) stimulus would test whether these voxels exhibit either inherently negative or simply anti-correlated BOLD responses. Significantly anti-correlated, but positive, BOLD signal changes during respiratory challenges were identified in voxels primarily located near edges of brain spaces containing CSF. These positive BOLD responses occurred earlier than the negative CDB response across most of gray matter voxels. These findings confirm earlier suggestions that in some brain regions, local, fractional changes in CSF volume may overwhelm BOLD-related signal changes, leading to signal anti-correlation. We show that regions with CDB anti-correlated signals coincide with most, but not all, of the regions with negative BOLD signal changes observed during a visual and motor stimulus task. Thus, the addition of a physiological challenge to fMRI experiments can help identify which negative BOLD signals are passive physiological anti-correlations and which may have a putative neuronal origin.

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

    PubMed

    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.

  13. Associations of resting-state fMRI functional connectivity with flow-BOLD coupling and regional vasculature.

    PubMed

    Tak, Sungho; Polimeni, Jonathan R; Wang, Danny J J; Yan, Lirong; Chen, J Jean

    2015-04-01

    There has been tremendous interest in applying functional magnetic resonance imaging-based resting-state functional connectivity (rs-fcMRI) measurements to the study of brain function. However, a lack of understanding of the physiological mechanisms of rs-fcMRI limits their ability to interpret rs-fcMRI findings. In this work, the authors examine the regional associations between rs-fcMRI estimates and dynamic coupling between the blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF), as well as resting macrovascular volume. Resting-state BOLD and CBF data were simultaneously acquired using a dual-echo pseudocontinuous arterial spin labeling (pCASL) technique, whereas macrovascular volume fraction was estimated using time-of-flight MR angiography. Functional connectivity within well-known functional networks—including the default mode, frontoparietal, and primary sensory-motor networks—was calculated using a conventional seed-based correlation approach. They found the functional connectivity strength to be significantly correlated with the regional increase in CBF-BOLD coupling strength and inversely proportional to macrovascular volume fraction. These relationships were consistently observed within all functional networks considered. Their findings suggest that highly connected networks observed using rs-fcMRI are not likely to be mediated by common vascular drainage linking distal cortical areas. Instead, high BOLD functional connectivity is more likely to reflect tighter neurovascular connections, attributable to neuronal pathways.

  14. 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

  15. 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.

  16. 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

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

    PubMed

    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.

  18. NMDA-dependent mechanisms only affect the BOLD response in the rat dentate gyrus by modifying local signal processing.

    PubMed

    Tiede, Regina; Krautwald, Karla; Fincke, Anja; Angenstein, Frank

    2012-03-01

    The role of N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms in the formation of a blood oxygen level-dependent (BOLD) response was studied using electrical stimulation of the right perforant pathway. Stimulation of this fiber bundle triggered BOLD responses in the right hippocampal formation and in the left entorhinal cortex. The perforant pathway projects to and activates the dentate gyrus monosynaptically, activation in the contralateral entorhinal cortex is multisynaptic and requires forwarding and processing of signals. Application of the NMDA receptor antagonist MK801 during stimulation had no effect on BOLD responses in the right dentate gyrus, but reduced the BOLD responses in the left entorhinal cortex. In contrast, application of MK801 before the first stimulation train reduced the BOLD response in both regions. Electrophysiological recordings revealed that the initial stimulation trains changed the local processing of the incoming signals in the dentate gyrus. This altered electrophysiological response was not further changed by a subsequent application of MK801, which is in agreement with an unchanged BOLD response. When MK801 was present during the first stimulation train, a dissimilar electrophysiological response pattern was observed and corresponds to an altered BOLD response, indicating that NMDA-dependent mechanisms indirectly affect the BOLD response, mainly via modifying local signal processing and subsequent propagation. PMID:22167232

  19. NMDA-dependent mechanisms only affect the BOLD response in the rat dentate gyrus by modifying local signal processing

    PubMed Central

    Tiede, Regina; Krautwald, Karla; Fincke, Anja; Angenstein, Frank

    2012-01-01

    The role of N-methyl--aspartate (NMDA) receptor-mediated mechanisms in the formation of a blood oxygen level-dependent (BOLD) response was studied using electrical stimulation of the right perforant pathway. Stimulation of this fiber bundle triggered BOLD responses in the right hippocampal formation and in the left entorhinal cortex. The perforant pathway projects to and activates the dentate gyrus monosynaptically, activation in the contralateral entorhinal cortex is multisynaptic and requires forwarding and processing of signals. Application of the NMDA receptor antagonist MK801 during stimulation had no effect on BOLD responses in the right dentate gyrus, but reduced the BOLD responses in the left entorhinal cortex. In contrast, application of MK801 before the first stimulation train reduced the BOLD response in both regions. Electrophysiological recordings revealed that the initial stimulation trains changed the local processing of the incoming signals in the dentate gyrus. This altered electrophysiological response was not further changed by a subsequent application of MK801, which is in agreement with an unchanged BOLD response. When MK801 was present during the first stimulation train, a dissimilar electrophysiological response pattern was observed and corresponds to an altered BOLD response, indicating that NMDA-dependent mechanisms indirectly affect the BOLD response, mainly via modifying local signal processing and subsequent propagation. PMID:22167232

  20. 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.

  1. 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

  2. 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

  3. 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

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

    PubMed

    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.

  5. 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

  6. Examining the regional and cerebral depth-dependent BOLD cerebrovascular reactivity response at 7T.

    PubMed

    Bhogal, Alex A; Philippens, Marielle E P; Siero, Jeroen C W; Fisher, Joseph A; Petersen, Esben Thade; Luijten, Peter R; Hoogduin, Hans

    2015-07-01

    Changes in cerebral blood flow (CBF) in response to hypercapnia induced changes in vascular tone, known as cerebrovascular reactivity (CVR), can be measured using the Blood Oxygenation Level Dependent (BOLD) MR contrast. We examine regional differences in the BOLD-CVR response to a progressively increasing hypercapnic stimulus as well as regional BOLD characteristics for the return to baseline normocapnia. CVR across 9 subjects was highest in the cerebral lobes and deep gray matter. Peak CVR in these regions was measured at 3.6±1.6mmHg above baseline end-tidal CO2. White matter CVR was generally reduced compared to that of the gray matter (peak white matter CVR was ~48% lower). A positive relationship between the end-tidal CO2 value at which peak CVR was measured and white matter depth is observed. Furthermore, the time required for the BOLD signal to return to baseline after cessation of the hypercapnic stimulus, was also related to white matter depth; the return, expressed as a time constant, was ~25% longer in white matter. To explain the observed differences in regional CVR response, a model is proposed that takes into account the local architecture of the cerebrovascular, which can result in changes in regional blood flow distribution as a function of end-tidal CO2.

  7. 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.

  8. 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.

  9. 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

  10. Neuronal activation induced BOLD and CBF responses upon acetazolamide administration in patients with steno-occlusive artery disease.

    PubMed

    Siero, Jeroen C W; Hartkamp, Nolan S; Donahue, Manus J; Harteveld, Anita A; Compter, Annette; Petersen, Esben T; Hendrikse, Jeroen

    2015-01-15

    Blood-oxygenation-level-dependent (BOLD) MRI is widely used for inferring neuronal activation and is becoming increasingly popular for assessing cerebrovascular reactivity (CVR) when combined with a vasoactive stimulus. The BOLD signal contains changes in cerebral blood flow (CBF) and thus information regarding neurovascular coupling and CVR. The BOLD signal, however, is also modulated by changes in cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2), as well as changes in the physiological baseline state. Here, we measured BOLD and CBF responses upon neuronal (visual) activation, before and after a vasodilatory challenge (acetazolamide, ACZ) in patients with vertebrobasilar steno-occlusive disease. After ACZ, the neuronal activation induced BOLD response was reduced or even negative (3 out of 8 subjects), whereas the CBF response remained similar. We show that BOLD alone cannot correctly assess the neuronal activation and underlying neurovascular coupling. The generally assumed positive relationship between BOLD and CBF responses may be severely compromised under changes in the physiological baseline state. Accompanying CBF measurements contain crucial information, and simulations suggest an altered flow-metabolism coupling in these patients.

  11. 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

  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. Against Boldness

    ERIC Educational Resources Information Center

    Kennedy, Mary M.

    2010-01-01

    This special issue, "Bold Ideas for a New Era in Teacher Education, Teacher Preparation, and Teacher Practice," seeks to examine the impact of bold ideas on our field. Authors were asked to propose particular bold ideas that they wanted to examine. I proposed to examine the concept of bold ideas itself. In this article, I challenge the notion that…

  14. 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

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

    PubMed

    Cook, Peter F; Spivak, Mark; Berns, Gregory S

    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 and

  16. 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.

  17. 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

  18. 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

  19. BOLD signal change and contrast reversing frequency: an event-related fMRI study in human primary visual cortex.

    PubMed

    Sun, Pei; Guo, Jianfei; Guo, Shichun; Chen, Jingyi; He, Le; Fu, Shimin

    2014-01-01

    It is believed that human primary visual cortex (V1) increases activity with increasing temporal frequency of a visual stimulus. Two kinds of visual stimulus were used in the previous studies, one is patterned-flash stimulus with a fixed onset period and an increasing average luminance with the increase of temporal frequency, the other is contrast reversing flickering checkerboard or grating with a constant average luminance across different temporal frequencies. That hemodynamic responses change as a function of reversal frequency of contrast reversing checkerboard is at odds with neurophysiological studies in animals and neuroimaging studies in humans. In the present study, we addressed the relationship between reversal frequency of contrast reversing checkerboard and hemodynamic response in human V1 using an event-related experimental paradigm and found that the transient characteristics of blood oxygenation level dependent response in human V1 depended very little on the reversal frequency of a contrast reversing checkerboard.

  20. 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.

  1. Reliability of negative BOLD in ipsilateral sensorimotor areas during unimanual task activity.

    PubMed

    McGregor, Keith M; Sudhyadhom, Atchar; Nocera, Joe; Seff, Ari; Crosson, Bruce; Butler, Andrew J

    2015-06-01

    Research using functional magnetic resonance imaging has for numerous years now reported the existence of a negative blood oxygenation level dependent (BOLD) response. Based on accumulating evidence, this negative BOLD signal appears to represent an active inhibition of cortical areas in which it is found during task activity. This particularly important with respect to motor function given that it is fairly well-established that, in younger adults, the ipsilateral sensorimotor cortex exhibits negative BOLD during unimanual movements in fMRI. This interhemispheric suppression of cortical activity may have useful implications for our understanding of both basic motor function and rehabilitation of injury or disease. However, to date, we are aware of no study that has tested the reliability of evoked negative BOLD in ipsilateral sensorimotor cortex in individuals across sessions. The current study employs a unimanual finger opposition task previously shown to evoke negative BOLD in ipsilateral sensorimotor cortex across three sessions. Reliability metrics across sessions indicates that both the magnitude and location of ipsilateral sensorimotor negative BOLD response is relatively stable over each of the three sessions. Moreover, the volume of negative BOLD in ipsilateral cortex was highly correlated with volume of positive BOLD activity in the contralateral primary motor cortex. These findings show that the negative BOLD signal can be reliably evoked in unimanual task paradigms, and that the signal dynamic could represent an active suppression of the ipsilateral sensorimotor cortex originating from the contralateral motor areas.

  2. Separating neural and vascular effects of caffeine using simultaneous EEG-FMRI: differential effects of caffeine on cognitive and sensorimotor brain responses.

    PubMed

    Diukova, Ana; Ware, Jennifer; Smith, Jessica E; Evans, C John; Murphy, Kevin; Rogers, Peter J; Wise, Richard G

    2012-08-01

    The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A(1) and A(2A) adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG-FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19

  3. Interhemispheric differences of fMRI responses to visual stimuli in patients with side-fixed migraine aura.

    PubMed

    Hougaard, Anders; Amin, Faisal Mohammad; Hoffmann, Michael B; Rostrup, Egill; Larsson, Henrik B W; Asghar, Mohammad Sohail; Larsen, Vibeke Andrée; Olesen, Jes; Ashina, Messoud

    2014-06-01

    Migraine sufferers with aura often report photosensitivity and visual discomfort outside of attacks and many consider bright or flickering light an attack-precipitating factor. The nature of this visual hypersensitivity and its relation to the underlying pathophysiology of the migraine aura is unknown. Using fMRI measurements during visual stimulation we examined the visual cortical responsiveness of patients with migraine with aura. We applied a within-patient design by assessing functional interhemispheric differences in patients consistently experiencing visual aura in the same visual hemifield. We recruited 20 patients with frequent side-fixed visual aura attacks (≥90% of auras occurring in the same visual hemifield) and 20 age and sex matched healthy controls and compared the fMRI blood oxygenation level dependent (BOLD) responses to visual stimulation between symptomatic and asymptomatic hemispheres during the interictal phase and between migraine patients and controls. BOLD responses were selectively increased in the symptomatic hemispheres. This was found in the inferior parietal lobule (P = 0.002), the inferior frontal gyrus (P = 0.003), and the superior parietal lobule (P = 0.017). The affected cortical areas comprise a visually driven functional network involved in oculomotor control, guidance of movement, motion perception, visual attention, and visual spatial memory. The patients also had significantly increased response in the same cortical areas when compared to controls (P < 0.05). We discovered a lateralized alteration of a visually driven functional network in patients with side-fixed aura. These findings suggest a hyperexcitability of the visual system in the interictal phase of migraine with visual aura.

  4. 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…

  5. Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

    PubMed

    Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

    2013-01-01

    A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

  6. 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

  7. Beyond BOLD: optimizing functional imaging in stroke populations.

    PubMed

    Veldsman, Michele; Cumming, Toby; Brodtmann, Amy

    2015-04-01

    Blood oxygenation level-dependent (BOLD) signal changes are often assumed to directly reflect neural activity changes. Yet the real relationship is indirect, reliant on numerous assumptions, and subject to several sources of noise. Deviations from the core assumptions of BOLD contrast functional magnetic resonance imaging (fMRI), and their implications, have been well characterized in healthy populations, but are frequently neglected in stroke populations. In addition to conspicuous local structural and vascular changes after stroke, there are many less obvious challenges in the imaging of stroke populations. Perilesional ischemic changes, remodeling in regions distant to lesion sites, and diffuse perfusion changes all complicate interpretation of BOLD signal changes in standard fMRI protocols. Most stroke patients are also older than the young populations on which assumptions of neurovascular coupling and the typical analysis pipelines are based. We present a review of the evidence to show that the basic assumption of neurovascular coupling on which BOLD-fMRI relies does not capture the complex changes arising from stroke, both pathological and recovery related. As a result, estimating neural activity using the canonical hemodynamic response function is inappropriate in a number of contexts. We review methods designed to better estimate neural activity in stroke populations. One promising alternative to event-related fMRI is a resting-state-derived functional connectivity approach. Resting-state fMRI is well suited to stroke populations because it makes no performance demands on patients and is capable of revealing network-based pathology beyond the lesion site.

  8. Physiologically informed dynamic causal modeling of fMRI data.

    PubMed

    Havlicek, Martin; Roebroeck, Alard; Friston, Karl; Gardumi, Anna; Ivanov, Dimo; Uludag, Kamil

    2015-11-15

    The functional MRI (fMRI) signal is an indirect measure of neuronal activity. In order to deconvolve the neuronal activity from the experimental fMRI data, biophysical generative models have been proposed describing the link between neuronal activity and the cerebral blood flow (the neurovascular coupling), and further the hemodynamic response and the BOLD signal equation. These generative models have been employed both for single brain area deconvolution and to infer effective connectivity in networks of multiple brain areas. In the current paper, we introduce a new fMRI model inspired by experimental observations about the physiological underpinnings of the BOLD signal and compare it with the generative models currently used in dynamic causal modeling (DCM), a widely used framework to study effective connectivity in the brain. We consider three fundamental aspects of such generative models for fMRI: (i) an adaptive two-state neuronal model that accounts for a wide repertoire of neuronal responses during and after stimulation; (ii) feedforward neurovascular coupling that links neuronal activity to blood flow; and (iii) a balloon model that can account for vascular uncoupling between the blood flow and the blood volume. Finally, we adjust the parameterization of the BOLD signal equation for different magnetic field strengths. This paper focuses on the form, motivation and phenomenology of DCMs for fMRI and the characteristics of the various models are demonstrated using simulations. These simulations emphasize a more accurate modeling of the transient BOLD responses - such as adaptive decreases to sustained inputs during stimulation and the post-stimulus undershoot. In addition, we demonstrate using experimental data that it is necessary to take into account both neuronal and vascular transients to accurately model the signal dynamics of fMRI data. By refining the models of the transient responses, we provide a more informed perspective on the underlying neuronal

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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…

  18. 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

  19. Explicit authenticity and stimulus features interact to modulate BOLD response induced by emotional speech.

    PubMed

    Drolet, Matthis; Schubotz, Ricarda I; Fischer, Julia

    2013-06-01

    Context has been found to have a profound effect on the recognition of social stimuli and correlated brain activation. The present study was designed to determine whether knowledge about emotional authenticity influences emotion recognition expressed through speech intonation. Participants classified emotionally expressive speech in an fMRI experimental design as sad, happy, angry, or fearful. For some trials, stimuli were cued as either authentic or play-acted in order to manipulate participant top-down belief about authenticity, and these labels were presented both congruently and incongruently to the emotional authenticity of the stimulus. Contrasting authentic versus play-acted stimuli during uncued trials indicated that play-acted stimuli spontaneously up-regulate activity in the auditory cortex and regions associated with emotional speech processing. In addition, a clear interaction effect of cue and stimulus authenticity showed up-regulation in the posterior superior temporal sulcus and the anterior cingulate cortex, indicating that cueing had an impact on the perception of authenticity. In particular, when a cue indicating an authentic stimulus was followed by a play-acted stimulus, additional activation occurred in the temporoparietal junction, probably pointing to increased load on perspective taking in such trials. While actual authenticity has a significant impact on brain activation, individual belief about stimulus authenticity can additionally modulate the brain response to differences in emotionally expressive speech.

  20. fMRI Differences between Subjects with Low and High Responses to Alcohol during a Stop Signal Task

    PubMed Central

    Schuckit, Marc A.; Tapert, Susan; Matthews, Scott C.; Paulus, Martin P.; Tolentino, Neil J.; Smith, Tom L.; Trim, Ryan S.; Hall, Shana; Simmons, Alan

    2011-01-01

    Background A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed. Methods Forty-nine drinking but not yet alcoholic matched pairs of 18-25-year-old subjects (N = 98; 53% female) with low and high LRs as established in separate alcohol challenges were evaluated in two event-related functional magnetic resonance imaging (fMRI) sessions (placebo and ~ 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session. Results Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level dependent (BOLD) signal during error and inhibitory processing, despite similar LR-group performance on the task. In most clusters with significant (corrected p<.05, clusters >1344 μl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition-related activation after alcohol compared to placebo. Conclusions This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks for a future life threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk for future heavy drinking and alcohol dependence. PMID:22003983

  1. 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

  2. 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.

  3. 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

  4. 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

  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. Transfer Function between EEG and BOLD Signals of Epileptic Activity

    PubMed Central

    Leite, Marco; Leal, Alberto; Figueiredo, Patrícia

    2013-01-01

    Simultaneous electroencephalogram (EEG)-functional Magnetic Resonance Imaging (fMRI) recordings have seen growing application in the evaluation of epilepsy, namely in the characterization of brain networks related to epileptic activity. In EEG-correlated fMRI studies, epileptic events are usually described as boxcar signals based on the timing information retrieved from the EEG, and subsequently convolved with a hemodynamic response function to model the associated Blood Oxygen Level Dependent (BOLD) changes. Although more flexible approaches may allow a higher degree of complexity for the hemodynamics, the issue of how to model these dynamics based on the EEG remains an open question. In this work, a new methodology for the integration of simultaneous EEG-fMRI data in epilepsy is proposed, which incorporates a transfer function from the EEG to the BOLD signal. Independent component analysis of the EEG is performed, and a number of metrics expressing different models of the EEG-BOLD transfer function are extracted from the resulting time courses. These metrics are then used to predict the fMRI data and to identify brain areas associated with the EEG epileptic activity. The methodology was tested on both ictal and interictal EEG-fMRI recordings from one patient with a hypothalamic hamartoma. When compared to the conventional analysis approach, plausible, consistent, and more significant activations were obtained. Importantly, frequency-weighted EEG metrics yielded superior results than those weighted solely on the EEG power, which comes in agreement with previous literature. Reproducibility, specificity, and sensitivity should be addressed in an extended group of patients in order to further validate the proposed methodology and generalize the presented proof of concept. PMID:23355832

  7. Origins of intersubject variability of blood oxygenation level dependent and arterial spin labeling fMRI: implications for quantification of brain activity.

    PubMed

    Gaxiola-Valdez, Ismael; Goodyear, Bradley G

    2012-12-01

    Accurate localization of brain activity using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been challenged because of the large BOLD signal within distal veins. Arterial spin labeling (ASL) techniques offer greater sensitivity to the microvasculature but possess low temporal resolution and limited brain coverage. In this study, we show that the physiological origins of BOLD and ASL depend on whether percent change or statistical significance is being considered. For BOLD and ASL fMRI data collected during a simple unilateral hand movement task, we found that in the area of the contralateral motor cortex the centre of gravity (CoG) of the intersubject coefficient of variation (CV) of BOLD fMRI was near the brain surface for percent change in signal, whereas the CoG of the intersubject CV for Z-score was in close proximity of sites of brain activity for both BOLD and ASL. These findings suggest that intersubject variability of BOLD percent change is vascular in origin, whereas the origin of inter-subject variability of Z-score is neuronal for both BOLD and ASL. For longer duration tasks (12 s or greater), however, there was a significant correlation between BOLD and ASL percent change, which was not evident for short duration tasks (6 s). These findings suggest that analyses directly comparing percent change in BOLD signal between pre-defined regions of interest using short duration stimuli, as for example in event-related designs, may be heavily weighted by large-vessel responses rather than neuronal responses.

  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.

  9. Characterizing Response to Elemental Unit of Acoustic Imaging Noise: An fMRI Study

    PubMed Central

    Luh, Wen-Ming; Talavage, Thomas M.

    2010-01-01

    Acoustic imaging noise produced during functional magnetic resonance imaging (fMRI) studies can hinder auditory fMRI research analysis by altering the properties of the acquired time-series data. Acoustic imaging noise can be especially confounding when estimating the time course of the hemodynamic response (HDR) in auditory event-related fMRI (fMRI) experiments. This study is motivated by the desire to establish a baseline function that can serve not only as a comparison to other quantities of acoustic imaging noise for determining how detrimental is one's experimental noise, but also as a foundation for a model that compensates for the response to acoustic imaging noise. Therefore, the amplitude and spatial extent of the HDR to the elemental unit of acoustic imaging noise (i.e., a single ping) associated with echoplanar acquisition were characterized and modeled. Results from this fMRI study at 1.5 T indicate that the group-averaged HDR in left and right auditory cortex to acoustic imaging noise (duration of 46 ms) has an estimated peak magnitude of 0.29% (right) to 0.48% (left) signal change from baseline, peaks between 3 and 5 s after stimulus presentation, and returns to baseline and remains within the noise range approximately 8 s after stimulus presentation. PMID:19304477

  10. 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

  11. Striatal BOLD Response Reflects the Impact of Herd Information on Financial Decisions

    PubMed Central

    Burke, Christopher J.; Tobler, Philippe N.; Schultz, Wolfram; Baddeley, Michelle

    2010-01-01

    Like other species, humans are sensitive to the decisions and actions of conspecifics, which can lead to herd behavior and undesirable outcomes such as stock market bubbles and bank runs. However, how the brain processes this socially derived influence is only poorly understood. Using functional magnetic resonance imaging (fMRI), we scanned participants as they made decisions on whether to buy stocks after observing others’ buying decisions. We demonstrate that activity in the ventral striatum, an area heavily implicated in reward processing, tracked the degree of influence on participants’ decisions arising from the observation of other peoples’ decisions. The signal did not track non-human, non-social control decisions. These findings lend weight to the notion that the ventral striatum is involved in the processing of complex social aspects of decision making and identify a possible neural basis for herd behavior. PMID:20589242

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

    PubMed Central

    Howarth, Clare; Kurth-Nelson, Zebulun; Mishra, Anusha

    2016-01-01

    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

  13. 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'.

  14. 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

  15. BOLD response to motion verbs in left posterior middle temporal gyrus during story comprehension.

    PubMed

    Wallentin, Mikkel; Nielsen, Andreas Højlund; Vuust, Peter; Dohn, Anders; Roepstorff, Andreas; Lund, Torben Ellegaard

    2011-12-01

    A primary focus within neuroimaging research on language comprehension is on the distribution of semantic knowledge in the brain. Studies have shown that the left posterior middle temporal gyrus (LPMT), a region just anterior to area MT/V5, is important for the processing of complex action knowledge. It has also been found that motion verbs cause activation in LPMT. In this experiment we investigated whether this effect could be replicated in a setting resembling real life language comprehension, i.e. without any overt behavioral task during passive listening to a story. During fMRI participants listened to a recording of the story "The Ugly Duckling". We incorporated a nuisance elimination regression approach for factoring out known nuisance variables both in terms of physiological noise, sound intensity, linguistic variables and emotional content. Compared to the remaining text, clauses containing motion verbs were accompanied by a robust activation of LPMT with no other significant effects, consistent with the hypothesis that this brain region is important for processing motion knowledge, even during naturalistic language comprehension conditions.

  16. Effects of Family History of Alcohol Use Disorders on Spatial Working Memory BOLD Response in Adolescents

    PubMed Central

    Spadoni, Andrea D.; Norman, Andria L.; Schweinsburg, Alecia D.; Tapert, Susan F.

    2008-01-01

    Background A positive family history (FH) of alcohol use disorders (AUD) has been linked to increased risk for the development of AUD, and neurocognitive factors have been postulated as important underlying mechanisms of familial alcoholism transmission. Methods We used functional magnetic resonance imaging (fMRI) during a spatial working memory (SWM) and vigilance paradigm to investigate potential neurodevelopmental differences linked to familial density of AUD in 72 adolescents aged 12 to 14 years. Results Youth with denser family histories of AUD showed less activation during a simple vigilance condition relative to SWM in cingulate and medial frontal gyri (β = 0.28, p = 0.03), and a trend for more relative activity during rest (β = −0.25, p = 0.07) in this cluster. Conclusions Youth with greater familial densities of AUD may be less successful at modulating activity of the default network, potentially indicating a greater propensity for task-independent thought or reduced inhibition of task-irrelevant processing. Failure to moderate activation of the default network may have implications for cognitive efficiency and goal directed behavior in youth with dense FH. Further, aberrant activation in cingulate regions may be linked to genetic variation in GABA receptor units, suggesting a useful endophenotype for risk associated with alcohol dependence. PMID:18540914

  17. 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.

  18. 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

  19. 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

  20. Comparing cerebrovascular reactivity measured using BOLD and cerebral blood flow MRI: The effect of basal vascular tension on vasodilatory and vasoconstrictive reactivity.

    PubMed

    Halani, Sheliza; Kwinta, Jonathan B; Golestani, Ali M; Khatamian, Yasha B; Chen, J Jean

    2015-04-15

    Cerebrovascular reactivity (CVR) is an important metric of cerebrovascular health. While the BOLD fMRI method in conjunction with carbon-dioxide (CO2) based vascular manipulation has been the most commonly used, the BOLD signal is not a direct measure of vascular changes, and the use of arterial-spin labeling (ASL) cerebral blood flow (CBF) imaging is increasingly advocated. Nonetheless, given the differing dependencies of BOLD and CBF on vascular baseline conditions and the diverse CO2 manipulation types currently used in the literature, knowledge of potential biases introduced by each technique is critical for the interpretation of CVR measurements. In this work, we use simultaneous BOLD-CBF acquisitions during both vasodilatory (hypercapnic) and vasoconstrictive (hypocapnic) stimuli to measure CVR. We further imposed different levels of baseline vascular tension by inducing hypercapnic and hypocapnic baselines, separately from normocapnia by 4mmHg. We saw significant and diverse dependencies on vascular stimulus and baseline condition in both BOLD and CBF CVR measurements: (i) BOLD-based CVR is more sensitive to basal vascular tension than CBF-based CVR; (ii) the use of a combination of vasodilatory and vasoconstrictive stimuli maximizes the sensitivity of CBF-based CVR to vascular tension changes; (iii) the BOLD and CBF vascular response delays are both significantly lengthened at predilated baseline. As vascular tension can often be altered by potential pathology, our findings are important considerations when interpreting CVR measurements in health and disease.

  1. Neural physiological modeling towards a hemodynamic response function for fMRI.

    PubMed

    Afonso, David M; Sanches, João M; Lauterbach, Martin H

    2007-01-01

    The BOLD signal provided by the functional MRI medical modality measures the ratio of oxy- to deoxyhaemoglobin at each location inside the brain. The detection of activated regions upon the application of an external stimulus, e.g., visual or auditive, is based on the comparison of the mentioned ratios of a rest condition (pre-stimulus) and of a stimulated condition (post-stimulus). Therefore, an accurate knowledge of the impulse response of the BOLD signal to neural stimulus in a given region is needed to design robust detectors that discriminate, with a high level of confidence activated from non activated regions. Usually, in the literature, the hemodynamic response has been modeled by known functions, e.g., gamma functions, fitting them, or not, to the experimental data. In this paper we present a different approach based on the physiologic behavior of the vascular and neural tissues. Here, a linear model based on reasonable physiological assumptions about oxygen consumption and vasodilatation processes are used to design a linear model from which a transfer function is derived. The estimation of the model parameters is performed by using the minimum square error (MSE) by forcing the adjustment of the stimulus response to the observations. Experimental results using real data have shown that the proposed model successfully explains the observations allowing to achieve small values for the fitting error.

  2. Developmental Changes of BOLD Signal Correlations with Global Human EEG Power and Synchronization during Working Memory

    PubMed Central

    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

  3. Calibrating the BOLD response without administering gases: comparison of hypercapnia calibration with calibration using an asymmetric spin echo.

    PubMed

    Blockley, Nicholas P; Griffeth, Valerie E M; Simon, Aaron B; Dubowitz, David J; Buxton, Richard B

    2015-01-01

    The calibrated BOLD (blood oxygen level dependent) technique was developed to quantify the BOLD signal in terms of changes in oxygen metabolism. In order to achieve this a calibration experiment must be performed, which typically requires a hypercapnic gas mixture to be administered to the participant. However, an emerging technique seeks to perform this calibration without administering gases using a refocussing based calibration. Whilst hypercapnia calibration seeks to emulate the physical removal of deoxyhaemoglobin from the blood, the aim of refocussing based calibration is to refocus the dephasing effect of deoxyhaemoglobin on the MR signal using a spin echo. However, it is not possible to refocus all of the effects that contribute to the BOLD signal and a scale factor is required to estimate the BOLD scaling parameter M. In this study the feasibility of a refocussing based calibration was investigated. The scale factor relating the refocussing calibration to M was predicted by simulations to be approximately linear and empirically measured to be 0.88±0.36 for the visual cortex and 0.93±0.32 for a grey matter region of interest (mean±standard deviation). Refocussing based calibration is a promising approach for greatly simplifying the calibrated BOLD methodology by eliminating the need for the subject to breathe special gas mixtures, and potentially provides the basis for a wider implementation of quantitative functional MRI.

  4. 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

  5. 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

  6. 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…

  7. 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

  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

    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

  10. 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

  11. 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.

  12. Spatial and temporal analysis of fMRI data on word and sentence reading.

    PubMed

    Haller, Sven; Klarhoefer, Markus; Schwarzbach, Jens; Radue, Ernst W; Indefrey, Peter

    2007-10-01

    Written language comprehension at the word and the sentence level was analysed by the combination of spatial and temporal analysis of functional magnetic resonance imaging (fMRI). Spatial analysis was performed via general linear modelling (GLM). Concerning the temporal analysis, local differences in neurovascular coupling may confound a direct comparison of blood oxygenation level-dependent (BOLD) response estimates between regions. To avoid this problem, we parametrically varied linguistic task demands and compared only task-induced within-region BOLD response differences across areas. We reasoned that, in a hierarchical processing system, increasing task demands at lower processing levels induce delayed onset of higher-level processes in corresponding areas. The flow of activation is thus reflected in the size of task-induced delay increases. We estimated BOLD response delay and duration for each voxel and each participant by fitting a model function to the event-related average BOLD response. The GLM showed increasing activations with increasing linguistic demands dominantly in the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG). The combination of spatial and temporal analysis allowed a functional differentiation of IFG subregions involved in written language comprehension. Ventral IFG region (BA 47) and STG subserve earlier processing stages than two dorsal IFG regions (BA 44 and 45). This is in accordance with the assumed early lexical semantic and late syntactic processing of these regions and illustrates the complementary information provided by spatial and temporal fMRI data analysis of the same data set.

  13. Photosynthesis and growth responses of mustard (Brassica juncea L. cv Pusa Bold) plants to free air carbon dioxide enrichment (FACE).

    PubMed

    Ruhil, Kamal; Sheeba; Ahmad, Altaf; Iqbal, Muhammad; Tripathy, Baishnab C

    2015-07-01

    Increased atmospheric [CO2] is likely to affect photosynthesis, plant growth, and yield potential of plants. Mustard (Brassica juncea L.) is an important oil seed crop that is widely grown in India. Therefore, the impact of elevated [CO2] (585 μmol mol(-1)) on pigment and protein content, chlorophyll a fluorescence, photosynthetic electron transport reactions, CO2 assimilation, biomass production, and seed yield potential was measured in B. juncea cv Pusa Bold, grown inside free air carbon dioxide enrichment (FACE) rings installed on the campus of Jawaharlal Nehru University, New Delhi, India. Plants were grown for three consecutive winter seasons (2010-2013), in ambient (385 μmol mol(-1)) or elevated [CO2], in field conditions. Elevated [CO2] had no significant effect on the minimal chlorophyll fluorescence (F 0), while the quantum efficiency of Photosystem II, measured as variable fluorescence (F v = F m-F 0) to maximum fluoresence (F m), increased by 3 %. Electron transport rate, photosystem I, photosystem II, and whole chain electron transport rates increased by 8 % in elevated [CO2]. However, the net photosynthesis rate increased by ≈50 % in three growing seasons under elevated [CO2] condition. The stomatal conductance and transpiration rate decreased resulting in higher photosynthetic water use efficiency. The photosynthesizing surface, i.e., leaf area index substantially increased leading to higher biomass and seed yield under elevated [CO2] condition. Acclimatory downregulation of photosynthesis and plant productivity was not observed in three consecutive growing years suggesting that in the absence of nutrient limitation, B. juncea is highly responsive to elevated CO2 whose yield potential shall increase in changing climatic conditions. PMID:25471475

  14. Photosynthesis and growth responses of mustard (Brassica juncea L. cv Pusa Bold) plants to free air carbon dioxide enrichment (FACE).

    PubMed

    Ruhil, Kamal; Sheeba; Ahmad, Altaf; Iqbal, Muhammad; Tripathy, Baishnab C

    2015-07-01

    Increased atmospheric [CO2] is likely to affect photosynthesis, plant growth, and yield potential of plants. Mustard (Brassica juncea L.) is an important oil seed crop that is widely grown in India. Therefore, the impact of elevated [CO2] (585 μmol mol(-1)) on pigment and protein content, chlorophyll a fluorescence, photosynthetic electron transport reactions, CO2 assimilation, biomass production, and seed yield potential was measured in B. juncea cv Pusa Bold, grown inside free air carbon dioxide enrichment (FACE) rings installed on the campus of Jawaharlal Nehru University, New Delhi, India. Plants were grown for three consecutive winter seasons (2010-2013), in ambient (385 μmol mol(-1)) or elevated [CO2], in field conditions. Elevated [CO2] had no significant effect on the minimal chlorophyll fluorescence (F 0), while the quantum efficiency of Photosystem II, measured as variable fluorescence (F v = F m-F 0) to maximum fluoresence (F m), increased by 3 %. Electron transport rate, photosystem I, photosystem II, and whole chain electron transport rates increased by 8 % in elevated [CO2]. However, the net photosynthesis rate increased by ≈50 % in three growing seasons under elevated [CO2] condition. The stomatal conductance and transpiration rate decreased resulting in higher photosynthetic water use efficiency. The photosynthesizing surface, i.e., leaf area index substantially increased leading to higher biomass and seed yield under elevated [CO2] condition. Acclimatory downregulation of photosynthesis and plant productivity was not observed in three consecutive growing years suggesting that in the absence of nutrient limitation, B. juncea is highly responsive to elevated CO2 whose yield potential shall increase in changing climatic conditions.

  15. 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

  16. Resting BOLD fluctuations in the primary somatosensory cortex correlate with tactile acuity.

    PubMed

    Haag, Lauren M; Heba, Stefanie; Lenz, Melanie; Glaubitz, Benjamin; Höffken, Oliver; Kalisch, Tobias; Puts, Nicholaas A; Edden, Richard A E; Tegenthoff, Martin; Dinse, Hubert; Schmidt-Wilcke, Tobias

    2015-03-01

    Sensory perception, including 2-point discrimination (2 ptD), is tightly linked to cortical processing of tactile stimuli in primary somatosensory cortices. While the role of cortical activity in response to a tactile stimulus has been widely investigated, the role of baseline cortical activity is largely unknown. Using resting state fMRI we investigated the relationship between local BOLD fluctuations in the primary somatosensory cortex (the representational field of the hand) and 2 ptD of the corresponding index finger (right and left). Cortical activity was measured using fractional amplitudes of the low frequency BOLD fluctuations (fALFF) and synchronicity using regional homogeneity (ReHo) of the S1 hand region during rest. 2 ptD correlated with higher ReHo values in the representational areas of the contralateral S1 cortex (left hand: p = .028; right hand: p = .049). 2 ptD additionally correlated with higher fALFF in the representational area of the left hand (p = .007) and showed a trend for a significant correlation in the representational area of the right hand (p = .051). Thus, higher BOLD amplitudes and synchronicity at rest, as measures of cortical activity and synchronicity, respectively, are related to better tactile discrimination abilities of the contralateral hand. Our findings extend the relationship seen between spontaneous BOLD fluctuations and sensory perception.

  17. 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

  18. Transferring Cognitive Tasks Between Brain Imaging Modalities: Implications for Task Design and Results Interpretation in fMRI Studies

    PubMed Central

    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

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

    PubMed Central

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

    2010-01-01

    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 to non-drug using controls. Within CD subjects, thalamic activation significantly correlated with treatment response. This study shows CD subjects in early abstinence have alteration 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. Brain responses to facial attractiveness induced by facial proportions: evidence from an fMRI study

    PubMed Central

    Shen, Hui; Chau, Desmond K. P.; Su, Jianpo; Zeng, Ling-Li; Jiang, Weixiong; He, Jufang; Fan, Jintu; Hu, Dewen

    2016-01-01

    Brain responses to facial attractiveness induced by facial proportions are investigated by using functional magnetic resonance imaging (fMRI), in 41 young adults (22 males and 19 females). The subjects underwent fMRI while they were presented with computer-generated, yet realistic face images, which had varying facial proportions, but the same neutral facial expression, baldhead and skin tone, as stimuli. Statistical parametric mapping with parametric modulation was used to explore the brain regions with the response modulated by facial attractiveness ratings (ARs). The results showed significant linear effects of the ARs in the caudate nucleus and the orbitofrontal cortex for all of the subjects, and a non-linear response profile in the right amygdala for only the male subjects. Furthermore, canonical correlation analysis was used to learn the most relevant facial ratios that were best correlated with facial attractiveness. A regression model on the fMRI-derived facial ratio components demonstrated a strong linear relationship between the visually assessed mean ARs and the predictive ARs. Overall, this study provided, for the first time, direct neurophysiologic evidence of the effects of facial ratios on facial attractiveness and suggested that there are notable gender differences in perceiving facial attractiveness as induced by facial proportions. PMID:27779211

  1. A neural correlate of visceral emotional responses: evidence from fMRI of the thoracic spinal cord

    PubMed Central

    Smith, Stephen D.; McIver, Theresa A.

    2015-01-01

    Functional magnetic resonance imaging (fMRI) of thoracic spinal cord neurons was used to examine the neural correlates of visceral emotional responses. Participants completed four spinal fMRI runs involving passive viewing (i.e. no movement) and motoric responses to negative or neutral images. Negative images, particularly in the movement condition, elicited robust activity in motoric nuclei, indicating ‘action preparedness’. These images also enhanced activity in autonomic and sensory nuclei, thus providing a clear neural representation of visceral responses to emotional stimuli. PMID:24993101

  2. 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…

  3. Dynamic BOLD functional connectivity in humans and its electrophysiological correlates.

    PubMed

    Tagliazucchi, Enzo; von Wegner, Frederic; Morzelewski, Astrid; Brodbeck, Verena; Laufs, Helmut

    2012-01-01

    Neural oscillations subserve many human perceptual and cognitive operations. Accordingly, brain functional connectivity is not static in time, but fluctuates dynamically following the synchronization and desynchronization of neural populations. This dynamic functional connectivity has recently been demonstrated in spontaneous fluctuations of the Blood Oxygen Level-Dependent (BOLD) signal, measured with functional Magnetic Resonance Imaging (fMRI). We analyzed temporal fluctuations in BOLD connectivity and their electrophysiological correlates, by means of long (≈50 min) joint electroencephalographic (EEG) and fMRI recordings obtained from two populations: 15 awake subjects and 13 subjects undergoing vigilance transitions. We identified positive and negative correlations between EEG spectral power (extracted from electrodes covering different scalp regions) and fMRI BOLD connectivity in a network of 90 cortical and subcortical regions (with millimeter spatial resolution). In particular, increased alpha (8-12 Hz) and beta (15-30 Hz) power were related to decreased functional connectivity, whereas gamma (30-60 Hz) power correlated positively with BOLD connectivity between specific brain regions. These patterns were altered for subjects undergoing vigilance changes, with slower oscillations being correlated with functional connectivity increases. Dynamic BOLD functional connectivity was reflected in the fluctuations of graph theoretical indices of network structure, with changes in frontal and central alpha power correlating with average path length. Our results strongly suggest that fluctuations of BOLD functional connectivity have a neurophysiological origin. Positive correlations with gamma can be interpreted as facilitating increased BOLD connectivity needed to integrate brain regions for cognitive performance. Negative correlations with alpha suggest a temporary functional weakening of local and long-range connectivity, associated with an idling state. PMID

  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. Dynamic modeling of neuronal responses in fMRI using cubature Kalman filtering.

    PubMed

    Havlicek, Martin; Friston, Karl J; Jan, Jiri; Brazdil, Milan; Calhoun, Vince D

    2011-06-15

    This paper presents a new approach to inverting (fitting) models of coupled dynamical systems based on state-of-the-art (cubature) Kalman filtering. Crucially, this inversion furnishes posterior estimates of both the hidden states and parameters of a system, including any unknown exogenous input. Because the underlying generative model is formulated in continuous time (with a discrete observation process) it can be applied to a wide variety of models specified with either ordinary or stochastic differential equations. These are an important class of models that are particularly appropriate for biological time-series, where the underlying system is specified in terms of kinetics or dynamics (i.e., dynamic causal models). We provide comparative evaluations with generalized Bayesian filtering (dynamic expectation maximization) and demonstrate marked improvements in accuracy and computational efficiency. We compare the schemes using a series of difficult (nonlinear) toy examples and conclude with a special focus on hemodynamic models of evoked brain responses in fMRI. Our scheme promises to provide a significant advance in characterizing the functional architectures of distributed neuronal systems, even in the absence of known exogenous (experimental) input; e.g., resting state fMRI studies and spontaneous fluctuations in electrophysiological studies. Importantly, unlike current Bayesian filters (e.g. DEM), our scheme provides estimates of time-varying parameters, which we will exploit in future work on the adaptation and enabling of connections in the brain. PMID:21396454

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

    PubMed Central

    Kim, Jongwan; Wang, Jing; Wedell, Douglas H.

    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

  7. 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

  8. 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

  9. 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

  10. The less BOLD, the wiser: support for the latent resource hypothesis after traumatic brain injury.

    PubMed

    Medaglia, John D; Chiou, Kathy S; Slocomb, Julia; Fitzpatrick, Neal M; Wardecker, Britney M; Ramanathan, Deepa; Vesek, Jeffrey; Good, David C; Hillary, Frank G

    2012-04-01

    Previous studies of the BOLD response in the injured brain have revealed neural recruitment relative to controls during working memory tasks in several brain regions, most consistently the right prefrontal cortex and anterior cingulate cortices. We previously proposed that the recruitment observed in this literature represents auxiliary support resources, and that recruitment of PFC is not abnormal or injury specific and should reduce as novelty and challenge decrease. The current study directly tests this hypothesis in the context of practice of a working memory task. It was hypothesized that individuals with brain injury would demonstrate recruitment of previously indicated regions, behavioral improvement following task practice, and a reduction in the BOLD signal in recruited regions after practice. Individuals with traumatic brain injury and healthy controls performed the n-back during fMRI acquisition, practiced each task out of the scanner, and returned to the scanner for additional fMRI n-back acquisition. Statistical parametric maps demonstrated a number of regions of recruitment in the 1-back in individuals with brain injury and a number of corresponding regions of reduced activation in individuals with brain injury following practice in both the 1-back and 2-back. Regions of interest demonstrated reduced activation following practice, including the anterior cingulate and right prefrontal cortices. Individuals with brain injury demonstrated modest behavioral improvements following practice. These findings suggest that neural recruitment in brain injury does not represent reorganization but a natural extension of latent mechanisms that engage transiently and are contingent upon cerebral challenge.

  11. Convergence of human brain mapping tools: neuronavigated TMS parameters and fMRI activity in the hand motor area.

    PubMed

    Sarfeld, Anna-Sophia; Diekhoff, Svenja; Wang, Ling E; Liuzzi, Gianpiero; Uludağ, Kamil; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

    2012-05-01

    Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are well-established tools for investigating the human motor system in-vivo. We here studied the relationship between movement-related fMRI signal changes in the primary motor cortex (M1) and electrophysiological properties of the hand motor area assessed with neuronavigated TMS in 17 healthy subjects. The voxel showing the highest task-related BOLD response in the left hand motor area during right hand movements was identified for each individual subject. This fMRI peak voxel in M1 served as spatial target for coil positioning during neuronavigated TMS. We performed correlation analyses between TMS parameters, BOLD signal estimates and effective connectivity parameters of M1 assessed with dynamic causal modeling (DCM). The results showed a negative correlation between the movement-related BOLD signal in left M1 and resting as well as active motor threshold (MT) obtained for left M1. The DCM analysis revealed that higher excitability of left M1 was associated with a stronger coupling between left supplementary motor area (SMA) and M1. Furthermore, BOLD activity in left M1 correlated with ipsilateral silent period (ISP), i.e. the stronger the task-related BOLD response in left M1, the higher interhemispheric inhibition effects targeting right M1. DCM analyses revealed a positive correlation between the coupling of left SMA with left M1 and the duration of ISP. The data show that TMS parameters assessed for the hand area of M1 do not only reflect the intrinsic properties at the stimulation site but also interactions with remote areas in the human motor system.

  12. BOLD coherence reveals segregated functional neural interactions when adapting to distinct torque perturbations

    PubMed Central

    Tunik, Eugene; Schmitt, Paul J.; Grafton, Scott T.

    2007-01-01

    In the natural world, we experience and adapt to multiple extrinsic perturbations. This poses a challenge to neural circuits in discriminating between different context-appropriate responses. Using event-related fMRI, we characterized the neural dynamics involved in this process by randomly delivering a position- or velocity-dependent torque perturbation to subjects’ arms during a target capture task. Each perturbation was color-cued during movement preparation to provide contextual information. Though trajectories differed between perturbations, subjects significantly reduced error under both conditions. This was paralleled by reduced BOLD signal in the right dentate nucleus, the left sensorimotor cortex, and the left intraparietal sulcus. Trials included ‘NoGo’ conditions to dissociate activity related to preparation from execution and adaptation. Subsequent analysis identified perturbation-specific neural processes underlying preparation (‘NoGo’) and adaptation (‘Go’) early and late into learning. Between-perturbation comparisons of BOLD magnitude revealed negligible differences for both preparation and adaptation trials. However, a network-level analysis of BOLD coherence revealed that by late learning, response preparation (‘NoGo’) was attributed to a relative focusing of coherence within cortical and basal ganglia networks in both perturbation conditions, demonstrating a common network interaction for establishing arbitrary visuomotor associations. Conversely, late-learning adaptation (‘Go’) was attributed to a focusing of BOLD coherence between a cortical-basal ganglia network in the viscous condition and between a cortical-cerebellar network in the positional condition. Our findings demonstrate that trial-to-trial acquisition of two distinct adaptive responses is attributed not to anatomically segregated regions, but to differential functional interactions within common sensorimotor circuits. PMID:17202232

  13. Precise spatial co-registration in simultaneous fNIRS and fMRI measurements using markers coaxially fixable to the optodes

    NASA Astrophysics Data System (ADS)

    Yamada, Toru; Matsuda, Keiji; Iwano, Takayuki; Umeyama, Shinji

    2014-03-01

    Similar to blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI), functional nearinfrared spectroscopy (fNIRS) observes regional hemodynamic responses associated with neuronal activation. However, the conventional criteria for detecting true positive fNIRS and fMRI signals appear to be based on different understandings of cerebral hemodynamics. Considerable numbers of fNIRS studies have ascribed the increase in oxygenated hemoglobin to a typical sign of functional activation, whereas the corresponding BOLD signal in fMRI directly correlates with a decrease in deoxygenated hemoglobin. This inconsistency requires solution through the simultaneous measurements of fNIRS and fMRI. In practice, however, there remain several technical problems associated with conducting simultaneous measurements with high reproducibility. One issue is the precise spatial registration of NIRS optodes in MR images. We prepared marker containers of an annular shape that can be coaxially fixed to the optode. Liquid paraffin with α-tocopheryl acetate, which exhibits a bright contrast in T1-weighted MR images of human heads, was solidified in each container by adding higher fatty acid. A subject wearing the marker-fixed optodes at parietal area participated in preliminary fNIRS and fMRI experiments; the subject was instructed to execute single-sided hand finger tapping. The positions showed that deoxygenated hemoglobin decreases in fNIRS coincided with the BOLD-positive region in fMRI. The prepared marker is chemically stable and repetitively usable. We believe that this simple method contributes precision to the co-registration of fNIRS and fMRI.

  14. Investigating intrinsic connectivity networks using simultaneous BOLD and CBF measurements.

    PubMed

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

    2014-10-01

    When the sensory cortex is stimulated and directly receiving afferent input, modulations can also be observed in the activity of other brain regions comprising spatially distributed, yet intrinsically connected networks, suggesting that these networks support brain function during task performance. Such networks can exhibit subtle or unpredictable task responses which can pass undetected by conventional general linear modelling (GLM). Additionally, the metabolic demand of these networks in response to stimulation remains incompletely understood. Here, we recorded concurrent BOLD and CBF measurements during median nerve stimulation (MNS) and compared GLM analysis with independent component analysis (ICA) for identifying the spatial, temporal and metabolic properties of responses in the primary sensorimotor cortex (S1/M1), and in the default mode (DMN) and fronto-parietal (FPN) networks. Excellent spatial and temporal agreement was observed between the positive BOLD and CBF responses to MNS detected by GLM and ICA in contralateral S1/M1. Values of the change in cerebral metabolic rate of oxygen consumption (Δ%CMRO2) and the Δ%CMRO2/Δ%CBF coupling ratio were highly comparable when using either GLM analysis or ICA to extract the contralateral S1/M1 responses, validating the use of ICA for estimating changes in CMRO2. ICA identified DMN and FPN network activity that was not detected by GLM analysis. Using ICA, spatially coincident increases/decreases in both BOLD and CBF signals to MNS were found in the FPN/DMN respectively. Calculation of CMRO2 changes in these networks during MNS showed that the Δ%CMRO2/Δ%CBF ratio is comparable between the FPN and S1/M1 but is larger in the DMN than in the FPN, assuming an equal value of the parameter M in the DMN, FPN and S1/M1. This work suggests that metabolism-flow coupling may differ between these two fundamental brain networks, which could originate from differences between task-positive and task-negative fMRI responses

  15. The voice of emotion: an FMRI study of neural responses to angry and happy vocal expressions

    PubMed Central

    van Reekum, Carien M.; Oakes, Terrence R.; Davidson, Richard J.

    2006-01-01

    The human voice is one of the principal conveyers of social and affective communication. Yet relatively little is known about the neural circuitry that supports the recognition of different vocally expressed emotions. We conducted an FMRI study to examine the brain responses to vocal expressions of anger and happiness, and to test whether specific brain regions showed preferential engagement in the processing of one emotion over the other. We also tested the extent to which simultaneously presented facial expressions of the same or different emotions would enhance brain responses, and to what degree such responses depend on attention towards the vocal expression. Forty healthy individuals were scanned while listening to vocal expressions of anger or happiness, while at the same time watching congruent or discrepant facial expressions. Happy voices elicited significantly more activation than angry voices in right anterior and posterior middle temporal gyrus (MTG), left posterior MTG and right inferior frontal gyrus. Furthermore, for the left MTG region, happy voices were related to higher activation only when paired with happy faces. Activation in the left insula, left amygdala and hippocampus, and rostral anterior cingulate cortex showed an effect of selectively attending to the vocal stimuli. Our results identify a network of regions implicated in the processing of vocal emotion, and suggest a particularly salient role for vocal expressions of happiness. PMID:17607327

  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. Quantifying the Microvascular Origin of BOLD-fMRI from First Principles with Two-Photon Microscopy and an Oxygen-Sensitive Nanoprobe

    PubMed Central

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

    2015-01-01

    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

  18. 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.

  19. The effect of intellectual ability on functional activation in a neurodevelopmental disorder: preliminary evidence from multiple fMRI studies in Williams syndrome

    PubMed Central

    2012-01-01

    Background Williams syndrome (WS) is a rare genetic disorder caused by the deletion of approximately 25 genes at 7q11.23 that involves mild to moderate intellectual disability (ID). When using functional magnetic resonance imaging (fMRI) to compare individuals with ID to typically developing individuals, there is a possibility that differences in IQ contribute to between-group differences in BOLD signal. If IQ is correlated with BOLD signal, then group-level analyses should adjust for IQ, or else IQ should be matched between groups. If, however, IQ is not correlated with BOLD signal, no such adjustment or criteria for matching (and exclusion) based on IQ is necessary. Methods In this study, we aimed to test this hypothesis systematically using four extant fMRI datasets in WS. Participants included 29 adult subjects with WS (17 men) demonstrating a wide range of standardized IQ scores (composite IQ mean = 67, SD = 17.2). We extracted average BOLD activation for both cognitive and task-specific anatomically defined regions of interest (ROIs) in each individual and correlated BOLD with composite IQ scores, verbal IQ scores and non-verbal IQ scores in Spearman rank correlation tests. Results Of the 312 correlations performed, only six correlations (2%) in four ROIs reached statistical significance at a P value < 0.01, but none survived correction for multiple testing. All six correlations were positive. Therefore, none supports the hypothesis that IQ is negatively correlated with BOLD response. Conclusions These data suggest that the inclusion of subjects with below normal IQ does not introduce a confounding factor, at least for some types of fMRI studies with low cognitive load. By including subjects who are representative of IQ range for the targeted disorder, findings are more likely to generalize to that population. PMID:23102261

  20. Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia.

    PubMed

    Fryer, Susanna L; Roach, Brian J; Ford, Judith M; Turner, Jessica A; van Erp, Theo G M; Voyvodic, James; Preda, Adrian; Belger, Aysenil; Bustillo, Juan; O'Leary, Daniel; Mueller, Bryon A; Lim, Kelvin O; McEwen, Sarah C; Calhoun, Vince D; Diaz, Michelle; Glover, Gary; Greve, Douglas; Wible, Cynthia G; Vaidya, Jatin; Potkin, Steven G; Mathalon, Daniel H

    2015-11-01

    The amplitude of low-frequency fluctuations (ALFF) in the blood oxygenation level-dependent (BOLD) signal during resting-state fMRI reflects the magnitude of local low-frequency BOLD oscillations, rather than interregional connectivity. ALFF is of interest to studies of cognition because fluctuations in spontaneous intrinsic brain activity relate to, and possibly even constrain, task-evoked brain responses in healthy people. Lower ALFF has been reported in schizophrenia, but the cognitive correlates of these reductions remain unknown. Here, we assess relationships between ALFF and attention and working memory in order to establish the functional relevance of intrinsic BOLD oscillatory power alterations with respect to specific cognitive impairments in schizophrenia. As part of the multisite FBIRN study, resting-state fMRI data were collected from schizophrenia subjects (SZ; n=168) and healthy controls (HC; n=166). Voxelwise fractional ALFF (fALFF), a normalized ALFF measure, was regressed on neuropsychological measures of sustained attention and working memory in SZ and HC to identify regions showing either common slopes across groups or slope differences between groups (all findings p<0.01 height, p<0.05 family-wise error cluster corrected). Poorer sustained attention was associated with smaller fALFF in the left superior frontal cortex and bilateral temporoparietal junction in both groups, with additional relationships in bilateral posterior parietal, posterior cingulate, dorsal anterior cingulate (ACC), and right dorsolateral prefrontal cortex (DLPFC) evident only in SZ. Poorer working memory was associated with smaller fALFF in bilateral ACC/mPFC, DLPFC, and posterior parietal cortex in both groups. Our findings indicate that smaller amplitudes of low-frequency BOLD oscillations during rest, measured by fALFF, were significantly associated with poorer cognitive performance, sometimes similarly in both groups and sometimes only in SZ, in regions known to

  1. 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

  2. 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

  3. 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

  4. Complex relationship between BOLD-fMRI and electrophysiological signals in different olfactory bulb layers.

    PubMed

    Li, Bo; Gong, Ling; Wu, Ruiqi; Li, Anan; Xu, Fuqiang

    2014-07-15

    Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI), one of the most powerful technologies in neuroscience, measures neural activity indirectly. Therefore, systematic correlation of BOLD signals with other neural activity measurements is critical to understanding and then using the technology. Numerous studies have revealed that the BOLD signal is determined by many factors and is better correlated with local field potentials (LFP) than single/multiple unit firing. The relationship between BOLD and LFP signals under higher spatial resolution is complex and remains unclear. Here, changes of BOLD and LFP signals in the glomerular (GL), mitral cell (MCL), and granular cell layers (GCL) of the olfactory bulb were evoked by odor stimulation and sequentially acquired using high-resolution fMRI and electrode array. The experimental results revealed a rather complex relationship between BOLD and LFP signals. Both signal modalities were increased layer-dependently by odor stimulation, but the orders of signal intensity were significantly different: GL>MCL>GCL and GCL>GL>MCL for BOLD and LFP, respectively. During odor stimulation, the temporal features of LFPs were similar for a given band in different layers, but different for different frequency bands in a given layer. The BOLD and LFP signals in the low gamma frequency band correlated the best. This study provides new evidence for the consistency between structure and function in understanding the neurophysiological basis of BOLD signals, but also reminds that caution must be taken in interpreting of BOLD signals in regard to neural activity.

  5. 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

  6. Examining the resting-state vascular connectivity using fMRA in comparison with fMRI: a preliminary study.

    PubMed

    Park, Chan-A; Kang, Chang-Ki; Kim, Young-Bo; Cho, Zang-Hee

    2015-08-01

    This study examined resting-state functional connectivity in the vascular system of the brain using functional magnetic resonance angiography (fMRA) with an ultra-high-field 7 T MRI. Four healthy individuals participated in the functional imaging study using fMRA and functional MRI (fMRI) for determination of vascular and blood oxygenation level-dependent (BOLD) connectivity, respectively. We calculated voxel-wise connectivity maps and measured the correlation coefficients of the region of interest (ROI)-wise connectivity in the resting-state human brain. Z-map in the posterior cingulate cortex showed more correlated voxels in fMRA than fMRI. There was little or weak interhemispheric vascular connectivity using fMRA in the lateral parietal cortex and the lateral temporal cortex. In contrast, both vascular and BOLD interhemispheric correlations in the precentral gyrus were strong. Correlation coefficients for ROI-wise connectivity analysis were statistically different between fMRA and fMRI in the left and right lateral parietal cortex and lateral temporal cortex (P=0.029). Unlike BOLD connectivity, vascular connectivity showed little interhemispheric correlation in the default mode network. These results could provide the vascular connectivity on the basis of arterial response that can only be obtained by fMRA with an ultra-high-field environment along with further studies. Therefore, this method could provide additional and supplementary information for investigating the vascular effect in patients with cerebrovascular disease. PMID:26076337

  7. 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

  8. 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…

  9. Adolescents’ fMRI Activation to a Response Inhibition Task Predicts Future Substance Use

    PubMed Central

    Mahmood, O.M.; Goldenberg, D.; Thayer, R.; Migliorini, R.; Simmons, A.N.; Tapert, S.F.

    2012-01-01

    Background Deficient behavioral regulation may be a risk factor for substance use disorders in adolescents. Abnormalities in brain regions critical to cognitive control have been linked to more intense and problematic future substance use (e.g., (Durazzo, Gazdzinski, Mon, & Meyerhoff, 2010; Falk, Berkman, Whalen, & Lieberman, 2011; Paulus, Tapert, & Schuckit, 2005). The goal of this study was to examine the degree to which brain response to an inhibition task measured in mid-adolescence can predict substance use 18 months later. Method Adolescents aged 16–19 (N=80) performed a go/no-go response inhibition task during fMRI at project baseline, and were followed 18 months later with a detailed interview on substance use and dependence symptoms. Participants were 39 high frequency users and 41 demographically similar low frequency users (458 versus 2 average lifetime drug use occasions at baseline, respectively). Results Across all subjects, no-go trials produced significant increases in neural response in the ventromedial prefrontal cortex and a region including the left angular and supramarginal gyri (p(FWE)<.01, cluster threshold ≥30 voxels). Less ventromedial prefrontal activation but more left angular gyrus activation predicted higher levels of substance use and dependence symptoms in the following 18 months, particularly for those who were high frequency users in mid-adolescence (p<.05). Conclusions These findings are consistent with studies showing that impairments in cognitive control have strong associations with substance use. We found a predictive relationship between atypical activation patterns at baseline and substance use behavior 18 months later, particularly among adolescents with histories of previous heavy use. PMID:23006248

  10. The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories.

    PubMed

    Carhart-Harris, R L; Wall, M B; Erritzoe, D; Kaelen, M; Ferguson, B; De Meer, I; Tanner, M; Bloomfield, M; Williams, T M; Bolstridge, M; Stewart, L; Morgan, C J; Newbould, R D; Feilding, A; Curran, H V; Nutt, D J

    2014-04-01

    3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine-releaser that is widely used as a recreational drug. Preliminary work has supported the potential of MDMA in psychotherapy for post-traumatic stress disorder (PTSD). The neurobiological mechanisms underlying its putative efficacy are, however, poorly understood. Psychotherapy for PTSD usually requires that patients revisit traumatic memories, and it has been argued that this is easier to do under MDMA. Functional magnetic resonance imaging (fMRI) was used to investigate the effect of MDMA on recollection of favourite and worst autobiographical memories (AMs). Nineteen participants (five females) with previous experience with MDMA performed a blocked AM recollection (AMR) paradigm after ingestion of 100 mg of MDMA-HCl or ascorbic acid (placebo) in a double-blind, repeated-measures design. Memory cues describing participants' AMs were read by them in the scanner. Favourite memories were rated as significantly more vivid, emotionally intense and positive after MDMA than placebo and worst memories were rated as less negative. Functional MRI data from 17 participants showed robust activations to AMs in regions known to be involved in AMR. There was also a significant effect of memory valence: hippocampal regions showed preferential activations to favourite memories and executive regions to worst memories. MDMA augmented activations to favourite memories in the bilateral fusiform gyrus and somatosensory cortex and attenuated activations to worst memories in the left anterior temporal cortex. These findings are consistent with a positive emotional-bias likely mediated by MDMA's pro-monoaminergic pharmacology.

  11. 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

  12. 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.

  13. 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

  14. Heterogeneity of stimulus-specific response modification-an fMRI study on neuroplasticity.

    PubMed

    Lahr, Jacob; Peter, Jessica; Bach, Michael; Mader, Irina; Nissen, Christoph; Normann, Claus; Kaller, Christoph P; Klöppel, Stefan

    2014-01-01

    Long-term potentiation (LTP) is a key element of synaptic plasticity. At the macroscopic level, similar effects can be induced in the human brain using repetitive stimulation with identical stimuli. High-frequency stimulation (HFS) can increase neuronal responses whereas low-frequency stimulation may produce the opposite effect. Optimal stimulation frequencies and characteristics for inducing stimulus-specific response modification (SRM) differ substantially from those applied to brain tissue slices but have been explored in recent studies. In contrast, the individual manifestation of this effect in terms of its spatial location and extent are unclear. Using functional magnetic resonance imaging (fMRI) in 18 subjects (mean age 25.3 years), we attempted to induce LTP-like effects by HFS with checkerboard flashes at 9 Hz for 120 s. As expected, flashes induced strong activation in primary and secondary visual cortices. Contrary to our expectations, we found clusters of decreased activations induced by pattern flashes after HFS in the primary and secondary visual cortices. On the level of the individual subject, some showed significantly increased activations in the post-HFS session while the majority showed significant decreases. The locations of areas showing altered activations before and after HFS were only partly overlapping. No association between location, extent and direction of the HFS-effect was observed. The findings are unexpected in the light of existing HFS-studies, but mirror the high inter-subject variability, concerning even the directionality of the induced effects shown for other indices of LTP-like plasticity in the human brain. As this variability is not observed in LTP at the cellular level, a better understanding of LTP-like mechanisms on the macroscopic level is essential for establishing tools to quantify individual synaptic plasticity in-vivo. PMID:25249962

  15. 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

  16. 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

  17. 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…

  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. 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.

  20. 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

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

    PubMed

    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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. Functional magnetic resonance imaging blood oxygenation level-dependent signal and magnetoencephalography evoked responses yield different neural functionality in reading.

    PubMed

    Vartiainen, Johanna; Liljeström, Mia; Koskinen, Miika; Renvall, Hanna; Salmelin, Riitta

    2011-01-19

    It is often implicitly assumed that the neural activation patterns revealed by hemodynamic methods, such as functional magnetic resonance imaging (fMRI), and electrophysiological methods, such as magnetoencephalography (MEG) and electroencephalography (EEG), are comparable. In early sensory processing that seems to be the case, but the assumption may not be correct in high-level cognitive tasks. For example, MEG and fMRI literature of single-word reading suggests differences in cortical activation, but direct comparisons are lacking. Here, while the same human participants performed the same reading task, analysis of MEG evoked responses and fMRI blood oxygenation level-dependent (BOLD) signals revealed marked functional and spatial differences in several cortical areas outside the visual cortex. Divergent patterns of activation were observed in the frontal and temporal cortex, in accordance with previous separate MEG and fMRI studies of reading. Furthermore, opposite stimulus effects in the MEG and fMRI measures were detected in the left occipitotemporal cortex: MEG evoked responses were stronger to letter than symbol strings, whereas the fMRI BOLD signal was stronger to symbol than letter strings. The EEG recorded simultaneously during MEG and fMRI did not indicate neurophysiological differences that could explain the observed functional discrepancies between the MEG and fMRI results. Acknowledgment of the complementary nature of hemodynamic and electrophysiological measures, as reported here in a cognitive task using evoked response analysis in MEG and BOLD signal analysis in fMRI, represents an essential step toward an informed use of multimodal imaging that reaches beyond mere combination of location and timing of neural activation.

  7. Dynamic and static contributions of the cerebrovasculature to the resting-state BOLD signal.

    PubMed

    Tak, Sungho; Wang, Danny J J; Polimeni, Jonathan R; Yan, Lirong; Chen, J Jean

    2014-01-01

    Functional magnetic resonance imaging (fMRI) in the resting state, particularly fMRI based on the blood-oxygenation level-dependent (BOLD) signal, has been extensively used to measure functional connectivity in the brain. However, the mechanisms of vascular regulation that underlie the BOLD fluctuations during rest are still poorly understood. In this work, using dual-echo pseudo-continuous arterial spin labeling and MR angiography (MRA), we assess the spatio-temporal contribution of cerebral blood flow (CBF) to the resting-state BOLD signals and explore how the coupling of these signals is associated with regional vasculature. Using a general linear model analysis, we found that statistically significant coupling between resting-state BOLD and CBF fluctuations is highly variable across the brain, but the coupling is strongest within the major nodes of established resting-state networks, including the default-mode, visual, and task-positive networks. Moreover, by exploiting MRA-derived large vessel (macrovascular) volume fraction, we found that the degree of BOLD-CBF coupling significantly decreased as the ratio of large vessels to tissue volume increased. These findings suggest that the portion of resting-state BOLD fluctuations at the sites of medium-to-small vessels (more proximal to local neuronal activity) is more closely regulated by dynamic regulations in CBF, and that this CBF regulation decreases closer to large veins, which are more distal to neuronal activity.

  8. Integration of EEG source imaging and fMRI during continuous viewing of natural movies.

    PubMed

    Whittingstall, Kevin; Bartels, Andreas; Singh, Vanessa; Kwon, Soyoung; Logothetis, Nikos K

    2010-10-01

    Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are noninvasive neuroimaging tools which can be used to measure brain activity with excellent temporal and spatial resolution, respectively. By combining the neural and hemodynamic recordings from these modalities, we can gain better insight into how and where the brain processes complex stimuli, which may be especially useful in patients with different neural diseases. However, due to their vastly different spatial and temporal resolutions, the integration of EEG and fMRI recordings is not always straightforward. One fundamental obstacle has been that paradigms used for EEG experiments usually rely on event-related paradigms, while fMRI is not limited in this regard. Therefore, here we ask whether one can reliably localize stimulus-driven EEG activity using the continuously varying feature intensities occurring in natural movie stimuli presented over relatively long periods of time. Specifically, we asked whether stimulus-driven aspects in the EEG signal would be co-localized with the corresponding stimulus-driven BOLD signal during free viewing of a movie. Secondly, we wanted to integrate the EEG signal directly with the BOLD signal, by estimating the underlying impulse response function (IRF) that relates the BOLD signal to the underlying current density in the primary visual area (V1). We made sequential fMRI and 64-channel EEG recordings in seven subjects who passively watched 2-min-long segments of a James Bond movie. To analyze EEG data in this natural setting, we developed a method based on independent component analysis (ICA) to reject EEG artifacts due to blinks, subject movement, etc., in a way unbiased by human judgment. We then calculated the EEG source strength of this artifact-free data at each time point of the movie within the entire brain volume using low-resolution electromagnetic tomography (LORETA). This provided for every voxel in the brain (i.e., in 3D space) an

  9. Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation.

    PubMed

    Siegel, Andrew M; Culver, Joseph P; Mandeville, Joseph B; Boas, David A

    2003-05-21

    The time courses of oxyhaemoglobin ([HbO2]), deoxyhaemoglobin ([HbR]) and total haemoglobin ([HbT]) concentration changes following cortical activation in rats by electrical forepaw stimulation were measured using diffuse optical tomography (DOT) and compared to similar measurements performed previously with fMRI at 2.0 T and 4.7 T. We also explored the qualitative effects of varying stimulus parameters on the temporal evolution of the hemodynamic response. DOT images were reconstructed at a depth of 1.5 mm over a 1 cm square area from 2 mm anterior to bregma to 8 mm posterior to bregma. The measurement set included 9 sources and 16 detectors with an imaging frame rate of 10 Hz. Both DOT [HbR] and [HbO2] time courses were compared to the fMRI BOLD time course during stimulation, and the DOT [HbT] time course was compared to the fMRI cerebral plasma volume (CPV) time course. We believe that DOT and fMRI can provide similar temporal information for both blood volume and deoxyhaemoglobin changes, which helps to cross-validate these two techniques and to demonstrate that DOT can be useful as a complementary modality to fMRI for investigating the hemodynamic response to neuronal activity.

  10. Spontaneous EEG alpha oscillation interacts with positive and negative BOLD responses in the visual-auditory cortices and default-mode network.

    PubMed

    Mayhew, Stephen D; Ostwald, Dirk; Porcaro, Camillo; Bagshaw, Andrew P

    2013-08-01

    The human brain is continually, dynamically active and spontaneous fluctuations in this activity play a functional role in affecting both behavioural and neuronal responses. However, the mechanisms through which this occurs remain poorly understood. Simultaneous EEG-fMRI is a promising technique to study how spontaneous activity modulates the brain's response to stimulation, as temporal indices of ongoing cortical excitability can be integrated with spatially localised evoked responses. Here we demonstrate an interaction between the ongoing power of the electrophysiological alpha oscillation and the magnitude of both positive (PBR) and negative (NBR) fMRI responses to two contrasts of visual checkerboard reversal. Furthermore, the amplitude of pre-stimulus EEG alpha-power significantly modulated the amplitude and shape of subsequent PBR and NBR to the visual stimulus. A nonlinear reduction of visual PBR and an enhancement of auditory NBR and default-mode network NBR were observed in trials preceded by high alpha-power. These modulated areas formed a functionally connected network during a separate resting-state recording. Our findings suggest that the "baseline" state of the brain exhibits considerable trial-to-trial variability which arises from fluctuations in the balance of cortical inhibition/excitation that are represented by respective increases/decreases in the power of the EEG alpha oscillation. The consequence of this spontaneous electrophysiological variability is modulated amplitudes of both PBR and NBR to stimulation. Fluctuations in alpha-power may subserve a functional relationship in the visual-auditory network, acting as mediator for both short and long-range cortical inhibition, the strength of which is represented in part by NBR. PMID:23507378

  11. fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity.

    PubMed

    Paret, Christian; Ruf, Matthias; Gerchen, Martin Fungisai; Kluetsch, Rosemarie; Demirakca, Traute; Jungkunz, Martin; Bertsch, Katja; Schmahl, Christian; Ende, Gabriele

    2016-01-15

    Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: p<.05 at cluster-level). Task-dependent increases in amygdala-vmPFC connectivity were predicted by picture arousal (β=.59, p<.05). A dynamic causal modeling analysis with Bayesian model selection aimed at further characterizing the underlying causal structure and favored a bottom-up model assuming predominant information flow from the amygdala to the vmPFC (xp=.90). The results were complemented by the observation of task-dependent alterations in functional connectivity of the vmPFC with the visual cortex and the ventrolateral PFC in the experimental group (Condition t-contrast: p<.05 at cluster-level). Taken together, the results underscore the potential of amygdala fMRI neurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation.

  12. Brain oxygenation responses to an autonomic challenge: a quantitative fMRI investigation of the Valsalva manoeuvre.

    PubMed

    Bohr, Iwo; McDonald, Claire; He, Jiabao; Kerr, Simon; Newton, Julia L; Blamire, Andrew M

    2015-10-01

    In late age, the autonomic nervous system (ANS) has diminished ability to maintain physiological homeostasis in the brain in response to challenges such as to systemic blood pressure changes caused by standing. We devised an fMRI experiment aiming to map the cerebral effects of an ANS challenge (Valsalva manoeuvre (VM)). We used dual-echo fMRI to measure the effective transverse relaxation rate (R2*, which is inversely proportional to brain tissue oxygenation levels) in 45 elderly subjects (median age 80 years old, total range 75-89) during performance of the VM. In addition, we collected fluid-attenuated inversion recovery (FLAIR) data from which we quantified white matter hyperintensity (WMH) volumes. We conducted voxelwise analysis of the dynamic changes in R2* during the VM to determine the distribution of oxygenation changes due to the autonomic stressor. In white matter, we observed significant decreases in oxygenation levels. These effects were predominantly located in posterior white matter and to a lesser degree in the right anterior brain, both concentrated around the border zones (watersheds) between cerebral perfusion territories. These areas are known to be particularly vulnerable to hypoxia and are prone to formation of white matter hyperintensities. Although we observed overlap between localisation of WMH and triggered deoxygenation on the group level, we did not find significant association between these independent variables using subjectwise statistics. This could suggest other than recurrent transient hypoxia mechanisms causing/contributing to the formation of WMH.

  13. fMRI investigation of response inhibition, emotion, impulsivity, and clinical high-risk behavior in adolescents

    PubMed Central

    Brown, Matthew R. G.; Benoit, James R. A.; Juhás, Michal; Dametto, Ericson; Tse, Tiffanie T.; MacKay, Marnie; Sen, Bhaskar; Carroll, Alan M.; Hodlevskyy, Oleksandr; Silverstone, Peter H.; Dolcos, Florin; Dursun, Serdar M.; Greenshaw, Andrew J.

    2015-01-01

    High-risk behavior in adolescents is associated with injury, mental health problems, and poor outcomes in later life. Improved understanding of the neurobiology of high-risk behavior and impulsivity shows promise for informing clinical treatment and prevention as well as policy to better address high-risk behavior. We recruited 21 adolescents (age 14–17) with a wide range of high-risk behavior tendencies, including medically high-risk participants recruited from psychiatric clinics. Risk tendencies were assessed using the Adolescent Risk Behavior Screen (ARBS). ARBS risk scores correlated highly (0.78) with impulsivity scores from the Barratt Impulsivity scale (BIS). Participants underwent 4.7 Tesla functional magnetic resonance imaging (fMRI) while performing an emotional Go/NoGo task. This task presented an aversive or neutral distractor image simultaneously with each Go or NoGo stimulus. Risk behavior and impulsivity tendencies exhibited similar but not identical associations with fMRI activation patterns in prefrontal brain regions. We interpret these results as reflecting differences in response inhibition, emotional stimulus processing, and emotion regulation in relation to participant risk behavior tendencies and impulsivity levels. The results are consistent with high impulsivity playing an important role in determining high risk tendencies in this sample containing clinically high-risk adolescents. PMID:26483645

  14. Neural correlates of experienced moral emotion: an fMRI investigation of emotion in response to prejudice feedback.

    PubMed

    Fourie, Melike M; Thomas, Kevin G F; Amodio, David M; Warton, Christopher M R; Meintjes, Ernesta M

    2014-01-01

    Guilt, shame, and embarrassment are quintessential moral emotions with important regulatory functions for the individual and society. Moral emotions are, however, difficult to study with neuroimaging methods because their elicitation is more intricate than that of basic emotions. Here, using functional MRI (fMRI), we employed a novel social prejudice paradigm to examine specific brain regions associated with real-time moral emotion, focusing on guilt and related moral-negative emotions. The paradigm induced intense moral-negative emotion (primarily guilt) in 22 low-prejudice individuals through preprogrammed feedback indicating implicit prejudice against Black and disabled people. fMRI data indicated that this experience of moral-negative emotion was associated with increased activity in anterior paralimbic structures, including the anterior cingulate cortex (ACC) and anterior insula, in addition to areas associated with mentalizing, including the dorsomedial prefrontal cortex, posterior cingulate cortex, and precuneus. Of significance was prominent conflict-related activity in the supragenual ACC, which is consistent with theories proposing an association between acute guilt and behavioral inhibition. Finally, a significant negative association between self-reported guilt and neural activity in the pregenual ACC suggested a role of self-regulatory processes in response to moral-negative affect. These findings are consistent with the multifaceted self-regulatory functions of moral-negative emotions in social behavior.

  15. Investigating brain response to music: a comparison of different fMRI acquisition schemes.

    PubMed

    Mueller, Karsten; Mildner, Toralf; Fritz, Thomas; Lepsien, Jöran; Schwarzbauer, Christian; Schroeter, Matthias L; Möller, Harald E

    2011-01-01

    Functional magnetic resonance imaging (fMRI) in auditory experiments is a challenge, because the scanning procedure produces considerable noise that can interfere with the auditory paradigm. The noise might either mask the auditory material presented, or interfere with stimuli designed to evoke emotions because it sounds loud and rather unpleasant. Therefore, scanning paradigms that allow interleaved auditory stimulation and image acquisition appear to be advantageous. The sparse temporal sampling (STS) technique uses a very long repetition time in order to achieve a stimulus presentation in the absence of scanner noise. Although only relatively few volumes are acquired for the resulting data sets, there have been recent studies where this method has furthered remarkable results. A new development is the interleaved silent steady state (ISSS) technique. Compared with STS, this method is capable of acquiring several volumes in the time frame between the auditory trials (while the magnetization is kept in a steady state during stimulus presentation). In order to draw conclusions about the optimum fMRI procedure with auditory stimulation, different echo-planar imaging (EPI) acquisition schemes were compared: Continuous scanning, STS, and ISSS. The total acquisition time of each sequence was adjusted to about 12.5 min. The results indicate that the ISSS approach exhibits the highest sensitivity in detecting subtle activity in sub-cortical brain regions.

  16. Objective Bayesian fMRI analysis-a pilot study in different clinical environments.

    PubMed

    Magerkurth, Joerg; Mancini, Laura; Penny, William; Flandin, Guillaume; Ashburner, John; Micallef, Caroline; De Vita, Enrico; Daga, Pankaj; White, Mark J; Buckley, Craig; Yamamoto, Adam K; Ourselin, Sebastien; Yousry, Tarek; Thornton, John S; Weiskopf, Nikolaus

    2015-01-01

    Functional MRI (fMRI) used for neurosurgical planning delineates functionally eloquent brain areas by time-series analysis of task-induced BOLD signal changes. Commonly used frequentist statistics protect against false positive results based on a p-value threshold. In surgical planning, false negative results are equally if not more harmful, potentially masking true brain activity leading to erroneous resection of eloquent regions. Bayesian statistics provides an alternative framework, categorizing areas as activated, deactivated, non-activated or with low statistical confidence. This approach has not yet found wide clinical application partly due to the lack of a method to objectively define an effect size threshold. We implemented a Bayesian analysis framework for neurosurgical planning fMRI. It entails an automated effect-size threshold selection method for posterior probability maps accounting for inter-individual BOLD response differences, which was calibrated based on the frequentist results maps thresholded by two clinical experts. We compared Bayesian and frequentist analysis of passive-motor fMRI data from 10 healthy volunteers measured on a pre-operative 3T and an intra-operative 1.5T MRI scanner. As a clinical case study, we tested passive motor task activation in a brain tumor patient at 3T under clinical conditions. With our novel effect size threshold method, the Bayesian analysis revealed regions of all four categories in the 3T data. Activated region foci and extent were consistent with the frequentist analysis results. In the lower signal-to-noise ratio 1.5T intra-operative scanner data, Bayesian analysis provided improved brain-activation detection sensitivity compared with the frequentist analysis, albeit the spatial extents of the activations were smaller than at 3T. Bayesian analysis of fMRI data using operator-independent effect size threshold selection may improve the sensitivity and certainty of information available to guide neurosurgery.

  17. Objective Bayesian fMRI analysis—a pilot study in different clinical environments

    PubMed Central

    Magerkurth, Joerg; Mancini, Laura; Penny, William; Flandin, Guillaume; Ashburner, John; Micallef, Caroline; De Vita, Enrico; Daga, Pankaj; White, Mark J.; Buckley, Craig; Yamamoto, Adam K.; Ourselin, Sebastien; Yousry, Tarek; Thornton, John S.; Weiskopf, Nikolaus

    2015-01-01

    Functional MRI (fMRI) used for neurosurgical planning delineates functionally eloquent brain areas by time-series analysis of task-induced BOLD signal changes. Commonly used frequentist statistics protect against false positive results based on a p-value threshold. In surgical planning, false negative results are equally if not more harmful, potentially masking true brain activity leading to erroneous resection of eloquent regions. Bayesian statistics provides an alternative framework, categorizing areas as activated, deactivated, non-activated or with low statistical confidence. This approach has not yet found wide clinical application partly due to the lack of a method to objectively define an effect size threshold. We implemented a Bayesian analysis framework for neurosurgical planning fMRI. It entails an automated effect-size threshold selection method for posterior probability maps accounting for inter-individual BOLD response differences, which was calibrated based on the frequentist results maps thresholded by two clinical experts. We compared Bayesian and frequentist analysis of passive-motor fMRI data from 10 healthy volunteers measured on a pre-operative 3T and an intra-operative 1.5T MRI scanner. As a clinical case study, we tested passive motor task activation in a brain tumor patient at 3T under clinical conditions. With our novel effect size threshold method, the Bayesian analysis revealed regions of all four categories in the 3T data. Activated region foci and extent were consistent with the frequentist analysis results. In the lower signal-to-noise ratio 1.5T intra-operative scanner data, Bayesian analysis provided improved brain-activation detection sensitivity compared with the frequentist analysis, albeit the spatial extents of the activations were smaller than at 3T. Bayesian analysis of fMRI data using operator-independent effect size threshold selection may improve the sensitivity and certainty of information available to guide neurosurgery

  18. The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people.

    PubMed

    Francis, S T; Head, K; Morris, P G; Macdonald, I A

    2006-01-01

    Flavanols are the main flavonoids found in cocoa and chocolate, and can be especially abundant in certain cocoas. Research over the past decade has identified flavanols as showing diverse beneficial physiologic and antioxidant effects, particularly in context of vascular function. The present study employed functional magnetic resonance imaging based on blood oxygenation level-dependent (BOLD) contrast to explore the effect of flavanols on the human brain. Magnetic resonance imaging was used to measure BOLD responses to a cognitive task in 16 healthy young subjects. The data presented show an increase in the BOLD signal intensity in response to a cognitive task following ingestion of flavanol-rich cocoa (5 days of 150 mg of cocoa flavanols). This may arise either as a result of altered neuronal activity, or a change in vascular responsiveness, or both--the net effect then being dependent on which of the two effects is dominant. No significant effects were evident in behavioral reaction times, switch cost, and heart rate after consumption of this moderate dose of cocoa flavanols. A pilot study evaluated the relationship between cerebral blood flow and a single acute dose (450 mg flavanols) of flavanol-rich cocoa and showed that flavanol-rich cocoa can increase the cerebral blood flow to gray matter, suggesting the potential of cocoa flavanols for treatment of vascular impairment, including dementia and strokes, and thus for maintaining cardiovascular health.

  19. Identification of Voxels Confounded by Venous Signals Using Resting-State fMRI Functional Connectivity Graph Community Identification.

    PubMed

    Kalcher, Klaudius; Boubela, Roland N; Huf, Wolfgang; Našel, Christian; Moser, Ewald

    2015-01-01

    Identifying venous voxels in fMRI datasets is important to increase the specificity of fMRI analyses to microvasculature in the vicinity of the neural processes triggering the BOLD response. This is, however, difficult to achieve in particular in typical studies where magnitude images of BOLD EPI are the only data available. In this study, voxelwise functional connectivity graphs were computed on minimally preprocessed low TR (333 ms) multiband resting-state fMRI data, using both high positive and negative correlations to define edges between nodes (voxels). A high correlation threshold for binarization ensures that most edges in the resulting sparse graph reflect the high coherence of signals in medium to large veins. Graph clustering based on the optimization of modularity was then employed to identify clusters of coherent voxels in this graph, and all clusters of 50 or more voxels were then interpreted as corresponding to medium to large veins. Indeed, a comparison with SWI reveals that 75.6±5.9% of voxels within these large clusters overlap with veins visible in the SWI image or lie outside the brain parenchyma. Some of the remaining differences between the two modalities can be explained by imperfect alignment or geometric distortions between the two images. Overall, the graph clustering based method for identifying venous voxels has a high specificity as well as the additional advantages of being computed in the same voxel grid as the fMRI dataset itself and not needing any additional data beyond what is usually acquired (and exported) in standard fMRI experiments. PMID:26733787

  20. Identification of Voxels Confounded by Venous Signals Using Resting-State fMRI Functional Connectivity Graph Community Identification

    PubMed Central

    Kalcher, Klaudius; Boubela, Roland N.; Huf, Wolfgang; Našel, Christian; Moser, Ewald

    2015-01-01

    Identifying venous voxels in fMRI datasets is important to increase the specificity of fMRI analyses to microvasculature in the vicinity of the neural processes triggering the BOLD response. This is, however, difficult to achieve in particular in typical studies where magnitude images of BOLD EPI are the only data available. In this study, voxelwise functional connectivity graphs were computed on minimally preprocessed low TR (333 ms) multiband resting-state fMRI data, using both high positive and negative correlations to define edges between nodes (voxels). A high correlation threshold for binarization ensures that most edges in the resulting sparse graph reflect the high coherence of signals in medium to large veins. Graph clustering based on the optimization of modularity was then employed to identify clusters of coherent voxels in this graph, and all clusters of 50 or more voxels were then interpreted as corresponding to medium to large veins. Indeed, a comparison with SWI reveals that 75.6±5.9% of voxels within these large clusters overlap with veins visible in the SWI image or lie outside the brain parenchyma. Some of the remaining differences between the two modalities can be explained by imperfect alignment or geometric distortions between the two images. Overall, the graph clustering based method for identifying venous voxels has a high specificity as well as the additional advantages of being computed in the same voxel grid as the fMRI dataset itself and not needing any additional data beyond what is usually acquired (and exported) in standard fMRI experiments. PMID:26733787

  1. Identification of Voxels Confounded by Venous Signals Using Resting-State fMRI Functional Connectivity Graph Community Identification.

    PubMed

    Kalcher, Klaudius; Boubela, Roland N; Huf, Wolfgang; Našel, Christian; Moser, Ewald

    2015-01-01

    Identifying venous voxels in fMRI datasets is important to increase the specificity of fMRI analyses to microvasculature in the vicinity of the neural processes triggering the BOLD response. This is, however, difficult to achieve in particular in typical studies where magnitude images of BOLD EPI are the only data available. In this study, voxelwise functional connectivity graphs were computed on minimally preprocessed low TR (333 ms) multiband resting-state fMRI data, using both high positive and negative correlations to define edges between nodes (voxels). A high correlation threshold for binarization ensures that most edges in the resulting sparse graph reflect the high coherence of signals in medium to large veins. Graph clustering based on the optimization of modularity was then employed to identify clusters of coherent voxels in this graph, and all clusters of 50 or more voxels were then interpreted as corresponding to medium to large veins. Indeed, a comparison with SWI reveals that 75.6±5.9% of voxels within these large clusters overlap with veins visible in the SWI image or lie outside the brain parenchyma. Some of the remaining differences between the two modalities can be explained by imperfect alignment or geometric distortions between the two images. Overall, the graph clustering based method for identifying venous voxels has a high specificity as well as the additional advantages of being computed in the same voxel grid as the fMRI dataset itself and not needing any additional data beyond what is usually acquired (and exported) in standard fMRI experiments.

  2. A studyforrest extension, simultaneous fMRI and eye gaze recordings during prolonged natural stimulation.

    PubMed

    Hanke, Michael; Adelhöfer, Nico; Kottke, Daniel; Iacovella, Vittorio; Sengupta, Ayan; Kaule, Falko R; Nigbur, Roland; Waite, Alexander Q; Baumgartner, Florian; Stadler, Jörg

    2016-10-25

    Here we present an update of the studyforrest (http://studyforrest.org) dataset that complements the previously released functional magnetic resonance imaging (fMRI) data for natural language processing with a new two-hour 3 Tesla fMRI acquisition while 15 of the original participants were shown an audio-visual version of the stimulus motion picture. We demonstrate with two validation analyses that these new data support modeling specific properties of the complex natural stimulus, as well as a substantial within-subject BOLD response congruency in brain areas related to the processing of auditory inputs, speech, and narrative when compared to the existing fMRI data for audio-only stimulation. In addition, we provide participants' eye gaze location as recorded simultaneously with fMRI, and an additional sample of 15 control participants whose eye gaze trajectories for the entire movie were recorded in a lab setting-to enable studies on attentional processes and comparative investigations on the potential impact of the stimulation setting on these processes.

  3. Fixation-related FMRI analysis in the domain of reading research: using self-paced eye movements as markers for hemodynamic brain responses during visual letter string processing.

    PubMed

    Richlan, Fabio; Gagl, Benjamin; Hawelka, Stefan; Braun, Mario; Schurz, Matthias; Kronbichler, Martin; Hutzler, Florian

    2014-10-01

    The present study investigated the feasibility of using self-paced eye movements during reading (measured by an eye tracker) as markers for calculating hemodynamic brain responses measured by functional magnetic resonance imaging (fMRI). Specifically, we were interested in whether the fixation-related fMRI analysis approach was sensitive enough to detect activation differences between reading material (words and pseudowords) and nonreading material (line and unfamiliar Hebrew strings). Reliable reading-related activation was identified in left hemisphere superior temporal, middle temporal, and occipito-temporal regions including the visual word form area (VWFA). The results of the present study are encouraging insofar as fixation-related analysis could be used in future fMRI studies to clarify some of the inconsistent findings in the literature regarding the VWFA. Our study is the first step in investigating specific visual word recognition processes during self-paced natural sentence reading via simultaneous eye tracking and fMRI, thus aiming at an ecologically valid measurement of reading processes. We provided the proof of concept and methodological framework for the analysis of fixation-related fMRI activation in the domain of reading research.

  4. Voluntary Explicit versus Involuntary Conceptual Memory Are Associated with Dissociable fMRI Responses in Hippocampus, Amygdala, and Parietal Cortex for Emotional and Neutral Word Pairs

    ERIC Educational Resources Information Center

    Ramponi, Cristina; Barnard, Philip J.; Kherif, Ferath; Henson, Richard N.

    2011-01-01

    Although functional neuroimaging studies have supported the distinction between explicit and implicit forms of memory, few have matched explicit and implicit tests closely, and most of these tested perceptual rather than conceptual implicit memory. We compared event-related fMRI responses during an intentional test, in which a group of…

  5. Event-Related Fmri Evidence of Frontotemporal Involvement in Aberrant Response Inhibition and Task Switching in Attention-Deficit/hyperactivity Disorder.

    ERIC Educational Resources Information Center

    Tamm, Leanne; Menon, Vinod; Ringel, Jessica; Reiss, Allan L.

    2004-01-01

    Objective: Response inhibition deficits are characteristic of individuals with attention-deficit/hyperactivity disorder (ADHD). Previous functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of this dysfunction have used block designs, making it difficult to disentangle activation differences specifically related…

  6. Real-time decoding of brain responses to visuospatial attention using 7T fMRI.

    PubMed

    Andersson, Patrik; Pluim, Josien P W; Siero, Jeroen C W; Klein, Stefan; Viergever, Max A; Ramsey, Nick F

    2011-01-01

    Brain-Computer interface technologies mean to create new communication channels between our mind and our environment, independent of the motor system, by detecting and classifying self regulation of local brain activity. BCIs can provide patients with severe paralysis a means to communicate and to live more independent lives. There has been a growing interest in using invasive recordings for BCI to improve the signal quality. This also potentially gives access to new control strategies previously inaccessible by non-invasive methods. However, before surgery, the best implantation site needs to be determined. The blood-oxygen-level dependent signal changes measured with fMRI have been shown to agree well spatially with those found with invasive electrodes, and are the best option for pre-surgical localization. We show, using real-time fMRI at 7T, that eye movement-independent visuospatial attention can be used as a reliable control strategy for BCIs. At this field strength even subtle signal changes can be detected in single trials thanks to the high contrast-to-noise ratio. A group of healthy subjects were instructed to move their attention between three (two peripheral and one central) spatial target regions while keeping their gaze fixated at the center. The activated regions were first located and thereafter the subjects were given real-time feedback based on the activity in these regions. All subjects managed to regulate local brain areas without training, which suggests that visuospatial attention is a promising new target for intracranial BCI. ECoG data recorded from one epilepsy patient showed that local changes in gamma-power can be used to separate the three classes. PMID:22110702

  7. Audiovisual non-verbal dynamic faces elicit converging fMRI and ERP responses.

    PubMed

    Brefczynski-Lewis, Julie; Lowitszch, Svenja; Parsons, Michael; Lemieux, Susan; Puce, Aina

    2009-05-01

    In an everyday social interaction we automatically integrate another's facial movements and vocalizations, be they linguistic or otherwise. This requires audiovisual integration of a continual barrage of sensory input-a phenomenon previously well-studied with human audiovisual speech, but not with non-verbal vocalizations. Using both fMRI and ERPs, we assessed neural activity to viewing and listening to an animated female face producing non-verbal, human vocalizations (i.e. coughing, sneezing) under audio-only (AUD), visual-only (VIS) and audiovisual (AV) stimulus conditions, alternating with Rest (R). Underadditive effects occurred in regions dominant for sensory processing, which showed AV activation greater than the dominant modality alone. Right posterior temporal and parietal regions showed an AV maximum in which AV activation was greater than either modality alone, but not greater than the sum of the unisensory conditions. Other frontal and parietal regions showed Common-activation in which AV activation was the same as one or both unisensory conditions. ERP data showed an early superadditive effect (AV > AUD + VIS, no rest), mid-range underadditive effects for auditory N140 and face-sensitive N170, and late AV maximum and common-activation effects. Based on convergence between fMRI and ERP data, we propose a mechanism where a multisensory stimulus may be signaled or facilitated as early as 60 ms and facilitated in sensory-specific regions by increasing processing speed (at N170) and efficiency (decreasing amplitude in auditory and face-sensitive cortical activation and ERPs). Finally, higher-order processes are also altered, but in a more complex fashion.

  8. Audiovisual non-verbal dynamic faces elicit converging fMRI and ERP responses.

    PubMed

    Brefczynski-Lewis, Julie; Lowitszch, Svenja; Parsons, Michael; Lemieux, Susan; Puce, Aina

    2009-05-01

    In an everyday social interaction we automatically integrate another's facial movements and vocalizations, be they linguistic or otherwise. This requires audiovisual integration of a continual barrage of sensory input-a phenomenon previously well-studied with human audiovisual speech, but not with non-verbal vocalizations. Using both fMRI and ERPs, we assessed neural activity to viewing and listening to an animated female face producing non-verbal, human vocalizations (i.e. coughing, sneezing) under audio-only (AUD), visual-only (VIS) and audiovisual (AV) stimulus conditions, alternating with Rest (R). Underadditive effects occurred in regions dominant for sensory processing, which showed AV activation greater than the dominant modality alone. Right posterior temporal and parietal regions showed an AV maximum in which AV activation was greater than either modality alone, but not greater than the sum of the unisensory conditions. Other frontal and parietal regions showed Common-activation in which AV activation was the same as one or both unisensory conditions. ERP data showed an early superadditive effect (AV > AUD + VIS, no rest), mid-range underadditive effects for auditory N140 and face-sensitive N170, and late AV maximum and common-activation effects. Based on convergence between fMRI and ERP data, we propose a mechanism where a multisensory stimulus may be signaled or facilitated as early as 60 ms and facilitated in sensory-specific regions by increasing processing speed (at N170) and efficiency (decreasing amplitude in auditory and face-sensitive cortical activation and ERPs). Finally, higher-order processes are also altered, but in a more complex fashion. PMID:19384602

  9. The Temporal Lobes Differentiate between the Voices of Famous and Unknown People: An Event-Related fMRI Study on Speaker Recognition

    PubMed Central

    Bethmann, Anja; Scheich, Henning; Brechmann, André

    2012-01-01

    It is widely accepted that the perception of human voices is supported by neural structures located along the superior temporal sulci. However, there is an ongoing discussion to what extent the activations found in fMRI studies are evoked by the vocal features themselves or are the result of phonetic processing. To show that the temporal lobes are indeed engaged in voice processing, short utterances spoken by famous and unknown people were presented to healthy young participants whose task it was to identify the familiar speakers. In two event-related fMRI experiments, the temporal lobes were found to differentiate between familiar and unfamiliar voices such that named voices elicited higher BOLD signal intensities than unfamiliar voices. Yet, the temporal cortices did not only discriminate between familiar and unfamiliar voices. Experiment 2, which required overtly spoken responses and allowed to distinguish between four familiarity grades, revealed that there was a fine-grained differentiation between all of these familiarity levels with higher familiarity being associated with larger BOLD signal amplitudes. Finally, we observed a gradual response change such that the BOLD signal differences between unfamiliar and highly familiar voices increased with the distance of an area from the transverse temporal gyri, especially towards the anterior temporal cortex and the middle temporal gyri. Therefore, the results suggest that (the anterior and non-superior portions of) the temporal lobes participate in voice-specific processing independent from phonetic components also involved in spoken speech material. PMID:23112826

  10. Correlating the alpha rhythm to BOLD using simultaneous EEG/fMRI: inter-subject variability.

    PubMed

    Gonçalves, S I; de Munck, J C; Pouwels, P J W; Schoonhoven, R; Kuijer, J P A; Maurits, N M; Hoogduin, J M; Van Someren, E J W; Heethaar, R M; Lopes da Silva, F H

    2006-03-01

    Simultaneous recording of electroencephalogram/functional magnetic resonance images (EEG/fMRI) was applied to identify blood oxygenation level-dependent (BOLD) changes associated with spontaneous variations of the alpha rhythm, which is considered the hallmark of the brain resting state. The analysis was focused on inter-subject variability associated with the resting state. Data from 7 normal subjects are presented. Confirming earlier findings, three subjects showed a negative correlation between the BOLD signal and the average power time series within the alpha band (8--12 Hz) in extensive areas of the occipital, parietal and frontal lobes. In small thalamic areas, the BOLD signal was positively correlated with the alpha power. For subjects 3 and 4, who displayed two different states during the data acquisition time, it was shown that the corresponding correlation patterns were different, thus demonstrating the state dependency of the results. In subject 5, the changes in BOLD were observed mainly in the frontal and temporal lobes. Subject 6 only showed positive correlations, thus contradicting the negative BOLD alpha power cortical correlations that were found in most subjects. Results suggest that the resting state varies over subjects and, sometimes, even within one subject. As the resting state plays an important role in many fMRI experiments, the inter-subject variability of this state should be addressed when comparing fMRI results from different subjects.

  11. Monkey cortex through fMRI glasses.

    PubMed

    Vanduffel, Wim; Zhu, Qi; Orban, Guy A

    2014-08-01

    In 1998 several groups reported the feasibility of fMRI experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category- and feature-selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging.

  12. Resting-state fMRI confounds and cleanup.

    PubMed

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

    2013-10-15

    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.

  13. The physics of functional magnetic resonance imaging (fMRI)

    NASA Astrophysics Data System (ADS)

    Buxton, Richard B.

    2013-09-01

    Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm3 spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology.

  14. The physics of functional magnetic resonance imaging (fMRI)

    PubMed Central

    Buxton, Richard B

    2015-01-01

    Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm3 spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology. PMID:24006360

  15. Neurodevelopment assessment of newborns with combined fMRI and DTI

    NASA Astrophysics Data System (ADS)

    Erberich, Stephan G.; Nielsen, Jon F.; Bluml, Stefan; Friedlich, Philippe; Seri, Istvan; Nelson, Marvin D.

    2004-04-01

    Functional Magnetic Resonance Imaging (fMRI) provides the location and regional extent of a task correlated activation in the brain. Recently we have demonstrated, that fMRI of passive sensory tasks (visual, auditory, motor) can be successfully used to map cortical activation in the newborn brain. However the interpretation of the functional response in the immature brain is difficult, as the blood oxygen level dependent (BOLD) physiological signal and location of the activation is quite different compared to adult fMRI responses of similar tasks. We expect, that the major reason for these differences are primarily caused by the immature myelination of the white matter tracts at this age. Diffusion tensor imaging (DTI) can be used to measure the white matter tract development in the newborn brain. The purpose of this paper is to report how to obtain and to combine fMRI and DTI data processing to enhance functional brain mapping in newborns. We obtained simultaneous fMRI and DTI data of 18 newborns, post-conceptional age (gestational age at study) between 34-week and 52-week, which were referred for clinical indicated MRI. 16 out of 18 subjects have been successfully investigated with combined fMRI and DTI and functional activation could be obtained. Fiber tracking was successfully in the visual and auditory cortex, but proofed difficult in the motor-cortex. The additional tract information supported the functional findings and the interpretation in the immature brain. The novel functional imaging in newborn is challenging because of the yet unknown physiological response and location of activation in the newborn brain. Therefore one need additional evidence that the functional findings are valid in the context of structural development. The maturation of myelination is an essential information to compare and to interpret fMRI in newborns. We conclude that the proposed method of combined fMRI and DTI, derived from adult neuroimaging, will be most relevant to

  16. Abnormal ERD/ERS but unaffected BOLD response in patients with Unverricht-Lundborg disease during index extension: a simultaneous EEG-fMRI study.

    PubMed

    Visani, E; Minati, L; Canafoglia, L; Gilioli, I; Granvillano, A; Varotto, G; Aquino, D; Fazio, P; Bruzzone, M G; Franceschetti, S; Panzica, F

    2011-03-01

    Electrophysiological studies indicate that Unverricht-Lundborg's disease (ULD), the most common form of progressive myoclonus epilepsy in Europe, is characterized by the involvement of multiple cortical regions in degenerative changes that lead to enhanced excitation and deficient inhibition. We searched for the haemodynamic correlates of these effects using functional MRI (fMRI) of self-paced index extensions, a well-accepted task highlighting significant differences. EEG and fMRI were simultaneously acquired in 11 ULD patients and 16 controls, performing the index extensions individually (event-related task) as well as repetitively (block task). ERD/ERS analysis was performed for the EEG data in the alpha and beta bands. fMRI time-series were analyzed using the traditional general linear model, as well as with an assumption-free approach, and by means of cross-region correlations representing functional connectivity. In line with the existing literature, ULD patients had enhanced desynchronization in the alpha band and reduced post-movement synchronization in the beta band. By contrast, fMRI did not reveal any difference between the two groups; there were no activation intensity, latency or extent effects, no significant engagement of additional regions, and no changes to functional connectivity. We conclude that, so long as the patients are executing a task which does not induce obvious action myoclonus, the hypothesized abnormalities in pyramidal neuron and interneuron dynamics are relatively subtle, embodied in processes which are not metabolically-demanding and take place at a time-scale invisible to fMRI. PMID:21107673

  17. Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study.

    PubMed

    Henningsson, S; Madsen, K H; Pinborg, A; Heede, M; Knudsen, G M; Siebner, H R; Frokjaer, V G

    2015-01-01

    Sex-hormone fluctuations may increase risk for developing depressive symptoms and alter emotional processing as supported by observations in menopausal and pre- to postpartum transition. In this double-blinded, placebo-controlled study, we used blood-oxygen level dependent functional magnetic resonance imaging (fMRI) to investigate if sex-steroid hormone manipulation with a gonadotropin-releasing hormone agonist (GnRHa) influences emotional processing. Fifty-six healthy women were investigated twice: at baseline (follicular phase of menstrual cycle) and 16 ± 3 days post intervention. At both sessions, fMRI-scans during exposure to faces expressing fear, anger, happiness or no emotion, depressive symptom scores and estradiol levels were acquired. The fMRI analyses focused on regions of interest for emotional processing. As expected, GnRHa initially increased and subsequently reduced estradiol to menopausal levels, which was accompanied by an increase in subclinical depressive symptoms relative to placebo. Women who displayed larger GnRHa-induced increase in depressive symptoms had a larger increase in both negative and positive emotion-elicited activity in the anterior insula. When considering the post-GnRHa scan only, depressive responses were associated with emotion-elicited activity in the anterior insula and amygdala. The effect on regional activity in anterior insula was not associated with the estradiol net decline, only by the GnRHa-induced changes in mood. Our data implicate enhanced insula recruitment during emotional processing in the emergence of depressive symptoms following sex-hormone fluctuations. This may correspond to the emotional hypersensitivity frequently experienced by women postpartum. PMID:26624927

  18. Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study

    PubMed Central

    Henningsson, S; Madsen, K H; Pinborg, A; Heede, M; Knudsen, G M; Siebner, H R; Frokjaer, V G

    2015-01-01

    Sex-hormone fluctuations may increase risk for developing depressive symptoms and alter emotional processing as supported by observations in menopausal and pre- to postpartum transition. In this double-blinded, placebo-controlled study, we used blood−oxygen level dependent functional magnetic resonance imaging (fMRI) to investigate if sex-steroid hormone manipulation with a gonadotropin-releasing hormone agonist (GnRHa) influences emotional processing. Fifty-six healthy women were investigated twice: at baseline (follicular phase of menstrual cycle) and 16±3 days post intervention. At both sessions, fMRI-scans during exposure to faces expressing fear, anger, happiness or no emotion, depressive symptom scores and estradiol levels were acquired. The fMRI analyses focused on regions of interest for emotional processing. As expected, GnRHa initially increased and subsequently reduced estradiol to menopausal levels, which was accompanied by an increase in subclinical depressive symptoms relative to placebo. Women who displayed larger GnRHa-induced increase in depressive symptoms had a larger increase in both negative and positive emotion-elicited activity in the anterior insula. When considering the post-GnRHa scan only, depressive responses were associated with emotion-elicited activity in the anterior insula and amygdala. The effect on regional activity in anterior insula was not associated with the estradiol net decline, only by the GnRHa-induced changes in mood. Our data implicate enhanced insula recruitment during emotional processing in the emergence of depressive symptoms following sex-hormone fluctuations. This may correspond to the emotional hypersensitivity frequently experienced by women postpartum. PMID:26624927

  19. Transcranial electrical stimulation of the occipital cortex during visual perception modifies the magnitude of BOLD activity: A combined tES-fMRI approach.

    PubMed

    Alekseichuk, Ivan; Diers, Kersten; Paulus, Walter; Antal, Andrea

    2016-10-15

    The aim of this study was to investigate if the blood oxygenation level-dependent (BOLD) changes in the visual cortex can be used as biomarkers reflecting the online and offline effects of transcranial electrical stimulation (tES). Anodal transcranial direct current stimulation (tDCS) and 10Hz transcranial alternating current stimulation (tACS) were applied for 10min duration over the occipital cortex of healthy adults during the presentation of different visual stimuli, using a crossover, double-blinded design. Control experiments were also performed, in which sham stimulation as well as another electrode montage were used. Anodal tDCS over the visual cortex induced a small but significant further increase in BOLD response evoked by a visual stimulus; however, no aftereffect was observed. Ten hertz of tACS did not result in an online effect, but in a widespread offline BOLD decrease over the occipital, temporal, and frontal areas. These findings demonstrate that tES during visual perception affects the neuronal metabolism, which can be detected with functional magnetic resonance imaging (fMRI). PMID:26608246

  20. Transcranial electrical stimulation of the occipital cortex during visual perception modifies the magnitude of BOLD activity: A combined tES-fMRI approach.

    PubMed

    Alekseichuk, Ivan; Diers, Kersten; Paulus, Walter; Antal, Andrea

    2016-10-15

    The aim of this study was to investigate if the blood oxygenation level-dependent (BOLD) changes in the visual cortex can be used as biomarkers reflecting the online and offline effects of transcranial electrical stimulation (tES). Anodal transcranial direct current stimulation (tDCS) and 10Hz transcranial alternating current stimulation (tACS) were applied for 10min duration over the occipital cortex of healthy adults during the presentation of different visual stimuli, using a crossover, double-blinded design. Control experiments were also performed, in which sham stimulation as well as another electrode montage were used. Anodal tDCS over the visual cortex induced a small but significant further increase in BOLD response evoked by a visual stimulus; however, no aftereffect was observed. Ten hertz of tACS did not result in an online effect, but in a widespread offline BOLD decrease over the occipital, temporal, and frontal areas. These findings demonstrate that tES during visual perception affects the neuronal metabolism, which can be detected with functional magnetic resonance imaging (fMRI).

  1. Evidence that neurovascular coupling underlying the BOLD effect increases with age during childhood.

    PubMed

    Schmithorst, Vincent J; Vannest, Jennifer; Lee, Gregory; Hernandez-Garcia, Luis; Plante, Elena; Rajagopal, Akila; Holland, Scott K

    2015-01-01

    Functional MRI using blood-oxygen-level-dependent (BOLD) imaging has provided unprecedented insights into the maturation of the human brain. Task-based fMRI studies have shown BOLD signal increases with age during development (ages 5-18) for many cognitive domains such as language and executive function, while functional connectivity (resting-state) fMRI studies investigating regionally synchronous BOLD fluctuations have revealed a developing functional organization of the brain from a local into a more distributed architecture. However, interpretation of these results is confounded by the fact that the BOLD signal is directly related to blood oxygenation driven by changes in blood flow and only indirectly related to neuronal activity, and may thus be affected by changing neuronal-vascular coupling. BOLD signal and cerebral blood flow (CBF) were measured simultaneously in a cohort of 113 typically developing awake participants ages 3-18 performing a narrative comprehension task. Using a novel voxelwise wild bootstrap analysis technique, an increased ratio of BOLD signal to relative CBF signal change with age (indicative of increased neuronal-vascular coupling) was seen in the middle temporal gyri and the left inferior frontal gyrus. Additionally, evidence of decreased relative oxygen metabolism (indicative of decreased neuronal activity) with age was found in the same regions. These findings raise concern that results of developmental BOLD studies cannot be unambiguously attributed to neuronal activity. Astrocytes and astrocytic processes may significantly affect the maturing functional architecture of the brain, consistent with recent research demonstrating a key role for astrocytes in mediating increased CBF following neuronal activity and for astrocyte processes in modulating synaptic connectivity.

  2. Brain Correlates of Phasic Autonomic Response to Acupuncture Stimulation: An Event-Related fMRI Study

    PubMed Central

    Napadow, Vitaly; Lee, Jeungchan; Kim, Jieun; Cina, Stephen; Maeda, Yumi; Barbieri, Riccardo; Harris, Richard E.; Kettner, Norman; Park, Kyungmo

    2013-01-01

    Autonomic nervous system (ANS) response to acupuncture has been investigated by multiple studies; however, the brain circuitry underlying this response is not well understood. We applied event-related fMRI (er-fMRI) in conjunction with ANS recording (heart rate, HR; skin conductance response, SCR). Brief manual acupuncture stimuli were delivered at acupoints ST36 and SP9, while sham stimuli were delivered at control location, SH1. Acupuncture produced activation in S2, insula, and mid-cingulate cortex, and deactivation in default mode network (DMN) areas. On average, HR deceleration (HR–) and SCR were noted following both real and sham acupuncture, though magnitude of response was greater following real acupuncture and inter-subject magnitude of response correlated with evoked sensation intensity. Acupuncture events with strong SCR also produced greater anterior insula activation than without SCR. Moreover, acupuncture at SP9, which produced greater SCR, also produced stronger sharp pain sensation, and greater anterior insula activation. Conversely, acupuncture-induced HR– was associated with greater DMN deactivation. Between-event correlation demonstrated that this association was strongest for ST36, which also produced more robust HR–. In fact, DMN deactivation was significantly more pronounced across acupuncture stimuli producing HR–, versus those events characterized by acceleration (HR+). Thus, differential brain response underlying acupuncture stimuli may be related to differential autonomic outflows and may result from heterogeneity in evoked sensations. Our er-fMRI approach suggests that ANS response to acupuncture, consistent with previously characterized orienting and startle/defense responses, arises from activity within distinct subregions of the more general brain circuitry responding to acupuncture stimuli. PMID:22504841

  3. Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data.

    PubMed

    Weiskopf, Nikolaus; Veit, Ralf; Erb, Michael; Mathiak, Klaus; Grodd, Wolfgang; Goebel, Rainer; Birbaumer, Niels

    2003-07-01

    A brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI) is presented which allows human subjects to observe and control changes of their own blood oxygen level-dependent (BOLD) response. This BCI performs data preprocessing (including linear trend removal, 3D motion correction) and statistical analysis on-line. Local BOLD signals are continuously fed back to the subject in the magnetic resonance scanner with a delay of less than 2 s from image acquisition. The mean signal of a region of interest is plotted as a time-series superimposed on color-coded stripes which indicate the task, i.e., to increase or decrease the BOLD signal. We exemplify the presented BCI with one volunteer intending to control the signal of the rostral-ventral and dorsal part of the anterior cingulate cortex (ACC). The subject achieved significant changes of local BOLD responses as revealed by region of interest analysis and statistical parametric maps. The percent signal change increased across fMRI-feedback sessions suggesting a learning effect with training. This methodology of fMRI-feedback can assess voluntary control of circumscribed brain areas. As a further extension, behavioral effects of local self-regulation become accessible as a new field of research.

  4. Post-stroke aphasia recovery assessed with fMRI and a picture identification task

    PubMed Central

    Szaflarski, Jerzy P.; Eaton, Kenneth; Ball, Angel L.; Banks, Christi; Vannest, Jennifer; Allendorfer, Jane B.; Page, Stephen; Holland, Scott K.

    2010-01-01

    Background Stroke patients often display deficits in language function such as correctly naming objects. Our aim was to evaluate the reliability and the patterns of post-stroke language recovery using a picture identification task during fMRI at 4T. Material and Methods 4 healthy and 4 left MCA stroke subjects with chronic (>1 year) aphasia. Ten fMRI scans were performed for each subject over a 10-week period using a picture identification task. Active condition involved presenting subjects with a panel of 4 figures (e.g., drawings of 4 animals) every 6 seconds; subjects indicated which figure matched the written name in the center. Control condition was same/different judgment task of pairs of geometric figures (squares, octagons or combination) presented every 6 seconds. Thirty-second active/control blocks were repeated 5 times each; responses were recorded. Results Patients and controls exhibited similar demographic characteristics: age (46 vs. 53 years), personal handedness (EHI; 89 vs. 95), familial handedness (93 vs. 95) or years of education (14.3 vs. 14.8). For the active condition, controls performed better than patients (97.7% vs. 89.1%, p<0.001); performance was similar for the control condition (99.5% vs. 98.8%, p=0.23). During fMRI, controls exhibited bilateral, L>R positive blood oxygenation-level dependent (BOLD) activations in frontal and temporal language areas and symmetric retro-splenial and posterior cingulate areas and symmetric negative BOLD activations in bilateral fronto-temporal language networks. However, the patient group showed positive BOLD activations predominantly in peri-stroke areas and negative BOLD activations in the unaffected (right) hemisphere. Both the control and patient groups displayed high activation reliability (as measured by the ICC) in left frontal and temporal language areas, although the ICC in frontal regions of the patients was spread over a much larger peri-stroke area. Conclusion This study documents the utility

  5. BOLD delay times using group delay in sickle cell disease

    NASA Astrophysics Data System (ADS)

    Coloigner, Julie; Vu, Chau; Bush, Adam; Borzage, Matt; Rajagopalan, Vidya; Lepore, Natasha; Wood, John

    2016-03-01

    Sickle cell disease (SCD) is an inherited blood disorder that effects red blood cells, which can lead to vasoocclusion, ischemia and infarct. This disease often results in neurological damage and strokes, leading to morbidity and mortality. Functional Magnetic Resonance Imaging (fMRI) is a non-invasive technique for measuring and mapping the brain activity. Blood Oxygenation Level-Dependent (BOLD) signals contain also information about the neurovascular coupling, vascular reactivity, oxygenation and blood propagation. Temporal relationship between BOLD fluctuations in different parts of the brain provides also a mean to investigate the blood delay information. We used the induced desaturation as a label to profile transit times through different brain areas, reflecting oxygen utilization of tissue. In this study, we aimed to compare blood flow propagation delay times between these patients and healthy subjects in areas vascularized by anterior, middle and posterior cerebral arteries. In a group comparison analysis with control subjects, BOLD changes in these areas were found to be almost simultaneous and shorter in the SCD patients, because of their increased brain blood flow. Secondly, the analysis of a patient with a stenosis on the anterior cerebral artery indicated that signal of the area vascularized by this artery lagged the MCA signal. These findings suggest that sickle cell disease causes blood propagation modifications, and that these changes could be used as a biomarker of vascular damage.

  6. Computing moment-to-moment BOLD activation for real-time neurofeedback.

    PubMed

    Hinds, Oliver; Ghosh, Satrajit; Thompson, Todd W; Yoo, Julie J; Whitfield-Gabrieli, Susan; Triantafyllou, Christina; Gabrieli, John D E

    2011-01-01

    Estimating moment-to-moment changes in blood oxygenation level dependent (BOLD) activation levels from functional magnetic resonance imaging (fMRI) data has applications for learned regulation of regional activation, brain state monitoring, and brain-machine interfaces. In each of these contexts, accurate estimation of the BOLD signal in as little time as possible is desired. This is a challenging problem due to the low signal-to-noise ratio of fMRI data. Previous methods for real-time fMRI analysis have either sacrificed the ability to compute moment-to-moment activation changes by averaging several acquisitions into a single activation estimate or have sacrificed accuracy by failing to account for prominent sources of noise in the fMRI signal. Here we present a new method for computing the amount of activation present in a single fMRI acquisition that separates moment-to-moment changes in the fMRI signal intensity attributable to neural sources from those due to noise, resulting in a feedback signal more reflective of neural activation. This method computes an incremental general linear model fit to the fMRI time series, which is used to calculate the expected signal intensity at each new acquisition. The difference between the measured intensity and the expected intensity is scaled by the variance of the estimator in order to transform this residual difference into a statistic. Both synthetic and real data were used to validate this method and compare it to the only other published real-time fMRI method.

  7. Neural Response during the Activation of the Attachment System in Patients with Borderline Personality Disorder: An fMRI Study.

    PubMed

    Buchheim, Anna; Erk, Susanne; George, Carol; Kächele, Horst; Martius, Philipp; Pokorny, Dan; Spitzer, Manfred; Walter, Henrik

    2016-01-01

    Individuals with borderline personality disorder (BPD) are characterized by emotional instability, impaired emotion regulation and unresolved attachment patterns associated with abusive childhood experiences. We investigated the neural response during the activation of the attachment system in BPD patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Eleven female patients with BPD without posttraumatic stress disorder (PTSD) and 17 healthy female controls matched for age and education were telling stories in the scanner in response to the Adult Attachment Projective Picture System (AAP), an eight-picture set assessment of adult attachment. The picture set includes theoretically-derived attachment scenes, such as separation, death, threat and potential abuse. The picture presentation order is designed to gradually increase the activation of the attachment system. Each picture stimulus was presented for 2 min. Analyses examine group differences in attachment classifications and neural activation patterns over the course of the task. Unresolved attachment was associated with increasing amygdala activation over the course of the attachment task in patients as well as controls. Unresolved controls, but not patients, showed activation in the right dorsolateral prefrontal cortex (DLPFC) and the rostral cingulate zone (RCZ). We interpret this as a neural signature of BPD patients' inability to exert top-down control under conditions of attachment distress. These findings point to possible neural mechanisms for underlying affective dysregulation in BPD in the context of attachment trauma and fear.

  8. Neural Response during the Activation of the Attachment System in Patients with Borderline Personality Disorder: An fMRI Study

    PubMed Central

    Buchheim, Anna; Erk, Susanne; George, Carol; Kächele, Horst; Martius, Philipp; Pokorny, Dan; Spitzer, Manfred; Walter, Henrik

    2016-01-01

    Individuals with borderline personality disorder (BPD) are characterized by emotional instability, impaired emotion regulation and unresolved attachment patterns associated with abusive childhood experiences. We investigated the neural response during the activation of the attachment system in BPD patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Eleven female patients with BPD without posttraumatic stress disorder (PTSD) and 17 healthy female controls matched for age and education were telling stories in the scanner in response to the Adult Attachment Projective Picture System (AAP), an eight-picture set assessment of adult attachment. The picture set includes theoretically-derived attachment scenes, such as separation, death, threat and potential abuse. The picture presentation order is designed to gradually increase the activation of the attachment system. Each picture stimulus was presented for 2 min. Analyses examine group differences in attachment classifications and neural activation patterns over the course of the task. Unresolved attachment was associated with increasing amygdala activation over the course of the attachment task in patients as well as controls. Unresolved controls, but not patients, showed activation in the right dorsolateral prefrontal cortex (DLPFC) and the rostral cingulate zone (RCZ). We interpret this as a neural signature of BPD patients’ inability to exert top-down control under conditions of attachment distress. These findings point to possible neural mechanisms for underlying affective dysregulation in BPD in the context of attachment trauma and fear. PMID:27531977

  9. Abnormal perilesional BOLD signal is not correlated with stroke patients' behavior.

    PubMed

    de Haan, Bianca; Rorden, Chris; Karnath, Hans-Otto

    2013-01-01

    Several functional magnetic resonance imaging (fMRI) studies of acute stroke have reported that patients with behavioral deficits show abnormal signal in intact regions of the damaged hemisphere close to the lesion border relative to homologous regions of the patient's intact hemisphere (causing an interhemispheric imbalance) as well as analogous regions in healthy controls. These effects have been interpreted as demonstrating a causal relationship between the abnormal fMRI signal and the pathological behavior. Here we explore an alternative explanation: perhaps the abnormal Blood-Oxygenation Level Dependent (BOLD) fMRI signal is merely a function of distance from the acute lesion. To investigate this hypothesis, we examined three patients with an acute right hemisphere cortical stroke who did not show any overt behavioral deficits, as well as nine healthy elderly controls. We acquired fMRI data while the participants performed a simple visual orientation judgment task. In patients, we observed an abnormal interhemispheric balance consisting of lower levels of percent signal change in perilesional areas of the damaged hemisphere relative to homologous areas in neurologically healthy controls. This suggests that the physiological changes and corresponding interhemispheric imbalance detected by fMRI BOLD in acute stroke observed close to the lesion border may not necessarily reflect changes in the neural function, nor necessarily influence the individuals' (e.g., attentional) behavior. PMID:24137123

  10. fMRI adaptation revisited.

    PubMed

    Larsson, Jonas; Solomon, Samuel G; Kohn, Adam

    2016-07-01

    Adaptation has been widely used in functional magnetic imaging (fMRI) studies to infer neuronal response properties in human cortex. fMRI adaptation has been criticized because of the complex relationship between fMRI adaptation effects and the multiple neuronal effects that could underlie them. Many of the longstanding concerns about fMRI adaptation have received empirical support from neurophysiological studies over the last decade. We review these studies here, and also consider neuroimaging studies that have investigated how fMRI adaptation effects are influenced by high-level perceptual processes. The results of these studies further emphasize the need to interpret fMRI adaptation results with caution, but they also provide helpful guidance for more accurate interpretation and better experimental design. In addition, we argue that rather than being used as a proxy for measurements of neuronal stimulus selectivity, fMRI adaptation may be most useful for studying population-level adaptation effects across cortical processing hierarchies.

  11. Quantitative β mapping for calibrated fMRI.

    PubMed

    Shu, Christina Y; Sanganahalli, Basavaraju G; Coman, Daniel; Herman, Peter; Rothman, Douglas L; Hyder, Fahmeed

    2016-02-01

    The metabolic and hemodynamic dependencies of the blood oxygenation level-dependent (BOLD) signal form the basis for calibrated fMRI, where the focus is on oxidative energy demanded by neural activity. An important part of calibrated fMRI is the power-law relationship between the BOLD signal and the deoxyhemoglobin concentration, which in turn is related to the ratio between oxidative demand (CMRO2) and blood flow (CBF). The power-law dependence between BOLD signal and deoxyhemoglobin concentration is signified by a scaling exponent β. Until recently most studies assumed a β value of 1.5, which is based on numerical simulations of the extravascular BOLD component. Since the basal value of CMRO2 and CBF can vary from subject-to-subject and/or region-to-region, a method to independently measure β in vivo should improve the accuracy of calibrated fMRI results. We describe a new method for β mapping through characterizing R2' - the most sensitive relaxation component of BOLD signal (i.e., the reversible magnetic susceptibility component that is predominantly of extravascular origin at high magnetic field) - as a function of intravascular magnetic susceptibility induced by an FDA-approved superparamagnetic contrast agent. In α-chloralose anesthetized rat brain, at 9.4 T, we measured β values of ~0.8 uniformly across large neocortical swathes, with lower magnitude and more heterogeneity in subcortical areas. Comparison of β maps in rats anesthetized with medetomidine and α-chloralose revealed that β is independent of neural activity levels at these resting states. We anticipate that this method for β mapping can help facilitate calibrated fMRI for clinical studies. PMID:26619788

  12. Functional connectivity in BOLD and CBF data: similarity and reliability of resting brain networks.

    PubMed

    Jann, Kay; Gee, Dylan G; Kilroy, Emily; Schwab, Simon; Smith, Robert X; Cannon, Tyrone D; Wang, Danny J J

    2015-02-01

    Resting-state functional connectivity (FC) fMRI (rs-fcMRI) offers an appealing approach to mapping the brain's intrinsic functional organization. Blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) are the two main rs-fcMRI approaches to assess alterations in brain networks associated with individual differences, behavior and psychopathology. While the BOLD signal is stronger with a higher temporal resolution, ASL provides quantitative, direct measures of the physiology and metabolism of specific networks. This study systematically investigated the similarity and reliability of resting brain networks (RBNs) in BOLD and ASL. A 2 × 2 × 2 factorial design was employed where each subject underwent repeated BOLD and ASL rs-fcMRI scans on two occasions on two MRI scanners respectively. Both independent and joint FC analyses revealed common RBNs in ASL and BOLD rs-fcMRI with a moderate to high level of spatial overlap, verified by Dice Similarity Coefficients. Test-retest analyses indicated more reliable spatial network patterns in BOLD (average modal Intraclass Correlation Coefficients: 0.905 ± 0.033 between-sessions; 0.885 ± 0.052 between-scanners) than ASL (0.545 ± 0.048; 0.575 ± 0.059). Nevertheless, ASL provided highly reproducible (0.955 ± 0.021; 0.970 ± 0.011) network-specific CBF measurements. Moreover, we observed positive correlations between regional CBF and FC in core areas of all RBNs indicating a relationship between network connectivity and its baseline metabolism. Taken together, the combination of ASL and BOLD rs-fcMRI provides a powerful tool for characterizing the spatiotemporal and quantitative properties of RBNs. These findings pave the way for future BOLD and ASL rs-fcMRI studies in clinical populations that are carried out across time and scanners.

  13. Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene influences fMRI signal responses during emotional stimulus processing.

    PubMed

    Hsu, David T; Mickey, Brian J; Langenecker, Scott A; Heitzeg, Mary M; Love, Tiffany M; Wang, Heng; Kennedy, Susan E; Peciña, Marta; Shafir, Tal; Hodgkinson, Colin A; Enoch, Mary-Anne; Goldman, David; Zubieta, Jon-Kar

    2012-02-29

    The corticotropin-releasing hormone (CRH) system coordinates neuroendocrine and behavioral responses to stress and has been implicated in the development of major depressive disorder (MDD). Recent reports suggest that GG-homozygous individuals of a single nucleotide polymorphism (rs110402) in the CRH receptor 1 (CRHR1) gene show behavioral and neuroendocrine evidence of stress vulnerability. The present study explores whether those observations extend to the neuronal processing of emotional stimuli in humans. CRHR1 was genotyped in 83 controls and a preliminary sample of 16 unmedicated patients with MDD who completed a functional magnetic resonance imaging scan while viewing blocks of positive, negative, and neutral words. In addition, potential mediating factors such as early life stress, sex, personality traits, and negative memory bias were examined. Robust differences in blood oxygenation level-dependent (BOLD) signal were found in healthy controls (A allele carriers > GG-homozygotes) in the right middle temporal/angular gyrus while subjects were viewing negative versus neutral words. Among GG-homozygotes, BOLD signal in the subgenual cingulate was greater in MDD participants (n = 9) compared with controls (n = 33). Conversely, among A-carriers, BOLD signal was smaller in MDD (n = 7) compared with controls (n = 50) in the hypothalamus, bilateral amygdala, and left nucleus accumbens. Early life stress, personality traits, and levels of negative memory bias were associated with brain activity depending on genotype. Results from healthy controls and a preliminary sample of MDD participants show that CRHR1 single nucleotide polymorphism rs110402 moderates neural responses to emotional stimuli, suggesting a potential mechanism of vulnerability for the development of MDD. PMID:22378896

  14. Detection of cannabinoid agonist evoked increase in BOLD contrast in rats using functional magnetic resonance imaging.

    PubMed

    Shah, Y B; Prior, M J W; Dixon, A L; Morris, P G; Marsden, C A

    2004-03-01

    BOLD-contrast functional magnetic resonance imaging (fMRI) was used to investigate the effects of the synthetic cannabinoid agonist HU210 on the rat brain in order to determine potential CNS sites of action for the functional effects of cannabinoids. After obtaining basal data, rats (n=8) were given the cannabinoid agonist HU210 (10 microg/kg i.v.) and volume data sets collected for 85 mins. Significant increases in functional BOLD activity were observed in specific brain regions including those important in pain (PAG), reward (VTA and accumbens) and motor function (striatum). In order to confirm cannabinoid receptor involvement in the HU210 evoked functional BOLD activity, rats (n=8) were pre-treated with the CB1 cannabinoid receptor antagonist SR141716A (100 microg/kg i.v.) prior to HU210. Pretreatment with SR141716A abolished all significant evoked HU210 functional BOLD activity. To exclude the involvement of potential systemic effects induced by the cannabinoid agonist administration on the observed evoked functional BOLD activity a separate experiment investigated the effect of HU210 (10 microg/kg i.v.) on mean arterial pressure and showed that HU210 had no significant effect on pressure under chloral hydrate anaesthesia. In summary, this study demonstrates that the cannabinoid agonist HU210 evokes a significant increase in BOLD functional activity in specific regions and that this was cannabinoid receptor mediated. Furthermore the study indicates the potential value of fMRI in rodents to delineate pharmacologically induced changes in regional brain function. PMID:14975693

  15. Repetition suppression: a means to index neural representations using BOLD?

    PubMed Central

    Behrens, Timothy E. J.

    2016-01-01

    Understanding how the human brain gives rise to complex cognitive processes remains one of the biggest challenges of contemporary neuroscience. While invasive recording in animal models can provide insight into neural processes that are conserved across species, our understanding of cognition more broadly relies upon investigation of the human brain itself. There is therefore an imperative to establish non-invasive tools that allow human brain activity to be measured at high spatial and temporal resolution. In recent years, various attempts have been made to refine the coarse signal available in functional magnetic resonance imaging (fMRI), providing a means to investigate neural activity at the meso-scale, i.e. at the level of neural populations. The most widely used techniques include repetition suppression and multivariate pattern analysis. Human neuroscience can now use these techniques to investigate how representations are encoded across neural populations and transformed by relevant computations. Here, we review the physiological basis, applications and limitations of fMRI repetition suppression with a brief comparison to multivariate techniques. By doing so, we show how fMRI repetition suppression holds promise as a tool to reveal complex neural mechanisms that underlie human cognitive function. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574308

  16. Repetition suppression: a means to index neural representations using BOLD?

    PubMed

    Barron, Helen C; Garvert, Mona M; Behrens, Timothy E J

    2016-10-01

    Understanding how the human brain gives rise to complex cognitive processes remains one of the biggest challenges of contemporary neuroscience. While invasive recording in animal models can provide insight into neural processes that are conserved across species, our understanding of cognition more broadly relies upon investigation of the human brain itself. There is therefore an imperative to establish non-invasive tools that allow human brain activity to be measured at high spatial and temporal resolution. In recent years, various attempts have been made to refine the coarse signal available in functional magnetic resonance imaging (fMRI), providing a means to investigate neural activity at the meso-scale, i.e. at the level of neural populations. The most widely used techniques include repetition suppression and multivariate pattern analysis. Human neuroscience can now use these techniques to investigate how representations are encoded across neural populations and transformed by relevant computations. Here, we review the physiological basis, applications and limitations of fMRI repetition suppression with a brief comparison to multivariate techniques. By doing so, we show how fMRI repetition suppression holds promise as a tool to reveal complex neural mechanisms that underlie human cognitive function.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574308

  17. Calibrated BOLD using direct measurement of changes in venous oxygenation.

    PubMed

    Driver, Ian D; Hall, Emma L; Wharton, Samuel J; Pritchard, Susan E; Francis, Susan T; Gowland, Penny A

    2012-11-15

    Calibration of the BOLD signal is potentially of great value in providing a closer measure of the underlying changes in brain function related to neuronal activity than the BOLD signal alone, but current approaches rely on an assumed relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF). This is poorly characterised in humans and does not reflect the predominantly venous nature of BOLD contrast, whilst this relationship may vary across brain regions and depend on the structure of the local vascular bed. This work demonstrates a new approach to BOLD calibration which does not require an assumption about the relationship between cerebral blood volume and cerebral blood flow. This method involves repeating the same stimulus both at normoxia and hyperoxia, using hyperoxic BOLD contrast to estimate the relative changes in venous blood oxygenation and venous CBV. To do this the effect of hyperoxia on venous blood oxygenation has to be calculated, which requires an estimate of basal oxygen extraction fraction, and this can be estimated from the phase as an alternative to using a literature estimate. Additional measurement of the relative change in CBF, combined with the blood oxygenation change can be used to calculate the relative change in CMRO(2) due to the stimulus. CMRO(2) changes of 18 ± 8% in response to a motor task were measured without requiring the assumption of a CBV/CBF coupling relationship, and are in agreement with previous approaches.

  18. BOLD Variability is Related to Dopaminergic Neurotransmission and Cognitive Aging.

    PubMed

    Guitart-Masip, Marc; Salami, Alireza; Garrett, Douglas; Rieckmann, Anna; Lindenberger, Ulman; Bäckman, Lars

    2016-05-01

    Dopamine (DA) losses are associated with various aging-related cognitive deficits. Typically, higher moment-to-moment brain signal variability in large-scale patterns of voxels in neocortical regions is linked to better cognitive performance and younger adult age, yet the physiological mechanisms regulating brain signal variability are unknown. We explored the relationship among adult age, DA availability, and blood oxygen level-dependent (BOLD) signal variability, while younger and older participants performed a spatial working memory (SWM) task. We quantified striatal and extrastriatal DA D1 receptor density with [(11)C]SCH23390 and positron emission tomography in all participants. We found that BOLD variability in a neocortical region was negatively related to age and positively related to SWM performance. In contrast, BOLD variability in subcortical regions and bilateral hippocampus was positively related to age and slower responses, and negatively related to D1 density in caudate and dorsolateral prefrontal cortex. Furthermore, BOLD variability in neocortical regions was positively associated with task-related disengagement of the default-mode network, a network whose activation needs to be suppressed for efficient SWM processing. Our results show that age-related DA losses contribute to changes in brain signal variability in subcortical regions and suggest a potential mechanism, by which neocortical BOLD variability supports cognitive performance.

  19. Differential cerebral response to somatosensory stimulation of an acupuncture point vs. two non-acupuncture points measured with EEG and fMRI

    PubMed Central

    Nierhaus, Till; Pach, Daniel; Huang, Wenjing; Long, Xiangyu; Napadow, Vitaly; Roll, Stephanie; Liang, Fanrong; Pleger, Burkhard; Villringer, Arno; Witt, Claudia M.

    2015-01-01

    Acupuncture can be regarded as a complex somatosensory stimulation. Here, we evaluate whether the point locations chosen for a somatosensory stimulation with acupuncture needles differently change the brain activity in healthy volunteers. We used EEG, event-related fMRI, and resting-state functional connectivity fMRI to assess neural responses to standardized needle stimulation of the acupuncture point ST36 (lower leg) and two control point locations (CP1 same dermatome, CP2 different dermatome). Cerebral responses were expected to differ for stimulation in two different dermatomes (CP2 different from ST36 and CP1), or stimulation at the acupuncture point vs. the control points. For EEG, mu rhythm power increased for ST36 compared to CP1 or CP2, but not when comparing the two control points. The fMRI analysis found more pronounced insula and S2 (secondary somatosensory cortex) activation, as well as precuneus deactivation during ST36 stimulation. The S2 seed-based functional connectivity analysis revealed increased connectivity to right precuneus for both comparisons, ST36 vs. CP1 and ST36 vs. CP2, however in different regions. Our results suggest that stimulation at acupuncture points may modulate somatosensory and saliency processing regions more readily than stimulation at non-acupuncture point locations. Also, our findings suggest potential modulation of pain perception due to acupuncture stimulation. PMID:25741269

  20. Primary somatosensory contribution to action observation brain activity-combining fMRI and cTBS.

    PubMed

    Valchev, Nikola; Gazzola, Valeria; Avenanti, Alessio; Keysers, Christian

    2016-08-01

    Traditionally the mirror neuron system (MNS) only includes premotor and posterior parietal cortices. However, somatosensory cortices, BA1/2 in particular, are also activated during action execution and observation. Here, we examine whether BA1/2 and the parietofrontal MNS integrate information by using functional magnetic resonance imaging (fMRI)-guided continuous theta-burst stimulation (cTBS) to perturb BA1/2. Measuring brain activity using fMRI while participants are under the influence of cTBS shows local cTBS effects in BA1/2 varied, with some participants showing decreases and others increases in the BOLD response to viewing actions vs control stimuli. We show how measuring cTBS effects using fMRI can harness this variance using a whole-brain regression. This analysis identifies brain regions exchanging action-specific information with BA1/2 by mapping voxels away from the coil with cTBS-induced, action-observation-specific BOLD contrast changes that mirror those under the coil. This reveals BA1/2 exchanges action-specific information with premotor, posterior parietal and temporal nodes of the MNS during action observation. Although anatomical connections between BA1/2 and these regions are well known, this is the first demonstration that these connections carry action-specific signals during observation and hence, that BA1/2 plays a causal role in the human MNS. PMID:26979966

  1. Primary somatosensory contribution to action observation brain activity—combining fMRI and cTBS

    PubMed Central

    Valchev, Nikola; Avenanti, Alessio; Keysers, Christian

    2016-01-01

    Traditionally the mirror neuron system (MNS) only includes premotor and posterior parietal cortices. However, somatosensory cortices, BA1/2 in particular, are also activated during action execution and observation. Here, we examine whether BA1/2 and the parietofrontal MNS integrate information by using functional magnetic resonance imaging (fMRI)-guided continuous theta-burst stimulation (cTBS) to perturb BA1/2. Measuring brain activity using fMRI while participants are under the influence of cTBS shows local cTBS effects in BA1/2 varied, with some participants showing decreases and others increases in the BOLD response to viewing actions vs control stimuli. We show how measuring cTBS effects using fMRI can harness this variance using a whole-brain regression. This analysis identifies brain regions exchanging action-specific information with BA1/2 by mapping voxels away from the coil with cTBS-induced, action-observation-specific BOLD contrast changes that mirror those under the coil. This reveals BA1/2 exchanges action-specific information with premotor, posterior parietal and temporal nodes of the MNS during action observation. Although anatomical connections between BA1/2 and these regions are well known, this is the first demonstration that these connections carry action-specific signals during observation and hence, that BA1/2 plays a causal role in the human MNS. PMID:26979966

  2. Individual Differences in Mathematical Competence Modulate Brain Responses to Arithmetic Errors: An fMRI Study

    ERIC Educational Resources Information Center

    Ansari, Daniel; Grabner, Roland H.; Koschutnig, Karl; Reishofer, Gernot; Ebner, Franz

    2011-01-01

    Data from both neuropsychological and neuroimaging studies have implicated the left inferior parietal cortex in calculation. Comparatively less attention has been paid to the neural responses associated with the commission of calculation errors and how the processing of arithmetic errors is modulated by individual differences in mathematical…

  3. Differentially Tuned Responses to Restricted versus Prolonged Awareness of Threat: A Preliminary fMRI Investigation

    ERIC Educational Resources Information Center

    Adams, Reginald B., Jr.; Franklin, Robert G., Jr.; Nelson, Anthony J.; Gordon, Heather L.; Kleck, Robert E.; Whalen, Paul J.; Ambady, Nalini

    2011-01-01

    Responses to threat occur via two known independent processing routes. We propose that early, reflexive processing is predominantly tuned to the detection of congruent combinations of facial cues that signal threat, whereas later, reflective processing is predominantly tuned to incongruent combinations of threat. To test this prediction, we…

  4. Volitional control of the anterior insula in criminal psychopaths using real-time fMRI neurofeedback: a pilot study

    PubMed Central

    Sitaram, Ranganatha; Caria, Andrea; Veit, Ralf; Gaber, Tilman; Ruiz, Sergio; Birbaumer, Niels

    2014-01-01

    This pilot study aimed to explore whether criminal psychopaths can learn volitional regulation of the left anterior insula with real-time fMRI neurofeedback. Our previous studies with healthy volunteers showed that learned control of the blood oxygenation-level dependent (BOLD) signal was specific to the target region, and not a result of general arousal and global unspecific brain activation, and also that successful regulation modulates emotional responses, specifically to aversive picture stimuli but not neutral stimuli. In this pilot study, four criminal psychopaths were trained to regulate the anterior insula by employing negative emotional imageries taken from previous episodes in their lives, in conjunction with contingent feedback. Only one out of the four participants learned to increase the percent differential BOLD in the up-regulation condition across training runs. Subjects with higher Psychopathic Checklist-Revised (PCL:SV) scores were less able to increase the BOLD signal in the anterior insula than their lower PCL:SV counterparts. We investigated functional connectivity changes in the emotional network due to learned regulation of the successful participant, by employing multivariate Granger Causality Modeling (GCM). Learning to up-regulate the left anterior insula not only increased the number of connections (causal density) in the emotional network in the single successful participant but also increased the difference between the number of outgoing and incoming connections (causal flow) of the left insula. This pilot study shows modest potential for training psychopathic individuals to learn to control brain activity in the anterior insula. PMID:25352793

  5. The Neostriatum and Response Selection in Overt Sentence Production: an fMRI Study

    PubMed Central

    Argyropoulos, Georgios P.; Tremblay, Pascale; Small, Steven L.

    2013-01-01

    A number of premotor and prefrontal brain areas have been recently shown to play a significant role in response selection in overt sentence production. These areas are anatomically connected to the basal ganglia, a set of subcortical structures that has been traditionally involved in response selection across behavioral domains. The putamen and the caudate, the two major inputs to the basal ganglia, have been shown to undertake motor- as well as non-motor-related selection operations in language processing. Here we investigate the role of these basal ganglia structures in sentence repetition and generation in healthy adults. Although sentence generation is known to activate prefrontal and premotor cortical areas that reciprocally connect with these two neostriatal structures, their specific contributions are not known. We present evidence suggesting that that the putamen undertakes articulation-related aspects across tasks, while the caudate selectively supports selection processes in sentence generation. PMID:23721723

  6. Sensitivity of the resting-state haemodynamic response function estimation to autonomic nervous system fluctuations.

    PubMed

    Wu, Guo-Rong; Marinazzo, Daniele

    2016-05-13

    The haemodynamic response function (HRF) is a key component of the blood oxygen level-dependent (BOLD) signal, providing the mapping between neural activity and the signal measured with functional magnetic resonance imaging (fMRI). Most of the time the HRF is associated with task-based fMRI protocols, in which its onset is explicitly included in the design matrix. On the other hand, the HRF also mediates the relationship between spontaneous neural activity and the BOLD signal in resting-state protocols, in which no explicit stimulus is taken into account. It has been shown that resting-state brain dynamics can be characterized by looking at sparse BOLD 'events', which can be retrieved by point process analysis. These events can be then used to retrieve the HRF at rest. Crucially, cardiac activity can also induce changes in the BOLD signal, thus affecting both the number of these events and the estimation of the haemodynamic response. In this study, we compare the resting-state haemodynamic response retrieved by means of a point process analysis, taking the cardiac fluctuations into account. We find that the resting-state HRF estimation is significantly modulated in the brainstem and surrounding cortical areas. From the analysis of two high-quality datasets with different temporal and spatial resolution, and through the investigation of intersubject correlation, we suggest that spontaneous point process response durations are associated with the mean interbeat interval and low-frequency power of heart rate variability in the brainstem. PMID:27044997

  7. Dynamics of fMRI signals during human brain activations to a stimulus

    NASA Astrophysics Data System (ADS)

    Liu, Haiying; Kato, Toshinori; Neves, Carlos

    2001-05-01

    In fMRI memory study, the temporal behavior of BOLD fMRI signals were consistently observed from various brain processing areas at 1.5 Tesla and consistent with the expected functions. Also, all the activations generally exhibit three types of temporal characteristics: short, sustained and delayed responses in relation to the primary stimuli. To address these cerebral multiphasic responses, a suitable functional data analysis scheme has been used, in which the neural response of a specific brain area to a pre-determined stimulation input of some sort was assumed to be linear. The visual memory study was performed on 6 normal subjects on a clinical MR scanner using a 5 min long rapid dynamical whole brain imaging using EPI acquisition during a single memory task, which involved a 45 sec visual presentation of three simple abstract geometric figures to the subject via LCD projector. The results showed that the activations in visual cortex were tightly correlated with the visual stimulus, while the activations detected in interior temporal, entorhinal cortex and inferior temporal area were delayed. Using the new technique, the brian activations were further characterized quantitatively in terms of delay and prolonged response. The resulting effective impulse response functions corresponding to these brain activations revealed much clearly all the temporal components.

  8. Affective context interferes with brain responses during cognitive processing in borderline personality disorder: fMRI evidence

    PubMed Central

    Soloff, Paul H.; White, Richard; Omari, Amro; Ramaseshan, Karthik; Diwadka, Vaibhav A.

    2015-01-01

    Emotion dysregulation in borderline personality disorder (BPD) is associated with loss of cognitive control in the face of intense negative emotion. Negative emotional context may interfere with cognitive processing through the dysmodulation of brain regions involved in regulation of emotion, impulse control, executive function and memory. Structural and metabolic brain abnormalities have been reported in these regions in BPD. Using novel fMRI protocols, we investigated the neural basis of negative affective interference with cognitive processing targeting these regions. Attention-driven Go No-Go and X-CPT (continuous performance test) protocols, using positive, negative and neutral Ekman faces, targeted the orbital frontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively. A stimulus-driven Episodic Memory task, using images from the International Affective Pictures System, targeted the hippocampus (HIP). Participants comprised 23 women with BPD, who were compared with 15 healthy controls. When Negative>Positive faces were compared in the Go No-Go task, BPD subjects had hyper-activation relative to controls in areas reflecting task-relevant processing: the superior parietal/precuneus and thebasal ganglia. Decreased activation was also noted in the OFC, and increased activation in the amygdala (AMY). In the X-CPT, BPD subjects again showed hyper-activation in task-relevant areas: the superior parietal/precuneus and the ACC. In the stimulus-driven Episodic Memory task, BPD subjects had decreased activation relative to controls in the HIP, ACC, superior parietal/precuneus, and dorsal prefrontal cortex (dPFC) (for encoding), and the ACC, dPFC, and HIP for retrieval of Negative>Positive pictures, reflecting impairment of task-relevant functions. Negative affective interference with cognitive processing in BPD differs from that in healthy controls and is associated with functional abnormalities in brain networks reported to have structural or metabolic

  9. Graph Theoretical Analysis of BOLD Functional Connectivity during Human Sleep without EEG Monitoring

    PubMed Central

    Lv, Jun; Liu, Dongdong; Ma, Jing; Wang, Xiaoying; Zhang, Jue

    2015-01-01

    Background Functional brain networks of human have been revealed to have small-world properties by both analyzing electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) time series. Methods & Results In our study, by using graph theoretical analysis, we attempted to investigate the changes of paralimbic-limbic cortex between wake and sleep states. Ten healthy young people were recruited to our experiment. Data from 2 subjects were excluded for the reason that they had not fallen asleep during the experiment. For each subject, blood oxygen level dependency (BOLD) images were acquired to analyze brain network, and peripheral pulse signals were obtained continuously to identify if the subject was in sleep periods. Results of fMRI showed that brain networks exhibited stronger small-world characteristics during sleep state as compared to wake state, which was in consistent with previous studies using EEG synchronization. Moreover, we observed that compared with wake state, paralimbic-limbic cortex had less connectivity with neocortical system and centrencephalic structure in sleep. Conclusions In conclusion, this is the first study, to our knowledge, has observed that small-world properties of brain functional networks altered when human sleeps without EEG synchronization. Moreover, we speculate that paralimbic-limbic cortex organization owns an efficient defense mechanism responsible for suppressing the external environment interference when humans sleep, which is consistent with the hypothesis that the paralimbic-limbic cortex may be functionally disconnected from brain regions which directly mediate their interactions with the external environment. Our findings also provide a reasonable explanation why stable sleep exhibits homeostasis which is far less susceptible to outside world. PMID:26360464

  10. Branding and a child's brain: an fMRI study of neural responses to logos.

    PubMed

    Bruce, Amanda S; Bruce, Jared M; Black, William R; Lepping, Rebecca J; Henry, Janice M; Cherry, Joseph Bradley C; Martin, Laura E; Papa, Vlad B; Davis, Ann M; Brooks, William M; Savage, Cary R

    2014-01-01

    Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children's brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing.

  11. Branding and a child's brain: an fMRI study of neural responses to logos.

    PubMed

    Bruce, Amanda S; Bruce, Jared M; Black, William R; Lepping, Rebecca J; Henry, Janice M; Cherry, Joseph Bradley C; Martin, Laura E; Papa, Vlad B; Davis, Ann M; Brooks, William M; Savage, Cary R

    2014-01-01

    Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children's brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing. PMID:22997054

  12. Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses

    PubMed Central

    Goldstein, Jill M.; Lancaster, Katie; Longenecker, Julia M.; Abbs, Brandon; Holsen, Laura M.; Cherkerzian, Sara; Whitfield-Gabrieli, Susan; Makris, Nicolas; Tsuang, Ming T.; Buka, Stephen L.; Seidman, Larry J.; Klibanski, Anne

    2015-01-01

    Psychosis involves dysregulation of response to stress, particularly to negative valence stimuli. Functional magnetic resonance imaging studies of psychosis have shown hyperactivity in hypothalamus, hippocampus, amygdala, and anterior cingulate cortex, and orbitofrontal and medial prefrontal cortices. Sex differences in these deficits may be associated with steroid hormone pathway abnormalities, i.e., dysregulation of the hypothalamic pituitary-adrenal and -gondal axes. We predicted abnormal steroid hormone levels in psychosis cases would be associated with hyperactivity in hypothalamus, amygdala, and hippocampus, and hypoactivity in prefrontal and anterior cingulate cortices in a sex-dependent way, with more severe deficits in men than women with psychosis. We studied 32 psychosis cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood throughout functional magnetic resonance imaging procedures. Males with psychosis showed hyperactivity across all hypothesized regions, including the hypothalamus and anterior cingulate cortex by family-wise corrected significance. Females showed hyperactivity in the hippocampus and amygdala and hypoactivity in orbital and medial prefrontal cortices, the latter by family-wise correction. Interaction of case status by sex was significant in the medial prefrontal cortex and, marginally so, in the left orbitofrontal cortex, with female cases (vs. healthy females and males) exhibiting the lowest activity. Male and female cases compared with their healthy counterparts were hypercortisolemic, which was associated with hyperactivity in prefrontal cortices in male cases and hypoactivity in female cases. This was further associated, respectively, with low bioavailable testosterone in male cases and low estradiol in female cases. Findings suggest disruptions in neural-hormone associations in response to stress are sex-dependent in psychosis, particularly in the prefrontal cortex. PMID

  13. Sensory-motor networks involved in speech production and motor control: an fMRI study.

    PubMed

    Behroozmand, Roozbeh; Shebek, Rachel; Hansen, Daniel R; Oya, Hiroyuki; Robin, Donald A; Howard, Matthew A; Greenlee, Jeremy D W

    2015-04-01

    Speaking is one of the most complex motor behaviors developed to facilitate human communication. The underlying neural mechanisms of speech involve sensory-motor interactions that incorporate feedback information for online monitoring and control of produced speech sounds. In the present study, we adopted an auditory feedback pitch perturbation paradigm and combined it with functional magnetic resonance imaging (fMRI) recordings in order to identify brain areas involved in speech production and motor control. Subjects underwent fMRI scanning while they produced a steady vowel sound /a/ (speaking) or listened to the playback of their own vowel production (playback). During each condition, the auditory feedback from vowel production was either normal (no perturbation) or perturbed by an upward (+600 cents) pitch-shift stimulus randomly. Analysis of BOLD responses during speaking (with and without shift) vs. rest revealed activation of a complex network including bilateral superior temporal gyrus (STG), Heschl's gyrus, precentral gyrus, supplementary motor area (SMA), Rolandic operculum, postcentral gyrus and right inferior frontal gyrus (IFG). Performance correlation analysis showed that the subjects produced compensatory vocal responses that significantly correlated with BOLD response increases in bilateral STG and left precentral gyrus. However, during playback, the activation network was limited to cortical auditory areas including bilateral STG and Heschl's gyrus. Moreover, the contrast between speaking vs. playback highlighted a distinct functional network that included bilateral precentral gyrus, SMA, IFG, postcentral gyrus and insula. These findings suggest that speech motor control involves feedback error detection in sensory (e.g. auditory) cortices that subsequently activate motor-related areas for the adjustment of speech parameters during speaking.

  14. Fluctuations in electrodermal activity reveal variations in single trial brain responses to painful laser stimuli--a fMRI/EEG study.

    PubMed

    Mobascher, A; Brinkmeyer, J; Warbrick, T; Musso, F; Wittsack, H J; Stoermer, R; Saleh, A; Schnitzler, A; Winterer, G

    2009-02-01

    Pain is a complex experience with sensory, emotional and cognitive aspects. It also includes a sympathetic response that can be captured by measuring the electrodermal activity (EDA). The present study was performed to investigate which brain areas are associated with sympathetic activation in experimental pain; an issue that has not been addressed with fMRI (functional magnetic resonance imaging) thus far. Twelve healthy subjects received painful laser stimulation to the left hand. The event-related fMRI BOLD (blood oxygen level dependent) response was measured together with simultaneous EEG (electroencephalography) and EDA recordings. Laser stimuli induced the expected EDA response, evoked EEG potentials and BOLD responses. Single trial EDA amplitudes were used to guide further analysis of fMRI and EEG data. We found significantly higher BOLD responses in trials with high EDA vs. low EDA trials, predominantly in the insula and somatosensory cortex (S1/S2). Likewise, in the EEG we found the N2 laser evoked potentials to have significantly higher amplitudes in trials with high vs. low EDA. Furthermore EDA-informed BOLD modeling explained additional signal variance in sensory areas and yielded higher group level activation. We conclude that the sympathetic response to pain is associated with activation in pain-processing brain regions, predominantly in sensory areas and that single trial (EDA)-information can add to BOLD modeling by taking some of the response variability across trials and subjects into account. Thus, EDA is a useful additional, objective index when pain is studied with fMRI/EEG which might be of particular relevance in the context of genetic- and pharmacoimaging. PMID:18848631

  15. Differential Brain Responses to Cries of Infants with Autistic Disorder and Typical Development: An fMRI Study

    ERIC Educational Resources Information Center

    Venuti, Paola; Caria, Andrea; Esposito, Gianluca; De Pisapia, Nicola; Bornstein, Marc H.; de Falco, Simona

    2012-01-01

    This study used fMRI to measure brain activity during adult processing of cries of infants with autistic disorder (AD) compared to cries of typically developing (TD) infants. Using whole brain analysis, we found that cries of infants with AD compared to those of TD infants elicited enhanced activity in brain regions associated with verbal and…

  16. Characterization and reduction of cardiac- and respiratory-induced noise as a function of the sampling rate (TR) in fMRI.

    PubMed

    Cordes, Dietmar; Nandy, Rajesh R; Schafer, Scott; Wager, Tor D

    2014-04-01

    It has recently been shown that both high-frequency and low-frequency cardiac and respiratory noise sources exist throughout the entire brain and can cause significant signal changes in fMRI data. It is also known that the brainstem, basal forebrain and spinal cord areas are problematic for fMRI because of the magnitude of cardiac-induced pulsations at these locations. In this study, the physiological noise contributions in the lower brain areas (covering the brainstem and adjacent regions) are investigated and a novel method is presented for computing both low-frequency and high-frequency physiological regressors accurately for each subject. In particular, using a novel optimization algorithm that penalizes curvature (i.e. the second derivative) of the physiological hemodynamic response functions, the cardiac- and respiratory-related response functions are computed. The physiological noise variance is determined for each voxel and the frequency-aliasing property of the high-frequency cardiac waveform as a function of the repetition time (TR) is investigated. It is shown that for the brainstem and other brain areas associated with large pulsations of the cardiac rate, the temporal SNR associated with the low-frequency range of the BOLD response has maxima at subject-specific TRs. At these values, the high-frequency aliased cardiac rate can be eliminated by digital filtering without affecting the BOLD-related signal. PMID:24355483

  17. Brain responses to altered auditory feedback during musical keyboard production: an fMRI study.

    PubMed

    Pfordresher, Peter Q; Mantell, James T; Brown, Steven; Zivadinov, Robert; Cox, Jennifer L

    2014-03-27

    Alterations of auditory feedback during piano performance can be profoundly disruptive. Furthermore, different alterations can yield different types of disruptive effects. Whereas alterations of feedback synchrony disrupt performed timing, alterations of feedback pitch contents can disrupt accuracy. The current research tested whether these behavioral dissociations correlate with differences in brain activity. Twenty pianists performed simple piano keyboard melodies while being scanned in a 3-T magnetic resonance imaging (MRI) scanner. In different conditions they experienced normal auditory feedback, altered auditory feedback (asynchronous delays or altered pitches), or control conditions that excluded movement or sound. Behavioral results replicated past findings. Neuroimaging data suggested that asynchronous delays led to increased activity in Broca's area and its right homologue, whereas disruptive alterations of pitch elevated activations in the cerebellum, area Spt, inferior parietal lobule, and the anterior cingulate cortex. Both disruptive conditions increased activations in the supplementary motor area. These results provide the first evidence of neural responses associated with perception/action mismatch during keyboard production. PMID:24513403

  18. Brain responses to altered auditory feedback during musical keyboard production: an fMRI study.

    PubMed

    Pfordresher, Peter Q; Mantell, James T; Brown, Steven; Zivadinov, Robert; Cox, Jennifer L

    2014-03-27

    Alterations of auditory feedback during piano performance can be profoundly disruptive. Furthermore, different alterations can yield different types of disruptive effects. Whereas alterations of feedback synchrony disrupt performed timing, alterations of feedback pitch contents can disrupt accuracy. The current research tested whether these behavioral dissociations correlate with differences in brain activity. Twenty pianists performed simple piano keyboard melodies while being scanned in a 3-T magnetic resonance imaging (MRI) scanner. In different conditions they experienced normal auditory feedback, altered auditory feedback (asynchronous delays or altered pitches), or control conditions that excluded movement or sound. Behavioral results replicated past findings. Neuroimaging data suggested that asynchronous delays led to increased activity in Broca's area and its right homologue, whereas disruptive alterations of pitch elevated activations in the cerebellum, area Spt, inferior parietal lobule, and the anterior cingulate cortex. Both disruptive conditions increased activations in the supplementary motor area. These results provide the first evidence of neural responses associated with perception/action mismatch during keyboard production.

  19. Convergent and Divergent fMRI Responses in Children and Adults to Increasing Language Production Demands

    PubMed Central

    Krishnan, Saloni; Leech, Robert; Mercure, Evelyne; Lloyd-Fox, Sarah; Dick, Frederic

    2015-01-01

    In adults, patterns of neural activation associated with perhaps the most basic language skill—overt object naming—are extensively modulated by the psycholinguistic and visual complexity of the stimuli. Do children's brains react similarly when confronted with increasing processing demands, or they solve this problem in a different way? Here we scanned 37 children aged 7–13 and 19 young adults who performed a well-normed picture-naming task with 3 levels of difficulty. While neural organization for naming was largely similar in childhood and adulthood, adults had greater activation in all naming conditions over inferior temporal gyri and superior temporal gyri/supramarginal gyri. Manipulating naming complexity affected adults and children quite differently: neural activation, especially over the dorsolateral prefrontal cortex, showed complexity-dependent increases in adults, but complexity-dependent decreases in children. These represent fundamentally different responses to the linguistic and conceptual challenges of a simple naming task that makes no demands on literacy or metalinguistics. We discuss how these neural differences might result from different cognitive strategies used by adults and children during lexical retrieval/production as well as developmental changes in brain structure and functional connectivity. PMID:24907249

  20. Lag structure in resting-state fMRI

    PubMed Central

    Snyder, A. Z.; Hacker, C. D.; Raichle, M. E.

    2014-01-01

    The discovery that spontaneous fluctuations in blood oxygen level-dependent (BOLD) signals contain information about the functional organization of the brain has caused a paradigm shift in neuroimaging. It is now well established that intrinsic brain activity is organized into spatially segregated resting-state networks (RSNs). Less is known regarding how spatially segregated networks are integrated by the propagation of intrinsic activity over time. To explore this question, we examined the latency structure of spontaneous fluctuations in the fMRI BOLD signal. Our data reveal that intrinsic activity propagates through and across networks on a timescale of ∼1 s. Variations in the latency structure of this activity resulting from sensory state manipulation (eyes open vs. closed), antecedent motor task (button press) performance, and time of day (morning vs. evening) suggest that BOLD signal lags reflect neuronal processes rather than hemodynamic delay. Our results emphasize the importance of the temporal structure of the brain's spontaneous activity. PMID:24598530

  1. Task-Dependent Semantic Interference in Language Production: An fMRI Study

    PubMed Central

    Spalek, Katharina; Thompson-Schill, Sharon L.

    2008-01-01

    We used fMRI to investigate competition during language production in two word production tasks: object naming and color naming of achromatic line drawings. Generally, fMRI activation was higher for color naming. The line drawings were followed by a word (the distractor word) that referred to either the object, a related object, or an unrelated object. The effect of the distractor word on the BOLD response was qualitatively different for the two tasks. The activation pattern suggests two different kinds of competition during lexical retrieval: (1) Task-relevant responses (e.g., red in color naming) compete with task-irrelevant responses (i.e., the object's name). This competition effect was dominant in prefrontal cortex. (2) Multiple task-relevant responses (i.e., target word and distractor word) compete for selection. This competition effect was dominant in ventral temporal cortex. This study provides further evidence for the distinct roles of frontal and temporal cortex in language production, while highlighting the effects of competition, albeit from different sources, in both regions. PMID:18619668

  2. Task-dependent semantic interference in language production: an fMRI study.

    PubMed

    Spalek, Katharina; Thompson-Schill, Sharon L

    2008-12-01

    We used fMRI to investigate competition during language production in two word production tasks: object naming and color naming of achromatic line drawings. Generally, fMRI activation was higher for color naming. The line drawings were followed by a word (the distractor word) that referred to either the object, a related object, or an unrelated object. The effect of the distractor word on the BOLD response was qualitatively different for the two tasks. The activation pattern suggests two different kinds of competition during lexical retrieval: (1) Task-relevant responses (e.g., red in color naming) compete with task-irrelevant responses (i.e., the object's name). This competition effect was dominant in prefrontal cortex. (2) Multiple task-relevant responses (i.e., target word and distractor word) compete for selection. This competition effect was dominant in ventral temporal cortex. This study provides further evidence for the distinct roles of frontal and temporal cortex in language production, while highlighting the effects of competition, albeit from different sources, in both regions.

  3. The PRESTO technique for fMRI.

    PubMed

    van Gelderen, P; Duyn, J H; Ramsey, N F; Liu, G; Moonen, C T W

    2012-08-15

    In the early days of BOLD fMRI, the acquisition of T(2)(*) weighted data was greatly facilitated by rapid scan techniques such as EPI. The latter, however, was only available on a few MRI systems that were equipped with specialized hardware that allowed rapid switching of the imaging gradients. For this reason, soon after the invention of fMRI, the scan technique PRESTO was developed to make rapid T(2)(*) weighted scanning available on standard clinical scanners. This method combined echo shifting, which allows for echo times longer than the sequence repetition time, with acquisition of multiple k-space lines per excitation. These two concepts were combined in order to achieve a method fast enough for fMRI, while maintaining a sufficiently long echo time for optimal contrast. PRESTO has been primarily used for 3D scanning, which minimized the contribution of large vessels due to inflow effects. Although PRESTO is still being used today, its appeal has lessened somewhat due to increased gradient performance of modern MRI scanners. Compared to 2D EPI, PRESTO may have somewhat reduced temporal stability, which is a disadvantage for fMRI that may not outweigh the advantage of reduced inflow effects provided by 3D scanning. In this overview, the history of the development of the PRESTO is presented, followed by a qualitative comparison with EPI. PMID:22245350

  4. Comparison of fMRI and PEPSI during language processing in children.

    PubMed

    Serafini, S; Steury, K; Richards, T; Corina, D; Abbott, R; Dager, S R; Berninger, V

    2001-02-01

    The present study explored the correlation between lactate as detected by MR spectroscopy (MRS) and blood oxygenation level dependent (BOLD) responses in male children during auditory-based language tasks. All subjects (N = 8) participated in one proton echo planar spectroscopic imaging (PEPSI) and one functional magnetic resonance imaging (fMRI) session that required phonological and lexical judgments to aurally presented stimuli. Valid PEPSI data was limited in the frontal areas of the brain due to the magnetic susceptibility of the eye orbits and frontal sinuses. Findings from the remainder of the brain indicate that subjects show a significant consistency across imaging techniques in the left temporal area during the lexical task, but not in any other measurable area or during the phonological task. Magn Reson Med 45:217-225, 2001.

  5. Comparison of fMRI and PEPSI during language processing in children.

    PubMed

    Serafini, S; Steury, K; Richards, T; Corina, D; Abbott, R; Dager, S R; Berninger, V

    2001-02-01

    The present study explored the correlation between lactate as detected by MR spectroscopy (MRS) and blood oxygenation level dependent (BOLD) responses in male children during auditory-based language tasks. All subjects (N = 8) participated in one proton echo planar spectroscopic imaging (PEPSI) and one functional magnetic resonance imaging (fMRI) session that required phonological and lexical judgments to aurally presented stimuli. Valid PEPSI data was limited in the frontal areas of the brain due to the magnetic susceptibility of the eye orbits and frontal sinuses. Findings from the remainder of the brain indicate that subjects show a significant consistency across imaging techniques in the left temporal area during the lexical task, but not in any other measurable area or during the phonological task. Magn Reson Med 45:217-225, 2001. PMID:11180429

  6. Neural substrates of figurative language during natural speech perception: an fMRI study

    PubMed Central

    Nagels, Arne; Kauschke, Christina; Schrauf, Judith; Whitney, Carin; Straube, Benjamin; Kircher, Tilo

    2013-01-01

    Many figurative expressions are fully conventionalized in everyday speech. Regarding the neural basis of figurative language processing, research has predominantly focused on metaphoric expressions in minimal semantic context. It remains unclear in how far metaphoric expressions during continuous text comprehension activate similar neural networks as isolated metaphors. We therefore investigated the processing of similes (figurative language, e.g., “He smokes like a chimney!”) occurring in a short story. Sixteen healthy, male, native German speakers listened to similes that came about naturally in a short story, while blood-oxygenation-level-dependent (BOLD) responses were measured with functional magnetic resonance imaging (fMRI). For the event-related analysis, similes were contrasted with non-figurative control sentences (CS). The stimuli differed with respect to figurativeness, while they were matched for frequency of words, number of syllables, plausibility, and comprehensibility. Similes contrasted with CS resulted in enhanced BOLD responses in the left inferior (IFG) and adjacent middle frontal gyrus. Concrete CS as compared to similes activated the bilateral middle temporal gyri as well as the right precuneus and the left middle frontal gyrus (LMFG). Activation of the left IFG for similes in a short story is consistent with results on single sentence metaphor processing. The findings strengthen the importance of the left inferior frontal region in the processing of abstract figurative speech during continuous, ecologically-valid speech comprehension; the processing of concrete semantic contents goes along with a down-regulation of bilateral temporal regions. PMID:24065897

  7. Analysis of Neural-BOLD Coupling Through Four Models of the Neural Metabolic Demand.

    PubMed

    Tyler, Christopher W; Likova, Lora T; Nicholas, Spero C

    2015-01-01

    The coupling of the neuronal energetics to the blood-oxygen-level-dependent (BOLD) response is still incompletely understood. To address this issue, we compared the fits of four plausible models of neurometabolic coupling dynamics to available data for simultaneous recordings of the local field potential and the local BOLD response recorded from monkey primary visual cortex over a wide range of stimulus durations. The four models of the metabolic demand driving the BOLD response were: direct coupling with the overall LFP; rectified coupling to the LFP; coupling with a slow adaptive component of the implied neural population response; and coupling with the non-adaptive intracellular input signal defined by the stimulus time course. Taking all stimulus durations into account, the results imply that the BOLD response is most closely coupled with metabolic demand derived from the intracellular input waveform, without significant influence from the adaptive transients and nonlinearities exhibited by the LFP waveform.

  8. Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance

    PubMed Central

    Bakker, Arnold; Albert, Marilyn S.; Krauss, Gregory; Speck, Caroline L.; Gallagher, Michela

    2015-01-01

    individuals with aMCI and therapeutic intervention using fMRI to detect target engagement in response to treatment. PMID:25844322

  9. fMRI Correlates of White Matter Hyperintensities in Late-Life Depression

    PubMed Central

    Aizenstein, Howard J.; Andreescu, Carmen; Edelman, Kathryn L.; Cochran, Jennifer L.; Price, Julie; Butters, Meryl A.; Karp, Jordan; Patel, Meenal; Reynolds, Charles F.

    2013-01-01

    Objective This study tests whether or not the structural white matter lesions that are characteristic of late-life depression are associated with alterations in the functional affective circuits of late-life depression. This study used an emotional faces paradigm that has been shown to engage the affective limbic brain regions. Method Thirty-three elderly depressed patients and 27 nondepressed comparison subjects participated in this study. The patients were recruited through the NIMH-sponsored Advanced Center for Interventions and Services Research for the Study of Late-Life Mood Disorders at the University of Pittsburgh Center for Bioethics and Health Law. Structural and functional MRI was used to assess white matter hyperintensity (WMH) burden and functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) response on a facial expression affective-reactivity task in both elderly participants with nonpsychotic and non-bipolar major depression (unmedicated) and nondepressed elderly comparison subjects. Results As expected, greater subgenual cingulate activity was observed in the depressed patients relative to the nondepressed comparison subjects. This same region showed greater task-related activity associated with a greater burden of cerebrovascular white matter change in the depressed group. Moreover, the depressed group showed a significantly greater interaction of WMH by fMRI activity effect than the nondepressed group. Conclusions The observation that high WMH burden in late-life depression is associated with greater BOLD response on the affective-reactivity task supports the model that white matter ischemia in elderly depressed patients disrupts brain mechanisms of affective regulation and leads to limbic hyperactivation. PMID:21799066

  10. Compassion, guilt and innocence: An fMRI study of responses to victims who are responsible for their fate.

    PubMed

    Fehse, Kai; Silveira, Sarita; Elvers, Katrin; Blautzik, Janusch

    2015-01-01

    Compassion is a human feeling towards an individual who is suffering. However, the responses toward a victim are not always compassionate and may, for example, be moderated by the perceived responsibility of the victim. In the present study, we investigated the neural correlates of compassion and specifically differentiated the responses to other individuals' misfortunes depending on whether the victim was responsible for the event that occurred. In particular, we identified increased activation of the left insula, medial prefrontal cortex (mPFC), and adjacent anterior cingulate cortex when the participants read sentences with innocent compared with responsible victims. The reverse contrast revealed increased activation of the bilateral temporoparietal junction, right precuneus, and right dorsolateral prefrontal cortex (dlPFC). Using a psycho-physiological interaction (PPI) analysis, we demonstrated that in the responsible condition, right dlPFC activation was accompanied by decreased activation in the left insula, anterior cingulate cortex (ACC), and mPFC. This inverse effective connectivity illustrates the antagonism of the dlPFC and mPFC in compassion-related appraisal of external events. More specifically, our results imply that regulatory mechanisms of compassion are related to the perception of responsibility.

  11. No Evidence for Automatic Remapping of Stimulus Features or Location Found with fMRI

    PubMed Central

    Lescroart, Mark D.; Kanwisher, Nancy; Golomb, Julie D.

    2016-01-01

    The input to our visual system shifts every time we move our eyes. To maintain a stable percept of the world, visual representations must be updated with each saccade. Near the time of a saccade, neurons in several visual areas become sensitive to the regions of visual space that their receptive fields occupy after the saccade. This process, known as remapping, transfers information from one set of neurons to another, and may provide a mechanism for visual stability. However, it is not clear whether remapping transfers information about stimulus features in addition to information about stimulus location. To investigate this issue, we recorded blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses while human subjects viewed images of faces and houses (two visual categories with many feature differences). Immediately after some image presentations, subjects made a saccade that moved the previously stimulated location to the opposite side of the visual field. We then used a combination of univariate analyses and multivariate pattern analyses to test whether information about stimulus location and stimulus features were remapped to the ipsilateral hemisphere after the saccades. We found no reliable indication of stimulus feature remapping in any region. However, we also found no reliable indication of stimulus location remapping, despite the fact that our paradigm was highly similar to previous fMRI studies of remapping. The absence of location remapping in our study precludes strong conclusions regarding feature remapping. However, these results also suggest that measurement of location remapping with fMRI depends strongly on the details of the experimental paradigm used. We highlight differences in our approach from the original fMRI studies of remapping, discuss potential reasons for the failure to generalize prior location remapping results, and suggest directions for future research. PMID:27378866

  12. Neural Correlates of Empathy with Pain Show Habituation Effects. An fMRI Study

    PubMed Central

    Preis, Mira A.; Kröner-Herwig, Birgit; Schmidt-Samoa, Carsten; Dechent, Peter; Barke, Antonia

    2015-01-01

    Background Neuroimaging studies have demonstrated that the actual experience of pain and the perception of another person in pain share common neural substrates, including the bilateral anterior insular cortex and the anterior midcingulate cortex. As many fMRI studies include the exposure of participants to repeated, similar stimuli, we examined whether empathic neural responses were affected by habituation and whether the participants' prior pain experience influenced these habituation effects. Method In 128 trials (four runs), 62 participants (31 women, 23.0 ± 4.2 years) were shown pictures of hands exposed to painful pressure (pain pictures) and unexposed (neutral pictures). After each trial, the participants rated the pain of the model. Prior to the experiment, participants were either exposed to the same pain stimulus (pain exposure group) or not (touch exposure group). In order to assess possible habituation effects, linear changes in the strength of the BOLD response to the pain pictures (relative to the neutral pictures) and in the ratings of the model’s pain were evaluated across the four runs. Results Although the ratings of the model’s pain remained constant over time, we found neural habituation in the bilateral anterior/midinsular cortex, the posterior midcingulate extending to dorsal posterior cingulate cortex, the supplementary motor area, the cerebellum, the right inferior parietal lobule, and the left superior frontal gyrus, stretching to the pregenual anterior cingulate cortex. The participant’s prior pain experience did neither affect their ratings of the model’s pain nor their maintenance of BOLD activity in areas associated with empathy. Interestingly, participants with high trait personal distress and fantasy tended to show less habituation in the anterior insula. Conclusion Neural structures showed a decrease of the BOLD signal, indicating habituation over the course of 45 minutes. This can be interpreted as a neuronal mechanism

  13. Trial-by-trial coupling between EEG and BOLD identifies networks related to alpha and theta EEG power increases during working memory maintenance.

    PubMed

    Scheeringa, René; Petersson, Karl Magnus; Oostenveld, Robert; Norris, David G; Hagoort, Peter; Bastiaansen, Marcel C M

    2009-02-01

    PET and fMRI experiments have previously shown that several brain regions in the frontal and parietal lobe are involved in working memory maintenance. MEG and EEG experiments have shown parametric increases with load for oscillatory activity in posterior alpha and frontal theta power. In the current study we investigated whether the areas found with fMRI can be associated with these alpha and theta effects by measuring simultaneous EEG and fMRI during a modified Sternberg task This allowed us to correlate EEG at the single trial level with the fMRI BOLD signal by forming a regressor based on single trial alpha and theta power estimates. We observed a right posterior, parametric alpha power increase, which was functionally related to decreases in BOLD in the primary visual cortex and in the posterior part of the right middle temporal gyrus. We relate this finding to the inhibition of neuronal activity that may interfere with WM maintenance. An observed parametric increase in frontal theta power was correlated to a decrease in BOLD in regions that together form the default mode network. We did not observe correlations between oscillatory EEG phenomena and BOLD in the traditional WM areas. In conclusion, the study shows that simultaneous EEG-fMRI recordings can be successfully used to identify the emergence of functional networks in the brain during the execution of a cognitive task.

  14. Brain Network Response to Acupuncture Stimuli in Experimental Acute Low Back Pain: An fMRI Study

    PubMed Central

    Shi, Yu; Liu, Ziping; Zhang, Shanshan; Li, Qiang; Guo, Shigui; Yang, Jiangming; Wu, Wen

    2015-01-01

    Most neuroimaging studies have demonstrated that acupuncture can significantly modulate brain activation patterns in healthy subjects, while only a few studies have examined clinical pain. In the current study, we combined an experimental acute low back pain (ALBP) model and functional magnetic resonance imaging (fMRI) to explore the neural mechanisms of acupuncture analgesia. All ALBP subjects first underwent two resting state fMRI scans at baseline and during a painful episode and then underwent two additional fMRI scans, once during acupuncture stimulation (ACUP) and once during tactile stimulation (SHAM) pseudorandomly, at the BL40 acupoint. Our results showed that, compared with the baseline, the pain state had higher regional homogeneity (ReHo) values in the pain matrix, limbic system, and default mode network (DMN) and lower ReHo values in frontal gyrus and temporal gyrus; compared with the OFF status, ACUP yielded broad deactivation in subjects, including nearly all of the limbic system, pain status, and DMN, and also evoked numerous activations in the attentional and somatosensory systems; compared with SHAM, we found that ACUP induced more deactivations and fewer activations in the subjects. Multiple brain networks play crucial roles in acupuncture analgesia, suggesting that ACUP exceeds a somatosensory-guided mind-body therapy for ALBP. PMID:26161117

  15. Brain Network Response to Acupuncture Stimuli in Experimental Acute Low Back Pain: An fMRI Study.

    PubMed

    Shi, Yu; Liu, Ziping; Zhang, Shanshan; Li, Qiang; Guo, Shigui; Yang, Jiangming; Wu, Wen

    2015-01-01

    Most neuroimaging studies have demonstrated that acupuncture can significantly modulate brain activation patterns in healthy subjects, while only a few studies have examined clinical pain. In the current study, we combined an experimental acute low back pain (ALBP) model and functional magnetic resonance imaging (fMRI) to explore the neural mechanisms of acupuncture analgesia. All ALBP subjects first underwent two resting state fMRI scans at baseline and during a painful episode and then underwent two additional fMRI scans, once during acupuncture stimulation (ACUP) and once during tactile stimulation (SHAM) pseudorandomly, at the BL40 acupoint. Our results showed that, compared with the baseline, the pain state had higher regional homogeneity (ReHo) values in the pain matrix, limbic system, and default mode network (DMN) and lower ReHo values in frontal gyrus and temporal gyrus; compared with the OFF status, ACUP yielded broad deactivation in subjects, including nearly all of the limbic system, pain status, and DMN, and also evoked numerous activations in the attentional and somatosensory systems; compared with SHAM, we found that ACUP induced more deactivations and fewer activations in the subjects. Multiple brain networks play crucial roles in acupuncture analgesia, suggesting that ACUP exceeds a somatosensory-guided mind-body therapy for ALBP. PMID:26161117

  16. Plasticity in animal personality traits: does prior experience alter the degree of boldness?

    PubMed Central

    Frost, Ashley J; Winrow-Giffen, Alexandria; Ashley, Paul J; Sneddon, Lynne U

    2006-01-01

    Theoreticians predict that animal ‘personality’ traits may be maladaptive if fixed throughout different contexts, so the present study aimed to test whether these traits are fixed or plastic. Rainbow trout (Onchorhyncus mykiss) were given emboldening or negative experiences in the forms of watching bold or shy individuals responding to novelty or winning or losing fights to examine whether prior experience affected boldness. Bold individuals that lost fights or watched shy demonstrators became more shy by increasing their latency to approach a novel object, whereas shy observers that watched bold demonstrators remained cautious and did not modify their responses to novelty. Shy winners became bolder and decreased their latency to approach a novel object, but shy losers also displayed this shift. In comparison, control groups showed no change in behaviour. Bold fishes given negative experiences reduced their boldness which may be an adaptive response; however, shy fishes may base their strategic decisions upon self-assessment of their relative competitive ability and increase their boldness in situations where getting to resources more quickly ensures they outcompete better competitors. PMID:17164196

  17. An application of the complex general linear model to analysis of fMRI single subjects multiple stimuli input data

    NASA Astrophysics Data System (ADS)

    Rio, Daniel; Rawlings, Robert; Woltz, Lawrence; Gilman, Jodi; Hommer, Daniel

    2009-02-01

    The general linear model (GLM) has been extensively applied to fMRI data in the time domain. However, traditionally time series data can be analyzed in the Fourier domain where the assumptions made as to the noise in the signal can be less restrictive and statistical tests are mathematically more rigorous. A complex form of the GLM in the Fourier domain has been applied to the analysis of fMRI (BOLD) data. This methodology has a number of advantages over temporal methods: 1. Noise in the fMRI data is modeled more generally and closer to that actually seen in the data. 2. Any input function is allowed regardless of the timing. 3. Non-parametric estimation of the transfer functions at each voxel are possible. 4. Rigorous statistical inference of single subjects is possible. This is demonstrated in the analysis of an experimental design with random exponentially distributed stimulus inputs (a two way ANOVA design with input stimuli images of alcohol, non-alcohol beverage and positive or negative images) sampled at 400 milliseconds. This methodology applied to a pair of subjects showed precise and interesting results (e.g. alcoholic beverage images attenuate the response of negative images in an alcoholic as compared to a control subject).

  18. "Extreme Bold" in the Faculty Ranks

    ERIC Educational Resources Information Center

    Kuusisto, Stephen

    2013-01-01

    Boldness, defense, and the necessity of talking back remain as central to life with disability in one's time as in Francis Bacon's age. "Therefore all deformed persons are extreme bold," Bacon wrote, "first, as in their own defence, as being exposed to scorn, but in process of time, by a general habit." Perhaps no word carries more weight in the…

  19. The neural correlates of volitional attention: A combined fMRI and ERP study.

    PubMed

    Bengson, Jesse J; Kelley, Todd A; Mangun, George R

    2015-07-01

    Studies of visual-spatial attention typically use instructional cues to direct attention to a relevant location, but in everyday vision, attention is often focused volitionally, in the absence of external signals. Although investigations of cued attention comprise hundreds of behavioral and physiological studies, remarkably few studies of voluntary attention have addressed the challenging question of how spatial attention is initiated and controlled in the absence of external instructions, which we refer to as willed attention. To explore this question, we employed a trial-by-trial spatial attention task using electroencephalography and functional magnetic resonance imaging (fMRI). The fMRI results reveal a unique network of brain regions for willed attention that includes the anterior cingulate cortex, left middle frontal gyrus (MFG), and the left and right anterior insula (AI). We also observed two event-related potentials (ERPs) associated with willed attention; one with a frontal distribution occurring 250-350 ms postdecision cue onset (EWAC: Early Willed Attention Component), and another occurring between 400 and 800 ms postdecision-cue onset (WAC: Willed Attention Component). In addition, each ERP component uniquely correlated across subjects with different willed attention-specific sites of BOLD activation. The EWAC was correlated with the willed attention-specific left AI and left MFG activations and the later WAC was correlated only with left AI. These results offer a comprehensive and novel view of the electrophysiological and anatomical profile of willed attention and further illustrate the relationship between scalp-recorded ERPs and the BOLD response.

  20. Task and Resting-State fMRI Reveal Altered Salience Responses to Positive Stimuli in Patients with Major Depressive Disorder.

    PubMed

    Yang, Yang; Zhong, Ning; Imamura, Kazuyuki; Lu, Shengfu; Li, Mi; Zhou, Haiyan; Li, Huaizhou; Yang, Xiaojing; Wan, Zhijiang; Wang, Gang; Hu, Bin; Li, Kuncheng

    2016-01-01

    Altered brain function in patients with major depressive disorder (MDD) has been repeatedly demonstrated by task-based and resting-state studies, respectively. However, less is known concerning whether overlapped abnormalities in functional activities across modalities exist in MDD patients. To find out the answer, we implemented an fMRI experiment and collected both task and resting-state data from 19 MDD patients and 19 matched, healthy, controls. A distraction paradigm involving emotionally valenced pictures was applied to induce affective responses in subjects. As a result, concurrent deficits were found in arousing activation during a positive task in both the reward circuit and salience network (SN) that is composed of the dorsal part of anterior cingulate cortex (dACC) and bilateral anterior insulae (AI) in only the MDD group. Subsequent amplitude of low frequency fluctuations (ALFF) and functional connectivity analyses based on resting-state data exhibited consistent alterations in the bilateral AI of MDD patients, and indicated patients' difficulties in regulating the balance between central executive network (CEN) and default mode network (DMN) due to altered connectivity among the CEN, DMN, and SN. Our findings provide new evidence demonstrating impaired salience processing and resulting alterations in responses to positive stimuli in MDD patients. Furthermore, brain abnormalities synchronized across functional states in MDD patients can be evidenced by a combination of task and resting-state fMRI analyses.

  1. Task and Resting-State fMRI Reveal Altered Salience Responses to Positive Stimuli in Patients with Major Depressive Disorder

    PubMed Central

    Yang, Yang; Zhong, Ning; Imamura, Kazuyuki; Lu, Shengfu; Li, Mi; Zhou, Haiyan; Li, Huaizhou; Yang, Xiaojing; Wan, Zhijiang; Wang, Gang; Hu, Bin; Li, Kuncheng

    2016-01-01

    Altered brain function in patients with major depressive disorder (MDD) has been repeatedly demonstrated by task-based and resting-state studies, respectively. However, less is known concerning whether overlapped abnormalities in functional activities across modalities exist in MDD patients. To find out the answer, we implemented an fMRI experiment and collected both task and resting-state data from 19 MDD patients and 19 matched, healthy, controls. A distraction paradigm involving emotionally valenced pictures was applied to induce affective responses in subjects. As a result, concurrent deficits were found in arousing activation during a positive task in both the reward circuit and salience network (SN) that is composed of the dorsal part of anterior cingulate cortex (dACC) and bilateral anterior insulae (AI) in only the MDD group. Subsequent amplitude of low frequency fluctuations (ALFF) and functional connectivity analyses based on resting-state data exhibited consistent alterations in the bilateral AI of MDD patients, and indicated patients’ difficulties in regulating the balance between central executive network (CEN) and default mode network (DMN) due to altered connectivity among the CEN, DMN, and SN. Our findings provide new evidence demonstrating impaired salience processing and resulting alterations in responses to positive stimuli in MDD patients. Furthermore, brain abnormalities synchronized across functional states in MDD patients can be evidenced by a combination of task and resting-state fMRI analyses. PMID:27192082

  2. [Functional connectivity analysis of the brain network using resting-state FMRI].

    PubMed

    Hayashi, Toshihiro

    2011-12-01

    Spatial patterns of spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signals reflect the underlying neural architecture. The study of the brain network based on these self-organized patterns is termed resting-state functional MRI (fMRI). This review article aims at briefly reviewing a basic concept of this technology and discussing its implications for neuropsychological studies. First, the technical aspects of resting-state fMRI, including signal sources, physiological artifacts, image acquisition, and analytical methods such as seed-based correlation analysis and independent component analysis, are explained, followed by a discussion on the major resting-state networks, including the default mode network. In addition, the structure-function correlation studied using diffuse tensor imaging and resting-state fMRI is briefly discussed. Second, I have discussed the reservations and potential pitfalls of 2 major imaging methods: voxel-based lesion-symptom mapping and task fMRI. Problems encountered with voxel-based lesion-symptom mapping can be overcome by using resting-state fMRI and evaluating undamaged brain networks in patients. Regarding task fMRI in patients, I have also emphasized the importance of evaluating the baseline brain activity because the amplitude of activation in BOLD fMRI is hard to interpret as the same baseline cannot be assumed for both patient and normal groups. PMID:22147450

  3. Finding Thalamic BOLD Correlates to Posterior Alpha EEG

    PubMed Central

    Liu, Zhongming; de Zwart, Jacco A.; Yao, Bing; van Gelderen, Peter; Kuo, Li-Wei; Duyn, Jeff H.

    2012-01-01

    Oscillatory electrical brain activity in the alpha (8–13Hz) band is a prominent feature of human electroencephalography (EEG) during alert wakefulness, and is commonly thought to arise primarily from the occipital and parietal parts of the cortex. While the thalamus is considered to play a supportive role in the generation and modulation of cortical alpha rhythms, its precise function remains controversial and incompletely understood. To address this, we evaluated the correlation between the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signals in the thalamus and the spontaneous modulation of posterior alpha rhythms based on EEG-fMRI data acquired concurrently during an eyes-closed task-free condition. We observed both negative and positive correlations in the thalamus. The negative correlations were mostly seen within the visual thalamus, with a preference for the pulvinar over lateral geniculate nuclei. The positive correlations were found at the anterior and medial dorsal nuclei. Through functional connectivity analysis of the fMRI data, the pulvinar was found to be functionally associated with the same widespread cortical visual areas where the fMRI signals were negatively correlated with the posterior alpha modulation. In contrast, the dorsal nuclei were part of a distinct functional network that included brain stem, cingulate cortex and cerebellum. These observations are consistent with previous animal electrophysiology studies and the notion that the visual thalamus, and the pulvinar in particular, is intimately involved in the generation and spontaneous modulation of posterior alpha rhythms, facilitated by its reciprocal and widespread interaction with the cortical visual areas. We further postulate that the anterior and medial dorsal nuclei, being part of the ascending neuromodulatory system, may indirectly modulate cortical alpha rhythms by affecting vigilance and arousal level. PMID:22986355

  4. Almost winning: induced MEG theta power in insula and orbitofrontal cortex increases during gambling near-misses and is associated with BOLD signal and gambling severity.

    PubMed

    Dymond, Simon; Lawrence, Natalia S; Dunkley, Benjamin T; Yuen, Kenneth S L; Hinton, Elanor C; Dixon, Mark R; Cox, W Miles; Hoon, Alice E; Munnelly, Anita; Muthukumaraswamy, Suresh D; Singh, Krish D

    2014-05-01

    In slot machine gambling, the "near-miss effect" (when a losing display physically resembles an actual win display) has been implicated in pathological gambling (PG). Functional magnetic resonance imaging (fMRI) with PG and non-PG participants shows that near-misses recruit reward-related circuitry, but little is known about the temporal dynamics and oscillatory changes underlying near-misses. The present multi-modal imaging study investigated the near-miss effect by combining the spatial resolution of blood oxygen-level dependent (BOLD)-fMRI with the spatial and temporal resolution of magnetoencephalography (MEG) during a slot machine task in PG and non-PG groups. Given previous findings on outcome (win and near-miss) processing, functional overlap was hypothesized between induced changes in temporal oscillations and BOLD response to wins and near-misses in PG. We first validated our task in a sample of varying gambling severity using BOLD-fMRI and then compared PG and non-PG participants using MEG to investigate changes in induced oscillatory power associated with win and near-miss, relative to loss, outcomes. Across both modalities, near-misses recruited similar brain regions to wins, including right inferior frontal gyrus and insula. Using MEG, increased theta-band (4-7Hz) oscillations to near-misses were observed in the insula and right orbitofrontal cortex (OFC). Furthermore, this theta-band activity was positively associated with gambling severity. These findings demonstrate that the near-miss effect in insula and OFC is associated with induced theta oscillations. The significance of these findings for theories of PG and the development of potential biomarkers and therapeutic targets is discussed.

  5. Simultaneous EEG-Correlated Ictal fMRI.

    PubMed

    Salek-Haddadi, Afraim; Merschhemke, Martin; Lemieux, Louis; Fish, David R

    2002-05-01

    The ability to continuously acquire simultaneous EEG and fMRI data during seizures presents a formidable challenge both clinically and technically. Published ictal fMRI reports have so far been unable to benefit from simultaneous electrographic recordings and remain largely assumptive. Unique findings from a Continuous EEG-correlated fMRI experiment are presented in which a focal subclinical seizure was captured in its entirety. For the first time dynamic and biphasic Blood Oxygen Level Dependent (BOLD) signal changes are shown using statistical parametric mapping time-locked to the ictal EEG activity localizing seizure generation and propagation sites, with millimeter resolution, to electroclinically concordant gray matter structures. Though presently of limited clinical applicability, a new avenue is opened for further research.

  6. Validation and optimization of hypercapnic-calibrated fMRI from oxygen-sensitive two-photon microscopy.

    PubMed

    Gagnon, Louis; Sakadžić, Sava; Lesage, Frédéric; Pouliot, Philippe; Dale, Anders M; Devor, Anna; Buxton, Richard B; Boas, David A

    2016-10-01

    Hypercapnic-calibrated fMRI allows the estimation of the relative changes in the cerebral metabolic rate of oxygen (rCMRO2) from combined BOLD and arterial spin labelling measurements during a functional task, and promises to permit more quantitative analyses of brain activity patterns. The estimation relies on a macroscopic model of the BOLD effect that balances oxygen delivery and consumption to predict haemoglobin oxygenation and the BOLD signal. The accuracy of calibrated fMRI approaches has not been firmly established, which is limiting their broader adoption. We use our recently developed microscopic vascular anatomical network model in mice as a ground truth simulator to test the accuracy of macroscopic, lumped-parameter BOLD models. In particular, we investigate the original Davis model and a more recent heuristic simplification. We find that these macroscopic models are inaccurate using the originally defined parameters, but that the accuracy can be significantly improved by redefining the model parameters to take on new values. In particular, we find that the parameter α that relates cerebral blood-volume changes to cerebral blood-flow changes is significantly smaller than typically assumed and that the optimal value changes with magnetic field strength. The results are encouraging in that they support the use of simple BOLD models to quantify BOLD signals, but further work is needed to understand the physiological interpretation of the redefined model parameters.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

  7. Validation and optimization of hypercapnic-calibrated fMRI from oxygen-sensitive two-photon microscopy.

    PubMed

    Gagnon, Louis; Sakadžić, Sava; Lesage, Frédéric; Pouliot, Philippe; Dale, Anders M; Devor, Anna; Buxton, Richard B; Boas, David A

    2016-10-01

    Hypercapnic-calibrated fMRI allows the estimation of the relative changes in the cerebral metabolic rate of oxygen (rCMRO2) from combined BOLD and arterial spin labelling measurements during a functional task, and promises to permit more quantitative analyses of brain activity patterns. The estimation relies on a macroscopic model of the BOLD effect that balances oxygen delivery and consumption to predict haemoglobin oxygenation and the BOLD signal. The accuracy of calibrated fMRI approaches has not been firmly established, which is limiting their broader adoption. We use our recently developed microscopic vascular anatomical network model in mice as a ground truth simulator to test the accuracy of macroscopic, lumped-parameter BOLD models. In particular, we investigate the original Davis model and a more recent heuristic simplification. We find that these macroscopic models are inaccurate using the originally defined parameters, but that the accuracy can be significantly improved by redefining the model parameters to take on new values. In particular, we find that the parameter α that relates cerebral blood-volume changes to cerebral blood-flow changes is significantly smaller than typically assumed and that the optimal value changes with magnetic field strength. The results are encouraging in that they support the use of simple BOLD models to quantify BOLD signals, but further work is needed to understand the physiological interpretation of the redefined model parameters.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574311

  8. Brain activation in response to randomized visual stimulation as obtained from conjunction and differential analysis: an fMRI study

    NASA Astrophysics Data System (ADS)

    Nasaruddin, N. H.; Yusoff, A. N.; Kaur, S.

    2014-11-01

    The objective of this multiple-subjects functional magnetic resonance imaging (fMRI) study was to identify the common brain areas that are activated when viewing black-and-white checkerboard pattern stimuli of various shapes, pattern and size and to investigate specific brain areas that are involved in processing static and moving visual stimuli. Sixteen participants viewed the moving (expanding ring, rotating wedge, flipping hour glass and bowtie and arc quadrant) and static (full checkerboard) stimuli during an fMRI scan. All stimuli have black-and-white checkerboard pattern. Statistical parametric mapping (SPM) was used in generating brain activation. Differential analyses were implemented to separately search for areas involved in processing static and moving stimuli. In general, the stimuli of various shapes, pattern and size activated multiple brain areas mostly in the left hemisphere. The activation in the right middle temporal gyrus (MTG) was found to be significantly higher in processing moving visual stimuli as compared to static stimulus. In contrast, the activation in the left calcarine sulcus and left lingual gyrus were significantly higher for static stimulus as compared to moving stimuli. Visual stimulation of various shapes, pattern and size used in this study indicated left lateralization of activation. The involvement of the right MTG in processing moving visual information was evident from differential analysis, while the left calcarine sulcus and left lingual gyrus are the areas that are involved in the processing of static visual stimulus.

  9. Effect of Retrieval Effort and Switching Demand on fMRI Activation During Semantic Word Generation in Schizophrenia

    PubMed Central

    Ragland, JD; Moelter, ST; Bhati, MT; Valdez, JN; Kohler, CG; Siegel, SJ; Gur, RC; Gur, RE

    2008-01-01

    Verbal fluency deficits in schizophrenia are difficult to interpret because the tasks are multi-factorial and groups differ in total words generated. We manipulated retrieval and switching demands by requiring alternation between over-learned sequences in which retrieval is relatively automatic (OS) and semantic categories requiring increased retrieval effort (SC). Controlled processing was also manipulated by including switching and non-switching conditions, and formal thought disorder (FTD) was assessed with the communication disorders index (CDI). The OS/SC semantic fluency paradigm was administered during fMRI to 13 patients with schizophrenia and 14 matched controls. Images were acquired on a 3 Tesla Siemens scanner using compressed image acquisition to allow for cued overt word production. Subjects alternated between OS, SC, OS-switch, SC-switch, and baseline blocks. Images were pre-processed in SPM-2, and a two-stage random effects analysis tested within and between group contrasts. There were no group performance differences. fMRI analysis did not reveal any group differences during the OS non-switching condition. Both groups produced expected activation in bilateral prefrontal and inferior parietal regions. However, during the SC condition patients had greater activation than controls in left prefrontal, right anterior cingulate, right superior temporal, bilateral thalamus, and left parietal regions. There was also evidence of patient over-activation in prefrontal, superior temporal, superior parietal, and visual association areas when a switching component was added. FTD was negatively correlated with BOLD response in the right anterior cingulate, cuneus and superior frontal gyrus during increased retrieval demand, and positively correlated with fMRI activation in the left lingual gyrus, right fusiform gyrus and left superior parietal lobule during increased switching demand. These results indicate that patients are able to successfully perform effortful

  10. Effects of background suppression on the sensitivity of dual-echo arterial spin labeling MRI for BOLD and CBF signal changes.

    PubMed

    Ghariq, Eidrees; Chappell, Michael A; Schmid, Sophie; Teeuwisse, Wouter M; van Osch, Matthias J P

    2014-12-01

    Dual-echo arterial spin labeling (DE-ASL) enables the simultaneous acquisition of BOLD and CBF fMRI data and is often used for calibrated BOLD and cerebrovascular CO2 reactivity measurements. DE-ASL, like all ASL techniques, suffers from a low intrinsic CBF SNR, which can be improved by suppressing the background signal via the inclusion of additional inversion pulses. However, until now this approach has been considered to be undesirable for DE-ASL, because the BOLD signal is extracted from the background signal and attenuating the background signal could decrease the sensitivity of DE-ASL scans for BOLD changes. In this study, the effect of background suppression on the sensitivity of DE-ASL MRI for BOLD and CBF signal changes with a visual stimulation paradigm was studied. Results showed that with an average background suppression level of 70% the BOLD sensitivity of DE-ASL MRI decreases slightly (15%), while the CBF sensitivity of the scans increased by almost a factor-of-two (81%). These findings support the conclusion that the gains in CBF sensitivity of DE-ASL MRI due to background suppression outweigh the slight decrease in sensitivity of these scans for BOLD changes, and thus that background suppression is highly recommended for DE-ASL.

  11. Fixation-Related fMRI Analysis in the Domain of Reading Research: Using Self-Paced Eye Movements as Markers for Hemodynamic Brain Responses During Visual Letter String Processing

    PubMed Central

    Richlan, Fabio; Gagl, Benjamin; Hawelka, Stefan; Braun, Mario; Schurz, Matthias; Kronbichler, Martin; Hutzler, Florian

    2014-01-01

    The present study investigated the feasibility of using self-paced eye movements during reading (measured by an eye tracker) as markers for calculating hemodynamic brain responses measured by functional magnetic resonance imaging (fMRI). Specifically, we were interested in whether the fixation-related fMRI analysis approach was sensitive enough to detect activation differences between reading material (words and pseudowords) and nonreading material (line and unfamiliar Hebrew strings). Reliable reading-related activation was identified in left hemisphere superior temporal, middle temporal, and occipito-temporal regions including the visual word form area (VWFA). The results of the present study are encouraging insofar as fixation-related analysis could be used in future fMRI studies to clarify some of the inconsistent findings in the literature regarding the VWFA. Our study is the first step in investigating specific visual word recognition processes during self-paced natural sentence reading via simultaneous eye tracking and fMRI, thus aiming at an ecologically valid measurement of reading processes. We provided the proof of concept and methodological framework for the analysis of fixation-related fMRI activation in the domain of reading research. PMID:23645718

  12. Understanding the dynamic relationship between cerebral blood flow and the BOLD signal: Implications for quantitative functional MRI.

    PubMed

    Simon, Aaron B; Buxton, Richard B

    2015-08-01

    Calibrated BOLD imaging, in which traditional measurements of the BOLD signal are combined with measurements of cerebral blood flow (CBF) within a BOLD biophysical model to estimate changes in oxygen metabolism (CMRO2), has been a valuable tool for untangling the physiological processes associated with neural stimulus-induced BOLD activation. However, to date this technique has largely been applied to the study of essentially steady-state physiological changes (baseline to activation) associated with block-design stimuli, and it is unclear whether this approach may be directly extended to the study of more dynamic, naturalistic experimental designs. In this study we tested an assumption underlying this technique whose validity is critical to the application of calibrated BOLD to the study of more dynamic stimuli, that information about fluctuations in venous cerebral blood volume (CBVv) can be captured indirectly by measuring fluctuations in CBF, making the independent measurement of CBVv unnecessary. To accomplish this, simultaneous arterial spin labeling and BOLD imaging were used to measure the CBF and BOLD responses to flickering checkerboards with contrasts that oscillated continuously with frequencies of ~0.02-0.16Hz. The measurements were then fit to a dynamic physiological model of the BOLD response in order to explore the range of consistent CMRO2 and CBVv responses. We found that the BOLD and CBF responses were most consistent with relatively tight dynamic coupling between CBF and CMRO2 and a CBVv response that was an order of magnitude slower than either CBF or CMRO2. This finding suggests that the assumption of tight flow-volume coupling may not be strictly valid, complicating the extension of calibrated BOLD to more naturalistic experimental designs.

  13. Detection of the brain response during a cognitive task using perfusion-based event-related functional MRI.

    PubMed

    Yee, S H; Liu, H L; Hou, J; Pu, Y; Fox, P T; Gao, J H

    2000-08-01

    Event-related (ER) fMRI has evoked great interest due to the ability to depict the dynamic features of human brain function during various cognitive tasks. Thus far, all cognitive ER-fMRI studies have been based on blood oxygenation level-dependent (BOLD) contrast techniques. Compared with BOLD-based fMRI techniques, perfusion-based fMRI is able to localize the region of neuronal activity more accurately. This report demonstrates, for the first time, the detection of the brain response to a cognitive task using high temporal resolution perfusion-based ER-fMRI. An English verb generation task was used in this study. Results show that perfusion-based ER-fMRI accurately depicts the activation in Broca's area. Average changes in regional relative cerebral blood flow reached a maximum value of 30.7% at approximately 6.5 s after the start of stimulation and returned to 10% of the maximum value at approximately 12.8 s. Our results show that perfusion-based ER-fMRI is a useful tool for cognitive neuroscience studies, providing comparable temporal resolution and better localization of brain function than BOLD ER-fMRI. PMID:10943717

  14. Quantum theory with bold operator tensors.

    PubMed

    Hardy, Lucien

    2015-08-01

    In this paper, we present a formulation of quantum theory in terms of bold operator tensors. A circuit is built up of operations where an operation corresponds to a use of an apparatus. We associate collections of operator tensors (which together comprise a bold operator) with these apparatus uses. We give rules for combining bold operator tensors such that, for a circuit, they give a probability distribution over the possible outcomes. If we impose certain physicality constraints on the bold operator tensors, then we get exactly the quantum formalism. We provide both symbolic and diagrammatic ways to represent these calculations. This approach is manifestly covariant in that it does not require us to foliate the circuit into time steps and then evolve a state. Thus, the approach forms a natural starting point for an operational approach to quantum field theory.

  15. A mixed L2 norm regularized HRF estimation method for rapid event-related fMRI experiments.

    PubMed

    Lei, Yu; Tong, Li; Yan, Bin

    2013-01-01

    Brain state decoding or "mind reading" via multivoxel pattern analysis (MVPA) has become a popular focus of functional magnetic resonance imaging (fMRI) studies. In brain decoding, stimulus presentation rate is increased as fast as possible to collect many training samples and obtain an effective and reliable classifier or computational model. However, for extremely rapid event-related experiments, the blood-oxygen-level-dependent (BOLD) signals evoked by adjacent trials are heavily overlapped in the time domain. Thus, identifying trial-specific BOLD responses is difficult. In addition, voxel-specific hemodynamic response function (HRF), which is useful in MVPA, should be used in estimation to decrease the loss of weak information across voxels and obtain fine-grained spatial information. Regularization methods have been widely used to increase the efficiency of HRF estimates. In this study, we propose a regularization framework called mixed L2 norm regularization. This framework involves Tikhonov regularization and an additional L2 norm regularization term to calculate reliable HRF estimates. This technique improves the accuracy of HRF estimates and significantly increases the classification accuracy of the brain decoding task when applied to a rapid event-related four-category object classification experiment. At last, some essential issues such as the impact of low-frequency fluctuation (LFF) and the influence of smoothing are discussed for rapid event-related experiments.

  16. Material-dependent and material-independent selection processes in the frontal and parietal lobes: an event-related fMRI investigation of response competition

    NASA Technical Reports Server (NTRS)

    Hazeltine, Eliot; Bunge, Silvia A.; Scanlon, Michael D.; Gabrieli, John D E.

    2003-01-01

    The present study used the flanker task [Percept. Psychophys. 16 (1974) 143] to identify neural structures that support response selection processes, and to determine which of these structures respond differently depending on the type of stimulus material associated with the response. Participants performed two versions of the flanker task while undergoing event-related functional magnetic resonance imaging (fMRI). Both versions of the task required participants to respond to a central stimulus regardless of the responses associated with simultaneously presented flanking stimuli, but one used colored circle stimuli and the other used letter stimuli. Competition-related activation was identified by comparing Incongruent trials, in which the flanker stimuli indicated a different response than the central stimulus, to Neutral stimuli, in which the flanker stimuli indicated no response. A region within the right inferior frontal gyrus exhibited significantly more competition-related activation for the color stimuli, whereas regions within the middle frontal gyri of both hemispheres exhibited more competition-related activation for the letter stimuli. The border of the right middle frontal and inferior frontal gyri and the anterior cingulate cortex (ACC) were significantly activated by competition for both types of stimulus materials. Posterior foci demonstrated a similar pattern: left inferior parietal cortex showed greater competition-related activation for the letters, whereas right parietal cortex was significantly activated by competition for both materials. These findings indicate that the resolution of response competition invokes both material-dependent and material-independent processes.

  17. The Need for Bold Thinking.

    PubMed

    Lowi-Young, Mimi; DuBois-Wing, Gwen

    2016-01-01

    Amol Verma and Sacha Bhatia's (2016) paper presents policy recommendations that merit serious consideration on a system-wide level. While they make compelling arguments about why provincial governments are ideally suited to adapt Triple Aim innovation, we are concerned that the current health system climate limits this possibility. In our commentary, we present our thoughts about the authors' admittedly aspirational goals and the realities of the pan-Canadian healthcare system. We commence our commentary by confirming our agreement about the potential inherent within the Triple Aim framework. Second, we argue how important progress can take place that may not reflect a provincial-wide system. Next, we maintain that a learning health system is an essential ingredient to advancing Triple Aim and other health system-wide improvements. Third, we wonder whether the stewardship role of government is real and possible. Finally, we question the concept of our current health system's readiness for system change. While we have raised some questions about Verma and Bhatia's thinking around provincial adoption of the Triple Aim, we applaud their ideas. We believe that transformation in provincial health systems requires bold thinking. PMID:27009585

  18. Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal

    PubMed Central

    Kiviniemi, Vesa; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Haapea, Marianne; Silven, Olli; Tervonen, Osmo

    2009-01-01

    Temporal blood oxygen level dependent (BOLD) contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD) trends of the form 1/fα. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF) after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H) characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow. PMID:19636388

  19. Investigating Inhibitory Control in Children with Epilepsy: An fMRI Study

    PubMed Central

    Triplett, Regina L.; Velanova, Katerina; Luna, Beatriz; Padmanabhan, Aarthi; Gaillard, William D.; Asato, Miya R.

    2014-01-01

    SUMMARY Objective Deficits in executive function are increasingly noted in children with epilepsy and have been associated with poor academic and psychosocial outcomes. Impaired inhibitory control contributes to executive dysfunction in children with epilepsy; however, its neuroanatomic basis has not yet been investigated. We used functional Magnetic Resonance Imaging (fMRI) to probe the integrity of activation in brain regions underlying inhibitory control in children with epilepsy. Methods This cross-sectional study consisted of 34 children aged 8 to 17 years: 17 with well-controlled epilepsy and 17 age-and sex-matched controls. Participants performed the antisaccade (AS) task, representative of inhibitory control, during fMRI scanning. We compared AS performance during neutral and reward task conditions and evaluated task-related blood-oxygen level dependent (BOLD) activation. Results Children with epilepsy demonstrated impaired AS performance compared to controls during both neutral (non-reward) and reward trials, but exhibited significant task improvement during reward trials. Post-hoc analysis revealed that younger patients made more errors than older patients and all controls. fMRI results showed preserved activation in task-relevant regions in patients and controls, with the exception of increased activation in the left posterior cingulate gyrus in patients specifically with generalized epilepsy across neutral and reward trials. Significance Despite impaired inhibitory control, children with epilepsy accessed typical neural pathways as did their peers without epilepsy. Children with epilepsy showed improved behavioral performance in response to the reward condition, suggesting potential benefits of the use of incentives in cognitive remediation. PMID:25223606

  20. The efficiency of fMRI region of interest analysis methods for detecting group differences

    PubMed Central

    Hutchison, Joanna L.; Hubbard, Nicholas A.; Brigante, Ryan M.; Turner, Monroe; Sandoval, Traci I.; Hillis, G. Andrew J.; Weaver, Travis; Rypma, Bart

    2014-01-01

    Background Using a standard space brain template is an efficient way of determining region-of-interest (ROI) boundaries for functional magnetic resonance imaging (fMRI) data analyses. However, ROIs based on landmarks on subject-specific (i.e., native space) brain surfaces are anatomically accurate and probably best reflect the regional blood oxygen level dependent (BOLD) response for the individual. Unfortunately, accurate native space ROIs are often time-intensive to delineate even when using automated methods. New Method We compared analyses of group differences when using standard versus native space ROIs using both volume and surface-based analyses. Collegiate and military-veteran participants completed a button press task and a digit-symbol verification task during fMRI acquisition. Data were analyzed within ROIs representing left and right motor and prefrontal cortices, in native and standard space. Volume and surface-based analysis results were also compared using both functional (i.e., percent signal change) and structural (i.e., voxel or node count) approaches. Results and Comparison with Existing Method(s) Results suggest that transformation into standard space can affect the outcome of structural and functional analyses (inflating/minimizing differences, based on cortical geography), and these transformations can affect conclusions regarding group differences with volumetric data. Conclusions Caution is advised when applying standard space ROIs to volumetric fMRI data. However, volumetric analyses show group differences and are appropriate in circumstances when time is limited. Surface-based analyses using functional ROIs generated the greatest group differences and were less susceptible to differences between native and standard space. We conclude that surface-based analyses are preferable with adequate time and computing resources. PMID:24487017

  1. Response to {open_quotes}Comment on {open_quote}Reversible work of formation of an embryo of a new phase within a uniform macroscopic mother phase{close_quote}thinsp{close_quotes} [J. Chem. Phys. {bold 111}, 3769 (1999)

    SciTech Connect

    Debenedetti, P.G.; Reiss, H.

    1999-08-01

    External constraints are necessary in order to calculate the energetics of embryo formation when the embryo is not a critical nucleus. The expression for the reversible work of formation obtained in by Debenedetti and Reiss [J. Chem. Phys. {bold 108}, 5498 (1998)] is rigorous and valid regardless of the relative densities of the embryo and mother phase. {copyright} {ital 1999 American Institute of Physics.}

  2. The neural mechanisms of semantic and response conflicts: an fMRI study of practice-related effects in the Stroop task.

    PubMed

    Chen, Zhencai; Lei, Xu; Ding, Cody; Li, Hong; Chen, Antao

    2013-02-01

    Previous studies have demonstrated that there are separate neural mechanisms underlying semantic and response conflicts in the Stroop task. However, the practice effects of these conflicts need to be elucidated and the possible involvements of common neural mechanisms are yet to be established. We employed functional magnetic resonance imaging (fMRI) in a 4-2 mapping practice-related Stroop task to determine the neural substrates under these conflicts. Results showed that different patterns of brain activations are associated with practice in the attentional networks (e.g., dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and posterior parietal cortex (PPC)) for both conflicts, response control regions (e.g., inferior frontal junction (IFJ), inferior frontal gyrus (IFG)/insula, and pre-supplementary motor areas (pre-SMA)) for semantic conflict, and posterior cortex for response conflict. We also found areas of common activation in the left hemisphere within the attentional networks, for the early practice stage in semantic conflict and the late stage in "pure" response conflict using conjunction analysis. The different practice effects indicate that there are distinct mechanisms underlying these two conflict types: semantic conflict practice effects are attributable to the automation of stimulus processing, conflict and response control; response conflict practice effects are attributable to the proportional increase of conflict-related cognitive resources. In addition, the areas of common activation suggest that the semantic conflict effect may contain a partial response conflict effect, particularly at the beginning of the task. These findings indicate that there are two kinds of response conflicts contained in the key-pressing Stroop task: the vocal-level (mainly in the early stage) and key-pressing (mainly in the late stage) response conflicts; thus, the use of the subtraction method for the exploration of semantic and response conflicts

  3. The contribution of different frequency bands of fMRI data to the correlation with EEG alpha rhythm.

    PubMed

    Zhan, Zhichao; Xu, Lele; Zuo, Tian; Xie, Dongliang; Zhang, Jiacai; Yao, Li; Wu, Xia

    2014-01-16

    Alpha rhythm is a prominent EEG rhythm observed during resting state and is thought to be related to multiple cognitive processes. Previous simultaneous electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) studies have demonstrated that alpha rhythm is associated with blood oxygen level dependent (BOLD) signals in several different functional networks. How these networks influence alpha rhythm respectively is unclear. The low-frequency oscillations (LFO) in spontaneous BOLD activity are thought to contribute to the local correlations in resting state. Recent studies suggested that either LFO or other components of fMRI can be further divided into sub-components on different frequency bands. We hypothesized that those BOLD sub-components characterized the contributions of different brain networks to alpha rhythm. To test this hypothesis, EEG and fMRI data were simultaneously recorded from 17 human subjects performing an eyes-close resting state experiment. EEG alpha rhythm was correlated with the filtered fMRI time courses at different frequency bands (0.01-0.08 Hz, 0.08-0.25 Hz, 0.01-0.027 Hz, 0.027-0.073 Hz, 0.073-0.198 Hz, and 0.198-0.25 Hz). The results demonstrated significant relations between alpha rhythm and the BOLD signals in the visual network and in the attention network at LFO band, especially at the very low frequency band (0.01-0.027 Hz). PMID:24275197

  4. BOLD fractional contribution to resting-state functional connectivity above 0.1 Hz.

    PubMed

    Chen, Jingyuan E; Glover, Gary H

    2015-02-15

    Blood oxygen level dependent (BOLD) spontaneous signals from resting-state (RS) brains have typically been characterized by low-pass filtered timeseries at frequencies ≤ 0.1 Hz, and studies of these low-frequency fluctuations have contributed exceptional understanding of the baseline functions of our brain. Very recently, emerging evidence has demonstrated that spontaneous activities may persist in higher frequency bands (even up to 0.8 Hz), while presenting less variable network patterns across the scan duration. However, as an indirect measure of neuronal activity, BOLD signal results from an inherently slow hemodynamic process, which in fact might be too slow to accommodate the observed high-frequency functional connectivity (FC). To examine whether the observed high-frequency spontaneous FC originates from BOLD contrast, we collected RS data as a function of echo time (TE). Here we focus on two specific resting state networks - the default-mode network (DMN) and executive control network (ECN), and the major findings are fourfold: (1) we observed BOLD-like linear TE-dependence in the spontaneous activity at frequency bands up to 0.5 Hz (the maximum frequency that can be resolved with TR=1s), supporting neural relevance of the RSFC at a higher frequency range; (2) conventional models of hemodynamic response functions must be modified to support resting state BOLD contrast, especially at higher frequencies; (3) there are increased fractions of non-BOLD-like contributions to the RSFC above the conventional 0.1 Hz (non-BOLD/BOLD contrast at 0.4-0.5 Hz is ~4 times that at <0.1 Hz); and (4) the spatial patterns of RSFC are frequency-dependent. Possible mechanisms underlying the present findings and technical concerns regarding RSFC above 0.1 Hz are discussed.

  5. Brain responses to erotic and other emotional stimuli in breast cancer survivors with and without distress about low sexual desire: a preliminary fMRI study.

    PubMed

    Versace, Francesco; Engelmann, Jeffrey M; Jackson, Edward F; Slapin, Aurelija; Cortese, Kristin M; Bevers, Therese B; Schover, Leslie R

    2013-12-01

    Many breast cancer survivors report a loss of sexual desire and arousability, consonant with the new DSM-V category of female sexual interest/arousal disorder. The cause of decreased sexual desire and pleasure after treatment for cancer is unknown. One possibility is that cancer, or treatment for cancer, damages brain circuits that are involved in reward-seeking. To test the hypothesis that brain reward systems are involved in decreased sexual desire in breast cancer survivors, we used functional magnetic resonance imaging (fMRI) to compare brain responses to erotica and other emotional stimuli in two groups of women previously treated for breast cancer with chemotherapy: those who were distressed about a perceived loss of sexual desire and those who may have had low desire, but were not distressed about it. Women distressed about their desire had reduced brain responses to erotica in the anterior cingulate and dorsolateral prefrontal cortex, which are part of the brain reward system. This study is the first to demonstrate, in cancer survivors, that problems with sexual desire/arousability are associated with blunted brain responses to erotica in reward systems. Future research is necessary to determine whether brain responses differ as a result of chemotherapy, hormone therapy, and menopausal status. This may contribute to the development of new, evidence-based interventions for one of the most prevalent and enduring side effects of cancer treatment. PMID:23955492

  6. Bayesian estimation of the hemodynamic response function in functional MRI

    NASA Astrophysics Data System (ADS)

    Marrelec, G.; Benali, H.; Ciuciu, P.; Poline, J.-B.

    2002-05-01

    Functional MRI (fMRI) is a recent, non-invasive technique allowing for the evolution of brain processes to be dynamically followed in various cognitive or behavioral tasks. In BOLD fMRI, what is actually measured is only indirectly related to neuronal activity through a process that is still under investigation. A convenient way to analyze BOLD fMRI data consists of considering the whole brain as a system characterized by a transfer response function, called the Hemodynamic Response Function (HRF). Precise and robust estimation of the HRF has not been achieved yet: parametric methods tend to be robust but require too strong constraints on the shape of the HRF, whereas non-parametric models are not reliable since the problem is badly conditioned. We therefore propose a full Bayesian, non-parametric method that makes use of basic but relevant a priori knowledge about the underlying physiological process to make robust inference about the HRF. We show that this model is very robust to decreasing signal-to-noise ratio and to the actual noise sampling distribution. We finally apply the method to real data, revealing a wide variety of HRF shapes.

  7. Differential Brain Responses to Cries of Infants with Autistic Disorder and Typical Development: An fMRI Study

    PubMed Central

    Venuti, Paola; Caria, Andrea; Esposito, Gianluca; De Pisapia, Nicola; Bornstein, Marc H.; de Falco, Simona

    2012-01-01

    This study used fMRI to measure brain activity during adult processing of cries of infants with autistic disorder (AD) compared to cries of typically developing (TD) infants. Using whole brain analysis, we found that cries of infants with AD compared to those of TD infants elicited enhanced activity in brain regions associated with verbal and prosodic processing, perhaps because altered acoustic patterns of AD cries render them especially difficult to interpret, and increased activity in brain regions associated with emotional processing, indicating that AD cries also elicit more negative feelings and may be perceived as more aversive and/or arousing. Perceived distress engendered by AD cries related to increased activation in brain regions associated with emotional processing. This study supports the hypothesis that cry is an early and meaningful anomaly displayed by children with AD. It could be that cries associated with AD alter parent-child interactions much earlier than the time that reliable AD diagnosis normally occurs. PMID:22835685

  8. Neural responses to witnessing peer rejection after being socially excluded: fMRI as a window into adolescents’ emotional processing

    PubMed Central

    Masten, Carrie L.; Eisenberger, Naomi I.; Pfeifer, Jennifer H.; Dapretto, Mirella

    2013-01-01

    During adolescence, concerns about peer rejection and acceptance become increasingly common. Adolescents regularly experience peer rejection firsthand and witness these behaviors among their peers. In the current study, neuroimaging techniques were employed to conduct a preliminary investigation of the affective and cognitive processes involved in witnessing peer acceptance and rejection—specifically when these witnessed events occur in the immediate aftermath of a firsthand experience with rejection. During an fMRI scan, twenty-three adolescents underwent a simulated experience of firsthand peer rejection. Then, immediately following this experience they watched as another adolescent was ostensibly first accepted and then rejected. Findings indicated that in the immediate aftermath of being rejected by peers, adolescents displayed neural activity consistent with distress when they saw another peer being accepted, and neural activity consistent with emotion regulation and mentalizing (e.g., perspective-taking) processes when they saw another peer being rejected. Furthermore, individuals displaying a heightened sensitivity to firsthand rejection were more likely to show neural activity consistent with distress when observing a peer being accepted. Findings are discussed in terms of how witnessing others being accepted or rejected relates to adolescents’ interpretations of both firsthand and observed experiences with peers. Additionally, the potential impact that witnessed events might have on the broader perpetuation of bullying at this age is also considered. PMID:24033579

  9. Quasi-periodic patterns (QPP): large-scale dynamics in resting state fMRI that correlate with local infraslow electrical activity.

    PubMed

    Thompson, Garth John; Pan, Wen-Ju; Magnuson, Matthew Evan; Jaeger, Dieter; Keilholz, Shella Dawn

    2014-01-01

    Functional connectivity measurements from resting state blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) are proving a powerful tool to probe both normal brain function and neuropsychiatric disorders. However, the neural mechanisms that coordinate these large networks are poorly understood, particularly in the context of the growing interest in network dynamics. Recent work in anesthetized rats has shown that the spontaneous BOLD fluctuations are tightly linked to infraslow local field potentials (LFPs) that are seldom recorded but comparable in frequency to the slow BOLD fluctuations. These findings support the hypothesis that long-range coordination involves low frequency neural oscillations and establishes infraslow LFPs as an excellent candidate for probing the neural underpinnings of the BOLD spatiotemporal patterns observed in both rats and humans. To further examine the link between large-scale network dynamics and infraslow LFPs, simultaneous fMRI and microelectrode recording were performed in anesthetized rats. Using an optimized filter to isolate shared components of the signals, we found that time-lagged correlation between infraslow LFPs and BOLD is comparable in spatial extent and timing to a quasi-periodic pattern (QPP) found from BOLD alone, suggesting that fMRI-measured QPPs and the infraslow LFPs share a common mechanism. As fMRI allows spatial resolution and whole brain coverage not available with electroencephalography, QPPs can be used to better understand the role of infraslow oscillations in normal brain function and neurological or psychiatric disorders.

  10. Multimodal description of whole brain connectivity: A comparison of resting state MEG, fMRI, and DWI.

    PubMed

    Garcés, Pilar; Pereda, Ernesto; Hernández-Tamames, Juan A; Del-Pozo, Francisco; Maestú, Fernando; Pineda-Pardo, José Ángel

    2016-01-01

    Structural and functional connectivity (SC and FC) have received much attention over the last decade, as they offer unique insight into the coordination of brain functioning. They are often assessed independently with three imaging modalities: SC using diffusion-weighted imaging (DWI), FC using functional magnetic resonance imaging (fMRI), and magnetoencephalography/electroencephalography (MEG/EEG). DWI provides information about white matter organization, allowing the reconstruction of fiber bundles. fMRI uses blood-oxygenation level-dependent (BOLD) contrast to indirectly map neuronal activation. MEG and EEG are direct measures of neuronal activity, as they are sensitive to the synchronous inputs in pyramidal neurons. Seminal studies have targeted either the electrophysiological substrate of BOLD or the anatomical basis of FC. However, multimodal comparisons have been scarcely performed, and the relation between SC, fMRI-FC, and MEG-FC is still unclear. Here we present a systematic comparison of SC, resting state fMRI-FC, and MEG-FC between cortical regions, by evaluating their similarities at three different scales: global network, node, and hub distribution. We obtained strong similarities between the three modalities, especially for the following pairwise combinations: SC and fMRI-FC; SC and MEG-FC at theta, alpha, beta and gamma bands; and fMRI-FC and MEG-FC in alpha and beta. Furthermore, highest node similarity was found for regions of the default mode network and primary motor cortex, which also presented the highest hubness score. Distance was partially responsible for these similarities since it biased all three connectivity estimates, but not the unique contributor, since similarities remained after controlling for distance.

  11. Like the back of the (right) hand? A new fMRI look on the hand laterality task.

    PubMed

    Zapparoli, Laura; Invernizzi, Paola; Gandola, Martina; Berlingeri, Manuela; De Santis, Antonio; Zerbi, Alberto; Banfi, Giuseppe; Paulesu, Eraldo

    2014-12-01

    There is a common saying for expressing familiarity with something. It refers to our hands, and strangely enough, in English, one says to know something like the back of the hand, whereas in other cultures, for example, Italy, Spain and France, the same expression is with the palm. Previous behavioural data have suggested that our ability to visually discriminate a right from a left hand is influenced by perspective. This behavioural finding has remained without neurophysiological counterparts. We used an implicit motor imagery task in which 30 right-handed subjects were asked to decide whether a picture portrayed a right rather than a left hand during an fMRI event-related experiment. Both views (back and palm) were used, and the hands were rotated by 45° in 8 possible angles. We replicated previous behavioural evidence by showing faster reaction times for the back-view and view-specific interaction effects with the angle of rotation: for the back view, the longest RTs were with the hand facing down at 180°; for the palm view, the longest RTs were at 90° with the hand pointing away from the midline. In addition, the RTs were particularly faster for back views of the right hand. fMRI measurements revealed a stronger BOLD signal increase in left premotor and parietal cortices for stimuli viewed from the palm, whereas back-view stimuli were associated with stronger occipital activations, suggesting a view-specific cognitive strategy: more visually oriented for the back of the hand; more in need of the support of a motoric imagery process for the palms. Right-hand back views were associated with comparatively smaller BOLD responses, attesting, together with the faster reaction times, to the lesser need for neural labour because of greater familiarity with that view of the hand. These differences suggest the existence of brain-encoded, view-dependent representations of body segments.

  12. Response inhibition failure to visual stimuli paired with a "single-type" stressor in PTSD patients: an fMRI pilot study.

    PubMed

    Brunetti, Marcella; Sepede, Gianna; Ferretti, Antonio; Mingoia, Gianluca; Romani, Gian Luca; Babiloni, Claudio

    2015-05-01

    Patients with post-traumatic stress disorder (PTSD) tend to misinterpret innocuous stimuli as potential threats, possibly due to a conditioning provoked by traumatic episodes. Previous neuroimaging evidence has shown an abnormal activation of the amygdala and prefrontal cortex in PTSD patients during fear conditioning and extinction. Nevertheless, the effects of a single-type adverse stressor on that circuit remain poorly explored. We tested the hypothesis that a single-type adverse episode is able to affect the prefrontal cortex and amygdala response to conditioned stimuli. To test this hypothesis, fMRI recordings were performed in PTSD patients and trauma-exposed controls during the observation of neutral and negative paired or non-paired pictures with an adverse stimulus by means of a single association. Results showed that left amygdala activation during negative reinforced stimuli was correlated with the score of PTSD clinical scale across all subjects. Furthermore, in the traumatized non-PTSD group, the activation of the dorso-medial prefrontal cortex and bilateral amygdala was lower during the observation of the reinforced (CS(+)) versus non-reinforced pictures (CS(-)) in response to emotionally negative stimuli. This was not the case in the PTSD patients. These results suggest that in PTSD patients, a single-episode conditioning unveils the failure of an inhibitory mechanism moderating the activity of the prefrontal cortex and amygdala in response to adverse and neutral stimuli. PMID:25791360

  13. Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism.

    PubMed

    Krach, Sören; Kamp-Becker, Inge; Einhäuser, Wolfgang; Sommer, Jens; Frässle, Stefan; Jansen, Andreas; Rademacher, Lena; Müller-Pinzler, Laura; Gazzola, Valeria; Paulus, Frieder M

    2015-11-01

    Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another's affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another's affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another's physical pain but still have problems with the vicarious representation of more complex emotions that matter in life. PMID:26367817

  14. The dorsal medial frontal cortex mediates automatic motor inhibition in uncertain contexts: evidence from combined fMRI and EEG studies.

    PubMed

    Albares, Marion; Lio, Guillaume; Criaud, Marion; Anton, Jean-Luc; Desmurget, Michel; Boulinguez, Philippe

    2014-11-01

    Response inhibition is commonly thought to rely on voluntary, reactive, selective, and relatively slow prefrontal mechanisms. In contrast, we suggest here that response inhibition is achieved automatically, nonselectively, within very short delays in uncertain environments. We modified a classical go/nogo protocol to probe context-dependent inhibitory mechanisms. Because no single neuroimaging method can definitely disentangle neural excitation and inhibition, we combined fMRI and EEG recordings in healthy humans. Any stimulus (go or nogo) presented in an uncertain context requiring action restraint was found to evoke activity changes in the supplementary motor complex (SMC) with respect to a control condition in which no response inhibition was required. These changes included: (1) An increase in event-related BOLD activity, (2) an attenuation of the early (170 ms) event related potential generated by a single, consistent source isolated by advanced blind source separation, and (3) an increase in the evoked-EEG Alpha power of this source. Considered together, these results suggest that the BOLD signal evoked by any stimulus in the SMC when the situation is unpredictable can be driven by automatic, nonselective, context-dependent inhibitory activities. This finding reveals the paradoxical mechanisms by which voluntary control of action may be achieved. The ability to provide controlled responses in unpredictable environments would require setting-up the automatic self-inhibitory circuitry within the SMC. Conversely, enabling automatic behavior when the environment becomes predictable would require top-down control to deactivate anticipatorily and temporarily the inhibitory set. PMID:24954611

  15. The Effect of Task-Irrelevant Fearful-Face Distractor on Working Memory Processing in Mild Cognitive Impairment versus Healthy Controls: An Exploratory fMRI Study in Female Participants

    PubMed Central

    Burhan, Amer M.; Anazodo, Udunna C.; Chung, Jun Ku; Arena, Amanda; Graff-Guerrero, Ariel; Mitchell, Derek G. V.

    2016-01-01

    In mild cognitive impairment (MCI), a risk state for Alzheimer's disease, patients have objective cognitive deficits with relatively preserved functioning. fMRI studies have identified anomalies during working memory (WM) processing in individuals with MCI. The effect of task-irrelevant emotional face distractor on WM processing in MCI remains unclear. We aim to explore the impact of fearful-face task-irrelevant distractor on WM processing in MCI using fMRI. Hypothesis. Compared to healthy controls (HC), MCI patients will show significantly higher BOLD signal in a priori identified regions of interest (ROIs) during a WM task with a task-irrelevant emotional face distractor. Methods. 9 right-handed female participants with MCI and 12 matched HC performed a WM task with standardized task-irrelevant fearful versus neutral face distractors randomized and counterbalanced across WM trials. MRI images were acquired during the WM task and BOLD signal was analyzed using statistical parametric mapping (SPM) to identify signal patterns during the task response phase. Results. Task-irrelevant fearful-face distractor resulted in higher activation in the amygdala, anterior cingulate, and frontal areas, in MCI participants compared to HC. Conclusions. This exploratory study suggests altered WM processing as a result of fearful-face distractor in MCI. PMID:26949290

  16. Functional Connectivity in MRI Is Driven by Spontaneous BOLD Events

    PubMed Central

    Allan, Thomas W.; Francis, Susan T.; Caballero-Gaudes, Cesar; Morris, Peter G.; Liddle, Elizabeth B.; Liddle, Peter F.; Brookes, Matthew J.; Gowland, Penny A.

    2015-01-01

    Functional brain signals are frequently decomposed into a relatively small set of large scale, distributed cortical networks that are associated with different cognitive functions. It is generally assumed that the connectivity of these networks is static in time and constant over the whole network, although there is increasing evidence that this view is too simplistic. This work proposes novel techniques to investigate the contribution of spontaneous BOLD events to the temporal dynamics of functional connectivity as assessed by ultra-high field functional magnetic resonance imaging (fMRI). The results show that: 1) spontaneous events in recognised brain networks contribute significantly to network connectivity estimates; 2) these spontaneous events do not necessarily involve whole networks or nodes, but clusters of voxels which act in concert, forming transiently synchronising sub-networks and 3) a task can significantly alter the number of localised spontaneous events that are detected within a single network. These findings support the notion that spontaneous events are the main driver of the large scale networks that are commonly detected by seed-based correlation and ICA. Furthermore, we found that large scale networks are manifestations of smaller, transiently synchronising sub-networks acting dynamically in concert, corresponding to spontaneous events, and which do not necessarily involve all voxels within the network nodes oscillating in unison. PMID:25922945

  17. Differences in aggression, activity and boldness between native and introduced populations of an invasive crayfish

    USGS Publications Warehouse

    Pintor, L.M.; Sih, A.; Bauer, M.L.

    2008-01-01

    Aggressiveness, along with foraging voracity and boldness, are key behavioral mechanisms underlying the competitive displacement and invasion success of exotic species. However, do aggressiveness, voracity and boldness of the invader depend on the presence of an ecologically similar native competitor in the invaded community? We conducted four behavioral assays to compare aggression, foraging voracity, threat response and boldness to forage under predation risk of multiple populations of exotic signal crayfish Pacifastacus leniusculus across its native and invaded range with and without a native congener, the Shasta crayfish P. fortis. We predicted that signal crayfish from the invaded range and sympatric with a native congener (IRS) should be more aggressive to outcompete a close competitor than populations from the native range (NR) or invaded range and allopatric to a native congener (IRA). Furthermore, we predicted that IRS populations of signal crayfish should be more voracious, but less bold to forage under predation risk since native predators and prey likely possess appropriate behavioral responses to the invader. Contrary to our predictions, results indicated that IRA signal crayfish were more aggressive towards conspecifics and more voracious and active foragers, yet also bolder to forage under predation risk in comparison to NR and IRS populations, which did not differ in behavior. Higher aggression/voracity/ boldness was positively correlated with prey consumption rates, and hence potential impacts on prey. We suggest that the positive correlations between aggression/voracity/boldness are the result of an overall aggression syndrome. Results of stream surveys indicated that IRA streams have significantly lower prey biomass than in IRS streams, which may drive invading signal crayfish to be more aggressive/voracious/bold to acquire resources to establish a population. ?? 2008 The Authors.

  18. fMRI evidence of word frequency and strength effects during episodic memory encoding.

    PubMed

    de Zubicaray, Greig I; McMahon, Katie L; Eastburn, Matthew M; Finnigan, Simon; Humphreys, Michael S

    2005-03-01

    Word frequency (WF) and strength effects are two important phenomena associated with episodic memory. The former refers to the superior hit-rate (HR) for low (LF) compared to high frequency (HF) words in recognition memory, while the latter describes the incremental effect(s) upon HRs associated with repeating an item at study. Using the "subsequent memory" method with event-related fMRI, we tested the attention-at-encoding (AE) [M. Glanzer, J.K. Adams, The mirror effect in recognition memory: data and theory, J. Exp. Psychol.: Learn Mem. Cogn. 16 (1990) 5-16] explanation of the WF effect. In addition to investigating encoding strength, we addressed if study involves accessing prior representations of repeated items via the same mechanism as that at test [J.L. McClelland, M. Chappell, Familiarity breeds differentiation: a subjective-likelihood approach to the effects of experience in recognition memory, Psychol. Rev. 105 (1998) 724-760], entailing recollection [K.J. Malmberg, J.E. Holden, R.M. Shiffrin, Modeling the effects of repetitions, similarity, and normative word frequency on judgments of frequency and recognition memory, J. Exp. Psychol.: Learn Mem. Cogn. 30 (2004) 319-331] and whether less processing effort is entailed for encoding each repetition [M. Cary, L.M. Reder, A dual-process account of the list-length and strength-based mirror effects in recognition, J. Mem. Lang. 49 (2003) 231-248]. The increased BOLD responses observed in the left inferior prefrontal cortex (LIPC) for the WF effect provide support for an AE account. Less effort does appear to be required for encoding each repetition of an item, as reduced BOLD responses were observed in the LIPC and left lateral temporal cortex; both regions demonstrated increased responses in the conventional subsequent memory analysis. At test, a left lateral parietal BOLD response was observed for studied versus unstudied items, while only medial parietal activity was observed for repeated items at study

  19. Chronotype Modulates Language Processing-Related Cerebral Activity during Functional MRI (fMRI)

    PubMed Central

    Warbrick, Tracy; Shah, N. J.

    2015-01-01

    Objective Based on individual daily physiological cycles, humans can be classified as early (EC), late (LC) and intermediate (IC) chronotypes. Recent studies have verified that chronotype-specificity relates to performance on cognitive tasks: participants perform more efficiently when tested in the chronotype-specific optimal time of day than when tested in their non-optimal time. Surprisingly, imaging studies focussing on the underlying neural mechanisms of potential chronotype-specificities are sparse. Moreover, chronotype-specific alterations of language-related semantic processing have been neglected so far. Methods 16 male, healthy ECs, 16 ICs and 16 LCs participated in a fast event-related functional Magnetic Resonance Imaging (fMRI) paradigm probing semantic priming. Subjects read two subsequently presented words (prime, target) and were requested to determine whether the target word was an existing word or a non-word. Subjects were tested during their individual evening hours when homeostatic sleep pressure and circadian alertness levels are high to ensure equal entrainment. Results Chronotype-specificity is associated with task-performance and brain activation. First, ECs exhibited slower reaction times than LCs. Second, ECs showed attenuated BOLD responses in several language-related brain areas, e.g. in the left postcentral gyrus, left and right precentral gyrus and in the right superior frontal gyrus. Additionally, increased BOLD responses were revealed for LCs as compared to ICs in task-related areas, e.g. in the right inferior parietal lobule and in the right postcentral gyrus. Conclusions These findings reveal that even basic language processes are associated with chronotype-specific neuronal mechanisms. Consequently, results might change the way we schedule patient evaluations and/or healthy subjects in e.g. experimental research and adding “chronotype” as a statistical covariate. PMID:26397824

  20. Using fMRI to decode true thoughts independent of intention to conceal.

    PubMed

    Yang, Zhi; Huang, Zirui; Gonzalez-Castillo, Javier; Dai, Rui; Northoff, Georg; Bandettini, Peter

    2014-10-01

    Multi-variate pattern analysis (MVPA) applied to BOLD-fMRI has proven successful at decoding complicated fMRI signal patterns associated with a variety of cognitive processes. One cognitive process, not yet investigated, is the mental representation of "Yes/No" thoughts that precede the actual overt response to a binary "Yes/No" question. In this study, we focus on examining: (1) whether spatial patterns of the hemodynamic response carry sufficient information to allow reliable decoding of "Yes/No" thoughts; and (2) whether decoding of "Yes/No" thoughts is independent of the intention to respond honestly or dishonestly. To achieve this goal, we conducted two separate experiments. Experiment 1, collected on a 3T scanner, examined the whole brain to identify regions that carry sufficient information to permit significantly above-chance prediction of "Yes/No" thoughts at the group level. In Experiment 2, collected on a 7T scanner, we focused on the regions identified in Experiment 1 to examine the capability of achieving high decoding accuracy at the single subject level. A set of regions--namely right superior temporal gyrus, left supra-marginal gyrus, and left middle frontal gyrus--exhibited high decoding power. Decoding accuracy for these regions increased with trial averaging. When 18 trials were averaged, the median accuracies were 82.5%, 77.5%, and 79.5%, respectively. When trials were separated according to deceptive intentions (set via experimental cues), and classifiers were trained on honest trials, but tested on trials where subjects were asked to deceive, the median accuracies of these regions still reached 66%, 75%, and 78.5%. These results provide evidence that concealed "Yes/No" thoughts are encoded in the BOLD signal, retaining some level of independence from the subject's intentions to answer honestly or dishonestly. These findings also suggest the theoretical possibility for more efficient brain-computer interfaces where subjects only need to think

  1. Synaesthesia or vivid imagery? A single case fMRI study of visually induced olfactory perception.

    PubMed

    Chan, Jason S; van den Bosch, Jasper J F; Theves, Stephanie; Hardt, Stefanie; Pflanz, Patrick; Lötsch, Jörn; Kaiser, Jochen; Naumer, Marcus J

    2014-01-01

    The most common form of synaesthesia is grapheme-colour synaesthesia. However, rarer forms of synaesthesia also exist, such as word-gustatory and olfactory-gustatory synaesthesia, whereby a word or smell will induce a specific. In this study we describe a single individual (LJ) who experiences a concurrent olfactory stimulus when presented with congruent visual images. For some visual stimuli, he perceives a strong and automatic olfactory percept, which has existed throughout his life. In this study, we explore whether his experiences are a new form of synaesthesia or simply vivid imagery. Unlike other forms of synaesthesia, the concurrent odour is congruent to the visual inducer. For example, a photograph of dress shoes will elicit the smell of leather. We presented LJ and several control participants with 75 images of everyday objects. Their task was to indicate the strength of any perceived odours induced by the visual images. LJ rated several of the images as inducing a concurrent odour, while controls did not have any such percept. Images that LJ reported as inducing the strongest odours were used, along with colour-matched control images, in the context of an fMRI experiment. Participants were given a one-back task to maintain attention. A block-design odour localizer was presented to localize the piriform cortex (primary olfactory cortex). We found an increased BOLD response in the piriform cortex for the odour-inducing images compared to the control images in LJ. There was no difference in BOLD response between these two stimulus types in the control participants. A subsequent olfactory imagery task did not elicit enhanced activity in the piriform cortex in LJ, suggesting his perceptual experiences may not be based on olfactory imagery. PMID:25577904

  2. The selectivity of responses to red-green colour and achromatic contrast in the human visual cortex: an fMRI adaptation study.

    PubMed

    Mullen, Kathy T; Chang, Dorita H F; Hess, Robert F

    2015-12-01

    There is controversy as to how responses to colour in the human brain are organized within the visual pathways. A key issue is whether there are modular pathways that respond selectively to colour or whether there are common neural substrates for both colour and achromatic (Ach) contrast. We used functional magnetic resonance imaging (fMRI) adaptation to investigate the responses of early and extrastriate visual areas to colour and Ach contrast. High-contrast red-green (RG) and Ach sinewave rings (0.5 cycles/degree, 2 Hz) were used as both adapting stimuli and test stimuli in a block design. We found robust adaptation to RG or Ach contrast in all visual areas. Cross-adaptation between RG and Ach contrast occurred in all areas indicating the presence of integrated, colour and Ach responses. Notably, we revealed contrasting trends for the two test stimuli. For the RG test, unselective processing (robust adaptation to both RG and Ach contrast) was most evident in the early visual areas (V1 and V2), but selective responses, revealed as greater adaptation between the same stimuli than cross-adaptation between different stimuli, emerged in the ventral cortex, in V4 and VO in particular. For the Ach test, unselective responses were again most evident in early visual areas but Ach selectivity emerged in the dorsal cortex (V3a and hMT+). Our findings support a strong presence of integrated mechanisms for colour and Ach contrast across the visual hierarchy, with a progression towards selective processing in extrastriate visual areas.

  3. fMRI Adaptation between Action Observation and Action Execution Reveals Cortical Areas with Mirror Neuron Properties in Human BA 44/45

    PubMed Central

    de la Rosa, Stephan; Schillinger, Frieder L.; Bülthoff, Heinrich H.; Schultz, Johannes; Uludag, Kamil

    2016-01-01

    Mirror neurons (MNs) are considered to be the supporting neural mechanism for action understanding. MNs have been identified in monkey’s area F5. The identification of MNs in the human homolog of monkeys’ area F5 Broadmann Area 44/45 (BA 44/45) has been proven methodologically difficult. Cross-modal functional MRI (fMRI) adaptation studies supporting the existence of MNs restricted their analysis to a priori candidate regions, whereas studies that failed to find evidence used non-object-directed (NDA) actions. We tackled these limitations by using object-directed actions (ODAs) differing only in terms of their object directedness in combination with a cross-modal adaptation paradigm and a whole-brain analysis. Additionally, we tested voxels’ blood oxygenation level-dependent (BOLD) response patterns for several properties previously reported as typical MN response properties. Our results revealed 52 voxels in left inferior frontal gyrus (IFG; particularly BA 44/45), which respond to both motor and visual stimulation and exhibit cross-modal adaptation between the execution and observation of the same action. These results demonstrate that part of human IFG, specifically BA 44/45, has BOLD response characteristics very similar to monkey’s area F5. PMID:26973496

  4. Endogenous opioid-dopamine neurotransmission underlie negative CBV fMRI signals.

    PubMed

    Shih, Yen-Yu I; Chiang, Yun-Chen; Shyu, Bai-Chuang; Jaw, Fu-Shan; Duong, Timothy Q; Chang, Chen

    2012-04-01

    Previous studies showed noxious unilateral forepaw electrical stimulation surprisingly evoked negative blood-oxygenation-level-dependent (BOLD), cerebral blood flow (CBF), and cerebral blood volume (CBV) fMRI responses in the bilateral striatum whereas the local neuronal spike and c-Fos activities increased. These negative responses are associated with vasoconstriction and appeared to override the increased hemodynamic responses that typically accompanied with increased neural activity. The current study aimed to investigate the role of μ-opioid system in modulating vasoconstriction in the striatum associated with noxious stimulation on a 4.7-Tesla MRI scanner. Specifically, we investigated: i) how morphine (a μ-opioid receptor agonist) affects the vasoconstriction in the bilateral striatum associated with noxious electrical forepaw stimulation in rats, and ii) how naloxone (an opioid receptor antagonist) and eticlopride (a dopamine D(2)/D(3) receptor antagonist) modulates the morphine effects onwards. Injection of morphine enhanced the negative striatal CBV responses to noxious stimulation. Sequential injection of naloxone in the same animals abolished the stimulus-evoked vasoconstriction. In a separate group of animals, injection of eticlopride following morphine also reduced the vasoconstriction. Our findings suggested that noxious stimulation endogenously activated opioid and dopamine receptors in the striatum and thus leading to vasoconstriction.

  5. BOLD and its connection to dopamine release in human striatum: a cross-cohort comparison.

    PubMed

    Lohrenz, Terry; Kishida, Kenneth T; Montague, P Read

    2016-10-01

    Activity in midbrain dopamine neurons modulates the release of dopamine in terminal structures including the striatum, and controls reward-dependent valuation and choice. This fluctuating release of dopamine is thought to encode reward prediction error (RPE) signals and other value-related information crucial to decision-making, and such models have been used to track prediction error signals in the striatum as encoded by BOLD signals. However, until recently there have been no comparisons of BOLD responses and dopamine responses except for one clear correlation of these two signals in rodents. No such comparisons have been made in humans. Here, we report on the connection between the RPE-related BOLD signal recorded in one group of subjects carrying out an investment task, and the corresponding dopamine signal recorded directly using fast-scan cyclic voltammetry in a separate group of Parkinson's disease patients undergoing DBS surgery while performing the same task. The data display some correspondence between the signal types; however, there is not a one-to-one relationship. Further work is necessary to quantify the relationship between dopamine release, the BOLD signal and the computational models that have guided our understanding of both at the level of the striatum.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574306

  6. BOLD and its connection to dopamine release in human striatum: a cross-cohort comparison.

    PubMed

    Lohrenz, Terry; Kishida, Kenneth T; Montague, P Read

    2016-10-01

    Activity in midbrain dopamine neurons modulates the release of dopamine in terminal structures including the striatum, and controls reward-dependent valuation and choice. This fluctuating release of dopamine is thought to encode reward prediction error (RPE) signals and other value-related information crucial to decision-making, and such models have been used to track prediction error signals in the striatum as encoded by BOLD signals. However, until recently there have been no comparisons of BOLD responses and dopamine responses except for one clear correlation of these two signals in rodents. No such comparisons have been made in humans. Here, we report on the connection between the RPE-related BOLD signal recorded in one group of subjects carrying out an investment task, and the corresponding dopamine signal recorded directly using fast-scan cyclic voltammetry in a separate group of Parkinson's disease patients undergoing DBS surgery while performing the same task. The data display some correspondence between the signal types; however, there is not a one-to-one relationship. Further work is necessary to quantify the relationship between dopamine release, the BOLD signal and the computational models that have guided our understanding of both at the level of the striatum.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

  7. BOLD and its connection to dopamine release in human striatum: a cross-cohort comparison

    PubMed Central

    Lohrenz, Terry; Kishida, Kenneth T.

    2016-01-01

    Activity in midbrain dopamine neurons modulates the release of dopamine in terminal structures including the striatum, and controls reward-dependent valuation and choice. This fluctuating release of dopamine is thought to encode reward prediction error (RPE) signals and other value-related information crucial to decision-making, and such models have been used to track prediction error signals in the striatum as encoded by BOLD signals. However, until recently there have been no comparisons of BOLD responses and dopamine responses except for one clear correlation of these two signals in rodents. No such comparisons have been made in humans. Here, we report on the connection between the RPE-related BOLD signal recorded in one group of subjects carrying out an investment task, and the corresponding dopamine signal recorded directly using fast-scan cyclic voltammetry in a separate group of Parkinson's disease patients undergoing DBS surgery while performing the same task. The data display some correspondence between the signal types; however, there is not a one-to-one relationship. Further work is necessary to quantify the relationship between dopamine release, the BOLD signal and the computational models that have guided our understanding of both at the level of the striatum. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574306

  8. Neural response to modulating the probability that actions of self or other result in auditory tones: A parametric fMRI study into causal ambiguity.

    PubMed

    de Bézenac, Christophe E; Sluming, Vanessa; Gouws, André; Corcoran, Rhiannon

    2016-09-01

    In normal circumstances we can easily distinguish between changes to the external world brought about by our own actions from those with external causes. However, in certain contexts our sense of ownership and agency over acts is not so clear. Neuroimaging studies have implicated a number of regions in the sense of agency, some of which have been shown to vary continuously with action-outcome discordance. However, little is known about dynamic, ambiguous contexts characterised by a lack of information for self-other differentiation, yet such ambiguous states are important in relation to symptoms and levels of consciousness that characterise certain mental health conditions. With a block-design fMRI paradigm, we investigated neural responses to changes in the probability that a participant's irregular finger taps over 12s would result in auditory tones as opposed to tones generated by 'another's finger taps'. The main findings were that misattribution increased in ambiguous conditions where the probability of a tone belonging to self and other was equal. Task-sensitive brain regions, previously identified in self-agency, motor cognition, and ambiguity processing, showed a quadratic response to our self-to-other manipulation, with particular sensitivity to self-control. Task performance (low error and bias) was related to attenuated response in ambiguous conditions while increased response in regions associated with the default mode network was associated with greater overall error and bias towards other. These findings suggest that causal ambiguity as it occurs over time is a prominent feature in sense of agency, one that may eventually contribute to a more comprehensive understanding of positive symptoms of psychosis.

  9. Neural response to modulating the probability that actions of self or other result in auditory tones: A parametric fMRI study into causal ambiguity.

    PubMed

    de Bézenac, Christophe E; Sluming, Vanessa; Gouws, André; Corcoran, Rhiannon

    2016-09-01

    In normal circumstances we can easily distinguish between changes to the external world brought about by our own actions from those with external causes. However, in certain contexts our sense of ownership and agency over acts is not so clear. Neuroimaging studies have implicated a number of regions in the sense of agency, some of which have been shown to vary continuously with action-outcome discordance. However, little is known about dynamic, ambiguous contexts characterised by a lack of information for self-other differentiation, yet such ambiguous states are important in relation to symptoms and levels of consciousness that characterise certain mental health conditions. With a block-design fMRI paradigm, we investigated neural responses to changes in the probability that a participant's irregular finger taps over 12s would result in auditory tones as opposed to tones generated by 'another's finger taps'. The main findings were that misattribution increased in ambiguous conditions where the probability of a tone belonging to self and other was equal. Task-sensitive brain regions, previously identified in self-agency, motor cognition, and ambiguity processing, showed a quadratic response to our self-to-other manipulation, with particular sensitivity to self-control. Task performance (low error and bias) was related to attenuated response in ambiguous conditions while increased response in regions associated with the default mode network was associated with greater overall error and bias towards other. These findings suggest that causal ambiguity as it occurs over time is a prominent feature in sense of agency, one that may eventually contribute to a more comprehensive understanding of positive symptoms of psychosis. PMID:27381929

  10. FMRI in Epilepsy

    NASA Astrophysics Data System (ADS)

    de Araújo, Dráulio B.; Araújo, David; Rosset, Sara; Wichert-Ana, Lauro; Baffa, Oswaldo; Ceiki Sakamoto, Américo; Pereira Leite, João; Santos, Antônio Carlos

    2004-09-01

    Localization of eloquent areas is of utmost importance in neurosurgical planning, especially in epilepsy surgery. Mass, destructive, or developmental lesions may distort brain anatomy. Functional MRI (fMRI) can localize eloquent areas despite these distortions and provide useful information for the planning of tailored resections. This paper deals with the major issues concerning the use of fMRI in epilepsy surgery, including its limitations. We present results derived from the clinical experience of the Epilepsy Surgery Center at Ribeirão Preto School of Medicine, where typical finger tapping and language fMRI paradigms were applied to 40 patients being considered for resective epilepsy surgery around eloquent cortex. Our results confirmed that although fMRI may not be used as a single tool for surgical planning, in conjunction with other methods it is useful in reducing the surgical time, it improves lesion resection, and prevents functional deficits.

  11. Transcranial alternating current stimulation affects the BOLD signal in a frequency and task‐dependent manner

    PubMed Central

    Cabral‐Calderin, Yuranny; Anne Weinrich, Christiane; Schmidt‐Samoa, Carsten; Poland, Eva; Dechent, Peter; Bähr, Mathias

    2015-01-01

    Abstract Transcranial alternating current stimulation (tACS) has emerged as a promising tool for manipulating ongoing brain oscillations. While previous studies demonstrated frequency‐specific effects of tACS on diverse cognitive functions, its effect on neural activity remains poorly understood. Here we asked how tACS modulates regional fMRI blood oxygenation level dependent (BOLD) signal as a function of frequency, current strength, and task condition. TACS was applied over the posterior cortex of healthy human subjects while the BOLD signal was measured during rest or task conditions (visual perception, passive video viewing and motor task). TACS was applied in a blockwise manner at different frequencies (10, 16, 60 and 80 Hz). The strongest tACS effects on BOLD activity were observed with stimulation at alpha (10 Hz) and beta (16 Hz) frequency bands, while effects of tACS at the gamma range were rather modest. Specifically, we found that tACS at 16 Hz induced BOLD activity increase in fronto‐parietal areas. Overall, tACS effects varied as a function of frequency and task, and were predominantly seen in regions that were not activated by the task. Also, the modulated regions were poorly predicted by current density modeling studies. Taken together, our results suggest that tACS does not necessarily exert its strongest effects in regions below the electrodes and that region specificity might be achieved with tACS due to varying susceptibility of brain regions to entrain to a given frequency. Hum Brain Mapp 37:94–121, 2016. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc PMID:26503692

  12. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Bold face type. 232.307...-GENERAL RULES AND REGULATIONS FOR ELECTRONIC FILINGS Preparation of Electronic Submissions § 232.307 Bold face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied...

  13. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Bold face type. 232.307...-GENERAL RULES AND REGULATIONS FOR ELECTRONIC FILINGS Preparation of Electronic Submissions § 232.307 Bold face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied...

  14. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Bold face type. 232.307...-GENERAL RULES AND REGULATIONS FOR ELECTRONIC FILINGS Preparation of Electronic Submissions § 232.307 Bold face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied...

  15. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Bold face type. 232.307...-GENERAL RULES AND REGULATIONS FOR ELECTRONIC FILINGS Preparation of Electronic Submissions § 232.307 Bold face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied...

  16. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Bold face type. 232.307...-GENERAL RULES AND REGULATIONS FOR ELECTRONIC FILINGS Preparation of Electronic Submissions § 232.307 Bold face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied...

  17. Is behavioral variation along the bold-shy continuum associated with variation in the stress axis in zebrafish?

    PubMed

    Oswald, Mary E; Drew, Robert E; Racine, Matt; Murdoch, Gordon K; Robison, Barrie D

    2012-01-01

    We tested whether boldness is associated with attenuation of the physiological stress response in behaviorally selected lines of zebrafish Danio rerio. We measured three component behaviors of boldness: cortisol levels under control and stressed conditions, growth rate, and expression of key genes linked to the hypothalamic-pituitary-interrenal axis in the brain. Surprisingly, bold animals did not differ from shy animals with respect to cortisol levels. However, significant differences between these animals in the expression of glucocorticoid receptors and genes that regulate production of stress hormones indicate that there may still be a relationship between bold behavior and the stress axis. Perhaps the most surprising result of this study was the degree of sexual dimorphism: female zebrafish were bolder than male zebrafish, had significantly lower levels of cortisol, and differed significantly in the expression of several genes in the brain. Our data indicate that a bold behavioral type is associated with transcriptional attenuation of stress axis genes, but we do not yet know whether evolution along the bold-shy continuum is attributable to genetic changes in the stress axis. The bold and shy zebrafish lines will be valuable tools for additional research into the relationship between stress and behavior and the mechanisms regulating sexual dimorphism in these traits. PMID:23099468

  18. Neural systems supporting lexical search guided by letter and semantic category cues: a self-paced overt response fMRI study of verbal fluency.

    PubMed

    Birn, Rasmus M; Kenworthy, Lauren; Case, Laura; Caravella, Rachel; Jones, Tyler B; Bandettini, Peter A; Martin, Alex

    2010-01-01

    Verbal fluency tasks have been widely used to evaluate language and executive control processes in the human brain. FMRI studies of verbal fluency, however, have used either silent word generation (which provides no behavioral measure) or cued generation of single words in order to contend with speech-related motion artifacts. In this study, we use a recently developed paradigm design to investigate the neural correlates of verbal fluency during overt, free recall, word generation so that performance and brain activity could be evaluated under conditions that more closely mirror standard behavioral test demands. We investigated verbal fluency to both letter and category cues in order to evaluate differential involvement of specific frontal and temporal lobe sites as a function of retrieval cue type, as suggested by previous neuropsychological and neuroimaging investigations. In addition, we incorporated both a task switching manipulation and an automatic speech condition in order to modulate the demand placed on executive functions. We found greater activation in the left hemisphere during category and letter fluency tasks, and greater right hemisphere activation during automatic speech. We also found that letter and category fluency tasks were associated with differential involvement of specific regions of the frontal and temporal lobes. These findings provide converging evidence that letter and category fluency performance is dependent on partially distinct neural circuitry. They also provide strong evidence that verbal fluency can be successfully evaluated in the MR environment using overt, self-paced, responses. PMID:19632335

  19. Multivoxel Pattern Analysis for fMRI Data: A Review

    PubMed Central

    Takerkart, Sylvain; Regragui, Fakhita; Boussaoud, Driss; Brovelli, Andrea

    2012-01-01

    Functional magnetic resonance imaging (fMRI) exploits blood-oxygen-level-dependent (BOLD) contrasts to map neural activity associated with a variety of brain functions including sensory processing, motor control, and cognitive and emotional functions. The general linear model (GLM) approach is used to reveal task-related brain areas by searching for linear correlations between the fMRI time course and a reference model. One of the limitations of the GLM approach is the assumption that the covariance across neighbouring voxels is not informative about the cognitive function under examination. Multivoxel pattern analysis (MVPA) represents a promising technique that is currently exploited to investigate the information contained in distributed patterns of neural activity to infer the functional role of brain areas and networks. MVPA is considered as a supervised classification problem where a classifier attempts to capture the relationships between spatial pattern of fMRI activity and experimental conditions. In this paper , we review MVPA and describe the mathematical basis of the classification algorithms used for decoding fMRI signals, such as support vector machines (SVMs). In addition, we describe the workflow of processing steps required for MVPA such as feature selection, dimensionality reduction, cross-validation, and classifier performance estimation based on receiver operating characteristic (ROC) curves. PMID:23401720

  20. Just watching the game ain't enough: striatal fMRI reward responses to successes and failures in a video game during active and vicarious playing.

    PubMed

    Kätsyri, Jari; Hari, Riitta; Ravaja, Niklas; Nummenmaa, Lauri

    2013-01-01

    Although the multimodal stimulation provided by modern audiovisual video games is pleasing by itself, the rewarding nature of video game playing depends critically also on the players' active engagement in the gameplay. The extent to which active engagement influences dopaminergic brain reward circuit responses remains unsettled. Here we show that striatal reward circuit responses elicited by successes (wins) and failures (losses) in a video game are stronger during active than vicarious gameplay. Eleven healthy males both played a competitive first-person tank shooter game (active playing) and watched a pre-recorded gameplay video (vicarious playing) while their hemodynamic brain activation was measured with 3-tesla functional magnetic resonance imaging (fMRI). Wins and losses were paired with symmetrical monetary rewards and punishments during active and vicarious playing so that the external reward context remained identical during both conditions. Brain activation was stronger in the orbitomedial prefrontal cortex (omPFC) during winning than losing, both during active and vicarious playing. In contrast, both wins and losses suppressed activations in the midbrain and striatum during active playing; however, the striatal suppression, particularly in the anterior putamen, was more pronounced during loss than win events. Sensorimotor confounds related to joystick movements did not account for the results. Self-ratings indicated losing to be more unpleasant during active than vicarious playing. Our findings demonstrate striatum to be selectively sensitive to self-acquired rewards, in contrast to frontal components of the reward circuit that process both self-acquired and passively received rewards. We propose that the striatal responses to repeated acquisition of rewards that are contingent on game related successes contribute to the motivational pull of video-game playing.

  1. Just watching the game ain't enough: striatal fMRI reward responses to successes and failures in a video game during active and vicarious playing

    PubMed Central

    Kätsyri, Jari; Hari, Riitta; Ravaja, Niklas; Nummenmaa, Lauri

    2013-01-01

    Although the multimodal stimulation provided by modern audiovisual video games is pleasing by itself, the rewarding nature of video game playing depends critically also on the players' active engagement in the gameplay. The extent to which active engagement influences dopaminergic brain reward circuit responses remains unsettled. Here we show that striatal reward circuit responses elicited by successes (wins) and failures (losses) in a video game are stronger during active than vicarious gameplay. Eleven healthy males both played a competitive first-person tank shooter game (active playing) and watched a pre-recorded gameplay video (vicarious playing) while their hemodynamic brain activation was measured with 3-tesla functional magnetic resonance imaging (fMRI). Wins and losses were paired with symmetrical monetary rewards and punishments during active and vicarious playing so that the external reward context remained identical during both conditions. Brain activation was stronger in the orbitomedial prefrontal cortex (omPFC) during winning than losing, both during active and vicarious playing. In contrast, both wins and losses suppressed activations in the midbrain and striatum during active playing; however, the striatal suppression, particularly in the anterior putamen, was more pronounced during loss than win events. Sensorimotor confounds related to joystick movements did not account for the results. Self-ratings indicated losing to be more unpleasant during active than vicarious playing. Our findings demonstrate striatum to be selectively sensitive to self-acquired rewards, in contrast to frontal components of the reward circuit that process both self-acquired and passively received rewards. We propose that the striatal responses to repeated acquisition of rewards that are contingent on game related successes contribute to the motivational pull of video-game playing. PMID:23781195

  2. Measurement, time-stamping, and analysis of electrodermal activity in fMRI

    NASA Astrophysics Data System (ADS)

    Smyser, Christopher; Grabowski, Thomas J.; Rainville, Pierre; Bechara, Antione; Razavi, Mehrdad; Mehta, Sonya; Eaton, Brent L.; Bolinger, Lizann

    2002-04-01

    A low cost fMRI-compatible system was developed for detecting electrodermal activity without inducing image artifact. Subject electrodermal activity was measured on the plantar surface of the foot using a standard recording circuit. Filtered analog skin conductance responses (SCR) were recorded with a general purpose, time-stamping data acquisition system. A conditioning paradigm involving painful thermal stimulation was used to demonstrate SCR detection and investigate neural correlates of conditioned autonomic activity. 128x128 pixel EPI-BOLD images were acquired with a GE 1.5T Signa scanner. Image analysis was performed using voxel-wise multiple linear regression. The covariate of interest was generated by convolving stimulus event onset with a standard hemodynamic response function. The function was time-shifted to determine optimal activation. Significance was tested using the t-statistic. Image quality was unaffected by the device, and conditioned and unconditioned SCRs were successfully detected. Conditioned SCRs correlated significantly with activity in the right anterior insular cortex. The effect was more robust when responses were scaled by SCR amplitude. The ability to measure and time register SCRs during fMRI acquisition enables studies of cognitive processes marked by autonomic activity, including those involving decision-making, pain, emotion, and addiction.

  3. Vascular action as the primary mechanism of cognitive effects of cholinergic, CNS-acting drugs, a rat phMRI BOLD study

    PubMed Central

    Kocsis, Pál; Gyertyán, István; Éles, János; Laszy, Judit; Hegedűs, Nikolett; Gajári, Dávid; Deli, Levente; Pozsgay, Zsófia; Dávid, Szabolcs; Tihanyi, Károly

    2014-01-01

    Concordant results of functional magnetic resonance imaging (fMRI) and behavioral tests prove that some non-blood–brain barrier-penetrating drugs produce robust central nervous system (CNS) effects. The anticholinergic scopolamine interferes with learning when tested in rats, which coincides with a negative blood-oxygen-level-dependent (BOLD) change in the prefrontal cortex (PFC) as demonstrated by fMRI. The peripherally acting butylscopolamine also evokes a learning deficit in a water-labyrinth test and provokes a negative BOLD signal in the PFC. Donepezil—a highly CNS-penetrating cholinesterase inhibitor—prevents the negative BOLD and cognitive deficits regardless whether the provoking agent is scopolamine or butylscopolamine. Interestingly, the non-BBB-penetrating cholinesterase inhibitor neostigmine also prevents or substantially inhibits those cognitive and fMRI changes. Intact cerebral blood flow and optimal metabolism are crucial for the normal functioning of neurons and other cells in the brain. Drugs that are not BBB penetrating yet act on the CNS highlight the importance of unimpaired circulation, and point to the cerebral vasculature as a primary target for drug action in diseases where impaired circulation and consequently suboptimal energy metabolism are followed by upstream pathologic events. PMID:24643080

  4. Bi-Directional Tuning of Amygdala Sensitivity in Combat Veterans Investigated with fMRI

    PubMed Central

    Brashers-Krug, Tom; Jorge, Ricardo

    2015-01-01

    Objectives Combat stress can be followed by persistent emotional consequences. It is thought that these emotional consequences are caused in part by increased amygdala reactivity. It is also thought that amygdala hyper-reactivity results from decreased inhibition from portions of the anterior cingulate cortex (ACC) in which activity is negatively correlated with activity in the amygdala. However, experimental support for these proposals has been inconsistent. Methods We showed movies of combat and civilian scenes during a functional magnetic resonance imaging (fMRI) session to 50 veterans of recent combat. We collected skin conductance responses (SCRs) as measures of emotional arousal. We examined the relation of blood oxygenation-level dependent (BOLD) signal in the amygdala and ACC to symptom measures and to SCRs. Results Emotional arousal, as measured with SCR, was greater during the combat movie than during the civilian movie and did not depend on symptom severity. As expected, amygdala signal during the less-arousing movie increased with increasing symptom severity. Surprisingly, during the more-arousing movie amygdala signal decreased with increasing symptom severity. These differences led to the unexpected result that amygdala signal in highly symptomatic subjects was lower during the more-arousing movie than during the less-arousing movie. Also unexpectedly, we found no significant inverse correlation between any portions of the amygdala and ACC. Rather, signal throughout more than 80% of the ACC showed a strong positive correlation with signal throughout more than 90% of the amygdala. Conclusions Amygdala reactivity can be tuned bi-directionally, either up or down, in the same person depending on the stimulus and the degree of post-traumatic symptoms. The exclusively positive correlations in BOLD activity between the amygdala and ACC contrast with findings that have been cited as evidence for inhibitory control of the amygdala by the ACC. The

  5. One-Class FMRI-Inspired EEG Model for Self-Regulation Training

    PubMed Central

    Kinreich, Sivan; Jackont, Gilan; Cohen, Avihay; Podlipsky-Klovatch, Ilana; Hendler, Talma; Intrator, Nathan

    2016-01-01

    Recent evidence suggests that learned self-regulation of localized brain activity in deep limbic areas such as the amygdala, may alleviate symptoms of affective disturbances. Thus far self-regulation of amygdala activity could be obtained only via fMRI guided neurofeedback, an expensive and immobile procedure. EEG on the other hand is relatively inexpensive and can be easily implemented in any location. However the clinical utility of EEG neurofeedback for affective disturbances remains limited due to low spatial resolution, which hampers the targeting of deep limbic areas such as the amygdala. We introduce an EEG prediction model of amygdala activity from a single electrode. The gold standard used for training is the fMRI-BOLD signal in the amygdala during simultaneous EEG/fMRI recording. The suggested model is based on a time/frequency representation of the EEG data with varying time-delay. Previous work has shown a strong inhomogeneity among subjects as is reflected by the models created to predict the amygdala BOLD response from EEG data. In that work, different models were constructed for different subjects. In this work, we carefully analyzed the inhomogeneity among subjects and were able to construct a single model for the majority of the subjects. We introduce a method for inhomogeneity assessment. This enables us to demonstrate a choice of subjects for which a single model could be derived. We further demonstrate the ability to modulate brain-activity in a neurofeedback setting using feedback generated by the model. We tested the effect of the neurofeedback training by showing that new subjects can learn to down-regulate the signal amplitude compared to a sham group, which received a feedback obtained by a different participant. This EEG based model can overcome substantial limitations of fMRI-NF. It can enable investigation of NF training using multiple sessions and large samples in various locations. PMID:27163677

  6. Language exposure induced neuroplasticity in the bilingual brain: a follow-up fMRI study.

    PubMed

    Tu, Liu; Wang, Junjing; Abutalebi, Jubin; Jiang, Bo; Pan, Ximin; Li, Meng; Gao, Wei; Yang, Yuchen; Liang, Bishan; Lu, Zhi; Huang, Ruiwang

    2015-03-01

    Although several studies have shown that language exposure crucially influence the cerebral representation of bilinguals, the effects of short-term change of language exposure in daily life upon language control areas in bilinguals are less known. To explore this issue, we employed follow-up fMRI to investigate whether differential exposure induces neuroplastic changes in the language control network in high-proficient Cantonese (L1)-Mandarin (L2) early bilinguals. The same 10 subjects underwent twice BOLD-fMRI scans while performing a silent narration task which corresponded to two different language exposure conditions, CON-1 (L1/L2 usage percentage, 50%:50%) and CON-2 (L1/L2 usage percentage, 90%:10%). We report a strong effect of language exposure in areas related to language control for the less exposed language. Interestingly, these significant effects were present after only a 30-day period of differential language exposure. In detail, we reached the following results: (1) the interaction effect of language and language exposure condition was found significantly in the left pars opercularis (BA 44) and marginally in the left MFG (BA 9); (2) in CON-2, increases of activation values in L2 were found significantly in bilateral BA 46 and BA 9, in the left BA44, and marginally in the left caudate; and (3) in CON-2, we found a significant negative correlation between language exposure to L2 and the BOLD activation value specifically in the left ACC. These findings strongly support the hypothesis that even short periods of differential exposure to a given language may induce significant neuroplastic changes in areas responsible for language control. The language which a bilingual is less exposed to and is also less used will be in need of increased mental control as shown by the increased activity of language control areas.

  7. The neural basis of parallel saccade programming: an fMRI study.

    PubMed

    Hu, Yanbo; Walker, Robin

    2011-11-01

    The neural basis of parallel saccade programming was examined in an event-related fMRI study using a variation of the double-step saccade paradigm. Two double-step conditions were used: one enabled the second saccade to be partially programmed in parallel with the first saccade while in a second condition both saccades had to be prepared serially. The intersaccadic interval, observed in the parallel programming (PP) condition, was significantly reduced compared with latency in the serial programming (SP) condition and also to the latency of single saccades in control conditions. The fMRI analysis revealed greater activity (BOLD response) in the frontal and parietal eye fields for the PP condition compared with the SP double-step condition and when compared with the single-saccade control conditions. By contrast, activity in the supplementary eye fields was greater for the double-step condition than the single-step condition but did not distinguish between the PP and SP requirements. The role of the frontal eye fields in PP may be related to the advanced temporal preparation and increased salience of the second saccade goal that may mediate activity in other downstream structures, such as the superior colliculus. The parietal lobes may be involved in the preparation for spatial remapping, which is required in double-step conditions. The supplementary eye fields appear to have a more general role in planning saccade sequences that may be related to error monitoring and the control over the execution of the correct sequence of responses.

  8. The contribution of primary and secondary somatosensory cortices to the representation of body parts and body sides: an fMRI adaptation study.

    PubMed

    Tamè, Luigi; Braun, Christoph; Lingnau, Angelika; Schwarzbach, Jens; Demarchi, Gianpaolo; Li Hegner, Yiwen; Farnè, Alessandro; Pavani, Francesco

    2012-12-01

    Although the somatosensory homunculus is a classically used description of the way somatosensory inputs are processed in the brain, the actual contributions of primary (SI) and secondary (SII) somatosensory cortices to the spatial coding of touch remain poorly understood. We studied adaptation of the fMRI BOLD response in the somatosensory cortex by delivering pairs of vibrotactile stimuli to the finger tips of the index and middle fingers. The first stimulus (adaptor) was delivered either to the index or to the middle finger of the right or left hand, and the second stimulus (test) was always administered to the left index finger. The overall BOLD response evoked by the stimulation was primarily contralateral in SI and was more bilateral in SII. However, our fMRI adaptation approach also revealed that both somatosensory cortices were sensitive to ipsilateral as well as to contralateral inputs. SI and SII adapted more after subsequent stimulation of homologous as compared with nonhomologous fingers, showing a distinction between different fingers. Most importantly, for both somatosensory cortices, this finger-specific adaptation occurred irrespective of whether the tactile stimulus was delivered to the same or to different hands. This result implies integration of contralateral and ipsilateral somatosensory inputs in SI as well as in SII. Our findings suggest that SI is more than a simple relay for sensory information and that both SI and SII contribute to the spatial coding of touch by discriminating between body parts (fingers) and by integrating the somatosensory input from the two sides of the body (hands).

  9. Single-trial discrimination for integrating simultaneous EEG and fMRI: Identifying cortical areas contributing to trial-to-trial variability in the auditory oddball task

    PubMed Central

    Goldman, Robin I; Wei, Cheng-Yu; Philiastides, Marios G.; Gerson, Adam D.; Friedman, David; Brown, Truman R.; Sajda, Paul

    2009-01-01

    The auditory oddball task is a well-studied stimulus paradigm used to investigate the neural correlates of simple target detection. It elicits several classic event-related potentials (ERPs), the most prominent being the P300 which is seen as a neural correlate of subjects' detection of rare (target) stimuli. Though trial-averaging is typically used to identify and characterize such ERPs, their latency and amplitude can vary on a trial-to-trial basis reflecting variability in the underlying neural information processing. Here we simultaneously recorded EEG and fMRI during an auditory oddball task and identified cortical areas correlated with the trial-to-trial variability of task-discriminating EEG components. Unique to our approach is a linear multivariate method for identifying task-discriminating components within specific stimulus- or response- locked time windows. We find fMRI activations indicative of distinct processes that contribute to the single-trial variability during target detection. These regions are different from those found using standard, including trial-averaged, regressors. Of particular note is strong activation of the lateral occipital complex (LOC). The LOC was not seen when using traditional event-related regressors. Though LOC is typically associated with visual/spatial attention, its activation in an auditory oddball task, where attention can wax and wane from trial-to-trial, indicates it may be part of a more general attention network involved in allocating resources for target detection and decision making. Our results show that trial-to-trial variability in EEG components, acquired simultaneously with fMRI, can yield task-relevant BOLD activations that are otherwise unobservable using traditional fMRI analysis. PMID:19345734

  10. Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers: an fMRI study.

    PubMed

    McBride, Dharma; Barrett, Sean P; Kelly, Jared T; Aw, Andrew; Dagher, Alain

    2006-12-01

    Cues associated with drug taking can trigger relapse, drug seeking, and craving in addicted individuals. Behavioral studies suggest that drug availability and withdrawal can affect the individual response to drug cues. Moreover, the importance of subjective craving in cue-induced relapse has been questioned and an alternative model put forward according to which drug cues trigger habitual drug-seeking behaviors independently of craving. We used functional magnetic resonance imaging to compare the brain response to smoking and control videotapes in 20 healthy smokers, while varying their expectancy to smoke and abstinence levels. The neural response to cigarette cues was strongly modulated by expectancy and, to a lesser extent, abstinence. In people expecting to smoke immediately after the scan, smoking cues activated brain areas implicated in arousal, attention, and cognitive control. However, when subjects knew they would not be allowed to smoke for 4 h, there was almost no brain activation in response to smoking cues, despite equivalent reported levels of craving. In the dorsolateral prefrontal cortex, the neural response was a function of both craving and expectancy. Thalamo-cingulate connectivity, thought to be an index of arousal, was greater during expectancy than nonexpectancy. Our findings confirm the importance of expectancy in the neural response to drug cues, and lend support to the theory that these cues act on brain areas involved in arousal and attention.

  11. Attention Diversion Improves Response Inhibition of Immediate Reward, But Only When it Is Beneficial: An fMRI Study.

    PubMed

    Scalzo, Franco; O'Connor, David A; Orr, Catherine; Murphy, Kevin; Hester, Robert

    2016-01-01

    Deficits of self-control are associated with a number of mental state disorders. The ability to direct attention away from an alluring stimulus appears to aid inhibition of an impulsive response. However, further functional imaging research is required to assess the impact of shifts in attention on self-regulating processes. We varied the level of attentional disengagement in an functional magnetic resonance imaging (fMRI)-based Go/No-go task to probe whether diversion of attention away from alluring stimuli facilitates response inhibition. We used the attention-grabbing characteristic of faces to exogenously direct attention away from stimuli and investigated the relative importance of attention and response inhibition mechanisms under different delayed reward scenarios [i.e., where forgoing an immediate reward ($1) led to a higher ($10) or no payoff in the future]. We found that diverting attention improved response inhibition performance, but only when resistance to an alluring stimulus led to delayed reward. Region of interest analyses indicated significant increased activity in posterior right inferior frontal gyrus during successful No-go trials for delayed reward trials compared to no delayed reward trials, and significant reduction in activity in the superior temporal gyri and left caudate in contexts of high attentional diversion. Our findings imply that strategies that increase the perceived benefits of response inhibition might assist individuals in abstaining from problematic impulsive behaviors. PMID:27616988

  12. Attention Diversion Improves Response Inhibition of Immediate Reward, But Only When it Is Beneficial: An fMRI Study

    PubMed Central

    Scalzo, Franco; O’Connor, David A.; Orr, Catherine; Murphy, Kevin; Hester, Robert

    2016-01-01

    Deficits of self-control are associated with a number of mental state disorders. The ability to direct attention away from an alluring stimulus appears to aid inhibition of an impulsive response. However, further functional imaging research is required to assess the impact of shifts in attention on self-regulating processes. We varied the level of attentional disengagement in an functional magnetic resonance imaging (fMRI)-based Go/No-go task to probe whether diversion of attention away from alluring stimuli facilitates response inhibition. We used the attention-grabbing characteristic of faces to exogenously direct attention away from stimuli and investigated the relative importance of attention and response inhibition mechanisms under different delayed reward scenarios [i.e., where forgoing an immediate reward ($1) led to a higher ($10) or no payoff in the future]. We found that diverting attention improved response inhibition performance, but only when resistance to an alluring stimulus led to delayed reward. Region of interest analyses indicated significant increased activity in posterior right inferior frontal gyrus during successful No-go trials for delayed reward trials compared to no delayed reward trials, and significant reduction in activity in the superior temporal gyri and left caudate in contexts of high attentional diversion. Our findings imply that strategies that increase the perceived benefits of response inhibition might assist individuals in abstaining from problematic impulsive behaviors.

  13. Attention Diversion Improves Response Inhibition of Immediate Reward, But Only When it Is Beneficial: An fMRI Study

    PubMed Central

    Scalzo, Franco; O’Connor, David A.; Orr, Catherine; Murphy, Kevin; Hester, Robert

    2016-01-01

    Deficits of self-control are associated with a number of mental state disorders. The ability to direct attention away from an alluring stimulus appears to aid inhibition of an impulsive response. However, further functional imaging research is required to assess the impact of shifts in attention on self-regulating processes. We varied the level of attentional disengagement in an functional magnetic resonance imaging (fMRI)-based Go/No-go task to probe whether diversion of attention away from alluring stimuli facilitates response inhibition. We used the attention-grabbing characteristic of faces to exogenously direct attention away from stimuli and investigated the relative importance of attention and response inhibition mechanisms under different delayed reward scenarios [i.e., where forgoing an immediate reward ($1) led to a higher ($10) or no payoff in the future]. We found that diverting attention improved response inhibition performance, but only when resistance to an alluring stimulus led to delayed reward. Region of interest analyses indicated significant increased activity in posterior right inferior frontal gyrus during successful No-go trials for delayed reward trials compared to no delayed reward trials, and significant reduction in activity in the superior temporal gyri and left caudate in contexts of high attentional diversion. Our findings imply that strategies that increase the perceived benefits of response inhibition might assist individuals in abstaining from problematic impulsive behaviors. PMID:27616988

  14. Deficient aversive-potentiated startle and the triarchic model of psychopathy: The role of boldness.

    PubMed

    Esteller, Àngels; Poy, Rosario; Moltó, Javier

    2016-05-01

    This study examined the contribution of the phenotypic domains of boldness, meanness, and disinhibition of the triarchic conceptualization of psychopathy (Patrick, Fowles, & Krueger, 2009) to deficient aversive-potentiated startle in a mixed-gender sample of 180 undergraduates. Eyeblink responses to noise probes were recorded during a passive picture-viewing task (erotica, neutral, threat, and mutilation). Deficient threat vs. neutral potentiation was uniquely related to increased boldness scores, thus suggesting that the diminished defensive reaction to aversive stimulation is specifically linked to the charm, social potency and venturesomeness features of psychopathy (boldness), but not to features such as callousness, coldheartedness and cruelty traits (meanness), even though both phenotypes theoretically share the same underlying low-fear disposition. Our findings provide further evidence of the differential association between distinct psychopathy components and deficits in defensive reactivity and strongly support the validity of the triarchic model of psychopathy in disentangling the etiology of this personality disorder.

  15. Deficient aversive-potentiated startle and the triarchic model of psychopathy: The role of boldness.

    PubMed

    Esteller, Àngels; Poy, Rosario; Moltó, Javier

    2016-05-01

    This study examined the contribution of the phenotypic domains of boldness, meanness, and disinhibition of the triarchic conceptualization of psychopathy (Patrick, Fowles, & Krueger, 2009) to deficient aversive-potentiated startle in a mixed-gender sample of 180 undergraduates. Eyeblink responses to noise probes were recorded during a passive picture-viewing task (erotica, neutral, threat, and mutilation). Deficient threat vs. neutral potentiation was uniquely related to increased boldness scores, thus suggesting that the diminished defensive reaction to aversive stimulation is specifically linked to the charm, social potency and venturesomeness features of psychopathy (boldness), but not to features such as callousness, coldheartedness and cruelty traits (meanness), even though both phenotypes theoretically share the same underlying low-fear disposition. Our findings provide further evidence of the differential association between distinct psychopathy components and deficits in defensive reactivity and strongly support the validity of the triarchic model of psychopathy in disentangling the etiology of this personality disorder. PMID:27033014

  16. Applicability of the {bold k}{center_dot}{bold p} method to the electronic structure of quantum dots

    SciTech Connect

    Fu, H.; Wang, L.; Zunger, A.

    1998-04-01

    The {bold k}{center_dot}{bold p} method has become the {open_quotes}standard model{close_quotes} for describing the electronic structure of nanometer-size quantum dots. In this paper we perform parallel {bold k}{center_dot}{bold p} (6{times}6 and 8{times}8) and direct-diagonalization pseudopotential studies on spherical quantum dots of an ionic material{emdash}CdSe, and a covalent material{emdash}InP. By using an equivalent input in both approaches, i.e., starting from a given atomic pseudopotential and deriving from it the Luttinger parameters in {bold k}{center_dot}{bold p} calculation, we investigate the effect of the different underlying wave-function representations used in {bold k}{center_dot}{bold p} and in the more exact pseudopotential direct diagonalization. We find that (i) the 6{times}6{bold k}{center_dot}{bold p} envelope function has a distinct (odd or even) parity, while atomistic wave function is parity-mixed. The 6{times}6{bold k}{center_dot}{bold p} approach produces an incorrect order of the highest valence states for both InP and CdSe dots: the p-like level is above the s-like level. (ii) It fails to reveal that the second conduction state in small InP dots is folded from the L point in the Brillouin zone. Instead, all states in {bold k}{center_dot}{bold p} are described as {Gamma}-like. (iii) The {bold k}{center_dot}{bold p} overestimates the confinement energies of both valence states and conduction states. A wave-function projection analysis shows that the principal reasons for these {bold k}{center_dot}{bold p} errors in dots are (a) use of restricted basis set, and (b) incorrect {ital bulk} dispersion relation. Error (a) can be reduced only by increasing the number of basis functions. Error (b) can be reduced by altering the {bold k}{center_dot}{bold p} implementation so as to bend upwards the second lowest bulk band, and to couple the conduction band into the s-like dot valence state. Our direct diagonalization approach provides an

  17. "What" and "where" in visual working memory: a computational neurodynamical perspective for integrating FMRI and single-neuron data.

    PubMed

    Deco, Gustavo; Rolls, Edmund T; Horwitz, Barry

    2004-05-01

    Single-neuron recordings, functional magnetic resonance imaging (fMRI) data, and the effects of lesions indicate that the prefrontal cortex (PFC) is involved in some types of working memory and related cognitive processes. Based on these data, two different models of the topographical and functional organization of the PFC have been proposed: organization-by-stimulus-domain, and organization-by-process. In this article, we utilize an integrate-and-fire network to model both single-neuron and fMRI data on short-term memory in order to understand data obtained in topologically different parts of the PFC during working memory tasks. We explicitly model the mechanisms that underlie working memory-related activity during the execution of delay tasks that have a "what"-then-"where" design (with both object and spatial delayed responses within the same trial). The model contains different populations of neurons (as found experimentally) in attractor networks that respond in the delay period to the stimulus object, the stimulus position, and to combinations of both object and position information. The pools are arranged hierarchically and have global inhibition through inhibitory interneurons to implement competition. It is shown that a biasing attentional input to define the current relevant information (object or location) enables the system to select the correct neuronal populations during the delay period in what is a biased competition model of attention. The processes occurring at the AMPA and NMDA synapses are dynamically modeled in the integrate-and-fire implementation to produce realistic spiking dynamics. It is shown that the fMRI data characteristic of the dorsal PFC and linked to spatial processing and manipulation of items can be reproduced in the model by a high level of inhibition, whereas the fMRI data characteristic of the ventral PFC and linked to object processing can be produced by a lower level of inhibition, even though the network is itself

  18. Unification of sentence processing via ear and eye: an fMRI study.

    PubMed

    Braze, David; Mencl, W Einar; Tabor, Whitney; Pugh, Kenneth R; Constable, R Todd; Fulbright, Robert K; Magnuson, James S; Van Dyke, Julie A; Shankweiler, Donald P

    2011-04-01

    We present new evidence based on fMRI for the existence and neural architecture of an abstract supramodal language system that can integrate linguistic inputs arising from different modalities such that speech and print each activate a common code. Working with sentence material, our aim was to find out where the putative supramodal system is located and how it responds to comprehension challenges. To probe these questions we examined BOLD activity in experienced readers while they performed a semantic categorization task with matched written or spoken sentences that were either well-formed or contained anomalies of syntactic form or pragmatic content. On whole-brain scans, both anomalies increased net activity over non-anomalous baseline sentences, chiefly at left frontal and temporal regions of heteromodal cortex. The anomaly-sensitive sites correspond approximately to those that previous studies (Michael et al., 2001; Constable et al., 2004) have found to be sensitive to other differences in sentence complexity (object relative minus subject relative). Regions of interest (ROIs) were defined by peak response to anomaly averaging over modality conditions. Each anomaly-sensitive ROI showed the same pattern of response across sentence types in each modality. Voxel-by-voxel exploration over the whole brain based on a cosine similarity measure of common function confirmed the specificity of supramodal zones.

  19. The highly sensitive brain: an fMRI study of sensory processing sensitivity and response to others' emotions

    PubMed Central

    Acevedo, Bianca P; Aron, Elaine N; Aron, Arthur; Sangster, Matthew-Donald; Collins, Nancy; Brown, Lucy L

    2014-01-01

    Background Theory and research suggest that sensory processing sensitivity (SPS), found in roughly 20% of humans and over 100 other species, is a trait associated with greater sensitivity and responsiveness to the environment and to social stimuli. Self-report studies have shown that high-SPS individuals are strongly affected by others' moods, but no previous study has examined neural systems engaged in response to others' emotions. Methods This study examined the neural correlates of SPS (measured by the standard short-form Highly Sensitive Person [HSP] scale) among 18 participants (10 females) while viewing photos of their romantic partners and of strangers displaying positive, negative, or neutral facial expressions. One year apart, 13 of the 18 participants were scanned twice. Results Across all conditions, HSP scores were associated with increased brain activation of regions involved in attention and action planning (in the cingulate and premotor area [PMA]). For happy and sad photo conditions, SPS was associated with activation of brain regions involved in awareness, integration of sensory information, empathy, and action planning (e.g., cingulate, insula, inferior frontal gyrus [IFG], middle temporal gyrus [MTG], and PMA). Conclusions As predicted, for partner images and for happy facial photos, HSP scores were associated with stronger activation of brain regions involved in awareness, empathy, and self-other processing. These results provide evidence that awareness and responsiveness are fundamental features of SPS, and show how the brain may mediate these traits. PMID:25161824

  20. Predator odor-evoked BOLD activation in the awake rat: Modulation by oxytocin and V1a vasopressin receptor antagonists

    PubMed Central

    Reed, Michael D.; Price, Katherine E.; Archbold, Jonathan; Moffa, Anthony; Febo, Marcelo

    2013-01-01

    Modulators of unconditioned fear are potential targets for developing treatments for anxiety disorders. We used blood oxygen level dependent (BOLD) MRI to investigate the pattern of brain activity during the presentation of a predator odor (cat fur) and a repulsive novel odor, butyric acid (BA), to awake rats. We further tested whether odor-evoked BOLD activation involved oxytocin (OT) and vasopressin V1a receptors. Animals were subdivided into groups either administered an intracerebroventricular injection of artificial cerebrospinal fluid (CSF), an OT receptor antagonist or a V1a antagonist (125 ng/10 μL each) 90 min before studies. BA odor evoked robust brain activation across olfactory, sensory, memory and limbic regions. The magnitude of BOLD activation across these regions was greater for BA than with cat fur. However, blockade of OT and V1a receptors differentially modulated odor evoked neural activity, particularly in the amygdala. OT and V1a antagonism preferentially modulated BOLD responding to BA in the cortical amygdala. While, OT and V1a antagonisms preferentially modulated BOLD responding to cat fur in the central amygdala. The data suggest that although OT receptors modulate BOLD activation in response to a novel and repulsive odor such as BA, vasopressin V1a receptors exert a modulatory influence on the neural response to a predator odor. PMID:23219972

  1. Prequit fMRI Responses to Pleasant Cues and Cigarette-Related Cues Predict Smoking Cessation Outcome

    PubMed Central

    2014-01-01

    Introduction: The reasons that some smokers find it harder to quit than others are unclear. Understanding how individual differences predict smoking cessation outcomes may allow the development of more successful personalized treatments for nicotine dependence. Theoretical models suggest that drug users might be characterized by increased sensitivity to drug cues and by reduced sensitivity to nondrug-related natural rewards. We hypothesized that baseline differences in brain sensitivity to natural rewards and cigarette-related cues would predict the outcome of a smoking cessation attempt. Methods: Using functional magnetic resonance imaging, we recorded prequit brain responses to neutral, emotional (pleasant and unpleasant), and cigarette-related cues from 55 smokers interested in quitting. We then assessed smoking abstinence, mood, and nicotine withdrawal symptoms during the course of a smoking cessation attempt. Results: Using cluster analysis, we identified 2 groups of smokers who differed in their baseline responses to pleasant cues and cigarette-related cues in the posterior visual association areas, the dorsal striatum, and the medial and dorsolateral prefrontal cortex. Smokers who showed lower prequit levels of brain reactivity to pleasant stimuli than to cigarette-related cues were less likely to be abstinent 6 months after their quit attempt, and they had higher levels of negative affect during the course of the quit attempt. Conclusions: Smokers with blunted brain responses to pleasant stimuli, relative to cigarette-related stimuli, had more difficulty quitting smoking. For these individuals, the lack of alternative forms of reinforcement when nicotine deprived might be an important factor underlying relapse. Normalizing these pathological neuroadaptations may help them achieve abstinence. PMID:24376278

  2. Molecular fMRI

    PubMed Central

    Bartelle, Benjamin B.; Barandov, Ali

    2016-01-01

    Comprehensive analysis of brain function depends on understanding the dynamics of diverse neural signaling processes over large tissue volumes in intact animals and humans. Most existing approaches to measuring brain signaling suffer from limited tissue penetration, poor resolution, or lack of specificity for well-defined neural events. Here we discuss a new brain activity mapping method that overcomes some of these problems by combining MRI with contrast agents sensitive to neural signaling. The goal of this “molecular fMRI” approach is to permit noninvasive whole-brain neuroimaging with specificity and resolution approaching current optical neuroimaging methods. In this article, we describe the context and need for molecular fMRI as well as the state of the technology today. We explain how major types of MRI probes work and how they can be sensitized to neurobiological processes, such as neurotransmitter release, calcium signaling, and gene expression changes. We comment both on past work in the field and on challenges and promising avenues for future development. SIGNIFICANCE STATEMENT Brain researchers currently have a choice between measuring neural activity using cellular-level recording techniques, such as electrophysiology and optical imaging, or whole-brain imaging methods, such as fMRI. Cellular level methods are precise but only address a small portion of mammalian brains; on the other hand, whole-brain neuroimaging techniques provide very little specificity for neural pathways or signaling components of interest. The molecular fMRI techniques we discuss have particular potential to combine the specificity of cellular-level measurements with the noninvasive whole-brain coverage of fMRI. On the other hand, molecular fMRI is only just getting off the ground. This article aims to offer a snapshot of the status and future prospects for development of molecular fMRI techniques. PMID:27076413

  3. Asymptotic properties of a bold random walk

    NASA Astrophysics Data System (ADS)

    Serva, Maurizio

    2014-08-01

    In a recent paper we proposed a non-Markovian random walk model with memory of the maximum distance ever reached from the starting point (home). The behavior of the walker is different from the simple symmetric random walk only when she is at this maximum distance, where, having the choice to move either farther or closer, she decides with different probabilities. If the probability of a forward step is higher than the probability of a backward step, the walker is bold and her behavior turns out to be superdiffusive; otherwise she is timorous and her behavior turns out to be subdiffusive. The scaling behavior varies continuously from subdiffusive (timorous) to superdiffusive (bold) according to a single parameter γ ∈R. We investigate here the asymptotic properties of the bold case in the nonballistic region γ ∈[0,1/2], a problem which was left partially unsolved previously. The exact results proved in this paper require new probabilistic tools which rely on the construction of appropriate martingales of the random walk and its hitting times.

  4. Visual Network Asymmetry and Default Mode Network Function in ADHD: An fMRI Study

    PubMed Central

    Hale, T. Sigi; Kane, Andrea M.; Kaminsky, Olivia; Tung, Kelly L.; Wiley, Joshua F.; McGough, James J.; Loo, Sandra K.; Kaplan, Jonas T.

    2014-01-01

    Background: A growing body of research has identified abnormal visual information processing in attention-deficit hyperactivity disorder (ADHD). In particular, slow processing speed and increased reliance on visuo-perceptual strategies have become evident. Objective: The current study used recently developed fMRI methods to replicate and further examine abnormal rightward biased visual information processing in ADHD and to further characterize the nature of this effect; we tested its association with several large-scale distributed network systems. Method: We examined fMRI BOLD response during letter and location judgment tasks, and directly assessed visual network asymmetry and its association with large-scale networks using both a voxelwise and an averaged signal approach. Results: Initial within-group analyses revealed a pattern of left-lateralized visual cortical activity in controls but right-lateralized visual cortical activity in ADHD children. Direct analyses of visual network asymmetry confirmed atypical rightward bias in ADHD children compared to controls. This ADHD characteristic was atypically associated with reduced activation across several extra-visual networks, including the default mode network (DMN). We also found atypical associations between DMN activation and ADHD subjects’ inattentive symptoms and task performance. Conclusion: The current study demonstrated rightward VNA in ADHD during a simple letter discrimination task. This result adds an important novel consideration to the growing literature identifying abnormal visual processing in ADHD. We postulate that this characteristic reflects greater perceptual engagement of task-extraneous content, and that it may be a basic feature of less efficient top-down task-directed control over visual processing. We additionally argue that abnormal DMN function may contribute to this characteristic. PMID:25076915

  5. Deriving angular displacement from optic flow: a fMRI study.

    PubMed

    Diekmann, Volker; Jürgens, Reinhart; Becker, Wolfgang

    2009-05-01

    Using fMRI we wished to identify brain areas subserving the conversion of velocity signals into estimates of self-displacement (velocity-to-displacement integration, VDI), a function which is a prerequisite for the ability to navigate without landmarks. As real self-motion is not feasible in an fMRI environment, we presented subjects with a ride along a circular path in virtual reality devoid of usable landmarks. We asked subjects to try and feel as if actually moving in the scene and to either detect and count changes in driving speed (V-task) or to estimate the angular displacement achieved during a ride (D-task). We examined the contrast between these two tasks with regard to two hypothesised key functions for VDI: (1) evoking an internal image of the self in space and (2) manipulating this image in proportion to perceived velocity at the pace of a time base. The BOLD-responses during both tasks were fairly similar showing activity with right hemispheric dominance in a large parieto-temporo-occipital area as well as in frontal and prefrontal areas. Contrast D-V revealed a mainly parieto-hippocampal network comprising precuneus and inferior parietal cortex, posterior parieto-occipital cortex, retrosplenial cortex and the hippocampal region, but also right superior frontal gyrus and right cerebellum. It can be viewed as a blend of networks known to be involved in mental rotation and in navigation, except for the lack of ventral premotor and prefrontal activity. A tentative interpretation proposes a scenario where precuneus, together perhaps with posterior parieto-occipital cortex, provides the postulated mental image of the self in space and uses it to interpret results computed in the hippocampal region. In the hippocampal region, VDI proper would take place based on a map of spatial orientation, with the appropriate time scale being an intrinsic property. In addition, a dedicated time keeping system in inferior parietal cortex appears to be involved.

  6. Branding and a child’s brain: an fMRI study of neural responses to logos

    PubMed Central

    Bruce, Jared M.; Black, William R.; Lepping, Rebecca J.; Henry, Janice M.; Cherry, Joseph Bradley C.; Martin, Laura E.; Papa, Vlad B.; Davis, Ann M.; Brooks, William M.; Savage, Cary R.

    2014-01-01

    Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children’s brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing. PMID:22997054

  7. State-space estimation of the input stimulus function using the Kalman filter: a communication system model for fMRI experiments.

    PubMed

    Ward, B Douglas; Mazaheri, Yousef

    2006-12-15

    The blood oxygenation level-dependent (BOLD) signal measured in functional magnetic resonance imaging (fMRI) experiments in response to input stimuli is temporally delayed and distorted due to the blurring effect of the voxel hemodynamic impulse response function (IRF). Knowledge of the IRF, obtained during the same experiment, or as the result of a separate experiment, can be used to dynamically obtain an estimate of the input stimulus function. Reconstruction of the input stimulus function allows the fMRI experiment to be evaluated as a communication system. The input stimulus function may be considered as a "message" which is being transmitted over a noisy "channel", where the "channel" is characterized by the voxel IRF. Following reconstruction of the input stimulus function, the received message is compared with the transmitted message on a voxel-by-voxel basis to determine the transmission error rate. Reconstruction of the input stimulus function provides insight into actual brain activity during task activation with less temporal blurring, and may be considered as a first step toward estimation of the true neuronal input function.

  8. fMRI activation maps based on the NN-ARx model.

    PubMed

    Riera, J; Bosch, J; Yamashita, O; Kawashima, R; Sadato, N; Okada, T; Ozaki, T

    2004-10-01

    The most significant progresses in the understanding of human brain functions have been possible due to the use of functional magnetic resonance imaging (fMRI), which when used in combination with other standard neuroimaging techniques (i.e., EEG) provides researchers with a potential tool to elucidate many biophysical principles, established previously by animal comparative studies. However, to date, most of the methods proposed in the literature seeking fMRI signs have been limited to the use of a top-down data analysis approach, thus ignoring a pool of physiological facts. In spite of the important contributions achieved by applying these methods to actual data, there is a disproportionate gap between theoretical models and data-analysis strategies while trying to focus on several new prospects, like for example fMRI/EEG data fusion, causality/connectivity patterns, and nonlinear BOLD signal dynamics. In this paper, we propose a new approach which will allow many of the abovementioned hot topics to be addressed in the near future with an underlying interpretability based on bottom-up modeling. In particular, the theta-MAP presented in the paper to test brain activation corresponds very well