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Sample records for bold fmri response

  1. Neural inhibition can explain negative BOLD responses: A mechanistic modelling and fMRI study.

    PubMed

    Sten, S; Lundengård, K; Witt, S T; Cedersund, G; Elinder, F; Engström, M

    2017-09-01

    Functional magnetic resonance imaging (fMRI) of hemodynamic changes captured in the blood oxygen level-dependent (BOLD) response contains information of brain activity. The BOLD response is the result of a complex neurovascular coupling and comes in at least two fundamentally different forms: a positive and a negative deflection. Because of the complexity of the signaling, mathematical modelling can provide vital help in the data analysis. For the positive BOLD response, there are plenty of mathematical models, both physiological and phenomenological. However, for the negative BOLD response, no physiologically based model exists. Here, we expand our previously developed physiological model with the most prominent mechanistic hypothesis for the negative BOLD response: the neural inhibition hypothesis. The model was trained and tested on experimental data containing both negative and positive BOLD responses from two studies: 1) a visual-motor task and 2) a working-memory task in conjunction with administration of the tranquilizer diazepam. Our model was able to predict independent validation data not used for training and provides a mechanistic underpinning for previously observed effects of diazepam. The new model moves our understanding of the negative BOLD response from qualitative reasoning to a quantitative systems-biology level, which can be useful both in basic research and in clinical use. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. BOLD fMRI mapping of brain responses to nociceptive stimuli in rats under ketamine anesthesia.

    PubMed

    Shih, Yen-Yu I; Chang, Chen; Chen, Jyh-Cheng; Jaw, Fu-Shan

    2008-10-01

    Ketamine is one of the most commonly used anesthetics, but its effects on nociceptive responses are not clearly defined. This study used blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to hemodynamically map responses to formalin stimuli under ketamine anesthesia. All imaging was performed on a 4.7-T fMRI system. During dynamic image acquisition, formalin was injected into the rat hindpaw as a painful stimulant. Correlation coefficients were calculated, and each image was registered and fused with the corresponding rat brain atlas so as to avoid inaccuracies arising from manual definition of the brain area and to achieve atlas-based normalization among subjects. Formalin injections were found to increase BOLD signals in the cingulate cortex, sensory-motor cortices, insular cortex, striatum, nucleus accumbens, medial thalamus, ventrolateral thalamic group, and hippocampus. Moreover, in contrast to previous pain investigations, the frontal subcortical regions were strongly activated in ketamine-anesthetized rats.

  3. 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

  4. A Critical Role for Purinergic Signalling in the Mechanisms Underlying Generation of BOLD fMRI Responses

    PubMed Central

    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.; Lythgoe, Mark F.

    2015-01-01

    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. PMID:25834053

  5. 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. Copyright © 2015 the authors 0270-6474/15/355284-09$15.00/0.

  6. fMRI BOLD Response to the Eyes Task in Offspring From Multiplex Alcohol Dependence Families

    PubMed Central

    Hill, Shirley Y.; Kostelnik, Bryan; Holmes, Brian; Goradia, Dhruman; McDermott, Michael; Diwadkar, Vaibhav; Keshavan, Matcheri

    2012-01-01

    Background Increased susceptibility for developing alcohol dependence (AD) may be related to structural and functional differences in brain circuits that influence social cognition and more specifically, theory of mind (ToM). Alcohol dependent individuals have a greater likelihood of having deficits in social skills and greater social alienation. These characteristics may be related to inherited differences in the neuroanatomical network that comprises the social brain. Methods Adolescent/young adult participants from multiplex AD families and controls (n = 16) were matched for gender, age, IQ, education, and handedness and administered the Eyes Task of Baron-Cohen during functional magnetic resonance imaging (fMRI). Results High-risk (HR) subjects showed significantly diminished blood oxygen level dependent (BOLD) response in comparison with low-risk control young adults in the right middle temporal gyrus (RMTG) and the left inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM tasks. Conclusions Offspring from multiplex families for AD may manifest one aspect of their genetic susceptibility by having a diminished BOLD response in brain regions associated with performance of ToM tasks. These results suggest that those at risk for developing AD may have reduced ability to empathize with others’ state of mind, possibly resulting in diminished social skill. PMID:18034695

  7. The Stability of the BOLD fMRI Response to Motor Tasks is altered in Patients with Chronic Ischemic Stroke

    PubMed Central

    Mazzetto-Betti, Kelley C.; Leoni, Renata F.; Pontes-Neto, Octavio M.; Santos, Antonio C.; Leite, Joao P.; Silva, Afonso C.; de Araujo, Draulio B.

    2010-01-01

    Background and Purpose Functional Magnetic Resonance Imaging (fMRI) is a powerful tool to investigate recovery of brain function in stroke patients. An inherent assumption in fMRI data analysis is that the Blood Oxygenation Level Dependent (BOLD) signal is stable over the course of the exam. In this study, we evaluated the validity of such assumption in chronic stroke patients. Methods Fifteen patients performed a simple motor task with repeated epochs using the paretic and the unaffected hand in separate runs. The corresponding BOLD signal time courses were extracted from the primary (M1) and supplementary motor areas (SMA) of both hemispheres. Statistical maps were obtained by the conventional General Linear Model (GLM) and by a parametric-GLM (p-GLM). Results Stable BOLD amplitude was observed when the task was executed with the unaffected hand. Conversely, the BOLD signal amplitude in both M1 and SMA was progressively attenuated in every patient when the task was executed with the paretic hand. The conventional GLM analysis failed to detect brain activation during movement of the paretic hand. However, the proposed p-GLM corrected the misdetection problem and showed robust activation in both M1 and SMA. Conclusions The use of data analysis tools that are built upon the premise of a stable BOLD signal may lead to misdetection of functional regions and underestimation of brain activity in stroke patients. The present data urges the use of caution when relying upon the BOLD response as a marker of brain reorganization in stroke patients. PMID:20705926

  8. Effect of hypoxia on BOLD fMRI response and total cerebral blood flow in migraine with aura patients.

    PubMed

    Arngrim, Nanna; Hougaard, Anders; Schytz, Henrik W; Vestergaard, Mark B; Britze, Josefine; Amin, Faisal Mohammad; Olsen, Karsten S; Larsson, Henrik Bw; Olesen, Jes; Ashina, Messoud

    2017-01-01

    Experimentally induced hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura (MA). We investigated the blood oxygenation level-dependent (BOLD) signal response to visual stimulation during hypoxia in MA patients and healthy volunteers. In a randomized double-blind crossover study design, 15 MA patients were allocated to 180 min of normobaric poikilocapnic hypoxia (capillary oxygen saturation 70-75%) or sham (normoxia) on two separate days and 14 healthy volunteers were exposed to hypoxia. The BOLD functional MRI (fMRI) signal response to visual stimulation was measured in the visual cortex ROIs V1-V5. Total cerebral blood flow (CBF) was calculated by measuring the blood velocity in the internal carotid arteries and the basilar artery using phase-contrast mapping (PCM) MRI. Hypoxia induced a greater decrease in BOLD response to visual stimulation in V1-V4 in MA patients compared to controls. There was no group difference in hypoxia-induced total CBF increase. In conclusion, the study demonstrated a greater hypoxia-induced decrease in BOLD response to visual stimulation in MA patients. We suggest this may represent a hypoxia-induced change in neuronal excitability or abnormal vascular response to visual stimulation, which may explain the increased sensibility to hypoxia in these patients leading to migraine attacks.

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

    PubMed Central

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

    2015-01-01

    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 multi-sensory, but not unisensory cues, was significantly related to participants’ level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. PMID:26475784

  10. 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

  11. Detection and characterization of single-trial fMRI bold responses: paradigm free mapping.

    PubMed

    Gaudes, César Caballero; Petridou, Natalia; Dryden, Ian L; Bai, Li; Francis, Susan T; Gowland, Penny A

    2011-09-01

    This work presents a novel method of mapping the brain's response to single stimuli in space and time without prior knowledge of the paradigm timing: paradigm free mapping (PFM). This method is based on deconvolution of the hemodynamic response from the voxel time series assuming a linear response and using a ridge-regression algorithm. Statistical inference is performed by defining a spatio-temporal t-statistic and by controlling for multiple comparisons using the false discovery rate procedure. The methodology was validated on five subjects who performed self-paced and visually cued finger tapping at 7 Tesla, with moderate (TR = 2 s) and high (TR = 0.4 s) temporal resolution. The results demonstrate that detection of single-trial BOLD events is feasible without a priori information on the stimulus paradigm. The proposed method opens up the possibility of designing temporally unconstrained paradigms to study the cortical response to unpredictable mental events.

  12. Prestimulus EEG alpha oscillations modulate task-related fMRI BOLD responses to auditory stimuli.

    PubMed

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

    2015-06-01

    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 the 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.

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

    PubMed Central

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

    2015-01-01

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

  14. Olfactory responses to natal stream water in sockeye salmon by BOLD fMRI.

    PubMed

    Bandoh, Hiroshi; Kida, Ikuhiro; Ueda, Hiroshi

    2011-01-17

    Many studies have shown that juvenile salmon imprint olfactory memory of natal stream odors during downstream migration, and adults recall this stream-specific odor information to discriminate their natal stream during upstream migration for spawning. The odor information processing of the natal stream in the salmon brain, however, has not been clarified. We applied blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to investigate the odor information processing of the natal stream in the olfactory bulb and telencephalon of lacustrine sockeye salmon (Oncorhynchus nerka). The strong responses to the natal stream water were mainly observed in the lateral area of dorsal telencephalon (Dl), which are homologous to the medial pallium (hippocampus) in terrestrial vertebrates. Although the concentration of L-serine (1 mM) in the control water was 20,000-times higher than that of total amino acid in the natal stream water (47.5 nM), the BOLD signals resulting from the natal stream water were stronger than those by L-serine in the Dl. We concluded that sockeye salmon could process the odor information of the natal stream by integrating information in the Dl area of the telencephalon.

  15. Baseline BOLD correlation predicts individuals' stimulus-evoked BOLD responses.

    PubMed

    Liu, Xiao; Zhu, Xiao-Hong; Chen, Wei

    2011-02-01

    To investigate whether individuals' ongoing neuronal activity at resting state can affect their response to brain stimulation, fMRI BOLD signals were imaged from the human visual cortex of fifteen healthy subjects in the absence and presence of visual stimulation. It was found that the temporal correlation strength but not amplitude of baseline BOLD signal fluctuations acquired under the eyes-fixed condition is positively correlated with the amplitude of stimulus-evoked BOLD responses across subjects. Moreover, the spatiotemporal correlations of baseline BOLD signals imply a coherent network covering the visual system, which is topographically indistinguishable from the "resting-state visual network" observed under the eyes-closed condition. The overall findings suggest that the synchronization of ongoing brain activity plays an important role in determining stimulus-evoked brain activity even at an early stage of the sensory system. The tight relationship between baseline BOLD correlation and stimulus-evoked BOLD amplitude provides an essential basis for understanding and interpreting the large inter-subject BOLD variability commonly observed in numerous fMRI studies and potentially for improving group fMRI analysis. This study highlights the importance to integrate the information from both resting-state coherent networks and task-evoked neural responses for a better understanding of how the brain functions.

  16. The relationship between BOLD fMRI response and the underlying white matter as measured by fractional anisotropy (FA): A systematic review.

    PubMed

    Warbrick, Tracy; Rosenberg, Jessica; Shah, N J

    2017-06-01

    Despite the relationship between brain structure and function being of fundamental interest in cognitive neuroscience, the relationship between the brain's white matter, measured using fractional anisotropy (FA), and the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) response is poorly understood. A systematic review of literature investigating the association between FA and fMRI BOLD response was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed and Web of Knowledge databases were searched up until 22.04.2016 using a predetermined set of search criteria. The search identified 363 papers, 28 of which met the specified inclusion criteria. Positive relationships were mainly observed in studies investigating the primary sensory and motor systems and in resting state data. Both positive and negative relationships were seen in studies using cognitive tasks. This systematic review suggests that there is a relationship between FA and the fMRI BOLD response and that the relationship is task and region dependent. Behavioural and/or clinical variables were shown to be essential in interpreting the relationships between imaging measures. The results highlight the heterogeneity in the methods used across papers in terms of fMRI task, population investigated and data analysis techniques. Further investigation and replication of current findings are required before definitive conclusions can be drawn. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The study of cerebral hemodynamic and neuronal response to visual stimulation using simultaneous NIR optical tomography and BOLD fMRI in humans

    PubMed Central

    Zhang, Xiaofeng; Toronov, Vladislav Y.; Fabiani, Monica; Gratton, Gabriele; Webb, Andrew G.

    2011-01-01

    The integration of near-infrared (NIR) and functional MRI (fMRI) studies is potentially a powerful method to investigate the physiological mechanism of human cerebral activity. However, current NIR methodologies do not provide adequate accuracy of localization and are not fully integrated with MRI in the sense of mutual enhancement of the two imaging modalities. Results are presented to address these issues by developing an MRI-compatible optical probe and using diffuse optical tomography for optical image reconstruction. We have developed a complete methodology that seamlessly integrates NIR tomography with fMRI data acquisition. In this paper, we apply this methodology to determine both hemodynamic and early neuronal responses in the visual cortex in humans. Early results indicate that the changes in deoxyhemoglobin concentration from optical data are co-localized with fMRI BOLD signal changes, but changes in oxyhemoglobin concentration (not measurable using fMRI) show interesting spatial differences. PMID:21776185

  18. The study of cerebral hemodynamic and neuronal response to visual stimulation using simultaneous NIR optical tomography and BOLD fMRI in humans

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaofeng; Toronov, Vladislav Y.; Fabiani, Monica; Gratton, Gabriele; Webb, Andrew G.

    2005-04-01

    The integration of near-infrared (NIR) and functional MRI (fMRI) studies is potentially a powerful method to investigate the physiological mechanism of human cerebral activity. However, current NIR methodologies do not provide adequate accuracy of localization and are not fully integrated with MRI in the sense of mutual enhancement of the two imaging modalities. Results are presented to address these issues by developing an MRI-compatible optical probe and using diffuse optical tomography for optical image reconstruction. We have developed a complete methodology that seamlessly integrates NIR tomography with fMRI data acquisition. In this paper, we apply this methodology to determine both hemodynamic and early neuronal responses in the visual cortex in humans. Early results indicate that the changes in deoxyhemoglobin concentration from optical data are co-localized with fMRI BOLD signal changes, but changes in oxyhemoglobin concentration (not measurable using fMRI) show small spatial differences.

  19. 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.

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

    PubMed Central

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

    2008-01-01

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

  1. 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

  2. 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

  3. 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.

  4. Differential localization of pain-related neural responses during acupuncture stimulation using Blood Oxygen Level Dependent (BOLD) fMRI in a canine model.

    PubMed

    Chang, Suk-Ki; Jahng, Geon-Ho; Lee, Sung-Ho; Choi, Il-Whan; Choi, Chi-Bong; Choi, Woo-Suk

    2012-01-01

    The objective of this study was to differentiate the neuronal responses, which was related or unrelated, to pain associated with acupuncture stimulation, and to localize the brain regions with response to stimulation that is unrelated to pain by using Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI). BOLD fMRI was performed in six normal healthy beagle dogs, during placebo and verum acupuncture stimulations, at the right side of BL60 (KunLun) acupoint before and after local anesthesia of the acupoint. The order of the four sessions was placebo; verum acupuncture stimulation; before local anesthesia; and followed by the same stimulation after local anesthesia. One-sample t-test analysis was performed to localize the activated or deactivated areas, during both pre-anesthesia and post-anesthesia. In order to compare the pre-anesthesia to post-anesthetic responses, and placebo to verum acupuncture stimulation, within-subject analysis was performed. The post-anesthetic verum acupuncture stimulation resulted in increased activations in the left somatic afferent area I and II, right visual and auditory association area, and the descending reticular activating system of the brainstem. In addition, differential areas during post-anesthesia compared to that of the pre-anesthesia were in the left olfactory peduncle and descending reticular activating system of the brainstem. These results indicate that the areas of specific neural pathway are considered to be unrelated to the pain response during acupuncture stimulation.

  5. Reproducibility of BOLD, Perfusion, and CMRO2 Measurements with Calibrated-BOLD fMRI

    PubMed Central

    Leontiev, Oleg; Buxton, Richard B.

    2007-01-01

    The coupling of changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during brain activation can be characterized by an empirical index, n, defined as the ratio between fractional CBF change and fractional CMRO2 change. The combination of blood oxygenation level dependent (BOLD) imaging with CBF measurements from arterial spin labeling (ASL) provides a potentially powerful experimental approach for measuring n, but the reproducibility of the technique previously has not been assessed. In this study, inter-subject variance and intra-subject reproducibility of the method were determined. Block design %BOLD and %CBF responses to visual stimulation and mild hypercapnia (5% CO2) were measured, and these data were used to compute the BOLD scaling factor M, %CMRO2 change with activation, and the coupling index n. Reproducibility was determined for three approaches to defining regions-of-interest (ROIs): 1) Visual area V1 determined from prior retinotopic maps, 2) BOLD-activated voxels from a separate functional localizer, and 3) CBF–activated voxels from a separate functional localizer. For estimates of %BOLD, %CMRO2 and n, intra-subject reproducibility was found to be best for regions selected according to CBF activation. Among all fMRI measurements, estimates of n were the most robust and were substantially more stable within individual subjects (coefficient of variation, CV=7.4%) than across the subject pool (CV=36.9%). The stability of n across days, despite wider variability of CBF and CMRO2 responses, suggests that the reproducibility of blood flow changes is limited by variation in the oxidative metabolic demand. We conclude that the calibrated BOLD approach provides a highly reproducible measurement of n that can serve as a useful quantitative probe of the coupling of blood flow and energy metabolism in the brain. PMID:17208013

  6. Reproducibility of BOLD, perfusion, and CMRO2 measurements with calibrated-BOLD fMRI.

    PubMed

    Leontiev, Oleg; Buxton, Richard B

    2007-03-01

    The coupling of changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation can be characterized by an empirical index, n, defined as the ratio between fractional CBF change and fractional CMRO(2) change. The combination of blood oxygenation level dependent (BOLD) imaging with CBF measurements from arterial spin labeling (ASL) provides a potentially powerful experimental approach for measuring n, but the reproducibility of the technique previously has not been assessed. In this study, inter-subject variance and intra-subject reproducibility of the method were determined. Block design %BOLD and %CBF responses to visual stimulation and mild hypercapnia (5% CO(2)) were measured, and these data were used to compute the BOLD scaling factor M, %CMRO(2) change with activation, and the coupling index n. Reproducibility was determined for three approaches to defining regions-of-interest (ROIs): 1) Visual area V1 determined from prior retinotopic maps, 2) BOLD-activated voxels from a separate functional localizer, and 3) CBF-activated voxels from a separate functional localizer. For estimates of %BOLD, %CMRO(2) and n, intra-subject reproducibility was found to be best for regions selected according to CBF activation. Among all fMRI measurements, estimates of n were the most robust and were substantially more stable within individual subjects (coefficient of variation, CV=7.4%) than across the subject pool (CV=36.9%). The stability of n across days, despite wider variability of CBF and CMRO(2) responses, suggests that the reproducibility of blood flow changes is limited by variation in the oxidative metabolic demand. We conclude that the calibrated BOLD approach provides a highly reproducible measurement of n that can serve as a useful quantitative probe of the coupling of blood flow and energy metabolism in the brain.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25449746

  8. On the Stability of BOLD fMRI Correlations.

    PubMed

    Laumann, Timothy O; Snyder, Abraham Z; Mitra, Anish; Gordon, Evan M; Gratton, Caterina; Adeyemo, Babatunde; Gilmore, Adrian W; Nelson, Steven M; Berg, Jeff J; Greene, Deanna J; McCarthy, John E; Tagliazucchi, Enzo; Laufs, Helmut; Schlaggar, Bradley L; Dosenbach, Nico U F; Petersen, Steven E

    2016-09-02

    Measurement of correlations between brain regions (functional connectivity) using blood oxygen level dependent (BOLD) fMRI has proven to be a powerful tool for studying the functional organization of the brain. Recently, dynamic functional connectivity has emerged as a major topic in the resting-state BOLD fMRI literature. Here, using simulations and multiple sets of empirical observations, we confirm that imposed task states can alter the correlation structure of BOLD activity. However, we find that observations of "dynamic" BOLD correlations during the resting state are largely explained by sampling variability. Beyond sampling variability, the largest part of observed "dynamics" during rest is attributable to head motion. An additional component of dynamic variability during rest is attributable to fluctuating sleep state. Thus, aside from the preceding explanatory factors, a single correlation structure-as opposed to a sequence of distinct correlation structures-may adequately describe the resting state as measured by BOLD fMRI. These results suggest that resting-state BOLD correlations do not primarily reflect moment-to-moment changes in cognitive content. Rather, resting-state BOLD correlations may predominantly reflect processes concerned with the maintenance of the long-term stability of the brain's functional organization.

  9. 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

  10. FMRI, antipsychotics and schizophrenia. Influence of different antipsychotics on BOLD-signal.

    PubMed

    Röder, Christian H; Hoogendam, Janna Marie; van der Veen, Frederik M

    2010-01-01

    In the last decade, functional Magnetic Resonance Imaging (FMRI) has been increasingly used to investigate the neurobiology of schizophrenia. This technique relies on changes in the blood-oxygen-level-dependent (BOLD) - signal, which changes in response to neural activity. Many FMRI studies on schizophrenia have examined medicated patients, but little is known about the effects of antipsychotic medication on the BOLD-signal. In this review we investigated to what extent studies in patients with schizophrenia (SC), who were treated with different antipsychotics, could give insight in the effects of antipsychotics on the BOLD-signal. A PubMed search was performed using the search items "schizophrenia", "FMRI", "antipsychotics" and "schizophrenia", "BOLD", "antipsychotics". Only articles in which there were at least two groups of patients with different treatments or in which patients were scanned twice with different treatments were selected. 18 articles, published between 1999 and 2009, fulfilled these criteria. Paradigms and results of these studies were compared regarding differences induced by the administered antipsychotics. This analysis showed no general effect of antipsychotics on the BOLD-signal. However, there is some evidence that the extent of blockade of the dopamine (DA) D(2) receptor does influence the BOLD-signal. Higher affinity to the dopamine D2 receptor, as expressed by a higher/lower inhibition constant (Ki) seems to cause a decrease in BOLD-signal.

  11. Differential Localization of Pain-Related and Pain-Unrelated Neural Responses for Acupuncture at BL60 Using BOLD fMRI

    PubMed Central

    Jahng, Geon-Ho; Ryu, Chang-Woo; Ko, Chang-Nam; Park, Jung-Mi

    2013-01-01

    The objective of this study was to differentiate between pain-related and pain-unrelated neural responses of acupuncture at BL60 to investigate the specific effects of acupuncture. A total of 19 healthy volunteers were evaluated. fMRI was performed with sham or verum acupuncture stimulation at the left BL60 before and after local anesthesia. To investigate the relative BOLD signal effect for each session, a one-sample t-test was performed for individual contrast maps, and a paired t-test to investigate the differences between the pre- and post-anesthetic signal effects. Regarding verum acupuncture, areas that were more activated before local anesthesia included the superior, middle, and medial frontal gyri, inferior parietal lobule, superior temporal gyrus, thalamus, middle temporal gyrus, cingulate gyrus, culmen, and cerebellar tonsil. The postcentral gyrus was more deactivated before local anesthesia. After local anesthesia, the middle occipital gyrus, inferior temporal gyrus, postcentral gyrus, precuneus, superior parietal lobule, and declive were deactivated. Pre-anesthetic verum acupuncture at BL60 activated areas of vision and pain transmission. Post-anesthetic verum acupuncture deactivated brain areas of visual function, which is considered to be a pain-unrelated acupuncture response. It indicates that specific effects of acupoint BL60 are to control vision sense as used in the clinical setting. PMID:23853664

  12. Laser-evoked potential P2 single-trial amplitudes covary with the fMRI BOLD response in the medial pain system and interconnected subcortical structures.

    PubMed

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

    2009-04-15

    Pain is a complex experience with sensory, emotional and cognitive aspects. The cortical representation of pain - the pain matrix - consists of a network of regions including the primary (S1) and secondary (S2) sensory cortex, insula, and anterior cingulate cortex (ACC). These structures interact with brain regions such as the prefrontal cortex and the amygdalae. Simultaneous EEG/fMRI (electroencephalography/functional magnetic resonance imaging) has recently been introduced as a method to study the spatiotemporal characteristics of cognitive processes with high spatial and high temporal resolution at the same time. The present study was conducted to clarify if single trial EEG-informed BOLD modeling supports the definition of functional compartments within the pain matrix and interconnected regions. Twenty healthy subjects received painful laser stimulation while EEG and the fMRI blood oxygen level dependent (BOLD) signal were recorded simultaneously. While the laser-evoked N2 potential provided no additional information for BOLD modeling, the regressor obtained from the single trial laser-evoked P2 potential explained additional variance in a network of cortical and subcortical structures that largely overlapped with the pain matrix. This modeling strategy yielded pronounced activation in the ACC, right amygdala and thalamus. Our results suggest that laser-evoked potential (LEP) informed fMRI can be used to visualize BOLD activation in the pain matrix with an emphasis on functional compartments (as defined by the temporal dynamics of the LEP) such as the medial pain system. Furthermore, our findings suggest a concerted effort of the ACC and the amygdala in the cognitive-emotional evaluation of pain.

  13. Matched-filter acquisition for BOLD fMRI.

    PubMed

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

    2014-10-15

    We introduce matched-filter fMRI, which improves BOLD (blood oxygen level dependent) sensitivity by variable-density image acquisition tailored to subsequent image smoothing. Image smoothing is an established post-processing technique used in the vast majority of fMRI studies. Here we show that the signal-to-noise ratio of the resulting smoothed data can be substantially increased by acquisition weighting with a weighting function that matches the k-space filter imposed by the smoothing operation. We derive the theoretical SNR advantage of this strategy and propose a practical implementation of 2D echo-planar acquisition matched to common Gaussian smoothing. To reliably perform the involved variable-speed trajectories, concurrent magnetic field monitoring with NMR probes is used. Using this technique, phantom and in vivo measurements confirm reliable SNR improvement in the order of 30% in a "resting-state" condition and prove robust in different regimes of physiological noise. Furthermore, a preliminary task-based visual fMRI experiment equally suggests a consistent BOLD sensitivity increase in terms of statistical sensitivity (average t-value increase of about 35%). In summary, our study suggests that matched-filter acquisition is an effective means of improving BOLD SNR in studies that rely on image smoothing at the post-processing level. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. IRON fMRI measurements of CBV and implications for BOLD signal

    PubMed Central

    Mandeville, Joseph B.

    2014-01-01

    Changes in cerebral blood volume (CBV) and blood magnetization each induce changes in the transverse relaxation rate of MRI signal that are associated with changes in cerebral activity. BOLD signal, the preeminent method for non-invasive localization of task-induced brain function in human subjects, reflects of combination of changes in CBV and blood magnetization. Intravenous injection of paramagnetic contrast media, usually iron oxide particles surrounded by larger macromolecules, can overwhelm the BOLD response and sensitize signal to blood plasma volume, a method we have deemed “IRON” fMRI. The practical advantage of this technique is the ability to optimize blood magnetization at any echo time, enabling high detection power and the use of short echo times; for these reasons, IRON fMRI has become a valuable imaging tool in animals models. The temporal response of blood plasma volume is quite different from blood flow and BOLD signal; thus, CBV has been identified as a prominent source of transient features of the BOLD response. This article reviews the methodological advantages of the IRON method and how CBV measurements have informed our understanding of the BOLD response. PMID:22281669

  15. Linear and nonlinear relationships between visual stimuli, EEG and BOLD fMRI signals.

    PubMed

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

    2010-04-15

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

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

    PubMed Central

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

    2010-01-01

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

  17. Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal.

    PubMed

    Hammett, Stephen T; Wall, Matthew B; Edwards, Thomas C; Smith, Andrew T

    2010-08-02

    Creatine monohydrate is an organic acid that plays a key role in ATP re-synthesis. Creatine levels in the human brain vary considerably and dietary supplementation has been found to enhance cognitive performance in healthy individuals. To explore the possibility that the fMRI Blood Oxygen Level Dependent (BOLD) response is influenced by creatine levels, BOLD responses to visual stimuli were measured in visual cortex before and after a week of creatine administration in healthy human volunteers. The magnitude of the BOLD response decreased by 16% following creatine supplementation of a similar dose to that previously shown to increase cerebral levels of phosphocreatine. We also confirmed that cognitive performance (memory span) is increased. These changes were not found in a placebo group. Possible mechanisms of BOLD change are considered. The results offer potential for insight into the coupling between neural activity and the BOLD response and the more immediate possibility of accounting for an important source of variability during fMRI analysis in clinical studies and other investigations where between-subjects variance is an issue.

  18. How Predictable are “Spontaneous Decisions” and “Hidden Intentions”? Comparing Classification Results Based on Previous Responses with Multivariate Pattern Analysis of fMRI BOLD Signals

    PubMed Central

    Lages, Martin; Jaworska, Katarzyna

    2012-01-01

    In two replication studies we examined response bias and dependencies in voluntary decisions. We trained a linear classifier to predict “spontaneous decisions” and in the second study “hidden intentions” from responses in preceding trials and achieved comparable prediction accuracies as reported for multivariate pattern classification based on voxel activities in frontopolar cortex. We discuss implications of our findings and suggest ways to improve classification analyses of fMRI BOLD signals that may help to reduce effects of response dependencies between trials. PMID:22408630

  19. 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

  20. Negative covariation between task-related responses in alpha/beta-band activity and BOLD in human sensorimotor cortex: an EEG and fMRI study of motor imagery and movements.

    PubMed

    Yuan, Han; Liu, Tao; Szarkowski, Rebecca; Rios, Cristina; Ashe, James; He, Bin

    2010-02-01

    Similar to the occipital alpha rhythm, electroencephalographic (EEG) signals in the alpha- and beta-frequency bands can be suppressed by movement or motor imagery and have thus been thought to represent the "idling state" of the sensorimotor cortex. A negative correlation between spontaneous alpha EEG and blood-oxygen-level-dependent (BOLD) signals has been reported in combined EEG and fMRI (functional Magnetic Resonance Imaging) experiments when subjects stayed at the resting state or alternated between the resting state and a task. However, the precise nature of the task-induced alpha modulation remains elusive. It was not clear whether alpha/beta rhythm suppressions may co-vary with BOLD when conducting tasks involving varying activations of the cortex. Here, we quantified the task-evoked responses of BOLD and alpha/beta-band power of EEG directly in the cortical source domain, by using source imaging technology, and examined their covariation across task conditions in a mixed block and event-related design. In this study, 13 subjects performed tasks of right-hand, right-foot or left-hand movement and motor imagery when EEG and fMRI data were separately collected. Task-induced increase of BOLD signal and decrease of EEG amplitudes in alpha and beta bands were shown to be co-localized at the somatotopic sensorimotor cortex. At the corresponding regions, the reciprocal changes of the two signals co-varied in the magnitudes across imagination and movement conditions. The spatial correspondence and negative covariation between the two measurements were further shown to exist at somatotopic brain regions associated with different body parts. These results suggest an inverse functional coupling relationship between task-induced changes of BOLD and low-frequency EEG signals.

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

    PubMed

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

    2013-02-01

    Linking regional metabolic changes with fluctuations in the local electromagnetic fields directly on the surface of the human cerebral cortex is of tremendous importance for a better understanding of detailed brain processes. Functional magnetic resonance imaging (fMRI) and intra-cranial electro-encephalography (iEEG) measure two technically unrelated but spatially and temporally complementary sets of functional descriptions of human brain activity. In order to allow fine-grained spatio-temporal human brain mapping at the population-level, an effective comparative framework for the cortex-based inter-subject analysis of iEEG and fMRI data sets is needed. We combined fMRI and iEEG recordings of the same patients with epilepsy during alternated intervals of passive movie viewing and music listening to explore the degree of local spatial correspondence and temporal coupling between blood oxygen level dependent (BOLD) fMRI changes and iEEG spectral power modulations across the cortical surface after cortex-based inter-subject alignment. To this purpose, we applied a simple model of the iEEG activity spread around each electrode location and the cortex-based inter-subject alignment procedure to transform discrete iEEG measurements into cortically distributed group patterns by establishing a fine anatomic correspondence of many iEEG cortical sites across multiple subjects. Our results demonstrate the feasibility of a multi-modal inter-subject cortex-based distributed analysis for combining iEEG and fMRI data sets acquired from multiple subjects with the same experimental paradigm but with different iEEG electrode coverage. The proposed iEEG-fMRI framework allows for improved group statistics in a common anatomical space and preserves the dynamic link between the temporal features of the two modalities. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Experimental design and the relative sensitivity of BOLD and perfusion fMRI.

    PubMed

    Aguirre, G K; Detre, J A; Zarahn, E; Alsop, D C

    2002-03-01

    This paper compares the statistical power of BOLD and arterial spin labeling perfusion fMRI for a variety of experimental designs within and across subjects. Based on theory and simulations, we predict that perfusion data are composed of independent observations in time under the null hypothesis, in contrast to BOLD data, which possess marked autocorrelation. We also present a method (sinc subtraction) of generating perfusion data from its raw source signal that minimizes the presence of oxygen-sensitive signal changes and can be used with any experimental design. Empirically, we demonstrate the absence of autocorrelation in perfusion noise, examine the shape of the hemodynamic response function for BOLD and perfusion, and obtain a measure of signal to noise for each method. This information is then used to generate a model of relative sensitivity of the BOLD and perfusion methods for within-subject experimental designs of varying temporal frequency. It is determined that perfusion fMRI provides superior sensitivity for within-subject experimental designs that concentrate their power at or below approximately 0.009 Hz (corresponding to a "blocked" experimental design of 60-s epochs). Additionally, evidence is presented that across-subject hypothesis tests may be more sensitive when conducted using perfusion imaging, despite the better within-subject signal to noise obtained in some cases with BOLD. ©2002 Elsevier Science (USA).

  3. Boosting BOLD fMRI by K-Space Density Weighted Echo Planar Imaging

    PubMed Central

    Zeller, Mario; Müller, Alexander; Gutberlet, Marcel; Nichols, Thomas; Hahn, Dietbert; Köstler, Herbert; Bartsch, Andreas J.

    2013-01-01

    Functional magnetic resonance imaging (fMRI) has become a powerful and influential method to non-invasively study neuronal brain activity. For this purpose, the blood oxygenation level-dependent (BOLD) effect is most widely used. T2* weighted echo planar imaging (EPI) is BOLD sensitive and the prevailing fMRI acquisition technique. Here, we present an alternative to its standard Cartesian recordings, i.e. k-space density weighted EPI, which is expected to increase the signal-to-noise ratio in fMRI data. Based on in vitro and in vivo pilot measurements, we show that fMRI by k-space density weighted EPI is feasible and that this new acquisition technique in fact boosted spatial and temporal SNR as well as the detection of local fMRI activations. Spatial resolution, spatial response function and echo time were identical for density weighted and conventional Cartesian EPI. The signal-to-noise ratio gain of density weighting can improve activation detection and has the potential to further increase the sensitivity of fMRI investigations. PMID:24040262

  4. Changes in fMRI BOLD dynamics reflect anticipation to moving objects.

    PubMed

    Schellekens, W; Ramsey, N F; van Wezel, R J A; Raemaekers, M

    2016-09-09

    The human brain is thought to respond differently to novel versus predictable neural input. In human visual cortex, neural response amplitude to visual input might be determined by the degree of predictability. We investigated how fMRI BOLD responses in human early visual cortex reflect the anticipation of a single moving bar's trajectory. We found that BOLD signals decreased linearly from onset to offset of the stimulus trajectory. Moreover, decreased amplitudes of BOLD responses coincided with an increased initial dip as the stimulus moved along its trajectory. Importantly, motion anticipation effects were absent, when motion coherence was disrupted by means of stimulus contrast reversals. These results show that human early visual cortex anticipates the trajectory of a coherently moving object at the initial stages of visual motion processing. The results can be explained by suppression of predictable input, plausibly underlying the formation of stable visual percepts.

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

    PubMed Central

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

    2013-01-01

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

  6. Line scanning fMRI reveals earlier onset of optogenetically evoked BOLD response in rat somatosensory cortex as compared to sensory stimulation.

    PubMed

    Albers, Franziska; Schmid, Florian; Wachsmuth, Lydia; Faber, Cornelius

    2016-12-21

    The combination of optogenetic control and fMRI readout in the brain is increasingly used to assess neuronal networks and underlying signal processing. However, how exactly optogenetic activation or inhibition reproduces normal physiological input has not been fully unraveled. To assess details of temporal dynamics of the hemodynamic response, temporal resolution in rodent fMRI is often not sufficient. Recent advances in human fMRI using faster acquisition schemes cannot be easily translated to small animals due to smaller dimensions, fast physiological motion, and higher sensitivity to artefacts. Here, we applied a one dimensional line scanning acquisition with 50ms temporal resolution in rat somatosensory cortex. We observed that optogenetic activation reproduces the hemodynamic response upon sensory stimulation, but shows a 160 to 340ms earlier onset of the response. This difference is explained by direct activation of all opsin-expressing and illuminated cortical layers, while hemodynamic response to sensory stimulation is delayed during intracortical transmission between cortical layers. Our results confirm that optogenetic activation is a valid model for physiological neuronal input, and that differences in temporal behavior of only a few hundred milliseconds can be resolved in rodent fMRI.

  7. Differentiating BOLD and non-BOLD signals in fMRI time series using multi-echo EPI.

    PubMed

    Kundu, Prantik; Inati, Souheil J; Evans, Jennifer W; Luh, Wen-Ming; Bandettini, Peter A

    2012-04-15

    A central challenge in the fMRI based study of functional connectivity is distinguishing neuronally related signal fluctuations from the effects of motion, physiology, and other nuisance sources. Conventional techniques for removing nuisance effects include modeling of noise time courses based on external measurements followed by temporal filtering. These techniques have limited effectiveness. Previous studies have shown using multi-echo fMRI that neuronally related fluctuations are Blood Oxygen Level Dependent (BOLD) signals that can be characterized in terms of changes in R(2)* and initial signal intensity (S(0)) based on the analysis of echo-time (TE) dependence. We hypothesized that if TE-dependence could be used to differentiate BOLD and non-BOLD signals, non-BOLD signal could be removed to denoise data without conventional noise modeling. To test this hypothesis, whole brain multi-echo data were acquired at 3 TEs and decomposed with Independent Components Analysis (ICA) after spatially concatenating data across space and TE. Components were analyzed for the degree to which their signal changes fit models for R(2)* and S(0) change, and summary scores were developed to characterize each component as BOLD-like or not BOLD-like. These scores clearly differentiated BOLD-like "functional network" components from non BOLD-like components related to motion, pulsatility, and other nuisance effects. Using non BOLD-like component time courses as noise regressors dramatically improved seed-based correlation mapping by reducing the effects of high and low frequency non-BOLD fluctuations. A comparison with seed-based correlation mapping using conventional noise regressors demonstrated the superiority of the proposed technique for both individual and group level seed-based connectivity analysis, especially in mapping subcortical-cortical connectivity. The differentiation of BOLD and non-BOLD components based on TE-dependence was highly robust, which allowed for the

  8. BOLD fMRI of visual and somatosensory–motor stimulations in baboons

    PubMed Central

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

    2010-01-01

    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 × 1.5 × 4 mm resolution) on a clinical 3 T-MRI scanner. BOLD fMRI responses to hypercapnic (5% CO2) 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. PMID:20471483

  9. Caffeine induced uncoupling of cerebral blood flow and oxygen metabolism: A calibrated-BOLD fMRI study

    PubMed Central

    Perthen, Joanna E; Lansing, Amy E; Liau, Joy; Liu, Thomas T; Buxton, Richard B

    2009-01-01

    Although functional MRI (fMRI) based on blood oxygenation-level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia calibrated-BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2). In this study, we implemented a quantitative R2* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated-BOLD method, to examine the CBF and CMRO2 responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200mg caffeine dose. A dual echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, ±11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, ±2.9) and CMRO2 (+20.7%, ±1.4), and caffeine decreased CBF (-34.5%, ±2.6) with a non-significant change in CMRO2 (+5.2%, ±6.4). The coupling between CBF and CMRO2 was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated-BOLD methodology using R2* is a promising approach for evaluating CBF and CMRO2 changes in response to pharmacological interventions. PMID:18191583

  10. Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI study.

    PubMed

    Perthen, Joanna E; Lansing, Amy E; Liau, Joy; Liu, Thomas T; Buxton, Richard B

    2008-03-01

    Although functional MRI (fMRI) based on blood oxygenation level-dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia-calibrated BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). In this study, we implemented a quantitative R(2)* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated BOLD method, to examine the CBF and CMRO(2) responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200-mg caffeine dose. A dual-echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, +/-11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, +/-2.9) and CMRO(2) (+20.7%, +/-1.4), and caffeine decreased CBF (-34.5%, +/-2.6) with a non-significant change in CMRO(2) (+5.2%, +/-6.4). The coupling between CBF and CMRO(2) was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated BOLD methodology using R(2) * is a promising approach for evaluating CBF and CMRO(2) changes in response to pharmacological interventions.

  11. Resting State Brain Function Analysis Using Concurrent BOLD in ASL Perfusion fMRI

    PubMed Central

    Zhu, Senhua; Fang, Zhuo; Hu, Siyuan; Wang, Ze; Rao, Hengyi

    2013-01-01

    The past decade has seen astounding discoveries about resting-state brain activity patterns in normal brain as well as their alterations in brain diseases. While the vast majority of resting-state studies are based on the blood-oxygen-level-dependent (BOLD) functional MRI (fMRI), arterial spin labeling (ASL) perfusion fMRI can simultaneously capture BOLD and cerebral blood flow (CBF) signals, providing a unique opportunity for assessing resting brain functions with concurrent BOLD (ccBOLD) and CBF signals. Before taking that benefit, it is necessary to validate the utility of ccBOLD signal for resting-state analysis using conventional BOLD (cvBOLD) signal acquired without ASL modulations. To address this technical issue, resting cvBOLD and ASL perfusion MRI were acquired from a large cohort (n = 89) of healthy subjects. Four widely used resting-state brain function analyses were conducted and compared between the two types of BOLD signal, including the posterior cingulate cortex (PCC) seed-based functional connectivity (FC) analysis, independent component analysis (ICA), analysis of amplitude of low frequency fluctuation (ALFF), and analysis of regional homogeneity (ReHo). Consistent default mode network (DMN) as well as other resting-state networks (RSNs) were observed from cvBOLD and ccBOLD using PCC-FC analysis and ICA. ALFF from both modalities were the same for most of brain regions but were different in peripheral regions suffering from the susceptibility gradients induced signal drop. ReHo showed difference in many brain regions, likely reflecting the SNR and resolution differences between the two BOLD modalities. The DMN and auditory networks showed highest CBF values among all RSNs. These results demonstrated the feasibility of ASL perfusion MRI for assessing resting brain functions using its concurrent BOLD in addition to CBF signal, which provides a potentially useful way to maximize the utility of ASL perfusion MRI. PMID:23750275

  12. Decreased BOLD responses in audiovisual processing.

    PubMed

    Wiersinga-Post, Esther; Tomaskovic, Sonja; Slabu, Lavinia; Renken, Remco; de Smit, Femke; Duifhuis, Hendrikus

    2010-12-29

    Audiovisual processing was studied in a functional magnetic resonance imaging study using the McGurk effect. Perceptual responses and the brain activity patterns were measured as a function of audiovisual delay. In several cortical and subcortical brain areas, BOLD responses correlated negatively with the perception of the McGurk effect. No brain areas with positively correlated BOLD responses were found. This was unexpected as most studies of audiovisual integration use additivity and super additivity - that is, increased BOLD responses after audiovisual stimulation compared with auditory-only and visual-only stimulation - as criteria for audiovisual integration. We argue that brain areas that show decreased BOLD responses that correlate with an integrated audiovisual percept should not be neglected from consideration as possibly involved in audiovisual integration.

  13. BOLD fMRI and Somatosensory Evoked Potentials Are Well Correlated Over a Broad Range of Frequency Content of Somatosensory Stimulation of the Rat Forepaw

    PubMed Central

    Goloshevsky, Artem G.; Silva, Afonso C.; Dodd, Stephen J.; Koretsky, Alan P.

    2008-01-01

    Electrical stimulation of the rat paw is commonly used to study the hemodynamic, metabolic, and neuronal mechanisms of functional MRI (fMRI) responses in somatosensory cortex. Several groups have reported good correlation between the Blood Oxygenation Level Dependent (BOLD) fMRI signal and somatosensory evoked potentials (SEPs) using short, typically 300 μs, square stimulation pulses. The spectral power of these short pulses is evenly distributed over a wide range of frequencies and thus the effects of the frequency content of the stimulation pulse on fMRI responses have not been previously described. Here, the effects that different stimulation pulse waveforms with a range of frequency content have on neuronal activity, as measured by SEPs, and on the amplitude of the BOLD fMRI signal in rat somatosensory cortex are investigated. The peak-to-peak SEP amplitudes increased as the power in the high frequency harmonics of the different pulse waveforms increased, using either triangular or sinusoidal stimuli waveforms from 9 Hz to 180 Hz. Similarly, BOLD fMRI response increased with increased high frequency content of the stimulation pulse. There was a linear correlation between SEPs and BOLD fMRI over the full range of frequency content in the stimulations. PMID:18206862

  14. 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

  15. Two pitfalls of BOLD fMRI magnitude-based neuroimage analysis: non-negativity and edge effect.

    PubMed

    Chen, Zikuan; Calhoun, Vince D

    2011-08-15

    BOLD fMRI is accepted as a noninvasive imaging modality for neuroimaging and brain mapping. A BOLD fMRI dataset consists of magnitude and phase components. Currently, only the magnitude is used for neuroimage analysis. In this paper, we show that the fMRI-magnitude-based neuroimage analysis may suffer two pitfalls: one is that the magnitude is non-negative and cannot differentiate positive from negative BOLD activity; the other is an edge effect that may manifest as an edge enhancement or a spatial interior dip artifact at a local uniform BOLD region. We demonstrate these pitfalls via numeric simulations using a BOLD fMRI model and also via a phantom experiment. We also propose a solution by making use of the fMRI phase image, the counterpart of the fMRI magnitude.

  16. Different neural responses to stranger and personally familiar faces in shy and bold adults.

    PubMed

    Beaton, Elliott A; Schmidt, Louis A; Schulkin, Jay; Antony, Martin M; Swinson, Richard P; Hall, Geoffrey B

    2008-06-01

    The shy-bold continuum is a fundamental behavioral trait conserved across human and nonhuman animals. Individual differences along the shy-bold continuum are presumed to arise from, and are maintained by, differences in the excitability of forebrain limbic areas involved in the evaluation of stimulus saliency. To test this hypothesis, the authors conducted an event-related functional MRI (fMRI) study in which brain scans were acquired on shy and bold adults during the presentation of neutral stranger and personally familiar faces. Shy adults exhibited greater bilateral amygdala activation during the presentation of stranger faces and greater left amygdala activation during personally familiar faces than their bold counterparts. Bold adults exhibited greater bilateral nucleus accumbens activation in response to stranger and personally familiar faces than shy adults. Findings suggest that there are distinct neural substrates underlying and maintaining individual differences along a shy-bold continuum in humans. (Copyright) 2008 APA, all rights reserved.

  17. Multi-echo fMRI: A review of applications in fMRI denoising and analysis of BOLD signals.

    PubMed

    Kundu, Prantik; Voon, Valerie; Balchandani, Priti; Lombardo, Michael V; Poser, Benedikt A; Bandettini, Peter A

    2017-07-01

    In recent years the field of fMRI research has enjoyed expanded technical abilities related to resolution, as well as use across many fields of brain research. At the same time, the field has also dealt with uncertainty related to many known and unknown effects of artifact in fMRI data. In this review we discuss an emerging fMRI technology, called multi-echo (ME)-fMRI, which focuses on improving the fidelity and interpretability of fMRI. Where the essential problem of standard single-echo fMRI is the indeterminacy of sources of signals, whether BOLD or artifact, this is not the case for ME-fMRI. By acquiring multiple echo images per slice, the ME approach allows T2* decay to be modeled at every voxel at every time point. Since BOLD signals arise by changes in T2* over time, an fMRI experiment sampling the T2* signal decay can be analyzed to distinguish BOLD from artifact signal constituents. While the ME approach has a long history of use in theoretical and validation studies, modern MRI systems enable whole-brain multi-echo fMRI at high resolution. This review covers recent multi-echo fMRI acquisition methods, and the analysis steps for this data to make fMRI at once more principled, straightforward, and powerful. After a brief overview of history and theory, T2* modeling and applications will be discussed. These applications include T2* mapping and combining echoes from ME data to increase BOLD contrast and mitigate dropout artifacts. Next, the modeling of fMRI signal changes to detect signal origins in BOLD-related T2* versus artifact-related S0 changes will be reviewed. A focus is on the use of ME-fMRI data to extract and classify components from spatial ICA, called multi-echo ICA (ME-ICA). After describing how ME-fMRI and ME-ICA lead to a general model for analysis of fMRI signals, applications in animal and human imaging will be discussed. Applications include removing motion artifacts in resting state data at subject and group level. New imaging methods such

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

    PubMed

    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.

  19. 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

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  2. Task-evoked BOLD responses are normal in areas of diaschisis after stroke.

    PubMed

    Fair, Damien A; Snyder, Abraham Z; Connor, Lisa Tabor; Nardos, Binyam; Corbetta, Maurizio

    2009-01-01

    Cerebral infarction can cause diaschisis, a reduction of blood flow and metabolism in areas of the cortex distant from the site of the lesion. Although the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal is increasingly used to examine the neural correlates of recovery in stroke, its reliability in areas of diaschisis is uncertain. The effect of chronic diaschisis as measured by resting positron emission tomography on task-evoked BOLD responses during word-stem completion in a block design fMRI study was examined in 3 patients, 6 months after a single left hemisphere stroke involving the inferior frontal gyrus and operculum. The BOLD responses were minimally affected in areas of chronic diaschisis. Within the confines of this study, the mechanism underlying the BOLD signal, which includes a mismatch between neuronally driven increases in blood flow and a corresponding increase in oxygen use, appears to be intact in areas of chronic diaschisis.

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

    PubMed Central

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

    2011-01-01

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

  4. 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

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

    NASA Astrophysics Data System (ADS)

    Alonso, Benito De Celis

    2012-10-01

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

  6. BOLD fMRI in Infants under Sedation: Comparing the Impact of Pentobarbital and Propofol on Auditory and Language Activation

    PubMed Central

    DiFrancesco, Mark W.; Robertson, Sara A.; Karunanayaka, Prasanna; Holland, Scott K.

    2013-01-01

    Purpose To elucidate differences in the disruption of language network function, as measured by BOLD fMRI, attributable to two common sedative agents administered to infants under clinical imaging protocols. Materials and Methods The sedatives pentobarbital (Nembutal) and Propofol, administered clinically to infants at one year of age, were compared with respect to BOLD activation profiles in response to passive story-listening stimulation. An intermittent event-related imaging protocol was utilized with which the temporal evolution of language processing resulting from this stimulation was explored. Results Propofol and Nembutal were found to have distinct and complementary responses to story-listening. Propofol exhibited more activation in higher processing networks with increasing response toward the end of narrative stimulus. Nembutal, in contrast, had much more robust activation of primary and secondary sensory cortices but a decreasing response over time in fronto-parietal default-mode regions. This may suggest a breakdown of top-down feedback for Propofol vs. the lack of bottom-up feed-forward processing for Nembutal. Conclusion Two popular sedative agents for use in children for clinical fMRI were found to induce distinct alteration of activation patterns from a language stimulus. This has ramifications for clinical fMRI of sedated infants and encourages further study to build a framework for more confident interpretation. PMID:23526799

  7. A model of neurovascular coupling and the BOLD response PART II.

    PubMed

    Mathias, E J; Plank, M J; David, T

    2017-04-01

    A mathematical model is developed which describes a signalling mechanism of neurovascular coupling with a model of a pyramidal neuron and its corresponding fMRI BOLD response. In the first part of two papers (Part I) we described the integration of the neurovascular coupling unit extended to include a complex neuron model, which includes the important Na/K ATPase pump, with a model that provides a BOLD signal taking its input from the cerebral blood flow and the metabolic rate of oxygen consumption. We showed that this produced a viable signal in terms of initial dip, positive and negative BOLD signals. In this paper (PART II) our model predicts the variations of the BOLD response due to variations in neuronal activity and indicates that the BOLD signal could be used as an initial biomarker for neuronal dysfunction or variations in the perfusion of blood to the cerebral tissue. We have compared the simulated hypoxic BOLD response to experimental BOLD signals observed in the hippocampus during hypoxia showing good agreement. This approach of combined quantitative modelling of neurovascular coupling response and its BOLD response will enable more specific assessment of a brain region.

  8. 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.

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

    PubMed

    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.

  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. Anesthetic Effects on Regional CBF, BOLD, and the Coupling Between Task-Induced Changes in CBF and BOLD: An fMRI Study in Normal Human Subjects

    PubMed Central

    Qiu, Maolin; Ramani, Ramachandran; Swetye, Michael; Rajeevan, Nallakkandi; Constable, R. Todd

    2009-01-01

    Functional MR imaging was performed in sixteen healthy human subjects measuring both regional cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) signal when visual and auditory stimuli were presented to subjects in the presence or absence of anesthesia. During anesthesia, 0.25 mean alveolar concentration (MAC) sevoflurane was administrated. We found that low-dose sevoflurane decreased the task-induced changes in both BOLD and CBF. Within the visual and auditory regions of interest inspected, both baseline CBF and the task-induced changes in CBF decreased significantly during anesthesia. Low-dose sevoflurane significantly altered the task-induced CBF-BOLD coupling; for a unit change of CBF, a larger change in BOLD was observed in the anesthesia condition than in the anesthesia-free condition. Low-dose sevoflurane was also found to have significant impact on the spatial nonuniformity of the task-induced coupling. The alteration of task-induced CBF-BOLD coupling by low-dose sevoflurane introduces ambiguity to the direct interpretation of functional MRI (fMRI) data based on only one of the indirect measures—CBF or BOLD. Our observations also indicate that the manipulation of the brain with an anesthetic agent complicates the model-based quantitative interpretation of fMRI data, in which the relative task-induced changes in oxidative metabolism are calculated by means of a calibrated model given the relative changes in the indirect vascular measures, usually CBF and BOLD. PMID:18816821

  14. Arterial spin labeling versus BOLD in direct challenge and drug-task interaction pharmacological fMRI.

    PubMed

    Stewart, Stephanie B; Koller, Jonathan M; Campbell, Meghan C; Black, Kevin J

    2014-01-01

    A carefully controlled study allowed us to compare the sensitivity of ASL (arterial spin labeling) and BOLD (blood oxygen level dependent) fMRI for detecting the effects of the adenosine A2a antagonist tozadenant in Parkinson disease. The study compared the effect of drug directly or the interaction of the drug with a cognitive task. Only ASL detected the direct effect of tozadenant. BOLD was more sensitive to the cognitive task, which (unlike most drugs) allows on-off comparisons over short periods of time. Neither ASL nor BOLD could detect a cognitive-pharmacological interaction. These results are consistent with the known relative advantages of each fMRI method, and suggest that for drug development, directly imaging pharmacodynamic effects with ASL may have advantages over cognitive-pharmacological interaction BOLD, which has hitherto been the more common approach to pharmacological fMRI.

  15. Eyeblink classical conditioning and BOLD fMRI of anesthesia-induced changes in the developing brain.

    PubMed

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

    2016-12-01

    Millions of children undergo general anesthesia each year in the USA alone, and a growing body of literature from animals and humans suggests that exposure to anesthesia at an early age can impact neuronal development, leading to learning and memory impairments later in childhood. Although a number of studies have reported behavioral and structural effects of anesthesia exposure during infancy, the functional manifestation of these changes has not been previous examined. In this study we used BOLD fMRI to measure the functional response to stimulation in the whisker barrel cortex of awake rabbits before and after learning a trace eyeblink classical conditioning paradigm. The functional changes, in terms of activated volume and time course, in rabbits exposed to isoflurane anesthesia during infancy was compared to unanesthetized controls when both groups reached young adulthood. Our findings show that whereas both groups exhibited decreased BOLD response duration after learning, the anesthesia-exposed group also showed a decrease in BOLD response volume in the whisker barrel cortex, particularly in the deeper infragranular layer. These results suggest that anesthesia exposure during infancy may affect the intracortical processes that mediate learning-related plasticity.

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

    PubMed Central

    Ganesan, Karthik; Ursekar, Meher

    2014-01-01

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

  17. Resting state BOLD fMRI for pre-surgical planning

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. 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.

  20. The BOLD response and the gamma oscillations respond differently than evoked potentials: an interleaved EEG-fMRI study

    PubMed Central

    Foucher, Jack R; Otzenberger, Hélène; Gounot, Daniel

    2003-01-01

    Background The integration of EEG and fMRI is attractive because of their complementary precision regarding time and space. But the relationship between the indirect hemodynamic fMRI signal and the more direct EEG signal is uncertain. Event-related EEG responses can be analyzed in two different ways, reflecting two different kinds of brain activity: evoked, i.e. phase-locked to the stimulus, such as evoked potentials, or induced, i.e. non phase-locked to the stimulus such as event-related oscillations. In order to determine which kind of EEG activity was more closely related with fMRI, EEG and fMRI signals were acquired together, while subjects were presented with two kinds of rare events intermingled with frequent distractors. Target events had to be signaled by pressing a button and Novel events had to be ignored. Results Both Targets and Novels triggered a P300, of larger amplitude in the Novel condition. On the opposite, the fMRI BOLD response was stronger in the Target condition. EEG event-related oscillations in the gamma band (32–38 Hz) reacted in a way similar to the BOLD response. Conclusions The reasons for such opposite differential reactivity between oscillations / fMRI on the one hand, and evoked potentials on the other, are discussed in the paper. Those results provide further arguments for a closer relationship between fast oscillations and the BOLD signal, than between evoked potentials and the BOLD signal. PMID:14499000

  1. 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

  2. CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study.

    PubMed

    Kraus, Thomas; Kiess, Olga; Hösl, Katharina; Terekhin, Pavel; Kornhuber, Johannes; Forster, Clemens

    2013-09-01

    It has recently been shown that electrical stimulation of sensory afferents within the outer auditory canal may facilitate a transcutaneous form of central nervous system stimulation. Functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) effects in limbic and temporal structures have been detected in two independent studies. In the present study, we investigated BOLD fMRI effects in response to transcutaneous electrical stimulation of two different zones in the left outer auditory canal. It is hypothesized that different central nervous system (CNS) activation patterns might help to localize and specifically stimulate auricular cutaneous vagal afferents. 16 healthy subjects aged between 20 and 37 years were divided into two groups. 8 subjects were stimulated in the anterior wall, the other 8 persons received transcutaneous vagus nervous stimulation (tVNS) at the posterior side of their left outer auditory canal. For sham control, both groups were also stimulated in an alternating manner on their corresponding ear lobe, which is generally known to be free of cutaneous vagal innervation. Functional MR data from the cortex and brain stem level were collected and a group analysis was performed. In most cortical areas, BOLD changes were in the opposite direction when comparing anterior vs. posterior stimulation of the left auditory canal. The only exception was in the insular cortex, where both stimulation types evoked positive BOLD changes. Prominent decreases of the BOLD signals were detected in the parahippocampal gyrus, posterior cingulate cortex and right thalamus (pulvinar) following anterior stimulation. In subcortical areas at brain stem level, a stronger BOLD decrease as compared with sham stimulation was found in the locus coeruleus and the solitary tract only during stimulation of the anterior part of the auditory canal. The results of the study are in line with previous fMRI studies showing robust BOLD signal decreases in

  3. BOLD fMRI activation induced by vagus nerve stimulation in seizure patients

    PubMed Central

    Liu, W; Mosier, K; Kalnin, A; Marks, D

    2003-01-01

    Design: Blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI) was employed to detect areas of the brain activated by vagus nerve stimulation in five patients with documented complex partial seizures. Methods: Functional MRI was done on a GE 1.5T Echospeed horizon scanner. Before each patient entered the scanner, the vagal nerve stimulator was set to a specific ON–OFF paradigm so that the data could be analysed using a box-car type of design. The brains were scanned both anatomically and functionally. The functional images were corrected for head motion and co-registered to the anatomical images. Maps of the activated areas were generated and analysed using the brain mapping software, SPM99. The threshold for activation was chosen as p < 0.001. Results: All patients showed activation in the frontal and occipital lobes. However, activation in the thalamus was seen only in the two patients with improved seizure control. Conclusions: BOLD fMRI can detect activation associated with vagus nerve stimulation. There may be a relation between thalamic activation and a favourable clinical outcome. PMID:12754361

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

    PubMed Central

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

    2011-01-01

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

  5. 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

  6. 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

  7. 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.

  8. Dynamic spatiotemporal variability of alpha-BOLD relationships during the resting-state and task-evoked responses.

    PubMed

    Mayhew, S D; Bagshaw, A P

    2017-07-15

    Accurate characterization of the spatiotemporal relationship between two of the most prominent neuroimaging measures of neuronal activity, the 8-13Hz, occipito-parietal EEG alpha oscillation and the BOLD fMRI signal, must encompass the intrinsically dynamic nature of both alpha power and brain function. Here, during the eyes-open resting state, we use a 16s sliding-window analysis and demonstrate that the mean spatial network of dynamic alpha-BOLD correlations is highly comparable to the static network calculated over six minutes. However, alpha-BOLD correlations showed substantial spatiotemporal variability within-subjects and passed through many different configurations such that the static network was fully represented in only ~10% of 16s epochs, with visual and parietal regions (coherent on average) often opposingly correlated with each other or with alpha. We find that the common assumption of static-alpha BOLD correlations greatly oversimplifies temporal variation in brain network dynamics. Fluctuations in alpha-BOLD coupling significantly depended upon the instantaneous amplitude of alpha power, and primary and lateral visual areas were most strongly negatively correlated with alpha during different alpha power states, possibly suggesting the action of multiple alpha mechanisms. Dynamic alpha-BOLD correlations could not be explained by eye-blinks/movements, head motion or non-neuronal physiological variability. Individual's mean alpha power and frequency were found to contribute to between-subject variability in alpha-BOLD correlations. Additionally, application to a visual stimulation dataset showed that dynamic alpha-BOLD correlations provided functional information pertaining to the brain's response to stimulation by exhibiting spatiotemporal fluctuations related to variability in the trial-by-trial BOLD response magnitude. Significantly weaker visual alpha-BOLD correlations were found both preceding and following small amplitude BOLD response trials

  9. Cerebral Blood Flow and BOLD Responses to a Memory Encoding Task: A Comparison Between Healthy Young and Elderly Adults

    PubMed Central

    Restom, Khaled; Bangen, Katherine J.; Bondi, Mark W.; Perthen, Joanna E.; Liu, Thomas T.

    2007-01-01

    Functional magnetic resonance imaging (fMRI) studies of the medial temporal lobe have primarily made use of the blood oxygenation level dependent (BOLD) response to neural activity. The interpretation of the BOLD signal as a measure of medial temporal lobe function can be complicated, however, by changes in the cerebrovascular system that can occur with both normal aging and age-related diseases, such as Alzheimer's disease. Quantitative measures of the functional cerebral blood flow (CBF) response offer a useful complement to BOLD measures, and have been shown to aid in the interpretation of fMRI studies. Despite these potential advantages, the application of ASL to fMRI studies of cognitive tasks and at-risk populations has been limited. In this study, we demonstrate the application of ASL fMRI to obtain measures of the CBF and BOLD responses to the encoding of natural scenes in healthy young (mean 25 years) and elderly (mean 74 years) adults. The percent CBF increase in the medial temporal lobe was significantly higher in the older adults, whereas the CBF levels during baseline and task conditions and during a separate resting-state scan were significantly lower in the older group. The older adults also showed slightly higher values for the BOLD response amplitude and the absolute change in CBF, but the age group differences were not significant. The percent CBF and BOLD responses are consistent with an age-related increase in the cerebral metabolic rate of oxygen metabolism (CMRO2) response to memory encoding. PMID:17590353

  10. Caffeine reduces the initial dip in the visual BOLD response at 3 T.

    PubMed

    Behzadi, Yashar; Liu, Thomas T

    2006-08-01

    Localized changes in oxygen consumption related to increased neural activity can result in a small and transient "initial dip" of the blood oxygenation level-dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI). The initial dip has been of great interest to the fMRI community because it may provide a more accurate and localized measure of neural activity than the conventional BOLD signal increase. Although potentially useful as a technique for human brain mapping, the initial dip is not always detected and has been a source of some controversy. In this study, the BOLD response to a 4-s long visual stimulus was measured with a 3-T MRI system in 5 healthy volunteers both before and immediately after a 200-mg oral caffeine dose. The caffeine dose significantly (P < 0.001) reduced or eliminated the initial dip in all subjects. These findings suggest that caffeine usage may be a key factor in the detection of the initial dip in human fMRI studies.

  11. A component based noise correction method (CompCor) for BOLD and perfusion based fMRI.

    PubMed

    Behzadi, Yashar; Restom, Khaled; Liau, Joy; Liu, Thomas T

    2007-08-01

    A component based method (CompCor) for the reduction of noise in both blood oxygenation level-dependent (BOLD) and perfusion-based functional magnetic resonance imaging (fMRI) data is presented. In the proposed method, significant principal components are derived from noise regions-of-interest (ROI) in which the time series data are unlikely to be modulated by neural activity. These components are then included as nuisance parameters within general linear models for BOLD and perfusion-based fMRI time series data. Two approaches for the determination of the noise ROI are considered. The first method uses high-resolution anatomical data to define a region of interest composed primarily of white matter and cerebrospinal fluid, while the second method defines a region based upon the temporal standard deviation of the time series data. With the application of CompCor, the temporal standard deviation of resting-state perfusion and BOLD data in gray matter regions was significantly reduced as compared to either no correction or the application of a previously described retrospective image based correction scheme (RETROICOR). For both functional perfusion and BOLD data, the application of CompCor significantly increased the number of activated voxels as compared to no correction. In addition, for functional BOLD data, there were significantly more activated voxels detected with CompCor as compared to RETROICOR. In comparison to RETROICOR, CompCor has the advantage of not requiring external monitoring of physiological fluctuations.

  12. 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

  13. 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.

  14. How and when the fMRI BOLD signal relates to underlying neural activity: The danger in dissociation

    PubMed Central

    Ekstrom, Arne

    2013-01-01

    Functional magnetic resonance imaging (fMRI) has become the dominant means of measuring behavior-related neural activity in the human brain. Yet the relation between the blood oxygen-level dependent (BOLD) signal and underlying neural activity remains an open and actively researched question. A widely accepted model, established for sensory neo-cortex, suggests that the BOLD signal reflects peri-synaptic activity in the form of the local field potential rather than the spiking rate of individual neurons. Several recent experimental results, however, suggest situations in which BOLD, spiking, and the local field potential dissociate. Two different models are discussed, based on the literature reviewed to account for this dissociation, a circuitry-based and vascular-based explanation. Both models are found to account for existing data under some testing situations and in certain brain regions. Because both the vascular and local circuitry-based explanations challenge the BOLD-LFP coupling model, these models provide guidance in predicting when BOLD can be expected to reflect neural processing and when the underlying relation with BOLD may be more complex than a direct correspondence. PMID:20026191

  15. 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

  16. 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

  17. 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

  18. Functional dissociation of transient and sustained fMRI BOLD components in human auditory cortex revealed with a streaming paradigm based on interaural time differences.

    PubMed

    Schadwinkel, Stefan; Gutschalk, Alexander

    2010-12-01

    A number of physiological studies suggest that feature-selective adaptation is relevant to the pre-processing for auditory streaming, the perceptual separation of overlapping sound sources. Most of these studies are focused on spectral differences between streams, which are considered most important for streaming. However, spatial cues also support streaming, alone or in combination with spectral cues, but physiological studies of spatial cues for streaming remain scarce. Here, we investigate whether the tuning of selective adaptation for interaural time differences (ITD) coincides with the range where streaming perception is observed. FMRI activation that has been shown to adapt depending on the repetition rate was studied with a streaming paradigm where two tones were differently lateralized by ITD. Listeners were presented with five different ΔITD conditions (62.5, 125, 187.5, 343.75, or 687.5 μs) out of an active baseline with no ΔITD during fMRI. The results showed reduced adaptation for conditions with ΔITD ≥ 125 μs, reflected by enhanced sustained BOLD activity. The percentage of streaming perception for these stimuli increased from approximately 20% for ΔITD = 62.5 μs to > 60% for ΔITD = 125 μs. No further sustained BOLD enhancement was observed when the ΔITD was increased beyond ΔITD = 125 μs, whereas the streaming probability continued to increase up to 90% for ΔITD = 687.5 μs. Conversely, the transient BOLD response, at the transition from baseline to ΔITD blocks, increased most prominently as ΔITD was increased from 187.5 to 343.75 μs. These results demonstrate a clear dissociation of transient and sustained components of the BOLD activity in auditory cortex.

  19. Hippocampal CA3 activation alleviates fMRI-BOLD responses in the rat prefrontal cortex induced by electrical VTA stimulation

    PubMed Central

    Scherf, Thomas

    2017-01-01

    Functional magnetic resonance imaging (fMRI) was used to identify brain- wide networks that are activated by electrical stimulation of either the ventral tegmental area (VTA) or hippocampal CA3 region. Stimulation of either one of these regions caused significant BOLD responses in common structures, such as the septum and left and right hippocampus, but also in unique structures, such as the medial prefrontal cortex region/anterior cingulum region (mPFC/ACC) and striatum, which were only activated during VTA stimulation. Concurrent stimulations of the two structures resulted in no additive BOLD responses but significantly reduced BOLD responses in the mPFC/ACC when compared with sole VTA stimulation. This reduction is caused by costimulation of the hippocampal CA3 region, which was itself not sufficient to modify BOLD signal intensities in the mPFC/ACC. Under this experimental condition, functional connectivity between VTA and mPFC/ACC in terms of neurophysiological interactions was causative, driven by direct electrical stimulation of VTA projecting neurons, the resulting functional connectivity in terms of correlated BOLD time series becoming masked as soon as hippocampal projections concurrently coactivated mPFC neurons. This result warns against misinterpretation of the absence of functional connectivity in fMRI data sets, because strong existing neurophysiological interactions can be obscured by unrelated network activities. PMID:28241047

  20. 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

  1. Abnormal striatal BOLD responses to reward anticipation and reward delivery in ADHD.

    PubMed

    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.

  2. fMRI bold signal analysis using a novel nonparametric statistical method

    NASA Astrophysics Data System (ADS)

    De Mazière, Patrick A.; Van Hulle, Marc M.

    2007-03-01

    We present in this article a novel analytical method that enables the application of nonparametric rank-order statistics to fMRI data analysis, since it takes the omnipresent serial correlations (temporal autocorrelations) properly into account. Comparative simulations, using the common General Linear Model and the permutation test, confirm the validity and usefulness of our approach. Our simulations, which are performed with both synthetic and real fMRI data, show that our method requires significantly less computation time than permutation-based methods, while offering the same order of robustness and returning more information about the evoked response when combined with/compared to the results obtained with the common General Lineal Model approach.

  3. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Sampling rate dependence of correlation at long time lags in BOLD fMRI measurements on humans and gel phantoms.

    PubMed

    Mikkelsen, Kaare B; Lund, Torben E

    2013-01-01

    The aim of this study is to investigate the effects of sampling rate on Hurst exponents derived from Blood Oxygenation Level Dependent functional Magnetic Resonance Imaging (BOLD fMRI) resting state time series. fMRI measurements were performed on 2 human subjects and a selection of gel phantoms. From these, Hurst exponents were calculated. It was found that low sampling rates induced non-trivial exponents at sharp material transitions, and that Hurst exponents of human measurements had a strong TR-dependence. The findings are compared to theoretical considerations regarding the fractional Gaussian noise model and resampling, and it is found that the implications are problematic. This result should have a direct influence on the way future studies of low-frequency variation in BOLD fMRI data are conducted, especially if the fractional Gaussian noise model is considered. We recommend either using a different model (examples of such are referenced in the conclusion), or standardizing experimental procedures along an optimal sampling rate.

  5. Spatiotemporal properties of the BOLD response in the songbirds' auditory circuit during a variety of listening tasks.

    PubMed

    Van Meir, Vincent; Boumans, Tiny; De Groof, Geert; Van Audekerke, Johan; Smolders, Alain; Scheunders, Paul; Sijbers, Jan; Verhoye, Marleen; Balthazart, Jacques; Van der Linden, Annemie

    2005-05-01

    Auditory fMRI in humans has recently received increasing attention from cognitive neuroscientists as a tool to understand mental processing of learned acoustic sequences and analyzing speech recognition and development of musical skills. The present study introduces this tool in a well-documented animal model for vocal learning, the songbird, and provides fundamental insight in the main technical issues associated with auditory fMRI in these songbirds. Stimulation protocols with various listening tasks lead to appropriate activation of successive relays in the songbirds' auditory pathway. The elicited BOLD response is also region and stimulus specific, and its temporal aspects provide accurate measures of the changes in brain physiology induced by the acoustic stimuli. Extensive repetition of an identical stimulus does not lead to habituation of the response in the primary or secondary telencephalic auditory regions of anesthetized subjects. The BOLD signal intensity changes during a stimulation and subsequent rest period have a very specific time course which shows a remarkable resemblance to auditory evoked BOLD responses commonly observed in human subjects. This observation indicates that auditory fMRI in the songbird may establish a link between auditory related neuro-imaging studies done in humans and the large body of neuro-ethological research on song learning and neuro-plasticity performed in songbirds.

  6. White Matter Integrity Is a Stronger Predictor of Motor Function Than BOLD Response in Patients With Stroke

    PubMed Central

    Qiu, Mingguo; Darling, Warren G.; Morecraft, Robert J.; Ni, Chun Chun; Rajendra, Justin; Butler, Andrew J.

    2013-01-01

    Objective Neuroimaging techniques, such as diffusion tensor imaging (DTI) and blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (fMRI), provide insights into the functional reorganization of the cortical motor system after stroke. This study explores the relationship between upper extremity motor function, white matter integrity, and BOLD response of cortical motor areas. Methods Seventeen patients met study inclusion criteria; of these 12 completed DTI assessment of white matter integrity and 9 completed fMRI assessment of motor-related activation. Primary clinical outcome measures were the Wolf Motor Function Test (WMFT) and the upper limb portion of the Fugl-Meyer (FM) motor assessment. Structural integrity of the posterior limb of the internal capsule was assessed by examining the fractional anisotropy (FA) asymmetry in the PLIC. Laterality index of motor cortical areas was measured as the BOLD response in each patient during a finger pinch task. Linear regression analyses were performed to determine whether clinical outcome was associated with structural or functional MRI measures. Results There were strong relationships between clinical outcome measures and FA asymmetry (eg, FM score [R2 = .655, P = .001] and WMFT asymmetry score [R2 = .651, P < .002]) but relationships with fMRI measures were weaker. Conclusion Clinical motor function is more closely related to the white matter integrity of the internal capsule than to BOLD response of motor areas in patients 3 to 9 months after stroke. Thus, use of DTI to assess white matter integrity in the internal capsule may provide more useful information than fMRI to interpret motor deficits following supratentorial brain injury. PMID:21357529

  7. 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

  8. BOLD fMRI integration into radiosurgery treatment planning of cerebral vascular malformations

    SciTech Connect

    Stancanello, Joseph; Cavedon, Carlo; Francescon, Paolo; Causin, Francesco; Avanzo, Michele; Colombo, Federico; Cerveri, Pietro; Ferrigno, Giancarlo; Uggeri, Fulvio

    2007-04-15

    Functional magnetic resonance imaging (fMRI) is used to distinguish areas of the brain responsible for different tasks and functions. It is possible, for example, by using fMRI images, to identify particular regions in the brain which can be considered as 'functional organs at risk' (fOARs), i.e., regions which would cause significant patient morbidity if compromised. The aim of this study is to propose and validate a method to exploit functional information for the identification of fOARs in CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery treatment planning; in particular, given the high spatial accuracy offered by the CyberKnife system, local nonrigid registration is used to reach accurate image matching. Five patients affected by arteriovenous malformations (AVMs) and scheduled to undergo radiosurgery were scanned prior to treatment using computed tomography (CT), three-dimensional (3D) rotational angiography (3DRA), T2 weighted and blood oxygenation level dependent echo planar imaging MRI. Tasks were chosen on the basis of lesion location by considering those areas which could be potentially close to treatment targets. Functional data were superimposed on 3DRA and CT used for treatment planning. The procedure for the localization of fMRI areas was validated by direct cortical stimulation on 38 AVM and tumor patients undergoing conventional surgery. Treatment plans studied with and without considering fOARs were significantly different, in particular with respect to both maximum dose and dose volume histograms; consideration of the fOARs allowed quality indices of treatment plans to remain almost constant or to improve in four out of five cases compared to plans with no consideration of fOARs. In conclusion, the presented method provides an accurate tool for the integration of functional information into AVM radiosurgery, which might help to minimize undesirable side effects and to make radiosurgery less invasive.

  9. 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). Copyright 2007 Wiley-Liss, Inc.

  10. 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.

  11. Arterial spin labeling for motor activation mapping at 3T with a 32-channel coil: reproducibility and spatial accuracy in comparison with BOLD fMRI.

    PubMed

    Raoult, Hélène; Petr, Jan; Bannier, Elise; Stamm, Aymeric; Gauvrit, Jean-Yves; Barillot, Christian; Ferré, Jean-Christophe

    2011-09-01

    Functional arterial spin labeling (fASL) is an innovative biomarker of neuronal activation that allows direct and absolute quantification of activation-related CBF and is less sensitive to venous contamination than BOLD fMRI. This study evaluated fASL for motor activation mapping in comparison with BOLD fMRI in terms of involved anatomical area localization, intra-individual reproducibility of location, quantification of neuronal activation, and spatial accuracy. Imaging was performed at 3T with a 32-channel coil and dedicated post-processing tools were used. Twelve healthy right-handed subjects underwent fASL and BOLD fMRI while performing a right hand motor activation task. Three sessions were performed 7days apart in similar physiological conditions. Our results showed an activation in the left primary hand motor area for all 36 sessions in both fASL and BOLD fMRI. The individual functional maps for fASL demonstrated activation in ipsilateral secondary motor areas more often than the BOLD fMRI maps. This finding was corroborated by the group maps. In terms of activation location, fASL reproducibility was comparable to BOLD fMRI, with a distance between activated volumes of 2.1mm and an overlap ratio for activated volumes of 0.76, over the 3 sessions. In terms of activation quantification, fASL reproducibility was higher, although not significantly, with a CVintra of 11.6% and an ICC value of 0.75. Functional ASL detected smaller activation volumes than BOLD fMRI but the areas had a high degree of co-localization. In terms of spatial accuracy in detecting activation in the hand motor area, fASL had a higher specificity (43.5%) and a higher positive predictive value (69.8%) than BOLD fMRI while maintaining high sensitivity (90.7%). The high intra-individual reproducibility and spatial accuracy of fASL revealed in the present study will subsequently be applied to pathological subjects. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Lack of generalizability of sex differences in the fMRI BOLD activity associated with language processing in adults

    PubMed Central

    Ihnen, S. K. Z.; Church, Jessica A.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    A lack of consensus exists as to whether there are sex differences in the fMRI BOLD signal correlates of language processing in the human brain. Here, whole-brain fMRI was used to examine the neural activity of 46 adults performing one of two sets of language tasks. Conservative quantitative and qualitative criteria identified a handful of statistically significant regions of “sex difference” within each task separately. When each of the two sets of regions was investigated in the group of subjects performing the other task set, however, most of the identified “sex differences” failed to generalize. Identical analyses of the same subjects divided into sex-matched pseudorandom control groups for each task set separately revealed that it is possible to observe a similar number of statistically significant regions of “group difference” in the task-associated BOLD signal, even when the groups do not differ on any of the measured behavioral parameters, or any obvious demographic characteristic. Together, these results suggest that one should be cautious when interpreting studies that purport to have identified regions of difference between groups, whether those groups are divided by sex or by any other criterion. In particular, generalization or replication of a result in independent data sets is necessary for establishing conclusive support for any hypothesis about differences in brain function between groups. PMID:19162200

  13. A model of neurovascular coupling and the BOLD response: PART I.

    PubMed

    Mathias, E J; Plank, M J; David, T

    2017-04-01

    The mechanisms with which neurons communicate with the vasculature to increase blood flow, termed neurovascular coupling is still unclear primarily due to the complex interactions between many parameters and the difficulty in accessing, monitoring and measuring them in the highly heterogeneous brain. Hence a solid theoretical framework based on existing experimental knowledge is necessary to study the relation between neural activity, the associated vasoactive factors released and their effects on the vasculature. Such a framework should also be related to experimental data so that it can be validated against repetitive experiments and generate verifiable hypothesis. We have developed a mathematical model which describes a signaling mechanism of neurovascular coupling with a model of pyramidal neuron and its corresponding fMRI BOLD response. In the first part of two papers we describe the integration of the neurovascular coupling unit extended to include a complex neuron model, which includes the important Na/K ATPase pump, with a model that provides a BOLD signal taking its input from the cerebral blood flow and the metabolic rate of oxygen consumption. We show that this produces a viable signal in terms of initial dip, positive and negative BOLD signals.

  14. All that glitters is not BOLD: inconsistencies in functional MRI

    NASA Astrophysics Data System (ADS)

    Renvall, Ville; Nangini, Cathy; Hari, Riitta

    2014-01-01

    The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is a widely-accepted marker of brain activity. The acquisition parameters (APs) of fMRI aim at maximizing the signals related to neuronal activity while minimizing unrelated signal fluctuations. Currently, a diverse set of APs is used to acquire BOLD fMRI data. Here we demonstrate that some fMRI responses are alarmingly inconsistent across APs, ranging from positive to negative, or disappearing entirely, under identical stimulus conditions. These discrepancies, resulting from non-BOLD effects masquerading as BOLD signals, have remained largely unnoticed because studies rarely employ more than one set of APs. We identified and characterized non-BOLD responses in several brain areas, including posterior cingulate cortex and precuneus, as well as AP-dependence of both the signal time courses and of seed-based functional networks, noticing that AP manipulation can inform about the origin of the measured signals.

  15. Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness.

    PubMed

    Liu, Xiaolin; Lauer, Kathryn K; Douglas Ward, B; Roberts, Christopher; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Chen, Guangyu; Xu, Zhan; Binder, Jeffrey R; Li, Shi-Jiang; Hudetz, Anthony G

    2017-02-15

    Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.

  16. Dependence of the negative BOLD response on somatosensory stimulus intensity.

    PubMed

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

    2010-10-15

    The primary somatosensory cortex (SI) has been shown to encode the intensity of a stimulus applied to the contralateral side of the body. Recent studies have demonstrated that ipsilateral SI is also involved in the processing of somatosensory information. In this study, we investigated the dependence of the negative BOLD response in ipsilateral SI on the intensity of somatosensory stimulation. Functional MRI was performed in 12 healthy subjects during electrical median nerve stimulation at four different intensities. A monotonic relationship between stimulus intensity and the strength of the negative BOLD response in ipsilateral SI was found. Additionally, a psychophysiological experiment revealed tight coupling between the stimulus intensity applied to one hand and increased perceptual threshold of the other hand. These findings indicate a stimulus intensity-dependent inhibition of ipsilateral SI.

  17. EEG-informed fMRI analysis during a hand grip task: estimating the relationship between EEG rhythms and the BOLD signal

    PubMed Central

    Sclocco, Roberta; Tana, Maria G.; Visani, Elisa; Gilioli, Isabella; Panzica, Ferruccio; Franceschetti, Silvana; Cerutti, Sergio; Bianchi, Anna M.

    2014-01-01

    In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neural activity, rather than with absolute power. Concurrently, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be also important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between the two signals. Here we propose a method to perform EEG-informed fMRI analysis where the changes in the spectral profile are modeled, and, at the same time, the distinction between rhythms is preserved. We compared our model with two other frequency-dependent regressors modeling using simultaneous EEG-fMRI data from healthy subjects performing a motor task. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related, well localized activated volumes. Furthermore, we showed that including among the regressors also EEG rhythms not primarily involved in the task enhances the performance of the analysis, even when only correlations with BOLD signal and specific EEG rhythms are explored. PMID:24744720

  18. Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study.

    PubMed

    Suarez, S V; Amadon, A; Giacomini, E; Wiklund, A; Changeux, J-P; Le Bihan, D; Granon, S

    2009-03-01

    The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity beta2-containing nicotinic receptors (beta2*nAChRs) are located. We intend to see which brain circuits are activated when nicotine is given in animals naïve for nicotine and whether the beta2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and beta2 knockout (KO) mice. Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, beta2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via alpha7 nicotinic receptors. Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on beta2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice.

  19. CBF/CMRO2 Coupling Measured with Calibrated-BOLD fMRI: Sources of Bias

    PubMed Central

    Leontiev, Oleg; Dubowitz, David J.; Buxton, Richard B.

    2007-01-01

    The coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during brain activation can be characterized by an empirical index n, the ratio of fractional CBF changes to fractional CMRO2 changes. Measurements of n have yielded varying results, and it is not known if the observed variability is due to measurement techniques or underlying physiology. The calibrated BOLD approach using hypercapnia offers a promising tool for assessing changes in CBF/CMRO2 coupling in health and disease, but potential systematic errors have not yet been characterized. The goal of this study was to experimentally evaluate the magnitude of bias in the estimate of n that arises from the way in which a region of interest (ROI) is chosen for averaging data, and to relate this potential bias to a more general theoretical consideration of the sources of systematic errors in the calibrated BOLD experiment. Results were compared for different approaches for defining an ROI within the visual cortex based on: 1) retinotopically-defined V1; 2) a functional CBF localizer; and 3) a functional BOLD localizer. Data in V1 yielded a significantly lower estimate of n (2.45) compared to either CBF (n = 3.45) or BOLD (n = 3.18) localizers. Different statistical thresholds produced biases in estimates of n with values ranging from 3.01 (low threshold) to 4.37 (high threshold). Possible sources of the observed biases are discussed. These results underscore the importance of a critical evaluation of the methodology, and the adoption of consistent standards for applying the calibrated BOLD approach to the evaluation of CBF/CMRO2 coupling. PMID:17524665

  20. CBF/CMRO2 coupling measured with calibrated BOLD fMRI: sources of bias.

    PubMed

    Leontiev, Oleg; Dubowitz, David J; Buxton, Richard B

    2007-07-15

    The coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during brain activation can be characterized by an empirical index n, the ratio of fractional CBF changes to fractional CMRO2 changes. Measurements of n have yielded varying results, and it is not known if the observed variability is due to measurement techniques or underlying physiology. The calibrated BOLD approach using hypercapnia offers a promising tool for assessing changes in CBF/CMRO2 coupling in health and disease, but potential systematic errors have not yet been characterized. The goal of this study was to experimentally evaluate the magnitude of bias in the estimate of n that arises from the way in which a region of interest (ROI) is chosen for averaging data and to relate this potential bias to a more general theoretical consideration of the sources of systematic errors in the calibrated BOLD experiment. Results were compared for different approaches for defining an ROI within the visual cortex based on: (1) retinotopically defined V1; (2) a functional CBF localizer; and (3) a functional BOLD localizer. Data in V1 yielded a significantly lower estimate of n (2.45) compared to either CBF (n=3.45) or BOLD (n=3.18) localizers. Different statistical thresholds produced biases in estimates of n with values ranging from 3.01 (low threshold) to 4.37 (high threshold). Possible sources of the observed biases are discussed. These results underscore the importance of a critical evaluation of the methodology, and the adoption of consistent standards for applying the calibrated BOLD approach to the evaluation of CBF/CMRO2 coupling.

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

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  2. Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals

    PubMed Central

    Kim, Seong-Gi; Ogawa, Seiji

    2012-01-01

    After its discovery in 1990, blood oxygenation level-dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) has been widely used to map brain activation in humans and animals. Since fMRI relies on signal changes induced by neural activity, its signal source can be complex and is also dependent on imaging parameters and techniques. In this review, we identify and describe the origins of BOLD fMRI signals, including the topics of (1) effects of spin density, volume fraction, inflow, perfusion, and susceptibility as potential contributors to BOLD fMRI, (2) intravascular and extravascular contributions to conventional gradient-echo and spin-echo BOLD fMRI, (3) spatial specificity of hemodynamic-based fMRI related to vascular architecture and intrinsic hemodynamic responses, (4) BOLD signal contributions from functional changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of O2 utilization (CMRO2), (5) dynamic responses of BOLD, CBF, CMRO2, and arterial and venous CBV, (6) potential sources of initial BOLD dips, poststimulus BOLD undershoots, and prolonged negative BOLD fMRI signals, (7) dependence of stimulus-evoked BOLD signals on baseline physiology, and (8) basis of resting-state BOLD fluctuations. These discussions are highly relevant to interpreting BOLD fMRI signals as physiological means. PMID:22395207

  3. 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.

  4. 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. Copyright © 2012

  5. Cerebrovascular reactivity mapping in patients with low grade gliomas undergoing presurgical sensorimotor mapping with BOLD fMRI.

    PubMed

    Zacà, Domenico; Jovicich, Jorge; Nadar, Sreenivasan R; Voyvodic, James T; Pillai, Jay J

    2014-08-01

    (i) to validate blood oxygenation level dependent (BOLD) breathhold cerebrovascular reactivity (BH CVR) mapping as an effective technique for potential detection of neurovascular uncoupling (NVU) in a cohort of patients with perirolandic low grade gliomas undergoing presurgical functional MRI (fMRI) for sensorimotor mapping, and (ii) to determine whether NVU potential, as assessed by BH CVR mapping, is prevalent in this tumor group. We retrospectively evaluated 12 patients, with histological diagnosis of grade II glioma, who performed multiple motor tasks and a BH task. Sensorimotor activation maps and BH CVR maps were compared in two automatically defined regions of interest (ROIs), ipsilateral to the lesion (i.e., ipsilesional) and contralateral to the lesion (i.e., contralesional). Motor task mean T-value was significantly higher in the contralesional ROIs (6.00 ± 1.74 versus 4.34 ± 1.68; P = 0.00004) as well as the BH mean T-value (4.74 ± 2.30 versus 4.09 ± 2.50; P = 0.009). The number of active voxels was significantly higher in the contralesional ROIs (Z = 2.99; P = 0.03). Actual NVU prevalence was 75%. Presurgical sensorimotor fMRI mapping can be affected by NVU-related false negative activation in low grade gliomas (76% of analyzed tasks). © 2013 Wiley Periodicals, Inc.

  6. Cerebrovascular reactivity mapping in patients with low grade gliomas undergoing presurgical sensorimotor mapping with BOLD fMRI

    PubMed Central

    Zacà, Domenico; Jovicich, Jorge; Nadar, Sreenivasan R.; Voyvodic, James T.; Pillai, Jay J.

    2013-01-01

    Purpose i) to validate Blood Oxygenation Level Dependent (BOLD) breath hold cerebrovascular reactivity mapping (BH CVR) as an effective technique for potential detection of neurovascular uncoupling (NVU) in a cohort of patients with perirolandic low grade gliomas undergoing presurgical functional magnetic resonance imaging (fMRI) for sensorimotor mapping, and ii) to determine whether NVU potential, as assessed by BH CVR mapping, is prevalent in this tumor group. Materials and Methods We retrospectively evaluated 12 patients, with histological diagnosis of grade II glioma, who performed multiple motor tasks and a BH task. Sensorimotor activation maps and BH CVR maps were compared in two automatically defined regions of interest (ROIs), ipsilateral to the lesion (i.e., ipsilesional) and contralateral to the lesion (i.e., contralesional). Results Motor task mean T-value was significantly higher in the contralesional ROIs (6.00±1.74 vs 4.34±1.68, p=0.00004) as well as the BH mean T-value (4.74±2.30 vs 4.09±2.50, p=0.009). The number of active voxels was significantly higher in the contralesional ROIs (Z=2.99, p=0.03). Actual NVU prevalence was 75%. Conclusion Presurgical sensorimotor fMRI mapping can be affected by NVU-related false negative activation in low grade gliomas (76% of analyzed tasks). PMID:24338845

  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. 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…

  9. Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: Implications for BOLD-fMRI

    PubMed Central

    Ances, Beau M.; Leontiev, Oleg; Perthen, Joanna E.; Liang, Christine; Lansing, Amy E.; Buxton, Richard B.

    2010-01-01

    Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO2). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (∼5.8%), differences in n (2.21±0.03 in VC and 1.58±0.03 in LN; Cohen d=1.71) produced substantially weaker (∼3.7×) subcortical than cortical BOLD responses relative to CMRO2 changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot be interpreted as a quantitative reflection of underlying metabolic changes, particularly when comparing cortical and sub-cortical regions. PMID:18164629

  10. Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI.

    PubMed

    Ances, Beau M; Leontiev, Oleg; Perthen, Joanna E; Liang, Christine; Lansing, Amy E; Buxton, Richard B

    2008-02-15

    Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO(2)). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (~5.8%), differences in n (2.21+/-0.03 in VC and 1.58+/-0.03 in LN; Cohen d=1.71) produced substantially weaker (~3.7x) subcortical than cortical BOLD responses relative to CMRO(2) changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot be interpreted as a quantitative reflection of underlying metabolic changes, particularly when comparing cortical and subcortical regions.

  11. 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

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

    PubMed

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

    2016-10-01

    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.

  13. Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease

    PubMed Central

    Price, J.L.; Yan, Z.; Morris, J.C.; Sheline, Y.I.

    2011-01-01

    Objective: Clinicopathologic phenotypes of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) often overlap, making discrimination difficult. We performed resting state blood oxygen level–dependent (BOLD) functional connectivity MRI (fcMRI) to determine whether there were differences between AD and DLB. Methods: Participants (n = 88) enrolled in a longitudinal study of memory and aging underwent 3-T fcMRI. Clinical diagnoses of probable DLB (n = 15) were made according to published criteria. Cognitively normal control participants (n = 38) were selected for the absence of cerebral amyloid burden as imaged with Pittsburgh compound B (PiB). Probable AD cases (n = 35) met published criteria and had appreciable amyloid deposits with PiB imaging. Functional images were collected using a gradient spin-echo sequence sensitive to BOLD contrast (T2* weighting). Correlation maps selected a seed region in the combined bilateral precuneus. Results: Participants with DLB had a functional connectivity pattern for the precuneus seed region that was distinct from AD; both the DLB and AD groups had functional connectivity patterns that differed from the cognitively normal group. In the DLB group, we found increased connectivity between the precuneus and regions in the dorsal attention network and the putamen. In contrast, we found decreased connectivity between the precuneus and other task-negative default regions and visual cortices. There was also a reversal of connectivity in the right hippocampus. Conclusions: Changes in functional connectivity in DLB indicate patterns of activation that are distinct from those seen in AD and may improve discrimination of DLB from AD and cognitively normal individuals. Since patterns of connectivity differ between AD and DLB groups, measurements of BOLD functional connectivity can shed further light on neuroanatomic connections that distinguish DLB from AD. PMID:21525427

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

    PubMed Central

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

    2011-01-01

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

  15. 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

  16. Improved spatial localization of post-stimulus BOLD undershoot relative to positive BOLD

    PubMed Central

    Zhao, Fuqiang; Jin, Tao; Wang, Ping; Kim, Seong-Gi

    2007-01-01

    The negative blood oxygenation level dependent (BOLD) signal following the cessation of stimulation (post-stimulus BOLD undershoot) is observed in functional magnetic resonance imaging (fMRI) studies. However, its spatial characteristics are unknown. To investigate this, gradient-echo BOLD fMRI in response to visual stimulus was obtained in isoflurane-anesthetized cats at 9.4 T. Since the middle cortical layer (layer 4) is known to have the highest metabolic and cerebral blood volume (CBV) responses, images were obtained to view the cortical cross-section. Robust post-stimulus BOLD undershoot was observed in all studies, and lasted longer than 30 sec after the cessation of 40-60 sec stimulation. The magnitude of post-stimulus BOLD undershoot was linearly dependent on echo time with little intercept when extrapolating to TE = 0, indicating the T2* change is the major cause of the BOLD undershoot. The post-stimulus BOLD undershoot was observed within the cortex and near the surface of the cortex, while the prolonged CBV elevation was observed only at the middle of the cortex. Within the cortex, the largest post-stimulus undershoot was detected at the middle of the cortex, similar to the CBV increase during the stimulation period. Our findings demonstrate that, even though there is significant contribution from pial vessel signals, the post-stimulus undershoot BOLD signal is useful to improve the spatial localization of fMRI to active cortical sites. PMID:17161623

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

    PubMed Central

    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. PMID:25385710

  18. 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.

  19. Reproducibility of hypocapnic cerebrovascular reactivity measurements using BOLD fMRI in combination with a paced deep breathing task.

    PubMed

    Sousa, I; Vilela, P; Figueiredo, P

    2014-09-01

    It has recently been proposed that hypocapnic cerebrovascular reactivity (CVR) can be assessed by measuring the blood oxygenation level dependent (BOLD) response to paced deep breathing (PDB) tasks inducing mild hypocapnia and vasoconstriction. In this work, we aim to assess the test-retest reproducibility and inter-subject variability of BOLD CVR measurements obtained using a PDB task and different methods to analyse the associated BOLD signal. The respiratory protocol consisted of alternating 40s of PDB with normal free breathing; expired CO2 pressure levels (PETCO2) were continuously monitored. CVR was quantified using either a timecourse curve analysis (TCA) approach, where the magnitude of response peaks is emphasized, or general linear modelling (GLM) including optimisation of the BOLD response latencies. The GLM fit was carried out using two types of response regressors: one that was computed as the convolution of PETCO2 traces with a gamma function and another that consisted of the convolution of PDB paradigm blocks with a physiological model of the respiratory response. Haemodynamic response latencies were optimised either on a voxel basis or for the whole imaging region. We found that the GLM method based on PDB task or PETCO2 traces and voxelwise optimisation of response latencies provided the most reproducible measures of CVR. For the average grey matter CVR, the inter-subject coefficient of variation (CVinter) / intra-subject coefficient of variation (CVintra) / intra-class correlation coefficient (ICC) were 20%/8%/0.8 and 27%/8%/0.9, using the task and PETCO2 timecourses, respectively. In terms of the spatial reproducibility, the group mean (±standard deviation) of the spatial ICC (ICCspatial) was 1.04±0.23 and 1.02±0.26, for the task and PETCO2 timecourses, respectively. These results indicate generally good reproducibility of the hypocapnic CVR maps obtained using the proposed PDB task and analysis methodology. This suggests that such protocol

  20. Oxytocin modulates unconditioned fear response in lactating dams: an fMRI study

    PubMed Central

    Febo, Marcelo; Shields, Jessica; Ferris, Craig F.; King, Jean A.

    2009-01-01

    Oxytocinergic neurotransmission during lactation contributes to reduction of anxiety levels and fear. However, our knowledge of where oxytocin acts in the brain to achieve this effect, particularly to an unconditioned fear stimulus, is incomplete. We used blood oxygenation level dependent (BOLD) fMRI to test whether central administration of oxytocin 45–60 minutes before fMRI scanning alters maternal brain activation in response to a predator scent (TMT, trimethylthiazoline). Comparison behavioral experiments that examined maternal responses to this unconditioned fear -inducing odor were carried out in a separate cohort of lactating rats given similar treatments. Behavioral experiments confirmed the effectiveness of oxytocin at reducing freezing behavior as compared to vehicle controls. Our fMRI findings indicate that oxytocin modulated both positive and negative BOLD responses across several olfactory and forebrain nuclei. Significantly greater percent increases in BOLD signal in response to TMT were observed in the anterior cingulate, bed nucleus of stria terminalis and perirhinal area of oxytocin pretreated rats. These animals also showed significantly larger percent decreases in BOLD in mammillary bodies, secondary motor cortex, gustatory cortex, prelimbic prefrontal cortex, orbital cortex, and the anterior olfactory nucleus. The observed pattern of brain activity suggests that oxytocin enhances neural processing in emotion and cognition driven brain areas such as the cingulate cortex, while dramatically reducing activity in areas also controlling autonomic, visceromotor and skeletomotor responses. The present data contribute to the growing literature suggesting the oxytocin modulate the integration of emotional and cognitive information through myriad brain regions to facilitate decreases in anxiety (even to an unconditioned stimulus) while potentially promoting pair-bonding, social memory and parental care. PMID:19766607

  1. BOLD Responses to Stimuli: Dependence on Frequency, Stimulus form, Amplitude, and Repetition Rate.

    NASA Astrophysics Data System (ADS)

    Robinson, Peter; Drysdale, Peter; van der Merwe, Helena; Kyriakou, Elizabeth; Rigozzi, Michelle; Germanoska, Biljana; Rennie, Christopher

    2006-03-01

    A quantitative theory is developed for the relationship between stimulus and the resulting Blood Oxygen Level Dependent (BOLD) functional MRI signal in the brain. The relationship of stimuli to neuronal activity during evoked responses is inferred from recent physiology-based modeling of evoked response potentials (ERPs). A hemodynamic model is then used to calculate the BOLD response to neuronal activity. The predicted response is analyzed vs. form, frequency, and amplitude of stimulus. The BOLD frequency response is very nearly linear in the parameter ranges of interest, with the form of a low-pass filter with a weak resonance at 0.07 Hz. For short stimuli, the response is closely proportional to the time-integrated stimulus-evoked activity, rather than the peak amplitude, as often assumed. There can thus be widely differing proportionalities between BOLD and peak activity, a likely reason for the weak expected correlation between ERPs and BOLD.

  2. Pain Does Not Follow the Boxcar Model: Temporal Dynamics of the BOLD FMRI Signal during Constant Current Painful Electric Nerve Stimulation

    PubMed Central

    Ibinson, JW; Vogt, KM

    2013-01-01

    The temporal dynamics of the blood oxygen level dependent (BOLD) signal, especially for painful stimulations, is not completely understood. In this study, the BOLD signal response to a long painful electrical stimulation (a continuous painful stimulation of 2 minutes) is directly compared to that of a short painful stimulation (four 30-s periods of painful stimulation interleaved with 30-s rest) in an effort to further probe the relationship between the temporal dynamics of the BOLD signal during constant intensity pain stimulation. Time course analysis showed that both stimulation protocols produced three similarly timed peaks in both data sets, suggesting an early and delayed BOLD response to painful stimulation initiation, and a response related to stimulus termination. Despite the continuous stimulation, the BOLD signal returned to baseline in the two-minute task. Even with this signal discrepancy, however, the activation maps of the two pain tasks differed only slightly, suggesting that the bulk of the activation is determined by the sharp rise in BOLD signal with stimulus onset. These findings imply that the BOLD signal response time course is not directly reflective of pain perception. PMID:24135433

  3. 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

  4. Variability of the BOLD response over time: an examination of within-session differences.

    PubMed

    Menz, Mareike M; Neumann, Jane; Müller, Karsten; Zysset, Stefan

    2006-09-01

    Model-based analysis methods for fMRI data assume a priori knowledge of the time course of the hemodynamic response (HR) in reaction to experimental stimuli or events. This knowledge is incorporated into the hemodynamic response function (HRF), which is a common model of the HR. Although it is already known that the HR varies across individuals and brain regions, few studies have investigated how variations within one session affect the results of statistical analysis using the general linear model (GLM). In this study, we formally tested for a possible variation of the BOLD response during prolonged functional measurement (120 min). To provoke performance of simple visual, motor, and cognitive tasks, we opted for a combination of a variant of the Stroop task and rotating L's. In selected regions of interest, time courses were extracted and compared with regard to mean and maximum amplitudes throughout the time of functional measurement. Additionally, parameter estimates derived from the GLM were tested for differences over time. Although differences between conditions were found to be significant, results did not show significant variance due to a within-factor time. Similarly, a temporal change in the relation between conditions, in terms of an interaction between the within-factor time and the within-factor condition, was not detectable by a repeated measures ANOVA. Similar results were obtained for analysis of mean and maximum amplitudes as well as for the analyses of parameter estimates.

  5. BOLD Correlates of Trial-by-Trial Reaction Time Variability in Gray and White Matter: A Multi-Study fMRI Analysis

    PubMed Central

    Yarkoni, Tal; Barch, Deanna M.; Gray, Jeremy R.; Conturo, Thomas E.; Braver, Todd S.

    2009-01-01

    Background Reaction time (RT) is one of the most widely used measures of performance in experimental psychology, yet relatively few fMRI studies have included trial-by-trial differences in RT as a predictor variable in their analyses. Using a multi-study approach, we investigated whether there are brain regions that show a general relationship between trial-by-trial RT variability and activation across a range of cognitive tasks. Methodology/Principal Findings The relation between trial-by-trial differences in RT and brain activation was modeled in five different fMRI datasets spanning a range of experimental tasks and stimulus modalities. Three main findings were identified. First, in a widely distributed set of gray and white matter regions, activation was delayed on trials with long RTs relative to short RTs, suggesting delayed initiation of underlying physiological processes. Second, in lateral and medial frontal regions, activation showed a “time-on-task” effect, increasing linearly as a function of RT. Finally, RT variability reliably modulated the BOLD signal not only in gray matter but also in diffuse regions of white matter. Conclusions/Significance The results highlight the importance of modeling trial-by-trial RT in fMRI analyses and raise the possibility that RT variability may provide a powerful probe for investigating the previously elusive white matter BOLD signal. PMID:19165335

  6. Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.

    PubMed

    Hubbard, Nicholas A; Turner, Monroe; Hutchison, Joanna L; Ouyang, Austin; Strain, Jeremy; Oasay, Larry; Sundaram, Saranya; Davis, Scott; Remington, Gina; Brigante, Ryan; Huang, Hao; Hart, John; Frohman, Teresa; Frohman, Elliot; Biswal, Bharat B; Rypma, Bart

    2016-11-01

    Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion tensor imaging to assess whether MS-related changes to the BOLD-HRF were affected by changes in white matter microstructural integrity. Our results showed MS-related reductions in BOLD-HRF peak amplitude. These MS-related amplitude decreases were influenced by individual differences in white matter microstructural integrity. Other MS-related factors including altered reaction time, limited spatial extent of BOLD activity, elevated lesion burden, or lesion proximity to regions of interest were not mediators of group differences in BOLD-HRF amplitude. Results are discussed in terms of functional hyperemic mechanisms and implications for analysis of BOLD signal differences. © The Author(s) 2015.

  7. Correlation between BOLD-fMRI and EEG signal changes in response to visual stimulus frequency in humans.

    PubMed

    Singh, Manbir; Kim, Sungheon; Kim, Tae-Seong

    2003-01-01

    The correlation between signals acquired using electroencephalography (EEG) and fMRI was investigated in humans during visual stimulation. Evoked potential EEG and BOLD fMRI data were acquired independently under similar conditions from eight subjects during stimulation by a checkerboard flashed at frequencies ranging from 2-12 Hz. The results indicate highly correlated changes in the strength of the EEG signal averaged over two occipital electrodes and the BOLD signal within the occipital lobe as a function of flash frequency for 7/8 subjects (average linear correlation coefficient of 0.76). Both signals peaked at approximately 8 Hz. For one subject the correlation coefficient was 0.20; the EEG signal peaked at 6 Hz and the BOLD signal peaked at 10 Hz. Overall, the EEG and BOLD signals, each averaged over 40-sec stimulation periods, appear to be coupled linearly during visual stimulation by a flashing checkerboard.

  8. Frequency-dependent tactile responses in rat brain by fMRI

    PubMed Central

    Sanganahalli, Basavaraju G.; Herman, Peter; Hyder, Fahmeed

    2009-01-01

    We measured frequency-dependent fMRI activations (at 11.7T) in the somatosensory cortex with whisker and forepaw stimuli in the same α-chloralose anesthetized rats. Whisker and forepaw stimuli were attained by computer-controlled pulses of air puffs and electrical currents, respectively. Air puffs deflected (±2 mm) the chosen whisker(s) in the right snout in the rostral and caudal direction, whereas electrical currents (2 mA amplitude, 0.3 ms duration) stimulated the left forepaw with subcutaneous copper electrodes placed between the second and fourth digits. In the same subject, unimodal stimulation of whisker and forepaw gave rise to significant BOLD signal increases in corresponding contralateral somatosensory areas of whisker barrel field (S1BF) and forelimb (S1FL), respectively, with no significant spatial overlap between these regions. The BOLD responses in S1BF and S1FL regions were found to be differentially variable with frequency of each stimulus type. In the S1BF, a linear increase in the BOLD response was observed with whisker stimulation frequency of up to ~12 Hz, beyond which the response seemed to saturate (and/or slightly attenuate) up to the maximum frequency studied (i.e., 30 Hz). In the S1FL, the magnitude of the BOLD response was largest at forepaw stimulation frequency between 1.5 and 3 Hz, beyond which the response diminished with little or no activity at frequencies higher than 20 Hz. The volume of tissue activated by each stimulus type followed a similar pattern as the stimulation frequency dependence. These results of bimodal whisker and forepaw stimuli in the same subject may provide a framework to study interactions of different tactile modules, both with fMRI and neurophysiology (i.e., inside and outside the magnet). PMID:18435491

  9. Cocaine and methamphetamine induce opposing changes in BOLD signal response in rats.

    PubMed

    Taheri, Saeid; Xun, Zhu; See, Ronald E; Joseph, Jane E; Reichel, Carmela M

    2016-07-01

    Neuroimaging studies in psychostimulant addicts have reported functional neural activity changes in brain regions involved in relapse. However, the difference between the effects of the psychostimulants methamphetamine and cocaine on neuronal activity in a similar setting not been clarified. Since studies in humans are limited by the inability to study the initial impact of psychostimulant drugs, we addressed this issue in a rat model. Here, we report methamphetamine and cocaine-induced blood-oxygen-level dependent (BOLD) signal change using functional magnetic resonance imaging (fMRI) in rats receiving drug for the first time during the imaging session. Twenty-three male Long Evans rats underwent fMRI imaging and received an intravenous infusion of methamphetamine, cocaine, or saline. Anatomical and pharmacological fMRI (pfMRI) were performed on a 7T BioSpec dedicated research MR scanner under isoflurane gas (1.5-2%). After collecting baseline data for 10min, rats received drug over the next 10min for a total 40min scan time. Data were then preprocessed and statistically analyzed in anatomically defined regions of interest (ROIs) that have been implicated in persistent drug seeking and relapse. Methamphetamine during the imaging session resulted in a sustained negative BOLD signal change in key regions of the relapse circuit, except for the prefrontal cortex. In contrast, cocaine evoked a positive or unchanged BOLD signal in these same regions. In all of the investigated ROIs, there were no changes in BOLD signal following saline. Acute methamphetamine and cocaine have distinct patterns of functional activity as measured by pfMRI. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Negative BOLD response in the hippocampus during short-term spatial memory retrieval.

    PubMed

    Nilsson, Jonna; Ferrier, I Nicol; Coventry, Kenny; Bester, Andre; Finkelmeyer, Andreas

    2013-08-01

    A parieto-medial temporal pathway is thought to underlie spatial navigation in humans. fMRI was used to assess the role of this pathway, including the hippocampus, in the cognitive processes likely to underlie navigation based on environmental cues. Participants completed a short-term spatial memory task in virtual space, which required no navigation but involved the recognition of a target location from a foil location based on environmental landmarks. The results showed that spatial memory retrieval based on environmental landmarks was indeed associated with increased signal in regions of the parieto-medial temporal pathway, including the superior parietal cortex, the retrosplenial cortex, and the lingual gyrus. However, the hippocampus demonstrated a signal decrease below the fixation baseline during landmark-based retrieval, whereas there was no signal change from baseline during retrieval based on viewer position. In a discussion of the origins of such negative BOLD response in the hippocampus, we consider both a suppression of default activity and an increase in activity without a corresponding boost in CBF as possible mechanisms.

  11. 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

  12. When the brain takes 'BOLD' steps: Real-time fMRI neurofeedback can further enhance the ability to gradually self-regulate regional brain activation.

    PubMed

    Sorger, Bettina; Kamp, Tabea; Weiskopf, Nikolaus; Peters, Judith Caroline; Goebel, Rainer

    2016-09-19

    Brain-computer interfaces (BCIs) based on real-time functional magnetic resonance imaging (rtfMRI) are currently explored in the context of developing alternative (motor-independent) communication and control means for the severely disabled. In such BCI systems, the user encodes a particular intention (e.g., an answer to a question or an intended action) by evoking specific mental activity resulting in a distinct brain state that can be decoded from fMRI activation. One goal in this context is to increase the degrees of freedom in encoding different intentions, i.e., to allow the BCI user to choose from as many options as possible. Recently, the ability to voluntarily modulate spatial and/or temporal blood oxygenation level-dependent (BOLD)-signal features has been explored implementing different mental tasks and/or different encoding time intervals, respectively. Our two-session fMRI feasibility study systematically investigated for the first time the possibility of using magnitudinal BOLD-signal features for intention encoding. Particularly, in our novel paradigm, participants (n=10) were asked to alternately self-regulate their regional brain-activation level to 30%, 60% or 90% of their maximal capacity by applying a selected activation strategy (i.e., performing a mental task, e.g., inner speech) and modulation strategies (e.g., using different speech rates) suggested by the experimenters. In a second step, we tested the hypothesis that the additional availability of feedback information on the current BOLD-signal level within a region of interest improves the gradual-self regulation performance. Therefore, participants were provided with neurofeedback in one of the two fMRI sessions. Our results show that the majority of the participants were able to gradually self-regulate regional brain activation to at least two different target levels even in the absence of neurofeedback. When provided with continuous feedback on their current BOLD-signal level, most

  13. 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

  14. 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

  15. Delineating the whole brain BOLD response to passive movement kinematics.

    PubMed

    Sulzer, James; Dueñas, Julio; Stämpili, Philipp; Hepp-Reymond, Marie-Claude; Kollias, Spyros; Seifritz, Erich; Gassert, Roger

    2013-06-01

    The field of brain-machine interfaces (BMIs) has made great advances in recent years, converting thought to movement, with some of the most successful implementations measuring directly from the motor cortex. However, the ability to record from additional regions of the brain could potentially improve flexibility and robustness of use. In addition, BMIs of the future will benefit from integrating kinesthesia into the control loop. Here, we examine whether changes in passively induced forefinger movement amplitude are represented in different regions than forefinger velocity via a MR compatible robotic manipulandum. Using functional magnetic resonance imaging (fMRI), five healthy participants were exposed to combinations of forefinger movement amplitude and velocity in a factorial design followed by an epoch-based analysis. We found that primary and secondary somatosensory regions were activated, as well as cingulate motor area, putamen and cerebellum, with greater activity from changes in velocity compared to changes in amplitude. This represents the first investigation into whole brain response to parametric changes in passive movement kinematics. In addition to informing BMIs, these results have implications towards neural correlates of robotic rehabilitation.

  16. FMRI evidence of 'mirror' responses to geometric shapes.

    PubMed

    Press, Clare; Catmur, Caroline; Cook, Richard; Widmann, Hannah; Heyes, Cecilia; Bird, Geoffrey

    2012-01-01

    Mirror neurons may be a genetic adaptation for social interaction. Alternatively, the associative hypothesis proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv) and inferior parietal lobule (IPL). Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control.

  17. 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.

  18. Specificity of stimulus-evoked fMRI responses in the mouse: the influence of systemic physiological changes associated with innocuous stimulation under four different anesthetics.

    PubMed

    Schroeter, Aileen; Schlegel, Felix; Seuwen, Aline; Grandjean, Joanes; Rudin, Markus

    2014-07-01

    Functional magnetic resonance (fMRI) in mice has become an attractive tool for mechanistic studies, for characterizing models of human disease, and for evaluation of novel therapies. Yet, controlling the physiological state of mice is challenging, but nevertheless important as changes in cardiovascular parameters might affect the hemodynamic readout which constitutes the basics of the fMRI signal. In contrast to rats, fMRI studies in mice report less robust brain activation of rather widespread character to innocuous sensory stimulation. Anesthesia is known to influence the characteristics of the fMRI signal. To evaluate modulatory effects imposed by the anesthesia on stimulus-evoked fMRI responses, we compared blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) signal changes to electrical hindpaw stimulation using the four commonly used anesthetics isoflurane, medetomidine, propofol and urethane. fMRI measurements were complemented by assessing systemic physiological parameters throughout the experiment. Unilateral stimulation of the hindpaw elicited widespread fMRI responses in the mouse brain displaying a bilateral pattern irrespective of the anesthetic used. Analysis of magnitude and temporal profile of BOLD and CBV signals indicated anesthesia-specific modulation of cerebral hemodynamic responses and differences observed for the four anesthetics could be largely explained by their known effects on animal physiology. Strikingly, independent of the anesthetic used our results reveal that fMRI responses are influenced by stimulus-induced cardiovascular changes, which indicate an arousal response, even to innocuous stimulation. This may mask specific fMRI signal associated to the stimulus. Hence, studying the processing of peripheral input in mice using fMRI techniques constitutes a major challenge and adapted paradigms and/or alternative fMRI readouts should also be considered when studying sensory processing in mice.

  19. 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.

  20. Generalized spike and waves: effect of discharge duration on brain networks as revealed by BOLD fMRI.

    PubMed

    Pugnaghi, Matteo; Carmichael, David W; Vaudano, Anna E; Chaudhary, Umair J; Benuzzi, Francesca; Di Bonaventura, Carlo; Giallonardo, Anna T; Rodionov, Roman; Walker, Matthew C; Duncan, John S; Meletti, Stefano; Lemieux, Louis

    2014-01-01

    In the past decade, the possibility of combining recordings of EEG and functional MRI (EEG-fMRI), has brought a new insight into the brain network underlying generalized spike wave discharges (GSWD). Nevertheless, how GSWD duration influences this network is not fully understood. In this study we aim to investigate whether GSWD duration had a threshold (non-linear) and/or a linear effect on the amplitude of the associated BOLD changes in any brain regions. This could help in elucidating if there is an hemodynamic background supporting the differentiation between interictal and ictal events. We studied a population of 42 patients with idiopathic generalized epilepsies (IGE) who underwent resting-state EEG-fMRI recordings in three centres (London, UK; Modena, Italy; Rome, Italy), applying a parametric analysis of the GSWD duration. Patients were classified as having Childhood Absence epilepsy, Juvenile Absence Epilepsy, or Juvenile Myoclonic Epilepsy. At the population level linear GSWD duration-related BOLD signal changes were found in a network of brain regions: mainly BOLD increase in thalami and cerebral ventricles, and BOLD decrease in posterior cingulate, precuneus and bilateral parietal regions. No region of significant BOLD change was found in the group analysis for the non-linear effect of GSWD duration. To explore the possible effect of both the different IGE sub-syndromes and the different protocols and scanning equipment used in the study, a full-factorial ANOVA design was performed revealing no significant differences. These findings support the idea that the amplitude of the BOLD changes is linearly related to the GSWD duration with no universal threshold effect of spike and wave duration on the brain network supporting this activity.

  1. The BOLD signal and neurovascular coupling in autism.

    PubMed

    Reynell, Clare; Harris, Julia J

    2013-10-01

    BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging) is commonly used to study differences in neuronal activity between human populations. As the BOLD response is an indirect measure of neuronal activity, meaningful interpretation of differences in BOLD responses between groups relies upon a stable relationship existing between neuronal activity and the BOLD response across these groups. However, this relationship can be altered by changes in neurovascular coupling or energy consumption, which would lead to problems in identifying differences in neuronal activity. In this review, we focus on fMRI studies of people with autism, and comparisons that are made of their BOLD responses with those of control groups. We examine neurophysiological differences in autism that may alter neurovascular coupling or energy use, discuss recent studies that have used fMRI to identify differences between participants with autism and control participants, and explore experimental approaches that could help attribute between-group differences in BOLD signals to either neuronal or neurovascular factors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. The BOLD signal and neurovascular coupling in autism

    PubMed Central

    Reynell, Clare; Harris, Julia J.

    2013-01-01

    BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging) is commonly used to study differences in neuronal activity between human populations. As the BOLD response is an indirect measure of neuronal activity, meaningful interpretation of differences in BOLD responses between groups relies upon a stable relationship existing between neuronal activity and the BOLD response across these groups. However, this relationship can be altered by changes in neurovascular coupling or energy consumption, which would lead to problems in identifying differences in neuronal activity. In this review, we focus on fMRI studies of people with autism, and comparisons that are made of their BOLD responses with those of control groups. We examine neurophysiological differences in autism that may alter neurovascular coupling or energy use, discuss recent studies that have used fMRI to identify differences between participants with autism and control participants, and explore experimental approaches that could help attribute between-group differences in BOLD signals to either neuronal or neurovascular factors. PMID:23917518

  3. Neural and vascular variability and the fMRI-BOLD response in normal aging.

    PubMed

    Kannurpatti, Sridhar S; Motes, Michael A; Rypma, Bart; Biswal, Bharat B

    2010-05-01

    Neural, vascular and structural variables contributing to the blood oxygen level-dependent (BOLD) signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (six male and six female; mean age: 24 years; range: 19-27 years) and 12 older healthy subjects (five male and seven female; mean age: 58 years; range: 55-71 years) with no history of head trauma and neurological disease were scanned. Functional magnetic resonance imaging measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold (BH) task. Activation volume and the BOLD response amplitude were estimated for the younger and older at both group and subject levels. Mean activation volume was reduced by 45%, 40% and 38% in the elderly group during the motor, cognitive and BH tasks, respectively, compared to the younger. Reduction in activation volume was substantially higher compared to the reduction in the gray matter volume of 14% in the older compared to the younger. A significantly larger variability in the intersubject BOLD signal change occurred during the motor task, compared to the cognitive task. BH-induced BOLD signal change between subjects was significantly less-variable in the motor task-activated areas in the younger compared to older whereas such a difference between age groups was not observed during the cognitive task. Hemodynamic scaling using the BH signal substantially reduced the BOLD signal variability during the motor task compared to the cognitive task. The results indicate that the origin of the BOLD signal variability between subjects was predominantly vascular during the motor task while being principally a consequence of neural variability during the cognitive task. Thus, in addition to gray matter differences, the type of task performed can have different vascular variability weighting that can influence age-related differences in brain functional response.

  4. Granger causality analysis of fMRI BOLD signals is invariant to hemodynamic convolution but not downsampling.

    PubMed

    Seth, Anil K; Chorley, Paul; Barnett, Lionel C

    2013-01-15

    Granger causality is a method for identifying directed functional connectivity based on time series analysis of precedence and predictability. The method has been applied widely in neuroscience, however its application to functional MRI data has been particularly controversial, largely because of the suspicion that Granger causal inferences might be easily confounded by inter-regional differences in the hemodynamic response function. Here, we show both theoretically and in a range of simulations, that Granger causal inferences are in fact robust to a wide variety of changes in hemodynamic response properties, including notably their time-to-peak. However, when these changes are accompanied by severe downsampling, and/or excessive measurement noise, as is typical for current fMRI data, incorrect inferences can still be drawn. Our results have important implications for the ongoing debate about lag-based analyses of functional connectivity. Our methods, which include detailed spiking neuronal models coupled to biophysically realistic hemodynamic observation models, provide an important 'analysis-agnostic' platform for evaluating functional and effective connectivity methods. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Brain responses to mechanical rectal stimulation in patients with faecal incontinence: an fMRI study.

    PubMed

    Mirbagheri, N; Hatton, S; Ng, K-S; Lagopoulos, J; Gladman, M A

    2017-10-01

    Continence is dependent on anorectal-brain interactions. Consequently, aberrations of the brain-gut axis may be important in the pathophysiology of faecal incontinence (FI) in certain patients. The aim of this study was to assess the feasibility of recording brain responses to rectal mechanical stimulation in patients with FI using functional magnetic resonance imaging (fMRI). A prospective, cohort pilot study was performed to assess brain responses during rectal stimulation in 14 patients [four men, mean (SD) age 62 (15) years]. Blood oxygen level dependent (BOLD) signals were measured by fMRI during rest and mechanical distension, involving random repetitions of isobaric phasic rectal distensions at fixed (15 and 45 mmHg) and variable (10% above sensory perception threshold) pressures. Increases in BOLD signals in response to high pressure rectal distension (45 mmHg) and maximum toleration were observed in the cingulate gyrus, thalamus, insular cortex, inferior frontal gyrus, cerebellum, caudate nucleus, supramarginal gyrus, putamen and amygdala. Additionally, activation of the supplementary motor cortex and caudate nucleus with inconsistent activity in the frontal lobe was observed. This study has demonstrated the feasibility of recording brain responses to rectal mechanical stimulation using fMRI in patients with FI, revealing activity in widespread areas of the brain involved in visceral sensory processing. The observed activity in the supplementary motor cortex and caudate nucleus, with relative paucity of activity in the frontal lobes, warrants investigation in future studies to determine whether aberrations in cerebral processing of rectal stimuli play a role in the pathogenesis of FI. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

  6. 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

  7. BOLD responses related to focal spikes and widespread bilateral synchronous discharges generated in the frontal lobe.

    PubMed

    An, Dongmei; Dubeau, François; Gotman, Jean

    2015-03-01

    To investigate whether specific frontal regions have a tendency to generate widespread bilateral synchronous discharges (WBSDs) and others focal spikes and to determine the regions most involved when WBSDs occur; to assess the relationships between the extent of electroencephalography (EEG) discharges and the extent of metabolic changes measured by EEG/functional magnetic resonance imaging (fMRI). Thirty-seven patients with interictal epileptic discharges (IEDs) with frontocentral predominance underwent EEG/fMRI. Patients were divided into a Focal (20 patients) group with focal frontal spikes and a WBSD group (17 patients). Maps of hemodynamic responses related to IEDs were compared between the two groups. The mean number ± SD of IEDs in the Focal group was 137.5 ± 38.1 and in the WBSD group, 73.5 ± 16.6 (p = 0.07). The volume of hemodynamic responses in the WBSD group was significantly larger than in the Focal group (mean, 243.3 ± 41.1 versus 114.8 ± 27.4 cm(3), p = 0.01). Maximum hemodynamic responses occurred in both groups in the following regions: dorsolateral prefrontal, mesial prefrontal, cingulate, and supplementary motor cortices. Maxima in premotor and motor cortex, frontal operculum, frontopolar, and orbitofrontal regions were found only in the Focal group, and maxima in thalamus and caudate only occurred in the WBSD group. Thalamic responses were significantly more common in the WBSD group (14/17) than in the Focal group (7/20), p = 0.004. Deactivation in the default mode network was significantly more common in the WBSD group (14/17) than in the Focal group (10/20), p = 0.04. The spatial distribution and extent of blood oxygen level-dependent (BOLD) responses correlate well with electrophysiologic changes. Focal frontal spikes and WBSDs are not region specific in the frontal lobe, and the same frontal region can generate focal and generalized discharges. This suggests that widespread discharges reflect widespread epileptogenicity rather than a

  8. Comparison of semantic and episodic memory BOLD fMRI activation in predicting cognitive decline in older adults

    PubMed Central

    Hantke, Nathan; Nielson, Kristy A.; Woodard, John L.; Guidotti Breting, Leslie M.; Butts, Alissa; Seidenberg, Michael; Smith, J. Carson; Durgerian, Sally; Lancaster, Melissa; Matthews, Monica; Sugarman, Michael A.; Rao, Stephen M.

    2013-01-01

    Previous studies suggest that task-activated fMRI can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively “Stable” or “Declining” based on ≥1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with APOE ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R2 = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R2 = .285; C index = .787), whereas the addition of EM did not (R2 = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer’s disease. PMID:23199565

  9. Complex motor task associated with non-linear BOLD responses in cerebro-cortical areas and cerebellum.

    PubMed

    Alahmadi, Adnan A S; Samson, Rebecca S; Gasston, David; Pardini, Matteo; Friston, Karl J; D'Angelo, Egidio; Toosy, Ahmed T; Wheeler-Kingshott, Claudia A M

    2016-06-01

    Previous studies have used fMRI to address the relationship between grip force (GF) applied to an object and BOLD response. However, whilst the majority of these studies showed a linear relationship between GF and neural activity in the contralateral M1 and ipsilateral cerebellum, animal studies have suggested the presence of non-linear components in the GF-neural activity relationship. Here, we present a methodology for assessing non-linearities in the BOLD response to different GF levels, within primary motor as well as sensory and cognitive areas and the cerebellum. To be sensitive to complex forms, we designed a feasible grip task with five GF targets using an event-related visually guided paradigm and studied a cohort of 13 healthy volunteers. Polynomial functions of increasing order were fitted to the data. (1) activated motor areas irrespective of GF; (2) positive higher-order responses in and outside M1, involving premotor, sensory and visual areas and cerebellum; (3) negative correlations with GF, predominantly involving the visual domain. Overall, our results suggest that there are physiologically consistent behaviour patterns in cerebral and cerebellar cortices; for example, we observed the presence of a second-order effect in sensorimotor areas, consistent with an optimum metabolic response at intermediate GF levels, while higher-order behaviour was found in associative and cognitive areas. At higher GF levels, sensory-related cortical areas showed reduced activation, interpretable as a redistribution of the neural activity for more demanding tasks. These results have the potential of opening new avenues for investigating pathological mechanisms of neurological diseases.

  10. 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

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

    PubMed

    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).

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

    PubMed Central

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

    2011-01-01

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

  13. Caffeine dose effect on activation-induced BOLD and CBF responses

    PubMed Central

    Chen, Yufen; Parrish, Todd B.

    2009-01-01

    Caffeine is a popular psychostimulant, typically found in beverages. While low to intermediate doses of caffeine are associated with positive feelings and increased mental performance and alertness, high doses induce negative feelings such as insomnia, anxiety and nervousness. We investigate if this nonlinear dose response is present for caffeine’s effects on functional activation. Twenty-seven healthy subjects were assigned randomly to four different groups: saline, 1mg/kg, 2.5mg/kg and 5mg/kg doses of caffeine. Simultaneous ASL/BOLD timeseries were collected both before and after an intravenous infusion of saline or caffeine and the task-induced CBF and BOLD percent changes were compared. The maximum increase in BOLD response was associated with the intermediate caffeine dose of 2.5mg/kg, which increased BOLD response by 32.2% and 32.5% in motor and visual areas respectively. The maximum increase in CBF response was associated with the highest caffeine dose of 5mg/kg. This difference could be related to different density of A1 and A2A adenosine receptors in the brain. PMID:19289172

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

    PubMed

    Soltysik, David A; Hyde, James S

    2008-06-01

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

  15. High Spatial Resolution Increases the Specificity of Block-Design BOLD fMRI Studies of Overt Vowel Production

    PubMed Central

    Soltysik, David A.; Hyde, James S.

    2008-01-01

    Functional MRI (fMRI) studies of tasks involving orofacial motion, such as speech, are prone to problems related to motion-induced magnetic field variations. Orofacial motion perturbs the static magnetic field, leading to signal changes that correlate with the task and corrupt activation maps with false positives or signal loss. These motion-induced signal changes represent a contraindication for the implementation of fMRI to study the neurophysiology of orofacial motion. An fMRI experiment of a structured, non-semantic vowel production task was performed using four different voxel volumes and three different slice orientations in an attempt to find a set of acquisition parameters leading to activation maps with maximum specificity. Results indicate that the use of small voxel volumes (2×2×3 mm3) yielded a significantly higher percentage of true positive activation compared to the use of larger voxel volumes. Slice orientation did not have as great an impact as spatial resolution, although coronal slices appeared superior at high spatial resolutions. Furthermore, it was found that combining the strategy of high spatial resolution with an optimum task duration and post-processing methods for separating true and false positives greatly improved the specificity of single-subject, block-design fMRI studies of structured, overt vowel production. PMID:18387825

  16. 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.

  17. 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.

  18. 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

  19. Test-retest reliability of evoked BOLD signals from a cognitive-emotive fMRI test battery.

    PubMed

    Plichta, Michael M; Schwarz, Adam J; Grimm, Oliver; Morgen, Katrin; Mier, Daniela; Haddad, Leila; Gerdes, Antje B M; Sauer, Carina; Tost, Heike; Esslinger, Christine; Colman, Peter; Wilson, Frederick; Kirsch, Peter; Meyer-Lindenberg, Andreas

    2012-04-15

    Even more than in cognitive research applications, moving fMRI to the clinic and the drug development process requires the generation of stable and reliable signal changes. The performance characteristics of the fMRI paradigm constrain experimental power and may require different study designs (e.g., crossover vs. parallel groups), yet fMRI reliability characteristics can be strongly dependent on the nature of the fMRI task. The present study investigated both within-subject and group-level reliability of a combined three-task fMRI battery targeting three systems of wide applicability in clinical and cognitive neuroscience: an emotional (face matching), a motivational (monetary reward anticipation) and a cognitive (n-back working memory) task. A group of 25 young, healthy volunteers were scanned twice on a 3T MRI scanner with a mean test-retest interval of 14.6 days. FMRI reliability was quantified using the intraclass correlation coefficient (ICC) applied at three different levels ranging from a global to a localized and fine spatial scale: (1) reliability of group-level activation maps over the whole brain and within targeted regions of interest (ROIs); (2) within-subject reliability of ROI-mean amplitudes and (3) within-subject reliability of individual voxels in the target ROIs. Results showed robust evoked activation of all three tasks in their respective target regions (emotional task=amygdala; motivational task=ventral striatum; cognitive task=right dorsolateral prefrontal cortex and parietal cortices) with high effect sizes (ES) of ROI-mean summary values (ES=1.11-1.44 for the faces task, 0.96-1.43 for the reward task, 0.83-2.58 for the n-back task). Reliability of group level activation was excellent for all three tasks with ICCs of 0.89-0.98 at the whole brain level and 0.66-0.97 within target ROIs. Within-subject reliability of ROI-mean amplitudes across sessions was fair to good for the reward task (ICCs=0.56-0.62) and, dependent on the particular ROI

  20. Bold-Independent Computational Entropy Assesses Functional Donut-Like Structures in Brain fMRI Images

    PubMed Central

    Peters, James F.; Ramanna, Sheela; Tozzi, Arturo; İnan, Ebubekir

    2017-01-01

    We introduce a novel method for the measurement of information level in fMRI (functional Magnetic Resonance Imaging) neural data sets, based on image subdivision in small polygons equipped with different entropic content. We show how this method, called maximal nucleus clustering (MNC), is a novel, fast and inexpensive image-analysis technique, independent from the standard blood-oxygen-level dependent signals. MNC facilitates the objective detection of hidden temporal patterns of entropy/information in zones of fMRI images generally not taken into account by the subjective standpoint of the observer. This approach befits the geometric character of fMRIs. The main purpose of this study is to provide a computable framework for fMRI that not only facilitates analyses, but also provides an easily decipherable visualization of structures. This framework commands attention because it is easily implemented using conventional software systems. In order to evaluate the potential applications of MNC, we looked for the presence of a fourth dimension's distinctive hallmarks in a temporal sequence of 2D images taken during spontaneous brain activity. Indeed, recent findings suggest that several brain activities, such as mind-wandering and memory retrieval, might take place in the functional space of a four dimensional hypersphere, which is a double donut-like structure undetectable in the usual three dimensions. We found that the Rényi entropy is higher in MNC areas than in the surrounding ones, and that these temporal patterns closely resemble the trajectories predicted by the possible presence of a hypersphere in the brain. PMID:28203153

  1. Bold-Independent Computational Entropy Assesses Functional Donut-Like Structures in Brain fMRI Images.

    PubMed

    Peters, James F; Ramanna, Sheela; Tozzi, Arturo; İnan, Ebubekir

    2017-01-01

    We introduce a novel method for the measurement of information level in fMRI (functional Magnetic Resonance Imaging) neural data sets, based on image subdivision in small polygons equipped with different entropic content. We show how this method, called maximal nucleus clustering (MNC), is a novel, fast and inexpensive image-analysis technique, independent from the standard blood-oxygen-level dependent signals. MNC facilitates the objective detection of hidden temporal patterns of entropy/information in zones of fMRI images generally not taken into account by the subjective standpoint of the observer. This approach befits the geometric character of fMRIs. The main purpose of this study is to provide a computable framework for fMRI that not only facilitates analyses, but also provides an easily decipherable visualization of structures. This framework commands attention because it is easily implemented using conventional software systems. In order to evaluate the potential applications of MNC, we looked for the presence of a fourth dimension's distinctive hallmarks in a temporal sequence of 2D images taken during spontaneous brain activity. Indeed, recent findings suggest that several brain activities, such as mind-wandering and memory retrieval, might take place in the functional space of a four dimensional hypersphere, which is a double donut-like structure undetectable in the usual three dimensions. We found that the Rényi entropy is higher in MNC areas than in the surrounding ones, and that these temporal patterns closely resemble the trajectories predicted by the possible presence of a hypersphere in the brain.

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

    PubMed

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

    2013-12-01

    Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway. On this basis, we hypothesized that dietary nitrate (NO3-) could influence the brain's hemodynamic response to neuronal stimulation. In the present study, 20 healthy male participants were given either sodium nitrate (NaNO3) or sodium chloride (NaCl) (saline placebo) in a crossover study and were shown visual stimuli based on the retinotopic characteristics of the visual cortex. Our primary measure of the hemodynamic response was the blood oxygenation level dependent (BOLD) response measured with high-resolution functional magnetic resonance imaging (0.64×0.64×1.8 mm) in the visual cortex. From this response, we made a direct estimate of key parameters characterizing the shape of the BOLD response (i.e. lag and amplitude). During elevated nitrate intake, corresponding to the nitrate content of a large plate of salad, both the hemodynamic lag and the BOLD amplitude decreased significantly (7.0±2% and 7.9±4%, respectively), and the variation across activated voxels of both measures decreased (12.3±4% and 15.3±7%, respectively). The baseline cerebral blood flow was not affected by nitrate. Our experiments demonstrate, for the first time, that dietary nitrate may modulate the local cerebral hemodynamic response to stimuli. A faster and smaller BOLD response, with less variation across local cortex, is consistent with an enhanced hemodynamic coupling during elevated nitrate intake. These findings suggest that dietary patterns, via the nitrate-nitrite-NO pathway, may be a potential way to affect key properties of neurovascular coupling. This could have major clinical implications, which remain to be explored. © 2013 Elsevier Inc. All rights reserved.

  3. Linear increases in BOLD response associated with increasing proportion of incongruent trials across time in a colour Stroop task.

    PubMed

    Mitchell, Rachel L C

    2010-05-01

    Selective attention is popularly assessed with colour Stroop tasks in which participants name the ink colour of colour words, whilst resisting interference from the natural tendency to read the words. Prior studies hinted that the key brain regions (dorsolateral prefrontal (dlPFC) and anterior cingulate cortex (ACC)) may vary their degree of involvement, dependent on attentional demand. This study aimed to determine whether a parametrically varied increase in attentional demand resulted in linearly increased activity in these regions, and/or whether additional regions would be recruited during high attentional demand. Twenty-eight healthy young adults underwent fMRI whilst naming the font colour of colour words. Linear increases in BOLD response were assessed with increasing percentage incongruent trials per block (0, 20, 40, 60, 80, and 100%). Whilst ACC activation increased linearly according to incongruity level, dlPFC activity appeared constant. Together with behavioural evidence of reduced Stroop interference, these data support a load-dependent conflict-related response in ACC, but not dlPFC.

  4. Variability of the coupling of blood flow and oxygen metabolism responses in the brain: a problem for interpreting BOLD studies but potentially a new window on the underlying neural activity

    PubMed Central

    Buxton, Richard B.; Griffeth, Valerie E. M.; Simon, Aaron B.; Moradi, Farshad

    2014-01-01

    Recent studies from our group and others using quantitative fMRI methods have found that variations of the coupling ratio of blood flow (CBF) and oxygen metabolism (CMRO2) responses to a stimulus have a strong effect on the BOLD response. Across a number of studies an empirical pattern is emerging in the way CBF and CMRO2 changes are coupled to neural activation: if the stimulus is modulated to create a stronger response (e.g., increasing stimulus contrast), CBF is modulated more than CMRO2; on the other hand, if the brain state is altered such that the response to the same stimulus is increased (e.g., modulating attention, adaptation, or excitability), CMRO2 is modulated more than CBF. Because CBF and CMRO2 changes conflict in producing BOLD signal changes, this finding has an important implication for conventional BOLD-fMRI studies: the BOLD response exaggerates the effects of stimulus variation but is only weakly sensitive to modulations of the brain state that alter the response to a standard stimulus. A speculative hypothesis is that variability of the coupling ratio of the CBF and CMRO2 responses reflects different proportions of inhibitory and excitatory evoked activity, potentially providing a new window on neural activity in the human brain. PMID:24966808

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

    PubMed Central

    Keller, Johannes; Grön, Georg

    2016-01-01

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

  6. Augmenting atypical antipsychotics with a cognitive enhancer (donepezil) improves regional brain activity in schizophrenia patients: a pilot double-blind placebo controlled BOLD fMRI study.

    PubMed

    Nahas, Ziad; George, Mark S; Horner, Michael D; Markowitz, John S; Li, Xingbao; Lorberbaum, Jeffrey P; Owens, Susan D; McGurk, Susan; DeVane, Lindsay; Risch, S Craig

    2003-06-01

    Cognitive impairments are cardinal features of schizophrenia and predictors of poor vocational and social outcome. Imaging studies with verbal fluency tasks (VFT) lead some to suggest that in schizophrenia, the combination of a failure to deactivate the left temporal lobe and a hypoactive frontal lobe reflects a functional disconnectivity between the left prefrontal cortex and temporal lobe. Others have theorized that an abnormal cingulate gyrus modulates such fronto-temporal connectivity. Thus addition of a cognitive enhancing medication to current antipsychotic therapy might improve functionality of networks necessary in working memory and internal concept generation. To test this hypothesis, we serially measured brain activity in 6 subjects on stable atypical antipsychotics performing a VFT, using BOLD fMRI. Measurements were made at baseline and again after groups were randomized to receive 12 weeks of donepezil (an acetylcholinesterase inhibitor) and placebo in a blind cross-over design. Donepezil addition provided a functional normalization with an increase in left frontal lobe and cingulate activity when compared to placebo and from baseline scans. This pilot study supports the cingulate's role in modulating cognition and neuronal connectivity in schizophrenia.

  7. Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease.

    PubMed

    Kazemifar, Samaneh; Manning, Kathryn Y; Rajakumar, Nagalingam; Gómez, Francisco A; Soddu, Andrea; Borrie, Michael J; Menon, Ravi S; Bartha, Robert

    2017-01-01

    Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid β1-42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD.

  8. Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease

    PubMed Central

    Manning, Kathryn Y.; Rajakumar, Nagalingam; Gómez, Francisco A.; Soddu, Andrea; Borrie, Michael J.

    2017-01-01

    Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid β1–42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD. PMID:28582450

  9. 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.

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

    PubMed

    Bazargani, Negar; Nosratinia, Aria

    2014-07-01

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

  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. Cerebellar lobules and dentate nuclei mirror cortical force-related-BOLD responses: Beyond all (linear) expectations.

    PubMed

    Alahmadi, Adnan A S; Pardini, Matteo; Samson, Rebecca S; Friston, Karl J; Toosy, Ahmed T; D'Angelo, Egidio; Gandini Wheeler-Kingshott, Claudia A M

    2017-02-27

    The relationship between the BOLD response and an applied force was quantified in the cerebellum using a power grip task. To investigate whether the cerebellum responds in an on/off way to motor demands or contributes to motor responses in a parametric fashion, similarly to the cortex, five grip force levels were investigated under visual feedback. Functional MRI data were acquired in 13 healthy volunteers and their responses were analyzed using a cerebellum-optimized pipeline. This allowed us to evaluate, within the cerebellum, voxelwise linear and non-linear associations between cerebellar activations and forces. We showed extensive non-linear activations (with a parametric design), covering the anterior and posterior lobes of the cerebellum with a BOLD-force relationship that is region-dependent. Linear responses were mainly located in the anterior lobe, similarly to the cortex, where linear responses are localized in M1. Complex responses were localized in the posterior lobe, reflecting its key role in attention and executive processing, required during visually guided movement. Given the highly organized responses in the cerebellar cortex, a key question is whether deep cerebellar nuclei show similar parametric effects. We found positive correlations with force in the ipsilateral dentate nucleus and negative correlations on the contralateral side, suggesting a somatotopic organization of the dentate nucleus in line with cerebellar and cortical areas. Our results confirm that there is cerebellar organization involving all grey matter structures that reflect functional segregation in the cortex, where cerebellar lobules and dentate nuclei contribute to complex motor tasks with different BOLD response profiles in relation to the forces. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  13. 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

  14. Comparison of Muscle BOLD Responses to Arterial Occlusion at 3T and 7T

    PubMed Central

    Towse, Theodore F.; Childs, Benjamin T.; Sabin, Shea A.; Bush, Emily C.; Elder, Christopher P.; Damon, Bruce M.

    2014-01-01

    Purpose The purpose of this study was to determine the feasibility of muscle BOLD (mBOLD) imaging at 7T by comparing the changes in R2* of muscle at 3 and 7T in response to a brief period of tourniquet-induced ischemia. Methods Eight subjects (3 male), aged 29.5 ± 6.1 years (mean ± standard deviation, SD), 167.0 ± 10.6 cm tall with a body mass of 62.0 ± 18.0 kg, participated in the study. Subjects reported to the lab on four separate occasions including a habituation session, two MRI scans, and in a subset of subjects, a session during which changes in blood flow and blood oxygenation were quantified using Doppler ultrasound (U/S) and near-infrared spectroscopy (NIRS) respectively. For statistical comparisons between 3T and 7T, R2* rate constants were calculated as R2* = 1/T2*. Results The mean pre-occlusion R2* value was greater at 7T than at 3T (60.16 ± 2.95 vs 35.17 ± 0.35 s−1 respectively, p <0.001). Also, the mean ΔR2*END and ΔR2*POST values were greater for 7T than for 3T (−2.36 ± 0.25 vs. −1.24 ± 0.39 s−1, respectively, Table 1). Conclusion Muscle BOLD contrast at 7T is as much as six-fold greater than at 3T. In addition to providing greater SNR and CNR, 7T mBOLD studies may offer further advantages in the form of greater sensitivity to pathological changes in the muscle microcirculation. PMID:25884888

  15. 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.

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

    PubMed Central

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

    2017-01-01

    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 80 s 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

  17. Prolactin and fMRI response to SKF38393 in the baboon

    PubMed Central

    Miller, Brad; Marks, Lauren A.; Koller, Jonathan M.; Newman, Blake J.; Bretthorst, G. Larry

    2013-01-01

    Background. This study’s goal was to provide dose–response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps (“time course studies”) were performed with three agonists, and the results were used to select promising agonists and to guide design details for the single-dose studies needed to generate dose–response curves. Methods. We studied 6 male baboons (Papio anubis) under low-dose isoflurane anesthesia after i.m. ketamine. Time course studies charted the changes in plasma prolactin levels over time after anesthesia alone or after an intravenous (i.v.) dose of the dopamine D1-like agonists SKF82958 and SKF38393 or the D2-like agonist pramipexole. In the single-dose dopamine agonist studies, one dose of SKF38393 (ranging from 0.0928–9.28 mg/kg, N = 5 animals) or pramipexole (0.00928–0.2 mg/kg, N = 1) was given i.v. during a 40-min blood oxygen level dependent (BOLD) fMRI session, to determine BOLD and plasma prolactin responses to different drug concentrations. BOLD response was quantified as the area under the time-signal curve for the first 15 min after the start of the drug infusion, compared to the linearly predicted signal from the baseline data before drug. The ED50 (estimated dose that produces 50% of the maximal possible response to drug) for SKF38393 was calculated for the serum prolactin response and for phMRI responses in hypothalamus, pituitary, striatum and midbrain. Results. Prolactin rose 2.4- to 12-fold with anesthesia alone, peaking around 50–90 min after ketamine administration

  18. Cortical Response Variation with Different Sound Pressure Levels: A Combined Event-Related Potentials and fMRI Study

    PubMed Central

    Arrubla, Jorge; Warbrick, Tracy; Hitz, Konrad; Wyss, Christine; Boers, Frank; Shah, N. Jon

    2014-01-01

    Introduction Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provides high spatial and temporal resolution. In this study we combined EEG and fMRI to investigate the structures involved in the processing of different sound pressure levels (SPLs). Methods EEG data were recorded simultaneously with fMRI from 16 healthy volunteers using MR compatible devices at 3 T. Tones with different SPLs were delivered to the volunteers and the N1/P2 amplitudes were included as covariates in the fMRI data analysis in order to compare the structures activated with high and low SPLs. Analysis of variance (ANOVA) and ROI analysis were also performed. Additionally, source localisation analysis was performed on the EEG data. Results The integration of averaged ERP parameters into the fMRI analysis showed an extended map of areas exhibiting covariation with the BOLD signal related to the auditory stimuli. The ANOVA and ROI analyses also revealed additional brain areas other than the primary auditory cortex (PAC) which were active with the auditory stimulation at different SPLs. The source localisation analyses showed additional sources apart from the PAC which were active with the high SPLs. Discussion The PAC and the insula play an important role in the processing of different SPLs. In the fMRI analysis, additional activation was found in the anterior cingulate cortex, opercular and orbito-frontal cortices with high SPLs. A strong response of the visual cortex was also found with the high SPLs, suggesting the presence of cross-modal effects. PMID:25279457

  19. Cortical response variation with different sound pressure levels: a combined event-related potentials and FMRI study.

    PubMed

    Neuner, Irene; Kawohl, Wolfram; Arrubla, Jorge; Warbrick, Tracy; Hitz, Konrad; Wyss, Christine; Boers, Frank; Shah, N Jon

    2014-01-01

    Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provides high spatial and temporal resolution. In this study we combined EEG and fMRI to investigate the structures involved in the processing of different sound pressure levels (SPLs). EEG data were recorded simultaneously with fMRI from 16 healthy volunteers using MR compatible devices at 3 T. Tones with different SPLs were delivered to the volunteers and the N1/P2 amplitudes were included as covariates in the fMRI data analysis in order to compare the structures activated with high and low SPLs. Analysis of variance (ANOVA) and ROI analysis were also performed. Additionally, source localisation analysis was performed on the EEG data. The integration of averaged ERP parameters into the fMRI analysis showed an extended map of areas exhibiting covariation with the BOLD signal related to the auditory stimuli. The ANOVA and ROI analyses also revealed additional brain areas other than the primary auditory cortex (PAC) which were active with the auditory stimulation at different SPLs. The source localisation analyses showed additional sources apart from the PAC which were active with the high SPLs. The PAC and the insula play an important role in the processing of different SPLs. In the fMRI analysis, additional activation was found in the anterior cingulate cortex, opercular and orbito-frontal cortices with high SPLs. A strong response of the visual cortex was also found with the high SPLs, suggesting the presence of cross-modal effects.

  20. Gestational Valproate Alters BOLD Activation in Response to Complex Social and Primary Sensory Stimuli

    PubMed Central

    Felix-Ortiz, Ada C.; Febo, Marcelo

    2012-01-01

    Valproic acid (VPA) has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. We hypothesized that midgestational (GD) exposure to VPA will lead to lasting deficits in social behavior and the processing of social stimuli. To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD 12.5. Starting on postnatal day 2 (PND2), animals were examined for physical and behavior abnormalities. Functional MRI studies were carried out after PND60. VPA and control animals were given vehicle or a central infusion of a V1a antagonist 90 minutes before imaging. During imaging sessions, rats were presented with a juvenile test male followed by a primary visual stimulus (2 Hz pulsed light) to examine the effects of prenatal VPA on neural processing. VPA rats showed greater increases in BOLD signal response to the social stimulus compared to controls in the temporal cortex, thalamus, midbrain and the hypothalamus. Blocking the V1a receptor reduced the BOLD response in VPA animals only. Neural responses to the visual stimulus, however, were lower in VPA animals. Blockade with the V1a antagonist did not revert this latter effect. Our data suggest that prenatal VPA affects the processing of social stimuli and perhaps social memory, partly through a mechanism that may involve vasopressin V1a neurotransmission. PMID:22615973

  1. A two-stage cascade model of BOLD responses in human visual cortex.

    PubMed

    Kay, Kendrick N; Winawer, Jonathan; Rokem, Ariel; Mezer, Aviv; Wandell, Brian A

    2013-01-01

    Visual neuroscientists have discovered fundamental properties of neural representation through careful analysis of responses to controlled stimuli. Typically, different properties are studied and modeled separately. To integrate our knowledge, it is necessary to build general models that begin with an input image and predict responses to a wide range of stimuli. In this study, we develop a model that accepts an arbitrary band-pass grayscale image as input and predicts blood oxygenation level dependent (BOLD) responses in early visual cortex as output. The model has a cascade architecture, consisting of two stages of linear and nonlinear operations. The first stage involves well-established computations-local oriented filters and divisive normalization-whereas the second stage involves novel computations-compressive spatial summation (a form of normalization) and a variance-like nonlinearity that generates selectivity for second-order contrast. The parameters of the model, which are estimated from BOLD data, vary systematically across visual field maps: compared to primary visual cortex, extrastriate maps generally have larger receptive field size, stronger levels of normalization, and increased selectivity for second-order contrast. Our results provide insight into how stimuli are encoded and transformed in successive stages of visual processing.

  2. 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

  3. 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. Copyright © 2016 the American Physiological Society.

  4. Cerebellar lobules and dentate nuclei mirror cortical force‐related‐BOLD responses: Beyond all (linear) expectations

    PubMed Central

    Pardini, Matteo; Samson, Rebecca S.; Friston, Karl J.; Toosy, Ahmed T.; D'Angelo, Egidio; Gandini Wheeler‐Kingshott, Claudia A.M.

    2017-01-01

    Abstract The relationship between the BOLD response and an applied force was quantified in the cerebellum using a power grip task. To investigate whether the cerebellum responds in an on/off way to motor demands or contributes to motor responses in a parametric fashion, similarly to the cortex, five grip force levels were investigated under visual feedback. Functional MRI data were acquired in 13 healthy volunteers and their responses were analyzed using a cerebellum‐optimized pipeline. This allowed us to evaluate, within the cerebellum, voxelwise linear and non‐linear associations between cerebellar activations and forces. We showed extensive non‐linear activations (with a parametric design), covering the anterior and posterior lobes of the cerebellum with a BOLD‐force relationship that is region‐dependent. Linear responses were mainly located in the anterior lobe, similarly to the cortex, where linear responses are localized in M1. Complex responses were localized in the posterior lobe, reflecting its key role in attention and executive processing, required during visually guided movement. Given the highly organized responses in the cerebellar cortex, a key question is whether deep cerebellar nuclei show similar parametric effects. We found positive correlations with force in the ipsilateral dentate nucleus and negative correlations on the contralateral side, suggesting a somatotopic organization of the dentate nucleus in line with cerebellar and cortical areas. Our results confirm that there is cerebellar organization involving all grey matter structures that reflect functional segregation in the cortex, where cerebellar lobules and dentate nuclei contribute to complex motor tasks with different BOLD response profiles in relation to the forces. Hum Brain Mapp 38:2566–2579, 2017. © 2017 Wiley Periodicals, Inc. PMID:28240422

  5. Negative cerebral blood volume fMRI response coupled with Ca²⁺-dependent brain activity in a dopaminergic road map of nociception.

    PubMed

    Hsu, Yi-Hua; Chang, Chen; Chen, Chiao-Chi V

    2014-04-15

    Decreased cerebral blood volume/flow (CBV/CBF) contributes to negative blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signals. But it is still strongly debated whether these negative BOLD or CBV/CBF signals are indicative of decreased or increased neuronal activity. The fidelity of Ca(2+) signals in reflecting neuronal excitation is well documented. However, the roles of Ca(2+) signals and Ca(2+)-dependent activity in negative fMRI signals have never been explored; an understanding of this is essential to unraveling the underlying mechanisms and correctly interpreting the hemodynamic response of interest. The present study utilized a nociception-induced negative CBV fMRI response as a model. Ca(2+) signals were investigated in vivo using Mn(2+)-enhanced MRI (MEMRI), and the downstream Ca(2+)-dependent signaling was investigated using phosphorylated cAMP response-element-binding (pCREB) immunohistology. The results showed that nociceptive stimulation led to (1) striatal CBV decreases, (2) Ca(2+) increases via the nigrostriatal pathway, and (3) substantial expression of pCREB in substantia nigra dopaminergic neurons and striatal neurons. Interestingly, the striatal negative fMRI response was abolished by blocking substantia nigra activity but was not affected by blocking the striatal activity. This suggests the importance of input activity other than output in triggering the negative CBV signals. These findings indicate that the striatal negative CBV fMRI signals are associated with Ca(2+) increases and Ca(2+)-dependent signaling along the nigrostriatal pathway. The obtained data reveal a new brain road map in response to nociceptive stimulation of hemodynamic changes in association with Ca(2+) signals within the dopaminergic system.

  6. Replicability and heterogeneity of awake unrestrained canine FMRI responses.

    PubMed

    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.

  7. Pharmacological MRI of the choroid and retina: blood flow and BOLD responses during nitroprusside infusion.

    PubMed

    Shih, Yen-Yu I; Li, Guang; Muir, Eric R; De La Garza, Bryan H; Kiel, Jeffrey W; Duong, Timothy Q

    2012-10-01

    Nitroprusside, a vasodilatory nitric oxide donor, is clinically used during vascular surgery and to lower blood pressure in acute hypertension. This article reports a novel application of blood flow (BF) and blood oxygenation level dependent (BOLD) MRI on an 11.7T scanner to image the rat chorioretinal BF and BOLD changes associated with graded nitroprusside infusion. At low doses (1 or 2 μg/kg/min), nitroprusside increased BF as expected but decreased BOLD signals, showing an intriguing BF-BOLD uncoupling. At high doses (3-5 μg/kg/min), nitroprusside decreased BF and markedly decreased BOLD signals. To our knowledge, this is the first pharmacological MRI application of the retina. This approach has potential to open up new avenues to study the drug-related hemodynamic functions and to evaluate the effects of novel therapeutic interventions on BOLD and BF in the normal and diseased retinas. Copyright © 2011 Wiley Periodicals, Inc.

  8. Testing the physiological plausibility of conflicting psychological models of response inhibition: A forward inference fMRI study.

    PubMed

    Criaud, Marion; Longcamp, Marieke; Anton, Jean-Luc; Nazarian, Bruno; Roth, Muriel; Sescousse, Guillaume; Strafella, Antonio P; Ballanger, Bénédicte; Boulinguez, Philippe

    2017-08-30

    The neural mechanisms underlying response inhibition and related disorders are unclear and controversial for several reasons. First, it is a major challenge to assess the psychological bases of behaviour, and ultimately brain-behaviour relationships, of a function which is precisely intended to suppress overt measurable behaviours. Second, response inhibition is difficult to disentangle from other parallel processes involved in more general aspects of cognitive control. Consequently, different psychological and anatomo-functional models coexist, which often appear in conflict with each other even though they are not necessarily mutually exclusive. The standard model of response inhibition in go/no-go tasks assumes that inhibitory processes are reactively and selectively triggered by the stimulus that participants must refrain from reacting to. Recent alternative models suggest that action restraint could instead rely on reactive but non-selective mechanisms (all automatic responses are automatically inhibited in uncertain contexts) or on proactive and non-selective mechanisms (a gating function by which reaction to any stimulus is prevented in anticipation of stimulation when the situation is unpredictable). Here, we assessed the physiological plausibility of these different models by testing their respective predictions regarding event-related BOLD modulations (forward inference using fMRI). We set up a single fMRI design which allowed for us to record simultaneously the different possible forms of inhibition while limiting confounds between response inhibition and parallel cognitive processes. We found BOLD dynamics consistent with non-selective models. These results provide new theoretical and methodological lines of inquiry for the study of basic functions involved in behavioural control and related disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 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

  10. Separating neural and vascular effects of caffeine using simultaneous EEG–FMRI: Differential effects of caffeine on cognitive and sensorimotor brain responses

    PubMed Central

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

    2012-01-01

    The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A1 and A2A 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

  11. 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.

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

    PubMed

    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

    2015-06-30

    Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex.

  13. Pharmacological fMRI--challenges in analysing drug-induced single-event BOLD responses.

    PubMed

    Pohlmann, Andreas; Barjat, Hervé; Tilling, Lorna C; James, Michael F

    2007-01-01

    The interest in BOLD contrast based phMRI is likely to increase in the coming years, but detecting a direct modulation of regional brain activity by drugs presents a challenging problem. Based on in-vivo MRI and simulations we highlight some of the issues in detecting especially small BOLD signals in rat phMRI experiments.

  14. Failure to modulate neural response to increased task demand in mild Alzheimer's disease: fMRI study of visuospatial processing.

    PubMed

    Vannini, Patrizia; Lehmann, Christoph; Dierks, Thomas; Jann, Kay; Viitanen, Matti; Wahlund, Lars-Olof; Almkvist, Ove

    2008-09-01

    Alzheimer's disease (AD) is characterized by disturbances of visuospatial cognition. Given that these impairments are closely related to metabolic and neuropathological changes, our study aimed to investigate the functional competency of brain regions in the visuospatial networks responsible for early clinical symptoms in AD using event-related functional magnetic resonance imaging (fMRI). Participants (13AD patients with mild symptoms and 13 age- and education-matched controls) performed an angle discrimination task with varying task demand. Using a novel approach that modeled the dependency of the blood oxygenation level-dependent (BOLD) signal on the subject's reaction time allowed us to investigate task demand-dependent signal changes between the groups. Both groups demonstrated overlapping neural networks engaged in angle discrimination, including the parieto-occipital and frontal regions. In several network regions, AD patients showed a significantly weaker and sometimes no BOLD signal due to increased task demand compared with controls, demonstrating failure to modulate the neural response to increased task demand. A general task demand-independent increase of activation in AD patients compared with controls was found in right middle temporal gyrus. This latter finding may indicate an attempt to compensate for dysfunctional areas in the dorsal visual pathway. These results confirm deficits in visuospatial abilities, which occur early in AD, and offer new insights into the neural mechanisms underlying this impairment.

  15. Spatial Nonuniformity of the Resting CBF and BOLD Responses to Sevoflurane: In Vivo Study of Normal Human Subjects With Magnetic Resonance Imaging

    PubMed Central

    Qiu, Maolin; Ramani, Ramachandran; Swetye, Michael; Constable, Robert Todd

    2009-01-01

    Pulsed arterial spin labeling magnetic resonance imaging (MRI) was performed to investigate the local coupling between resting regional cerebral blood flow (rCBF) and BOLD (blood oxygen level dependent) signal changes in 22 normal human subjects during the administration of 0.25 MAC (minimum alveolar concentration) sevoflurane. Two states were compared with subjects at rest: anesthesia and no-anesthesia. Regions of both significantly increased and decreased resting-state rCBF were observed. Increases were limited primarily to subcortical structures and insula, whereas, decreases were observed primarily in neocortical regions. No significant change was found in global CBF (gCBF). By simultaneously measuring rCBF and BOLD, region-specific anesthetic effects on the coupling between rCBF and BOLD were identified. Multiple comparisons of the agent-induced rCBF and BOLD changes demonstrated significant (P < 0.05) spatial variability in rCBF–BOLD coupling. The slope of the linear regression line for AC, where rCBF was increased by sevoflurane, was markedly smaller than the slope for those ROIs where rCBF was decreased by sevoflurane, indicating a bigger change in BOLD per unit change in rCBF in regions where rCBF was increased by sevoflurane. These results suggest that it would be inaccurate to use a global quantitative model to describe coupling across all brain regions and in all anesthesia conditions. The observed spatial nonuniformity of rCBF and BOLD signal changes suggests that any interpretation of BOLD fMRI data in the presence of an anesthetic requires consideration of these insights. PMID:17948882

  16. fMRI Evidence of ‘Mirror’ Responses to Geometric Shapes

    PubMed Central

    Press, Clare; Catmur, Caroline; Cook, Richard; Widmann, Hannah; Heyes, Cecilia; Bird, Geoffrey

    2012-01-01

    Mirror neurons may be a genetic adaptation for social interaction [1]. Alternatively, the associative hypothesis [2], [3] proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv) and inferior parietal lobule (IPL). Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control. PMID:23251653

  17. Large enhancement of perfusion contribution on fMRI signal

    PubMed Central

    Wang, Xiao; Zhu, Xiao-Hong; Zhang, Yi; Chen, Wei

    2012-01-01

    The perfusion contribution to the total functional magnetic resonance imaging (fMRI) signal was investigated using a rat model with mild hypercapnia at 9.4 T, and human subjects with visual stimulation at 4 T. It was found that the total fMRI signal change could be approximated as a linear superposition of ‘true' blood oxygenation level-dependent (BOLD; T2/T2*) effect and the blood flow-related (T1) effect. The latter effect was significantly enhanced by using short repetition time and large radiofrequency pulse flip angle and became comparable to the ‘true' BOLD signal in response to a mild hypercapnia in the rat brain, resulting in an improved contrast-to-noise ratio (CNR). Bipolar diffusion gradients suppressed the intravascular signals but had no significant effect on the flow-related signal. Similar results of enhanced fMRI signal were observed in the human study. The overall results suggest that the observed flow-related signal enhancement is likely originated from perfusion, and this enhancement can improve CNR and the spatial specificity for mapping brain activity and physiology changes. The nature of mixed BOLD and perfusion-related contributions in the total fMRI signal also has implication on BOLD quantification, in particular, the BOLD calibration model commonly used to estimate the change of cerebral metabolic rate of oxygen. PMID:22395206

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

    PubMed Central

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

    2012-01-01

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

  19. Audiovisual synchrony enhances BOLD responses in a brain network including multisensory STS while also enhancing target-detection performance for both modalities

    PubMed Central

    Marchant, Jennifer L; Ruff, Christian C; Driver, Jon

    2012-01-01

    The brain seeks to combine related inputs from different senses (e.g., hearing and vision), via multisensory integration. Temporal information can indicate whether stimuli in different senses are related or not. A recent human fMRI study (Noesselt et al. [2007]: J Neurosci 27:11431–11441) used auditory and visual trains of beeps and flashes with erratic timing, manipulating whether auditory and visual trains were synchronous or unrelated in temporal pattern. A region of superior temporal sulcus (STS) showed higher BOLD signal for the synchronous condition. But this could not be related to performance, and it remained unclear if the erratic, unpredictable nature of the stimulus trains was important. Here we compared synchronous audiovisual trains to asynchronous trains, while using a behavioral task requiring detection of higher-intensity target events in either modality. We further varied whether the stimulus trains had predictable temporal pattern or not. Synchrony (versus lag) between auditory and visual trains enhanced behavioral sensitivity (d') to intensity targets in either modality, regardless of predictable versus unpredictable patterning. The analogous contrast in fMRI revealed BOLD increases in several brain areas, including the left STS region reported by Noesselt et al. [2007: J Neurosci 27:11431–11441]. The synchrony effect on BOLD here correlated with the subject-by-subject impact on performance. Predictability of temporal pattern did not affect target detection performance or STS activity, but did lead to an interaction with audiovisual synchrony for BOLD in inferior parietal cortex. PMID:21953980

  20. 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

  1. 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

    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.

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

    PubMed Central

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

    2015-01-01

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

  3. 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…

  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. The history and role of long duration stimulation in fMRI.

    PubMed

    Krueger, Gunnar; Granziera, Cristina

    2012-08-15

    During the past 20 years, BOLD fMRI has developed towards a central and fundamental tool in neuroscience. It has been shown that the BOLD response provides an indicator of neuronal activity in the brain. Consequently, for an accurate interpretation of findings in BOLD MRI experiments and to draw meaningful conclusions about the temporal evolution of neural events, a deep understanding of the nature of the BOLD contrast has become of essential importance. Since the dynamics of the major direct determinants of the BOLD signal (CBF, CBV and CMRO(2)) range between seconds and minutes, long duration stimulation was an early key strategy needed to study and understand the BOLD characteristics. This paper summarizes and discusses the thoughts and rationales of the long duration stimulation studies. Copyright © 2012. Published by Elsevier Inc.

  6. 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.

  7. 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

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

    PubMed

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

    2014-07-01

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

  9. 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

  10. Nonlinear estimation of the BOLD signal.

    PubMed

    Johnston, Leigh A; Duff, Eugene; Mareels, Iven; Egan, Gary F

    2008-04-01

    Signal variations in functional Magnetic Resonance Imaging experiments essentially reflect the vascular system response to increased demand for oxygen caused by neuronal activity, termed the blood oxygenation level dependent (BOLD) effect. The most comprehensive model to date of the BOLD signal is formulated as a mixed continuous-discrete-time system of nonlinear stochastic differential equations. Previous approaches to the analysis of this system have been based on linearised approximations of the dynamics, which are limited in their ability to capture the inherent nonlinearities in the physiological system. In this paper we present a nonlinear filtering method for simultaneous estimation of the hidden physiological states and the system parameters, based on an iterative coordinate descent framework. State estimates of the cerebral blood flow, cerebral blood volume and deoxyhaemoglobin content are determined using a particle filter, demonstrated via simulation to be accurate, robust and efficient in comparison to linearisation-based techniques. The adaptive state and parameter estimation algorithm generates physiologically reasonable parameter estimates for experimental fMRI data. It is anticipated that signal processing techniques for modelling and estimation will become increasingly important in fMRI analyses as limitations of linear and linearised modelling are reached.

  11. A general analysis of calibrated BOLD methodology for measuring CMRO2 responses: comparison of a new approach with existing methods.

    PubMed

    Blockley, Nicholas P; Griffeth, Valerie E M; Buxton, Richard B

    2012-03-01

    The amplitude of the BOLD response to a stimulus is not only determined by changes in cerebral blood flow (CBF) and oxygen metabolism (CMRO(2)), but also by baseline physiological parameters such as haematocrit, oxygen extraction fraction (OEF) and blood volume. The calibrated BOLD approach aims to account for this physiological variation by performing an additional calibration scan. This calibration typically consists of a hypercapnia or hyperoxia respiratory challenge, although we propose that a measurement of the reversible transverse relaxation rate, R(2)', might also be used. A detailed model of the BOLD effect was used to simulate each of the calibration experiments, as well as the activation experiment, whilst varying a number of physiological parameters associated with the baseline state and response to activation. The effectiveness of the different calibration methods was considered by testing whether the BOLD response to activation scaled by the calibration parameter combined with the measured CBF provides sufficient information to reliably distinguish different levels of CMRO(2) response despite underlying physiological variability. In addition the effect of inaccuracies in the underlying assumptions of each technique were tested, e.g. isometabolism during hypercapnia. The three primary findings of the study were: 1) The new calibration method based on R(2)' worked reasonably well, although not as well as the ideal hypercapnia method; 2) The hyperoxia calibration method was significantly worse because baseline haematocrit and OEF must be assumed, and these physiological parameters have a significant effect on the measurements; and 3) the venous blood volume change with activation is an important confounding variable for all of the methods, with the hypercapnia method being the most robust when this is uncertain.

  12. A general analysis of calibrated BOLD methodology for measuring CMRO2 responses: comparison of a new approach with existing methods

    PubMed Central

    Blockley, Nicholas P.; Griffeth, Valerie E. M.; Buxton, Richard B.

    2011-01-01

    The amplitude of the BOLD response to a stimulus is not only determined by changes in cerebral blood flow (CBF) and oxygen metabolism (CMRO2), but also by baseline physiological parameters such as haematocrit, oxygen extraction fraction (OEF) and blood volume. The calibrated BOLD approach aims to account for this physiological variation by performing an additional calibration scan. This calibration typically consists of a hypercapnia or hyperoxia respiratory challenge, although we propose that a measurement of the reversible transverse relaxation rate, R2′, might also be used. A detailed model of the BOLD effect was used to simulate each of the calibration experiments, as well as the activation experiment, whilst varying a number of physiological parameters associated with the baseline state and response to activation. The effectiveness of the different calibration methods was considered by testing whether the BOLD response to activation scaled by the calibration parameter combined with the measured CBF provides sufficient information to reliably distinguish different levels of CMRO2 response despite underlying physiological variability. In addition the effect of inaccuracies in the underlying assumptions of each technique were tested, e.g. isometabolism during hypercapnia. The three primary findings of the study were: 1) The new calibration method based on R2′ worked reasonably well, although not as well as the ideal hypercapnia method; 2) The hyperoxia calibration method was significantly worse because baseline haematocrit and OEF must be assumed, and these physiological parameters have a significant effect on the measurements; and 3) the venous blood volume change with activation is an important confounding variable for all of the methods, with the hypercapnia method being the most robust when this is uncertain. PMID:22155329

  13. Effect of tolperisone on the resting brain and on evoked responses, an phMRI BOLD study.

    PubMed

    Kocsis, Pál; Gajári, Dávid; Deli, Levente; Gőcze, Krisztina Zsedrovitsné; Pozsgay, Zsófia; Tihanyi, Károly

    2013-10-01

    Tolperisone is a voltage gated sodium channel blocker, centrally acting muscle relaxant drug, with a very advantageous side effect profile. Like other sodium channel blockers, it has weak affinity to the resting state and high affinity to the open/inactivated state of the channel. In this paper, its effect on BOLD responses in rat brain were elucidated both on the resting brain and paw stimulation evoked BOLD responses. Tolperisone did not exert any visible effect on resting brain, but strongly inhibited the paw stimulation evoked BOLD responses, showing somewhat higher efficacy in brain areas involved in pain sensation. This finding is in a good agreement with its sodium channel blocking profile. In the resting brain, most of the channels are in resting state. Electric train stimuli of the paw results in over activated neurons, where most sodium channels are in open or inactivated state. These data suggest that the very advantageous profile of tolperisone can be explained by its selective action on open or inactivated sodium channels of over-activated neurons in various brain regions rather than by a selective effect in the spinal cord as suggested previously.

  14. 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

  15. Post-contractile BOLD contrast in skeletal muscle at 7 T reveals inter-individual heterogeneity in the physiological responses to muscle contraction.

    PubMed

    Towse, Theodore F; Elder, Christopher P; Bush, Emily C; Klockenkemper, Samuel W; Bullock, Jared T; Dortch, Richard D; Damon, Bruce M

    2016-12-01

    Muscle blood oxygenation-level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre-contraction signal intensity were observed in the soleus muscle. We observed considerable inter-subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (TR : 1000 and 2500 ms) to determine the potential of T1 -related inflow effects on the magnitude of the post-contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two TR values (3.8 ± 0.9 versus 4.0 ± 0.6% for TR  = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post-contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction.

  16. 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.

  17. BOLD Granger causality reflects vascular anatomy.

    PubMed

    Webb, J Taylor; Ferguson, Michael A; Nielsen, Jared A; Anderson, Jeffrey S

    2013-01-01

    A number of studies have tried to exploit subtle phase differences in BOLD time series to resolve the order of sequential activation of brain regions, or more generally the ability of signal in one region to predict subsequent signal in another region. More recently, such lag-based measures have been applied to investigate directed functional connectivity, although this application has been controversial. We attempted to use large publicly available datasets (FCON 1000, ADHD 200, Human Connectome Project) to determine whether consistent spatial patterns of Granger Causality are observed in typical fMRI data. For BOLD datasets from 1,240 typically developing subjects ages 7-40, we measured Granger causality between time series for every pair of 7,266 spherical ROIs covering the gray matter and 264 seed ROIs at hubs of the brain's functional network architecture. Granger causality estimates were strongly reproducible for connections in a test and replication sample (n=620 subjects for each group), as well as in data from a single subject scanned repeatedly, both during resting and passive video viewing. The same effect was even stronger in high temporal resolution fMRI data from the Human Connectome Project, and was observed independently in data collected during performance of 7 task paradigms. The spatial distribution of Granger causality reflected vascular anatomy with a progression from Granger causality sources, in Circle of Willis arterial inflow distributions, to sinks, near large venous vascular structures such as dural venous sinuses and at the periphery of the brain. Attempts to resolve BOLD phase differences with Granger causality should consider the possibility of reproducible vascular confounds, a problem that is independent of the known regional variability of the hemodynamic response.

  18. BOLD Granger Causality Reflects Vascular Anatomy

    PubMed Central

    Webb, J. Taylor; Ferguson, Michael A.; Nielsen, Jared A.; Anderson, Jeffrey S.

    2013-01-01

    A number of studies have tried to exploit subtle phase differences in BOLD time series to resolve the order of sequential activation of brain regions, or more generally the ability of signal in one region to predict subsequent signal in another region. More recently, such lag-based measures have been applied to investigate directed functional connectivity, although this application has been controversial. We attempted to use large publicly available datasets (FCON 1000, ADHD 200, Human Connectome Project) to determine whether consistent spatial patterns of Granger Causality are observed in typical fMRI data. For BOLD datasets from 1,240 typically developing subjects ages 7–40, we measured Granger causality between time series for every pair of 7,266 spherical ROIs covering the gray matter and 264 seed ROIs at hubs of the brain’s functional network architecture. Granger causality estimates were strongly reproducible for connections in a test and replication sample (n=620 subjects for each group), as well as in data from a single subject scanned repeatedly, both during resting and passive video viewing. The same effect was even stronger in high temporal resolution fMRI data from the Human Connectome Project, and was observed independently in data collected during performance of 7 task paradigms. The spatial distribution of Granger causality reflected vascular anatomy with a progression from Granger causality sources, in Circle of Willis arterial inflow distributions, to sinks, near large venous vascular structures such as dural venous sinuses and at the periphery of the brain. Attempts to resolve BOLD phase differences with Granger causality should consider the possibility of reproducible vascular confounds, a problem that is independent of the known regional variability of the hemodynamic response. PMID:24349569

  19. Altered emotional and BOLD responses to negative, positive and ambiguous performance feedback in OCD.

    PubMed

    Becker, Michael P I; Nitsch, Alexander M; Schlösser, Ralf; Koch, Kathrin; Schachtzabel, Claudia; Wagner, Gerd; Miltner, Wolfgang H R; Straube, Thomas

    2014-08-01

    While abnormal processing of performance feedback has been associated with obsessive-compulsive disorder (OCD), neural responses to different kinds of feedback information, especially to ambiguous feedback are widely unknown. Using fMRI and a performance adaptive time-estimation task, we acquired blood oxygenation level-dependant responses and emotional ratings to positive, negative and ambiguous performance feedback in patients and healthy controls. Negative and ambiguous feedback led to increased levels of anxiety, guilt and shame in patients. Both negative and ambiguous feedback, as compared to positive feedback, induced increased activation of the insular cortex in patients. Furthermore, patients showed no differential activation to negative feedback in the putamen and to ambiguous feedback in the ventromedial prefrontal cortex (VMPFC). Finally, negative feedback induced increased activation in the midcingulate cortex in patients compared to controls. Findings indicate that both negative and ambiguous performance feedbacks are associated with abnormal negative emotions and altered brain activation, in particular increased insula activation, while activation in the putamen and VMPFC does not differentiate between feedback types in OCD patients. This suggests a parallel pattern of increased and decreased neural sensitivity to different kinds of feedback information and a general emotional hyperresponsivity to negative and ambiguous performance feedback in OCD. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. A nonlinear BOLD model accounting for refractory effect by applying the longitudinal relaxation in NMR to the linear BOLD model.

    PubMed

    Jung, Kwan-Jin

    2009-09-01

    A mathematical model to regress the nonlinear blood oxygen level-dependent (BOLD) fMRI signal has been developed by incorporating the refractory effect into the linear BOLD model of the biphasic gamma variate function. The refractory effect was modeled as a relaxation of two separate BOLD capacities corresponding to the biphasic components of the BOLD signal in analogy with longitudinal relaxation of magnetization in NMR. When tested with the published fMRI data of finger tapping, the nonlinear BOLD model with the refractory effect reproduced the nonlinear BOLD effects such as reduced poststimulus undershoot and saddle pattern in a prolonged stimulation as well as the reduced BOLD signal for repetitive stimulation.

  1. Blood oxygenation level-dependent (BOLD) functional MRI of visual stimulation in the rat retina at 11.7 T.

    PubMed

    De La Garza, Bryan H; Muir, Eric R; Li, Guang; Shih, Yen-Yu I; Duong, Timothy Q

    2011-02-01

    Although optically based imaging techniques provide valuable functional and physiological information of the retina, they are mostly limited to the probing of the retinal surface and require an unobstructed light path. MRI, in contrast, could offer physiological and functional data without depth limitation. Blood oxygenation level-dependent functional MRI (BOLD fMRI) of the thin rat retina is, however, challenging because of the need for high spatial resolution, and the potential presence of eye movement and susceptibility artifacts. This study reports a novel application of high-resolution (111 × 111 × 1000 µm(3)) BOLD fMRI of visual stimulation in the anesthetized rat retina at 11.7 T. A high-field MRI scanner was utilized to improve the signal-to-noise ratio, spatial resolution and BOLD sensitivity. Visual stimuli (8 Hz diffuse achromatic light) robustly increased BOLD responses in the retina [5.0 ± 0.8% from activated pixels and 3.1 ± 1.1% from the whole-retina region of interest (mean ± SD), n = 12 trials on six rats, p < 0.05 compared with baseline]. Some activated pixels were detected surrounding the pupil and ciliary muscle because of accommodation reflex to visual stimuli, and were reduced with atropine and phenylephrine eye drops. BOLD fMRI scans without visual stimulations showed no significantly activated pixels (whole-retina BOLD changes were 0.08 ± 0.34%, n = 6 trials on five rats, not statistically different from baseline, p > 0.05). BOLD fMRI of visual stimulation has the potential to provide clinically relevant data to probe hemodynamic neurovascular coupling and dysfunction of the retina with depth resolution. Copyright © 2010 John Wiley & Sons, Ltd.

  2. Analysis of oxygen metabolism implies a neural origin for the negative BOLD response in human visual cortex

    PubMed Central

    Pasley, Brian N.; Inglis, Ben A.; Freeman, Ralph D.

    2007-01-01

    The sustained negative blood oxygenation level-dependent (BOLD) response in functional MRI is observed universally, but its interpretation is controversial. The origin of the negative response is of fundamental importance because it could provide a measurement of neural deactivation. However, a substantial component of the negative response may be due to a non-neural hemodynamic artifact. To distinguish these possibilities, we have measured evoked BOLD, cerebral blood flow (CBF), and oxygen metabolism responses to a fixed visual stimulus from two different baseline conditions. One is a normal resting baseline and the other is a lower baseline induced by a sustained negative response. For both baseline conditions, CBF and oxygen metabolism responses reach the same peak amplitude. Consequently, evoked responses from the negative baseline are larger than those from the resting baseline. The larger metabolic response from negative baseline presumably reflects a greater neural response that is required to reach the same peak amplitude as that from resting baseline. Furthermore, the ratio of CBF to oxygen metabolism remains approximately the same from both baseline states (∼2:1). This tight coupling between hemodynamic and metabolic components implies that the magnitude of any hemodynamic artifact is inconsequential. We conclude that the negative response is a functionally significant index of neural deactivation in early visual cortex. PMID:17113313

  3. Analysis of oxygen metabolism implies a neural origin for the negative BOLD response in human visual cortex.

    PubMed

    Pasley, Brian N; Inglis, Ben A; Freeman, Ralph D

    2007-06-01

    The sustained negative blood oxygenation level-dependent (BOLD) response in functional MRI is observed universally, but its interpretation is controversial. The origin of the negative response is of fundamental importance because it could provide a measurement of neural deactivation. However, a substantial component of the negative response may be due to a non-neural hemodynamic artifact. To distinguish these possibilities, we have measured evoked BOLD, cerebral blood flow (CBF), and oxygen metabolism responses to a fixed visual stimulus from two different baseline conditions. One is a normal resting baseline, and the other is a lower baseline induced by a sustained negative response. For both baseline conditions, CBF and oxygen metabolism responses reach the same peak amplitude. Consequently, evoked responses from the negative baseline are larger than those from the resting baseline. The larger metabolic response from negative baseline presumably reflects a greater neural response that is required to reach the same peak amplitude as that from resting baseline. Furthermore, the ratio of CBF to oxygen metabolism remains approximately the same from both baseline states (approximately 2:1). This tight coupling between hemodynamic and metabolic components implies that the magnitude of any hemodynamic artifact is inconsequential. We conclude that the negative response is a functionally significant index of neural deactivation in early visual cortex.

  4. 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…

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

    PubMed Central

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

    2015-01-01

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

  6. Effects of Risk Genes on BOLD Activation in Presymptomatic Carriers of Familial Alzheimer's Disease Mutations during a Novelty Encoding Task

    PubMed Central

    Medina, Luis D.; Braskie, Meredith; Rodriguez-Agudelo, Yaneth; Geschwind, Daniel H.; Macias-Islas, Miguel A.; Cummings, Jeffrey L.; Bookheimer, Susan

    2011-01-01

    Prior functional magnetic resonance imaging (fMRI) studies have found increased activity-related blood oxygen level–dependent (BOLD) signal in cognitively normal persons at genetic risk for Alzheimer's disease (AD). This has been interpreted as a compensatory response to incipient AD pathology. We studied the effects of fully penetrant familial Alzheimer's disease (FAD) mutations and apolipoprotein E (APOE) genotype on BOLD fMRI during a novelty encoding task in presymptomatic subjects. Twenty-three Mexican or Mexican-American persons at-risk for inheriting FAD mutations performed a block design novelty encoding task, and activation exhibited by FAD mutation carriers (MCs) was contrasted with that of noncarriers (NCs) and among APOE genotype groups. FAD MCs (n = 14) showed decreased BOLD activation in the anterior cingulate gyrus relative to 9 NCs. No increased activation was seen in MCs relative to NCs. Four APOE ε3/4 carriers demonstrated increased BOLD signal compared with 14 ε3/3 carriers in the occipital and perisylvian cortices bilaterally. There were no areas where ε3/3 carriers activated more than ε3/4 carriers. Our findings of increased fMRI activation associated with APOE genotype but not with FAD mutations suggest that APOE exerts an effect on the BOLD signal that is not readily explained as a compensatory phenomenon. PMID:20729396

  7. Do alcohol-dependent patients show different neural activation during response inhibition than healthy controls in an alcohol-related fMRI go/no-go-task?

    PubMed

    Czapla, Marta; Baeuchl, Christian; Simon, Joe J; Richter, Barbara; Kluge, Matthias; Friederich, Hans-Christoph; Mann, Karl; Herpertz, Sabine C; Loeber, Sabine

    2017-03-01

    Alcohol dependence is associated with impaired response inhibition and heightened cue reactivity towards alcohol-related stimuli. Several brain areas, but mainly prefrontal structures, have been linked to response inhibition in addiction. This study aimed at combining both aspects: salience of drug-associated cues and response inhibition using a go/no-go task with alcohol-associated stimuli during functional magnetic resonance imaging (fMRI). Nineteen abstinent alcohol-dependent patients (ADP) and 21 healthy control subjects (HC) were compared on blood oxygen level-dependent (BOLD) responses during successful inhibition of no-go stimuli and successful reactions to go stimuli. ADP and HC did not significantly differ in their behavioural performance in the task. However, both groups performed worse during the inhibition of alcoholic-associated stimuli compared to neutral stimuli. On the neural level, ADP displayed enhanced BOLD activity relative to HC during successful response inhibition in several areas involved in visual processing, cognitive and impulse control, including occipital structures, anterior cingulate gyrus, medial frontal gyrus and medial orbitofrontal cortex. We interpret these findings as a possible compensation strategy for impaired cognitive processing. Furthermore, the results underline the impact of salience of alcohol-related stimuli on response inhibition, which seems to affect both ADP and HC.

  8. 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.

  9. BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone

    PubMed Central

    Moore, Kelsey; Madularu, Dan; Iriah, Sade; Yee, Jason R.; Kulkarni, Praveen; Darcq, Emmanuel; Kieffer, Brigitte L.; Ferris, Craig F.

    2016-01-01

    Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (μ) opioid receptor knock-outs (MuKO) in response to oxycodone (OXY). Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of positive BOLD showed enhanced activation across the brain in WT mice within 15 min of intraperitoneal administration of 2.5 mg of OXY. BOLD activation was detected in 72 regions out of 122, and was most prominent in areas of high μ opioid receptor density (thalamus, ventral tegmental area, substantia nigra, caudate putamen, basal amygdala, and hypothalamus), and focus on pain circuits indicated strong activation in major pain processing centers (central amygdala, solitary tract, parabrachial area, insular cortex, gigantocellularis area, ventral thalamus primary sensory cortex, and prelimbic cortex). Importantly, the OXY-induced positive BOLD was eliminated in MuKO mice in most regions, with few exceptions (some cerebellar nuclei, CA3 of the hippocampus, medial amygdala, and preoptic areas). This result indicates that most effects of OXY on positive BOLD are mediated by the μ opioid receptor (on-target effects). OXY also caused an increase in negative BOLD in WT mice in few regions (16 out of 122) and, unlike the positive BOLD response the negative BOLD was only partially eliminated in the MuKO mice (cerebellum), and in some case intensified (hippocampus). Negative BOLD analysis therefore shows activation and deactivation events in the absence of the μ receptor for some areas where receptor expression is normally extremely low or absent (off-target effects). Together, our approach permits establishing opioid-induced BOLD activation maps in awake mice. In addition, comparison of WT and MuKO mutant mice reveals both on-target and off-target activation events, and set an OXY brain

  10. BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone.

    PubMed

    Moore, Kelsey; Madularu, Dan; Iriah, Sade; Yee, Jason R; Kulkarni, Praveen; Darcq, Emmanuel; Kieffer, Brigitte L; Ferris, Craig F

    2016-01-01

    Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (μ) opioid receptor knock-outs (MuKO) in response to oxycodone (OXY). Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of positive BOLD showed enhanced activation across the brain in WT mice within 15 min of intraperitoneal administration of 2.5 mg of OXY. BOLD activation was detected in 72 regions out of 122, and was most prominent in areas of high μ opioid receptor density (thalamus, ventral tegmental area, substantia nigra, caudate putamen, basal amygdala, and hypothalamus), and focus on pain circuits indicated strong activation in major pain processing centers (central amygdala, solitary tract, parabrachial area, insular cortex, gigantocellularis area, ventral thalamus primary sensory cortex, and prelimbic cortex). Importantly, the OXY-induced positive BOLD was eliminated in MuKO mice in most regions, with few exceptions (some cerebellar nuclei, CA3 of the hippocampus, medial amygdala, and preoptic areas). This result indicates that most effects of OXY on positive BOLD are mediated by the μ opioid receptor (on-target effects). OXY also caused an increase in negative BOLD in WT mice in few regions (16 out of 122) and, unlike the positive BOLD response the negative BOLD was only partially eliminated in the MuKO mice (cerebellum), and in some case intensified (hippocampus). Negative BOLD analysis therefore shows activation and deactivation events in the absence of the μ receptor for some areas where receptor expression is normally extremely low or absent (off-target effects). Together, our approach permits establishing opioid-induced BOLD activation maps in awake mice. In addition, comparison of WT and MuKO mutant mice reveals both on-target and off-target activation events, and set an OXY brain

  11. fMRI mapping of the visual system in the mouse brain with interleaved snapshot GE-EPI.

    PubMed

    Niranjan, Arun; Christie, Isabel N; Solomon, Samuel G; Wells, Jack A; Lythgoe, Mark F

    2016-06-10

    The use of functional magnetic resonance imaging (fMRI) in mice is increasingly prevalent, providing a means to non-invasively characterise functional abnormalities associated with genetic models of human diseases. The predominant stimulus used in task-based fMRI in the mouse is electrical stimulation of the paw. Task-based fMRI in mice using visual stimuli remains underexplored, despite visual stimuli being common in human fMRI studies. In this study, we map the mouse brain visual system with BOLD measurements at 9.4T using flashing light stimuli with medetomidine anaesthesia. BOLD responses were observed in the lateral geniculate nucleus, the superior colliculus and the primary visual area of the cortex, and were modulated by the flashing frequency, diffuse vs focussed light and stimulus context. Negative BOLD responses were measured in the visual cortex at 10Hz flashing frequency; but turned positive below 5Hz. In addition, the use of interleaved snapshot GE-EPI improved fMRI image quality without diminishing the temporal contrast-noise-ratio. Taken together, this work demonstrates a novel methodological protocol in which the mouse brain visual system can be non-invasively investigated using BOLD fMRI.

  12. Hemodynamic response function in patients with stroke-induced aphasia: Implications for fMRI data analysis

    PubMed Central

    Bonakdarpour, B.; Parrish, T.B.; Thompson, C.K.

    2007-01-01

    Functional MRI is based on changes in cerebral microvasculature triggered by increased neuronal oxidative metabolism. This change in blood flow follows a pattern known as the hemodynamic response function (HRF), which typically peaks 4–6 s following stimulus delivery. However, in the presence of cerebrovascular disease the HRF may not follow this normal pattern, due to either the temporal signal to noise (tSNR) ratio or delays in the HRF, which may result in misinterpretation or underestimation of fMRI signal. The present study examined the HRF and SNR in five individuals with aphasia resulting from stroke and four unimpaired participants using a lexical decision task and a long trial event-related design. T1-weighted images were acquired using an MP-RAGE sequence and BOLD T2*-weighted images were acquired using Echo Planar Imaging to measure time to peak (TTP) in the HRF. Data were analyzed using Brain Voyager in four anatomic regions known to be involved in language processing: Broca’s area and the posterior perisylvian network (PPN) (including Wernicke’s area, the angular and supramarginal gyri) and right hemisphere homologues of these regions. The occipital area also was examined as a control region. Analyses showed that the TTP in three out of five patients in the left perisylvian area was increased significantly as compared to normal individuals and the left primary visual cortex in the same patients. In two other patients no significant delays were detected. We also found that the SNR for BOLD signal detection may by insufficient in damaged areas. These findings indicate that obtaining physiologic (TTP) and quality assurance (tSNR) information is essential for studying activation patterns in brain-damaged patients in order to avoid errors in interpretation of the data. An example of one such misinterpretation and the need for alternative data analysis strategies is discussed. PMID:17467297

  13. Neurophysiological and BOLD signal uncoupling of giant somatosensory evoked potentials in progressive myoclonic epilepsy: a case-series study

    PubMed Central

    Storti, Silvia F.; Del Felice, Alessandra; Canafoglia, Laura; Formaggio, Emanuela; Brigo, Francesco; Alessandrini, Franco; Bongiovanni, Luigi G.; Menegaz, Gloria; Manganotti, Paolo

    2017-01-01

    In progressive myoclonic epilepsy (PME), a rare epileptic syndrome caused by a variety of genetic disorders, the combination of peripheral stimulation and functional magnetic resonance imaging (fMRI) can shed light on the mechanisms underlying cortical dysfunction. The aim of the study is to investigate sensorimotor network modifications in PME by assessing the relationship between neurophysiological findings and blood oxygen level dependent (BOLD) activation. Somatosensory-evoked potential (SSEP) obtained briefly before fMRI and BOLD activation during median-nerve electrical stimulation were recorded in four subjects with typical PME phenotype and compared with normative data. Giant scalp SSEPs with enlarger N20-P25 complex compared to normal data (mean amplitude of 26.2 ± 8.2 μV after right stimulation and 27.9 ± 3.7 μV after left stimulation) were detected. Statistical group analysis showed a reduced BOLD activation in response to median nerve stimulation in PMEs compared to controls over the sensorimotor (SM) areas and an increased response over subcortical regions (p < 0.01, Z > 2.3, corrected). PMEs show dissociation between neurophysiological and BOLD findings of SSEPs (giant SSEP with reduced BOLD activation over SM). A direct pathway connecting a highly restricted area of the somatosensory cortex with the thalamus can be hypothesized to support the higher excitability of these areas. PMID:28294187

  14. Simultaneous GCaMP6-based fiber photometry and fMRI in rats.

    PubMed

    Liang, Zhifeng; Ma, Yuncong; Watson, Glenn D R; Zhang, Nanyin

    2017-09-01

    Understanding the relationship between neural and vascular signals is essential for interpretation of functional MRI (fMRI) results with respect to underlying neuronal activity. Simultaneously measuring neural activity using electrophysiology with fMRI has been highly valuable in elucidating the neural basis of the blood oxygenation-level dependent (BOLD) signal. However, this approach is also technically challenging due to the electromagnetic interference that is observed in electrophysiological recordings during MRI scanning. Recording optical correlates of neural activity, such as calcium signals, avoids this issue, and has opened a new avenue to simultaneously acquire neural and BOLD signals. The present study is the first to demonstrate the feasibility of simultaneously and repeatedly acquiring calcium and BOLD signals in animals using a genetically encoded calcium indicator, GCaMP6. This approach was validated with a visual stimulation experiment, during which robust increases of both calcium and BOLD signals in the superior colliculus were observed. In addition, repeated measurement in the same animal demonstrated reproducible calcium and BOLD responses to the same stimuli. Taken together, simultaneous GCaMP6-based fiber photometry and fMRI recording presents a novel, artifact-free approach to simultaneously measuring neural and fMRI signals. Furthermore, given the cell-type specificity of GCaMP6, this approach has the potential to mechanistically dissect the contributions of individual neuron populations to BOLD signal, and ultimately reveal its underlying neural mechanisms. The current study established the method for simultaneous GCaMP6-based fiber photometry and fMRI in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Congruence of BOLD response across intertemporal choice conditions: fictive and real money gains and losses.

    PubMed

    Bickel, Warren K; Pitcock, Jeffery A; Yi, Richard; Angtuaco, Edgardo J C

    2009-07-08

    Intertemporal choice is predicated on the valuation of commodities with respect to delay until their receipt. Subjective value of a future outcome decreases, or is discounted, as a function of that delay (Bickel and Johnson, 2003). Although behavioral studies suggest no difference between the devaluation of real and fictive outcomes, no neuroimaging studies have investigated potential differences in the underlying deliberative process. Here, we compare behavioral and neural correlates of intertemporal valuation of real and hypothetical monetary gains as well as hypothetical losses, which have been posited to involve different mechanisms. Behavioral and neuroimaging sessions were conducted in which participants made intertemporal choice decisions in a gains condition using both real and hypothetical $100 money and in a loss condition using a fictive $100 money. Within-subject comparison of behavioral data revealed no significant difference between levels of discounting across the three conditions. Random-effects analysis of functional magnetic resonance imaging (fMRI) data of each of the three discounting conditions independently revealed significant signal change in limbic (anterior cingulate, striatum, posterior cingulate) and executive functioning areas (lateral prefrontal cortex), whereas a repeated-measures ANOVA failed to detect differences in signal change across the three discounting conditions after correcting for multiple comparisons. These data support a concordance between real and hypothetical conditions from delay-discounting studies and further suggest a congruence of the fMRI blood oxygen level-dependent signal across brain regions associated with the deliberative process of different forms of intertemporal choice.

  16. Decoupling of BOLD amplitude and pattern classification of orientation-selective activity in human visual cortex.

    PubMed

    Albers, Anke Marit; Meindertsma, Thomas; Toni, Ivan; de Lange, Floris P

    2017-09-22

    Multivariate pattern analysis (MVPA) of fMRI data has allowed the investigation of neural representations of stimuli on the basis of distributed patterns of activity within a brain region, independently from overall brain activity. For instance, several studies on early visual cortex have reported reliable MVPA decoding of the identity of a stimulus representation that was kept in working memory or internally generated, despite the fact that the overall BOLD response was low or even at baseline levels. Here we ask how it is possible that reliable stimulus information can be decoded from early visual cortex even when the overall BOLD signal remains low. We reanalyzed a data set in which human participants (N = 24) imagined or kept in working memory an oriented visual grating. We divided voxels from V1, V2, and V3 into groups based on orientation preference, and compared the time course of mean BOLD responses to preferred and non-preferred orientations with the time course of the multivariate decoding performance. Decoding accuracy related to a numerically small, but reliable univariate difference in the mean BOLD response to preferred and non-preferred stimuli. The time course of the difference in BOLD responses to preferred and non-preferred orientations was highly similar to the time course of the multivariate pattern classification accuracy. The reliability of the classification strongly correlated with the magnitude of differences in BOLD signal between preferred and non-preferred stimuli. These activity differences were small compared to the large overall BOLD modulations. This suggests that a substantial part of the task-related BOLD response to visual stimulation might not be stimulus-specific. Rather, stimulus-evoked BOLD signals in early visual cortex during a task context may be an amalgam of small stimulus-specific responses and large task-related but non-stimulus-specific responses. The latter are not evident during the maintenance or internal

  17. Convolution power spectrum analysis for FMRI data based on prior image signal.

    PubMed

    Zhang, Jiang; Chen, Huafu; Fang, Fang; Liao, Wei

    2010-02-01

    Functional MRI (fMRI) data-processing methods based on changes in the time domain involve, among other things, correlation analysis and use of the general linear model with statistical parametric mapping (SPM). Unlike conventional fMRI data analysis methods, which aim to model the blood-oxygen-level-dependent (BOLD) response of voxels as a function of time, the theory of power spectrum (PS) analysis focuses completely on understanding the dynamic energy change of interacting systems. We propose a new convolution PS (CPS) analysis of fMRI data, based on the theory of matched filtering, to detect brain functional activation for fMRI data. First, convolution signals are computed between the measured fMRI signals and the image signal of prior experimental pattern to suppress noise in the fMRI data. Then, the PS density analysis of the convolution signal is specified as the quantitative analysis energy index of BOLD signal change. The data from simulation studies and in vivo fMRI studies, including block-design experiments, reveal that the CPS method enables a more effective detection of some aspects of brain functional activation, as compared with the canonical PS SPM and the support vector machine methods. Our results demonstrate that the CPS method is useful as a complementary analysis in revealing brain functional information regarding the complex nature of fMRI time series.

  18. Frequency-specific electrocorticographic correlates of working memory delay period fMRI activity.

    PubMed

    Khursheed, Faraz; Tandon, Nitin; Tertel, Kathrin; Pieters, Thomas A; Disano, Michael A; Ellmore, Timothy M

    2011-06-01

    Electrocorticography (ECoG) and functional MRI (BOLD-fMRI) have been used previously to measure brain activity during working memory delay periods. These studies have separately reported oscillation changes in the theta (4-8 Hz) band and BOLD-fMRI increases during delay periods when information is maintained in memory. However, it is not known how intracranial cortical field potential (CFP) changes relate to BOLD-fMRI responses during delay periods. To answer this question, fMRI was obtained from six epilepsy patients during a visual working memory task. Then, following subdural macroelectrode implant, continuous ECoG was used to record CFPs during the same task. Time-frequency analyses showed delay period gamma band oscillation amplitude increases on electrodes located near fMRI activity, while in the theta band changes were higher for electrodes located away from fMRI activation. The amplitude of the ECoG gamma band response was significantly positively correlated with the fMRI response, while a negative correlation was found for the theta band. The findings are consistent with previous reports of local field potential (LFP) coupling in the gamma band with BOLD-fMRI responses during visual stimulation in monkeys, but are novel in that the relationship reported here persists after the disappearance of visual stimuli while information is being maintained in memory. We conclude that there is a relationship between BOLD-fMRI increases and human working memory delay period gamma oscillation increases and theta decreases. The spectral profile change provides a basis for comparison of working memory delay period BOLD-fMRI with field potential recordings in animals and other human intracranial EEG studies.

  19. Temporal sensitivity of event-related fMRI.

    PubMed

    Hernandez, Luis; Badre, David; Noll, Douglas; Jonides, John

    2002-10-01

    The temporal resolution of event-related fMRI is limited by the low sampling rate of typical MR whole brain protocols and by the slow rate of the BOLD response. Within the assumptions of the General Linear Model, we explore the tolerance of regression analyses of fMRI data to errors in the timing of the model relative to the experimental data under a number of circumstances. Given the sensitivity of the analysis to temporal shifts of the model relative to the data, one can search for the time a neuronal event occurs with temporal resolution on the order of a few hundred milliseconds with 95% confidence. This confidence level is strongly dependent on the signal-to-noise ratio of the observed BOLD responses (approximately +/-200 ms in our example of visual stimulation data collected at 1.5 T).

  20. Neural activity during production of rorschach responses: An fMRI study.

    PubMed

    Giromini, Luciano; Viglione, Donald J; Zennaro, Alessandro; Cauda, Franco

    2017-04-30

    Recently, a lot of effort has been made to ground Rorschach interpretations to their evidence base. To date, however, no studies have yet described, via fMRI, what brain areas get involved when one takes the Rorschach. To fill this gap in the literature, we administered the ten-inkblot stimuli to 26 healthy volunteers during fMRI. Analysis of BOLD signals revealed that, compared to fixating a cross, looking at the Rorschach inkblots while thinking of what they might be associated with higher temporo-occipital and fronto-parietal activations, and with greater activity in some small, sub-cortical regions included in the limbic system. These findings are in line with the traditional conceptualization of the test, as they suggest that taking the Rorschach involves (a) high-level visual processing, (b) top-down as well as bottom-up attentional processes, and (c) perception and processing of emotions and emotional memories. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  1. 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

  2. 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

  3. Mapping between fMRI responses to movies and their natural language annotations.

    PubMed

    Vodrahalli, Kiran; Chen, Po-Hsuan; Liang, Yingyu; Baldassano, Christopher; Chen, Janice; Yong, Esther; Honey, Christopher; Hasson, Uri; Ramadge, Peter; Norman, Kenneth A; Arora, Sanjeev

    2017-06-23

    Several research groups have shown how to map fMRI responses to the meanings of presented stimuli. This paper presents new methods for doing so when only a natural language annotation is available as the description of the stimulus. We study fMRI data gathered from subjects watching an episode of BBCs Sherlock (Chen et al., 2017), and learn bidirectional mappings between fMRI responses and natural language representations. By leveraging data from multiple subjects watching the same movie, we were able to perform scene classification with 72% accuracy (random guessing would give 4%) and scene ranking with average rank in the top 4% (random guessing would give 50%). The key ingredients underlying this high level of performance are (a) the use of the Shared Response Model (SRM) and its variant SRM-ICA (Chen et al., 2015; Zhang et al., 2016) to aggregate fMRI data from multiple subjects, both of which are shown to be superior to standard PCA in producing low-dimensional representations for the tasks in this paper; (b) a sentence embedding technique adapted from the natural language processing (NLP) literature (Arora et al., 2017) that produces semantic vector representation of the annotations; (c) using previous timestep information in the featurization of the predictor data. These optimizations in how we featurize the fMRI data and text annotations provide a substantial improvement in classification performance, relative to standard approaches. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. How much luxury is there in 'luxury perfusion'? An analysis of the BOLD response in the visual areas V1 and V2.

    PubMed

    Marcar, Valentine L; Loenneker, Thomas; Straessle, Andrea; Girard, Franck; Martin, Ernst

    2004-09-01

    We re-analyzed the functional magnetic resonance imaging data from a study involving awake, adult, human volunteers in order to examine the influence of vascular density on the blood oxygenation level-dependent (BOLD) response. We employed a flashed and reversing stimulus paradigm where the latter stimulated twice the number of receptive fields and with it doubled the neuronal metabolic load (CMRO2) compared to the former stimulus. The blood flow increase to these stimuli was identical, so that differences in the BOLD response are due to differences in the oxygen extraction fraction. By comparing the BOLD response in human striate cortex (V1) and its neighbor, extra-striate area V2 to the two stimuli, we were able to determine the influence of the higher vascular density of striate cortex on the BOLD response. In striate cortex, the extent of activation, as measured by the number of activated voxels, was larger for the flashed than for the reversing stimulus. In extra-striate area V2, no such difference in the extent of activation was noted. Gauging the local concentration of HbR using deltaR2*, we found it to be significantly lower for the flashed than for the reversing checkerboard. We estimated the HbR concentration in extra-striate area V2 to be double that of striate cortex independent of the stimulus presented. A frequency distribution of the deltaR2* values for the flashed and reversing checkerboard revealed a shift consistent with an increase in the HbR concentration between areas V1 and V2. The metabolically most demanding stimulus, the reversing checkerboard was associated with the highest HbR concentration and with the largest number of voxels with a negative BOLD response.

  5. Negative BOLD in default-mode structures measured with EEG-MREG is larger in temporal than extra-temporal epileptic spikes

    PubMed Central

    Jacobs, Julia; Menzel, Antonia; Ramantani, Georgia; Körbl, Katharina; Assländer, Jakob; Schulze-Bonhage, Andreas; Hennig, Jürgen; LeVan, Pierre

    2014-01-01

    Introduction: EEG-fMRI detects BOLD changes associated with epileptic interictal discharges (IED) and can identify epileptogenic networks in epilepsy patients. Besides positive BOLD changes, negative BOLD changes have sometimes been observed in the default-mode network, particularly using group analysis. A new fast fMRI sequence called MREG (Magnetic Resonance Encephalography) shows increased sensitivity to detect IED-related BOLD changes compared to the conventional EPI sequence, including frequent occurrence of negative BOLD responses in the DMN. The present study quantifies the concordance between the DMN and negative BOLD related to IEDs of temporal and extra-temporal origin. Methods: Focal epilepsy patients underwent simultaneous EEG-MREG. Areas of overlap were calculated between DMN regions, defined as precuneus, posterior cingulate, bilateral inferior parietal and mesial prefrontal cortices according to a standardized atlas, and significant negative BOLD changes revealed by an event-related analysis based on the timings of IED seen on EEG. Correlation between IED number/lobe of origin and the overlap were calculated. Results: 15 patients were analyzed, some showing IED over more than one location resulting in 30 different IED types. The average overlap between negative BOLD and DMN was significantly larger in temporal (23.7 ± 19.6 cm3) than extra-temporal IEDs (7.4 ± 5.1 cm3, p = 0.008). There was no significant correlation between the number of IEDs and the overlap between DMN structures and negative BOLD areas. Discussion: MREG results in an increased sensitivity to detect negative BOLD responses related to focal IED in single patients, with responses often occurring in DMN regions. In patients with high overlap with the DMN, this suggests that epileptic IEDs may be associated with a brief decrease in attention and cognitive ability. Interestingly this observation was not dependent on the frequency of IED but more common in IED of temporal origin. PMID

  6. Characterizing response to elemental unit of acoustic imaging noise: an FMRI study.

    PubMed

    Tamer, Gregory G; Luh, Wen-Ming; Talavage, Thomas M

    2009-07-01

    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.

  7. Predicting goals in action episodes attenuates BOLD response in inferior frontal and occipitotemporal cortex.

    PubMed

    Wurm, Moritz F; Hrkać, Mari; Morikawa, Yuka; Schubotz, Ricarda I

    2014-11-01

    Actions are usually made of several action steps gearing towards an overarching goal. During observation of such action episodes the overarching action goal becomes more and more clear and upcoming action steps can be predicted with increasing precision. To tap this process, the present fMRI study investigated the dynamic changes of neural activity during the observation of distinct action steps that cohere by an overarching goal. Our hypotheses specifically addressed the role of the inferior frontal gyrus (IFG), a region assumed to be a key hub for integration functions during action processing, as well as the role of regions involved in action perception (often referred to as action observation network or AON) that should benefit from the predictability of forthcoming action steps. Participants watched separate action steps that formed a coherent action goal or not (factor goal coherence) and were performed by a single actor or not (factor actor coherence). Independent of actor coherence, neural activity in IFG and occipitotemporal cortex decreased as a function of goal predictability during the unfolding of goal-coherent episodes. In addition, we identified a network (precuneus, dorsolateral prefrontal and orbitofrontal cortex, angular gyrus, and middle temporal gyrus) that showed increased activity for goal coherence. We conclude that IFG fosters the integration of action steps to build overarching goals. Identifying the unifying goal of an action episode allows anticipation, and thus efficient processing, of forthcoming action steps. To this end, past action steps of the action episode are buffered and recollected with recourse to episodic memory.

  8. 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.

  9. 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

  10. Relationship of the BOLD signal with VEP for ultrashort duration visual stimuli (0.1 to 5 ms) in humans

    PubMed Central

    Yeşilyurt, Barış; Whittingstall, Kevin; Uğurbil, Kâmil; Logothetis, Nikos K; Uludağ, Kâmil

    2010-01-01

    There is currently a great interest to combine electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to study brain function. Earlier studies have shown different EEG components to correlate well with the fMRI signal arguing for a complex relationship between both measurements. In this study, using separate EEG and fMRI measurements, we show that (1) 0.1 ms visual stimulation evokes detectable hemodynamic and visual-evoked potential (VEP) responses, (2) the negative VEP deflection at ∼80 ms (N2) co-varies with stimulus duration/intensity such as with blood oxygenation level-dependent (BOLD) response; the positive deflection at ∼120 ms (P2) does not, and (3) although the N2 VEP–BOLD relationship is approximately linear, deviation is evident at the limit of zero N2 VEP. The latter finding argues that, although EEG and fMRI measurements can co-vary, they reflect partially independent processes in the brain tissue. Finally, it is shown that the stimulus-induced impulse response function (IRF) at 0.1 ms and the intrinsic IRF during rest have different temporal dynamics, possibly due to predominance of neuromodulation during rest as compared with neurotransmission during stimulation. These results extend earlier findings regarding VEP–BOLD coupling and highlight the component- and context-dependency of the relationship between evoked potentials and hemodynamic responses. PMID:19844243

  11. Music of the 7Ts: Predicting and Decoding Multivoxel fMRI Responses with Acoustic, Schematic, and Categorical Music Features

    PubMed Central

    Casey, Michael A.

    2017-01-01

    Underlying the experience of listening to music are parallel streams of auditory, categorical, and schematic qualia, whose representations and cortical organization remain largely unresolved. We collected high-field (7T) fMRI data in a music listening task, and analyzed the data using multivariate decoding and stimulus-encoding models. Twenty subjects participated in the experiment, which measured BOLD responses evoked by naturalistic listening to twenty-five music clips from five genres. Our first analysis applied machine classification to the multivoxel patterns that were evoked in temporal cortex. Results yielded above-chance levels for both stimulus identification and genre classification–cross-validated by holding out data from multiple of the stimuli during model training and then testing decoding performance on the held-out data. Genre model misclassifications were significantly correlated with those in a corresponding behavioral music categorization task, supporting the hypothesis that geometric properties of multivoxel pattern spaces underlie observed musical behavior. A second analysis employed a spherical searchlight regression analysis which predicted multivoxel pattern responses to music features representing melody and harmony across a large area of cortex. The resulting prediction-accuracy maps yielded significant clusters in the temporal, frontal, parietal, and occipital lobes, as well as in the parahippocampal gyrus and the cerebellum. These maps provide evidence in support of our hypothesis that geometric properties of music cognition are neurally encoded as multivoxel representational spaces. The maps also reveal a cortical topography that differentially encodes categorical and absolute-pitch information in distributed and overlapping networks, with smaller specialized regions that encode tonal music information in relative-pitch representations. PMID:28769835

  12. Music of the 7Ts: Predicting and Decoding Multivoxel fMRI Responses with Acoustic, Schematic, and Categorical Music Features.

    PubMed

    Casey, Michael A

    2017-01-01

    Underlying the experience of listening to music are parallel streams of auditory, categorical, and schematic qualia, whose representations and cortical organization remain largely unresolved. We collected high-field (7T) fMRI data in a music listening task, and analyzed the data using multivariate decoding and stimulus-encoding models. Twenty subjects participated in the experiment, which measured BOLD responses evoked by naturalistic listening to twenty-five music clips from five genres. Our first analysis applied machine classification to the multivoxel patterns that were evoked in temporal cortex. Results yielded above-chance levels for both stimulus identification and genre classification-cross-validated by holding out data from multiple of the stimuli during model training and then testing decoding performance on the held-out data. Genre model misclassifications were significantly correlated with those in a corresponding behavioral music categorization task, supporting the hypothesis that geometric properties of multivoxel pattern spaces underlie observed musical behavior. A second analysis employed a spherical searchlight regression analysis which predicted multivoxel pattern responses to music features representing melody and harmony across a large area of cortex. The resulting prediction-accuracy maps yielded significant clusters in the temporal, frontal, parietal, and occipital lobes, as well as in the parahippocampal gyrus and the cerebellum. These maps provide evidence in support of our hypothesis that geometric properties of music cognition are neurally encoded as multivoxel representational spaces. The maps also reveal a cortical topography that differentially encodes categorical and absolute-pitch information in distributed and overlapping networks, with smaller specialized regions that encode tonal music information in relative-pitch representations.

  13. Response inhibition in pedophilia: an FMRI pilot study.

    PubMed

    Habermeyer, Benedikt; Esposito, Fabrizio; Händel, Nadja; Lemoine, Patrick; Kuhl, Hans Christian; Klarhöfer, Markus; Mager, Ralph; Mokros, Andreas; Dittmann, Volker; Seifritz, Erich; Graf, Marc

    2013-01-01

    The failure to inhibit pleasurable but inappropriate urges is associated with frontal lobe pathology and has been suggested as a possible cause of pedophilic behavior. However, imaging and neuropsychological findings about frontal pathology in pedophilia are heterogeneous. In our study we therefore address inhibition behaviorally and by means of functional imaging, aiming to assess how inhibition in pedophilia is related to a differential recruitment of frontal brain areas. Eleven pedophilic subjects and 7 nonpedophilic controls underwent fMRI while performing a go/no-go task composed of neutral letters. Pedophilic subjects showed a slower reaction time and less accurate visual target discrimination. fMRI voxel-level ANOVA revealed as a main effect of the go/no-go task an activation of prefrontal and parietal brain regions in the no-go condition, while the left anterior cingulate, precuneus and gyrus angularis became more activated in the go condition. In addition, a group × task interaction was found in the left precuneus and gyrus angularis. This interaction was based on an attenuated deactivation of these brain regions in the pedophilic group during performance of the no-go condition. The positive correlation between blood oxygen level-dependent imaging signal and reaction time in these brain areas indicates that attenuated deactivation is related to the behavioral findings. Slower reaction time and less accurate visual target discrimination in pedophilia was accompanied by attenuated deactivation of brain areas belonging to the default mode network. Our findings thus support the notion that behavioral differences might also derive from self-related processes and not necessarily from frontal lobe pathology. © 2013 S. Karger AG, Basel.

  14. Congruence of BOLD Response across Intertemporal Choice Conditions: Fictive and Real Money Gains and Losses: Behavioral and Neural Differences in Discounting

    PubMed Central

    Bickel, Warren K.; Pitcock, Jeffery A.; Yi, Richard; Edgardo, J.C. Angtuaco

    2009-01-01

    Intertemporal choice is predicated on the valuation of commodities with respect to delay until their receipt. Subjective value of a future outcome decreases, or is discounted, as a function of that delay (Bickel and Johnson, 2003). While behavioral studies suggest no difference between the devaluation of real and fictive outcomes, no neuroimaging studies have investigated potential differences in the underlying deliberative process. Here we compare behavioral and neural correlates of intertemporal valuation of real and hypothetical monetary gains as well as hypothetical losses, which have been posited to involve different mechanisms. Behavioral and neuroimaging sessions were conducted in which participants made intertemporal choice decisions in a gains condition using both real and hypothetical $100 money, and in a loss condition using a fictive $100 money. Within-subject comparison of behavioral data revealed no significant difference between levels of discounting across the three conditions. Random-effects analysis of fMRI data of each of the three discounting conditions independently revealed significant signal change in limbic (anterior cingulate, striatum, posterior cingulate) and executive functioning areas (lateral pre-frontal cortex), while a repeated measures ANOVA failed to detect differences in signal change across the three discounting conditions after correcting for multiple comparisons. These data support a concordance between real and hypothetical conditions from delay discounting studies and further suggest a congruence of the fMRI BOLD signal across brain regions associated with the deliberative process of different forms of intertemporal choice. PMID:19587291

  15. 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.

  16. Paradigm-free mapping with morphological component analysis: getting most out of fMRI data

    NASA Astrophysics Data System (ADS)

    Caballero Gaudes, César; Van De Ville, Dimitri; Petridou, Natalia; Lazeyras, François; Gowland, Penny

    2011-09-01

    Functional magnetic resonance imaging (fMRI) is a non-invasive imaging technique that maps the brain's response to neuronal activity based on the blood oxygenation level dependent (BOLD) effect. This work proposes a novel method for fMRI data analysis that enables the decomposition of the fMRI signal in its sources based on morphological descriptors. Beyond traditional fMRI hypothesis-based or blind data-driven exploratory approaches, this method allows the detection of BOLD responses without prior timing information. It is based on the deconvolution of the neuronal-related haemodynamic component of the fMRI signal with paradigm free mapping and also furnishes estimates of the movement-related effects, instrumental drifts and physiological fluctuations. Our algorithm is based on an overcomplete representation of the fMRI voxel time series with an additive linear model that is recovered by means of a L1-norm regularized least-squares estimators and an adapted block coordinate relaxation procedure. The performance of the technique is evaluated with simulated data and real experimental data acquired at 3T.

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

    PubMed

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

    2012-01-01

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

  18. 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…

  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. Does Chronic Tinnitus Alter the Emotional Response Function of the Amygdala?: A Sound-Evoked fMRI Study

    PubMed Central

    Davies, Jeff E.; Gander, Phillip E.; Hall, Deborah A.

    2017-01-01

    Tinnitus is often associated with strong negative thoughts and emotions which can contribute to a distressing and chronic long-term condition. The amygdala, the “feeling and reacting” part of the brain, may play a key role in this process. Although implicated in several theoretical models of tinnitus, quantification of activity in the human amygdala has only been made possible more recently through neuroimaging methods such as functional magnetic resonance imaging (fMRI) but benefits from modified scanning parameters using a double-echo acquisition for improved BOLD sensitivity. This study thus examined the role of the amygdala in emotional sound processing in people with tinnitus using a novel double-echo imaging sequence for optimal detectability of subcortical activity. Our hypotheses were: (1) emotionally evocative sound clips rated as pleasant or unpleasant would elicit stronger amygdalar activation than sound clips rated as neutral, (2) people with tinnitus have greater amygdalar activation in response to emotionally evocative sounds (relative to neutral sounds) compared to controls. Methods: Twelve participants all with chronic, constant tinnitus took part. We also recruited 11 age and hearing-matched controls. Participants listened to a range of emotionally evocative sound clips; rated as pleasant, unpleasant or neutral. A region-of-interest analysis was chosen to test our a priori hypotheses. Results: Both groups displayed a robust and similar overall response to sounds vs. silence in the following ascending auditory pathways; inferior colliculus, medial geniculate body and the primary auditory cortex. In support of our first hypothesis, the amygdala's response to pleasant and unpleasant sound clips was significantly greater than neutral sounds. Opposing our second hypothesis, we found that the amygdala's overall response to pleasant and unpleasant sounds (compared to neutral sounds) was actually lower in the tinnitus group as compared to the controls

  1. Simultaneous EEG and fMRI reveals a causally connected subcortical-cortical network during reward anticipation.

    PubMed

    Plichta, Michael M; Wolf, Isabella; Hohmann, Sarah; Baumeister, Sarah; Boecker, Regina; Schwarz, Adam J; Zangl, Maria; Mier, Daniela; Diener, Carsten; Meyer, Patric; Holz, Nathalie; Ruf, Matthias; Gerchen, Martin F; Bernal-Casas, David; Kolev, Vasil; Yordanova, Juliana; Flor, Herta; Laucht, Manfred; Banaschewski, Tobias; Kirsch, Peter; Meyer-Lindenberg, Andreas; Brandeis, Daniel

    2013-09-04

    Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been used to study the neural correlates of reward anticipation, but the interrelation of EEG and fMRI measures remains unknown. The goal of the present study was to investigate this relationship in response to a well established reward anticipation paradigm using simultaneous EEG-fMRI recording in healthy human subjects. Analysis of causal interactions between the thalamus (THAL), ventral-striatum (VS), and supplementary motor area (SMA), using both mediator analysis and dynamic causal modeling, revealed that (1) THAL fMRI blood oxygenation level-dependent (BOLD) activity is mediating intermodal correlations between the EEG contingent negative variation (CNV) signal and the fMRI BOLD signal in SMA and VS, (2) the underlying causal connectivity network consists of top-down regulation from SMA to VS and SMA to THAL along with an excitatory information flow through a THAL→VS→SMA route during reward anticipation, and (3) the EEG CNV signal is best predicted by a combination of THAL fMRI BOLD response and strength of top-down regulation from SMA to VS and SMA to THAL. Collectively, these findings represent a likely neurobiological mechanism mapping a primarily subcortical process, i.e., reward anticipation, onto a cortical signature.

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

    PubMed

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

    2009-01-15

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

  3. 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. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. 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.

  5. Single stimulus fMRI produces a neural individual difference measure for Autism Spectrum Disorder.

    PubMed

    Lu, James; Kishida, Ken; De Asis Cruz, Josepheen; Lohrenz, Terry; Deering, Diane Treadwell; Beauchamp, Michael; Montague, P Read

    2015-05-01

    Functional magnetic resonance imaging typically makes inferences about neural substrates of cognitive phenomena at the group level. We report the use of a single-stimulus BOLD response in the cingulate cortex that differentiates individual children with autism spectrum disorder from matched typically developing control children with sensitivity and specificity of 63.6% and 73.7% respectively. The approach consists of passive viewing of 'self' and 'other' faces from which an individual difference measure is derived from the BOLD response to the first 'self' image only; the method, penalized logistic regression, requires no averaging over stimulus presentations or individuals. These findings show that single-stimulus fMRI responses can be extracted from individual subjects and used profitably as a neural individual difference measure. The result suggests that single-stimulus fMRI can be developed to produce quantitative neural biomarkers for other developmental disorders and may even be useful in the rapid typing of cognition in healthy individuals.

  6. Functional MRI evidence for distinctive binding and consolidation pathways for face-name associations: analysis of activation maps and BOLD response amplitudes.

    PubMed

    Robinson-Long, Melissa; Eslinger, Paul J; Wang, Jianli; Meadowcroft, Mark; Yang, Qing X

    2009-10-01

    Although some of the anatomical underpinnings of learning and memory systems have been identified, there remains little understanding of how the brain moves from acquiring new information to retaining it. This study was designed to further explore and elucidate the neural mechanisms underlying encoding and memory in a common real-life task, that is, face-name associations. One possible outcome is that the tasks will recruit different neural structures mediating these processes, which can be identified through contrast analysis of activations. Alternatively, it is possible that similar anatomical regions, such as the hippocampus and parahippocampal gyrus, may be involved in both tasks. In that case, analysis of blood oxygenation level dependent (BOLD) amplitude differences between the tasks in those common neural structures may be able to detect whether physiological activation differences occur in encoding versus memory. Five healthy adult participants underwent high-field magnetic resonance imaging (MRI) while learning face-name pairs (encoding phase) and during a multiple-choice recognition task after a brief delay (memory phase). Average activation and BOLD response amplitudes in specific regions of interest and whole-brain activation maps were analyzed. Common activations were observed in the encoding and recognition memory tasks in several regions of interest encompassing the medial temporal and inferior occipital regions. However, higher BOLD response amplitudes occurred in the right fusiform gyrus and the right hippocampus during encoding. In contrast, higher amplitudes were detected in the lingual gyrus bilaterally during recognition memory. Encoding activated distributed prefrontal and temporal cortical regions bilaterally, which mediate attentional, executive, language, and memory systems. Recognition memory recruited a different network of regions encompassing convergence zones in the left prefrontal cortex and the parietal-occipital-temporal region

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

    PubMed

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

    2014-10-15

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

  8. Incongruent abstract stimulus-response bindings result in response interference: FMRI and EEG evidence from visual object classification priming.

    PubMed

    Horner, Aidan J; Henson, Richard N

    2012-03-01

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

  9. 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.

  10. Single-trial coupling of EEG and fMRI reveals the involvement of early anterior cingulate cortex activation in effortful decision making.

    PubMed

    Mulert, Christoph; Seifert, Christian; Leicht, Gregor; Kirsch, Valerie; Ertl, Matthias; Karch, Susanne; Moosmann, Matthias; Lutz, Jürgen; Möller, Hans-Jürgen; Hegerl, Ulrich; Pogarell, Oliver; Jäger, Lorenz

    2008-08-01

    While the precise role of the anterior cingulate cortex (ACC) is still being discussed, it has been suggested that ACC activity might reflect the amount of mental effort associated with cognitive processing. So far, not much is known about the temporal dynamics of ACC activity in effort-related decision making or auditory attention, because fMRI is limited concerning its temporal resolution and electroencephalography (EEG) is limited concerning its spatial resolution. Single-trial coupling of EEG and fMRI can be used to predict the BOLD signal specifically related to amplitude variations of electrophysiological components. The striking feature of single-trial coupling is its ability to separate different aspects of the BOLD signal according to their specific relationship to a distinct neural process. In the present study we investigated 10 healthy subjects with a forced choice reaction task under both low and high effort conditions and a control condition (passive listening) using simultaneous EEG and fMRI. We detected a significant effect of mental effort only for the N1 potential, but not for the P300 potential. In the fMRI analysis, ACC activation was present only in the high effort condition. We used single-trial coupling of EEG and fMRI in order to separate information specific to N1-amplitude variations from the unrelated BOLD response. Under high effort conditions we were able to detect circumscribed BOLD activations specific to the N1 potential in the ACC (t=4.7) and the auditory cortex (t=6.1). Comparing the N1-specific BOLD activity of the high effort condition versus the control condition we found only activation of the ACC (random effects analysis, corrected for multiple comparisons, t=4.4). These findings suggest a role of early ACC activation in effort-related decision making and provide a direct link between the N1 component and its corresponding BOLD signal.

  11. 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

  12. Impaired fMRI activation in patients with primary brain tumors.

    PubMed

    Jiang, Zhen; Krainik, Alexandre; David, Olivier; Salon, Caroline; Troprès, Irène; Hoffmann, Dominique; Pannetier, Nicolas; Barbier, Emmanuel L; Bombìn, Eduardo Ramos; Warnking, Jan; Pasteris, Caroline; Chabardes, Stefan; Berger, François; Grand, Sylvie; Segebarth, Christoph; Gay, Emmanuel; Le Bas, Jean-François

    2010-08-15

    To characterize peritumoral BOLD contrast disorders, 25 patients referred for resection of primary frontal or parietal neoplasms (low-grade glioma (LGG) (n=8); high-grade glioma (HGG) (n=7); meningioma (n=10)) without macroscopic tumoral infiltration of the primary sensorimotor cortex (SM1) were examined preoperatively using BOLD fMRI during simple motor tasks. Overall cerebral BOLD signal was estimated using vasoreactivity to carbogen inhalation. Using bolus of gadolinium, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were estimated. In a 1cm(3) region-of-interest centered on maximal T-value in SM1 contralateral to movements, interhemispheric asymmetry was evaluated using interhemispheric ratios for BOLD and perfusion parameters. During motor tasks contralateral to the tumor, ipsitumoral sensorimotor activations were decreased in HGG and meningiomas, correlated to the distance between the tumor and SM1. Whereas CBV was decreased in ipsitumoral SM1 for HGG, it remained normal in meningiomas. Changes in basal perfusion could not explain motor activation impairment in SM1. Decreased interhemispheric ratio of the BOLD response to carbogen was the best predictor to model the asymmetry of motor activation (R=0.51). Moreover, 94.9+/-4.9% of all motor activations overlapped significant BOLD response to carbogen inhalation.

  13. Group analysis of FMRI and NIR data simultaneously acquired during visual stimulation in humans

    NASA Astrophysics Data System (ADS)

    Toronov, Vladislav Y.; Zhang, Xiaofeng; Webb, Andrew G.

    2006-08-01

    We use our new combined functional near infrared spectro-imaging (fNIRSI) and magnetic resonance imaging (MRI) technique to compare fMRI and fNIRSI data at different activation conditions, to obtain new information about the underlying physiology of the blood oxygen level dependent (BOLD) signal used in fMRI, and to assess statistical characteristics of spatial functional information provided by the group analysis of fNIRSI data. To achieve these goals we have acquired simultaneously fNIRSI and fMRJ data during the presentation of the checkerboard reversing with different frequencies, and analyzed these data following the standard correlation and group analysis of variance pathway used in functional neuroimaging. We have found that while the time courses of oxy-, deoxy-, and total- hemoglobin responses are equally well correlated with the time course of the BOLD response, the spatial pattern and magnitude of the BOLD response is better related to those of the oxy-, and total- hemoglobin responses rather than to the deoxyhemoglobin response. The statistical significance of the fNIRSI group maps is inferior to that of fMRI, and can be particularly compromised by the anatomical features of subjects.

  14. Abstinent adolescent marijuana users show altered fMRI response during spatial working memory☆

    PubMed Central

    Schweinsburg, Alecia D.; Nagel, Bonnie J.; Schweinsburg, Brian C.; Park, Ann; Theilmann, Rebecca J.; Tapert, Susan F.

    2010-01-01

    Marijuana is the most widely used illicit substance among teenagers, yet little is known about the possible neural influence of heavy marijuana use during adolescence. We previously demonstrated an altered functional magnetic resonance imaging (fMRI) activity related to spatial working memory (SWM) among adolescents who were heavy users of after an average of 8 days of abstinence, but the persisting neural effects remain unclear. To characterize the potentially persisting neurocognitive effects of heavy marijuana use in adolescence, we examined fMRI response during SWM among abstinent marijuana-using teens. Participants were 15 MJ teens and 17 demographically similar non-using controls, ages 16–18. Teens underwent biweekly urine toxicology screens to ensure abstinence for 28 days before fMRI acquisition. Groups performed similarly on the SWM task, but MJ teens demonstrated lower activity in right dorsolateral prefrontal and occipital cortices, yet significantly more activation in right posterior parietal cortex. MJ teens showed abnormalities in brain response during a SWM task compared with controls, even after 1 month of abstinence. The activation pattern among MJ teens may reflect different patterns of utilization of spatial rehearsal and attention strategies, and could indicate altered neurodevelopment or persisting abnormalities associated with heavy marijuana use in adolescence. PMID:18356027

  15. Decreased sleep duration is associated with increased fMRI responses to emotional faces in children.

    PubMed

    Reidy, Brooke L; Hamann, Stephan; Inman, Cory; Johnson, Katrina C; Brennan, Patricia A

    2016-04-01

    In adults and children, sleep loss is associated with affective dysregulation and increased responsivity to negative stimuli. Adult functional neuroimaging (fMRI) studies have demonstrated associations between restricted sleep and neural alterations in the amygdala and reward circuitry when viewing emotional picture and face stimuli. Despite this, few studies have examined the associations between short sleep duration and emotional responsivity in typically developing children, and no studies have investigated this relationship using fMRI. The current study examined the relationship between sleep duration and fMRI activation to emotional facial expressions in 15 male children (ages 7-11 years). During fMRI scanning, subjects viewed and made perceptual judgments regarding negative, neutral, and positive emotional faces. Maternal reported child sleep duration was negatively associated with (a) activation in the bilateral amygdala, left insula, and left temporal pole activation when viewing negative (i.e., fearful, disgust) vs. neutral faces, (b) right orbitofrontal and bilateral prefrontal activation when viewing disgust vs. neutral faces, and (c) bilateral orbitofrontal, right anterior cingulate, and left amygdala activation when viewing happy vs. neutral faces. Consistent with our prediction, we also noted that emotion-dependent functional connectivity between the bilateral amygdala and prefrontal cortex, cingulate, fusiform, and occipital cortex was positively associated with sleep duration. Paralleling similar studies in adults, these findings collectively suggest that decreased sleep duration in school-aged children may contribute to enhanced reactivity of brain regions involved in emotion and reward processing, as well as decreased emotion-dependent functional connectivity between the amygdala and brain regions associated with emotion regulation.

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

    PubMed Central

    Kaiser, Daniel; Azzalini, Damiano C.

    2016-01-01

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

  17. Enhanced Thalamic Functional Connectivity with No fMRI Responses to Affected Forelimb Stimulation in Stroke-Recovered Rats

    PubMed Central

    Shim, Woo H.; Suh, Ji-Yeon; Kim, Jeong K.; Jeong, Jaeseung; Kim, Young R.

    2017-01-01

    Neurological recovery after stroke has been extensively investigated to provide better understanding of neurobiological mechanism, therapy, and patient management. Recent advances in neuroimaging techniques, particularly functional MRI (fMRI), have widely contributed to unravel the relationship between the altered neural function and stroke-affected brain areas. As results of previous investigations, the plastic reorganization and/or gradual restoration of the hemodynamic fMRI responses to neural stimuli have been suggested as relevant mechanisms underlying the stroke recovery process. However, divergent study results and modality-dependent outcomes have clouded the proper interpretation of variable fMRI signals. Here, we performed both evoked and resting state fMRI (rs-fMRI) to clarify the link between the fMRI phenotypes and post-stroke functional recovery. The experiments were designed to examine the altered neural activity within the contra-lesional hemisphere and other undamaged brain regions using rat models with large unilateral stroke, which despite the severe injury, exhibited nearly full recovery at ∼6 months after stroke. Surprisingly, both blood oxygenation level-dependent and blood volume-weighted (CBVw) fMRI activities elicited by electrical stimulation of the stroke-affected forelimb were completely absent, failing to reveal the neural origin of the behavioral recovery. In contrast, the functional connectivity maps showed highly robust rs-fMRI activity concentrated in the contra-lesional ventromedial nucleus of thalamus (VM). The negative finding in the stimuli-induced fMRI study using the popular rat middle cerebral artery model denotes weak association between the fMRI hemodynamic responses and neurological improvement. The results strongly caution the indiscreet interpretation of stroke-affected fMRI signals and demonstrate rs-fMRI as a complementary tool for efficiently characterizing stroke recovery. PMID:28119575

  18. Real-time automated spectral assessment of the BOLD response for neurofeedback at 3 and 7T.

    PubMed

    Koush, Yury; Elliott, Mark A; Scharnowski, Frank; Mathiak, Klaus

    2013-09-15

    Echo-planar imaging is the dominant functional MRI data acquisition scheme for evaluating the BOLD signal. To date, it remains the only approach providing neurofeedback from spatially localized brain activity. Real-time functional single-voxel proton spectroscopy (fSVPS) may be an alternative for spatially specific BOLD neurofeedback at 7T because it allows for a precise estimation of the local T2* signal, EPI-specific artifacts may be avoided, and the signal contrast may increase. In order to explore and optimize this alternative neurofeedback approach, we tested fully automated real-time fSVPS spectral estimation procedures to approximate T2* BOLD signal changes from the unsuppressed water peak, i.e. lorentzian non-linear complex spectral fit (LNLCSF) in frequency and frequency-time domain. The proposed approaches do not require additional spectroscopic localizers in contrast to conventional T2* approximation based on linear regression of the free induction decay (FID). For methods comparison, we evaluated quality measures for signals from the motor and the visual cortex as well as a real-time feedback condition at high (3T) and at ultra-high (7T) magnetic field strengths. Using these methods, we achieved reliable and fast water peak spectral parameter estimations. At 7T, we observed an absolute increase of spectra line narrowing due to the BOLD effect, but quality measures did not improve due to artifactual line broadening. Overall, the automated fSVPS approach can be used to assess dynamic spectral changes in real-time, and to provide localized T2* neurofeedback at 3 and 7T. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2003-10-01

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

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

    PubMed

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

    2012-10-01

    We used functional magnetic resonance imaging (fMRI) to investigate brain processes underlying control of emotional responses towards a person in distress by cognitive social distance modulation. fMRI and peripheral physiological responses (startle response and electrodermal activity) were recorded from 24 women while they watched victim-offender scenes and modulated their social distance to the victim by cognitive reappraisal. We found that emotional responses, including startle eyeblink and amygdala responses, can effectively be modulated by social distance modulation. Furthermore, our data provide evidence that activity in the dorsomedial prefrontal cortex (dmPFC) and the anterior paracingulate cortex (aPCC), two brain regions that have previously been associated with brain processes related to distant and close others, is differentially modulated by intentional social distance modulation: activity in the dmPFC increased with increasing disengagement from the victim and activity in the aPCC increased with increasing engagement with the victim. We suggest that these two regions play opposing roles in cognitive modulation of social distance and affective responses towards persons in distress that enable the adaptive and flexible social behavior observed in humans. Copyright © 2011 Wiley Periodicals, Inc.

  1. Modulation of BOLD Response in Motion-sensitive Lateral Temporal Cortex by Real and Fictive Motion Sentences

    PubMed Central

    Saygin, Ayse Pinar; McCullough, Stephen; Alac, Morana; Emmorey, Karen

    2013-01-01

    Can linguistic semantics affect neural processing in feature-specific visual regions? Specifically, when we hear a sentence describing a situation that includes motion, do we engage neural processes that are part of the visual perception of motion? How about if a motion verb was used figuratively, not literally? We used fMRI to investigate whether semantic content can “penetrate” and modulate neural populations that are selective to specific visual properties during natural language comprehension. Participants were presented audiovisually with three kinds of sentences: motion sentences (“The wild horse crossed the barren field.”), static sentences, (“The black horse stood in the barren field.”), and fictive motion sentences (“The hiking trail crossed the barren field.”). Motion-sensitive visual areas (MT+) were localized individually in each participant as well as face-selective visual regions (fusiform face area; FFA). MT+ was activated significantly more for motion sentences than the other sentence types. Fictive motion sentences also activated MT+ more than the static sentences. Importantly, no modulation of neural responses was found in FFA. Our findings suggest that the neural substrates of linguistic semantics include early visual areas specifically related to the represented semantics and that figurative uses of motion verbs also engage these neural systems, but to a lesser extent. These data are consistent with a view of language comprehension as an embodied process, with neural substrates as far reaching as early sensory brain areas that are specifically related to the represented semantics. PMID:19925197

  2. Simultaneous Acquisition of Gradient Echo / Spin Echo BOLD and Perfusion with a Separate Labeling Coil

    PubMed Central

    Glielmi, C.B.; Xu, Q.; Craddock, R.C.; Hu, X.

    2010-01-01

    Arterial spin labeling (ASL) based cerebral blood flow (CBF) imaging complements blood oxygenation level dependent (BOLD) imaging with a measure that is more quantitative and has better specificity to neuronal activation. Relative to gradient echo (GE) BOLD, spin echo (SE) BOLD has better spatial specificity because it is less biased to large draining veins. While there have been many studies comparing simultaneously acquired CBF data with GE BOLD data in fMRI, there have been few studies comparing CBF with SE BOLD and no study comparing all three. We present a pulse sequence that simultaneously acquires CBF data with a separate labeling coil, GE BOLD and SE BOLD images. Simultaneous acquisition avoids inter-scan variability, allowing more direct assessment and comparison of each contrast’s relative specificity and reproducibility. Furthermore, it facilitates studies that may benefit from multiple complementary measures. PMID:20648682

  3. Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

    PubMed

    Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

    2017-05-31

    Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation.SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

  4. Effects of age on negative BOLD signal changes in the primary somatosensory cortex.

    PubMed

    Gröschel, Sonja; Sohns, Jan Martin; Schmidt-Samoa, Carsten; Baudewig, Jürgen; Becker, Lars; Dechent, Peter; Kastrup, Andreas

    2013-05-01

    In addition to a contralateral activation of the primary and secondary somatosensory cortices, peripheral sensory stimulation has been shown to elicit responses in the ipsilateral primary somatosensory cortex (SI). In particular, evidence is accumulating that processes of interhemispheric inhibition as depicted by negative blood oxygenation level dependent (BOLD) signal changes are part of somatosensory processes. The aim of the study was to analyze age-related differences in patterns of cerebral activation in the somatosensory system in general and processes of interhemispheric inhibition in particular. For this, a functional magnetic resonance imaging (fMRI) study was performed including 14 younger (mean age 23.3±0.9years) and 13 healthy older participants (mean age 73.2±8.3years). All subjects were scanned during peripheral electrical median nerve stimulation (40Hz) to obtain BOLD responses in the somatosensory system. Moreover, the individual current perception threshold (CPT) as a quantitative measure of sensory function was determined in a separate psychophysical testing. Significant increases in BOLD signal across the entire group could be measured within the contralateral SI, in the bilateral secondary somatosensory cortex (SII), the contralateral supplementary motor area and the insula. Negative BOLD signal changes were delineated in ipsilateral SI/MI as well as in the ipsilateral thalamus and basal ganglia. After comparing the two groups, only the cortical deactivation in ipsilateral SI in the early stimulation phase as well as the activation in contralateral SI and SII in the late stimulation block remained as statistically significant differences between the two groups. The psychophysical experiments yielded a significant age-dependent effect of CPT change with less difference in the older group which is in line with the significantly smaller alterations in maximal BOLD signal change in the contra- and ipsilateral SI found between the two groups

  5. Assessment of rodent brain activity using combined [(15)O]H2O-PET and BOLD-fMRI.

    PubMed

    Wehrl, Hans F; Martirosian, Petros; Schick, Fritz; Reischl, Gerald; Pichler, Bernd J

    2014-04-01

    The study of brain activation in small animals is of high interest for neurological research. In this study, we proposed a protocol to monitor brain activation in rats following whisker stimulation using the short half-life PET tracer [(15)O]H2O as a marker for cerebral blood flow. This technique enables the study of baseline and activation conditions in fast succession within the same scanning session. Furthermore, we compared the results obtained from PET imaging with additional BOLD-fMRI data acquired in the same animals within the same anesthetic session in immediate succession. Although the maximum relative signal changes during brain activity observed with PET were substantially higher compared to the BOLD-fMRI results, statistical analyses showed that the number of activated voxels in PET was lower compared to the fMRI measurements. Furthermore, there was a difference in the activation centers in both the shape and location between PET and fMRI. The discrepancy in the number of activated voxels could be attributed to a lower overall contrast-to-noise ratio of the PET images compared to BOLD-fMRI, whereas the difference in the spatial location indicates a more fundamental process, involving the different physiological origins of the PET and BOLD-fMRI response. This study clearly demonstrates that [(15)O]H2O-PET activation studies may be performed in small laboratory animals, and shows the complementary nature of studying brain activation using [(15)O]H2O-PET and fMRI.

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

    PubMed

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

    2009-01-01

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

  7. Effects of prenatal marijuana on response inhibition: an fMRI study of young adults.

    PubMed

    Smith, Andra M; Fried, Peter A; Hogan, Matthew J; Cameron, Ian

    2004-01-01

    The neurophysiological effects of prenatal marijuana exposure on response inhibition were assessed in 18- to 22-year-olds. Thirty-one participants from the Ottawa Prenatal Prospective Study (OPPS) performed a blocked design Go/No-Go task while neural activity was imaged with functional magnetic resonance imaging (fMRI). The OPPS is a longitudinal study that provides a unique body of information collected from each participant over 20 years, including prenatal drug history, detailed cognitive/behavioral performance from infancy to young adulthood, and current and past drug usage. The fMRI results showed that with increased prenatal marijuana exposure, there was a significant increase in neural activity in bilateral prefrontal cortex and right premotor cortex during response inhibition. There was also an attenuation of activity in left cerebellum with increased prenatal exposure to marijuana when challenging the response inhibition neural circuitry. Prenatally exposed offspring had significantly more commission errors than nonexposed participants, but all participants were able to perform the task with more than 85% accuracy. These findings were observed when controlling for present marijuana use and prenatal exposure to nicotine, alcohol and caffeine, and suggest that prenatal marijuana exposure is related to changes in neural activity during response inhibition that last into young adulthood.

  8. Crosslinking EEG time-frequency decomposition and fMRI in error monitoring.

    PubMed

    Hoffmann, Sven; Labrenz, Franziska; Themann, Maria; Wascher, Edmund; Beste, Christian

    2014-03-01

    Recent studies implicate a common response monitoring system, being active during erroneous and correct responses. Converging evidence from time-frequency decompositions of the response-related ERP revealed that evoked theta activity at fronto-central electrode positions differentiates correct from erroneous responses in simple tasks, but also in more complex tasks. However, up to now it is unclear how different electrophysiological parameters of error processing, especially at the level of neural oscillations are related, or predictive for BOLD signal changes reflecting error processing at a functional-neuroanatomical level. The present study aims to provide crosslinks between time domain information, time-frequency information, MRI BOLD signal and behavioral parameters in a task examining error monitoring due to mistakes in a mental rotation task. The results show that BOLD signal changes reflecting error processing on a functional-neuroanatomical level are best predicted by evoked oscillations in the theta frequency band. Although the fMRI results in this study account for an involvement of the anterior cingulate cortex, middle frontal gyrus, and the Insula in error processing, the correlation of evoked oscillations and BOLD signal was restricted to a coupling of evoked theta and anterior cingulate cortex BOLD activity. The current results indicate that although there is a distributed functional-neuroanatomical network mediating error processing, only distinct parts of this network seem to modulate electrophysiological properties of error monitoring.

  9. 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

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

    PubMed

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

    2016-01-01

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

  11. Brain responses to facial attractiveness induced by facial proportions: evidence from an fMRI study.

    PubMed

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

    2016-10-25

    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.

  12. 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

  13. A decomposition model and voxel selection framework for fMRI analysis to predict neural response of visual stimuli.

    PubMed

    Raut, Savita V; Yadav, Dinkar M

    2017-04-06

    This paper presents an fMRI signal analysis methodology using geometric mean curve decomposition (GMCD) and mutual information-based voxel selection framework. Previously, the fMRI signal analysis has been conducted using empirical mean curve decomposition (EMCD) model and voxel selection on raw fMRI signal. The erstwhile methodology loses frequency component, while the latter methodology suffers from signal redundancy. Both challenges are addressed by our methodology in which the frequency component is considered by decomposing the raw fMRI signal using geometric mean rather than arithmetic mean and the voxels are selected from EMCD signal using GMCD components, rather than raw fMRI signal. The proposed methodologies are adopted for predicting the neural response. Experimentations are conducted in the openly available fMRI data of six subjects, and comparisons are made with existing decomposition models and voxel selection frameworks. Subsequently, the effect of degree of selected voxels and the selection constraints are analyzed. The comparative results and the analysis demonstrate the superiority and the reliability of the proposed methodology.

  14. 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

  15. 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…

  16. 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…

  17. Silent echo-planar imaging for auditory FMRI.

    PubMed

    Schmitter, S; Diesch, E; Amann, M; Kroll, A; Moayer, M; Schad, L R

    2008-09-01

    The effect of the acoustic scanner noise produced by gradient coil switching on the auditory evoked BOLD signal represents a well-known problem in auditory functional MRI (FMRI). In this paper, a new low-noise echo-planar imaging (EPI) sequence is presented that is optimized for auditory FMRI measurements. The sequence produces a narrow-band acoustic frequency spectrum by using a sinusoidal readout echo train and a constant phase encoding gradient. This narrow band is adapted to the frequency response function of the MR scanner by varying the switching frequency of the sinusoidal readout gradient. Compared to a manufacturer-provided standard EPI sequence, the acoustic noise reduction amounts to up to 20 dBA. Using a simple block design paradigm contrasting presentation of a pure tone during ON blocks and "silence" (absence of the tone) during OFF blocks, the new low-noise sequence was evaluated and compared to the standard EPI sequence. Statistical parametric mapping (SPM) resulted in higher levels of significance of auditory activation for the low-noise sequence. These findings strongly suggest that the low-noise sequence may generate enhanced BOLD contrasts compared to the standard EPI sequences commonly used in FMRI.

  18. Bayesian spatiotemporal model of fMRI data.

    PubMed

    Quirós, Alicia; Diez, Raquel Montes; Gamerman, Dani

    2010-01-01

    This research describes a new Bayesian spatiotemporal model to analyse block-design BOLD fMRI studies. In the temporal dimension, we parameterise the hemodynamic response function's (HRF) shape with a potential increase of signal and a subsequent exponential decay. In the spatial dimension, we use Gaussian Markov random fields (GMRF) priors on activation characteristics parameters (location and magnitude) that embody our prior knowledge that evoked responses are spatially contiguous and locally homogeneous. The result is a spatiotemporal model with a small number of parameters, all of them interpretable. Simulations from the model are performed in order to ascertain the performance of the sampling scheme and the ability of the posterior to estimate model parameters, as well as to check the model sensitivity to signal to noise ratio. Results are shown on synthetic data and on real data from a block-design fMRI experiment.

  19. Deconvolution analyses with tent functions reveal delayed and long-sustained increases of BOLD signals with acupuncture stimulation.

    PubMed

    Murase, Tomokazu; Umeda, Masahiro; Fukunaga, Masaki; Tanaka, Chuzo; Higuchi, Toshihiro

    2013-01-01

    We used deconvolution analysis to examine temporal changes in brain activity after acupuncture stimulation and assess brain responses without expected reference functions. We also examined temporal changes in brain activity after sham acupuncture (noninsertive) and scrubbing stimulation. We divided 26 healthy right-handed adults into a group of 13 who received real acupuncture with manual manipulation and a group of 13 who received both tactical stimulations. Functional magnetic resonance imaging (fMRI) sequences consisted of four 15-s stimulation blocks (ON) interspersed between one 30-s and four 45-s rest blocks (OFF) for a total scanning time of 270 s. We analyzed data by using Statistical Parametric Mapping 8 (SPM8), MarsBaR, and Analysis of Functional NeuroImages (AFNI) software. For statistical analysis, we used 3dDeconvolve, part of the AFNI package, to extract the impulse response functions (IRFs) of the fMRI signals on a voxel-wise basis, and we tested the time courses of the extracted IRFs for the stimulations. We found stimulus-specific impulse responses of blood oxygen level-dependent (BOLD) signals in various brain regions. We observed significantly delayed and long-sustained increases of BOLD signals in several brain regions following real acupuncture compared to sham acupuncture and palm scrubbing, which we attribute to peripheral nocireceptors, flare responses, and processing of the central nervous system. Acupuncture stimulation induced continued activity that was stronger than activity after the other stimulations. We used tent function deconvolution to process fMRI data for acupuncture stimulation and found delayed increasing and delayed decreasing changes in BOLD signal in the somatosensory areas and areas related to pain perception. Deconvolution analyses with tent functions are expected to be useful in extracting complicated and associated brain activity that is delayed and sustained for a long period after various stimulations.

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

    PubMed Central

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

    2009-01-01

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

  1. From EEG to BOLD: brain mapping and estimating transfer functions in simultaneous EEG-fMRI acquisitions.

    PubMed

    Sato, João R; Rondinoni, Carlo; Sturzbecher, Marcio; de Araujo, Draulio B; Amaro, Edson

    2010-05-01

    Simultaneous acquisition of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) aims to disentangle the description of brain processes by exploiting the advantages of each technique. Most studies in this field focus on exploring the relationships between fMRI signals and the power spectrum at some specific frequency bands (alpha, beta, etc.). On the other hand, brain mapping of EEG signals (e.g., interictal spikes in epileptic patients) usually assumes an haemodynamic response function for a parametric analysis applying the GLM, as a rough approximation. The integration of the information provided by the high spatial resolution of MR images and the high temporal resolution of EEG may be improved by referencing them by transfer functions, which allows the identification of neural driven areas without strong assumptions about haemodynamic response shapes or brain haemodynamic's homogeneity. The difference on sampling rate is the first obstacle for a full integration of EEG and fMRI information. Moreover, a parametric specification of a function representing the commonalities of both signals is not established. In this study, we introduce a new data-driven method for estimating the transfer function from EEG signal to fMRI signal at EEG sampling rate. This approach avoids EEG subsampling to fMRI time resolution and naturally provides a test for EEG predictive power over BOLD signal fluctuations, in a well-established statistical framework. We illustrate this concept in resting state (eyes closed) and visual simultaneous fMRI-EEG experiments. The results point out that it is possible to predict the BOLD fluctuations in occipital cortex by using EEG measurements.

  2. Magnitude and phase behavior of multiresolution BOLD signal

    PubMed Central

    Chen, Zikuan; Calhoun, Vince D.

    2010-01-01

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

  3. Craving correlates with mesolimbic responses to heroin-related cues in short-term abstinence from heroin: an event-related fMRI study.

    PubMed

    Li, Qiang; Wang, Yarong; Zhang, Yi; Li, Wei; Yang, Weichuan; Zhu, Jia; Wu, Ning; Chang, Haifeng; Zheng, Ying; Qin, Wei; Zhao, Liyan; Yuan, Kai; Liu, Jixin; Wang, Wei; Tian, Jie

    2012-08-21

    Craving is an important factor in relapse to drug abuse, and cue-induced craving is an especially powerful form of this construct. Neuroimaging methods have been utilized to study drug cue-induced craving and neural correlates in the human brain. However, very few studies have focused on characterizing craving and the neural responses to heroin-related cues in short-term abstinent heroin-dependent patients. Twenty-four heroin-dependent subjects and 20 demographically matched drug-naïve subjects participated in this study. An event-related cue-reactivity paradigm was employed, while changes in blood oxygen level-dependent (BOLD) signals were acquired by functional magnetic resonance imaging (fMRI). The heroin-dependent group reported significantly increased craving following exposure to heroin-related cues. Direct comparison between the two groups showed that brain activation to heroin-related minus neutral cues was significantly greater for the heroin-dependent group in the bilateral nucleus accumbens (NAc), caudate, putamen, amygdala, hippocampus/parahippocampus, midcingulate cortex, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), medial frontal gyrus (MeFG), midbrain, thalamus, left anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and subcallosal gyrus. Changes in craving in the heroin-dependent group correlated positively with brain activation in the bilateral NAc, caudate, right putamen, and left ACC. The abstinence duration correlated positively with brain activation in the left caudate and right parahippocampal gyrus. In conclusion, the cue-reactivity paradigm significantly activated neural responses in the mesolimbic dopamine (DA) system and prefrontal cortex (PFC) and induced increased craving in short-term abstinent heroin-dependent patients. We suggest that these response patterns characterize the high vulnerability of relapse in short-term abstinent heroin-dependent subjects. Copyright © 2012 Elsevier B.V. All

  4. Sustained blood oxygenation and volume response to repetition rate-modulated sound in human auditory cortex.

    PubMed

    Seifritz, Erich; Di Salle, Francesco; Esposito, Fabrizio; Bilecen, Deniz; Neuhoff, John G; Scheffler, Klaus

    2003-10-01

    The blood oxygen level-dependent (BOLD) signal time course in the auditory cortex is characterized by two components, an initial transient peak and a subsequent sustained plateau with smaller amplitude. Because the T(2)(*) signal detected by functional magnetic resonance imaging (fMRI) depends on at least two counteracting factors, blood oxygenation and volume, we examined whether the reduction in the sustained BOLD signal results from decreased levels of oxygenation or from increased levels of blood volume. We used conventional fMRI to quantify the BOLD signal and fMRI in combination with superparamagnetic contrast agent to quantify blood volume and employed repetition rate-modulated sounds in a silent background to manipulate the response amplitude in the auditory cortex. In the BOLD signal, the initial peak reached 3.3% with pulsed sound and 1.9% with continuous sound, whereas the sustained BOLD signal fell to 2.2% with pulsed sound and to 0.5% with continuous sound, respectively. The repetition rate-dependent reduction in the sustained BOLD amplitude was accompanied by concordant changes in sustained blood volume levels, which, compared to silence, increased by approximately 30% with pulsed and by approximately 10% with continuous sound. Thus, our data suggest that the reduced amplitude of the sustained BOLD signal reflects stimulus-dependent modulation of blood oxygenation rather than blood volume-related effects.

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

    PubMed Central

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

    2011-01-01

    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. Adjudicating between face-coding models with individual-face fMRI responses

    PubMed Central

    Kriegeskorte, Nikolaus

    2017-01-01

    The perceptual representation of individual faces is often explained with reference to a norm-based face space. In such spaces, individuals are encoded as vectors where identity is primarily conveyed by direction and distinctiveness by eccentricity. Here we measured human fMRI responses and psychophysical similarity judgments of individual face exemplars, which were generated as realistic 3D animations using a computer-graphics model. We developed and evaluated multiple neurobiologically plausible computational models, each of which predicts a representational distance matrix and a regional-mean activation profile for 24 face stimuli. In the fusiform face area, a face-space coding model with sigmoidal ramp tuning provided a better account of the data than one based on exemplar tuning. However, an image-processing model with weighted banks of Gabor filters performed similarly. Accounting for the data required the inclusion of a measurement-level population averaging mechanism that approximates how fMRI voxels locally average distinct neuronal tunings. Our study demonstrates the importance of comparing multiple models and of modeling the measurement process in computational neuroimaging. PMID:28746335

  7. 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.

  8. 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

  9. 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.

  10. Semantic processing and response inhibition.

    PubMed

    Chiang, Hsueh-Sheng; Motes, Michael A; Mudar, Raksha A; Rao, Neena K; Mansinghani, Sethesh; Brier, Matthew R; Maguire, Mandy J; Kraut, Michael A; Hart, John

    2013-11-13

    The present study examined functional MRI (fMRI) BOLD signal changes in response to object categorization during response selection and inhibition. Young adults (N=16) completed a Go/NoGo task with varying object categorization requirements while fMRI data were recorded. Response inhibition elicited increased signal change in various brain regions, including medial frontal areas, compared with response selection. BOLD signal in an area within the right angular gyrus was increased when higher-order categorization was mandated. In addition, signal change during response inhibition varied with categorization requirements in the left inferior temporal gyrus (lIT). lIT-mediated response inhibition when inhibiting the response only required lower-order categorization, but lIT mediated both response selection and inhibition when selecting and inhibiting the response required higher-order categorization. The findings characterized mechanisms mediating response inhibition associated with semantic object categorization in the 'what' visual object memory system.

  11. Multimodal imaging of repetition priming: Using fMRI, MEG, and intracranial EEG to reveal spatiotemporal profiles of word processing

    PubMed Central

    McDonald, Carrie R.; Thesen, Thomas; Carlson, Chad; Blumberg, Mark; Girard, Holly M.; Trongnetrpunya, Amy; Sherfey, Jason S.; Devinsky, Orrin; Kuzniecky, Rubin; Dolye, Werner K.; Cash, Sydney S.; Leonard, Matt K.; Hagler, Donald J.; Dale, Anders M.; Halgren, Eric

    2010-01-01

    Repetition priming is a core feature of memory processing whose anatomical correlates remain poorly understood. In this study, we use advanced multimodal imaging (functional magnetic resonance imaging (fMRI) and magnetoencephalography; MEG) to investigate the spatiotemporal profile of repetition priming. We use intracranial electroencephalography (iEEG) to validate our fMRI/MEG measurements. Twelve controls completed a semantic judgment task with fMRI and MEG that included words presented once (new, ‘N’) and words that repeated (old, ‘O’). Six patients with epilepsy completed the same task during iEEG recordings. Blood-oxygen level dependent (BOLD) responses for N vs O words were examined across the cortical surface and within regions of interest. MEG waveforms for N vs O words were estimated using a noise-normalized minimum norm solution, and used to interpret the timecourse of fMRI. Spatial concordance was observed between fMRI and MEG repetition effects from 350–450ms within bilateral occipitotemporal and medial temporal, left prefrontal, and left posterior temporal cortex. Additionally, MEG revealed widespread sources within left temporoparietal regions, whereas fMRI revealed bilateral reductions in occipitotemporal and left superior frontal, and increases in inferior parietal, precuneus, and dorsolateral prefrontal activity. BOLD suppression in left posterior temporal, left inferior prefrontal, and right occipitotemporal cortex correlated with MEG repetition-related reductions. IEEG responses from all three regions supported the timecourse of MEG and localization of fMRI. Furthermore, iEEG decreases to repeated words were associated with decreased gamma power in several regions, providing evidence that gamma oscillations are tightly coupled to cognitive phenomena and reflect regional activations seen in the BOLD signal. PMID:20620212

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

    PubMed Central

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

    2010-01-01

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

  13. 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

  14. 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

  15. White versus gray matter: fMRI hemodynamic responses show similar characteristics, but differ in peak amplitude

    PubMed Central

    2012-01-01

    Background There is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation. Results Examination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes. Conclusions Overall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T. PMID:22852798

  16. Reconstructing the spectrotemporal modulations of real-life sounds from fMRI response patterns

    PubMed Central

    Santoro, Roberta; Moerel, Michelle; De Martino, Federico; Valente, Giancarlo; Ugurbil, Kamil; Yacoub, Essa; Formisano, Elia

    2017-01-01

    Ethological views of brain functioning suggest that sound representations and computations in the auditory neural system are optimized finely to process and discriminate behaviorally relevant acoustic features and sounds (e.g., spectrotemporal modulations in the songs of zebra finches). Here, we show that modeling of neural sound representations in terms of frequency-specific spectrotemporal modulations enables accurate and specific reconstruction of real-life sounds from high-resolution functional magnetic resonance imaging (fMRI) response patterns in the human auditory cortex. Region-based analyses indicated that response patterns in separate portions of the auditory cortex are informative of distinctive sets of spectrotemporal modulations. Most relevantly, results revealed that in early auditory regions, and progressively more in surrounding regions, temporal modulations in a range relevant for speech analysis (∼2–4 Hz) were reconstructed more faithfully than other temporal modulations. In early auditory regions, this effect was frequency-dependent and only present for lower frequencies (<∼2 kHz), whereas for higher frequencies, reconstruction accuracy was higher for faster temporal modulations. Further analyses suggested that auditory cortical processing optimized for the fine-grained discrimination of speech and vocal sounds underlies this enhanced reconstruction accuracy. In sum, the present study introduces an approach to embed models of neural sound representations in the analysis of fMRI response patterns. Furthermore, it reveals that, in the human brain, even general purpose and fundamental neural processing mechanisms are shaped by the physical features of real-world stimuli that are most relevant for behavior (i.e., speech, voice). PMID:28420788

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

    PubMed

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

    2016-01-01

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

  18. Current Serum Lipoprotein Levels and fMRI Response to Working Memory in Midlife

    PubMed Central

    Gonzales, Mitzi M.; Tarumi, Takashi; Eagan, Danielle E.; Tanaka, Hirofumi; Biney, Fedora O.; Haley, Andreana P.

    2011-01-01

    Aims Given that high cholesterol levels at midlife are a risk factor for future cognitive decline, the goal of the current study was to determine if cholesterol-related alterations in the cerebrovascular response to cognition could be detected at midlife. Methods Forty adults, aged 40–60 years, performed a 2-Back working memory task during fMRI. The associations between serum total cholesterol, HDL-cholesterol, and total cholesterol/HDL-cholesterol concentrations to task-related activation intensity were modeled using multivariate multiple regression (two-tailed p < 0.02). Results Higher levels of total cholesterol/HDL-cholesterol related to reduced working memory-related activation intensity in the left inferior parietal lobe, right superior frontal gyrus, and right middle frontal gyrus. Conclusion These data provide preliminary support for a deleterious effect of elevated total cholesterol/HDL-cholesterol ratio on cerebrovascular support for cognition in midlife. PMID:21494033

  19. 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

  20. 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.

  1. 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

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

    PubMed

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

    2016-05-21

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

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

    PubMed

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

    2012-08-01

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

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

    PubMed Central

    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

    2015-01-01

    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

  5. 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

  6. Physiological characterization of a robust survival rodent fMRI method.

    PubMed

    Brynildsen, Julia K; Hsu, Li-Ming; Ross, Thomas J; Stein, Elliot A; Yang, Yihong; Lu, Hanbing

    2017-01-01

    Anesthetics are commonly used in preclinical functional MRI studies. It is well-appreciated that proper choice of anesthetics is of critical importance for maintaining a physiologically normal range of autonomic functioning. A recent study, using a low dose of dexmedetomidine (active isomer of medetomidine) in combination with a low dose of isoflurane, suggested stable measurements across repeated fMRI experiments in individual animals with each session lasting up to several hours. The rat default mode network has been successfully identified using this preparation, indicating that this protocol minimally disturbs brain network functions. However, medetomidine is known to cause peripheral vasoconstriction, respiratory suppression, and bradycardia, each of which could independently confound the BOLD signal. The goal of this study was to systematically characterize physiological conditions for fMRI experiments under this anesthetic regimen. To this end, we acquired somatosensory stimulation "task-evoked" and resting-state fMRI to evaluate the integrity of neurovascular coupling and brain network function during three time windows (0-30min, 30-90min, and 90-150min) following dexmedetomidine initiation. Results demonstrate that both evoked BOLD response and resting-state fMRI signal remained stable during the 90-150min time window, while autonomic physiological parameters maintained near-normal conditions during this period. Our data suggest that using a spontaneously-inhaled, low dose of isoflurane in combination with a continuous low dose of dexmedetomidine is a viable option for longitudinal imaging studies in rats.

  7. 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…

  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. Cortical sensory map rearrangement after spinal cord injury: fMRI responses linked to Nogo signalling.

    PubMed

    Endo, Toshiki; Spenger, Christian; Tominaga, Teiji; Brené, Stefan; Olson, Lars

    2007-11-01

    Cortical sensory maps can reorganize in the adult brain in an experience-dependent manner. We monitored somatosensory cortical reorganization after sensory deafferentation using functional magnetic resonance imaging (fMRI) in rats subjected to complete transection of the mid-thoracic spinal cord. Cortical representation in response to spared forelimb stimulation was observed to enlarge and invade adjacent sensory-deprived hind limb territory in the primary somatosensory cortex as early as 3 days after injury. Functional MRI also demonstrated long-term cortical plasticity accompanied by increased thalamic activation. To support the notion that alterations of cortical neuronal circuitry after spinal cord injury may underlie the fMRI changes, we quantified transcriptional activities of several genes related to cortical plasticity including the Nogo receptor (NgR), its co-receptor LINGO-1 and brain derived neurotrophic factor (BDNF), using in situ hybridization. We demonstrate that NgR and LINGO-1 are down-regulated specifically in cortical areas deprived of sensory input and in adjacent cortex from 1 day after injury, while BDNF is up-regulated. Our results demonstrate that cortical neurons react to sensory deprivation by decreasing transcriptional activities of genes encoding the Nogo receptor components in the sensory deprived and the anatomically adjacent non-deprived area. Combined with the BDNF up-regulation, these changes presumably allow structural changes in the neuropil. Our observations therefore suggest an involvement of Nogo signalling in cortical activity-dependent plasticity in the somatosensory system. In spinal cord injury, cortical reorganization as shown here can become a disadvantage, much like the situation in amblyopia or phantom sensation. Successful strategies to repair sensory pathways at the spinal cord level may not lead to proper reestablishment of cortical connections, once deprived hind limb cortical areas have been reallocated to forelimb

  10. 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.

  11. 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

  12. Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: Implications for functional connectivity at rest.

    PubMed

    Shmuel, Amir; Leopold, David A

    2008-07-01

    Recent studies have demonstrated large amplitude spontaneous fluctuations in functional-MRI (fMRI) signals in humans in the resting state. Importantly, these spontaneous fluctuations in blood-oxygenation-level-dependent (BOLD) signal are often synchronized over distant parts of the brain, a phenomenon termed functional-connectivity. Functional-connectivity is widely assumed to reflect interregional coherence of fluctuations in activity of the underlying neuronal networks. Despite the large body of human imaging literature on spontaneous activity and functional-connectivity in the resting state, the link to underlying neural activity remains tenuous. Through simultaneous fMRI and intracortical neurophysiological recording, we demonstrate correlation between slow fluctuations in BOLD signals and concurrent fluctuations in the underlying locally measured neuronal activity. This correlation varied with time-lag of BOLD relative to neuronal activity, resembling a traditional hemodynamic response function with peaks at approximately 6 s lag of BOLD signal. The correlations were reliably detected when the neuronal signal consisted of either the spiking rate of a small group of neurons, or relative power changes in the multi-unit activity band, and particularly in the local field potential gamma band. Analysis of correlation between the voxel-by-voxel fMRI time-series and the neuronal activity measured within one cortical site showed patterns of correlation that slowly traversed cortex. BOLD fluctuations in widespread areas in visual cortex of both hemispheres were significantly correlated with neuronal activity from a single recording site in V1. To the extent that our V1 findings can be generalized to other cortical areas, fMRI-based functional-connectivity between remote regions in the resting state can be linked to synchronization of slow fluctuations in the underlying neuronal signals.

  13. Decoding Articulatory Features from fMRI Responses in Dorsal Speech Regions.

    PubMed

    Correia, Joao M; Jansma, Bernadette M B; Bonte, Milene

    2015-11-11

    The brain's circuitry for perceiving and producing speech may show a notable level of overlap that is crucial for normal development and behavior. The extent to which sensorimotor integration plays a role in speech perception remains highly controversial, however. Methodological constraints related to experimental designs and analysis methods have so far prevented the disentanglement of neural responses to acoustic versus articulatory speech features. Using a passive listening paradigm and multivariate decoding of single-trial fMRI responses to spoken syllables, we investigated brain-based generalization of articulatory features (place and manner of articulation, and voicing) beyond their acoustic (surface) form in adult human listeners. For example, we trained a classifier to discriminate place of articulation within stop syllables (e.g., /pa/ vs /ta/) and tested whether this training generalizes to fricatives (e.g., /fa/ vs /sa/). This novel approach revealed generalization of place and manner of articulation at multiple cortical levels within the dorsal auditory pathway, including auditory, sensorimotor, motor, and somatosensory regions, suggesting the representation of sensorimotor information. Additionally, generalization of voicing included the right anterior superior temporal sulcus associated with the perception of human voices as well as somatosensory regions bilaterally. Our findings highlight the close connection between brain systems for speech perception and production, and in particular, indicate the availability of articulatory codes during passive speech perception. Sensorimotor integration is central to verbal communication and provides a link between auditory signals of speech perception and motor programs of speech production. It remains highly controversial, however, to what extent the brain's speech perception system actively uses articulatory (motor), in addition to acoustic/phonetic, representations. In this study, we examine the role of

  14. 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.

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

    PubMed

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

    2011-07-01

    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.

  16. 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

  17. Impulsivity and aggression mediate regional brain responses in Borderline Personality Disorder: An fMRI study.

    PubMed

    Soloff, Paul H; Abraham, Kristy; Burgess, Ashley; Ramaseshan, Karthik; Chowdury, Asadur; Diwadkar, Vaibhav A

    2017-02-28

    Fronto-limbic brain networks involved in regulation of impulsivity and aggression are abnormal in Borderline Personality Disorder (BPD). However, it is unclear whether, or to what extent, these personality traits actually modulate brain responses during cognitive processing. Using fMRI, we examined the effects of trait impulsivity, aggression, and depressed mood on regional brain responses in 31 female BPD and 25 control subjects during a Go No-Go task using Ekman faces as targets. First-level contrasts modeled effects of negative emotional context. Second-level regression models used trait impulsivity, aggression and depressed mood as predictor variables of regional brain activations. In BPD, trait impulsivity was positively correlated with activation in the dorsal anterior cingulate cortex, orbital frontal cortex (OFC), basal ganglia (BG), and dorsolateral prefrontal cortex, with no areas of negative correlation. In contrast, aggression was negatively correlated with activation in OFC, hippocampus, and BG, with no areas of positive correlation. Depressed mood had a generally dampening effect on activations. Effects of trait impulsivity on healthy controls differed from effects in BPD, suggesting a disorder-specific response. Negative emotional context and trait impulsivity, but not aggression or depression, diminished task performance across both groups. Negative emotional context may interfere with cognitive functioning in BPD through interaction with the neurobiology of personality traits.

  18. The spatiospectral characterization of brain networks: fusing concurrent EEG spectra and fMRI maps.

    PubMed

    Bridwell, David A; Wu, Lei; Eichele, Tom; Calhoun, Vince D

    2013-04-01

    Different imaging modalities capture different aspects of brain activity. Functional magnetic resonance imaging (fMRI) reveals intrinsic networks whose BOLD signals have periods from 100 s (0.01 Hz) to about 10s (0.1 Hz). Electroencephalographic (EEG) recordings, in contrast, commonly reflect cortical electrical fluctuations with periods up to 20 ms (50 Hz) or above. We examined the correspondence between intrinsic fMRI and EEG network activity at rest in order to characterize brain networks both spatially (with fMRI) and spectrally (with EEG). Brain networks were separately identified within the concurrently recorded fMRI and EEG at the aggregate group level with group independent component analysis and the association between spatial fMRI and frequency by spatial EEG sources was examined by deconvolving their component time courses. The two modalities are considered linked if the estimated impulse response function (IRF) is significantly non-zero at biologically plausible delays. We found that negative associations were primarily present within two of five alpha components, which highlights the importance of considering multiple alpha sources in EEG-fMRI. Positive associations were primarily present within the lower (e.g. delta and theta) and higher (e.g. upper beta and lower gamma) spectral regions, sometimes within the same fMRI components. Collectively, the results demonstrate a promising approach to characterize brain networks spatially and spectrally, and reveal that positive and negative associations appear within partially distinct regions of the EEG spectrum.

  19. Effects of spatial fMRI resolution on the classification of naturalistic movies.

    PubMed

    Mandelkow, H; de Zwart, J A; Duyn, J H

    2017-08-24

    Studies involving multivariate pattern analysis (MVPA) of BOLD fMRI data generally attribute the success of the information-theoretic approach to BOLD signal contrast on the fine spatial scale of millimeters facilitating the classification or decoding of perceptual stimuli. However, to date MVPA studies that have actually explored fMRI resolutions at less than 2 mm voxel size are rare and limited to small sets of unnatural stimuli (like visual gratings) as well as specific sub-regions of the brain, notably the primary somatosensory cortices. To investigate what spatial scale best supports high information extraction under more general conditions this study combined naturalistic movie stimuli with high-resolution fMRI at 7 T and linear discriminant analysis (LDA) of global and local BOLD signal patterns. Contrary to predictions, LDA and similar classifiers reached a maximum in classification accuracy (CA) at a smoothed resolution close to 3 mm, well above the 1.2 mm voxel size of the fMRI acquisition. Maximal CAs around 90% were contingent upon global fMRI signal patterns comprising 4 k-16 k of the most reactive voxels distributed sparsely throughout the occipital and ventro-temporal cortices. A Searchlight analysis of local fMRI patterns largely confirmed the global results, but also revealed a small subset of brain regions in early visual cortex showing limited increases in CA with higher resolution. Principal component analysis of the global and local fMRI signal patterns suggested that reproducible neuronal contributions were spatially auto-correlated and smooth, while other components of higher spatial frequency were likely related to physiological noise and responsible for the reduced CA at higher resolution. Systematic differences between experiments and subjects suggested that higher CA was significantly correlated with more consistent behavior revealed by eye tracking. Thus, the optimal resolution of fMRI data for MVPA was mainly limited by

  20. 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

  1. [fMRI study of deliberate deception].

    PubMed

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

    2012-01-01

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

  2. A blind deconvolution approach to recover effective connectivity brain networks from resting state fMRI data.

    PubMed

    Wu, Guo-Rong; Liao, Wei; Stramaglia, Sebastiano; Ding, Ju-Rong; Chen, Huafu; Marinazzo, Daniele

    2013-04-01

    A great improvement to the insight on brain function that we can get from fMRI data can come from effective connectivity analysis, in which the flow of information between even remote brain regions is inferred by the parameters of a predictive dynamical model. As opposed to biologically inspired models, some techniques as Granger causality (GC) are purely data-driven and rely on statistical prediction and temporal precedence. While powerful and widely applicable, this approach could suffer from two main limitations when applied to BOLD fMRI data: confounding effect of hemodynamic response function (HRF) and conditioning to a large number of variables in presence of short time series. For task-related fMRI, neural population dynamics can be captured by modeling signal dynamics with explicit exogenous inputs; for resting-state fMRI on the other hand, the absence of explicit inputs makes this task more difficult, unless relying on some specific prior physiological hypothesis. In order to overcome these issues and to allow a more general approach, here we present a simple and novel blind-deconvolution technique for BOLD-fMRI signal. In a recent study it has been proposed that relevant information in resting-state fMRI can be obtained by inspecting the discrete events resulting in relatively large amplitude BOLD signal peaks. Following this idea, we consider resting fMRI as 'spontaneous event-related', we individuate point processes corresponding to signal fluctuations with a given signature, extract a region-specific HRF and use it in deconvolution, after following an alignment procedure. Coming to the second limitation, a fully multivariate conditioning with short and noisy data leads to computational problems due to overfitting. Furthermore, conceptual issues arise in presence of redundancy. We thus apply partial conditioning to a limited subset of variables in the framework of information theory, as recently proposed. Mixing these two improvements we compare the

  3. 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

  4. Contextual effects on cognitive control and BOLD activation in single versus mixed saccade tasks.

    PubMed

    Pierce, Jordan E; McDowell, Jennifer E

    2017-03-31

    The context or trial history of a task influences response efficiency in mixed paradigms based on cognitive control demands for task set selection. In the current study, the impact of context on prosaccade and antisaccade trials in single and mixed tasks was investigated with BOLD fMRI. Prosaccades require a look towards a newly appearing target, while antisaccades require cognitive control for prepotent response inhibition and generation of a saccade to the opposite location. Results indicated slower prosaccade reaction times and more antisaccade errors for switched than repeated or single trials, and slower antisaccade reaction times for single than mixed trials. BOLD activation was greater for the mixed than the single context in frontal eye fields and precuneus, while switch trials had greater activation than repeat trials in posterior parietal and middle occipital cortex. Greater antisaccade activation was observed overall in saccade circuitry, although effects were evident primarily for the mixed task when considered separately. Finally, an interaction was observed in superior frontal cortex, precuneus, anterior cingulate, and thalamus with strong responses for antisaccade switch trials in the latter two regions. Altogether this response pattern demonstrated the sensitivity of cognitive control to changing task conditions, especially due to task switching costs. Such context-specific differences highlight the importance of trial history when assessing cognitive control.

  5. 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

  6. 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

  7. Vowel-specific mismatch responses in the anterior superior temporal gyrus: an fMRI study.

    PubMed

    Leff, Alexander P; Iverson, Paul; Schofield, Thomas M; Kilner, James M; Crinion, Jennifer T; Friston, Karl J; Price, Cathy J

    2009-04-01

    There have been many functional imaging studies that have investigated the neural correlates of speech perception by contrasting neural responses to speech and "speech-like" but unintelligible control stimuli. A potential drawback of this approach is that intelligibility is necessarily conflated with a change in the acoustic parameters of the stimuli. The approach we have adopted is to take advantage of the mismatch response elicited by an oddball paradigm to probe neural responses in temporal lobe structures to a parametrically varied set of deviants in order to identify brain regions involved in vowel processing. Thirteen normal subjects were scanned using a functional magnetic resonance imaging (fMRI) paradigm while they listened to continuous trains of auditory stimuli. Three classes of stimuli were used: 'vowel deviants' and two classes of control stimuli: one acoustically similar ('single formants') and the other distant (tones). The acoustic differences between the standard and deviants in both the vowel and single-formant classes were designed to match each other closely. The results revealed an effect of vowel deviance in the left anterior superior temporal gyrus (aSTG). This was most significant when comparing all vowel deviants to standards, irrespective of their psychoacoustic or physical deviance. We also identified a correlation between perceptual discrimination and deviant-related activity in the dominant superior temporal sulcus (STS), although this effect was not stimulus specific. The responses to vowel deviants were in brain regions implicated in the processing of intelligible or meaningful speech, part of the so-called auditory "what" processing stream. Neural components of this pathway would be expected to respond to sudden, perhaps unexpected changes in speech signal that result in a change to narrative meaning.

  8. Determining the Precise Cerebral Response to Acupuncture: An Improved fMRI Study

    PubMed Central

    Shan, Baoci; Li, Yongzhong; Li, Lin; Xue, Jingquan; Nie, Binbin

    2012-01-01

    Background In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects’ psychological attitude to acupuncture and their physical state are the three most confounding factors. Objective To obtain more precise and accurate cerebral fMRI mapping of acupuncture. Design and Setting A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China. Participants Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D. Interventions Group A received real acupuncture (RA) and treatment instruction (TI); Group B received RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and TI; Group D received SA and NI. Results Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas. Conclusions The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results. PMID:23152865

  9. Counterfactual thinking and reward processing: an fMRI study of responses to gamble outcomes.

    PubMed

    Henderson, Sarah E; Norris, Catherine J

    2013-01-01

    The process of comparing obtained outcomes to alternative possible outcomes, known as counterfactual thinking, is inescapable in daily life; however, the neurocognitive mechanisms underlying counterfactual thinking and how they influence emotional responses to better and worse outcomes is not well understood. We conducted an event-related functional magnetic resonance imaging (fMRI) gambling study in which participants were informed of two equally possible outcomes of a card gamble before they selected a card. Participants reported experiencing mixed emotions (i.e., both positive and negative affect) for disappointing wins (winning the lesser of two amounts) and relieving losses (losing the lesser of two amounts). Neuroimaging results supported the hypothesis that these mixed emotions were associated with activation of a fronto-parietal network, which subsequently influenced processing in reward and punishment regions (dorsal and ventral striatum, right anterior insula). The fronto-parietal network was sensitive to outcomes that resulted in mixed emotions, whereas reward and punishment regions were sensitive to comparisons between obtained and unobtained outcomes. These findings provide insight into the neurocognitive mechanisms underlying the mixed emotional experiences that result from counterfactual comparisons, and inform our understanding of how the brain is optimized to use the wealth of environmental information to inform current and future behavior.

  10. EEG and FMRI coregistration to investigate the cortical oscillatory activities during finger movement.

    PubMed

    Formaggio, Emanuela; Storti, Silvia Francesca; Avesani, Mirko; Cerini, Roberto; Milanese, Franco; Gasparini, Anna; Acler, Michele; Pozzi Mucelli, Roberto; Fiaschi, Antonio; Manganotti, Paolo

    2008-12-01

    Electroencephalography combined with functional magnetic resonance imaging (EEG-fMRI) may be used to identify blood oxygenation level dependent (BOLD) signal changes associated with physiological and pathological EEG event. In this study we used EEG-fMRI to determine the possible correlation between topographical movement-related EEG changes in brain oscillatory activity recorded from EEG electrodes over the scalp and fMRI-BOLD cortical responses in motor areas during finger movement. Thirty-two channels of EEG were recorded in 9 subjects during eyes-open condition inside a 1.5 T magnetic resonance (MR) scanner using a MR-compatible EEG recording system. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. For EEG data analysis we used the event-related-synchronization/desynchronization (ERS/ERD) approach to investigate where movement-related decreases in alpha and beta power are located. For image statistical analysis we used a general linear model (GLM) approach. There was a significant correlation between the positive-negative ratio of BOLD signal peaks and ERD values in the electrodes over the region of activation. We conclude that combined EEG-fMRI may be used to investigate movement-related oscillations of the human brain inside an MRI scanner and the movement-related changes in the EMG or EEG signals are useful to identify the brain activation sources responsible for BOLD-signal changes.

  11. 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…

  12. 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…

  13. A new approach to measure single-event related brain activity using real-time fMRI: feasibility of sensory, motor, and higher cognitive tasks.

    PubMed

    Posse, S; Binkofski, F; Schneider, F; Gembris, D; Frings, W; Habel, U; Salloum, J B; Mathiak, K; Wiese, S; Kiselev, V; Graf, T; Elghahwagi, B; Grosse-Ruyken, M L; Eickermann, T

    2001-01-01

    Real-time fMRI is a rapidly emerging methodology that enables monitoring changes in brain activity during an ongoing experiment. In this article we demonstrate the feasibility of performing single-event sensory, motor, and higher cognitive tasks in real-time on a clinical whole-body scanner. This approach requires sensitivity optimized fMRI methods: Using statistical parametric mapping we quantified the spatial extent of BOLD contrast signal changes as a function of voxel size and demonstrate that sacrificing spatial resolution and readout bandwidth improves the detection of signal changes in real time. Further increases in BOLD contrast sensitivity were obtained by using real-time multi-echo EPI. Real-time image analysis was performed using our previously described Functional Imaging in REal time (FIRE) software package, which features real-time motion compensation, sliding window correlation analysis, and automatic reference vector optimization. This new fMRI methodology was validated using single-block design paradigms of standard visual, motor, and auditory tasks. Further, we demonstrate the sensitivity of this method for online detection of higher cognitive functions during a language task using single-block design paradigms. Finally, we used single-event fMRI to characterize the variability of the hemodynamic impulse response in primary and supplementary motor cortex in consecutive trials using single movements. Real-time fMRI can improve reliability of clinical and research studies and offers new opportunities for studying higher cognitive functions.

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

    PubMed Central

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

    2010-01-01

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

  15. Baseline blood oxygenation modulates response amplitude

    PubMed Central

    Lu, Hanzhang; Zhao, Chenguang; Ge, Yulin; Lewis-Amezcua, Kelly

    2008-01-01

    Although BOLD fMRI provides a useful tool for probing neuronal activities, large inter-subject variations in signal amplitude are commonly observed. Understanding the physiologic basis for these variations will have a significant impact on many fMRI studies. First, the physiologic modulator can be used as a regressor to reduce variations across subjects, thereby improving statistical power for detecting group differences. Second, if a pathologic condition or a drug treatment is shown to change fMRI responses, monitoring this modulatory parameter is useful in correctly interpreting the fMRI changes to neuronal deficits/recruitments. Here we present evidence that the task-evoked fMRI signals are modulated by baseline blood oxygenation. To measure global blood oxygenation, we used a recently developed technique, T2-Relaxation-Under-Spin-Tagging MRI, yielding baseline oxygenation of 63.7±7.2% in sagittal sinus with an estimation error of 1.3%. It was found that individuals with higher baseline oxygenation tend to have a smaller fMRI signal and vice versa. For every 10% difference in baseline oxygenation across subjects, the BOLD and cerebral blood flow signal differ by -0.4% and -30.0%, respectively, when using visual stimulation. TRUST MRI is a useful measurement for fMRI studies to control for the modulatory effects of baseline oxygenation that are unique to each subject. PMID:18666103

  16. Neurophysiologic correlates of fMRI in human motor cortex.

    PubMed

    Hermes, Dora; Miller, Kai J; Vansteensel, Mariska J; Aarnoutse, Erik J; Leijten, Frans S S; Ramsey, Nick F

    2012-07-01

    The neurophysiological underpinnings of functional magnetic resonance imaging (fMRI) are not well understood. To understand the relationship between the fMRI blood oxygen level dependent (BOLD) signal and neurophysiology across large areas of cortex, we compared task related BOLD change during simple finger movement to brain surface electric potentials measured on a similar spatial scale using electrocorticography (ECoG). We found that spectral power increases in high frequencies (65-95 Hz), which have been related to local neuronal activity, colocalized with spatially focal BOLD peaks on primary sensorimotor areas. Independent of high frequencies, decreases in low frequency rhythms (<30 Hz), thought to reflect an aspect of cortical-subcortical interaction, colocalized with weaker BOLD signal increase. A spatial regression analysis showed that there was a direct correlation between the amplitude of the task induced BOLD change on different areas of primary sensorimotor cortex and the amplitude of the high frequency change. Low frequency change explained an additional, different part of the spatial BOLD variance. Together, these spectral power changes explained a significant 36% of the spatial variance in the BOLD signal change (R(2) = 0.36). These results suggest that BOLD signal change is largely induced by two separate neurophysiological mechanisms, one being spatially focal neuronal processing and the other spatially distributed low frequency rhythms. Copyright © 2011 Wiley-Liss, Inc.

  17. 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.

  18. Phase-synchronization-based parcellation of resting state fMRI signals reveals topographically organized clusters in early visual cortex.

    PubMed

    Gravel, Nicolás; Harvey, Ben M; Renken, Remco J; Dumoulin, Serge O; Cornelissen, Frans W

    2017-09-01

    Resting-state fMRI is widely used to study brain function and connectivity. However, interpreting patterns of resting state (RS) fMRI activity remains challenging as they may arise from different neuronal mechanisms than those triggered by exogenous events. Currently, this limits the use of RS-fMRI for understanding cortical function in health and disease. Here, we examine the phase synchronization (PS) properties of blood-oxygen level dependent (BOLD) signals obtained during visual field mapping (VFM) and RS with 7T fMRI. This data-driven approach exploits spatiotemporal covariations in the phase of BOLD recordings to establish the presence of clusters of synchronized activity. We find that, in both VFM and RS data, selecting the most synchronized neighboring recording sites identifies spatially localized PS clusters that follow the topographic organization of the visual cortex. However, in activity obtained during VFM, PS is spatially more extensive than in RS activity, likely reflecting stimulus-driven interactions between local responses. Nevertheless, the similarity of the PS clusters obtained for RS and stimulus-driven fMRI suggest that they share a common neuroanatomical origin. Our finding justifies and facilitates direct comparison of RS and stimulus-evoked activity. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2015-01-01

    Abnormal fMRI habituation in autism spectrum disorders (ASD) 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 fearful faces, houses, and scrambled images were collected. We found significantly reduced habituation to fearful faces but not houses in ASD. In addition, amygdala habituation to faces had robust discriminability (ASD versus TD; area under the curve (AUC) = .852, p<.000). In contrast, habituation to houses had no predictive value (AUC = .573, p =.365). Amygdala habituation to emotional faces may be useful for quantifying risk in ASD. PMID:26340957

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

    PubMed Central

    Horner, Aidan J.; Henson, Richard N.

    2013-01-01

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

  1. The NIH experience in first advancing fMRI.

    PubMed

    Turner, Robert

    2012-08-15

    The introduction of functional MRI at NIH in 1992 was the outcome of research goals first formulated by Turner in 1983. Between 1988 and 1990, Turner worked at NIH on actively-shielded gradient coils and the implementation of EPI-based techniques, especially diffusion-weighted EPI. His work on hypoxia in cat brain in 1990 directly inspired Ken Kwong's demonstration of BOLD contrast in humans at MGH in May 1991. Turner collaborated actively with this MGH team, the first group to map entirely noninvasively human brain activity due to visual stimulation. He introduced BOLD fMRI at NIH in February 1992. This paper reviews the steps that led up to BOLD EPI, and Turner's initial applications of BOLD fMRI at NIH.

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

    PubMed Central

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

    2015-01-01

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

  3. Involvement of NMDA receptor subtypes in cortical spreading depression in rats assessed by fMRI.

    PubMed

    Shatillo, Artem; Salo, Raimo A; Giniatullin, Rashid; Gröhn, Olli H

    2015-06-01

    Cortical spreading depression (CSD) is a phenomenon implicated in migraine with aura and associated with other neurological disorders (e.g. stroke, brain trauma). Current evidence points to the essential role of NMDA receptors in CSD mechanisms. However, the roles of multiple subunits of NMDA receptors expressed in neurons, glia and blood vessels in vivo, are little explored. Using BOLD fMRI of urethane anesthetized rats as an integrative CSD readout, we tested the involvement of different NMDA receptor subtypes in CSD induction and propagation. Rats were treated with a non-selective NMDA blocker (MK-801), NR2B antagonist (ifenprodil) or a NR2A selective antagonist (TCN-201). CSD was induced during fMRI scanning by application of KCl onto the cerebral cortex and fMRI data were collected by 9.4 T MRI. The non-specific NMDA antagonist MK-801 completely blocked CSD, which was not observed in the NR2A group where TCN-201 did not alter the CSD features. Unexpectedly, the NR2B specific antagonist ifenprodil largely promoted the initial negative phase of the BOLD CSD response, likely due to altered neurovascular coupling. Our data suggest key roles and differential involvement of NMDA receptor subtypes in CSD generation and propagation, highlighting an important role for the NR2B subtype. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Brain regions responsible for tinnitus distress and loudness: a resting-state FMRI study.

    PubMed

    Ueyama, Takashi; Donishi, Tomohiro; Ukai, Satoshi; Ikeda, Yorihiko; Hotomi, Muneki; Yamanaka, Noboru; Shinosaki, Kazuhiro; Terada, Masaki; Kaneoke, Yoshiki

    2013-01-01

    Subjective tinnitus is characterized by the perception of phantom sound without an external auditory stimulus. We hypothesized that abnormal functionally connected regions in the central nervous system might underlie the pathophysiology of chronic subjective tinnitus. Statistical significance of functional connectivity (FC) strength is affected by the regional autocorrelation coefficient (AC). In this study, we used resting-state functional MRI (fMRI) and measured regional mean FC strength (mean cross-correlation coefficient between a region and all other regions without taking into account the effect of AC (rGC) and with taking into account the effect of AC (rGCa) to elucidate brain regions related to tinnitus symptoms such as distress, depression and loudness. Consistent with previous studies, tinnitus loudness was not related to tinnitus-related distress and depressive state. Although both rGC and rGCa revealed similar brain regions where the values showed a statistically significant relationship with tinnitus-related symptoms, the regions for rGCa were more localized and more clearly delineated the regions related specifically to each symptom. The rGCa values in the bilateral rectus gyri were positively correlated and those in the bilateral anterior and middle cingulate gyri were negatively correlated with distress and depressive state. The rGCa values in the bilateral thalamus, the bilateral hippocampus, and the left caudate were positively correlated and those in the left medial superior frontal gyrus and the left posterior cingulate gyrus were negatively correlated with tinnitus loudness. These results suggest that distinct brain regions are responsible for tinnitus symptoms. The regions for distress and depressive state are known to be related to depression, while the regions for tinnitus loudness are known to be related to the default mode network and integration of multi-sensory information.

  5. Enhanced Sympathetic Arousal in Response to fMRI Scanning Correlates with Task Induced Activations and Deactivations

    PubMed Central

    Muehlhan, Markus; Lueken, Ulrike; Siegert, Jens; Wittchen, Hans-Ulrich; Smolka, Michael N.; Kirschbaum, Clemens

    2013-01-01

    It has been repeatedly shown that functional magnetic resonance imaging (fMRI) triggers distress and neuroendocrine response systems. Prior studies have revealed that sympathetic arousal increases, particularly at the beginning of the examination. Against this background it appears likely that those stress reactions during the scanning procedure may influence task performance and neural correlates. However, the question how sympathetic arousal elicited by the scanning procedure itself may act as a potential confounder of fMRI data remains unresolved today. Thirty-seven scanner naive healthy subjects performed a simple cued target detection task. Levels of salivary alpha amylase (sAA), as a biomarker for sympathetic activity, were assessed in samples obtained at several time points during the lab visit. SAA increased two times, immediately prior to scanning and at the end of the scanning procedure. Neural activation related to motor preparation and timing as well as task performance was positively correlated with the first increase. Furthermore, the first sAA increase was associated with task induced deactivation (TID) in frontal and parietal regions. However, these effects were restricted to the first part of the experiment. Consequently, this bias of scanner related sympathetic activation should be considered in future fMRI investigations. It is of particular importance for pharmacological investigations studying adrenergic agents and the comparison of groups with different stress vulnerabilities like patients and controls or adolescents and adults. PMID:23967320

  6. Time course of superior temporal sulcus activity in response to eye gaze: a combined fMRI and MEG study

    PubMed Central

    Kochiyama, Takanori; Uono, Shota; Yoshikawa, Sakiko

    2008-01-01

    The human superior temporal sulcus (STS) has been suggested to be involved in gaze processing, but temporal data regarding this issue are lacking. We investigated this topic by combining fMRI and MEG in four normal subjects. Photographs of faces with either averted or straight eye gazes were presented and subjects passively viewed the stimuli. First, we analyzed the brain areas involved using fMRI. A group analysis revealed activation of the STS for averted compared to straight gazes, which was confirmed in all subjects. We then measured brain activity using MEG, and conducted a 3D spatial filter analysis. The STS showed higher activity in response to averted versus straight gazes during the 150–200 ms period, peaking at around 170 ms, after stimulus onset. In contrast, the fusiform gyrus, which was detected by the main effect of stimulus presentations in fMRI analysis, exhibited comparable activity across straight and averted gazes at about 170 ms. These results indicate involvement of the human STS in rapid processing of the eye gaze of another individual. PMID:19015114

  7. 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

  8. 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.

  9. FMRI Signal Analysis Using Empirical Mean Curve Decomposition

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  11. 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…

  12. 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…

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

    PubMed Central

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

    2013-01-01

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

  14. Distinct fMRI Responses to Self-Induced versus Stimulus Motion during Free Viewing in the Macaque.

    PubMed

    Russ, Brian E; Kaneko, Takaaki; Saleem, Kadharbatcha S; Berman, Rebecca A; Leopold, David A

    2016-09-14

    Visual motion responses in the brain are shaped by two distinct sources: the physical movement of objects in the environment and motion resulting from one's own actions. The latter source, termed visual reafference, stems from movements of the head and body, and in primates from the frequent saccadic eye movements that mark natural vision. To study the relative contribution of reafferent and stimulus motion during natural vision, we measured fMRI activity in the brains of two macaques as they freely viewed >50 hours of naturalistic video footage depicting dynamic social interactions. We used eye movements obtained during scanning to estimate the level of reafferent retinal motion at each moment in time. We also estimated the net stimulus motion by analyzing the video content during the same time periods. Mapping the responses to these distinct sources of retinal motion, we found a striking dissociation in the distribution of visual responses throughout the brain. Reafferent motion drove fMRI activity in the early retinotopic areas V1, V2, V3, and V4, particularly in their central visual field representations, as well as lateral aspects of the caudal inferotemporal cortex (area TEO). However, stimulus motion dominated fMRI responses in the superior temporal sulcus, including areas MT, MST, and FST as well as more rostral areas. We discuss this pronounced separation of motion processing in the context of natural vision, saccadic suppression, and the brain's utilization of corollary discharge signals. Visual motion arises not only from events in the external world, but also from the movements of the observer. For example, even if objects are stationary in the world, the act of walking through a room or shifting one's eyes causes motion on the retina. This "reafferent" motion propagates into the brain as signals that must be interpreted in the context of real object motion. The delineation of whole-brain responses to stimulus versus self-generated retinal motion

  15. Distinct fMRI Responses to Self-Induced versus Stimulus Motion during Free Viewing in the Macaque

    PubMed Central

    Kaneko, Takaaki; Saleem, Kadharbatcha S.; Berman, Rebecca A.; Leopold, David A.

    2016-01-01

    Visual motion responses in the brain are shaped by two distinct sources: the physical movement of objects in the environment and motion resulting from one's own actions. The latter source, termed visual reafference, stems from movements of the head and body, and in primates from the frequent saccadic eye movements that mark natural vision. To study the relative contribution of reafferent and stimulus motion during natural vision, we measured fMRI activity in the brains of two macaques as they freely viewed >50 hours of naturalistic video footage depicting dynamic social interactions. We used eye movements obtained during scanning to estimate the level of reafferent retinal motion at each moment in time. We also estimated the net stimulus motion by analyzing the video content during the same time periods. Mapping the responses to these distinct sources of retinal motion, we found a striking dissociation in the distribution of visual responses throughout the brain. Reafferent motion drove fMRI activity in the early retinotopic areas V1, V2, V3, and V4, particularly in their central visual field representations, as well as lateral aspects of the caudal inferotemporal cortex (area TEO). However, stimulus motion dominated fMRI responses in the superior temporal sulcus, including areas MT, MST, and FST as well as more rostral areas. We discuss this pronounced separation of motion processing in the context of natural vision, saccadic suppression, and the brain's utilization of corollary discharge signals. SIGNIFICANCE STATEMENT Visual motion arises not only from events in the external world, but also from the movements of the observer. For example, even if objects are stationary in the world, the act of walking through a room or shifting one's eyes causes motion on the retina. This “reafferent” motion propagates into the brain as signals that must be interpreted in the context of real object motion. The delineation of whole-brain responses to stimulus versus self

  16. Brain Activation in Response to Visceral Stimulation in Rats with Amygdala Implants of Corticosterone: An fMRI Study

    PubMed Central

    Johnson, Anthony C.; Myers, Brent; Lazovic, Jelena; Towner, Rheal; Greenwood-Van Meerveld, Beverley

    2010-01-01

    Background Although visceral pain of gastrointestinal (GI) origin is the major complaint in patients with irritable bowel syndrome (IBS) it remains poorly understood. Brain imaging studies suggest a defect in brain-gut communication in IBS with a greater activation of central arousal circuits including the amygdala. Previously, we found that stereotaxic implantation of corticosterone (CORT) onto the amygdala in rats induced anxiety and colonic hypersensitivity. In the present study we used functional magnetic resonance imaging (fMRI) to identify specific brain sites activated in a rat model characterized by anxiety and colonic hypersensitivity. Methodology/Principal Findings Anesthetized male rats received micropellets (30 µg each) of either CORT or cholesterol (CHOL), to serve as a control, implanted stereotaxically on the dorsal margin of each amygdala. Seven days later, rats were anesthetized and placed in the fMRI magnet (7T). A series of isobaric colorectal balloon distensions (CRD - 90s ‘off’, 30s ‘on’, 8 replicates) at two pressures (40 and 60 mmHg) were performed in a standard block-design. Cross correlation statistical analysis was used to determine significant differences between distended and non-distended states in CORT and CHOL-treated animals. Analysis of the imaging data demonstrated greater overall brain activation in response to CRD in rats with CORT implants compared to CHOL controls. Additionally, CORT implants produced significant positive bilateral increases in MRI signal in response to CRD in specific nuclei known as integration sites important in anxiety and pain perception. Conclusions and Significance These data indicate that chronic exposure of the amygdala to elevated levels of CORT enhances overall brain activation in response to CRD, and identified other specific brain regions activated in response to mechanical distension of the colon. These results demonstrate the feasibility of performing fMRI imaging in a rodent model that

  17. Mapping and correction of vascular hemodynamic latency in the BOLD signal.

    PubMed

    Chang, Catie; Thomason, Moriah E; Glover, Gary H

    2008-10-15

    Correlation and causality metrics can be applied to blood-oxygen level-dependent (BOLD) signal time series in order to infer neural synchrony and directions of information flow from fMRI data. However, the BOLD signal reflects both the underlying neural activity and the vascular response, the latter of which is governed by local vasomotor physiology. The presence of potential vascular latency differences thus poses a confound in the detection of neural synchrony as well as inferences about the causality of neural processes. In the present study, we investigate the use of a breath holding (BH) task for characterizing and correcting for voxel-wise neurovascular latency differences across the whole brain. We demonstrate that BH yields reliable measurements of relative timing differences between voxels, and further show that a BH-derived latency correction can impact both functional connectivity maps of the resting-state default-mode network and activation maps of an event-related working memory (WM) task.

  18. Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues.

    PubMed

    McClernon, Francis J; Kozink, Rachel V; Rose, Jed E

    2008-08-01

    Exposure to smoking cues increases craving for cigarettes and can precipitate relapse. Whereas brain imaging studies have identified a distinct network of brain regions subserving the processing of smoking cues, little is known about the influence of individual difference factors and withdrawal symptoms on brain cue reactivity. Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level-dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerström test of nicotine dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables.

  19. The role of the GABAergic and dopaminergic systems in the brain response to an intragastric load of alcohol in conscious rats.

    PubMed

    Tsurugizawa, T; Uematsu, A; Uneyama, H; Torii, K

    2010-12-01

    The brain's response to ethanol intake has been extensively investigated using electrophysiological recordings, brain lesion techniques, and c-Fos immunoreactivity. However, few studies have investigated this phenomenon using functional magnetic resonance imaging (fMRI). In the present study, we used fMRI to investigate the blood oxygenation level-dependent (BOLD) signal response to an intragastric (IG) load of ethanol in conscious, ethanol-naive rats. An intragastrically infused 10% ethanol solution induced a significant decrease in the intensity of the BOLD signal in several regions of the brain, including the bilateral amygdala (AMG), nucleus accumbens (NAc), hippocampus, ventral pallidum, insular cortex, and cingulate cortex, and an increase in the BOLD signal in the ventral tegmental area (VTA) and hypothalamic regions. Treatment with bicuculline, which is an antagonist of the gamma-aminobutyric acid A (GABA(A)) receptor, increased the BOLD signal intensity in the regions that had shown decreases in the BOLD signal after the IG infusion of 10% ethanol solution, but it did not affect the BOLD signal increase in the hypothalamus. Treatment with SCH39166, which is an antagonist of D1-like receptors, eliminated the increase in the BOLD signal intensity in the hypothalamic areas but did not affect the BOLD signal decrease following the 10% ethanol infusion. These results indicate that an IG load of ethanol caused both a GABA(A) receptor-mediated BOLD decrease in the limbic system and the cortex and a D1-like receptor-mediated BOLD increase in the hypothalamic regions in ethanol-naive rats.

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

    PubMed

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

    2015-12-01

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

  1. 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.

  2. Increased BOLD signal in the fusiform gyrus during implicit emotion processing in anorexia nervosa.

    PubMed

    Fonville, Leon; Giampietro, Vincent; Surguladze, Simon; Williams, Steven; Tchanturia, Kate

    2014-01-01

    The behavioural literature in anorexia nervosa (AN) has suggested impairments in psychosocial functioning and studies using facial expression processing tasks (FEPT) have reported poorer recognition and slower identification of emotions. Functional magnetic resonance imaging (fMRI) was used alongside a FEPT, depicting neutral, mildly happy and happy faces, to examine the neural correlates of implicit emotion processing in AN. Participants were instructed to specify the gender of the faces. Levels of depression, anxiety, obsessive-compulsive symptoms and eating disorder behaviour were obtained and principal component analysis (PCA) was performed to acquire uncorrelated variables. fMRI analysis revealed a greater blood-oxygenation level dependent (BOLD) response in AN in the right fusiform gyrus to all facial expressions. This response showed a linear increase with the happiness of the facial expression and was found to be stronger in those not taking medication. PCA analysis revealed a single component indicating a greater level of general clinical symptoms. Neuroimaging findings would suggest that alterations in implicit emotion processing in AN occur during early perceptual processing of social signals and illustrate greater engagement on the FEPT. The lack of separate components using PCA suggests that the questionnaires used might not be suited as predictive measures.

  3. Intra- and Inter- Subject Variability of High Field fMRI Digit Maps in Somatosensory Area 3b of New World Monkeys

    PubMed Central

    Zhang, Na; Wang, Feng; Turner, Greg H.; Gore, John C.; Avison, Malcolm J.; Chen, Li M.

    2009-01-01

    This study evaluates the intra- and inter- subject variability of digit maps in area 3b of anesthetized squirrel monkeys. Maps were collected using high field Blood Oxygenation Level Dependent (BOLD) fMRI. BOLD responses to individual digit stimulations were mapped and their response properties (location, area of activation, % signal change, time to peak response) were compared within and across imaging sessions separated by up to 20 months. During single digit stimulation using a block design, the spatio-temporal response of the BOLD signal for individual runs within and across sessions and animals was well conserved, with a time to peak BOLD response of 20 ± 4 sec. The variability in the center of BOLD activation in area 3b was 0.41 ± 0.24 mm (mean ± SD) across individual 5–7 minutes runs within a scanning session and 0.55 ± 0.15 mm across sessions. The average signal change across all animals, runs and sessions was 0.62 ± 0.38 %, and varied 32% within and 40% across sessions. In a comparison of the stability and reproducibility of the area of single digit activation obtained using three approaches, use of a fixed statistical threshold (p<10−5) yielded an average area of 4.8 ± 3.5 mm2 (mean ± SD), adaptive statistical thresholding 1.32 ± 1.259 mm2 (mean ± SD), and combined fixed statistical and adaptive BOLD signal amplitude 4.4 ± 2.5 mm2 (mean ± SD) across image runs and sessions. The somatotopic organization was stable within animals across sessions, while across animals, there was some variation in overall activation pattern and inter-digit distances. These results confirm that BOLD activation maps of single digits in area 3b as characterized by activation center, signal amplitudes, and temporal profile are very stable. The activation sizes determined by various criteria are the most variable measure in this preparation, but adaptive statistical thresholding appears to yield the most stable and reproducible maps. This study serves as a baseline

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

    PubMed

    Mendola, Janine D; Conner, Ian P

    2007-02-27

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

  5. Eye Dominance Predicts fMRI Signals in Human Retinotopic Cortex

    PubMed Central

    Mendola, Janine D.; Conner, Ian P.

    2009-01-01

    There have been many attempts to define eye dominance in normal subjects, but limited consensus exists, and relevant physiological data is scarce. In this study, we consider two different behavioral methods for assignment of eye dominance, and how well they predict fMRI signals evoked by monocular stimulation. Sighting eye dominance was assessed with two standard tests, the Porta Test, and a ‘hole in hand’ variation of the Miles Test. Acuity dominance was tested with a standard eye chart and with a computerized test of grating acuity. We found limited agreement between the sighting and acuity methods for assigning dominance in our individual subjects. We then compared the fMRI response generated by dominant eye stimulation to that generated by non-dominant eye, according to both methods, in 7 normal subjects. The stimulus consisted of a high contrast hemifield stimulus alternating with no stimulus in a blocked paradigm. In separate scans, we used standard techniques to label the borders of visual areas V1, V2, V3, VP, V4, V3A, and MT. These regions of interest (ROIs) were used to analyze each visual area separately. We found that percent change in fMRI BOLD signal was stronger for the dominant eye as defined by the acuity method, and this effect was significant for areas located in the ventral occipital territory (V1v, V2v, VP, V4). In contrast, assigning dominance based on sighting produced no significant interocular BOLD differences. We conclude that interocular BOLD differences in normal subjects exist, and may be predicted by acuity measures. PMID:17194544

  6. Aging effects on functional auditory and visual processing using fMRI with variable sensory loading.

    PubMed

    Cliff, Michael; Joyce, Dan W; Lamar, Melissa; Dannhauser, Thomas; Tracy, Derek K; Shergill, Sukhwinder S

    2013-05-01

    Traditionally, studies investigating the functional implications of age-related structural brain alterations have focused on higher cognitive processes; by increasing stimulus load, these studies assess behavioral and neurophysiological performance. In order to understand age-related changes in these higher cognitive processes, it is crucial to examine changes in visual and auditory processes that are the gateways to higher cognitive functions. This study provides evidence for age-related functional decline in visual and auditory processing, and regional alterations in functional brain processing, using non-invasive neuroimaging. Using functional magnetic resonance imaging (fMRI), younger (n=11; mean age=31) and older (n=10; mean age=68) adults were imaged while observing flashing checkerboard images (passive visual stimuli) and hearing word lists (passive auditory stimuli) across varying stimuli presentation rates. Younger adults showed greater overall levels of temporal and occipital cortical activation than older adults for both auditory and visual stimuli. The relative change in activity as a function of stimulus presentation rate showed differences between young and older participants. In visual cortex, the older group showed a decrease in fMRI blood oxygen level dependent (BOLD) signal magnitude as stimulus frequency increased, whereas the younger group showed a linear increase. In auditory cortex, the younger group showed a relative increase as a function of word presentation rate, while older participants showed a relatively stable magnitude of fMRI BOLD response across all rates. When analyzing participants across all ages, only the auditory cortical activation showed a continuous, monotonically decreasing BOLD signal magnitude as a function of age. Our preliminary findings show an age-related decline in demand-related, passive early sensory processing. As stimulus demand increases, visual and auditory cortex do not show increases in activity in older

  7. Stability of fMRI striatal response to alcohol cues: a hierarchical linear modeling approach.

    PubMed

    Schacht, Joseph P; Anton, Raymond F; Randall, Patrick K; Li, Xingbao; Henderson, Scott; Myrick, Hugh

    2011-05-01

    In functional magnetic resonance imaging (fMRI) studies of alcohol-dependent individuals, alcohol cues elicit activation of the ventral and dorsal aspects of the striatum (VS and DS), which are believed to underlie aspects of reward learning critical to the initiation and maintenance of alcohol dependence. Cue-elicited striatal activation may represent a biological substrate through which treatment efficacy may be measured. However, to be useful for this purpose, VS or DS activation must first demonstrate stability across time. Using hierarchical linear modeling (HLM), this study tested the stability of cue-elicited activation in anatomically and functionally defined regions of interest in bilateral VS and DS. Nine non-treatment-seeking alcohol-dependent participants twice completed an alcohol cue reactivity task during two fMRI scans separated by 14 days. HLM analyses demonstrated that, across all participants, alcohol cues elicited significant activation in each of the regions of interest. At the group level, these activations attenuated slightly between scans, but session-wise differences were not significant. Within-participants stability was best in the anatomically defined right VS and DS and in a functionally defined region that encompassed right caudate and putamen (intraclass correlation coefficients of .75, .81, and .76, respectively). Thus, within this small sample, alcohol cue-elicited fMRI activation had good reliability in the right striatum, though a larger sample is necessary to ensure generalizability and further evaluate stability. This study also demonstrates the utility of HLM analytic techniques for serial fMRI studies, in which separating within-participants variance (individual changes in activation) from between-participants factors (time or treatment) is critical. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  9. Can depression be diagnosed by response to mother's face? A personalized attachment-based paradigm for diagnostic fMRI.

    PubMed

    Zhang, Xian; Yaseen, Zimri S; Galynker, Igor I; Hirsch, Joy; Winston, Arnold

    2011-01-01

    Objective measurement of depression remains elusive. Depression has been associated with insecure attachment, and both have been associated with changes in brain reactivity in response to viewing standard emotional and neutral faces. In this study, we developed a method to calculate predicted scores for the Beck Depression Inventory II (BDI-II) using personalized stimuli: fMRI imaging of subjects viewing pictures of their own mothers. 28 female subjects ages 18-30 (14 healthy controls and 14 unipolar depressed diagnosed by MINI psychiatric interview) were scored on the Beck Depression Inventory II (BDI-II) and the Adult Attachment Interview (AAI) coherence of mind scale of global attachment security. Subjects viewed pictures of Mother (M), Friend (F) and Stranger (S), during functional magnetic resonance imaging (fMRI). Using a principal component regression method (PCR), a predicted Beck Depression Inventory II (BDI-II) score was obtained from activity patterns in the paracingulate gyrus (Brodmann area 32) and compared to clinical diagnosis and the measured BDI-II score. The same procedure was performed for AAI coherence of mind scores. Activity patterns in BA-32 identified depressed subjects. The categorical agreement between the derived BDI-II score (using the standard clinical cut-score of 14 on the BDI-II) and depression diagnosis by MINI psychiatric interview was 89%, with sensitivity 85.7% and specificity 92.8%. Predicted and measured BDI-II scores had a correlation of 0.55. Prediction of attachment security was not statistically significant. Brain activity in response to viewing one's mother may be diagnostic of depression. Functional magnetic resonance imaging using personalized paradigms has the potential to provide objective assessments, even when behavioral measures are not informative. Further, fMRI based diagnostic algorithms may enhance our understanding of the neural mechanisms of depression by identifying distinctive neural features of the illness.

  10. 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

  11. Risk assessment of aggressive behavior in Chinese patients with schizophrenia by fMRI and COMT gene

    PubMed Central

    Tang, Xiaoli; Jin, Jun; Tang, Yi; Cao, Jinbo; Huang, Junjie

    2017-01-01

    Background Blood–oxygen-level dependent functional magnetic resonance imaging (BOLD-fMRI) maps cerebral activity by the hemodynamic response. Catechol-O-methyltransferase (COMT) gene is involved in the metabolism of dopamine. It is reported that both of these can be used to assess the aggression risk in patients with schizophrenia. However, these methods to assess the aggression risk patients with schizophrenia have not been established in China. Therefore, we deliver here a systematic review and meta-analysis based on the studies dealing with Chinese patients. Method Nine fMRI studies and 12 gene studies were included. The data of each study were extracted and summarized. Odds ratios with 95% confidence intervals were estimated on allele, dominant, and recessive models. Publication bias was evaluated by Begg’s funnel plot. Results Positive BOLD-fMRI values in the lower central neural system (CNS) and negative values in the high-level CNS were observed in the patients with aggression risk. A strong association was derived from the recessive gene model of COMT polymorphism rs4680 and risk in aggression behavior (odds ratio =2.10). No significant publication bias was identified. Conclusion Aggression behavior in patients with schizophrenia can be indicated by positive BOLD-fMRI values in the lower CNS and negative values in the high-level CNS and by a recessive gene model in COMT polymorphism rs4680. A combined test of fMRI and COMT gene could increase the predictive value. PMID:28223811

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

    NASA Astrophysics Data System (ADS)

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

    2003-05-01

    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.

  13. Attention to detail: why considering task demands is essential for single-trial analysis of BOLD correlates of the visual P1 and N1.

    PubMed

    Warbrick, Tracy; Arrubla, Jorge; Boers, Franks; Neuner, Irene; Shah, N Jon

    2014-03-01

    Single-trial fluctuations in the EEG signal have been shown to temporally correlate with the fMRI BOLD response and are valuable for modeling trial-to-trial fluctuations in responses. The P1 and N1 components of the visual ERP are sensitive to different attentional modulations, suggesting that different aspects of stimulus processing can be modeled with these ERP parameters. As such, different patterns of BOLD covariation for P1 and N1 informed regressors would be expected; however, current findings are equivocal. We investigate the effects of variations in attention on P1 and N1 informed BOLD activation in a visual oddball task. Simultaneous EEG-fMRI data were recorded from 13 healthy participants during three conditions of a visual oddball task: Passive, Count, and Respond. We show that the P1 and N1 components of the visual ERP can be used in the integration-by-prediction method of EEG-fMRI data integration to highlight brain regions related to target detection and response production. Our data suggest that the P1 component of the ERP reflects changes in sensory encoding of stimulus features and is more informative for the Passive and Count conditions. The N1, on the other hand, was more informative for the Respond condition, suggesting that it can be used to model the processing of stimulus, meaning specifically discriminating one type of stimulus from another, and processes involved in integrating sensory information with response selection. Our results show that an understanding of the underlying electrophysiology is necessary for a thorough interpretation of EEG-informed fMRI analysis.

  14. Resolution and reproducibility of BOLD and perfusion functional MRI at 3.0 Tesla.

    PubMed

    van Gelderen, Peter; W H Wu, Carolyn; de Zwart, Jacco A; Cohen, Leonardo; Hallett, Mark; Duyn, Jeff H

    2005-09-01

    Visual and somatosensory activation studies were performed on normal subjects to compare the spatial discrimination and reproducibility between functional MRI (fMRI) methods based on blood oxygen level-dependent (BOLD) and perfusion contrast. To allow simultaneous measurement of BOLD and perfusion contrast, a dedicated MRI acquisition technique was developed. Repeated experiments of sensory stimulation of single digits of the right hand showed an average variability of activation amplitude of 25% for BOLD data, and a significantly lower variability of 21% for perfusion data. No significant difference in the variability of the locus of activity was observed between the BOLD and perfusion data. In somatotopy experiments, digits II and V were subjected to passive sensory stimulation. Both the BOLD and perfusion data showed substantial overlap in the activation patterns from the two digits. In a retinotopy study, two stimuli were alternated to excite different patches of V1. Again there was substantial overlap between the activation patterns from both stimuli, although the perfusion performed somewhat better than the BOLD method. Particularly for the visual studies, the overlap in activation patterns was more than expected based on the fine-scale retinotopic mapping of cortical activity, suggesting that both BOLD and perfusion contrast mechanisms contribute substantially to the point-spread function (PSF).

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

    PubMed

    Paret, Christian; Ruf, Matthi