PARTICLE FILTERING WITH SEQUENTIAL PARAMETER LEARNING FOR NONLINEAR BOLD fMRI SIGNALS.

PubMed

Xia, Jing; Wang, Michelle Yongmei

Analyzing the blood oxygenation level dependent (BOLD) effect in the functional magnetic resonance imaging (fMRI) is typically based on recent ground-breaking time series analysis techniques. This work represents a significant improvement over existing approaches to system identification using nonlinear hemodynamic models. It is important for three reasons. First, instead of using linearized approximations of the dynamics, we present a nonlinear filtering based on the sequential Monte Carlo method to capture the inherent nonlinearities in the physiological system. Second, we simultaneously estimate the hidden physiological states and the system parameters through particle filtering with sequential parameter learning to fully take advantage of the dynamic information of the BOLD signals. Third, during the unknown static parameter learning, we employ the low-dimensional sufficient statistics for efficiency and avoiding potential degeneration of the parameters. The performance of the proposed method is validated using both the simulated data and real BOLD fMRI data.

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

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.

Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves.

PubMed

Schwalm, Miriam; Schmid, Florian; Wachsmuth, Lydia; Backhaus, Hendrik; Kronfeld, Andrea; Aedo Jury, Felipe; Prouvot, Pierre-Hugues; Fois, Consuelo; Albers, Franziska; van Alst, Timo; Faber, Cornelius; Stroh, Albrecht

2017-09-15

Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses.

Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves

PubMed Central

Backhaus, Hendrik; Kronfeld, Andrea; Aedo Jury, Felipe; Prouvot, Pierre-Hugues; Fois, Consuelo; Albers, Franziska; van Alst, Timo

2017-01-01

Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses. PMID:28914607

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

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

PubMed Central

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

2016-01-01

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

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

BOLD fMRI and DTI in strabismic amblyopes following occlusion therapy.

PubMed

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

2016-08-01

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

Corticostriatal and Dopaminergic Response to Beer Flavor with Both fMRI and [(11) C]raclopride Positron Emission Tomography.

PubMed

Oberlin, Brandon G; Dzemidzic, Mario; Harezlak, Jaroslaw; Kudela, Maria A; Tran, Stella M; Soeurt, Christina M; Yoder, Karmen K; Kareken, David A

2016-09-01

Cue-evoked drug-seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine (DA) transmission. Using [(11) C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST DA release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST blood oxygenation level-dependent (BOLD) responses to beer flavor are related to VST DA release and motivation to drink. Male beer drinkers (n = 28, age = 24 ± 2, drinks/wk = 16 ± 10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade(®) (appetitive control). We tested for correlations between BOLD activation in fMRI and VST DA responses in PET, and drinking-related variables. Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest. Both imaging modalities showed a right-lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males) and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting. Copyright © 2016 by the Research Society on

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

PubMed

Kim, Seong-Gi; Ogawa, Seiji

2012-07-01

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 O(2) utilization (CMRO(2)), (5) dynamic responses of BOLD, CBF, CMRO(2), 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.

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

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.

Estimating neural response functions from fMRI

PubMed Central

Kumar, Sukhbinder; Penny, William

2014-01-01

This paper proposes a methodology for estimating Neural Response Functions (NRFs) from fMRI data. These NRFs describe non-linear relationships between experimental stimuli and neuronal population responses. The method is based on a two-stage model comprising an NRF and a Hemodynamic Response Function (HRF) that are simultaneously fitted to fMRI data using a Bayesian optimization algorithm. This algorithm also produces a model evidence score, providing a formal model comparison method for evaluating alternative NRFs. The HRF is characterized using previously established “Balloon” and BOLD signal models. We illustrate the method with two example applications based on fMRI studies of the auditory system. In the first, we estimate the time constants of repetition suppression and facilitation, and in the second we estimate the parameters of population receptive fields in a tonotopic mapping study. PMID:24847246

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

PubMed Central

Claise, Béatrice; Jean, Betty

2015-01-01

For different functional magnetic resonance imaging experiments using blood oxygenation level-dependent (BOLD) contrast, the acquisition of T 2*-weighted scans at a high spatial resolution may be advantageous in terms of time-course signal-to-noise ratio and of BOLD sensitivity when the regions are prone to susceptibility artifacts. In this study, we explore this solution by examining how spatial resolution influences activations elicited when appetizing food pictures are viewed. Twenty subjects were imaged at 3 T with two different voxel volumes, 3.4 μl and 27 μl. Despite the diminution of brain coverage, we found that high-resolution acquisition led to a better detection of activations. Though known to suffer to different degrees from susceptibility artifacts, the activations detected by high spatial resolution were notably consistent with those reported in published activation likelihood estimation meta-analyses, corresponding to taste-responsive regions. Furthermore, these regions were found activated bilaterally, in contrast with previous findings. Both the reduction of partial volume effect, which improves BOLD contrast, and the mitigation of susceptibility artifact, which boosts the signal to noise ratio in certain regions, explained the better detection noted with high resolution. The present study provides further evidences that high spatial resolution is a valuable solution for human BOLD fMRI, especially for studying food-related stimuli. PMID:26550990

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

Prospects for Quantitative fMRI: Investigating the Effects of Caffeine on Baseline Oxygen Metabolism and the Response to a Visual Stimulus in Humans

PubMed Central

Griffeth, Valerie E.M.; Perthen, Joanna E.; Buxton, Richard B.

2011-01-01

Functional magnetic resonance imaging (fMRI) provides an indirect reflection of neural activity change in the working brain through detection of blood oxygenation level dependent (BOLD) signal changes. Although widely used to map patterns of brain activation, fMRI has not yet met its potential for clinical and pharmacological studies due to difficulties in quantitatively interpreting the BOLD signal. This difficulty is due to the BOLD response being strongly modulated by two physiological factors in addition to the level of neural activity: the amount of deoxyhemoglobin present in the baseline state and the coupling ratio, n, of evoked changes in blood flow and oxygen metabolism. In this study, we used a quantitative fMRI approach with dual measurement of blood flow and BOLD responses to overcome these limitations and show that these two sources of modulation work in opposite directions following caffeine administration in healthy human subjects. A strong 27% reduction in baseline blood flow and a 22% increase in baseline oxygen metabolism after caffeine consumption led to a decrease in baseline blood oxygenation and was expected to increase the subsequent BOLD response to the visual stimulus. Opposing this, caffeine reduced n through a strong 61% increase in the evoked oxygen metabolism response to the visual stimulus. The combined effect was that BOLD responses pre- and post-caffeine were similar despite large underlying physiological changes, indicating that the magnitude of the BOLD response alone should not be interpreted as a direct measure of underlying neurophysiological changes. Instead, a quantitative methodology based on dual-echo measurement of blood flow and BOLD responses is a promising tool for applying fMRI to disease and drug studies in which both baseline conditions and the coupling of blood flow and oxygen metabolism responses to a stimulus may be altered. PMID:21586328

High Efficiency Multi-shot Interleaved Spiral-In/Out Acquisition for High Resolution BOLD fMRI

PubMed Central

Jung, Youngkyoo; Samsonov, Alexey A.; Liu, Thomas T.; Buracas, Giedrius T.

2012-01-01

Growing demand for high spatial resolution BOLD functional MRI faces a challenge of the spatial resolution vs. coverage or temporal resolution tradeoff, which can be addressed by methods that afford increased acquisition efficiency. Spiral acquisition trajectories have been shown to be superior to currently prevalent echo-planar imaging in terms of acquisition efficiency, and high spatial resolution can be achieved by employing multiple-shot spiral acquisition. The interleaved spiral in-out trajectory is preferred over spiral-in due to increased BOLD signal CNR and higher acquisition efficiency than that of spiral-out or non-interleaved spiral in/out trajectories (1), but to date applicability of the multi-shot interleaved spiral in-out for high spatial resolution imaging has not been studied. Herein we propose multi-shot interleaved spiral in-out acquisition and investigate its applicability for high spatial resolution BOLD fMRI. Images reconstructed from interleaved spiral-in and -out trajectories possess artifacts caused by differences in T2* decay, off-resonance and k-space errors associated with the two trajectories. We analyze the associated errors and demonstrate that application of conjugate phase reconstruction and spectral filtering can substantially mitigate these image artifacts. After applying these processing steps, the multishot interleaved spiral in-out pulse sequence yields high BOLD CNR images at in-plane resolution below 1x1 mm while preserving acceptable temporal resolution (4 s) and brain coverage (15 slices of 2 mm thickness). Moreover, this method yields sufficient BOLD CNR at 1.5 mm isotropic resolution for detection of activation in hippocampus associated with cognitive tasks (Stern memory task). The multi-shot interleaved spiral in-out acquisition is a promising technique for high spatial resolution BOLD fMRI applications. PMID:23023395

Complexity and Synchronicity of Resting State BOLD FMRI in Normal Aging and Cognitive Decline

PubMed Central

Liu, Collin Y; Krishnan, Anitha P; Yan, Lirong; Smith, Robert X; Kilroy, Emily; Alger, Jeffery R; Ringman, John M; Wang, Danny JJ

2012-01-01

Purpose To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state BOLD fMRI in normal aging and cognitive decline associated with familial Alzheimer’s disease (fAD). Materials and Methods Resting state BOLD fMRI data were acquired at 3T from 2 independent cohorts of subjects consisting of healthy young (age 23±2 years, n=8) and aged volunteers (age 66±3 years, n=8), as well as 22 fAD associated subjects (14 mutation carriers, age 41.2±15.8 years; and 8 non-mutation carrying family members, age 28.8±5.9 years). Mean ApEn values were compared between the two age groups, and correlated with cognitive performance in the fAD group. Cross-ApEn (C-ApEn) was further calculated to assess the asynchrony between precuneus and the rest of the brain. Results Complexity of brain activity measured by mean ApEn in gray and white matter decreased with normal aging. In the fAD group, cognitive impairment was associated with decreased mean ApEn in gray matter as well as decreased regional ApEn in right precuneus, right lateral parietal regions, left precentral gyrus, and right paracentral gyrus. A pattern of asynchrony between BOLD fMRI series emerged from C-ApEn analysis, with significant regional anti-correlation with cross-correlation coefficient of functional connectivity analysis. Conclusion ApEn and C-ApEn may be useful for assessing the complexity and synchronicity of brain activity in normal aging and cognitive decline associated with neurodegenerative diseases PMID:23225622

Early anti-correlated BOLD signal changes of physiologic origin.

PubMed

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

2014-02-15

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

Early anti-correlated BOLD signal changes of physiologic origin

PubMed Central

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

2014-01-01

Negative BOLD signals that are synchronous with resting state fluctuations have been observed in large vessels in the cortical sulci and surrounding the ventricles. In this study, we investigated the origin of these negative BOLD signals by applying a Cued Deep Breathing (CDB) task to create transient hypocapnia and a resultant global fMRI signal decrease. We hypothesized that a global stimulus would amplify the effect in large vessels and that using a global negative (vasoconstrictive) stimulus would test whether these voxels exhibit either inherently negative or simply anti-correlated BOLD responses. Significantly anti-correlated, but positive, BOLD signal changes during respiratory challenges were identified in voxels primarily located near edges of brain spaces containing CSF. These positive BOLD responses occurred earlier than the negative CDB response across most of gray matter voxels. These findings confirm earlier suggestions that in some brain regions, local, fractional changes in CSF volume may overwhelm BOLD-related signal changes, leading to signal anti-correlation. We show that regions with CDB anti-correlated signals coincide with most, but not all, of the regions with negative BOLD signal changes observed during a visual and motor stimulus task. Thus, the addition of a physiological challenge to fMRI experiments can help identify which negative BOLD signals are passive physiological anti-correlations and which may have a putative neuronal origin. PMID:24211818

Investigation of BOLD fMRI Resonance Frequency Shifts and Quantitative Susceptibility Changes at 7 T

PubMed Central

Bianciardi, Marta; van Gelderen, Peter; Duyn, Jeff H.

2013-01-01

Although blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) experiments of brain activity generally rely on the magnitude of the signal, they also provide frequency information that can be derived from the phase of the signal. However, because of confounding effects of instrumental and physiological origin, BOLD related frequency information is difficult to extract and therefore rarely used. Here, we explored the use of high field (7 T) and dedicated signal processing methods to extract frequency information and use it to quantify and interpret blood oxygenation and blood volume changes. We found that optimized preprocessing improves detection of task-evoked and spontaneous changes in phase signals and resonance frequency shifts over large areas of the cortex with sensitivity comparable to that of magnitude signals. Moreover, our results suggest the feasibility of mapping BOLD quantitative susceptibility changes in at least part of the activated area and its largest draining veins. Comparison with magnitude data suggests that the observed susceptibility changes originate from neuronal activity through induced blood volume and oxygenation changes in pial and intracortical veins. Further, from frequency shifts and susceptibility values, we estimated that, relative to baseline, the fractional oxygen saturation in large vessels increased by 0.02–0.05 during stimulation, which is consistent to previously published estimates. Together, these findings demonstrate that valuable information can be derived from fMRI imaging of BOLD frequency shifts and quantitative susceptibility changes. PMID:23897623

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

Evaluation of preprocessing steps to compensate for magnetic field distortions due to body movements in BOLD fMRI

PubMed Central

Barry, Robert L.; Williams, Joy M.; Klassen, L. Martyn; Gallivan, Jason P.; Culham, Jody C.

2009-01-01

Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is currently the dominant technique for non-invasive investigation of brain functions. One of the challenges with BOLD fMRI, particularly at high fields, is compensation for the effects of spatiotemporally varying magnetic field inhomogeneities (ΔB0) caused by normal subject respiration, and in some studies, movement of the subject during the scan to perform tasks related to the functional paradigm. The presence of ΔB0 during data acquisition distorts reconstructed images and introduces extraneous fluctuations in the fMRI time series that decrease the BOLD contrast-to-noise ratio. Optimization of the fMRI data-processing pipeline to compensate for geometric distortions is of paramount importance to ensure high quality of fMRI data. To investigate ΔB0 caused by subject movement, echo-planar imaging scans were collected with and without concurrent motion of a phantom arm. The phantom arm was constructed and moved by the experimenter to emulate forearm motions while subjects remained still and observed a visual stimulation paradigm. These data were then subjected to eight different combinations of preprocessing steps. The best preprocessing pipeline included navigator correction, a complex phase regressor, and spatial smoothing. The synergy between navigator correction and phase regression reduced geometric distortions better than either step in isolation, and preconditioned the data to make them more amenable to the benefits of spatial smoothing. The combination of these steps provided a 10% increase in t-statistics compared to only navigator correction and spatial smoothing, and reduced the noise and false activations in regions where no legitimate effects would occur. PMID:19695810

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

PubMed

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

2014-08-01

The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation. Copyright © 2014. Published by Elsevier Inc.

Negative BOLD with Large Increases in Neuronal Activity

PubMed Central

Khubchandani, Manjula; Motelow, Joshua E.; Sanganahalli, Basavaraju G.; Hyder, Fahmeed

2008-01-01

Blood oxygen level–dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used in neuroscience to study brain activity. However, BOLD fMRI does not measure neuronal activity directly but depends on cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) consumption. Using fMRI, CBV, CBF, neuronal recordings, and CMRO2 modeling, we investigated how the signals are related during seizures in rats. We found that increases in hemodynamic, neuronal, and metabolic activity were associated with positive BOLD signals in the cortex, but with negative BOLD signals in hippocampus. Our data show that negative BOLD signals do not necessarily imply decreased neuronal activity or CBF, but can result from increased neuronal activity, depending on the interplay between hemodynamics and metabolism. Caution should be used in interpreting fMRI signals because the relationship between neuronal activity and BOLD signals may depend on brain region and state and can be different during normal and pathological conditions. PMID:18063563

Grouping individual independent BOLD effects: a new way to ICA group analysis

NASA Astrophysics Data System (ADS)

Duann, Jeng-Ren; Jung, Tzyy-Ping; Sejnowski, Terrence J.; Makeig, Scott

2009-04-01

A new group analysis method to summarize the task-related BOLD responses based on independent component analysis (ICA) was presented. As opposite to the previously proposed group ICA (gICA) method, which first combined multi-subject fMRI data in either temporal or spatial domain and applied ICA decomposition only once to the combined fMRI data to extract the task-related BOLD effects, the method presented here applied ICA decomposition to the individual subjects' fMRI data to first find the independent BOLD effects specifically for each individual subject. Then, the task-related independent BOLD component was selected among the resulting independent components from the single-subject ICA decomposition and hence grouped across subjects to derive the group inference. In this new ICA group analysis (ICAga) method, one does not need to assume that the task-related BOLD time courses are identical across brain areas and subjects as used in the grand ICA decomposition on the spatially concatenated fMRI data. Neither does one need to assume that after spatial normalization, the voxels at the same coordinates represent exactly the same functional or structural brain anatomies across different subjects. These two assumptions have been problematic given the recent BOLD activation evidences. Further, since the independent BOLD effects were obtained from each individual subject, the ICAga method can better account for the individual differences in the task-related BOLD effects. Unlike the gICA approach whereby the task-related BOLD effects could only be accounted for by a single unified BOLD model across multiple subjects. As a result, the newly proposed method, ICAga, was able to better fit the task-related BOLD effects at individual level and thus allow grouping more appropriate multisubject BOLD effects in the group analysis.

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

BOLD repetition decreases in object-responsive ventral visual areas depend on spatial attention.

PubMed

Eger, E; Henson, R N A; Driver, J; Dolan, R J

2004-08-01

Functional imaging studies of priming-related repetition phenomena have become widely used to study neural object representation. Although blood oxygenation level-dependent (BOLD) repetition decreases can sometimes be observed without awareness of repetition, any role for spatial attention in BOLD repetition effects remains largely unknown. We used fMRI in 13 healthy subjects to test whether BOLD repetition decreases for repeated objects in ventral visual cortices depend on allocation of spatial attention to the prime. Subjects performed a size-judgment task on a probe object that had been attended or ignored in a preceding prime display of 2 lateralized objects. Reaction times showed faster responses when the probe was the same object as the attended prime, independent of the view tested (identical vs. mirror image). No behavioral effect was evident from unattended primes. BOLD repetition decreases for attended primes were found in lateral occipital and fusiform regions bilaterally, which generalized across identical and mirror-image repeats. No repetition decreases were observed for ignored primes. Our results suggest a critical role for attention in achieving visual representations of objects that lead to both BOLD signal decreases and behavioral priming on repeated presentation.

Sustained negative BOLD response in human fMRI finger tapping task.

PubMed

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

2011-01-01

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

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

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

PubMed Central

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

2010-01-01

Neural, vascular and structural variables contributing to the BOLD signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (6M and 6F; mean age: 24 years; range: 19–27 years) and twelve older healthy subjects (5M and 7F; mean age: 58 years; range: 55–71 years) with no history of head trauma and neurological disease were scanned. FMRI measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold 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 breath hold 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 inter-subject 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. PMID:20117893

Caffeine reduces resting-state BOLD functional connectivity in the motor cortex.

PubMed

Rack-Gomer, Anna Leigh; Liau, Joy; Liu, Thomas T

2009-05-15

In resting-state functional magnetic resonance imaging (fMRI), correlations between spontaneous low-frequency fluctuations in the blood oxygenation level dependent (BOLD) signal are used to assess functional connectivity between different brain regions. Changes in resting-state BOLD connectivity measures are typically interpreted as changes in coherent neural activity across spatially distinct brain regions. However, this interpretation can be complicated by the complex dependence of the BOLD signal on both neural and vascular factors. For example, prior studies have shown that vasoactive agents that alter baseline cerebral blood flow, such as caffeine and carbon dioxide, can significantly alter the amplitude and dynamics of the task-related BOLD response. In this study, we examined the effect of caffeine (200 mg dose) on resting-state BOLD connectivity in the motor cortex across a sample of healthy young subjects (N=9). We found that caffeine significantly (p<0.05) reduced measures of resting-state BOLD connectivity in the motor cortex. Baseline cerebral blood flow and spectral energy in the low-frequency BOLD fluctuations were also significantly decreased by caffeine. These results suggest that caffeine usage should be carefully considered in the design and interpretation of resting-state BOLD fMRI studies.

BOLD response to semantic and syntactic processing during hypoglycemia is load-dependent.

PubMed

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 ∼50mg/dL); in the other, plasma glucose was maintained at euglycemic levels (∼100mg/dL). During scans subjects were presented with sentences of contrasting syntactic (embedding vs. conjunction) and semantic (reversibility vs. irreversibility) load. Semantic factors dominated the overall load effects on both performance (p<0.001) and BOLD response (p<0.01, corrected). Differential BOLD signal was observed in frontal, temporal, temporo-parietal and medio-temporal regions. Hypoglycemia and syntactic factors significantly impacted performance (p=0.002) and BOLD response (p<0.01, corrected) in the reversible clause conditions, more extensively in reversible-embedded than in reversible-conjoined clauses. Hypoglycemia resulted in a robust decrease in performance on reversible clauses and exerted attenuating effects on BOLD unselectively across cortical circuits. The dominance of reversibility in all measures underscores the distinction between the syntactic and semantic contrasts. The syntactic is based in a quantitative difference in algorithms interpreting embedded and conjoined structures. We suggest that the semantic is based in a qualitative difference between algorithmic mapping of arguments in reversible clauses and heuristic linking in irreversible clauses. Because heuristics drastically reduce resource demand, the operations they support would resist the load-dependent cognitive consequences of hypoglycemia. © 2011 Elsevier Inc. All rights reserved.

Latencies in BOLD response during visual attention processes.

PubMed

Kellermann, Thilo; Reske, Martina; Jansen, Andreas; Satrapi, Peyman; Shah, N Jon; Schneider, Frank; Habel, Ute

2011-04-22

One well-investigated division of attentional processes focuses on alerting, orienting and executive control, which can be assessed applying the attentional network test (ANT). The goal of the present study was to add further knowledge about the temporal dynamics of relevant neural correlates. As a right hemispheric dominance for alerting and orienting has previously been reported for intrinsic but not for phasic alertness, we additionally addressed a potential impact of this lateralization of attention by employing a lateralized version of the ANT, capturing phasic alertness processes. Sixteen healthy subjects underwent event-related functional magnetic resonance imaging (fMRI) while performing the ANT. Analyses of BOLD magnitude replicated the engagement of a fronto-parietal network in the attentional subsystems. The amplitudes of the attentional contrasts interacted with visual field presentation in the sense that the thalamus revealed a greater involvement for spatially cued items presented in the left visual field. Comparisons of BOLD latencies in visual cortices, first, verified faster BOLD responses following contra-lateral stimulus presentation. Second and more importantly, we identified attention-modulated activation in secondary visual and anterior cingulate cortices. Results are discussed in terms of bottom-up and lateralization processes. Although intrinsic and phasic alertness are distinct cognitive processes, we propose that neural substrates of intrinsic alertness may be accessed by phasic alertness provided that the attention-dominant (i.e., the right) hemisphere is activated directly by a warning stimulus. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

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

PubMed Central

See, Ronald E.; Joseph, Jane E.; Reichel, Carmela M.

2016-01-01

Background 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. Objective 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. Methods 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 10 min, rats received drug over the next 10 min for a total 40 min 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. Results 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. Conclusion Acute methamphetamine and cocaine have distinct patterns of functional activity as measured by pfMRI. PMID:27103569

Reduced CMRO₂ and cerebrovascular reserve in patients with severe intracranial arterial stenosis: a combined multiparametric qBOLD oxygenation and BOLD fMRI study.

PubMed

Bouvier, Julien; Detante, Olivier; Tahon, Florence; Attye, Arnaud; Perret, Thomas; Chechin, David; Barbieux, Marianne; Boubagra, Kamel; Garambois, Katia; Tropres, Irène; Grand, Sylvie; Barbier, Emmanuel L; Krainik, Alexandre

2015-02-01

Multiparametric quantitative blood oxygenation level dependent (mqBOLD) magnetic resonance Imaging (MRI) approach allows mapping tissular oxygen saturation (StO2 ) and cerebral metabolic rate of oxygen (CMRO2 ). To identify hemodynamic alteration related to severe intracranial arterial stenosis (SIAS), functional MRI of cerebrovascular reserve (CVR BOLD fMRI) to hypercapnia has been proposed. Diffusion imaging suggests chronic low grade ischemia in patients with impaired CVR. The aim of the present study was to evaluate how oxygen parameters (StO2 and CMRO2 ), assessed with mqBOLD approach, correlate with CVR in patients (n = 12) with SIAS and without arterial occlusion. The perfusion (dynamic susceptibility contrast), oxygenation, and CVR were compared. The MRI protocol conducted at 3T lasted approximately 1 h. Regions of interest measures on maps were delineated on segmented gray matter (GM) of middle cerebral artery territories. We have shown that decreased CVR is spatially associated with decreased CMRO2 in GM of patients with SIAS. Further, the degree of ipsilateral CVR reduction was well-correlated with the amplitude of the CMRO2 deficit. The altered CMRO2 suggests the presence of a moderate ischemia explained by both a decrease in perfusion and in CVR. CVR and mqBOLD method may be helpful in the selection of patients with SIAS to advocate for medical therapy or percutaneous transluminal angioplasty-stenting. © 2014 Wiley Periodicals, Inc.

Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

PubMed

Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

2018-06-01

External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

Physiological denoising of BOLD fMRI data using Regressor Interpolation at Progressive Time Delays (RIPTiDe) processing of concurrent fMRI and near-infrared spectroscopy (NIRS).

PubMed

Frederick, Blaise deB; Nickerson, Lisa D; Tong, Yunjie

2012-04-15

Confounding noise in BOLD fMRI data arises primarily from fluctuations in blood flow and oxygenation due to cardiac and respiratory effects, spontaneous low frequency oscillations (LFO) in arterial pressure, and non-task related neural activity. Cardiac noise is particularly problematic, as the low sampling frequency of BOLD fMRI ensures that these effects are aliased in recorded data. Various methods have been proposed to estimate the noise signal through measurement and transformation of the cardiac and respiratory waveforms (e.g. RETROICOR and respiration volume per time (RVT)) and model-free estimation of noise variance through examination of spatial and temporal patterns. We have previously demonstrated that by applying a voxel-specific time delay to concurrently acquired near infrared spectroscopy (NIRS) data, we can generate regressors that reflect systemic blood flow and oxygenation fluctuations effects. Here, we apply this method to the task of removing physiological noise from BOLD data. We compare the efficacy of noise removal using various sets of noise regressors generated from NIRS data, and also compare the noise removal to RETROICOR+RVT. We compare the results of resting state analyses using the original and noise filtered data, and we evaluate the bias for the different noise filtration methods by computing null distributions from the resting data and comparing them with the expected theoretical distributions. Using the best set of processing choices, six NIRS-generated regressors with voxel-specific time delays explain a median of 10.5% of the variance throughout the brain, with the highest reductions being seen in gray matter. By comparison, the nine RETROICOR+RVT regressors together explain a median of 6.8% of the variance in the BOLD data. Detection of resting state networks was enhanced with NIRS denoising, and there were no appreciable differences in the bias of the different techniques. Physiological noise regressors generated using

Accounting for the role of hematocrit in between-subject variations of MRI-derived baseline cerebral hemodynamic parameters and functional BOLD responses.

PubMed

Xu, Feng; Li, Wenbo; Liu, Peiying; Hua, Jun; Strouse, John J; Pekar, James J; Lu, Hanzhang; van Zijl, Peter C M; Qin, Qin

2018-01-01

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T 1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO 2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO 2 to maintain constant CMRO 2 . Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%-22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

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

2016-10-01

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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Controlled inspiration depth reduces variance in breath-holding-induced BOLD signal.

PubMed

Thomason, Moriah E; Glover, Gary H

2008-01-01

Recent studies have shown that blood oxygen level dependent (BOLD) response amplitude during short periods of breath holding (BH) measured by functional magnetic resonance imaging (fMRI) can be an effective metric for intersubject calibration procedures. However, inconsistency in the depth of inspiration during the BH scan may account for a portion of BOLD variation observed in such scans, and it is likely to reduce the effectiveness of the calibration measurement. While modulation of BOLD signal has been correlated with end-tidal CO2 and other measures of breathing, fluctuations in performance of BH have not been studied in the context of their impact on BOLD signal. Here, we studied the degree to which inspiration depth corresponds to BOLD signal change and tested the effectiveness of a method designed to control inspiration level through visual cues during the BH task paradigm. We observed reliable differences in BOLD signal amplitude corresponding to the depth of inspiration. It was determined that variance in BOLD signal response to BH could be significantly reduced when subjects were given visual feedback during task inspiration periods. The implications of these findings for routine BH studies of BOLD-derived neurovascular response are discussed.

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

PubMed Central

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

2012-01-01

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

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

Non-neural BOLD variability in block and event-related paradigms.

PubMed

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

2011-01-01

Block and event-related stimulus designs are typically used in fMRI studies depending on the importance of detection power or estimation efficiency. The extent of vascular contribution to variability in block and event-related fMRI-BOLD response is not known. With scaling, the extent of vascular variability in the fMRI-BOLD response during block and event-related design tasks was investigated. Blood oxygen level-dependent (BOLD) contrast data from healthy volunteers performing a block design motor task and an event-related memory task requiring performance of a motor response were analyzed from the regions of interest (ROIs) surrounding the primary and supplementary motor cortices. Average BOLD signal change was significantly larger during the block design compared to the event-related design. In each subject, BOLD signal change across voxels in the ROIs had higher variation during the block design task compared to the event-related design task. Scaling using the resting state fluctuation of amplitude (RSFA) and breath-hold (BH), which minimizes BOLD variation due to vascular origins, reduced the within-subject BOLD variability in every subject during both tasks but significantly reduced BOLD variability across subjects only during the block design task. The strong non-neural source of intra- and intersubject variability of BOLD response during the block design compared to event-related task indicates that study designs optimizing for statistical power through enhancement of the BOLD contrast (for, e.g., block design) can be affected by enhancement of non-neural sources of BOLD variability. Copyright © 2011. Published by Elsevier Inc.

Functional magnetic resonance imaging (fMRI) response to alcohol pictures predicts subsequent transition to heavy drinking in college students.

PubMed

Dager, Alecia D; Anderson, Beth M; Rosen, Rivkah; Khadka, Sabin; Sawyer, Broderick; Jiantonio-Kelly, Rachel E; Austad, Carol S; Raskin, Sarah A; Tennen, Howard; Wood, Rebecca M; Fallahi, Carolyn R; Pearlson, Godfrey D

2014-04-01

Young adults show the highest rates of escalating drinking, yet the neural risk mechanisms remain unclear. Heavy drinkers show variant functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to alcohol cues, which may presage increasing drinking. In this longitudinal study, we ascertained whether BOLD response to alcohol pictures predicted subsequent heavy drinking among college students. Participants were 43 18-21-year-olds in the United States who underwent BOLD scanning and completed monthly substance use surveys over the following year. Participants were categorized according to baseline and follow-up drinking into 13 continuously moderate drinkers, 16 continuously heavy drinkers and 14 transitioners who drank moderately at baseline but heavily by follow-up. During fMRI scanning at baseline, participants viewed alcohol and matched non-alcohol beverage images. We observed group differences in alcohol cue-elicited BOLD response in bilateral caudate, orbitofrontal cortex, medial frontal cortex/anterior cingulate and left insula (clusters > 2619 ml, voxelwise F(2,40)  > 3.23, P < 0.05, whole-brain corrected P < 0.05), where transitioners hyperactivated compared with moderate and heavy drinkers (all Tukey P < 0.05). Exploratory factor analysis revealed a single brain network differentiating those who subsequently increased drinking. Exploratory regressions showed that, compared with other risk factors (e.g., alcoholism family history, impulsivity), BOLD response best predicted escalating drinking amount and alcohol-related problems. Neural response to pictures of alcohol is substantially enhanced among United States college students who subsequently escalate drinking. Greater cue-reactivity is associated with larger increases in drinking and alcohol-related problems, regardless of other baseline factors. Thus, neural cue-reactivity could uniquely facilitate identifying individuals at greatest risk for future

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…

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.

Intersession reliability of fMRI activation for heat pain and motor tasks

PubMed Central

Quiton, Raimi L.; Keaser, Michael L.; Zhuo, Jiachen; Gullapalli, Rao P.; Greenspan, Joel D.

2014-01-01

As the practice of conducting longitudinal fMRI studies to assess mechanisms of pain-reducing interventions becomes more common, there is a great need to assess the test–retest reliability of the pain-related BOLD fMRI signal across repeated sessions. This study quantitatively evaluated the reliability of heat pain-related BOLD fMRI brain responses in healthy volunteers across 3 sessions conducted on separate days using two measures: (1) intraclass correlation coefficients (ICC) calculated based on signal amplitude and (2) spatial overlap. The ICC analysis of pain-related BOLD fMRI responses showed fair-to-moderate intersession reliability in brain areas regarded as part of the cortical pain network. Areas with the highest intersession reliability based on the ICC analysis included the anterior midcingulate cortex, anterior insula, and second somatosensory cortex. Areas with the lowest intersession reliability based on the ICC analysis also showed low spatial reliability; these regions included pregenual anterior cingulate cortex, primary somatosensory cortex, and posterior insula. Thus, this study found regional differences in pain-related BOLD fMRI response reliability, which may provide useful information to guide longitudinal pain studies. A simple motor task (finger-thumb opposition) was performed by the same subjects in the same sessions as the painful heat stimuli were delivered. Intersession reliability of fMRI activation in cortical motor areas was comparable to previously published findings for both spatial overlap and ICC measures, providing support for the validity of the analytical approach used to assess intersession reliability of pain-related fMRI activation. A secondary finding of this study is that the use of standard ICC alone as a measure of reliability may not be sufficient, as the underlying variance structure of an fMRI dataset can result in inappropriately high ICC values; a method to eliminate these false positive results was used in this

SNR and functional sensitivity of BOLD and perfusion-based fMRI using arterial spin labeling with spiral SENSE at 3 T.

PubMed

Perthen, Joanna E; Bydder, Mark; Restom, Khaled; Liu, Thomas T

2008-05-01

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies using parallel imaging to reduce the readout window have reported a loss in temporal signal-to-noise ratio (SNR) that is less than would be expected given a purely thermal noise model. In this study, the impact of parallel imaging on the noise components and functional sensitivity of both BOLD and perfusion-based fMRI data was investigated. Dual-echo arterial spin labeling data were acquired on five subjects using sensitivity encoding (SENSE), at reduction factors (R) of 1, 2 and 3. Direct recording of cardiac and respiratory activity during data acquisition enabled the retrospective removal of physiological noise. The temporal SNR of the perfusion time series closely followed the thermal noise prediction of a radicalR loss in SNR as the readout window was shortened, with temporal SNR values (relative to the R=1 data) of 0.72 and 0.56 for the R=2 and R=3 data, respectively, after accounting for physiological noise. However, the BOLD temporal SNR decreased more slowly than predicted even after accounting for physiological noise, with relative temporal SNR values of 0.80 and 0.63 for the R=2 and R=3 data, respectively. Spectral analysis revealed that the BOLD trends were dominated by low-frequency fluctuations, which were not dominant in the perfusion data due to signal processing differences. The functional sensitivity, assessed using mean F values over activated regions of interest (ROIs), followed the temporal SNR trends for the BOLD data. However, results for the perfusion data were more dependent on the threshold used for ROI selection, most likely due to the inherently low SNR of functional perfusion data.

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.

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

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

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

PubMed Central

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

2013-01-01

BOLD fMRI has provided a wealth of information about the aging brain. A common finding is that posterior regions of the brain manifest an age-related decrease in activation while the anterior regions show an age-related increase. Several neurocognitive models have been proposed to interpret these findings. However, one issue that has not been sufficiently considered to date is that the BOLD signal is based on vascular responses secondary to neural activity. Thus the above findings could be in part due to a vascular change, especially in view of the expected decline of vascular health with age. In the present study, we aim to examine age-related differences in memory-encoding fMRI response in the context of vascular aging. One hundred and thirty healthy subjects ranging from 20 to 89 years old underwent a scene-viewing fMRI task and, in the same session, cerebrovascular reactivity (CVR) was measured in each subject using a CO2-inhalation task. Without accounting for the influence of vascular changes, the task-activated fMRI signal showed the typical age-related decrease in visual cortex and medial temporal lobe (MTL), but manifested an increase in the right inferior frontal gyrus (IFG). In the same individuals, an age-related CVR reduction was observed in all of these regions. We then used a previously proposed normalization approach to calculate a CVR-corrected fMRI signal, which was defined as the uncorrected signal divided by CVR. Based on the CVR-corrected fMRI signal, an age-related increase is now seen in both the left and right side of IFG; and no brain regions showed a signal decrease with age. We additionally used a model-based approach to examine the fMRI data in the context of CVR, which again suggested an age-related change in the two frontal regions, but not in the visual and MTL regions. PMID:23624491

Placental baseline conditions modulate the hyperoxic BOLD-MRI response.

PubMed

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

2018-01-01

Human pregnancies complicated by placental dysfunction may be characterized by a high hyperoxic Blood oxygen level-dependent (BOLD) MRI response. The pathophysiology behind this phenomenon remains to be established. The aim of this study was to evaluate whether it is associated with altered placental baseline conditions, including a lower oxygenation and altered tissue morphology, as estimated by the placental transverse relaxation time (T2*). We included 49 normal pregnancies (controls) and 13 pregnancies complicated by placental dysfunction (cases), defined by a birth weight < 10th percentile in combination with placental pathological signs of vascular malperfusion. During maternal oxygen inhalation, we measured the relative ΔBOLD response ((hyperoxic BOLD - baseline BOLD)/baseline BOLD) from a dynamic single-echo gradient-recalled echo (GRE) MRI sequence and the absolute ΔT2* (hyperoxic T2*- baseline T2*) from breath-hold multi-echo GRE sequences. In the control group, the relative ΔBOLD response increased during gestation from 5% in gestational week 20 to 20% in week 40. In the case group, the relative ΔBOLD response was significantly higher (mean Z-score 4.94; 95% CI 2.41, 7.47). The absolute ΔT2*, however, did not differ between controls and cases (p = 0.37), whereas the baseline T2* was lower among cases (mean Z-score -3.13; 95% CI -3.94, -2.32). Furthermore, we demonstrated a strong negative linear correlation between the Log 10 ΔBOLD response and the baseline T2* (r = -0.88, p < 0.0001). The high hyperoxic ΔBOLD response demonstrated in pregnancies complicated by placental dysfunction may simply reflect altered baseline conditions, as the absolute increase in placental oxygenation (ΔT2*) does not differ between groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Orientation-specific contextual modulation of the fMRI BOLD response to luminance and chromatic gratings in human visual cortex.

PubMed

McDonald, J Scott; Seymour, Kiley J; Schira, Mark M; Spehar, Branka; Clifford, Colin W G

2009-05-01

The responses of orientation-selective neurons in primate visual cortex can be profoundly affected by the presence and orientation of stimuli falling outside the classical receptive field. Our perception of the orientation of a line or grating also depends upon the context in which it is presented. For example, the perceived orientation of a grating embedded in a surround tends to be repelled from the predominant orientation of the surround. Here, we used fMRI to investigate the basis of orientation-specific surround effects in five functionally-defined regions of visual cortex: V1, V2, V3, V3A/LO1 and hV4. Test stimuli were luminance-modulated and isoluminant gratings that produced responses similar in magnitude. Less BOLD activation was evident in response to gratings with parallel versus orthogonal surrounds across all the regions of visual cortex investigated. When an isoluminant test grating was surrounded by a luminance-modulated inducer, the degree of orientation-specific contextual modulation was no larger for extrastriate areas than for V1, suggesting that the observed effects might originate entirely in V1. However, more orientation-specific modulation was evident in extrastriate cortex when both test and inducer were luminance-modulated gratings than when the test was isoluminant; this difference was significant in area V3. We suggest that the pattern of results in extrastriate cortex may reflect a refinement of the orientation-selectivity of surround suppression specific to the colour of the surround or, alternatively, processes underlying the segmentation of test and inducer by spatial phase or orientation when no colour cue is available.

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

Spatiotemporal characteristics and vascular sources of neural-specific and -nonspecific fMRI signals at submillimeter columnar resolution

PubMed Central

Moon, Chan Hong; Fukuda, Mitsuhiro; Kim, Seong-Gi

2012-01-01

The neural specificity of hemodynamic-based functional magnetic resonance imaging (fMRI) signals are dependent on both the vascular regulation and the sensitivity of the applied fMRI technique to different types and sizes of blood vessels. In order to examine the specificity of MRI-detectable hemodynamic responses, submillimeter blood oxygenation-level dependent (BOLD) and cerebral blood volume (CBV) fMRI studies were performed in a well-established cat orientation column model at 9.4 Tesla. Neural-nonspecific and -specific signals were separated by comparing the fMRI responses of orthogonal orientation stimuli. The BOLD response was dominantly neural-nonspecific, mostly originating from pial and intracortical emerging veins, and thus was highly correlated with baseline blood volume. Uneven baseline CBV may displace or distort small functional domains in high-resolution BOLD maps. The CBV response in the parenchyma exhibited dual spatiotemporal characteristics, a fast and early neural-nonspecific response (with 4.3-s time constant) and a slightly slower and delayed neural-specific response (with 9.4-s time constant). The nonspecific CBV signal originates from early-responding arteries and arterioles, while the specific CBV response, which is not correlated with baseline blood volume, arises from late-responding microvessels including small pre-capillary arterioles and capillaries. Our data indicate that although the neural specificity of CBV fMRI signals is dependent on stimulation duration, high-resolution functional maps can be obtained from steady-state CBV studies. PMID:22960251

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

PubMed Central

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

2017-01-01

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 (<0.1 Hz) 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. PMID:27993673

Reduced BOLD response to periodic visual stimulation.

PubMed

Parkes, Laura M; Fries, Pascal; Kerskens, Christian M; Norris, David G

2004-01-01

The blood oxygenation level-dependent (BOLD) response to entrained neuronal firing in the human visual cortex and lateral geniculate nuclei was investigated. Periodic checkerboard flashes at a range of frequencies (4-20 Hz) were used to drive the visual cortex neurons into entrained oscillatory firing. This is compared to a checkerboard flashing aperiodically, with the same average number of flashes per unit time. A magnetoencephalography (MEG) measurement was made to confirm that the periodic paradigm elicited entrainment. We found that for frequencies of 10 and 15 Hz, the periodic stimulus gave a smaller BOLD response than for the aperiodic stimulus. Detailed investigation at 15 Hz showed that the aperiodic stimulus gave a similar BOLD increase regardless of the magnitude of jitter (+/-17 ms compared to +/-33 ms), indicating that flashes need to be precise to at least 17 ms to maintain entrainment. This is also evidence that for aperiodic stimuli, the amplitude of the BOLD response ordinarily reflects the total number of flashes per unit time, irrespective of the precise spacing between them, suggesting that entrainment is the main cause of the BOLD reduction in the periodic condition. The results indicate that, during entrainment, there is a reduction in the neuronal metabolic demand. We suggest that because of the selective frequency band of this effect, it could be connected to synchronised reverberations around an internal feedback loop.

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

PubMed

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

2015-03-31

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

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

PubMed

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

2016-10-05

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'. © 2016 The Author(s).

Calibrated FMRI.

PubMed

Hoge, Richard D

2012-08-15

Functional magnetic resonance imaging with blood oxygenation level-dependent (BOLD) contrast has had a tremendous influence on human neuroscience in the last twenty years, providing a non-invasive means of mapping human brain function with often exquisite sensitivity and detail. However the BOLD method remains a largely qualitative approach. While the same can be said of anatomic MRI techniques, whose clinical and research impact has not been diminished in the slightest by the lack of a quantitative interpretation of their image intensity, the quantitative expression of BOLD responses as a percent of the baseline T2*- weighted signal has been viewed as necessary since the earliest days of fMRI. Calibrated MRI attempts to dissociate changes in oxygen metabolism from changes in blood flow and volume, the latter three quantities contributing jointly to determine the physiologically ambiguous percent BOLD change. This dissociation is typically performed using a "calibration" procedure in which subjects inhale a gas mixture containing small amounts of carbon dioxide or enriched oxygen to produce changes in blood flow and BOLD signal which can be measured under well-defined hemodynamic conditions. The outcome is a calibration parameter M which can then be substituted into an expression providing the fractional change in oxygen metabolism given changes in blood flow and BOLD signal during a task. The latest generation of calibrated MRI methods goes beyond fractional changes to provide absolute quantification of resting-state oxygen consumption in micromolar units, in addition to absolute measures of evoked metabolic response. This review discusses the history, challenges, and advances in calibrated MRI, from the personal perspective of the author. Copyright © 2012 Elsevier Inc. All rights reserved.

Inferring neural activity from BOLD signals through nonlinear optimization.

PubMed

Vakorin, Vasily A; Krakovska, Olga O; Borowsky, Ron; Sarty, Gordon E

2007-11-01

The blood oxygen level-dependent (BOLD) fMRI signal does not measure neuronal activity directly. This fact is a key concern for interpreting functional imaging data based on BOLD. Mathematical models describing the path from neural activity to the BOLD response allow us to numerically solve the inverse problem of estimating the timing and amplitude of the neuronal activity underlying the BOLD signal. In fact, these models can be viewed as an advanced substitute for the impulse response function. In this work, the issue of estimating the dynamics of neuronal activity from the observed BOLD signal is considered within the framework of optimization problems. The model is based on the extended "balloon" model and describes the conversion of neuronal signals into the BOLD response through the transitional dynamics of the blood flow-inducing signal, cerebral blood flow, cerebral blood volume and deoxyhemoglobin concentration. Global optimization techniques are applied to find a control input (the neuronal activity and/or the biophysical parameters in the model) that causes the system to follow an admissible solution to minimize discrepancy between model and experimental data. As an alternative to a local linearization (LL) filtering scheme, the optimization method escapes the linearization of the transition system and provides a possibility to search for the global optimum, avoiding spurious local minima. We have found that the dynamics of the neural signals and the physiological variables as well as the biophysical parameters can be robustly reconstructed from the BOLD responses. Furthermore, it is shown that spiking off/on dynamics of the neural activity is the natural mathematical solution of the model. Incorporating, in addition, the expansion of the neural input by smooth basis functions, representing a low-pass filtering, allows us to model local field potential (LFP) solutions instead of spiking solutions.

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

PubMed

Gaxiola-Valdez, Ismael; Goodyear, Bradley G

2012-12-01

Accurate localization of brain activity using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been challenged because of the large BOLD signal within distal veins. Arterial spin labeling (ASL) techniques offer greater sensitivity to the microvasculature but possess low temporal resolution and limited brain coverage. In this study, we show that the physiological origins of BOLD and ASL depend on whether percent change or statistical significance is being considered. For BOLD and ASL fMRI data collected during a simple unilateral hand movement task, we found that in the area of the contralateral motor cortex the centre of gravity (CoG) of the intersubject coefficient of variation (CV) of BOLD fMRI was near the brain surface for percent change in signal, whereas the CoG of the intersubject CV for Z-score was in close proximity of sites of brain activity for both BOLD and ASL. These findings suggest that intersubject variability of BOLD percent change is vascular in origin, whereas the origin of inter-subject variability of Z-score is neuronal for both BOLD and ASL. For longer duration tasks (12 s or greater), however, there was a significant correlation between BOLD and ASL percent change, which was not evident for short duration tasks (6 s). These findings suggest that analyses directly comparing percent change in BOLD signal between pre-defined regions of interest using short duration stimuli, as for example in event-related designs, may be heavily weighted by large-vessel responses rather than neuronal responses. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Generate the scale-free brain music from BOLD signals

PubMed Central

Lu, Jing; Guo, Sijia; Chen, Mingming; Wang, Weixia; Yang, Hua; Guo, Daqing; Yao, Dezhong

2018-01-01

Abstract Many methods have been developed to translate a human electroencephalogram (EEG) into music. In addition to EEG, functional magnetic resonance imaging (fMRI) is another method used to study the brain and can reflect physiological processes. In 2012, we established a method to use simultaneously recorded fMRI and EEG signals to produce EEG-fMRI music, which represents a step toward scale-free brain music. In this study, we used a neural mass model, the Jansen–Rit model, to simulate activity in several cortical brain regions. The interactions between different brain regions were represented by the average normalized diffusion tensor imaging (DTI) structural connectivity with a coupling coefficient that modulated the coupling strength. Seventy-eight brain regions were adopted from the Automated Anatomical Labeling (AAL) template. Furthermore, we used the Balloon–Windkessel hemodynamic model to transform neural activity into a blood-oxygen-level dependent (BOLD) signal. Because the fMRI BOLD signal changes slowly, we used a sampling rate of 250 Hz to produce the temporal series for music generation. Then, the BOLD music was generated for each region using these simulated BOLD signals. Because the BOLD signal is scale free, these music pieces were also scale free, which is similar to classic music. Here, to simulate the case of an epileptic patient, we changed the parameter that determined the amplitude of the excitatory postsynaptic potential (EPSP) in the neural mass model. Finally, we obtained BOLD music for healthy and epileptic patients. The differences in levels of arousal between the 2 pieces of music may provide a potential tool for discriminating the different populations if the differences can be confirmed by more real data. PMID:29480872

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

PubMed

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

2016-03-01

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

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

PubMed Central

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

2015-01-01

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

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

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional magnetic resonance imaging (FMRI) with auditory stimulation in songbirds.

PubMed

Van Ruijssevelt, Lisbeth; De Groof, Geert; Van der Kant, Anne; Poirier, Colline; Van Audekerke, Johan; Verhoye, Marleen; Van der Linden, Annemie

2013-06-03

The neurobiology of birdsong, as a model for human speech, is a pronounced area of research in behavioral neuroscience. Whereas electrophysiology and molecular approaches allow the investigation of either different stimuli on few neurons, or one stimulus in large parts of the brain, blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) allows combining both advantages, i.e. compare the neural activation induced by different stimuli in the entire brain at once. fMRI in songbirds is challenging because of the small size of their brains and because their bones and especially their skull comprise numerous air cavities, inducing important susceptibility artifacts. Gradient-echo (GE) BOLD fMRI has been successfully applied to songbirds (1-5) (for a review, see (6)). These studies focused on the primary and secondary auditory brain areas, which are regions free of susceptibility artifacts. However, because processes of interest may occur beyond these regions, whole brain BOLD fMRI is required using an MRI sequence less susceptible to these artifacts. This can be achieved by using spin-echo (SE) BOLD fMRI (7,8) . In this article, we describe how to use this technique in zebra finches (Taeniopygia guttata), which are small songbirds with a bodyweight of 15-25 g extensively studied in behavioral neurosciences of birdsong. The main topic of fMRI studies on songbirds is song perception and song learning. The auditory nature of the stimuli combined with the weak BOLD sensitivity of SE (compared to GE) based fMRI sequences makes the implementation of this technique very challenging.

Real-time fMRI neurofeedback of the mediodorsal and anterior thalamus enhances correlation between thalamic BOLD activity and alpha EEG rhythm.

PubMed

Zotev, Vadim; Misaki, Masaya; Phillips, Raquel; Wong, Chung Ki; Bodurka, Jerzy

2018-02-01

Real-time fMRI neurofeedback (rtfMRI-nf) with simultaneous EEG allows volitional modulation of BOLD activity of target brain regions and investigation of related electrophysiological activity. We applied this approach to study correlations between thalamic BOLD activity and alpha EEG rhythm. Healthy volunteers in the experimental group (EG, n = 15) learned to upregulate BOLD activity of the target region consisting of the mediodorsal (MD) and anterior (AN) thalamic nuclei using rtfMRI-nf during retrieval of happy autobiographical memories. Healthy subjects in the control group (CG, n = 14) were provided with a sham feedback. The EG participants were able to significantly increase BOLD activities of the MD and AN. Functional connectivity between the MD and the inferior precuneus was significantly enhanced during the rtfMRI-nf task. Average individual changes in the occipital alpha EEG power significantly correlated with the average MD BOLD activity levels for the EG. Temporal correlations between the occipital alpha EEG power and BOLD activities of the MD and AN were significantly enhanced, during the rtfMRI-nf task, for the EG compared to the CG. Temporal correlations with the alpha power were also significantly enhanced for the posterior nodes of the default mode network, including the precuneus/posterior cingulate, and for the dorsal striatum. Our findings suggest that the temporal correlation between the MD BOLD activity and posterior alpha EEG power is modulated by the interaction between the MD and the inferior precuneus, reflected in their functional connectivity. Our results demonstrate the potential of the rtfMRI-nf with simultaneous EEG for noninvasive neuromodulation studies of human brain function. © 2017 Wiley Periodicals, Inc.

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

Integrating EEG and fMRI in epilepsy.

PubMed

Formaggio, Emanuela; Storti, Silvia Francesca; Bertoldo, Alessandra; Manganotti, Paolo; Fiaschi, Antonio; Toffolo, Gianna Maria

2011-02-14

Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies enables to non-invasively investigate human brain function and to find the direct correlation of these two important measures of brain activity. Presurgical evaluation of patients with epilepsy is one of the areas where EEG and fMRI integration has considerable clinical relevance for localizing the brain regions generating interictal epileptiform activity. The conventional analysis of EEG-fMRI data is based on the visual identification of the interictal epileptiform discharges (IEDs) on scalp EEG. The convolution of these EEG events, represented as stick functions, with a model of the fMRI response, i.e. the hemodynamic response function, provides the regressor for general linear model (GLM) analysis of fMRI data. However, the conventional analysis is not automatic and suffers of some subjectivity in IEDs classification. Here, we present an easy-to-use and automatic approach for combined EEG-fMRI analysis able to improve IEDs identification based on Independent Component Analysis and wavelet analysis. EEG signal due to IED is reconstructed and its wavelet power is used as a regressor in GLM. The method was validated on simulated data and then applied on real data set consisting of 2 normal subjects and 5 patients with partial epilepsy. In all continuous EEG-fMRI recording sessions a good quality EEG was obtained allowing the detection of spontaneous IEDs and the analysis of the related BOLD activation. The main clinical finding in EEG-fMRI studies of patients with partial epilepsy is that focal interictal slow-wave activity was invariably associated with increased focal BOLD responses in a spatially related brain area. Our study extends current knowledge on epileptic foci localization and confirms previous reports suggesting that BOLD activation associated with slow activity might have a role in localizing the epileptogenic region even in the absence of clear

Generate the scale-free brain music from BOLD signals.

PubMed

Lu, Jing; Guo, Sijia; Chen, Mingming; Wang, Weixia; Yang, Hua; Guo, Daqing; Yao, Dezhong

2018-01-01

Many methods have been developed to translate a human electroencephalogram (EEG) into music. In addition to EEG, functional magnetic resonance imaging (fMRI) is another method used to study the brain and can reflect physiological processes. In 2012, we established a method to use simultaneously recorded fMRI and EEG signals to produce EEG-fMRI music, which represents a step toward scale-free brain music. In this study, we used a neural mass model, the Jansen-Rit model, to simulate activity in several cortical brain regions. The interactions between different brain regions were represented by the average normalized diffusion tensor imaging (DTI) structural connectivity with a coupling coefficient that modulated the coupling strength. Seventy-eight brain regions were adopted from the Automated Anatomical Labeling (AAL) template. Furthermore, we used the Balloon-Windkessel hemodynamic model to transform neural activity into a blood-oxygen-level dependent (BOLD) signal. Because the fMRI BOLD signal changes slowly, we used a sampling rate of 250 Hz to produce the temporal series for music generation. Then, the BOLD music was generated for each region using these simulated BOLD signals. Because the BOLD signal is scale free, these music pieces were also scale free, which is similar to classic music. Here, to simulate the case of an epileptic patient, we changed the parameter that determined the amplitude of the excitatory postsynaptic potential (EPSP) in the neural mass model. Finally, we obtained BOLD music for healthy and epileptic patients. The differences in levels of arousal between the 2 pieces of music may provide a potential tool for discriminating the different populations if the differences can be confirmed by more real data. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

PubMed

Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

2015-10-01

Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

MDMA (Ecstasy) use is associated with reduced BOLD signal change during semantic recognition in abstinent human polydrug users: a preliminary fMRI study

PubMed Central

Raj, Vidya; Liang, Han-Chun; Woodward, Neil D.; Bauernfeind, Amy L.; Lee, Junghee; Dietrich, Mary; Park, Sohee; Cowan, Ronald L.

2011-01-01

Objectives MDMA users have impaired verbal memory, and voxel-based morphometry has demonstrated decreased gray matter in Brodmann area (BA) 18, 21 and 45. Because these regions play a role in verbal memory, we hypothesized that MDMA users would show altered brain activation in these areas during performance of an fMRI task that probed semantic verbal memory. Methods Polysubstance users enriched for MDMA exposure participated in a semantic memory encoding and recognition fMRI task that activated left BA 9, 18, 21/22 and 45. Primary outcomes were percent BOLD signal change in left BA 9, 18, 21/22 and 45, accuracy and response time. Results During semantic recognition, lifetime MDMA use was associated with decreased activation in left BA 9, 18 and 21/22 but not 45. This was partly influenced by contributions from cannabis and cocaine use. MDMA exposure was not associated with accuracy or response time during the semantic recognition task. Conclusions During semantic recognition, MDMA exposure is associated with reduced regional brain activation in regions mediating verbal memory. These findings partially overlap with prior structural evidence for reduced gray matter in MDMA users and may, in part, explain the consistent verbal memory impairments observed in other studies of MDMA users. PMID:19304866

Dopamine modulates striatal response to reward and punishment in patients with Parkinson's disease: a pharmacological challenge fMRI study.

PubMed

Argyelan, Miklos; Herzallah, Mohammad; Sako, Wataru; DeLucia, Ivana; Sarpal, Deepak; Vo, An; Fitzpatrick, Toni; Moustafa, Ahmed A; Eidelberg, David; Gluck, Mark

2018-05-02

It is well established that Parkinson's disease leads to impaired learning from reward and enhanced learning from punishment. The administration of dopaminergic medications reverses this learning pattern. However, few studies have investigated the neural underpinnings of these cognitive processes. In this study, using fMRI, we tested a group of Parkinson's disease patients on and off dopaminergic medications and matched healthy individuals. All individuals completed an fMRI cognitive task that dissociates feedback learning from reward versus punishment. The administration of dopaminergic medications attenuated blood oxygen level dependent (BOLD) responses to punishment in the bilateral putamen, in bilateral dorsolateral prefrontal cortex and the left premotor cortex. Further, the administration of dopaminergic medications resulted in a higher ratio of BOLD activity between reward and punishment trials in these brain areas. BOLD activity in these brain areas was significantly correlated with learning from punishment, but not from reward trials. Furthermore, the administration of dopaminergic medications altered BOLD activity in the right insula and ventromedial prefrontal cortex when Parkinson's disease patients were anticipating feedback. These findings are in agreement with a large body of literature indicating that Parkinson's disease is associated with enhanced learning from punishment. However, it was surprising that dopaminergic medications modulated punishment learning as opposed to reward learning, although reward learning has been directly linked to dopaminergic function. We argue that these results might be attributed to both a change in the balance between direct and indirect pathway activation in the basal ganglia as well as the differential activity of D1 versus D2 dopamine receptors.

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

2018-05-15

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

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. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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

2012-11-15

Orientation-selective responses can be decoded from fMRI activity patterns in the human visual cortex, using multivariate pattern analysis (MVPA). To what extent do these feature-selective activity patterns depend on the strength and quality of the sensory input, and might the reliability of these activity patterns be predicted by the gross amplitude of the stimulus-driven BOLD response? Observers viewed oriented gratings that varied in luminance contrast (4, 20 or 100%) or spatial frequency (0.25, 1.0 or 4.0 cpd). As predicted, activity patterns in early visual areas led to better discrimination of orientations presented at high than low contrast, with greater effects of contrast found in area V1 than in V3. A second experiment revealed generally better decoding of orientations at low or moderate as compared to high spatial frequencies. Interestingly however, V1 exhibited a relative advantage at discriminating high spatial frequency orientations, consistent with the finer scale of representation in the primary visual cortex. In both experiments, the reliability of these orientation-selective activity patterns was well predicted by the average BOLD amplitude in each region of interest, as indicated by correlation analyses, as well as decoding applied to a simple model of voxel responses to simulated orientation columns. Moreover, individual differences in decoding accuracy could be predicted by the signal-to-noise ratio of an individual's BOLD response. Our results indicate that decoding accuracy can be well predicted by incorporating the amplitude of the BOLD response into simple simulation models of cortical selectivity; such models could prove useful in future applications of fMRI pattern classification. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2012-01-01

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

Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.

PubMed

Chai, Yuhui; Sheng, Jingwei; Bandettini, Peter A; Gao, Jia-Hong

2018-05-01

Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal. © 2018 Wiley Periodicals, Inc.

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

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.

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.

Computing moment to moment BOLD activation for real-time neurofeedback

PubMed Central

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

2013-01-01

Estimating moment to moment changes in blood oxygenation level dependent (BOLD) activation levels from functional magnetic resonance imaging (fMRI) data has applications for learned regulation of regional activation, brain state monitoring, and brain-machine interfaces. In each of these contexts, accurate estimation of the BOLD signal in as little time as possible is desired. This is a challenging problem due to the low signal-to-noise ratio of fMRI data. Previous methods for real-time fMRI analysis have either sacrificed the ability to compute moment to moment activation changes by averaging several acquisitions into a single activation estimate or have sacrificed accuracy by failing to account for prominent sources of noise in the fMRI signal. Here we present a new method for computing the amount of activation present in a single fMRI acquisition that separates moment to moment changes in the fMRI signal intensity attributable to neural sources from those due to noise, resulting in a feedback signal more reflective of neural activation. This method computes an incremental general linear model fit to the fMRI timeseries, which is used to calculate the expected signal intensity at each new acquisition. The difference between the measured intensity and the expected intensity is scaled by the variance of the estimator in order to transform this residual difference into a statistic. Both synthetic and real data were used to validate this method and compare it to the only other published real-time fMRI method. PMID:20682350

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. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-05-01

Blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath-hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task-related BOLD signal changes. Three methods of analyzing the breath-hold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue and the peri-infarct tissue, both sub-acutely (∼2 weeks) and chronically (∼4 months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri-infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared with the controls may be confounded by a reduced CVR, longitudinal group-level BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath-hold-based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

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

PubMed

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, Matthew K; Hagler, Donald J; Dale, Anders M; Halgren, Eric

2010-11-01

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 to 450 ms 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. Copyright 2010 Elsevier Inc. All rights reserved.

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

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

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

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

PubMed

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

2014-03-01

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

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.

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.

Brain-state dependent astrocytic Ca2+ signals are coupled to both positive and negative BOLD-fMRI signals.

PubMed

Wang, Maosen; He, Yi; Sejnowski, Terrence J; Yu, Xin

2018-02-13

Astrocytic Ca 2+ -mediated gliovascular interactions regulate the neurovascular network in situ and in vivo. However, it is difficult to measure directly both the astrocytic activity and fMRI to relate the various forms of blood-oxygen-level-dependent (BOLD) signaling to brain states under normal and pathological conditions. In this study, fMRI and GCaMP-mediated Ca 2+ optical fiber recordings revealed distinct evoked astrocytic Ca 2+ signals that were coupled with positive BOLD signals and intrinsic astrocytic Ca 2+ signals that were coupled with negative BOLD signals. Both evoked and intrinsic astrocytic calcium signal could occur concurrently or respectively during stimulation. The intrinsic astrocytic calcium signal can be detected globally in multiple cortical sites in contrast to the evoked astrocytic calcium signal only detected at the activated cortical region. Unlike propagating Ca 2+ waves in spreading depolarization/depression, the intrinsic Ca 2+ spikes occurred simultaneously in both hemispheres and were initiated upon the activation of the central thalamus and midbrain reticular formation. The occurrence of the intrinsic astrocytic calcium signal is strongly coincident with an increased EEG power level of the brain resting-state fluctuation. These results demonstrate highly correlated astrocytic Ca 2+ spikes with bidirectional fMRI signals based on the thalamic regulation of cortical states, depicting a brain-state dependency of both astrocytic Ca 2+ and BOLD fMRI signals.

The physics of functional magnetic resonance imaging (fMRI)

NASA Astrophysics Data System (ADS)

Buxton, Richard B.

2013-09-01

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

The physics of functional magnetic resonance imaging (fMRI)

PubMed Central

Buxton, Richard B

2015-01-01

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

The physics of functional magnetic resonance imaging (fMRI).

PubMed

Buxton, Richard B

2013-09-01

Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm(3) spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology.

Right anterior cerebellum BOLD responses reflect age related changes in Simon task sequential effects.

PubMed

Aisenberg, D; Sapir, A; Close, A; Henik, A; d'Avossa, G

2018-01-31

Participants are slower to report a feature, such as color, when the target appears on the side opposite the instructed response, than when the target appears on the same side. This finding suggests that target location, even when task-irrelevant, interferes with response selection. This effect is magnified in older adults. Lengthening the inter-trial interval, however, suffices to normalize the congruency effect in older adults, by re-establishing young-like sequential effects (Aisenberg et al., 2014). We examined the neurological correlates of age related changes by comparing BOLD signals in young and old participants performing a visual version of the Simon task. Participants reported the color of a peripheral target, by a left or right-hand keypress. Generally, BOLD responses were greater following incongruent than congruent targets. Also, they were delayed and of smaller amplitude in old than young participants. BOLD responses in visual and motor regions were also affected by the congruency of the previous target, suggesting that sequential effects may reflect remapping of stimulus location onto the hand used to make a response. Crucially, young participants showed larger BOLD responses in right anterior cerebellum to incongruent targets, when the previous target was congruent, but smaller BOLD responses to incongruent targets when the previous target was incongruent. Old participants, however, showed larger BOLD responses to congruent than incongruent targets, irrespective of the previous target congruency. We conclude that aging may interfere with the trial by trial updating of the mapping between the task-irrelevant target location and response, which takes place during the inter-trial interval in the cerebellum and underlays sequential effects in a Simon task. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Predicting the practice effects on the blood oxygenation level-dependent (BOLD) function of fMRI in a symbolic manipulation task

NASA Astrophysics Data System (ADS)

Qin, Yulin; Sohn, Myeong-Ho; Anderson, John R.; Stenger, V. Andrew; Fissell, Kate; Goode, Adam; Carter, Cameron S.

2003-04-01

Based on adaptive control of thought-rational (ACT-R), a cognitive architecture for cognitive modeling, researchers have developed an information-processing model to predict the blood oxygenation level-dependent (BOLD) response of functional MRI in symbol manipulation tasks. As an extension of this research, the current event-related functional MRI study investigates the effect of relatively extensive practice on the activation patterns of related brain regions. The task involved performing transformations on equations in an artificial algebra system. This paper shows that the base-level activation learning in the ACT-R theory can predict the change of the BOLD response in practice in a left prefrontal region reflecting retrieval of information. In contrast, practice has relatively little effect on the form of BOLD response in the parietal region reflecting imagined transformations to the equation or the motor region reflecting manual programming.

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

PubMed

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.

Simultaneous Multi-Slice fMRI using Spiral Trajectories

PubMed Central

Zahneisen, Benjamin; Poser, Benedikt A.; Ernst, Thomas; Stenger, V. Andrew

2014-01-01

Parallel imaging methods using multi-coil receiver arrays have been shown to be effective for increasing MRI acquisition speed. However parallel imaging methods for fMRI with 2D sequences show only limited improvements in temporal resolution because of the long echo times needed for BOLD contrast. Recently, Simultaneous Multi-Slice (SMS) imaging techniques have been shown to increase fMRI temporal resolution by factors of four and higher. In SMS fMRI multiple slices can be acquired simultaneously using Echo Planar Imaging (EPI) and the overlapping slices are un-aliased using a parallel imaging reconstruction with multiple receivers. The slice separation can be further improved using the “blipped-CAIPI” EPI sequence that provides a more efficient sampling of the SMS 3D k-space. In this paper a blipped-spiral SMS sequence for ultra-fast fMRI is presented. The blipped-spiral sequence combines the sampling efficiency of spiral trajectories with the SMS encoding concept used in blipped-CAIPI EPI. We show that blipped spiral acquisition can achieve almost whole brain coverage at 3 mm isotropic resolution in 168 ms. It is also demonstrated that the high temporal resolution allows for dynamic BOLD lag time measurement using visual/motor and retinotopic mapping paradigms. The local BOLD lag time within the visual cortex following the retinotopic mapping stimulation of expanding flickering rings is directly measured and easily translated into an eccentricity map of the cortex. PMID:24518259

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

PubMed

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

2014-09-22

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

Development of the Complex General Linear Model in the Fourier Domain: Application to fMRI Multiple Input-Output Evoked Responses for Single Subjects

PubMed Central

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. PMID:23840281

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.

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

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.

Effects of hypoglycemia on human brain activation measured with fMRI.

PubMed

Anderson, Adam W; Heptulla, Rubina A; Driesen, Naomi; Flanagan, Daniel; Goldberg, Philip A; Jones, Timothy W; Rife, Fran; Sarofin, Hedy; Tamborlane, William; Sherwin, Robert; Gore, John C

2006-07-01

Functional magnetic resonance imaging (fMRI) was used to measure the effects of acute hypoglycemia caused by passive sensory stimulation on brain activation. Visual stimulation was used to generate blood-oxygen-level-dependent (BOLD) contrast, which was monitored during hyperinsulinemic hypoglycemic and euglycemic clamp studies. Hypoglycemia (50 +/- 1 mg glucose/dl) decreased the fMRI signal relative to euglycemia in 10 healthy human subjects: the fractional signal change was reduced by 28 +/- 12% (P < .05). These changes were reversed when euglycemia was restored. These data provide a basis of comparison for studies that quantify hypoglycemia-related changes in fMRI activity during cognitive tasks based on visual stimuli and demonstrate that variations in blood glucose levels may modulate BOLD signals in the healthy brain.

Noncanonical spike-related BOLD responses in focal epilepsy

PubMed Central

Lemieux, Louis; Laufs, Helmut; Carmichael, David; Paul, Joseph Suresh; Walker, Matthew C; Duncan, John S

2008-01-01

Till now, most studies of the Blood Oxygen Level-Dependent (BOLD) response to interictal epileptic discharges (IED) have assumed that its time course matches closely to that of brief physiological stimuli, commonly called the canonical event-related haemodynamic response function (canonical HRF). Analyses based on that assumption have produced significant response patterns that are generally concordant with prior electroclinical data. In this work, we used a more flexible model of the event-related response, a Fourier basis set, to investigate the presence of other responses in relation to individual IED in 30 experiments in patients with focal epilepsy. We found significant responses that had a noncanonical time course in 37% of cases, compared with 40% for the conventional, canonical HRF-based approach. In two cases, the Fourier analysis suggested activations where the conventional model did not. The noncanonical activations were almost always remote from the presumed generator of epileptiform activity. In the majority of cases with noncanonical responses, the noncanonical responses in single-voxel clusters were suggestive of artifacts. We did not find evidence for IED-related noncanonical HRFs arising from areas of pathology, suggesting that the BOLD response to IED is primarily canonical. Noncanonical responses may represent a number of phenomena, including artefacts and propagated epileptiform activity. Hum Brain Mapp 2008. © 2007 Wiley-Liss, Inc. PMID:17510926

Longitudinal decrease in blood oxygenation level dependent response in cerebral amyloid angiopathy.

PubMed

Switzer, Aaron R; McCreary, Cheryl; Batool, Saima; Stafford, Randall B; Frayne, Richard; Goodyear, Bradley G; Smith, Eric E

2016-01-01

Lower blood oxygenation level dependent (BOLD) signal changes in response to a visual stimulus in functional magnetic resonance imaging (fMRI) have been observed in cross-sectional studies of cerebral amyloid angiopathy (CAA), and are presumed to reflect impaired vascular reactivity. We used fMRI to detect a longitudinal change in BOLD responses to a visual stimulus in CAA, and to determine any correlations between these changes and other established biomarkers of CAA progression. Data were acquired from 22 patients diagnosed with probable CAA (using the Boston Criteria) and 16 healthy controls at baseline and one year. BOLD data were generated from the 200 most active voxels of the primary visual cortex during the fMRI visual stimulus (passively viewing an alternating checkerboard pattern). In general, BOLD amplitudes were lower at one year compared to baseline in patients with CAA (p = 0.01) but were unchanged in controls (p = 0.18). The longitudinal difference in BOLD amplitudes was significantly lower in CAA compared to controls (p < 0.001). White matter hyperintensity (WMH) volumes and number of cerebral microbleeds, both presumed to reflect CAA-mediated vascular injury, increased over time in CAA (p = 0.007 and p = 0.001, respectively). Longitudinal increases in WMH (rs = 0.04, p = 0.86) or cerebral microbleeds (rs = -0.18, p = 0.45) were not associated with the longitudinal decrease in BOLD amplitudes.

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

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

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.

Haptic fMRI: Reliability and performance of electromagnetic haptic interfaces for motion and force neuroimaging experiments.

PubMed

Menon, Samir; Zhu, Jack; Goyal, Deeksha; Khatib, Oussama

2017-07-01

Haptic interfaces compatible with functional magnetic resonance imaging (Haptic fMRI) promise to enable rich motor neuroscience experiments that study how humans perform complex manipulation tasks. Here, we present a large-scale study (176 scans runs, 33 scan sessions) that characterizes the reliability and performance of one such electromagnetically actuated device, Haptic fMRI Interface 3 (HFI-3). We outline engineering advances that ensured HFI-3 did not interfere with fMRI measurements. Observed fMRI temporal noise levels with HFI-3 operating were at the fMRI baseline (0.8% noise to signal). We also present results from HFI-3 experiments demonstrating that high resolution fMRI can be used to study spatio-temporal patterns of fMRI blood oxygenation dependent (BOLD) activation. These experiments include motor planning, goal-directed reaching, and visually-guided force control. Observed fMRI responses are consistent with existing literature, which supports Haptic fMRI's effectiveness at studying the brain's motor regions.

Effects of nonspatial selective and divided visual attention on fMRI BOLD responses.

PubMed

Weerda, Riklef; Vallines, Ignacio; Thomas, James P; Rutschmann, Roland M; Greenlee, Mark W

2006-09-01

Using an uncertainty paradigm and functional magnetic resonance imaging (fMRI) we studied the effect of nonspatial selective and divided visual attention on the activity of specific areas of human extrastriate visual cortex. The stimuli were single ovals that differed from an implicit standard oval in either colour or width. The subjects' task was to classify the current stimulus as one of two possible alternatives per stimulus dimension. Three different experimental conditions were conducted: "colour-certainty", "shape-certainty" and "uncertainty". In all experimental conditions, the stimulus differed in only one stimulus dimension per trial. In the two certainty conditions, the subjects knew in advance which dimension this would be. During the uncertainty condition they had no such previous knowledge and had to monitor both dimensions simultaneously. Statistical analysis of the fMRI data (with SPM2) revealed a modest effect of the attended stimulus dimension on the neural activity in colour sensitive area V4 (more activity during attention to colour) and in shape sensitive area LOC (more activity during attention to shape). Furthermore, cortical areas known to be related to attention and working memory processes (e.g., lateral prefrontal and posterior parietal cortex) exhibit higher activity during the condition of divided attention ("uncertainty") than during that of selective attention ("certainty").

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. 2010 Elsevier Inc. All

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

Retinotopic mapping with Spin Echo BOLD at 7 Tesla

PubMed Central

Olman, Cheryl A.; Van de Moortele, Pierre-Francois; Schumacher, Jennifer F.; Guy, Joe; Uğurbil, Kâmil; Yacoub, Essa

2010-01-01

For blood oxygenation level-dependent (BOLD) functional MRI experiments, contrast-to-noise ratio (CNR) increases with increasing field strength for both gradient echo (GE) and spin echo (SE) BOLD techniques. However, susceptibility artifacts and non-uniform coil sensitivity profiles complicate large field-of-view fMRI experiments (e.g., experiments covering multiple visual areas instead of focusing on a single cortical region). Here, we use SE BOLD to acquire retinotopic mapping data in early visual areas, testing the feasibility of SE BOLD experiments spanning multiple cortical areas at 7 Tesla. We also use a recently developed method for normalizing signal intensity in T1-weighted anatomical images to enable automated segmentation of the cortical gray matter for scans acquired at 7T with either surface or volume coils. We find that the CNR of the 7T GE data (average single-voxel, single-scan stimulus coherence: 0.41) is almost twice that of the 3T GE BOLD data (average coherence: 0.25), with the CNR of the SE BOLD data (average coherence: 0.23) comparable to that of the 3T GE data. Repeated measurements in individual subjects find that maps acquired with 1.8 mm resolution at 3T and 7T with GE BOLD and at 7T with SE BOLD show no systematic differences in either the area or the boundary locations for V1, V2 and V3, demonstrating the feasibility of high-resolution SE BOLD experiments with good sensitivity throughout multiple visual areas. PMID:20656431

Working memory component processes: isolating BOLD signal changes.

PubMed

Motes, Michael A; Rypma, Bart

2010-01-15

The chronology of the component processes subserving working memory (WM) and hemodynamic response lags has hindered the use of fMRI for exploring neural substrates of WM. In the present study, however, participants completed full trials that involved encoding two or six letters, maintaining the memory set over a delay, and then deciding whether a probe was in the memory set or not. Additionally, they completed encode-only, encode-and-maintain, and encode-and-decide partial trials intermixed with the full trials. The inclusion of partial trials allowed for the isolation of BOLD signal changes to the different trial periods. The results showed that only lateral and medial prefrontal cortex regions differentially responded to the 2- and 6-letter memory sets over the trial periods, showing greater activation to 6-letter sets during the encode and maintain trial periods. Thus, the data showed the differential involvement of PFC in the encoding and maintenance of supra- and sub-capacity memory sets and show the efficacy of using fMRI partial trial methods to study WM component processes.

Working Memory Component Processes: Isolating BOLD Signal-Changes

PubMed Central

Motes, Michael A.; Rypma, Bart

2009-01-01

The chronology of the component processes subserving working memory (WM) and hemodynamic response lags have hindered the use of fMRI for exploring neural substrates of WM. In the present study, however, participants completed full trials that involved encoding two or six letters, maintaining the memory-set over a delay, and then deciding whether a probe was in the memory-set or not. Additionally, they completed encode only, encode and maintain, and encode and decide partial-trials intermixed with the full-trials. The inclusion of partial-trials allowed for the isolation of BOLD signal-changes to the different trial-periods. The results showed that only lateral and medial prefrontal cortex regions differentially responded to the 2- and 6-letter memory-sets over the trial-periods, showing greater activation to 6-letter sets during the encode and maintain trial-periods. Thus, the data showed the differential involvement of PFC in the encoding and maintenance of supra- and sub-capacity memory-sets and show the efficacy of using fMRI partial-trial methods to study WM component processes. PMID:19732840

Computational advances towards linking BOLD and behavior.

PubMed

Serences, John T; Saproo, Sameer

2012-03-01

Traditionally, fMRI studies have focused on analyzing the mean response amplitude within a cortical area. However, the mean response is blind to many important patterns of cortical modulation, which severely limits the formulation and evaluation of linking hypotheses between neural activity, BOLD responses, and behavior. More recently, multivariate pattern classification analysis (MVPA) has been applied to fMRI data to evaluate the information content of spatially distributed activation patterns. This approach has been remarkably successful at detecting the presence of specific information in targeted brain regions, and provides an extremely flexible means of extracting that information without a precise generative model for the underlying neural activity. However, this flexibility comes at a cost: since MVPA relies on pooling information across voxels that are selective for many different stimulus attributes, it is difficult to infer how specific sub-sets of tuned neurons are modulated by an experimental manipulation. In contrast, recently developed encoding models can produce more precise estimates of feature-selective tuning functions, and can support the creation of explicit linking hypotheses between neural activity and behavior. Although these encoding models depend on strong - and often untested - assumptions about the response properties of underlying neural generators, they also provide a unique opportunity to evaluate population-level computational theories of perception and cognition that have previously been difficult to assess using either single-unit recording or conventional neuroimaging techniques. Copyright © 2011. Published by Elsevier Ltd.

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

Spatial nonuniformity of the resting CBF and BOLD responses to sevoflurane: in vivo study of normal human subjects with magnetic resonance imaging.

PubMed

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

2008-12-01

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. Copyright 2007 Wiley-Liss, Inc.

Automated Real-Time Behavioral and Physiological Data Acquisition and Display Integrated with Stimulus Presentation for fMRI

PubMed Central

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

2011-01-01

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

The effect of sleep deprivation on BOLD activity elicited by a divided attention task.

PubMed

Jackson, Melinda L; Hughes, Matthew E; Croft, Rodney J; Howard, Mark E; Crewther, David; Kennedy, Gerard A; Owens, Katherine; Pierce, Rob J; O'Donoghue, Fergal J; Johnston, Patrick

2011-06-01

Sleep loss, widespread in today's society and associated with a number of clinical conditions, has a detrimental effect on a variety of cognitive domains including attention. This study examined the sequelae of sleep deprivation upon BOLD fMRI activation during divided attention. Twelve healthy males completed two randomized sessions; one after 27 h of sleep deprivation and one after a normal night of sleep. During each session, BOLD fMRI was measured while subjects completed a cross-modal divided attention task (visual and auditory). After normal sleep, increased BOLD activation was observed bilaterally in the superior frontal gyrus and the inferior parietal lobe during divided attention performance. Subjects reported feeling significantly more sleepy in the sleep deprivation session, and there was a trend towards poorer divided attention task performance. Sleep deprivation led to a down regulation of activation in the left superior frontal gyrus, possibly reflecting an attenuation of top-down control mechanisms on the attentional system. These findings have implications for understanding the neural correlates of divided attention and the neurofunctional changes that occur in individuals who are sleep deprived.

Ridding fMRI data of motion-related influences: Removal of signals with distinct spatial and physical bases in multiecho data.

PubMed

Power, Jonathan D; Plitt, Mark; Gotts, Stephen J; Kundu, Prantik; Voon, Valerie; Bandettini, Peter A; Martin, Alex

2018-02-27

"Functional connectivity" techniques are commonplace tools for studying brain organization. A critical element of these analyses is to distinguish variance due to neurobiological signals from variance due to nonneurobiological signals. Multiecho fMRI techniques are a promising means for making such distinctions based on signal decay properties. Here, we report that multiecho fMRI techniques enable excellent removal of certain kinds of artifactual variance, namely, spatially focal artifacts due to motion. By removing these artifacts, multiecho techniques reveal frequent, large-amplitude blood oxygen level-dependent (BOLD) signal changes present across all gray matter that are also linked to motion. These whole-brain BOLD signals could reflect widespread neural processes or other processes, such as alterations in blood partial pressure of carbon dioxide (pCO 2 ) due to ventilation changes. By acquiring multiecho data while monitoring breathing, we demonstrate that whole-brain BOLD signals in the resting state are often caused by changes in breathing that co-occur with head motion. These widespread respiratory fMRI signals cannot be isolated from neurobiological signals by multiecho techniques because they occur via the same BOLD mechanism. Respiratory signals must therefore be removed by some other technique to isolate neurobiological covariance in fMRI time series. Several methods for removing global artifacts are demonstrated and compared, and were found to yield fMRI time series essentially free of motion-related influences. These results identify two kinds of motion-associated fMRI variance, with different physical mechanisms and spatial profiles, each of which strongly and differentially influences functional connectivity patterns. Distance-dependent patterns in covariance are nearly entirely attributable to non-BOLD artifacts.

Application of calibrated fMRI in Alzheimer's disease.

PubMed

Lajoie, Isabelle; Nugent, Scott; Debacker, Clément; Dyson, Kenneth; Tancredi, Felipe B; Badhwar, AmanPreet; Belleville, Sylvie; Deschaintre, Yan; Bellec, Pierre; Doyon, Julien; Bocti, Christian; Gauthier, Serge; Arnold, Douglas; Kergoat, Marie-Jeanne; Chertkow, Howard; Monchi, Oury; Hoge, Richard D

2017-01-01

Calibrated fMRI based on arterial spin-labeling (ASL) and blood oxygen-dependent contrast (BOLD), combined with periods of hypercapnia and hyperoxia, can provide information on cerebrovascular reactivity (CVR), resting blood flow (CBF), oxygen extraction fraction (OEF), and resting oxidative metabolism (CMRO 2 ). Vascular and metabolic integrity are believed to be affected in Alzheimer's disease (AD), thus, the use of calibrated fMRI in AD may help understand the disease and monitor therapeutic responses in future clinical trials. In the present work, we applied a calibrated fMRI approach referred to as Quantitative O2 (QUO2) in a cohort of probable AD dementia and age-matched control participants. The resulting CBF, OEF and CMRO 2 values fell within the range from previous studies using positron emission tomography (PET) with 15 O labeling. Moreover, the typical parietotemporal pattern of hypoperfusion and hypometabolism in AD was observed, especially in the precuneus, a particularly vulnerable region. We detected no deficit in frontal CBF, nor in whole grey matter CVR, which supports the hypothesis that the effects observed were associated specifically with AD rather than generalized vascular disease. Some key pitfalls affecting both ASL and BOLD methods were encountered, such as prolonged arterial transit times (particularly in the occipital lobe), the presence of susceptibility artifacts obscuring medial temporal regions, and the challenges associated with the hypercapnic manipulation in AD patients and elderly participants. The present results are encouraging and demonstrate the promise of calibrated fMRI measurements as potential biomarkers in AD. Although CMRO 2 can be imaged with 15 O PET, the QUO2 method uses more widely available imaging infrastructure, avoids exposure to ionizing radiation, and integrates with other MRI-based measures of brain structure and function.

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

PubMed

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

2013-11-01

What basic visual structures underlie human face detection and how can we extract such structures directly from the amplitude of neural responses elicited by face processing? Here, we address these issues by investigating an extension of noise-based image classification to BOLD responses recorded in high-level visual areas. First, we assess the applicability of this classification method to such data and, second, we explore its results in connection with the neural processing of faces. To this end, we construct luminance templates from white noise fields based on the response of face-selective areas in the human ventral cortex. Using behaviorally and neurally-derived classification images, our results reveal a family of simple but robust image structures subserving face representation and detection. Thus, we confirm the role played by classical face selective regions in face detection and we help clarify the representational basis of this perceptual function. From a theory standpoint, our findings support the idea of simple but highly diagnostic neurally-coded features for face detection. At the same time, from a methodological perspective, our work demonstrates the ability of noise-based image classification in conjunction with fMRI to help uncover the structure of high-level perceptual representations. Copyright © 2012 Wiley Periodicals, Inc.

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

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.

Investigating the dependence of BOLD contrast on oxidative metabolism.

PubMed

Schwarzbauer, C; Heinke, W

1999-03-01

Most functional magnetic resonance imaging (fMRI) studies are based on measuring the changes in the blood oxygenation level-dependent (BOLD) contrast that arise from a complex interplay between cerebral hemodynamics and oxidative metabolism. To separate these effects, we consecutively applied two different stimuli: visual stimulation (black/white checkerboard alternating with a frequency of 8 Hz) and hypercapnia (inspiration of 5% CO2). Changes in cerebral blood flow (deltaCBF) and the effective transverse relaxation time (T2*) were measured in an interleaved manner by combining a previously described spin-labeling technique with BOLD-based fMRI. In six healthy volunteers, T2* was significantly longer during hypercapnia than during visual stimulation, whereas the corresponding deltaCBF values were the same at the given level of significance (P<0.01). This finding is explained by a significant increase in oxygen consumption under visual stimulation. The average T2* changes in the visual cortex related to cerebral hemodynamics and oxidative metabolism were 10.6+/-3.0% and -4.7+/-1.2%, respectively, resulting in a net increase of 5.9+/-2.3%. Although the hemodynamic effect is dominant, the increase in oxidative metabolism gives rise to a significant decrease in BOLD contrast. The calculated average change in the cerebral metabolic rate of oxygen (CMRO2), 4.4+/-1.1% (N = 6), is in excellent agreement with previous results obtained by positron emission tomography.

Bayesian spatiotemporal model of fMRI data using transfer functions.

PubMed

Quirós, Alicia; Diez, Raquel Montes; Wilson, Simon P

2010-09-01

This research describes a new Bayesian spatiotemporal model to analyse BOLD fMRI studies. In the temporal dimension, we describe the shape of the hemodynamic response function (HRF) with a transfer function model. The spatial continuity and local homogeneity of the evoked responses are modelled by a Gaussian Markov random field prior on the parameter indicating activations. The proposal constitutes an extension of the spatiotemporal model presented in a previous approach [Quirós, A., Montes Diez, R. and Gamerman, D., 2010. Bayesian spatiotemporal model of fMRI data, Neuroimage, 49: 442-456], offering more flexibility in the estimation of the HRF and computational advantages in the resulting MCMC algorithm. 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 a real data set from a block-design fMRI experiment. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Spatiotemporal dynamics of the brain at rest--exploring EEG microstates as electrophysiological signatures of BOLD resting state networks.

PubMed

Yuan, Han; Zotev, Vadim; Phillips, Raquel; Drevets, Wayne C; Bodurka, Jerzy

2012-05-01

Neuroimaging research suggests that the resting cerebral physiology is characterized by complex patterns of neuronal activity in widely distributed functional networks. As studied using functional magnetic resonance imaging (fMRI) of the blood-oxygenation-level dependent (BOLD) signal, the resting brain activity is associated with slowly fluctuating hemodynamic signals (~10s). More recently, multimodal functional imaging studies involving simultaneous acquisition of BOLD-fMRI and electroencephalography (EEG) data have suggested that the relatively slow hemodynamic fluctuations of some resting state networks (RSNs) evinced in the BOLD data are related to much faster (~100 ms) transient brain states reflected in EEG signals, that are referred to as "microstates". To further elucidate the relationship between microstates and RSNs, we developed a fully data-driven approach that combines information from simultaneously recorded, high-density EEG and BOLD-fMRI data. Using independent component analysis (ICA) of the combined EEG and fMRI data, we identified thirteen microstates and ten RSNs that are organized independently in their temporal and spatial characteristics, respectively. We hypothesized that the intrinsic brain networks that are active at rest would be reflected in both the EEG data and the fMRI data. To test this hypothesis, the rapid fluctuations associated with each microstate were correlated with the BOLD-fMRI signal associated with each RSN. We found that each RSN was characterized further by a specific electrophysiological signature involving from one to a combination of several microstates. Moreover, by comparing the time course of EEG microstates to that of the whole-brain BOLD signal, on a multi-subject group level, we unraveled for the first time a set of microstate-associated networks that correspond to a range of previously described RSNs, including visual, sensorimotor, auditory, attention, frontal, visceromotor and default mode networks. These

The neuroscience of investing: fMRI of the reward system.

PubMed

Peterson, Richard L

2005-11-15

Functional magnetic resonance imaging (fMRI) has proven a useful tool for observing neural BOLD signal changes during complex cognitive and emotional tasks. Yet the meaning and applicability of the fMRI data being gathered is still largely unknown. The brain's reward system underlies the fundamental neural processes of goal evaluation, preference formation, positive motivation, and choice behavior. fMRI technology allows researchers to dynamically visualize reward system processes. Experimenters can then correlate reward system BOLD activations with experimental behavior from carefully controlled experiments. In the SPAN lab at Stanford University, directed by Brian Knutson Ph.D., researchers have been using financial tasks during fMRI scanning to correlate emotion, behavior, and cognition with the reward system's fundamental neural activations. One goal of the SPAN lab is the development of predictive models of behavior. In this paper we extrapolate our fMRI results toward understanding and predicting individual behavior in the uncertain and high-risk environment of the financial markets. The financial market price anomalies of "value versus glamour" and "momentum" may be real-world examples of reward system activation biasing collective behavior. On the individual level, the investor's bias of overconfidence may similarly be related to reward system activation. We attempt to understand selected "irrational" investor behaviors and anomalous financial market price patterns through correlations with findings from fMRI research of the reward system.

Blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for prediction of breast cancer chemotherapy response: a pilot study.

PubMed

Jiang, Lan; Weatherall, Paul T; McColl, Roderick W; Tripathy, Debu; Mason, Ralph P

2013-05-01

To determine whether a simple noninvasive method of assessing tumor oxygenation is feasible in the clinical setting and can provide useful, potentially predictive information. Tumor microcirculation and oxygenation play critical roles in tumor growth and responsiveness to cytotoxic treatment and may provide prognostic indicators for cancer therapy. Deoxyhemoglobin is paramagnetic and can serve as an endogenous contrast agent causing signal loss in echo planar magnetic resonance imaging (MRI) (blood oxygenation level-dependent [BOLD]-MRI). We used BOLD-MRI to provide early evaluation of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MRI was performed on 11 patients with biopsy-proven malignancy. MRI exams were scheduled before, during, and after chemotherapy. The BOLD study applied a 6-minute oxygen breathing challenge. Seven patients successfully completed the exams. Before chemotherapy, BOLD contrast enhancement was observed in all tumors, but the patients, who ultimately had complete pathological response, exhibited a significantly higher BOLD response to oxygen breathing. We have successfully implemented an oxygen-breathing challenge BOLD contrast technique as part of the standard breast MRI exam in patients with locally advanced breast cancer. The preliminary observation that a large BOLD response correlated with better treatment response suggests a predictive capability for BOLD MRI. Copyright © 2012 Wiley Periodicals, Inc.

Spatial band-pass filtering aids decoding musical genres from auditory cortex 7T fMRI.

PubMed

Sengupta, Ayan; Pollmann, Stefan; Hanke, Michael

2018-01-01

Spatial filtering strategies, combined with multivariate decoding analysis of BOLD images, have been used to investigate the nature of the neural signal underlying the discriminability of brain activity patterns evoked by sensory stimulation -- primarily in the visual cortex. Reported evidence indicates that such signals are spatially broadband in nature, and are not primarily comprised of fine-grained activation patterns. However, it is unclear whether this is a general property of the BOLD signal, or whether it is specific to the details of employed analyses and stimuli. Here we performed an analysis of publicly available, high-resolution 7T fMRI on the response BOLD response to musical genres in primary auditory cortex that matches a previously conducted study on decoding visual orientation from V1.  The results show that the pattern of decoding accuracies with respect to different types and levels of spatial filtering is comparable to that obtained from V1, despite considerable differences in the respective cortical circuitry.

High spatial correspondence at a columnar level between activation and resting state fMRI signals and local field potentials.

PubMed

Shi, Zhaoyue; Wu, Ruiqi; Yang, Pai-Feng; Wang, Feng; Wu, Tung-Lin; Mishra, Arabinda; Chen, Li Min; Gore, John C

2017-05-16

Although blood oxygenation level-dependent (BOLD) fMRI has been widely used to map brain responses to external stimuli and to delineate functional circuits at rest, the extent to which BOLD signals correlate spatially with underlying neuronal activity, the spatial relationships between stimulus-evoked BOLD activations and local correlations of BOLD signals in a resting state, and whether these spatial relationships vary across functionally distinct cortical areas are not known. To address these critical questions, we directly compared the spatial extents of stimulated activations and the local profiles of intervoxel resting state correlations for both high-resolution BOLD at 9.4 T and local field potentials (LFPs), using 98-channel microelectrode arrays, in functionally distinct primary somatosensory areas 3b and 1 in nonhuman primates. Anatomic images of LFP and BOLD were coregistered within 0.10 mm accuracy. We found that the point spread functions (PSFs) of BOLD and LFP responses were comparable in the stimulus condition, and both estimates of activations were slightly more spatially constrained than local correlations at rest. The magnitudes of stimulus responses in area 3b were stronger than those in area 1 and extended in a medial to lateral direction. In addition, the reproducibility and stability of stimulus-evoked activation locations within and across both modalities were robust. Our work suggests that the intrinsic resolution of BOLD is not a limiting feature in practice and approaches the intrinsic precision achievable by multielectrode electrophysiology.

High spatial correspondence at a columnar level between activation and resting state fMRI signals and local field potentials

PubMed Central

Shi, Zhaoyue; Wu, Ruiqi; Yang, Pai-Feng; Wang, Feng; Wu, Tung-Lin; Mishra, Arabinda; Chen, Li Min; Gore, John C.

2017-01-01

Although blood oxygenation level-dependent (BOLD) fMRI has been widely used to map brain responses to external stimuli and to delineate functional circuits at rest, the extent to which BOLD signals correlate spatially with underlying neuronal activity, the spatial relationships between stimulus-evoked BOLD activations and local correlations of BOLD signals in a resting state, and whether these spatial relationships vary across functionally distinct cortical areas are not known. To address these critical questions, we directly compared the spatial extents of stimulated activations and the local profiles of intervoxel resting state correlations for both high-resolution BOLD at 9.4 T and local field potentials (LFPs), using 98-channel microelectrode arrays, in functionally distinct primary somatosensory areas 3b and 1 in nonhuman primates. Anatomic images of LFP and BOLD were coregistered within 0.10 mm accuracy. We found that the point spread functions (PSFs) of BOLD and LFP responses were comparable in the stimulus condition, and both estimates of activations were slightly more spatially constrained than local correlations at rest. The magnitudes of stimulus responses in area 3b were stronger than those in area 1 and extended in a medial to lateral direction. In addition, the reproducibility and stability of stimulus-evoked activation locations within and across both modalities were robust. Our work suggests that the intrinsic resolution of BOLD is not a limiting feature in practice and approaches the intrinsic precision achievable by multielectrode electrophysiology. PMID:28461461

Test-retest reliability of an fMRI paradigm for studies of cardiovascular reactivity.

PubMed

Sheu, Lei K; Jennings, J Richard; Gianaros, Peter J

2012-07-01

We examined the reliability of measures of fMRI, subjective, and cardiovascular reactions to standardized versions of a Stroop color-word task and a multisource interference task. A sample of 14 men and 12 women (30-49 years old) completed the tasks on two occasions, separated by a median of 88 days. The reliability of fMRI BOLD signal changes in brain areas engaged by the tasks was moderate, and aggregating fMRI BOLD signal changes across the tasks improved test-retest reliability metrics. These metrics included voxel-wise intraclass correlation coefficients (ICCs) and overlap ratio statistics. Task-aggregated ratings of subjective arousal, valence, and control, as well as cardiovascular reactions evoked by the tasks showed ICCs of 0.57 to 0.87 (ps < .001), indicating moderate-to-strong reliability. These findings support using these tasks as a battery for fMRI studies of cardiovascular reactivity. Copyright © 2012 Society for Psychophysiological Research.

Electrodermal Recording and fMRI to Inform Sensorimotor Recovery in Stroke Patients

PubMed Central

MacIntosh, Bradley J.; McIlroy, William E.; Mraz, Richard; Staines, W. Richard; Black, Sandra E.; Graham, Simon J.

2016-01-01

Background Functional magnetic resonance imaging (fMRI) appears to be useful for investigating motor recovery after stroke. Some of the potential confounders of brain activation studies, however, could be mitigated through complementary physiological monitoring. Objective To investigate a sensorimotor fMRI battery that included simultaneous measurement of electrodermal activity in subjects with hemiparetic stroke to provide a measure related to the sense of effort during motor performance. Methods Bilateral hand and ankle tasks were performed by 6 patients with stroke (2 subacute, 4 chronic) during imaging with blood oxygen level-dependent (BOLD) fMRI using an event-related design. BOLD percent changes, peak activation, and laterality index values were calculated in the sensorimotor cortex. Electrodermal recordings were made concurrently and used as a regressor. Results Sensorimotor BOLD time series and percent change values provided evidence of an intact motor network in each of these well-recovered patients. During tasks involving the hemiparetic limb, electrodermal activity changes were variable in amplitude, and electrodermal activity time-series data showed significant correlations with fMRI in 3 of 6 patients. No such correlations were observed for control tasks involving the unaffected lower limb. Conclusions Electrodermal activity activation maps implicated the contralesional over the ipsilesional hemisphere, supporting the notion that stroke patients may require higher order motor processing to perform simple tasks. Electrodermal activity recordings may be useful as a physiological marker of differences in effort required during movements of a subject’s hemiparetic compared with the unaffected limb during fMRI studies. PMID:18784267

High efficiency multishot interleaved spiral-in/out: acquisition for high-resolution BOLD fMRI.

PubMed

Jung, Youngkyoo; Samsonov, Alexey A; Liu, Thomas T; Buracas, Giedrius T

2013-08-01

Growing demand for high spatial resolution blood oxygenation level dependent (BOLD) functional magnetic resonance imaging faces a challenge of the spatial resolution versus coverage or temporal resolution tradeoff, which can be addressed by methods that afford increased acquisition efficiency. Spiral acquisition trajectories have been shown to be superior to currently prevalent echo-planar imaging in terms of acquisition efficiency, and high spatial resolution can be achieved by employing multiple-shot spiral acquisition. The interleaved spiral in/out trajectory is preferred over spiral-in due to increased BOLD signal contrast-to-noise ratio (CNR) and higher acquisition efficiency than that of spiral-out or noninterleaved spiral in/out trajectories (Law & Glover. Magn Reson Med 2009; 62:829-834.), but to date applicability of the multishot interleaved spiral in/out for high spatial resolution imaging has not been studied. Herein we propose multishot interleaved spiral in/out acquisition and investigate its applicability for high spatial resolution BOLD functional magnetic resonance imaging. Images reconstructed from interleaved spiral-in and -out trajectories possess artifacts caused by differences in T2 decay, off-resonance, and k-space errors associated with the two trajectories. We analyze the associated errors and demonstrate that application of conjugate phase reconstruction and spectral filtering can substantially mitigate these image artifacts. After applying these processing steps, the multishot interleaved spiral in/out pulse sequence yields high BOLD CNR images at in-plane resolution below 1 × 1 mm while preserving acceptable temporal resolution (4 s) and brain coverage (15 slices of 2 mm thickness). Moreover, this method yields sufficient BOLD CNR at 1.5 mm isotropic resolution for detection of activation in hippocampus associated with cognitive tasks (Stern memory task). The multishot interleaved spiral in/out acquisition is a promising technique for

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

Functional brain activation differences in stuttering identified with a rapid fMRI sequence

PubMed Central

Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

2011-01-01

The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech motor and auditory brain activity in children who stutter closer to the age at which recovery from stuttering is documented. Rapid sequences may be preferred for individuals or populations who do not tolerate long scanning sessions. In this report, we document the application of a picture naming and phoneme monitoring task in three minute fMRI sequences with adults who stutter (AWS). If relevant brain differences are found in AWS with these approaches that conform to previous reports, then these approaches can be extended to younger populations. Pairwise contrasts of brain BOLD activity between AWS and normally fluent adults indicated the AWS showed higher BOLD activity in the right inferior frontal gyrus (IFG), right temporal lobe and sensorimotor cortices during picture naming and and higher activity in the right IFG during phoneme monitoring. The right lateralized pattern of BOLD activity together with higher activity in sensorimotor cortices is consistent with previous reports, which indicates rapid fMRI sequences can be considered for investigating stuttering in younger participants. PMID:22133409

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

PubMed Central

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

2010-01-01

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

Differential Hemodynamic Response in Affective Circuitry with Aging: An fMRI Study of Novelty, Valence, and Arousal

PubMed Central

Moriguchi, Yoshiya; Negreira, Alyson; Weierich, Mariann; Dautoff, Rebecca; Dickerson, Bradford C.; Wright, Christopher I.; Barrett, Lisa Feldman

2011-01-01

Emerging evidence indicates that stimulus novelty is affectively potent and reliably engages the amygdala and other portions of the affective workspace in the brain. Using fMRI, we examined whether novel stimuli remain affectively salient across the lifespan, and therefore, whether novelty processing—a potentially survival-relevant function—is preserved with aging. Nineteen young and 22 older healthy adults were scanned during observing novel and familiar affective pictures while estimating their own subjectively experienced aroused levels. We investigated age-related difference of magnitude of activation, hemodynamic time course, and functional connectivity of BOLD responses in the amygdala. Although there were no age-related differences in the peak response of the amygdala to novelty, older individuals showed a narrower, sharper (i.e., “peakier”) hemodynamic time course in response to novel stimuli, as well as decreased connectivity between the left amygdala and the affective areas including orbito-frontal regions. These findings have relevance for understanding age-related differences in memory and affect regulation. PMID:20521849

Nonlinear correlations impair quantification of episodic memory by mesial temporal BOLD activity.

PubMed

Klamer, Silke; Zeltner, Lena; Erb, Michael; Klose, Uwe; Wagner, Kathrin; Frings, Lars; Groen, Georg; Veil, Cornelia; Rona, Sabine; Lerche, Holger; Milian, Monika

2013-07-01

Episodic memory processes can be investigated using different functional MRI (fMRI) paradigms. The purpose of the present study was to examine correlations between neuropsychological memory test scores and BOLD signal changes during fMRI scanning using three different memory tasks. Twenty-eight right-handed healthy subjects underwent three paradigms, (a) a word pair, (b) a space-labyrinth, and (c) a face-name association paradigm. These paradigms were compared for their value in memory quantification and lateralization by calculating correlations between the BOLD signals in the mesial temporal lobe and behavioral data derived from a neuropsychological test battery. As expected, group analysis showed left-sided activation for the verbal, a tendency to right-sided activation for the spatial, and bilateral activation for the face-name paradigm. No linear correlations were observed between neuropsychological data and activation in the temporo-mesial region. However, we found significant u-shaped correlations between behavioral memory performance and activation in both the verbal and the face-name paradigms, that is, BOLD signal changes were greater not only among participants who performed best on the neuropsychological tests, but also among the poorest performers. The figural learning task did not correlate with the activations in the space-labyrinth paradigm at all. We interpreted the u-shaped correlations to be due to compensatory hippocampal activations associated with low performance when people try unsuccessfully to remember presented items. Because activation levels did not linearly increase with memory performance, the latter cannot be quantified by fMRI alone, but only be used in conjunction with neuropsychological testing. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Magnetic susceptibility induced echo time shifts: Is there a bias in age-related fMRI studies?

PubMed Central

Ngo, Giang-Chau; Wong, Chelsea N.; Guo, Steve; Paine, Thomas; Kramer, Arthur F.; Sutton, Bradley P.

2016-01-01

Purpose To evaluate the potential for bias in functional MRI (fMRI) aging studies resulting from age-related differences in magnetic field distributions which can impact echo time and functional contrast. Materials and Methods Magnetic field maps were taken on 31 younger adults (age: 22 ± 2.9 years) and 46 older adults (age: 66 ± 4.5 years) on a 3 T scanner. Using the spatial gradients of the magnetic field map for each participant, an echo planar imaging (EPI) trajectory was simulated. The effective echo time, time at which the k-space trajectory is the closest to the center of k-space, was calculated. This was used to examine both within-subject and across-age-group differences in the effective echo time maps. The Blood Oxygenation Level Dependent (BOLD) percent signal change resulting from those echo time shifts was also calculated to determine their impact on fMRI aging studies. Result For a single subject, the effective echo time varied as much as ± 5 ms across the brain. An unpaired t-test between the effective echo time across age group resulted in significant differences in several regions of the brain (p<0.01). The difference in echo time was only approximately 1 ms, however which is not expected to have an important impact on BOLD fMRI percent signal change (< 4%). Conclusion Susceptibility-induced magnetic field gradients induce local echo time shifts in gradient echo fMRI images, which can cause variable BOLD sensitivity across the brain. However, the age-related differences in BOLD signal are expected to be small for an fMRI study at 3 T. PMID:27299727

Question/statement judgments: an fMRI study of intonation processing.

PubMed

Doherty, Colin P; West, W Caroline; Dilley, Laura C; Shattuck-Hufnagel, Stefanie; Caplan, David

2004-10-01

We examined changes in fMRI BOLD signal associated with question/statement judgments in an event-related paradigm to investigate the neural basis of processing one aspect of intonation. Subjects made judgments about digitized recordings of three types of utterances: questions with rising intonation (RQ; e.g., "She was talking to her father?"), statements with a falling intonation (FS; e.g., "She was talking to her father."), and questions with a falling intonation and a word order change (FQ; e.g., "Was she talking to her father?"). Functional echo planar imaging (EPI) scans were collected from 11 normal subjects. There was increased BOLD activity in bilateral inferior frontal and temporal regions for RQ over either FQ or FS stimuli. The study provides data relevant to the location of regions responsive to intonationally marked illocutionary differences between questions and statements.

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

PubMed

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

2014-01-01

Functional connectivity measurements from resting state blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) are proving a powerful tool to probe both normal brain function and neuropsychiatric disorders. However, the neural mechanisms that coordinate these large networks are poorly understood, particularly in the context of the growing interest in network dynamics. Recent work in anesthetized rats has shown that the spontaneous BOLD fluctuations are tightly linked to infraslow local field potentials (LFPs) that are seldom recorded but comparable in frequency to the slow BOLD fluctuations. These findings support the hypothesis that long-range coordination involves low frequency neural oscillations and establishes infraslow LFPs as an excellent candidate for probing the neural underpinnings of the BOLD spatiotemporal patterns observed in both rats and humans. To further examine the link between large-scale network dynamics and infraslow LFPs, simultaneous fMRI and microelectrode recording were performed in anesthetized rats. Using an optimized filter to isolate shared components of the signals, we found that time-lagged correlation between infraslow LFPs and BOLD is comparable in spatial extent and timing to a quasi-periodic pattern (QPP) found from BOLD alone, suggesting that fMRI-measured QPPs and the infraslow LFPs share a common mechanism. As fMRI allows spatial resolution and whole brain coverage not available with electroencephalography, QPPs can be used to better understand the role of infraslow oscillations in normal brain function and neurological or psychiatric disorders. © 2013.

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

PubMed Central

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

2013-01-01

Functional connectivity measurements from resting state blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) are proving a powerful tool to probe both normal brain function and neuropsychiatric disorders. However, the neural mechanisms that coordinate these large networks are poorly understood, particularly in the context of the growing interest in network dynamics. Recent work in anesthetized rats has shown that the spontaneous BOLD fluctuations are tightly linked to infraslow local field potentials (LFPs) that are seldom recorded but comparable in frequency to the slow BOLD fluctuations. These findings support the hypothesis that long-range coordination involves low frequency neural oscillations and establishes infraslow LFPs as an excellent candidate for probing the neural underpinnings of the BOLD spatiotemporal patterns observed in both rats and humans. To further examine the link between large-scale network dynamics and infraslow LFPs, simultaneous fMRI and microelectrode recording were performed in anesthetized rats. Using an optimized filter to isolate shared components of the signals, we found that time-lagged correlation between infraslow LFPs and BOLD is comparable in spatial extent and timing to a quasi-periodic pattern (QPP) found from BOLD alone, suggesting that fMRI-measured QPPs and the infraslow LFPs share a common mechanism. As fMRI allows spatial resolution and whole brain coverage not available with electroencephalography, QPPs can be used to better understand the role of infraslow oscillations in normal brain function and neurological or psychiatric disorders. PMID:24071524

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

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. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Olfactory Deficit Detected by fMRI in Early Alzheimer’s Disease

PubMed Central

Wang, Jianli; Eslinger, Paul J.; Doty, Richard L.; Zimmerman, Erin K.; Grunfeld, Robert; Sun, Xiaoyu; Connor, James R.; Price, Joseph L.; Smith, Michael B.; Yang, Qing X.

2012-01-01

Alzheimer’s disease (AD) is accompanied by smell dysfunction, as measured by psychophysical tests. Currently it is unknown whether AD-related alterations in central olfactory system neural activity, as measured by functional magnetic resonance imaging (fMRI), are detectable beyond those observed in healthy elderly. Moreover, it is not known whether such changes are correlated with indices of odor perception and dementia. To investigate these issues, twelve early stage AD patients and thirteen non-demented controls underwent fMRI while being exposed to each of three concentrations of lavender oil odorant. All participants were administered the University of Pennsylvania Smell Identification Test (UPSIT), the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale-2 (DRS-2), and the Clinical Dementia Rating Scale (CDR). The Blood oxygen level-dependent (BOLD) signal at primary olfactory cortex (POC) was weaker in AD than in HC subjects. At the lowest odorant concentration, the BOLD signals within POC, hippocampus, and insula were significantly correlated with UPSIT, MMSE, DRS-2, and CDR scores. The BOLD signal intensity and activation volume within the POC increased significantly as a function of odorant concentration in the AD group, but not in the control group. These findings demonstrate that olfactory fMRI is sensitive to the AD-related olfactory and functional cognitive decline. PMID:20709038

Contributions of dopaminergic and non-dopaminergic neurons to VTA-stimulation induced neurovascular responses in brain reward circuits.

PubMed

Brocka, Marta; Helbing, Cornelia; Vincenz, Daniel; Scherf, Thomas; Montag, Dirk; Goldschmidt, Jürgen; Angenstein, Frank; Lippert, Michael

2018-04-30

Mapping the activity of the human mesolimbic dopamine system by BOLD-fMRI is a tempting approach to non-invasively study the action of the brain reward system during different experimental conditions. However, the contribution of dopamine release to the BOLD signal is disputed. To assign the actual contribution of dopaminergic and non-dopaminergic VTA neurons to the formation of BOLD responses in target regions of the mesolimbic system, we used two optogenetic approaches in rats. We either activated VTA dopaminergic neurons selectively, or dopaminergic and mainly glutamatergic projecting neurons together. We further used electrical stimulation to non-selectively activate neurons in the VTA. All three stimulation conditions effectively activated the mesolimbic dopaminergic system and triggered dopamine releases into the NAcc as measured by in vivo fast-scan cyclic voltammetry. Furthermore, both optogenetic stimulation paradigms led to indistinguishable self-stimulation behavior. In contrast to these similarities, however, the BOLD response pattern differed greatly between groups. In general, BOLD responses were weaker and sparser with increasing stimulation specificity for dopaminergic neurons. In addition, repetitive stimulation of the VTA caused a progressive decoupling of dopamine release and BOLD signal strength, and dopamine receptor antagonists were unable to block the BOLD signal elicited by VTA stimulation. To exclude that the sedation during fMRI is the cause of minimal mesolimbic BOLD in response to specific dopaminergic stimulation, we repeated our experiments using CBF SPECT in awake animals. Again, we found activations only for less-specific stimulation. Based on these results we conclude that canonical BOLD responses in the reward system represent mainly the activity of non-dopaminergic neurons. Thus, the minor effects of projecting dopaminergic neurons are concealed by non-dopaminergic activity, a finding which highlights the importance of a careful

fMRI reveals two distinct cerebral networks subserving speech motor control.

PubMed

Riecker, A; Mathiak, K; Wildgruber, D; Erb, M; Hertrich, I; Grodd, W; Ackermann, H

2005-02-22

There are few data on the cerebral organization of motor aspects of speech production and the pathomechanisms of dysarthric deficits subsequent to brain lesions and diseases. The authors used fMRI to further examine the neural basis of speech motor control. In eight healthy volunteers, fMRI was performed during syllable repetitions synchronized to click trains (2 to 6 Hz; vs a passive listening task). Bilateral hemodynamic responses emerged at the level of the mesiofrontal and sensorimotor cortex, putamen/pallidum, thalamus, and cerebellum (two distinct activation spots at either side). In contrast, dorsolateral premotor cortex and anterior insula showed left-sided activation. Calculation of rate/response functions revealed a negative linear relationship between repetition frequency and blood oxygen level-dependent (BOLD) signal change within the striatum, whereas both cerebellar hemispheres exhibited a step-wise increase of activation at approximately 3 Hz. Analysis of the temporal dynamics of the BOLD effect found the various cortical and subcortical brain regions engaged in speech motor control to be organized into two separate networks (medial and dorsolateral premotor cortex, anterior insula, and superior cerebellum vs sensorimotor cortex, basal ganglia, and inferior cerebellum). These data provide evidence for two levels of speech motor control bound, most presumably, to motor preparation and execution processes. They also help to explain clinical observations such as an unimpaired or even accelerated speaking rate in Parkinson disease and slowed speech tempo, which does not fall below a rate of 3 Hz, in cerebellar disorders.

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2014-07-15

Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI), one of the most powerful technologies in neuroscience, measures neural activity indirectly. Therefore, systematic correlation of BOLD signals with other neural activity measurements is critical to understanding and then using the technology. Numerous studies have revealed that the BOLD signal is determined by many factors and is better correlated with local field potentials (LFP) than single/multiple unit firing. The relationship between BOLD and LFP signals under higher spatial resolution is complex and remains unclear. Here, changes of BOLD and LFP signals in the glomerular (GL), mitral cell (MCL), and granular cell layers (GCL) of the olfactory bulb were evoked by odor stimulation and sequentially acquired using high-resolution fMRI and electrode array. The experimental results revealed a rather complex relationship between BOLD and LFP signals. Both signal modalities were increased layer-dependently by odor stimulation, but the orders of signal intensity were significantly different: GL>MCL>GCL and GCL>GL>MCL for BOLD and LFP, respectively. During odor stimulation, the temporal features of LFPs were similar for a given band in different layers, but different for different frequency bands in a given layer. The BOLD and LFP signals in the low gamma frequency band correlated the best. This study provides new evidence for the consistency between structure and function in understanding the neurophysiological basis of BOLD signals, but also reminds that caution must be taken in interpreting of BOLD signals in regard to neural activity. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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

PubMed Central

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

2016-01-01

Cerebrovascular reactivity (CVR) is an important metric of cerebrovascular health. While the BOLD fMRI method in conjunction with carbon-dioxide (CO2) based vascular manipulation has been the most commonly used, the BOLD signal is not a direct measure of vascular changes, and the use of arterial-spin labeling (ASL) cerebral blood flow (CBF) imaging is increasingly advocated. Nonetheless, given the differing dependencies of BOLD and CBF on vascular baseline conditions and the diverse CO2 manipulation types currently used in the literature, knowledge of potential biases introduced by each technique is critical for the interpretation of CVR measurements. In this work, we use simultaneous BOLD-CBF acquisitions during both vasodilatory (hypercapnic) and vasoconstrictive (hypocapnic) stimuli to measure CVR. We further imposed different levels of baseline vascular tension by inducing hypercapnic and hypocapnic baselines, separately from normocapnia by 4 mm Hg. We saw significant and diverse dependencies on vascular stimulus and baseline condition in both BOLD and CBF CVR measurements: (i) BOLD-based CVR is more sensitive to basal vascular tension than CBF-based CVR; (ii) the use of a combination of vasodilatory and vasoconstrictive stimuli maximizes the sensitivity of CBF-based CVR to vascular tension changes; (iii) the BOLD and CBF vascular response delays are both significantly lengthened at predilated baseline. As vascular tension can often be altered by potential pathology, our findings are important considerations when interpreting CVR measurements in health and disease. PMID:25655446

Functional cortical and subcortical abnormalities in pedophilia: a combined study using a choice reaction time task and fMRI.

PubMed

Poeppl, Timm B; Nitschke, Joachim; Dombert, Beate; Santtila, Pekka; Greenlee, Mark W; Osterheider, Michael; Mokros, Andreas

2011-06-01

Pedophiles show sexual interest in prepubescent children but not in adults. Research into the neurofunctional mechanisms of paraphilias has gathered momentum over the last years. To elucidate the underlying neural processing of sexual interest among pedophiles and to highlight the differences in comparison with nonparaphilic sexual interest in adults. Nine pedophilic patients and 11 nonpedophilic control subjects underwent functional magnetic resonance imaging (fMRI) while viewing pictures of nude (prepubescents, pubescents, and adults) and neutral content, as well as performing a concomitant choice reaction time task (CRTT). Brain blood oxygen level-dependent (BOLD) signals and response latencies in the CRTT during exposure to each picture category. Analysis of behavioral data showed group differences in reaction times regarding prepubescent and adult but not pubescent stimuli. During stimulation with pictures displaying nude prepubescents, pedophiles showed increased BOLD response in brain areas known to be involved in processing of visual sexual stimuli. Comparison of pedophilic patients with the control group discovered differences in BOLD responses with respect to prepubescent and adult but not to pubescent stimuli. Differential effects in particular occurred in the cingulate gyrus and insular region. The brain response of pedophiles to visual sexual stimulation by images of nude prepubescents is comparable with previously described neural patterns of sexual processing in nonpedophilic human males evoked by visual stimuli depicting nude adults. Nevertheless, group differences found in the cingulate gyrus and the insular region suggest an important role of these brain areas in pedophilic sexual interest. Furthermore, combining attention-based methods like CRTT with fMRI may be a viable option for future diagnostic procedures regarding pedophilia. © 2011 International Society for Sexual Medicine.

Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation

PubMed Central

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

2015-01-01

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

Implicit sequence-specific motor learning after sub-cortical stroke is associated with increased prefrontal brain activations: An fMRI study

PubMed Central

Meehan, Sean K.; Randhawa, Bubblepreet; Wessel, Brenda; Boyd, Lara A.

2010-01-01

Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence-specific motor learning as compared to general improvements in motor control. Nine healthy participants and 9 individuals with chronic, right focal sub-cortical stroke performed a continuous joystick-based tracking task during an initial fMRI session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence-specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequences during early practice and again at the retention test. Both groups demonstrated implicit sequence-specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased BOLD response in left dorsal premotor cortex (BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence-specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal-based attentional network for implicit motor learning after stroke. The present study is the first to highlight the importance of the prefrontal cortex for implicit sequence-specific motor learning after stroke. PMID:20725908

fMRI and MRS measures of neuroplasticity in the pharyngeal motor cortex

PubMed Central

Michou, Emilia; Williams, Steve; Vidyasagar, Rishma; Downey, Darragh; Mistry, Satish; Edden, Richard A.E.; Hamdy, Shaheen

2016-01-01

Introduction Paired associative stimulation (PAS), is a novel non-invasive technique where two neural substrates are employed in a temporally coordinated manner in order to modulate cortico-motor excitability within the motor cortex (M1). In swallowing, combined pharyngeal electrical and transcranial-magnetic-stimulation induced beneficial neurophysiological and behavioural effects in healthy subjects and dysphagic stroke patients. Here, we aimed to investigate the whole-brain changes in neural activation during swallowing using functional magnetic resonance imaging (fMRI) following PAS application and in parallel assess associated GABA changes with magnetic resonance spectroscopy (MRS). Methods Healthy adults (n = 11, 38 ± 9 years old) were randomised to receive real and sham PAS to the ‘stronger’ motor cortex pharyngeal representation, on 2 separate visits. Following PAS, event-related fMRI was performed to assess changes in brain activation in response to water and saliva swallowing and during rest. Data were analysed (SPM8) at P < .001. MRS data were acquired using MEGA-PRESS before and after the fMRI acquisitions on both visits and GABA concentrations were measured (AMARES, jMRUI). Results Following real PAS, BOLD signal changes (group analyses) increased at the site of stimulation during water and saliva swallowing, compared to sham PAS. It is also evident that PAS induced significant increases in BOLD signal to contralateral (to stimulation) hemispheric areas that are of importance to the swallowing neural network. Following real PAS, GABA: creatine ratio showed a trend to increase contralateral to PAS. Conclusion Targeted PAS applied to the human pharyngeal motor cortex induces local and remote changes in both primary and non-primary areas for water and saliva tasks. There is a possibility that changes of the inhibitory neurotransmitter, GABA, may play a role in the changes in BOLD signal. These findings provide evidence for the mechanisms underlying

Trait and state anxiety is marked by increased working memory-related parietal BOLD signal.

PubMed

Ford, Talitha C; Simpson, Tamara; McPhee, Grace; Stough, Con; Downey, Luke A

2018-05-16

Anxiety is associated with compromised cognitive control functions, such as working memory. State and trait anxiety within the non-clinical population can be utilised to investigate potential neural markers for anxiety, which may help to elucidate potential prevention and intervention methods. Thirty-two healthy adults (20 female, 12 male), aged between 30 and 65 years, performed a 2-back task whilst fMRI BOLD signal was acquired using a 3T scanner. Mean BOLD signal was obtained in cognitive control network regions of interest of: left and right dorsolateral prefrontal cortex (DLPFC) and posterior parietal lobe (PPL), and medial prefrontal cortex (MPFC). State and trait anxiety levels were recorded. Higher overall anxiety was moderately associated with more left and right PPL BOLD signal; there was a weak relationship between anxiety and left DLPFC BOLD signal. MPFC BOLD signal and trait anxiety were moderately associated with overall 2-back task performance. These findings suggest that non-clinical anxiety affects the recruitment of cortical resources during working memory, but that anxiety does not impair performance during a 2-back task. Copyright © 2018 Elsevier B.V. All rights reserved.

Real-time fMRI and its application to neurofeedback.

PubMed

Weiskopf, Nikolaus

2012-08-15

Real-time fMRI (rtfMRI) allows immediate access to experimental results by analyzing data as fast as they are acquired. It was devised soon after the inception of fMRI and has undergone a rapid development since then. The availability of results during the ongoing experiment facilitates a variety of applications such as quality assurance or fast functional localization. RtfMRI can also be used as a brain-computer interface (BCI) with high spatial resolution and whole-brain coverage, overcoming limitations of EEG based BCIs. This review will focus on the application of rtfMRI BCIs to neurofeedback, i.e., the online feedback of the blood oxygen level dependent (BOLD) response. I will motivate its development and place its beginnings into the contemporary scientific context by providing an account of our early work at the University of Tübingen, followed by a review of the accomplishments and the current state of rtfMRI neurofeedback. RtfMRI neurofeedback has been used to train self-regulation of the local BOLD response in various different brain areas and to study consequential behavioral effects. Behavioral effects such as modulation of pain, reaction time, linguistic or emotional processing have been shown in healthy and/or patient populations. RtfMRI neurofeedback presents a new paradigm for studying the relation between brain behavior and physiology, because the latter can be regarded as the independent variable (unlike in conventional neuroimaging studies where behavior is the independent variable). The initial results in patient populations improving pain, tinnitus, depression or modulating perception in schizophrenia are encouraging and merit further controlled clinical studies. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of covert and overt paradigms in clinical language fMRI.

PubMed

Partovi, Sasan; Konrad, Florian; Karimi, Sasan; Rengier, Fabian; Lyo, John K; Zipp, Lisa; Nennig, Ernst; Stippich, Christoph

2012-05-01

The aim of this study was to assess the intrasubject and intersubject reproducibility of functional magnetic resonance imaging (fMRI) language paradigms on language localization and lateralization. Fourteen healthy volunteers were enrolled prospectively and underwent language fMRI using visually triggered covert and overt sentence generation (SG) and word generation (WG) paradigms. Semiautomated analysis of all functional data was performed using Brain Voyager on an individual basis. Regions of interest for Broca's area, Wernicke's area, and their contralateral homologues were drawn. The Euclidean coordinates of the center of gravidity (x, y, and z) of the respective blood oxygenation level-dependent (BOLD) activation cluster, and the correlation of the measured hemodynamic response to the applied reference function (r), relative BOLD signal change as BOLD signal characteristics were measured in each region of interest. Regional lateralization indexes were calculated for Broca's area, Wernicke's area, and their contralateral homologues separately. Wilcoxon's signed-rank test was applied for statistical comparisons (P values < .05 were considered significant). Ten of the 14 volunteers had three repeated measurements to test intrasession reproducibility and intersession reproducibility. Overall activation rates for the four paradigms were 89% for covert SG, 82% for overt SG, 89% for covert WG, and 100% for overt WG. When comparing covert and overt paradigms, language localization was significantly different in 17% (Euclidean coordinates) and 19% (BOLD signal characteristics), respectively. Language lateralization was significantly different in 75%. Intrasubject and intersubject reproducibility was excellent, with 3.3% significant differences among all five parameters for language localization and 0% significant differences for language lateralization using covert paradigms. Covert language paradigms (SG and WG) provided highly robust and reproducible localization and

Evidence accumulation detected in BOLD signal using slow perceptual decision making.

PubMed

Krueger, Paul M; van Vugt, Marieke K; Simen, Patrick; Nystrom, Leigh; Holmes, Philip; Cohen, Jonathan D

2017-04-01

We assessed whether evidence accumulation could be observed in the BOLD signal during perceptual decision making. This presents a challenge since the hemodynamic response is slow, while perceptual decisions are typically fast. Guided by theoretical predictions of the drift diffusion model, we slowed down decisions by penalizing participants for incorrect responses. Second, we distinguished BOLD activity related to stimulus detection (modeled using a boxcar) from activity related to integration (modeled using a ramp) by minimizing the collinearity of GLM regressors. This was achieved by dissecting a boxcar into its two most orthogonal components: an "up-ramp" and a "down-ramp." Third, we used a control condition in which stimuli and responses were similar to the experimental condition, but that did not engage evidence accumulation of the stimuli. The results revealed an absence of areas in parietal cortex that have been proposed to drive perceptual decision making but have recently come into question; and newly identified regions that are candidates for involvement in evidence accumulation. Previous fMRI studies have either used fast perceptual decision making, which precludes the measurement of evidence accumulation, or slowed down responses by gradually revealing stimuli. The latter approach confounds perceptual detection with evidence accumulation because accumulation is constrained by perceptual input. We slowed down the decision making process itself while leaving perceptual information intact. This provided a more sensitive and selective observation of brain regions associated with the evidence accumulation processes underlying perceptual decision making than previous methods. Copyright © 2017 Elsevier B.V. All rights reserved.

Focal BOLD-fMRI changes in bicuculline-induced tonic-clonic seizures in the rat

PubMed Central

DeSalvo, Matthew N.; Schridde, Ulrich; Mishra, Asht M.; Motelow, Joshua E.; Purcaro, Michael J.; Danielson, Nathan; Bai, Xiaoxiao; Hyder, Fahmeed; Blumenfeld, Hal

2010-01-01

Generalized tonic-clonic seizures cause widespread physiological changes throughout the cerebral cortex and subcortical structures in the brain. Using combined blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 9.4 T and electroencephalography (EEG) these changes can be characterized with high spatiotemporal resolution. We studied BOLD changes in anesthetized Wistar rats during bicuculline-induced tonic-clonic seizures. Bicuculline, a GABAA receptor antagonist, was injected systemically and seizure activity was observed on EEG as high amplitude, high-frequency polyspike discharges followed by clonic paroxysmal activity of lower frequency, with mean electrographic seizure duration of 349 s. Our aim was to characterize the spatial localization, direction, and timing of BOLD signal changes during the pre-ictal, ictal and post-ictal periods. Group analysis was performed across seizures using paired t-maps of BOLD signal superimposed on high resolution anatomical images. Regional analysis was then performed using volumes of interest to quantify BOLD timecourses. In the pre-ictal period we found focal BOLD increases in specific areas of somatosensory cortex (S1, S2) and thalamus several seconds before seizure onset. During seizures we observed BOLD increases in cortex, brainstem and thalamus and BOLD decreases in the hippocampus. The largest ictal BOLD increases remained in the focal regions of somatosensory cortex showing pre-ictal increases. During the post-ictal period we observed widespread BOLD decreases. These findings support a model in which “generalized” tonic-clonic seizures begin with focal changes before electrographic seizure onset, which progress to non-uniform changes during seizures, possibly shedding light on the etiology and pathophysiology of similar seizures in humans. PMID:20079442

The cerebral control of speech tempo: opposite relationship between speaking rate and BOLD signal changes at striatal and cerebellar structures.

PubMed

Riecker, Axel; Kassubek, Jan; Gröschel, Klaus; Grodd, Wolfgang; Ackermann, Hermann

2006-01-01

So far, only sparse data on the cerebral organization of speech motor control are available. In order to further delineate the neural basis of articulatory functions, fMRI measurements were performed during self-paced syllable repetitions at six different frequencies (2-6 Hz). Bilateral hemodynamic main effects, calculated across all syllable rates considered, emerged within sensorimotor cortex, putamen, thalamus and cerebellum. At the level of the caudatum and the anterior insula, activation was found restricted to the left side. The computation of rate-to-response functions of the BOLD signal revealed a negative linear relationship between syllable frequency and response magnitude within the striatum whereas cortical areas and cerebellar hemispheres exhibited an opposite activation pattern. Dysarthric patients with basal ganglia disorders show unimpaired or even accelerated speaking rate whereas, in contrast, cerebellar dysfunctions give rise to slowed speech tempo which does not fall below a rate of about 3 Hz. The observed rate-to-response profiles of the BOLD signal thus might help to elucidate the pathophysiological mechanisms of dysarthric deficits in central motor disorders.

Spatial Mnemonic Encoding: Theta Power Decreases and Medial Temporal Lobe BOLD Increases Co-Occur during the Usage of the Method of Loci

PubMed Central

Volberg, Gregor; Goldhacker, Markus; Hanslmayr, Simon

2016-01-01

Abstract The method of loci is one, if not the most, efficient mnemonic encoding strategy. This spatial mnemonic combines the core cognitive processes commonly linked to medial temporal lobe (MTL) activity: spatial and associative memory processes. During such processes, fMRI studies consistently demonstrate MTL activity, while electrophysiological studies have emphasized the important role of theta oscillations (3–8 Hz) in the MTL. However, it is still unknown whether increases or decreases in theta power co-occur with increased BOLD signal in the MTL during memory encoding. To investigate this question, we recorded EEG and fMRI separately, while human participants used the spatial method of loci or the pegword method, a similarly associative but nonspatial mnemonic. The more effective spatial mnemonic induced a pronounced theta power decrease source localized to the left MTL compared with the nonspatial associative mnemonic strategy. This effect was mirrored by BOLD signal increases in the MTL. Successful encoding, irrespective of the strategy used, elicited decreases in left temporal theta power and increases in MTL BOLD activity. This pattern of results suggests a negative relationship between theta power and BOLD signal changes in the MTL during memory encoding and spatial processing. The findings extend the well known negative relation of alpha/beta oscillations and BOLD signals in the cortex to theta oscillations in the MTL. PMID:28101523

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.

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

PubMed Central

Hadjistassou, Constantinos; Moyle, Keri; Ventikos, Yiannis

2016-01-01

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

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

PubMed

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

2015-04-01

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

A Stimulus-Locked Vector Autoregressive Model for Slow Event-Related fMRI Designs

PubMed Central

Siegle, Greg

2009-01-01

Summary Neuroscientists have become increasingly interested in exploring dynamic relationships among brain regions. Such a relationship, when directed from one region toward another, is denoted by “effective connectivity.” An fMRI experimental paradigm which is well-suited for examination of effective connectivity is the slow event-related design. This design presents stimuli at sufficient temporal spacing for determining within-trial trajectories of BOLD activation, allowing for the analysis of stimulus-locked temporal covariation of brain responses in multiple regions. This may be especially important for emotional stimuli processing, which can evolve over the course of several seconds, if not longer. However, while several methods have been devised for determining fMRI effective connectivity, few are adapted to event-related designs, which include non-stationary BOLD responses and multiple levels of nesting. We propose a model tailored for exploring effective connectivity of multiple brain regions in event-related fMRI designs - a semi-parametric adaptation of vector autoregressive (VAR) models, termed “stimulus-locked VAR” (SloVAR). Connectivity coefficients vary as a function of time relative to stimulus onset, are regularized via basis expansions, and vary randomly across subjects. SloVAR obtains flexible, data-driven estimates of effective connectivity and hence is useful for building connectivity models when prior information on dynamic regional relationships is sparse. Indices derived from the coefficient estimates can also be used to relate effective connectivity estimates to behavioral or clinical measures. We demonstrate the SloVAR model on a sample of clinically depressed and normal controls, showing that early but not late cortico-amygdala connectivity appears crucial to emotional control and early but not late cortico-cortico connectivity predicts depression severity in the depressed group, relationships that would have been missed in a more

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. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Spatiotemporal frequency tuning of BOLD and gamma band MEG responses compared in primary visual cortex.

PubMed

Muthukumaraswamy, Suresh D; Singh, Krish D

2008-05-01

In this study, the spatial and temporal frequency tuning characteristics of the MEG gamma (40-60 Hz) rhythm and the BOLD response in primary visual cortex were measured and compared. In an identical MEG/fMRI paradigm, 10 participants viewed reversing square wave gratings at 2 spatial frequencies [0.5 and 3 cycles per degree (cpd)] reversing at 5 temporal frequencies (0, 1 6, 10, 15 Hz). Three-dimensional images of MEG source power were generated with synthetic aperture magnetometry (SAM) and showed a high degree of spatial correspondence with BOLD responses in primary visual cortex with a mean spatial separation of 6.5 mm, but the two modalities showed different tuning characteristics. The gamma rhythm showed a clear increase in induced power for the high spatial frequency stimulus while BOLD showed no difference in activity for the two spatial frequencies used. Both imaging modalities showed a general increase of activity with temporal frequency, however, BOLD plateaued around 6-10 Hz while the MEG generally increased with a dip exhibited at 6 Hz. These results demonstrate that the two modalities may show activation in similar spatial locations but that the functional pattern of these activations may differ in a complex manner, suggesting that they may be tuned to different aspects of neuronal activity.

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

PubMed Central

Bethmann, Anja; Scheich, Henning; Brechmann, André

2012-01-01

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

[Does the individual adaptation of standardized speech paradigmas for clinical functional magnetic resonance imaging (fMRI) effect the localization of the language-dominant hemisphere and of Broca's and Wernicke's areas].

PubMed

Konrad, F; Nennig, E; Ochmann, H; Kress, B; Sartor, K; Stippich, C

2005-03-01

Functional magnetic resonance imaging (fMRI) localizes Broca's area (B) and Wernicke's area (W) and the hemisphere dominant for language. In clinical fMRI, adapting the stimulation paradigms to each patient's individual cognitive capacity is crucial for diagnostic success. To interpret clinical fMRI findings correctly, we studied the effect of varying frequency and number of stimuli on functional localization, determination of language dominance and BOLD signals. Ten volunteers (VP) were investigated at 1.5 Tesla during visually triggered sentence generation using a standardized block design. In four different measurements, the stimuli were presented to each VP with frequencies of 1/1 s, (1/2) s, (1/3) s and (1/6) s. The functional localizations and the correlations of the measured BOLD signals to the applied hemodynamic reference function (r) were almost independent from frequency and number of the stimuli in both hemispheres, whereas the relative BOLD signal changes (DeltaS) in B and W increased with the stimulation rate, which also changed the lateralization indices. The strongest BOLD activations were achieved with the highest stimulation rate or with the maximum language production task, respectively. The adaptation of language paradigms necessary in clinical fMRI does not alter the functional localizations but changes the BOLD signals and language lateralization which should not be attributed to the underlying brain pathology.

Functional MR imaging assessment of a non-responsive brain injured patient.

PubMed

Moritz, C H; Rowley, H A; Haughton, V M; Swartz, K R; Jones, J; Badie, B

2001-10-01

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.

Against Boldness

ERIC Educational Resources Information Center

Kennedy, Mary M.

2010-01-01

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

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.

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

Phenotypic regional fMRI activation patterns during memory encoding in MCI and AD

PubMed Central

Browndyke, Jeffrey N.; Giovanello, Kelly; Petrella, Jeffrey; Hayden, Kathleen; Chiba-Falek, Ornit; Tucker, Karen A.; Burke, James R.; Welsh-Bohmer, Kathleen A.

2014-01-01

Background Reliable blood-oxygen-level-dependent (BOLD) fMRI phenotypic biomarkers of Alzheimer's disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature. Methods A series of random-effects, activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based upon a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis. Results ALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal controls across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe (MTL), specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal controls. Conclusions ALE consistencies broadly support the presence of frontal compensatory activity, MTL activity alteration, and posterior midline “default mode” hyperactivation during episodic memory encoding attempts in the diseased or prospective pre-disease condition. Taken together these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD. PMID:22841497

fMRI: blood oxygen level-dependent activation during a working memory-selective attention task in children born extremely preterm.

PubMed

Griffiths, Silja Torvik; Gundersen, Hilde; Neto, Emanuel; Elgen, Irene; Markestad, Trond; Aukland, Stein M; Hugdahl, Kenneth

2013-08-01

Extremely preterm (EPT)/extremely low-birth-weight (ELBW) children attaining school age and adolescence often have problems with executive functions such as working memory and selective attention. Our aim was to investigate a hypothesized difference in blood oxygen level-dependent (BOLD) activation during a selective attention-working memory task in EPT/ELBW children as compared with term-born controls. A regional cohort of 28 EPT/ELBW children and 28 term-born controls underwent functional magnetic resonance imaging (fMRI) scanning at 11 y of age while performing a combined Stroop n-back task. Group differences in BOLD activation were analyzed with Statistical Parametric Mapping 8 analysis software package, and reaction times (RTs) and response accuracy (RA) were compared in a multifactorial ANOVA test. The BOLD activation pattern in the preterm group involved the same areas (cingulate, prefrontal, and parietal cortexes), but all areas displayed significantly less activation than those in the control group, particularly when the cognitive load was increased. The RA results corresponded with the activation data in that the preterm group had significantly fewer correct responses. No group difference was found regarding RTs. Children born EPT/ELBW displayed reduced working memory and selective attention capacity as compared with term-born controls. These impairments had neuronal correlates with reduced BOLD activation in areas responsible for online stimulus monitoring, working memory, and cognitive control.

BOLD temporal dynamics of rat superior colliculus and lateral geniculate nucleus following short duration visual stimulation.

PubMed

Lau, Condon; Zhou, Iris Y; Cheung, Matthew M; Chan, Kevin C; Wu, Ed X

2011-04-29

The superior colliculus (SC) and lateral geniculate nucleus (LGN) are important subcortical structures for vision. Much of our understanding of vision was obtained using invasive and small field of view (FOV) techniques. In this study, we use non-invasive, large FOV blood oxygenation level-dependent (BOLD) fMRI to measure the SC and LGN's response temporal dynamics following short duration (1 s) visual stimulation. Experiments are performed at 7 tesla on Sprague Dawley rats stimulated in one eye with flashing light. Gradient-echo and spin-echo sequences are used to provide complementary information. An anatomical image is acquired from one rat after injection of monocrystalline iron oxide nanoparticles (MION), a blood vessel contrast agent. BOLD responses are concentrated in the contralateral SC and LGN. The SC BOLD signal measured with gradient-echo rises to 50% of maximum amplitude (PEAK) 0.2±0.2 s before the LGN signal (p<0.05). The LGN signal returns to 50% of PEAK 1.4±1.2 s before the SC signal (p<0.05). These results indicate the SC signal rises faster than the LGN signal but settles slower. Spin-echo results support these findings. The post-MION image shows the SC and LGN lie beneath large blood vessels. This subcortical vasculature is similar to that in the cortex, which also lies beneath large vessels. The LGN lies closer to the large vessels than much of the SC. The differences in response timing between SC and LGN are very similar to those between deep and shallow cortical layers following electrical stimulation, which are related to depth-dependent blood vessel dilation rates. This combined with the similarities in vasculature between subcortex and cortex suggest the SC and LGN timing differences are also related to depth-dependent dilation rates. This study shows for the first time that BOLD responses in the rat SC and LGN following short duration visual stimulation are temporally different.

The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm

PubMed Central

Licata, Stephanie C.; Nickerson, Lisa D.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

2013-01-01

Networks of brain regions having synchronized fluctuations of the blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) time-series at rest, or “resting state networks” (RSNs), are emerging as a basis for understanding intrinsic brain activity. RSNs are topographically consistent with activity-related networks subserving sensory, motor, and cognitive processes, and studying their spontaneous fluctuations following acute drug challenge may provide a way to understand better the neuroanatomical substrates of drug action. The present within-subject double-blind study used BOLD fMRI at 3T to investigate the functional networks influenced by the non-benzodiazepine hypnotic zolpidem (Ambien®). Zolpidem is a positive modulator of γ-aminobutyric acidA (GABAA) receptors, and engenders sedative effects that may be explained in part by how it modulates intrinsic brain activity. Healthy participants (n= 12) underwent fMRI scanning 45 min after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured while participants gazed at a static fixation point (i.e., at rest). Data were analyzed using group independent component analysis (ICA) with dual regression and results indicated that compared to placebo, the highest dose of zolpidem increased functional connectivity within a number of sensory, motor, and limbic networks. These results are consistent with previous studies showing an increase in functional connectivity at rest following administration of the positive GABAA receptor modulators midazolam and alcohol, and suggest that investigating how zolpidem modulates intrinsic brain activity may have implications for understanding the etiology of its powerful sedative effects. PMID:23296183

Monkey cortex through fMRI glasses

PubMed Central

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

2015-01-01

In 1998 several groups reported the feasibility of functional magnetic resonance imaging (fMRI) experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category and feature selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging. PMID:25102559

Monkey cortex through fMRI glasses.

PubMed

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

2014-08-06

In 1998 several groups reported the feasibility of fMRI experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category- and feature-selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

Relating resting-state fMRI and EEG whole-brain connectomes across frequency bands.

PubMed

Deligianni, Fani; Centeno, Maria; Carmichael, David W; Clayden, Jonathan D

2014-01-01

Whole brain functional connectomes hold promise for understanding human brain activity across a range of cognitive, developmental and pathological states. So called resting-state (rs) functional MRI studies have contributed to the brain being considered at a macroscopic scale as a set of interacting regions. Interactions are defined as correlation-based signal measurements driven by blood oxygenation level dependent (BOLD) contrast. Understanding the neurophysiological basis of these measurements is important in conveying useful information about brain function. Local coupling between BOLD fMRI and neurophysiological measurements is relatively well defined, with evidence that gamma (range) frequency EEG signals are the closest correlate of BOLD fMRI changes during cognitive processing. However, it is less clear how whole-brain network interactions relate during rest where lower frequency signals have been suggested to play a key role. Simultaneous EEG-fMRI offers the opportunity to observe brain network dynamics with high spatio-temporal resolution. We utilize these measurements to compare the connectomes derived from rs-fMRI and EEG band limited power (BLP). Merging this multi-modal information requires the development of an appropriate statistical framework. We relate the covariance matrices of the Hilbert envelope of the source localized EEG signal across bands to the covariance matrices derived from rs-fMRI with the means of statistical prediction based on sparse Canonical Correlation Analysis (sCCA). Subsequently, we identify the most prominent connections that contribute to this relationship. We compare whole-brain functional connectomes based on their geodesic distance to reliably estimate the performance of the prediction. The performance of predicting fMRI from EEG connectomes is considerably better than predicting EEG from fMRI across all bands, whereas the connectomes derived in low frequency EEG bands resemble best rs-fMRI connectivity.

Relating resting-state fMRI and EEG whole-brain connectomes across frequency bands

PubMed Central

Deligianni, Fani; Centeno, Maria; Carmichael, David W.; Clayden, Jonathan D.

2014-01-01

Whole brain functional connectomes hold promise for understanding human brain activity across a range of cognitive, developmental and pathological states. So called resting-state (rs) functional MRI studies have contributed to the brain being considered at a macroscopic scale as a set of interacting regions. Interactions are defined as correlation-based signal measurements driven by blood oxygenation level dependent (BOLD) contrast. Understanding the neurophysiological basis of these measurements is important in conveying useful information about brain function. Local coupling between BOLD fMRI and neurophysiological measurements is relatively well defined, with evidence that gamma (range) frequency EEG signals are the closest correlate of BOLD fMRI changes during cognitive processing. However, it is less clear how whole-brain network interactions relate during rest where lower frequency signals have been suggested to play a key role. Simultaneous EEG-fMRI offers the opportunity to observe brain network dynamics with high spatio-temporal resolution. We utilize these measurements to compare the connectomes derived from rs-fMRI and EEG band limited power (BLP). Merging this multi-modal information requires the development of an appropriate statistical framework. We relate the covariance matrices of the Hilbert envelope of the source localized EEG signal across bands to the covariance matrices derived from rs-fMRI with the means of statistical prediction based on sparse Canonical Correlation Analysis (sCCA). Subsequently, we identify the most prominent connections that contribute to this relationship. We compare whole-brain functional connectomes based on their geodesic distance to reliably estimate the performance of the prediction. The performance of predicting fMRI from EEG connectomes is considerably better than predicting EEG from fMRI across all bands, whereas the connectomes derived in low frequency EEG bands resemble best rs-fMRI connectivity. PMID:25221467

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

PubMed

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

2016-10-15

The aim of this study was to investigate if the blood oxygenation level-dependent (BOLD) changes in the visual cortex can be used as biomarkers reflecting the online and offline effects of transcranial electrical stimulation (tES). Anodal transcranial direct current stimulation (tDCS) and 10Hz transcranial alternating current stimulation (tACS) were applied for 10min duration over the occipital cortex of healthy adults during the presentation of different visual stimuli, using a crossover, double-blinded design. Control experiments were also performed, in which sham stimulation as well as another electrode montage were used. Anodal tDCS over the visual cortex induced a small but significant further increase in BOLD response evoked by a visual stimulus; however, no aftereffect was observed. Ten hertz of tACS did not result in an online effect, but in a widespread offline BOLD decrease over the occipital, temporal, and frontal areas. These findings demonstrate that tES during visual perception affects the neuronal metabolism, which can be detected with functional magnetic resonance imaging (fMRI). Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2003-07-01

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

Correlating brain blood oxygenation level dependent (BOLD) fractal dimension mapping with magnetic resonance spectroscopy (MRS) in Alzheimer's disease.

PubMed

Warsi, Mohammed A; Molloy, William; Noseworthy, Michael D

2012-10-01

To correlate temporal fractal structure of resting state blood oxygen level dependent (rsBOLD) functional magnetic resonance imaging (fMRI) with in vivo proton magnetic resonance spectroscopy ((1)H-MRS), in Alzheimer's disease (AD) and healthy age-matched normal controls (NC). High temporal resolution (4 Hz) rsBOLD signal and single voxel (left putamen) magnetic resonance spectroscopy data was acquired in 33 AD patients and 13 NC. The rsBOLD data was analyzed using two types of fractal dimension (FD) analysis based on relative dispersion and frequency power spectrum. Comparisons in FD were performed between AD and NC, and FD measures were correlated with (1)H-MRS findings. Temporal fractal analysis of rsBOLD, was able to differentiate AD from NC subjects (P = 0.03). Low FD correlated with markers of AD severity including decreased concentrations of N-acetyl aspartate (R = 0.44, P = 0.015) and increased myoinositol (mI) (R = -0.45, P = 0.012). Based on these results we suggest fractal analysis of rsBOLD could provide an early marker of AD.

Characterization and Reduction of Cardiac- and Respiratory-Induced Noise as a Function of the Sampling Rate (TR) in fMRI

PubMed Central

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

2014-01-01

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

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

Resting-state functional MRI as a tool for evaluating brain hemodynamic responsiveness to external stimuli in rats.

PubMed

Paasonen, Jaakko; Salo, Raimo A; Huttunen, Joanna K; Gröhn, Olli

2017-09-01

Anesthesia is a major confounding factor in functional MRI (fMRI) experiments attributed to its effects on brain function. Recent evidence suggests that parameters obtained with resting-state fMRI (rs-fMRI) are coupled with anesthetic depth. Therefore, we investigated whether parameters obtained with rs-fMRI, such as functional connectivity (FC), are also directly related to blood-oxygen-level-dependent (BOLD) responses. A simple rs-fMRI protocol was implemented in a pharmacological fMRI study to evaluate the coupling between hemodynamic responses and FC under five anesthetics (α-chloralose, isoflurane, medetomidine, thiobutabarbital, and urethane). Temporal change in the FC was evaluated at 1-hour interval. Supplementary forepaw stimulation experiments were also conducted. Under thiobutabarbital anesthesia, FC was clearly coupled with nicotine-induced BOLD responses. Good correlation values were also obtained under isoflurane and medetomidine anesthesia. The observations in the thiobutabarbital group were supported by forepaw stimulation experiments. Additionally, the rs-fMRI protocol revealed significant temporal changes in the FC in the α-chloralose, thiobutabarbital, and urethane groups. Our results suggest that FC can be used to estimate brain hemodynamic responsiveness to stimuli and evaluate the level and temporal changes of anesthesia. Therefore, analysis of the fMRI baseline signal may be highly valuable tool for controlling the outcome of preclinical fMRI experiments. Magn Reson Med 78:1136-1146, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Reliable quantification of BOLD fMRI cerebrovascular reactivity despite poor breath-hold performance.

PubMed

Bright, Molly G; Murphy, Kevin

2013-12-01

Cerebrovascular reactivity (CVR) can be mapped using BOLD fMRI to provide a clinical insight into vascular health that can be used to diagnose cerebrovascular disease. Breath-holds are a readily accessible method for producing the required arterial CO2 increases but their implementation into clinical studies is limited by concerns that patients will demonstrate highly variable performance of breath-hold challenges. This study assesses the repeatability of CVR measurements despite poor task performance, to determine if and how robust results could be achieved with breath-holds in patients. Twelve healthy volunteers were scanned at 3 T. Six functional scans were acquired, each consisting of 6 breath-hold challenges (10, 15, or 20 s duration) interleaved with periods of paced breathing. These scans simulated the varying breath-hold consistency and ability levels that may occur in patient data. Uniform ramps, time-scaled ramps, and end-tidal CO2 data were used as regressors in a general linear model in order to measure CVR at the grey matter, regional, and voxelwise level. The intraclass correlation coefficient (ICC) quantified the repeatability of the CVR measurement for each breath-hold regressor type and scale of interest across the variable task performances. The ramp regressors did not fully account for variability in breath-hold performance and did not achieve acceptable repeatability (ICC<0.4) in several regions analysed. In contrast, the end-tidal CO2 regressors resulted in "excellent" repeatability (ICC=0.82) in the average grey matter data, and resulted in acceptable repeatability in all smaller regions tested (ICC>0.4). Further analysis of intra-subject CVR variability across the brain (ICCspatial and voxelwise correlation) supported the use of end-tidal CO2 data to extract robust whole-brain CVR maps, despite variability in breath-hold performance. We conclude that the incorporation of end-tidal CO2 monitoring into scanning enables robust, repeatable

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.

The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults.

PubMed

Tsvetanov, Kamen A; Henson, Richard N A; Tyler, Lorraine K; Davis, Simon W; Shafto, Meredith A; Taylor, Jason R; Williams, Nitin; Cam-Can; Rowe, James B

2015-06-01

In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath-hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age-related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population-based Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task-based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects of age on task

The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults

PubMed Central

Henson, Richard N. A.; Tyler, Lorraine K.; Davis, Simon W.; Shafto, Meredith A.; Taylor, Jason R.; Williams, Nitin; Cam‐CAN; Rowe, James B.

2015-01-01

Abstract In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood‐oxygenation level‐dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting‐state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath‐hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age‐related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population‐based Cambridge Centre for Ageing and Neuroscience cohort (Cam‐CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task‐based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects

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

Mapping the MRI voxel volume in which thermal noise matches physiological noise--implications for fMRI.

PubMed

Bodurka, J; Ye, F; Petridou, N; Murphy, K; Bandettini, P A

2007-01-15

This work addresses the choice of the imaging voxel volume in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Noise of physiological origin that is present in the voxel time course is a prohibitive factor in the detection of small activation-induced BOLD signal changes. If the physiological noise contribution dominates over the temporal fluctuation contribution in the imaging voxel, further increases in the voxel signal-to-noise ratio (SNR) will have diminished corresponding increases in temporal signal-to-noise (TSNR), resulting in reduced corresponding increases in the ability to detect activation induced signal changes. On the other hand, if the thermal and system noise dominate (suggesting a relatively low SNR) further decreases in SNR can prohibit detection of activation-induced signal changes. Here we have proposed and called the "suggested" voxel volume for fMRI the volume where thermal plus system-related and physiological noise variances are equal. Based on this condition we have created maps of fMRI suggested voxel volume from our experimental data at 3T, since this value will spatially vary depending on the contribution of physiologic noise in each voxel. Based on our fast EPI segmentation technique we have found that for gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) brain compartments the mean suggested cubical voxel volume is: (1.8 mm)3, (2.1 mm)3 and (1.4 mm)3, respectively. Serendipitously, (1.8 mm)3 cubical voxel volume for GM approximately matches the cortical thickness, thus optimizing BOLD contrast by minimizing partial volume averaging. The introduced suggested fMRI voxel volume can be a useful parameter for choice of imaging volume for functional studies.

Sensory-Motor Networks Involved in Speech Production and Motor Control: An fMRI Study

PubMed Central

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

2015-01-01

Speaking is one of the most complex motor behaviors developed to facilitate human communication. The underlying neural mechanisms of speech involve sensory-motor interactions that incorporate feedback information for online monitoring and control of produced speech sounds. In the present study, we adopted an auditory feedback pitch perturbation paradigm and combined it with functional magnetic resonance imaging (fMRI) recordings in order to identify brain areas involved in speech production and motor control. Subjects underwent fMRI scanning while they produced a steady vowel sound /a/ (speaking) or listened to the playback of their own vowel production (playback). During each condition, the auditory feedback from vowel production was either normal (no perturbation) or perturbed by an upward (+600 cents) pitch shift stimulus randomly. Analysis of BOLD responses during speaking (with and without shift) vs. rest revealed activation of a complex network including bilateral superior temporal gyrus (STG), Heschl's gyrus, precentral gyrus, supplementary motor area (SMA), Rolandic operculum, postcentral gyrus and right inferior frontal gyrus (IFG). Performance correlation analysis showed that the subjects produced compensatory vocal responses that significantly correlated with BOLD response increases in bilateral STG and left precentral gyrus. However, during playback, the activation network was limited to cortical auditory areas including bilateral STG and Heschl's gyrus. Moreover, the contrast between speaking vs. playback highlighted a distinct functional network that included bilateral precentral gyrus, SMA, IFG, postcentral gyrus and insula. These findings suggest that speech motor control involves feedback error detection in sensory (e.g. auditory) cortices that subsequently activate motor-related areas for the adjustment of speech parameters during speaking. PMID:25623499

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

PubMed

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

2015-04-01

Speaking is one of the most complex motor behaviors developed to facilitate human communication. The underlying neural mechanisms of speech involve sensory-motor interactions that incorporate feedback information for online monitoring and control of produced speech sounds. In the present study, we adopted an auditory feedback pitch perturbation paradigm and combined it with functional magnetic resonance imaging (fMRI) recordings in order to identify brain areas involved in speech production and motor control. Subjects underwent fMRI scanning while they produced a steady vowel sound /a/ (speaking) or listened to the playback of their own vowel production (playback). During each condition, the auditory feedback from vowel production was either normal (no perturbation) or perturbed by an upward (+600 cents) pitch-shift stimulus randomly. Analysis of BOLD responses during speaking (with and without shift) vs. rest revealed activation of a complex network including bilateral superior temporal gyrus (STG), Heschl's gyrus, precentral gyrus, supplementary motor area (SMA), Rolandic operculum, postcentral gyrus and right inferior frontal gyrus (IFG). Performance correlation analysis showed that the subjects produced compensatory vocal responses that significantly correlated with BOLD response increases in bilateral STG and left precentral gyrus. However, during playback, the activation network was limited to cortical auditory areas including bilateral STG and Heschl's gyrus. Moreover, the contrast between speaking vs. playback highlighted a distinct functional network that included bilateral precentral gyrus, SMA, IFG, postcentral gyrus and insula. These findings suggest that speech motor control involves feedback error detection in sensory (e.g. auditory) cortices that subsequently activate motor-related areas for the adjustment of speech parameters during speaking. Copyright © 2015 Elsevier Inc. All rights reserved.

Mapping interictal epileptic discharges using mutual information between concurrent EEG and fMRI.

PubMed

Caballero-Gaudes, César; Van de Ville, Dimitri; Grouiller, Frédéric; Thornton, Rachel; Lemieux, Louis; Seeck, Margitta; Lazeyras, François; Vulliemoz, Serge

2013-03-01

The mapping of haemodynamic changes related to interictal epileptic discharges (IED) in simultaneous electroencephalography (EEG) and functional MRI (fMRI) studies is usually carried out by means of EEG-correlated fMRI analyses where the EEG information specifies the model to test on the fMRI signal. The sensitivity and specificity critically depend on the accuracy of EEG detection and the validity of the haemodynamic model. In this study we investigated whether an information theoretic analysis based on the mutual information (MI) between the presence of epileptic activity on EEG and the fMRI data can provide further insights into the haemodynamic changes related to interictal epileptic activity. The important features of MI are that: 1) both recording modalities are treated symmetrically; 2) no requirement for a-priori models for the haemodynamic response function, or assumption of a linear relationship between the spiking activity and BOLD responses, and 3) no parametric model for the type of noise or its probability distribution is necessary for the computation of MI. Fourteen patients with pharmaco-resistant focal epilepsy underwent EEG-fMRI and intracranial EEG and/or surgical resection with positive postoperative outcome (seizure freedom or considerable reduction in seizure frequency) was available in 7/14 patients. We used nonparametric statistical assessment of the MI maps based on a four-dimensional wavelet packet resampling method. The results of MI were compared to the statistical parametric maps obtained with two conventional General Linear Model (GLM) analyses based on the informed basis set (canonical HRF and its temporal and dispersion derivatives) and the Finite Impulse Response (FIR) models. The MI results were concordant with the electro-clinically or surgically defined epileptogenic area in 8/14 patients and showed the same degree of concordance as the results obtained with the GLM-based methods in 12 patients (7 concordant and 5 discordant). In

A task-related and resting state realistic fMRI simulator for fMRI data validation

NASA Astrophysics Data System (ADS)

Hill, Jason E.; Liu, Xiangyu; Nutter, Brian; Mitra, Sunanda

2017-02-01

After more than 25 years of published functional magnetic resonance imaging (fMRI) studies, careful scrutiny reveals that most of the reported results lack fully decisive validation. The complex nature of fMRI data generation and acquisition results in unavoidable uncertainties in the true estimation and interpretation of both task-related activation maps and resting state functional connectivity networks, despite the use of various statistical data analysis methodologies. The goal of developing the proposed STANCE (Spontaneous and Task-related Activation of Neuronally Correlated Events) simulator is to generate realistic task-related and/or resting-state 4D blood oxygenation level dependent (BOLD) signals, given the experimental paradigm and scan protocol, by using digital phantoms of twenty normal brains available from BrainWeb (http://brainweb.bic.mni.mcgill.ca/brainweb/). The proposed simulator will include estimated system and modelled physiological noise as well as motion to serve as a reference to measured brain activities. In its current form, STANCE is a MATLAB toolbox with command line functions serving as an open-source add-on to SPM8 (http://www.fil.ion.ucl.ac.uk/spm/software/spm8/). The STANCE simulator has been designed in a modular framework so that the hemodynamic response (HR) and various noise models can be iteratively improved to include evolving knowledge about such models.

fMRI brain mapping during motion capture and FES induced motor tasks: signal to noise ratio assessment.

PubMed

Gandolla, Marta; Ferrante, Simona; Casellato, Claudia; Ferrigno, Giancarlo; Molteni, Franco; Martegani, Alberto; Frattini, Tiziano; Pedrocchi, Alessandra

2011-10-01

Functional Electrical Stimulation (FES) is a well known clinical rehabilitation procedure, however the neural mechanisms that underlie this treatment at Central Nervous System (CNS) level are still not completely understood. Functional magnetic resonance imaging (fMRI) is a suitable tool to investigate effects of rehabilitative treatments on brain plasticity. Moreover, monitoring the effective executed movement is needed to correctly interpret activation maps, most of all in neurological patients where required motor tasks could be only partially accomplished. The proposed experimental set-up includes a 1.5 T fMRI scanner, a motion capture system to acquire kinematic data, and an electro-stimulation device. The introduction of metallic devices and of stimulation current in the MRI room could affect fMRI acquisitions so as to prevent a reliable activation maps analysis. What we are interested in is that the Blood Oxygenation Level Dependent (BOLD) signal, marker of neural activity, could be detected within a given experimental condition and set-up. In this paper we assess temporal Signal to Noise Ratio (SNR) as image quality index. BOLD signal change is about 1-2% as revealed by a 1.5 T scanner. This work demonstrates that, with this innovative set-up, in the main cortical sensorimotor regions 1% BOLD signal change can be detected at least in the 93% of the sub-volumes, and almost 100% of the sub-volumes are suitable for 2% signal change detection. The integrated experimental set-up will therefore allows to detect FES induced movements fMRI maps simultaneously with kinematic acquisitions so as to investigate FES-based rehabilitation treatments contribution at CNS level. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

An fMRI compatible wrist robotic interface to study brain development in neonates.

PubMed

Allievi, A G; Melendez-Calderon, A; Arichi, T; Edwards, A D; Burdet, E

2013-06-01

A comprehensive understanding of the mechanisms that underlie brain development in premature infants and newborns is crucial for the identification of interventional therapies and rehabilitative strategies. fMRI has the potential to identify such mechanisms, but standard techniques used in adults cannot be implemented in infant studies in a straightforward manner. We have developed an MR safe wrist stimulating robot to systematically investigate the functional brain activity related to both spontaneous and induced wrist movements in premature babies using fMRI. We present the technical aspects of this development and the results of validation experiments. Using the device, the cortical activity associated with both active and passive finger movements were reliably identified in a healthy adult subject. In two preterm infants, passive wrist movements induced a well localized positive BOLD response in the contralateral somatosensory cortex. Furthermore, in a single preterm infant, spontaneous wrist movements were found to be associated with an adjacent cluster of activity, at the level of the infant's primary motor cortex. The described device will allow detailed and objective fMRI studies of somatosensory and motor system development during early human life and following neonatal brain injury.

Age differences in the motor control of speech: An fMRI study of healthy aging.

PubMed

Tremblay, Pascale; Sato, Marc; Deschamps, Isabelle

2017-05-01

Healthy aging is associated with a decline in cognitive, executive, and motor processes that are concomitant with changes in brain activation patterns, particularly at high complexity levels. While speech production relies on all these processes, and is known to decline with age, the mechanisms that underlie these changes remain poorly understood, despite the importance of communication on everyday life. In this cross-sectional group study, we investigated age differences in the neuromotor control of speech production by combining behavioral and functional magnetic resonance imaging (fMRI) data. Twenty-seven healthy adults underwent fMRI while performing a speech production task consisting in the articulation of nonwords of different sequential and motor complexity. Results demonstrate strong age differences in movement time (MT), with longer and more variable MT in older adults. The fMRI results revealed extensive age differences in the relationship between BOLD signal and MT, within and outside the sensorimotor system. Moreover, age differences were also found in relation to sequential complexity within the motor and attentional systems, reflecting both compensatory and de-differentiation mechanisms. At very high complexity level (high motor complexity and high sequence complexity), age differences were found in both MT data and BOLD response, which increased in several sensorimotor and executive control areas. Together, these results suggest that aging of motor and executive control mechanisms may contribute to age differences in speech production. These findings highlight the importance of studying functionally relevant behavior such as speech to understand the mechanisms of human brain aging. Hum Brain Mapp 38:2751-2771, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Causal Inference for fMRI Time Series Data with Systematic Errors of Measurement in a Balanced On/Off Study of Social Evaluative Threat.

PubMed

Sobel, Michael E; Lindquist, Martin A

2014-07-01

Functional magnetic resonance imaging (fMRI) has facilitated major advances in understanding human brain function. Neuroscientists are interested in using fMRI to study the effects of external stimuli on brain activity and causal relationships among brain regions, but have not stated what is meant by causation or defined the effects they purport to estimate. Building on Rubin's causal model, we construct a framework for causal inference using blood oxygenation level dependent (BOLD) fMRI time series data. In the usual statistical literature on causal inference, potential outcomes, assumed to be measured without systematic error, are used to define unit and average causal effects. However, in general the potential BOLD responses are measured with stimulus dependent systematic error. Thus we define unit and average causal effects that are free of systematic error. In contrast to the usual case of a randomized experiment where adjustment for intermediate outcomes leads to biased estimates of treatment effects (Rosenbaum, 1984), here the failure to adjust for task dependent systematic error leads to biased estimates. We therefore adjust for systematic error using measured "noise covariates" , using a linear mixed model to estimate the effects and the systematic error. Our results are important for neuroscientists, who typically do not adjust for systematic error. They should also prove useful to researchers in other areas where responses are measured with error and in fields where large amounts of data are collected on relatively few subjects. To illustrate our approach, we re-analyze data from a social evaluative threat task, comparing the findings with results that ignore systematic error.

An fMRI study of working memory in first-degree unaffected relatives of schizophrenia patients.

PubMed

Meda, Shashwath A; Bhattarai, Manish; Morris, Nicholas A; Astur, Robert S; Calhoun, Vince D; Mathalon, Daniel H; Kiehl, Kent A; Pearlson, Godfrey D

2008-09-01

Identifying intermediate phenotypes of genetically complex psychiatric illnesses such as schizophrenia is important. First-degree relatives of persons with schizophrenia have increased genetic risk for the disorder and tend to show deficits on working memory (WM) tasks. An open question is the relationship between such behavioral endophenotypes and the corresponding brain activation patterns revealed during functional imaging. We measured task performance during a Sternberg WM task and used functional magnetic resonance imaging (fMRI) to assess whether 23 non-affected first-degree relatives showed altered performance and functional activation compared to 43 matched healthy controls. We predicted that a significant proportion of unaffected first-degree relatives would show either aberrant task performance and/or abnormal related fMRI blood oxygen level dependent (BOLD) patterns. While task performance in the relatives was not different than that of controls they were significantly slower in responding to probes., Schizophrenia relatives displayed reduced activation, most markedly in bilateral dorsolateral/ventrolateral (DLPFC/VLPFC) prefrontal and posterior parietal cortex when encoding stimuli and in bilateral DLPFC and parietal areas during response selection. Additionally, fMRI differences in both conditions were modulated by load, with a parametric increase in between-group differences with load in several key regions during encoding and an opposite effect during response selection.

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

fMRI and EEG responses to periodic visual stimulation.

PubMed

Guy, C N; ffytche, D H; Brovelli, A; Chumillas, J

1999-08-01

EEG/VEP and fMRI responses to periodic visual stimulation are reported. The purpose of these experiments was to look for similar patterns in the time series produced by each method to help understand the relationship between the two. The stimulation protocol was the same for both sets of experiments and consisted of five complete cycles of checkerboard pattern reversal at 1.87 Hz for 30 s followed by 30 s of a stationary checkerboard. The fMRI data was analyzed using standard methods, while the EEG was analyzed with a new measurement of activation-the VEPEG. Both VEPEG and fMRI time series contain the fundamental frequency of the stimulus and quasi harmonic components-an unexplained double frequency commonly found in fMRI data. These results have prompted a reappraisal of the methods for analyzing fMRI data and have suggested a connection between our findings and much older published invasive electrophysiological measurements of blood flow and the partial pressures of oxygen and carbon dioxide. Overall our new analysis suggests that fMRI signals are strongly dependant on hydraulic blood flow effects. We distinguish three categories of fMRI signal corresponding to: focal activated regions of brain tissue; diffuse nonspecific regions of steal; and major cerebral vessels of arterial supply or venous drainage. Each category of signal has its own finger print in frequency, amplitude, and phase. Finally, we put forward the hypothesis that modulations in blood flow are not only the consequence but are also the cause of modulations in functional activity. Copyright 1999 Academic Press.

BOLD delay times using group delay in sickle cell disease

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

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

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

PubMed

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

2007-06-01

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.

Paced respiration with end-expiration technique offers superior BOLD signal repeatability for breath-hold studies.

PubMed

Scouten, A; Schwarzbauer, C

2008-11-01

As a simple, non-invasive method of blood oxygenation level-dependent (BOLD) signal calibration, the breath-hold task offers considerable potential for the quantification of neuronal activity from functional magnetic resonance imaging (fMRI) measurements. With an aim to improve the precision of this calibration method, the impact of respiratory rate control on the BOLD signal achieved with the breath-hold task was investigated. In addition to self-paced breathing, three different computer-paced breathing rates were imposed during the periods between end-expiration breath-hold blocks. The resulting BOLD signal timecourses and statistical activation maps were compared in eleven healthy human subjects. Results indicate that computer-paced respiration produces a larger peak BOLD signal increase with breath-hold than self-paced breathing, in addition to lower variability between trials. This is due to the more significant post-breath-hold signal undershoot present in self-paced runs, a characteristic which confounds the definition of baseline and is difficult to accurately model. Interestingly, the specific respiratory rate imposed between breath-hold periods generally does not have a statistically significant impact on the BOLD signal change. This result can be explained by previous reports of humans adjusting their inhalation depth to compensate for changes in rate, with the end-goal of maintaining homeostatic ventilation. The advantage of using end-expiration relative to end-inspiration breath-hold is apparent in view of the high repeatability of the BOLD signal in the present study, which does not suffer from the previously reported high variability associated with uncontrolled inspiration depth when using the end-inspiration technique.

Cholinergic enhancement reduces functional connectivity and BOLD variability in visual extrastriate cortex during selective attention.

PubMed

Ricciardi, Emiliano; Handjaras, Giacomo; Bernardi, Giulio; Pietrini, Pietro; Furey, Maura L

2013-01-01

Enhancing cholinergic function improves performance on various cognitive tasks and alters neural responses in task specific brain regions. We have hypothesized that the changes in neural activity observed during increased cholinergic function reflect an increase in neural efficiency that leads to improved task performance. The current study tested this hypothesis by assessing neural efficiency based on cholinergically-mediated effects on regional brain connectivity and BOLD signal variability. Nine subjects participated in a double-blind, placebo-controlled crossover fMRI study. Following an infusion of physostigmine (1 mg/h) or placebo, echo-planar imaging (EPI) was conducted as participants performed a selective attention task. During the task, two images comprised of superimposed pictures of faces and houses were presented. Subjects were instructed periodically to shift their attention from one stimulus component to the other and to perform a matching task using hand held response buttons. A control condition included phase-scrambled images of superimposed faces and houses that were presented in the same temporal and spatial manner as the attention task; participants were instructed to perform a matching task. Cholinergic enhancement improved performance during the selective attention task, with no change during the control task. Functional connectivity analyses showed that the strength of connectivity between ventral visual processing areas and task-related occipital, parietal and prefrontal regions reduced significantly during cholinergic enhancement, exclusively during the selective attention task. Physostigmine administration also reduced BOLD signal temporal variability relative to placebo throughout temporal and occipital visual processing areas, again during the selective attention task only. Together with the observed behavioral improvement, the decreases in connectivity strength throughout task-relevant regions and BOLD variability within stimulus

Cholinergic enhancement reduces functional connectivity and BOLD variability in visual extrastriate cortex during selective attention

PubMed Central

Ricciardi, Emiliano; Handjaras, Giacomo; Bernardi, Giulio; Pietrini, Pietro; Furey, Maura L.

2012-01-01

Enhancing cholinergic function improves performance on various cognitive tasks and alters neural responses in task specific brain regions. Previous findings by our group strongly suggested that the changes in neural activity observed during increased cholinergic function may reflect an increase in neural efficiency that leads to improved task performance. The current study was designed to assess the effects of cholinergic enhancement on regional brain connectivity and BOLD signal variability. Nine subjects participated in a double-blind, placebo-controlled crossover functional magnetic resonance imaging (fMRI) study. Following an infusion of physostigmine (1mg/hr) or placebo, echo-planar imaging (EPI) was conducted as participants performed a selective attention task. During the task, two images comprised of superimposed pictures of faces and houses were presented. Subjects were instructed periodically to shift their attention from one stimulus component to the other and to perform a matching task using hand held response buttons. A control condition included phase-scrambled images of superimposed faces and houses that were presented in the same temporal and spatial manner as the attention task; participants were instructed to perform a matching task. Cholinergic enhancement improved performance during the selective attention task, with no change during the control task. Functional connectivity analyses showed that the strength of connectivity between ventral visual processing areas and task-related occipital, parietal and prefrontal regions was reduced significantly during cholinergic enhancement, exclusively during the selective attention task. Cholinergic enhancement also reduced BOLD signal temporal variability relative to placebo throughout temporal and occipital visual processing areas, again during the selective attention task only. Together with the observed behavioral improvement, the decreases in connectivity strength throughout task-relevant regions and

Improving temporal resolution in fMRI using a 3D spiral acquisition and low rank plus sparse (L+S) reconstruction.

PubMed

Petrov, Andrii Y; Herbst, Michael; Andrew Stenger, V

2017-08-15

Rapid whole-brain dynamic Magnetic Resonance Imaging (MRI) is of particular interest in Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI). Faster acquisitions with higher temporal sampling of the BOLD time-course provide several advantages including increased sensitivity in detecting functional activation, the possibility of filtering out physiological noise for improving temporal SNR, and freezing out head motion. Generally, faster acquisitions require undersampling of the data which results in aliasing artifacts in the object domain. A recently developed low-rank (L) plus sparse (S) matrix decomposition model (L+S) is one of the methods that has been introduced to reconstruct images from undersampled dynamic MRI data. The L+S approach assumes that the dynamic MRI data, represented as a space-time matrix M, is a linear superposition of L and S components, where L represents highly spatially and temporally correlated elements, such as the image background, while S captures dynamic information that is sparse in an appropriate transform domain. This suggests that L+S might be suited for undersampled task or slow event-related fMRI acquisitions because the periodic nature of the BOLD signal is sparse in the temporal Fourier transform domain and slowly varying low-rank brain background signals, such as physiological noise and drift, will be predominantly low-rank. In this work, as a proof of concept, we exploit the L+S method for accelerating block-design fMRI using a 3D stack of spirals (SoS) acquisition where undersampling is performed in the k z -t domain. We examined the feasibility of the L+S method to accurately separate temporally correlated brain background information in the L component while capturing periodic BOLD signals in the S component. We present results acquired in control human volunteers at 3T for both retrospective and prospectively acquired fMRI data for a visual activation block-design task. We show that a SoS fMRI acquisition with an

Neuronal synchrony and the relation between the blood-oxygen-level dependent response and the local field potential

PubMed Central

Nguyen, Mai; Winawer, Jonathan

2017-01-01

The most widespread measures of human brain activity are the blood-oxygen-level dependent (BOLD) signal and surface field potential. Prior studies report a variety of relationships between these signals. To develop an understanding of how to interpret these signals and the relationship between them, we developed a model of (a) neuronal population responses and (b) transformations from neuronal responses into the functional magnetic resonance imaging (fMRI) BOLD signal and electrocorticographic (ECoG) field potential. Rather than seeking a transformation between the two measures directly, this approach interprets each measure with respect to the underlying neuronal population responses. This model accounts for the relationship between BOLD and ECoG data from human visual cortex in V1, V2, and V3, with the model predictions and data matching in three ways: across stimuli, the BOLD amplitude and ECoG broadband power were positively correlated, the BOLD amplitude and alpha power (8–13 Hz) were negatively correlated, and the BOLD amplitude and narrowband gamma power (30–80 Hz) were uncorrelated. The two measures provide complementary information about human brain activity, and we infer that features of the field potential that are uncorrelated with BOLD arise largely from changes in synchrony, rather than level, of neuronal activity. PMID:28742093

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

Presurgical motor, somatosensory and language fMRI: Technical feasibility and limitations in 491 patients over 13 years.

PubMed

Tyndall, Anthony J; Reinhardt, Julia; Tronnier, Volker; Mariani, Luigi; Stippich, Christoph

2017-01-01

To analyse the long-term feasibility and limitations of presurgical fMRI in a cohort of tumour and epilepsy patients with different MR-scanners at 1.5 and 3.0 T. Four hundred and ninety-one consecutive patients undergoing presurgical fMRI between 2000 and 2012 on five different MR-scanners using established paradigms and semi-automated data processing were included. Success rates of task performance and BOLD-activation were determined for motor and somatosensory somatotopic mapping and language localisation. Procedural success, failures and imaging artifacts were analysed. MR-field strengths were compared. Two thousand three hundred fifteen of 2348 (98.6 %) attempted paradigms (1033 motor, 1220 speech, 95 somatosensory) were successfully performed. 100 paradigms (4.3 %) were repetition runs. 23 speech, 6 motor and 2 sensory paradigms failed for non-compliance and technical issues. Most language paradigm failures were noted in overt sentence generation. Average significant BOLD-activation was higher for motor than language paradigms (95.8 vs. 81.6 %). Most language paradigms showed significantly higher activation rates at 3 T compared to 1.5 T, whereas no significant difference was found for motor paradigms. fMRI proved very robust for the presurgical localisation of the different motor and somatosensory body representations, as well as Broca's and Wernicke's language areas across different MR-scanners at 1.5 and 3.0 T over 13 years. • Standardised presurgical motor and language fMRI is robust across various MRI platforms. • Motor fMRI is less dependent on field strength than language fMRI. • fMRI task failures are relatively low and are reduced by paradigm repetition.

EEG-Informed fMRI: A Review of Data Analysis Methods

PubMed Central

Abreu, Rodolfo; Leal, Alberto; Figueiredo, Patrícia

2018-01-01

The simultaneous acquisition of electroencephalography (EEG) with functional magnetic resonance imaging (fMRI) is a very promising non-invasive technique for the study of human brain function. Despite continuous improvements, it remains a challenging technique, and a standard methodology for data analysis is yet to be established. Here we review the methodologies that are currently available to address the challenges at each step of the data analysis pipeline. We start by surveying methods for pre-processing both EEG and fMRI data. On the EEG side, we focus on the correction for several MR-induced artifacts, particularly the gradient and pulse artifacts, as well as other sources of EEG artifacts. On the fMRI side, we consider image artifacts induced by the presence of EEG hardware inside the MR scanner, and the contamination of the fMRI signal by physiological noise of non-neuronal origin, including a review of several approaches to model and remove it. We then provide an overview of the approaches specifically employed for the integration of EEG and fMRI when using EEG to predict the blood oxygenation level dependent (BOLD) fMRI signal, the so-called EEG-informed fMRI integration strategy, the most commonly used strategy in EEG-fMRI research. Finally, we systematically review methods used for the extraction of EEG features reflecting neuronal phenomena of interest. PMID:29467634

Improved sensitivity and specificity for resting state and task fMRI with multiband multi-echo EPI compared to multi-echo EPI at 7 T.

PubMed

Boyacioğlu, Rasim; Schulz, Jenni; Koopmans, Peter J; Barth, Markus; Norris, David G

2015-10-01

A multiband multi-echo (MBME) sequence is implemented and compared to a matched standard multi-echo (ME) protocol to investigate the potential improvement in sensitivity and spatial specificity at 7 T for resting state and task fMRI. ME acquisition is attractive because BOLD sensitivity is less affected by variation in T2*, and because of the potential for separating BOLD and non-BOLD signal components. MBME further reduces TR thus increasing the potential reduction in physiological noise. In this study we used FSL-FIX to clean ME and MBME resting state and task fMRI data (both 3.5mm isotropic). After noise correction, the detection of resting state networks improves with more non-artifactual independent components being observed. Additional activation clusters for task data are discovered for MBME data (increased sensitivity) whereas existing clusters become more localized for resting state (improved spatial specificity). The results obtained indicate that MBME is superior to ME at high field strengths. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigating the Group-Level Impact of Advanced Dual-Echo fMRI Combinations

PubMed Central

Kettinger, Ádám; Hill, Christopher; Vidnyánszky, Zoltán; Windischberger, Christian; Nagy, Zoltán

2016-01-01

Multi-echo fMRI data acquisition has been widely investigated and suggested to optimize sensitivity for detecting the BOLD signal. Several methods have also been proposed for the combination of data with different echo times. The aim of the present study was to investigate whether these advanced echo combination methods provide advantages over the simple averaging of echoes when state-of-the-art group-level random-effect analyses are performed. Both resting-state and task-based dual-echo fMRI data were collected from 27 healthy adult individuals (14 male, mean age = 25.75 years) using standard echo-planar acquisition methods at 3T. Both resting-state and task-based data were subjected to a standard image pre-processing pipeline. Subsequently the two echoes were combined as a weighted average, using four different strategies for calculating the weights: (1) simple arithmetic averaging, (2) BOLD sensitivity weighting, (3) temporal-signal-to-noise ratio weighting and (4) temporal BOLD sensitivity weighting. Our results clearly show that the simple averaging of data with the different echoes is sufficient. Advanced echo combination methods may provide advantages on a single-subject level but when considering random-effects group level statistics they provide no benefit regarding sensitivity (i.e., group-level t-values) compared to the simple echo-averaging approach. One possible reason for the lack of clear advantages may be that apart from increasing the average BOLD sensitivity at the single-subject level, the advanced weighted averaging methods also inflate the inter-subject variance. As the echo combination methods provide very similar results, the recommendation is to choose between them depending on the availability of time for collecting additional resting-state data or whether subject-level or group-level analyses are planned. PMID:28018165

Anatomical and functional assemblies of brain BOLD oscillations

PubMed Central

Baria, Alexis T.; Baliki, Marwan N.; Parrish, Todd; Apkarian, A. Vania

2011-01-01

Brain oscillatory activity has long been thought to have spatial properties, the details of which are unresolved. Here we examine spatial organizational rules for the human brain oscillatory activity as measured by blood oxygen level-dependent (BOLD). Resting state BOLD signal was transformed into frequency space (Welch’s method), averaged across subjects, and its spatial distribution studied as a function of four frequency bands, spanning the full bandwidth of BOLD. The brain showed anatomically constrained distribution of power for each frequency band. This result was replicated on a repository dataset of 195 subjects. Next, we examined larger-scale organization by parceling the neocortex into regions approximating Brodmann Areas (BAs). This indicated that BAs of simple function/connectivity (unimodal), vs. complex properties (transmodal), are dominated by low frequency BOLD oscillations, and within the visual ventral stream we observe a graded shift of power to higher frequency bands for BAs further removed from the primary visual cortex (increased complexity), linking frequency properties of BOLD to hodology. Additionally, BOLD oscillation properties for the default mode network demonstrated that it is composed of distinct frequency dependent regions. When the same analysis was performed on a visual-motor task, frequency-dependent global and voxel-wise shifts in BOLD oscillations could be detected at brain sites mostly outside those identified with general linear modeling. Thus, analysis of BOLD oscillations in full bandwidth uncovers novel brain organizational rules, linking anatomical structures and functional networks to characteristic BOLD oscillations. The approach also identifies changes in brain intrinsic properties in relation to responses to external inputs. PMID:21613505

To be so bold: boldness is repeatable and related to within individual behavioural variability in North Island robins.

PubMed

He, Ruchuan; Pagani-Núñez, Emilio; Chevallier, Clément; Barnett, Craig R A

2017-07-01

Behavioural research traditionally focusses on the mean responses of a group of individuals rather than variation in behaviour around the mean or among individuals. However, examining the variation in behaviour among and within individuals may also yield important insights into the evolution and maintenance of behaviour. Repeatability is the most commonly used measure of variability among individuals in behavioural research. However, there are other forms of variation within populations that have received less attention. One such measure is intraindividual variation in behaviour (IIV), which is a short-term fluctuation of within-individual behaviour. Such variation in behaviour might be important during interactions because it could decrease the ability of conspecific and heterospecific individuals to predict the behaviour of the subject, thus increasing the cost of the interaction. In this experiment, we made repeated measures of the latency of North Island robins to attack a prey in a novel situation (a form of boldness) and examined (i) repeatability of boldness (the propensity to take a risk), (ii) IIV of boldness, and (iii) whether there was a significant relationship between these two traits (a behavioural syndrome). We found that boldness was highly repeatable, that there were high levels of IIV in boldness, and that there was a negative relationship between boldness and IIV in boldness. This suggests that despite high levels of repeatability for this behaviour, there were also still significant differences in IIV among different individuals within the population. Moreover, bolder individuals had significantly less IIV in their boldness, which suggests that they were forming routines (which reduces behavioural variability) compared to shyer individuals. Our results definitively demonstrate that IIV itself varies across individuals and is linked with key behavioural traits, and we argue for the importance of future studies aimed at understanding its causes

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

PubMed

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

2015-07-01

Studies of visual-spatial attention typically use instructional cues to direct attention to a relevant location, but in everyday vision, attention is often focused volitionally, in the absence of external signals. Although investigations of cued attention comprise hundreds of behavioral and physiological studies, remarkably few studies of voluntary attention have addressed the challenging question of how spatial attention is initiated and controlled in the absence of external instructions, which we refer to as willed attention. To explore this question, we employed a trial-by-trial spatial attention task using electroencephalography and functional magnetic resonance imaging (fMRI). The fMRI results reveal a unique network of brain regions for willed attention that includes the anterior cingulate cortex, left middle frontal gyrus (MFG), and the left and right anterior insula (AI). We also observed two event-related potentials (ERPs) associated with willed attention; one with a frontal distribution occurring 250-350 ms postdecision cue onset (EWAC: Early Willed Attention Component), and another occurring between 400 and 800 ms postdecision-cue onset (WAC: Willed Attention Component). In addition, each ERP component uniquely correlated across subjects with different willed attention-specific sites of BOLD activation. The EWAC was correlated with the willed attention-specific left AI and left MFG activations and the later WAC was correlated only with left AI. These results offer a comprehensive and novel view of the electrophysiological and anatomical profile of willed attention and further illustrate the relationship between scalp-recorded ERPs and the BOLD response. © 2015 Wiley Periodicals, Inc.

Neural Correlates of Facial Mimicry: Simultaneous Measurements of EMG and BOLD Responses during Perception of Dynamic Compared to Static Facial Expressions

PubMed Central

Rymarczyk, Krystyna; Żurawski, Łukasz; Jankowiak-Siuda, Kamila; Szatkowska, Iwona

2018-01-01

Facial mimicry (FM) is an automatic response to imitate the facial expressions of others. However, neural correlates of the phenomenon are as yet not well established. We investigated this issue using simultaneously recorded EMG and BOLD signals during perception of dynamic and static emotional facial expressions of happiness and anger. During display presentations, BOLD signals and zygomaticus major (ZM), corrugator supercilii (CS) and orbicularis oculi (OO) EMG responses were recorded simultaneously from 46 healthy individuals. Subjects reacted spontaneously to happy facial expressions with increased EMG activity in ZM and OO muscles and decreased CS activity, which was interpreted as FM. Facial muscle responses correlated with BOLD activity in regions associated with motor simulation of facial expressions [i.e., inferior frontal gyrus, a classical Mirror Neuron System (MNS)]. Further, we also found correlations for regions associated with emotional processing (i.e., insula, part of the extended MNS). It is concluded that FM involves both motor and emotional brain structures, especially during perception of natural emotional expressions. PMID:29467691

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

FAIR exempting separate T (1) measurement (FAIREST): a novel technique for online quantitative perfusion imaging and multi-contrast fMRI.

PubMed

Lai, S; Wang, J; Jahng, G H

2001-01-01

A new pulse sequence, dubbed FAIR exempting separate T(1) measurement (FAIREST) in which a slice-selective saturation recovery acquisition is added in addition to the standard FAIR (flow-sensitive alternating inversion recovery) scheme, was developed for quantitative perfusion imaging and multi-contrast fMRI. The technique allows for clean separation between and thus simultaneous assessment of BOLD and perfusion effects, whereas quantitative cerebral blood flow (CBF) and tissue T(1) values are monitored online. Online CBF maps were obtained using the FAIREST technique and the measured CBF values were consistent with the off-line CBF maps obtained from using the FAIR technique in combination with a separate sequence for T(1) measurement. Finger tapping activation studies were carried out to demonstrate the applicability of the FAIREST technique in a typical fMRI setting for multi-contrast fMRI. The relative CBF and BOLD changes induced by finger-tapping were 75.1 +/- 18.3 and 1.8 +/- 0.4%, respectively, and the relative oxygen consumption rate change was 2.5 +/- 7.7%. The results from correlation of the T(1) maps with the activation images on a pixel-by-pixel basis show that the mean T(1) value of the CBF activation pixels is close to the T(1) of gray matter while the mean T(1) value of the BOLD activation pixels is close to the T(1) range of blood and cerebrospinal fluid. Copyright 2001 John Wiley & Sons, Ltd.

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

PubMed

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

2009-01-01

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

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

PubMed

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

2007-02-07

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

Relationship between fMRI response during a nonverbal memory task and marijuana use in college students.

PubMed

Dager, Alecia D; Tice, Madelynn R; Book, Gregory A; Tennen, Howard; Raskin, Sarah A; Austad, Carol S; Wood, Rebecca M; Fallahi, Carolyn R; Hawkins, Keith A; Pearlson, Godfrey D

2018-04-26

Marijuana (MJ) is widely used among college students, with peak use between ages 18-22. Research suggests memory dysfunction in adolescent and young adult MJ users, but the neural correlates are unclear. We examined functional magnetic resonance imaging (fMRI) response during a memory task among college students with varying degrees of MJ involvement. Participants were 64 college students, ages 18-20, who performed a visual encoding and recognition task during fMRI. MJ use was ascertained for 3 months prior to scanning; 27 individuals reported past 3-month MJ use, and 33 individuals did not. fMRI response was modeled during encoding based on whether targets were subsequently recognized (correct encoding), and during recognition based on target identification (hits). fMRI response in left and right inferior frontal gyrus (IFG) and hippocampal regions of interest was examined between MJ users and controls. There were no group differences between MJ users and controls on fMRI response during encoding, although single sample t-tests revealed that MJ users failed to activate the hippocampus. During recognition, MJ users showed less fMRI response than controls in right hippocampus (Cohen's d = 0.55), left hippocampus (Cohen's d = 0.67) and left IFG (Cohen's d = 0.61). Heavier MJ involvement was associated with lower fMRI response in left hippocampus and left IFG. This study provides evidence of MJ-related prefrontal and hippocampal dysfunction during recognition memory in college students. These findings may contribute to our previously identified decrements in academic performance in college MJ users and could have substantial implications for academic and occupational functioning. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of fMRI and PEPSI during language processing in children.

PubMed

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

2001-02-01

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

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

Iterative approach of dual regression with a sparse prior enhances the performance of independent component analysis for group functional magnetic resonance imaging (fMRI) data.

PubMed

Kim, Yong-Hwan; Kim, Junghoe; Lee, Jong-Hwan

2012-12-01

This study proposes an iterative dual-regression (DR) approach with sparse prior regularization to better estimate an individual's neuronal activation using the results of an independent component analysis (ICA) method applied to a temporally concatenated group of functional magnetic resonance imaging (fMRI) data (i.e., Tc-GICA method). An ordinary DR approach estimates the spatial patterns (SPs) of neuronal activation and corresponding time courses (TCs) specific to each individual's fMRI data with two steps involving least-squares (LS) solutions. Our proposed approach employs iterative LS solutions to refine both the individual SPs and TCs with an additional a priori assumption of sparseness in the SPs (i.e., minimally overlapping SPs) based on L(1)-norm minimization. To quantitatively evaluate the performance of this approach, semi-artificial fMRI data were created from resting-state fMRI data with the following considerations: (1) an artificially designed spatial layout of neuronal activation patterns with varying overlap sizes across subjects and (2) a BOLD time series (TS) with variable parameters such as onset time, duration, and maximum BOLD levels. To systematically control the spatial layout variability of neuronal activation patterns across the "subjects" (n=12), the degree of spatial overlap across all subjects was varied from a minimum of 1 voxel (i.e., 0.5-voxel cubic radius) to a maximum of 81 voxels (i.e., 2.5-voxel radius) across the task-related SPs with a size of 100 voxels for both the block-based and event-related task paradigms. In addition, several levels of maximum percentage BOLD intensity (i.e., 0.5, 1.0, 2.0, and 3.0%) were used for each degree of spatial overlap size. From the results, the estimated individual SPs of neuronal activation obtained from the proposed iterative DR approach with a sparse prior showed an enhanced true positive rate and reduced false positive rate compared to the ordinary DR approach. The estimated TCs of the

Time course based artifact identification for independent components of resting-state FMRI.

PubMed

Rummel, Christian; Verma, Rajeev Kumar; Schöpf, Veronika; Abela, Eugenio; Hauf, Martinus; Berruecos, José Fernando Zapata; Wiest, Roland

2013-01-01

In functional magnetic resonance imaging (fMRI) coherent oscillations of the blood oxygen level-dependent (BOLD) signal can be detected. These arise when brain regions respond to external stimuli or are activated by tasks. The same networks have been characterized during wakeful rest when functional connectivity of the human brain is organized in generic resting-state networks (RSN). Alterations of RSN emerge as neurobiological markers of pathological conditions such as altered mental state. In single-subject fMRI data the coherent components can be identified by blind source separation of the pre-processed BOLD data using spatial independent component analysis (ICA) and related approaches. The resulting maps may represent physiological RSNs or may be due to various artifacts. In this methodological study, we propose a conceptually simple and fully automatic time course based filtering procedure to detect obvious artifacts in the ICA output for resting-state fMRI. The filter is trained on six and tested on 29 healthy subjects, yielding mean filter accuracy, sensitivity and specificity of 0.80, 0.82, and 0.75 in out-of-sample tests. To estimate the impact of clearly artifactual single-subject components on group resting-state studies we analyze unfiltered and filtered output with a second level ICA procedure. Although the automated filter does not reach performance values of visual analysis by human raters, we propose that resting-state compatible analysis of ICA time courses could be very useful to complement the existing map or task/event oriented artifact classification algorithms.

Different cerebral connectivity of obese and lean children studied with fMRI

NASA Astrophysics Data System (ADS)

Anaya Moreno, Maryan A.; Hernández López, Javier M.; Hidalgo Tobón, Silvia; Dies Suarez, Pilar; Barragán Pérez, Eduardo; De Celis Alonso, Benito

2014-11-01

In this work we studied the different fMRI brain activations and connections between normal weighted (NW) and obese (OB) infants for different types of food odours. A total of 30 right handed volunteers (infants 8.4±2 years) of both sexes were studied. Infants were divided in two group, one with BMI between 19 and 24 kg/m2 and the other with BMI over 30 kg/m2. The first part of this project consisted of a study in which fMRI BOLD activations to pleasant, neutral and healthy food was performed on both groups. Cerebellum regions were found to be more active in the NW group over the OB when presented with odour cues. OB volunteers in contrast showed larger activations in cingulate cortex structures than their NW counterparts when presented with food odours. The second part of this study performed connectivity studies (ROI to ROI) comparing both groups for each smell. The NW group presented for the onion smell a strong reward anticipation connection between the gustatory cortex and the cingulate cortex which the OB group did not have. In contrast the OB group presented strong orbitofrontal connections (decision making) with gustatory and somatosensory cortex when stimulated with the chocolate odour which the NW did not present. We can conclude that clear differences in fMRI BOLD activation as well as connectivity between the OB and NW groups were found. This points at a very different processing mechanisms of odour cues in infants. To our knowledge this study has never been performed before on infants.

Bayesian deconvolution of [corrected] fMRI data using bilinear dynamical systems.

PubMed

Makni, Salima; Beckmann, Christian; Smith, Steve; Woolrich, Mark

2008-10-01

In Penny et al. [Penny, W., Ghahramani, Z., Friston, K.J. 2005. Bilinear dynamical systems. Philos. Trans. R. Soc. Lond. B Biol. Sci. 360(1457) 983-993], a particular case of the Linear Dynamical Systems (LDSs) was used to model the dynamic behavior of the BOLD response in functional MRI. This state-space model, called bilinear dynamical system (BDS), is used to deconvolve the fMRI time series in order to estimate the neuronal response induced by the different stimuli of the experimental paradigm. The BDS model parameters are estimated using an expectation-maximization (EM) algorithm proposed by Ghahramani and Hinton [Ghahramani, Z., Hinton, G.E. 1996. Parameter Estimation for Linear Dynamical Systems. Technical Report, Department of Computer Science, University of Toronto]. In this paper we introduce modifications to the BDS model in order to explicitly model the spatial variations of the haemodynamic response function (HRF) in the brain using a non-parametric approach. While in Penny et al. [Penny, W., Ghahramani, Z., Friston, K.J. 2005. Bilinear dynamical systems. Philos. Trans. R. Soc. Lond. B Biol. Sci. 360(1457) 983-993] the relationship between neuronal activation and fMRI signals is formulated as a first-order convolution with a kernel expansion using basis functions (typically two or three), in this paper, we argue in favor of a spatially adaptive GLM in which a local non-parametric estimation of the HRF is performed. Furthermore, in order to overcome the overfitting problem typically associated with simple EM estimates, we propose a full Variational Bayes (VB) solution to infer the BDS model parameters. We demonstrate the usefulness of our model which is able to estimate both the neuronal activity and the haemodynamic response function in every voxel of the brain. We first examine the behavior of this approach when applied to simulated data with different temporal and noise features. As an example we will show how this method can be used to improve

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

PubMed

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

2013-01-01

Previous studies suggest that task-activated functional magnetic resonance imaging (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 Apolipoprotein E (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 (R(2) = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R(2) = .285; C index = .787), whereas the addition of EM did not (R(2) = .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.

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

PubMed Central

Luh, Wen-Ming; Talavage, Thomas M.

2010-01-01

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

Novel fMRI working memory paradigm accurately detects cognitive impairment in Multiple Sclerosis

PubMed Central

Nelson, Flavia; Akhtar, Mohammad A.; Zúñiga, Edward; Perez, Carlos A.; Hasan, Khader M.; Wilken, Jeffrey; Wolinsky, Jerry S.; Narayana, Ponnada A.; Steinberg, Joel L.

2016-01-01

Background Cognitive impairment (CI) cannot be diagnosed by MRI. Functional MRI (fMRI) paradigms such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory. Preliminary findings using I/DMT, showed differences in Blood Oxygenation Level Dependent (BOLD) activation between impaired (MSCI, n=12) and non-impaired (MSNI, n=9) MS patients. Objectives To confirm CI detection based on I/DMT’ BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and EDSS in magnitude of BOLD signal were also sought. Methods Fifty patients [EDSS mean (m) = 3.2, DD m =12 yr., age m =40yr.] underwent the Minimal Assessment of Cognitive Function in MS (MACFIMS) and the I/DMT. Working-memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS. Results 10 MSNI, 30 MSCI and 4 borderline patients were included in analyses. ANOVA showed MSNI had significantly greater WMa than MSCI, in the left (L) prefrontal cortex and L supplementary motor area (p = 0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas (p = 0.005, 0.004 respectively). Conclusion I/DMT-based BOLD activation detects CI in MS, larger studies are needed to confirm these findings. PMID:27613119

Activation of dorsolateral prefrontal cortex in a dual neuropsychological screening test: an fMRI approach.

PubMed

Tachibana, Atsumichi; Noah, J Adam; Bronner, Shaw; Ono, Yumie; Hirano, Yoshiyuki; Niwa, Masami; Watanabe, Kazuko; Onozuka, Minoru

2012-05-28

The Kana Pick-out Test (KPT), which uses Kana or Japanese symbols that represent syllables, requires parallel processing of discrete (pick-out) and continuous (reading) dual tasks. As a dual task, the KPT is thought to test working memory and executive function, particularly in the prefrontal cortex (PFC), and is widely used in Japan as a clinical screen for dementia. Nevertheless, there has been little neurological investigation into PFC activity during this test. We used functional magnetic resonance imaging (fMRI) to evaluate changes in the blood oxygenation level-dependent (BOLD) signal in young healthy adults during performance of a computerized KPT dual task (comprised of reading comprehension and picking out vowels) and compared it to its single task components (reading or vowel pick-out alone). Behavioral performance of the KPT degraded compared to its single task components. Performance of the KPT markedly increased BOLD signal intensity in the PFC, and also activated sensorimotor, parietal association, and visual cortex areas. In conjunction analyses, bilateral BOLD signal in the dorsolateral PFC (Brodmann's areas 45, 46) was present only in the KPT. Our results support the central bottleneck theory and suggest that the dorsolateral PFC is an important mediator of neural activity for both short-term storage and executive processes. Quantitative evaluation of the KPT with fMRI in healthy adults is the first step towards understanding the effects of aging or cognitive impairment on KPT performance.

The role of the DLPFC in inductive reasoning of MCI patients and normal agings: an fMRI study.

PubMed

Yang, YanHui; Liang, PeiPeng; Lu, ShengFu; Li, KunCheng; Zhong, Ning

2009-08-01

Previous studies of young people have revealed that the left dorsolateral prefrontal cortex (DLPFC) plays an important role in inductive reasoning. An fMRI experiment was performed in this study to examine whether the left DLPFC was involved in inductive reasoning of MCI patients and normal aging, and whether the activation pattern of this region was different between MCI patients and normal aging. The fMRI results indicated that MCI patients had no difference from normal aging in behavior performance (reaction time and accuracy) and the activation pattern of DLPFC. However, the BOLD response of the DLPFC region for MCI patients was weaker than that for normal aging, and the functional connectivity between the bilateral DLPFC regions for MCI patients was significantly higher than for normal aging. Taken together, these results indicated that DLPFC plays an important role in inductive reasoning of aging, and the functional abnormity of DLPFC may be an earlier marker of MCI before structural alterations.

Whole-brain functional magnetic resonance imaging mapping of acute nociceptive responses induced by formalin in rats using atlas registration-based event-related analysis.

PubMed

Shih, Yen-Yu I; Chen, You-Yin; Chen, Chiao-Chi V; Chen, Jyh-Cheng; Chang, Chen; Jaw, Fu-Shan

2008-06-01

Nociceptive neuronal activation in subcortical regions has not been well investigated in functional magnetic resonance imaging (fMRI) studies. The present report aimed to use the blood oxygenation level-dependent (BOLD) fMRI technique to map nociceptive responses in both subcortical and cortical regions by employing a refined data processing method, the atlas registration-based event-related (ARBER) analysis technique. During fMRI acquisition, 5% formalin (50 mul) was injected into the left hindpaw to induce nociception. ARBER was then used to normalize the data among rats, and images were analyzed using automatic selection of the atlas-based region of interest. It was found that formalin-induced nociceptive processing increased BOLD signals in both cortical and subcortical regions. The cortical activation was distributed over the cingulate, motor, somatosensory, insular, and visual cortices, and the subcortical activation involved the caudate putamen, hippocampus, periaqueductal gray, superior colliculus, thalamus, and hypothalamus. With the aid of ARBER, the present study revealed a detailed activation pattern that possibly indicated the recruitment of various parts of the nociceptive system. The results also demonstrated the utilization of ARBER in establishing an fMRI-based whole-brain nociceptive map. The formalin induced nociceptive images may serve as a template of central nociceptive responses, which can facilitate the future use of fMRI in evaluation of new drugs and preclinical therapies for pain. (c) 2008 Wiley-Liss, Inc.

Evolutionary Dynamics of Fearfulness and Boldness: A Stochastic Simulation Model

PubMed Central

Lu, Nan; Ji, Ting; Zhang, Jia-Hua; Sun, Yue-Hua; Tao, Yi

2012-01-01

A stochastic simulation model is investigated for the evolution of anti-predator behavior in birds. The main goal is to reveal the effects of population size, predation threats, and energy lost per escape on the evolutionary dynamics of fearfulness and boldness. Two pure strategies, fearfulness and boldness, are assumed to have different responses for the predator attacks and nonlethal disturbance. On the other hand, the co-existence mechanism of fearfulness and boldness is also considered. For the effects of total population size, predation threats, and energy lost per escape, our main results show that: (i) the fearful (bold) individuals will be favored in a small (large) population, i.e. in a small (large) population, the fearfulness (boldness) can be considered to be an ESS; (ii) in a population with moderate size, fearfulness would be favored under moderate predator attacks; and (iii) although the total population size is the most important factor for the evolutionary dynamics of both fearful and bold individuals, the small energy lost per escape enables the fearful individuals to have the ability to win the advantage even in a relatively large population. Finally, we show also that the co-existence of fearful and bold individuals is possible when the competitive interactions between individuals are introduced. PMID:22412859

Evolutionary dynamics of fearfulness and boldness: a stochastic simulation model.

PubMed

Lu, Nan; Ji, Ting; Zhang, Jia-Hua; Sun, Yue-Hua; Tao, Yi

2012-01-01

A stochastic simulation model is investigated for the evolution of anti-predator behavior in birds. The main goal is to reveal the effects of population size, predation threats, and energy lost per escape on the evolutionary dynamics of fearfulness and boldness. Two pure strategies, fearfulness and boldness, are assumed to have different responses for the predator attacks and nonlethal disturbance. On the other hand, the co-existence mechanism of fearfulness and boldness is also considered. For the effects of total population size, predation threats, and energy lost per escape, our main results show that: (i) the fearful (bold) individuals will be favored in a small (large) population, i.e. in a small (large) population, the fearfulness (boldness) can be considered to be an ESS; (ii) in a population with moderate size, fearfulness would be favored under moderate predator attacks; and (iii) although the total population size is the most important factor for the evolutionary dynamics of both fearful and bold individuals, the small energy lost per escape enables the fearful individuals to have the ability to win the advantage even in a relatively large population. Finally, we show also that the co-existence of fearful and bold individuals is possible when the competitive interactions between individuals are introduced.

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

PubMed

Ward, B Douglas; Mazaheri, Yousef

2006-12-15

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

Influence of Alcohol Use on Neural Response to Go/No-Go Task in College Drinkers

PubMed Central

Ahmadi, Aral; Pearlson, Godfrey D; Meda, Shashwath A; Dager, Alecia; Potenza, Marc N; Rosen, Rivkah; Austad, Carol S; Raskin, Sarah A; Fallahi, Carolyn R; Tennen, Howard; Wood, Rebecca M; Stevens, Michael C

2013-01-01

Impaired inhibition of prepotent motor response may represent an important risk factor for alcoholism. Alcohol use may also increase impulsive behavior, including impaired response inhibition. Little is known about the brain function underlying response inhibition among college-age drinkers based on their drinking patterns, despite college-age drinkers demonstrating high rates of alcohol-use disorders. Our major objective was to compare behavior and associated brain activity measured with fMRI during a response-inhibition task in matched heavy- and light-alcohol-drinking college students. Participants were light (N=36) and heavy (N=56) drinkers, aged 18–20 years. We characterized blood oxygen level-dependent (BOLD) responses, while participants performed an fMRI Go/No-Go task to quantify inhibitory behavior and brain activity. Behaviorally, group performance differences were observed for Go correct-hit and No-Go false-alarm reaction times with increased reaction times in heavy compared with light drinkers. During fMRI No-Go correct rejections, light drinkers exhibited greater BOLD response than did heavy drinkers in left supplementary motor area (SMA), bilateral parietal lobule, right hippocampus, bilateral middle frontal gyrus, left superior temporal gyrus, and cingulate gyrus/anterior cingulate cortex (Brodmann area 24). Group differences in Go/No-Go-related regional activations correlated with alcohol- and impulsivity-related measures. These findings suggest that heavy alcohol drinkers may have dysfunction in brain regions underlying attention and response inhibition, leading to diminished abilities to suppress prepotent responding. The extent to which these tendencies relate to impulsive decision-making and behaviors in real-life settings and may guide intervention development warrants additional investigation. PMID:23670589

From blood oxygenation level dependent (BOLD) signals to brain temperature maps.

PubMed

Sotero, Roberto C; Iturria-Medina, Yasser

2011-11-01

A theoretical framework is presented for converting Blood Oxygenation Level Dependent (BOLD) images to brain temperature maps, based on the idea that disproportional local changes in cerebral blood flow (CBF) as compared with cerebral metabolic rate of oxygen consumption (CMRO₂) during functional brain activity, lead to both brain temperature changes and the BOLD effect. Using an oxygen limitation model and a BOLD signal model, we obtain a transcendental equation relating CBF and CMRO₂ changes with the corresponding BOLD signal, which is solved in terms of the Lambert W function. Inserting this result in the dynamic bioheat equation describing the rate of temperature changes in the brain, we obtain a nonautonomous ordinary differential equation that depends on the BOLD response, which is solved numerically for each brain voxel. Temperature maps obtained from a real BOLD dataset registered in an attention to visual motion experiment were calculated, obtaining temperature variations in the range: (-0.15, 0.1) which is consistent with experimental results. The statistical analysis revealed that significant temperature activations have a similar distribution pattern than BOLD activations. An interesting difference was the activation of the precuneus in temperature maps, a region involved in visuospatial processing, an effect that was not observed on BOLD maps. Furthermore, temperature maps were more localized to gray matter regions than the original BOLD maps, showing less activated voxels in white matter and cerebrospinal fluid.

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

Plasticity of boldness in rainbow trout, Oncorhynchus mykiss: do hunger and predation influence risk-taking behaviour?

PubMed

Thomson, Jack S; Watts, Phillip C; Pottinger, Tom G; Sneddon, Lynne U

2012-05-01

Boldness, a measure of an individual's propensity for taking risks, is an important determinant of fitness but is not necessarily a fixed trait. Dependent upon an individual's state, and given certain contexts or challenges, individuals may be able to alter their inclination to be bold or shy in response. Furthermore, the degree to which individuals can modulate their behaviour has been linked with physiological responses to stress. Here we attempted to determine whether bold and shy rainbow trout, Oncorhynchus mykiss, can exhibit behavioural plasticity in response to changes in state (nutritional availability) and context (predation threat). Individual trout were initially assessed for boldness using a standard novel object paradigm; subsequently, each day for one week fish experienced either predictable, unpredictable, or no simulated predator threat in combination with a high (2% body weight) or low (0.15%) food ration, before being reassessed for boldness. Bold trout were generally more plastic, altering levels of neophobia and activity relevant to the challenge, whereas shy trout were more fixed and remained shy. Increased predation risk generally resulted in an increase in the expression of three candidate genes linked to boldness, appetite regulation and physiological stress responses - ependymin, corticotrophin releasing factor and GABA(A) - but did not produce a significant increase in plasma cortisol. The results suggest a divergence in the ability of bold and shy trout to alter their behavioural profiles in response to internal and exogenous factors, and have important implications for our understanding of the maintenance of different behavioural phenotypes in natural populations. Copyright © 2012 Elsevier Inc. All rights reserved.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.

PubMed

Carhart-Harris, Robin L; Erritzoe, David; Williams, Tim; Stone, James M; Reed, Laurence J; Colasanti, Alessandro; Tyacke, Robin J; Leech, Robert; Malizia, Andrea L; Murphy, Kevin; Hobden, Peter; Evans, John; Feilding, Amanda; Wise, Richard G; Nutt, David J

2012-02-07

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

PubMed Central

Carhart-Harris, Robin L.; Erritzoe, David; Williams, Tim; Stone, James M.; Reed, Laurence J.; Colasanti, Alessandro; Tyacke, Robin J.; Leech, Robert; Malizia, Andrea L.; Murphy, Kevin; Hobden, Peter; Evans, John; Feilding, Amanda; Wise, Richard G.; Nutt, David J.

2012-01-01

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition. PMID:22308440

Numb rats walk - a behavioural and fMRI comparison of mild and moderate spinal cord injury.

PubMed

Hofstetter, Christoph P; Schweinhardt, Petra; Klason, Tomas; Olson, Lars; Spenger, Christian

2003-12-01

Assessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD-signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague-Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hot plate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.

Anticipatory reward processing among cocaine-dependent individuals with and without concurrent methadone-maintenance treatment: Relationship to treatment response*

PubMed Central

Yip, Sarah W.; DeVito, Elise E.; Kober, Hedy; Worhunsky, Patrick D.; Carroll, Kathleen M.; Potenza, Marc N.

2016-01-01

Background Cocaine dependence among opioid-dependent methadone-maintained individuals is a significant public health problem and is particularly challenging to treat. The neurobiology of this clinically complex population has not been previously assessed using fMRI. Methods fMRI data from cocaine-dependent, methadone-maintained (CD-MM) patients (n=24), cocaine-dependent (CD) patients (n=20) and healthy comparison (HC; n=21) participants were acquired during monetary incentive delay task performance. All patients were scanned prior to treatment for cocaine dependence. Between-group differences in anticipatory reward and loss processing were assessed using whole-brain ANOVAs in SPM12 (pFWE<.05). Correlations between durations of abstinence during treatment and BOLD responses within the insula and caudate were also explored. Results Main effects of diagnostic group, primarily involving decreased BOLD responses among CD-MM patients in comparison to HCs, were observed during anticipatory reward and loss processing within regions of posterior cingulate cortex, precuneus, inferior frontal gyrus and dorsolateral prefrontal cortex. BOLD responses within the right caudate were negatively associated with percentage of cocaine-negative urines during treatment among CD-MM patients, but not among non-methadone-maintained CD patients. Conclusions These data suggest neurofunctional differences that may be related to treatment outcomes for behavioral therapies between cocaine-dependent individuals with and without methadone-maintenance treatment. These findings may relate to differences in treatment efficacies and to the elevated relapse rates observed in methadone-maintained populations. PMID:27430401

Physiologic underpinnings of negative BOLD cerebrovascular reactivity in brain ventricles.

PubMed

Thomas, Binu P; Liu, Peiying; Aslan, Sina; King, Kevin S; van Osch, Matthias J P; Lu, Hanzhang

2013-12-01

With a growing need for specific biomarkers in vascular diseases, there has been a surging interest in mapping cerebrovascular reactivity (CVR) of the brain. This index can be measured by conducting a hypercapnia challenge while acquiring blood-oxygenation-level-dependent (BOLD) signals. A BOLD signal increase with hypercapnia is the expected outcome and represents the majority of literature reports; in this work we report an intriguing observation of an apparently negative BOLD CVR response at 3T, during inhalation of 5% CO2 with balance medical air. These "negative-CVR" clusters were specifically located in the ventricular regions of the brain, where CSF is abundant and results in an intense baseline signal. The amplitude of the CVR response was -0.51±0.44% (N=14, age 26±4 years). We hypothesized that this observation might not be due to a decrease in oxygenation but rather a volume effect in which bright CSF signal is replaced by a less intensive blood signal as a result of vasodilation. To test this, we performed an inversion-recovery (IR) experiment to suppress the CSF signal (N=10, age 27±5 years). This maneuver in imaging sequence reversed the sign of the signal response (to 0.66±0.25%), suggesting that the volume change was the predominant reason for the apparently negative CVR in the BOLD experiment. Further support of this hypothesis was provided by a BOLD hyperoxia experiment, in which no voxels showed a negative response, presumably because vasodilation is not usually associated with this challenge. Absolute CBF response to hypercapnia was measured in a new group of subjects (N=8, age 29±7 years) and it was found that CBF in ventricular regions increased by 48% upon CO2 inhalation, suggesting that blood oxygenation most likely increased rather than decreased. The findings from this study suggest that CO2 inhalation results in the dilation of ventricular vessels accompanied by shrinkage in CSF space, which is responsible for the apparently negative

Heritability of boldness and aggressiveness in the zebrafish.

PubMed

Ariyomo, Tolulope O; Carter, Mauricio; Watt, Penelope J

2013-03-01

Behavioural traits that are consistent over time and in different contexts are often referred to as personality traits. These traits influence fitness because they play a major role in foraging, reproduction and survival, and so it is assumed that they have little or no additive genetic variance and, consequently, low heritability because, theoretically, they are under strong selection. Boldness and aggressiveness are two personality traits that have been shown to affect fitness. By crossing single males to multiple females, we estimated the heritability of boldness and aggressiveness in the zebrafish, Danio rerio. The additive genetic variance was statistically significant for both traits and the heritability estimates (95 % confidence intervals) for boldness and aggressiveness were 0.76 (0.49, 0.90) and 0.36 (0.10, 0.72) respectively. Furthermore, there were significant maternal effects accounting for 18 and 9 % of the proportion of phenotypic variance in boldness and aggressiveness respectively. This study shows that there is a significant level of genetic variation in this population that would allow these traits to evolve in response to selection.

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

PubMed Central

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

2016-01-01

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

Shyness and boldness in pumpkinseed sunfish: individual differences are context-specific.

PubMed

Coleman; Wilson

1998-10-01

Natural selection often promotes a mix of behavioural phenotypes in a population. Adaptive variation in the propensity to take risks might explain individual differences in shyness and boldness in humans and other species. It is often implicitly assumed that shyness and boldness are general personality traits expressed across many situations. From the evolutionary standpoint, however, individual differences that are adaptive in one context (e.g. predator defence) may not be adaptive in other contexts (e.g. exploration of the physical environment or intraspecific social interactions). We measured the context specificity of shyness and boldness in a natural population of juvenile pumpkinseed sunfish, Lepomis gibbosus, by exposing the fish to a potentially threatening stimulus (a red-tipped metrestick extended towards the individual) and a nonthreatening stimulus (a novel food source). We also related these measures of shyness and boldness to behaviours observed during focal observations, both before and after the introduction of a predator (largemouth bass, Micropterus salmoides). Consistent individual differences were found within both contexts, but individual differences did not correlate across contexts. Furthermore, fish that were scored as intermediate in their response to the metrestick behaved most boldly as foragers and in response to the bass predators. These results suggest that shyness and boldness are context-specific and may not exist as a one-dimensional behavioural continuum even within a single context. Copyright 1998 The Association for the Study of Animal Behaviour.

Implications of oxidative stress in the brain plasticity originated by fasting: a BOLD-fMRI study.

PubMed

Belaïch, Rachida; Boujraf, Saïd; Benzagmout, Mohammed; Magoul, Rabia; Maaroufi, Mustapha; Tizniti, Siham

2017-11-01

The goal of this study was assessing the intermittent fasting effect on brain plasticity and oxidative stress (OS) using blood-oxygenation-level dependent (BOLD)-functional magnetic resonance image (fMRI) approach. Evidences of physiological and molecular phenomena involved in this process are discussed and compared to reported literature. Six fully healthy male non-smokers volunteered in this study. All volunteers were right handed, and have an equilibrated, consistent and healthy daily nutritional habit, and a healthy lifestyle. Participants were allowed consuming food during evening and night time while fasting with self-prohibiting food and liquids during 14 hours/day from sunrise to sunset. All participants underwent identical brain BOLD-fMRI protocol. The images were acquired in the Department of Radiology and Clinical Imaging of the University Hospital of Fez, Fez, Morocco. The anatomical brain and BOLD-fMRIs were acquired using a 1.5-Tesla scanner (Signa, General Electric, Milwaukee, United States). BOLD-fMRI image acquisition was done using single-shot gradient echo echo-planer imaging sequence. BOLD-fMRI paradigm consisted of the motor task where volunteers were asked to perform finger taping of the right hand. Two BOLD-fMRI scan sessions were performed, the first one between the 5th and 10th days preceding the start of fasting and the second between days 25th and 28th of the fasting month. All sessions were performed between 3:30 PM and 5:30 PM. Although individual maps were originated from different individual participants, they cover the same anatomic area in each case. Image processing and statistical analysis were conducted with Statistical Parameter Mapping version 8 (2008, Welcome Department of Cognitive Neurology, London UK). The maximal BOLD signal changes were calculated for each subject in the motor area M1; Activation maps were calculated and overlaid on the anatomical images. Group analysis of the data was performed, and the average volume

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

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.

A Sensitivity Analysis of fMRI Balloon Model.

PubMed

Zayane, Chadia; Laleg-Kirati, Taous Meriem

2015-01-01

Functional magnetic resonance imaging (fMRI) allows the mapping of the brain activation through measurements of the Blood Oxygenation Level Dependent (BOLD) contrast. The characterization of the pathway from the input stimulus to the output BOLD signal requires the selection of an adequate hemodynamic model and the satisfaction of some specific conditions while conducting the experiment and calibrating the model. This paper, focuses on the identifiability of the Balloon hemodynamic model. By identifiability, we mean the ability to estimate accurately the model parameters given the input and the output measurement. Previous studies of the Balloon model have somehow added knowledge either by choosing prior distributions for the parameters, freezing some of them, or looking for the solution as a projection on a natural basis of some vector space. In these studies, the identification was generally assessed using event-related paradigms. This paper justifies the reasons behind the need of adding knowledge, choosing certain paradigms, and completing the few existing identifiability studies through a global sensitivity analysis of the Balloon model in the case of blocked design experiment.

Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients.

PubMed

Alsaadi, Hanin M; Van Vugt, Dean A

2015-11-01

This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures. We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.

Functional brain imaging in irritable bowel syndrome with rectal balloon-distention by using fMRI.

PubMed

Yuan, Yao-Zong; Tao, Ran-Jun; Xu, Bin; Sun, Jing; Chen, Ke-Min; Miao, Fei; Zhang, Zhong-Wei; Xu, Jia-Yu

2003-06-01

Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity is a key factor in the pathophysiology of IBS. The aim of this study was to examine the effect of rectal balloon-distention stimulus by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) in visceral pain center and to compare the distribution, extent, and intensity of activated areas between IBS patients and normal controls. Twenty-six patients with IBS and eleven normal controls were tested for rectal sensation, and the subjective pain intensity at 90 ml and 120 ml rectal balloon-distention was reported by using Visual Analogue Scale. Then, BOLD-fMRI was performed at 30 ml, 60 ml, 90 ml, and 120 ml rectal balloon-distention in all subjects. Rectal distention stimulation increased the activity of anterior cingulate cortex (35/37), insular cortex (37/37), prefrontal cortex (37/37), and thalamus (35/37) in most cases. At 120 ml of rectal balloon-distention, the activation area and percentage change in MR signal intensity of the regions of interest (ROI) at IC, PFC, and THAL were significantly greater in patients with IBS than that in controls. Score of pain sensation at 90 ml and 120 ml rectal balloon-distention was significantly higher in patients with IBS than that in controls. Using fMRI, some patients with IBS can be detected having visceral hypersensitivity in response to painful rectal balloon-distention. fMRI is an objective brain imaging technique to measure the change in regional cerebral activation more precisely. In this study, IC and PFC of the IBS patients were the major loci of the CNS processing of visceral perception.

Effect of hypnotherapy and educational intervention on brain response to visceral stimulusin the irritable bowel syndrome

PubMed Central

Lowén, Mats B.O.; Mayer, Emeran A.; Sjöberg, Martha; Tillisch, Kirsten; Naliboff, Bruce; Labus, Jennifer; Lundberg, Peter; Ström, Magnus; Engström, Maria; Walter, Susanna A.

2013-01-01

SUMMARY Background Gut directed hypnotherapy can reduce IBS symptoms but the mechanisms underlying this therapeutic effect remain unknown. Aim We determined the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. Methods 44 women with moderate to severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). 31 patients completed treatments and post treatment fMRI. Results Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high intensity distension in the dorsal and ventral anterior insula (cluster size 142, p=0.006, and cluster size 101, p=0.005, respectively). Moreover HYP responders demonstrated a pre-post treatment BOLD attenuation in posterior insula (cluster sizes 59, p=0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, p=0.05). Pre-post differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalizing effect on the central processing abnormality of visceral signals in IBS. Conclusions The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalized by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. PMID:23617618

Investigating Inhibitory Control in Children with Epilepsy: An fMRI Study

PubMed Central

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

2014-01-01

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

Quantification of the power changes in BOLD signals using Welch spectrum method during different single-hand motor imageries.

PubMed

Zhang, Jiang; Yuan, Zhen; Huang, Jin; Yang, Qin; Chen, Huafu

2014-12-01

Motor imagery is an experimental paradigm implemented in cognitive neuroscience and cognitive psychology. To investigate the asymmetry of the strength of cortical functional activity due to different single-hand motor imageries, functional magnetic resonance imaging (fMRI) data from right handed normal subjects were recorded and analyzed during both left-hand and right-hand motor imagery processes. Then the average power of blood oxygenation level-dependent (BOLD) signals in temporal domain was calculated using the developed tool that combines Welch power spectrum and the integral of power spectrum approach of BOLD signal changes during motor imagery. Power change analysis results indicated that cortical activity exhibited a stronger power in the precentral gyrus and medial frontal gyrus with left-hand motor imagery tasks compared with that from right-hand motor imagery tasks. These observations suggest that right handed normal subjects mobilize more cortical nerve cells for left-hand motor imagery. Our findings also suggest that the approach based on power differences of BOLD signals is a suitable quantitative analysis tool for quantification of asymmetry of brain activity intensity during motor imagery tasks. Copyright © 2014 Elsevier Inc. All rights reserved.

Removing the effect of response time on brain activity reveals developmental differences in conflict processing in the posterior medial prefrontal cortex.

PubMed

Carp, Joshua; Fitzgerald, Kate Dimond; Taylor, Stephan F; Weissman, Daniel H

2012-01-02

In functional magnetic resonance imaging (fMRI) studies, researchers often attempt to ensure that group differences in brain activity are not confounded with group differences in mean reaction time (RT). However, even when groups are matched for performance, they may differ in terms of the RT-BOLD relationship: the degree to which brain activity varies with RT on a trial-by-trial basis. Group activation differences might therefore be influenced by group differences in the relationship between brain activity and time on task. Here, we investigated whether correcting for this potential confound alters group differences in brain activity. Specifically, we reanalyzed data from a functional MRI study of response conflict in children and adults, in which conventional analyses indicated that conflict-related activity did not differ between groups. We found that the RT-BOLD relationship was weaker in children than in adults. Consequently, after removing the effect of RT on brain activity, children exhibited greater conflict-related activity than adults in both the posterior medial prefrontal cortex and the right dorsolateral prefrontal cortex. These results identify the RT-BOLD relationship as an important potential confound in fMRI studies of group differences. They also suggest that the magnitude of the RT-BOLD relationship may be a useful biomarker of brain maturity. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome.

PubMed

Lowén, M B O; Mayer, E A; Sjöberg, M; Tillisch, K; Naliboff, B; Labus, J; Lundberg, P; Ström, M; Engström, M; Walter, S A

2013-06-01

Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown. To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45 mmHg) and low-intensity (15 mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI. Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P = 0.006, and cluster size 101, P = 0.005 respectively). Moreover HYP responders demonstrated a pre-post treatment BOLD attenuation in posterior insula (cluster sizes 59, P = 0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P = 0.05). Pre-post differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS. The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. NCT01815164. © 2013 John Wiley & Sons Ltd.

Cortical connective field estimates from resting state fMRI activity.

PubMed

Gravel, Nicolás; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V; Dumoulin, Serge O; Renken, Remco; Curčić-Blake, Branislava; Cornelissen, Frans W

2014-01-01

One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that-despite some variability in CF estimates between RS scans-neural properties such as CF maps and CF size can be derived from resting state data.

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

PubMed

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

2016-01-01

Structural and functional connectivity (SC and FC) have received much attention over the last decade, as they offer unique insight into the coordination of brain functioning. They are often assessed independently with three imaging modalities: SC using diffusion-weighted imaging (DWI), FC using functional magnetic resonance imaging (fMRI), and magnetoencephalography/electroencephalography (MEG/EEG). DWI provides information about white matter organization, allowing the reconstruction of fiber bundles. fMRI uses blood-oxygenation level-dependent (BOLD) contrast to indirectly map neuronal activation. MEG and EEG are direct measures of neuronal activity, as they are sensitive to the synchronous inputs in pyramidal neurons. Seminal studies have targeted either the electrophysiological substrate of BOLD or the anatomical basis of FC. However, multimodal comparisons have been scarcely performed, and the relation between SC, fMRI-FC, and MEG-FC is still unclear. Here we present a systematic comparison of SC, resting state fMRI-FC, and MEG-FC between cortical regions, by evaluating their similarities at three different scales: global network, node, and hub distribution. We obtained strong similarities between the three modalities, especially for the following pairwise combinations: SC and fMRI-FC; SC and MEG-FC at theta, alpha, beta and gamma bands; and fMRI-FC and MEG-FC in alpha and beta. Furthermore, highest node similarity was found for regions of the default mode network and primary motor cortex, which also presented the highest hubness score. Distance was partially responsible for these similarities since it biased all three connectivity estimates, but not the unique contributor, since similarities remained after controlling for distance. © 2015 Wiley Periodicals, Inc.

Does boldness explain vulnerability to angling in Eurasian perch Perca fluviatilis?

PubMed

Vainikka, Anssi; Tammela, Ilkka; Hyvärinen, Pekka

2016-04-01

Consistent individual differences (CIDs) in behavior are of interest to both basic and applied research, because any selection acting on them could induce evolution of animal behavior. It has been suggested that CIDs in the behavior of fish might explain individual differences in vulnerability to fishing. If so, fishing could impose selection on fish behavior. In this study, we assessed boldness-indicating behaviors of Eurasian perch Perca fluviatilis using individually conducted experiments measuring the time taken to explore a novel arena containing predator (burbot, Lota lota ) cues. We studied if individual differences in boldness would explain vulnerability of individually tagged perch to experimental angling in outdoor ponds, or if fishing would impose selection on boldness-indicating behavior. Perch expressed repeatable individual differences in boldness-indicating behavior but the individual boldness-score (the first principal component) obtained using principal component analysis combining all the measured behavioral responses did not explain vulnerability to experimental angling. Instead, large body size appeared as the only statistically significant predictor of capture probability. Our results suggest that angling is selective for large size, but not always selective for high boldness.

Does boldness explain vulnerability to angling in Eurasian perch Perca fluviatilis?

PubMed Central

Vainikka, Anssi; Tammela, Ilkka; Hyvärinen, Pekka

2016-01-01

Abstract Consistent individual differences (CIDs) in behavior are of interest to both basic and applied research, because any selection acting on them could induce evolution of animal behavior. It has been suggested that CIDs in the behavior of fish might explain individual differences in vulnerability to fishing. If so, fishing could impose selection on fish behavior. In this study, we assessed boldness-indicating behaviors of Eurasian perch Perca fluviatilis using individually conducted experiments measuring the time taken to explore a novel arena containing predator (burbot, Lota lota) cues. We studied if individual differences in boldness would explain vulnerability of individually tagged perch to experimental angling in outdoor ponds, or if fishing would impose selection on boldness-indicating behavior. Perch expressed repeatable individual differences in boldness-indicating behavior but the individual boldness-score (the first principal component) obtained using principal component analysis combining all the measured behavioral responses did not explain vulnerability to experimental angling. Instead, large body size appeared as the only statistically significant predictor of capture probability. Our results suggest that angling is selective for large size, but not always selective for high boldness. PMID:29491897

Association between glutamate/glutamine and blood oxygen level dependent signal in the left dorsolateral prefrontal region during verbal working memory.

PubMed

Vijayakumari, Anupa A; Thomas, Bejoy; Menon, Ramshekhar N; Kesavadas, Chandrasekharan

2018-04-11

Functional MRI (fMRI) has provided much insight into the changes in the neuronal activity on the basis of blood oxygen level dependent (BOLD) phenomenon. The dynamic changes in the metabolites can be detected using functional proton magnetic resonance spectroscopy (H-fMRS). The strategy of combining fMRI and H-fMRS would facilitate the understanding of the neurochemical interpretation of the BOLD signal. The dorsolateral prefrontal region is critically involved in the processing of working memory (WM), as demonstrated by the studies involving the neuroimaging, neuropsychological, and electrophysiological experiments. In this study, we tested the association between BOLD signal and changes in brain metabolites in the left dorsolateral prefrontal region using N-back verbal WM task. We used single-voxel task-based H-MRS acquired in the left dorsolateral prefrontal region and fMRI during the performance of N-back verbal WM task to investigate the association between changes in metabolites and BOLD response in 10 healthy participants. The correlation between changes in metabolites and percent signal change was examined by the Pearson correlation. The Pearson correlation analysis revealed a significant positive correlation between the BOLD signal and glutamate/glutamine in the left dorsolateral prefrontal region during the verbal WM. Our finding suggests that glutamate/glutamine cycle plays a critical role in the neuronal activation as reflected by the changes in the BOLD response.

Implications of neurovascular uncoupling in functional magnetic resonance imaging (fMRI) of brain tumors.

PubMed

Pak, Rebecca W; Hadjiabadi, Darian H; Senarathna, Janaka; Agarwal, Shruti; Thakor, Nitish V; Pillai, Jay J; Pathak, Arvind P

2017-11-01

Functional magnetic resonance imaging (fMRI) serves as a critical tool for presurgical mapping of eloquent cortex and changes in neurological function in patients diagnosed with brain tumors. However, the blood-oxygen-level-dependent (BOLD) contrast mechanism underlying fMRI assumes that neurovascular coupling remains intact during brain tumor progression, and that measured changes in cerebral blood flow (CBF) are correlated with neuronal function. Recent preclinical and clinical studies have demonstrated that even low-grade brain tumors can exhibit neurovascular uncoupling (NVU), which can confound interpretation of fMRI data. Therefore, to avoid neurosurgical complications, it is crucial to understand the biophysical basis of NVU and its impact on fMRI. Here we review the physiology of the neurovascular unit, how it is remodeled, and functionally altered by brain cancer cells. We first discuss the latest findings about the components of the neurovascular unit. Next, we synthesize results from preclinical and clinical studies to illustrate how brain tumor induced NVU affects fMRI data interpretation. We examine advances in functional imaging methods that permit the clinical evaluation of brain tumors with NVU. Finally, we discuss how the suppression of anomalous tumor blood vessel formation with antiangiogenic therapies can "normalize" the brain tumor vasculature, and potentially restore neurovascular coupling.

Spiral Imaging in fMRI

PubMed Central

Glover, Gary H.

2011-01-01

T2*-weighted Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) requires efficient acquisition methods in order to fully sample the brain in a several second time period. The most widely used approach is Echo Planar Imaging (EPI), which utilizes a Cartesian trajectory to cover k-space. This trajectory is subject to ghosts from off-resonance and gradient imperfections and is intrinsically sensitive to cardiac-induced pulsatile motion from substantial first- and higher order moments of the gradient waveform near the k-space origin. In addition, only the readout direction gradient contributes significant energy to the trajectory. By contrast, the Spiral method samples k-space with an Archimedean or similar trajectory that begins at the k-space center and spirals to the edge (Spiral-out), or its reverse, ending at the origin (Spiral-in). Spiral methods have reduced sensitivity to motion, shorter readout times, improved signal recovery in most frontal and parietal brain regions, and exhibit blurring artifacts instead of ghosts or geometric distortion. Methods combining Spiral-in and Spiral-out trajectories have further advantages in terms of diminished susceptibility-induced signal dropout and increased BOLD signal. In measurements of temporal signal to noise ratio measured in 8 subjects, Spiral-in/out exhibited significant increases over EPI in voxel volumes recovered in frontal and whole brain regions (18% and 10%, respectively). PMID:22036995

Is boldness a resource-holding potential trait? Fighting prowess and changes in startle response in the sea anemone, Actinia equina.

PubMed

Rudin, Fabian S; Briffa, Mark

2012-05-22

Contest theory predicts the evolution of a stable mixture of different strategies for fighting. Here, we investigate the possibility that stable between-individual differences in startle-response durations influence fighting ability or 'resource-holding potential' (RHP) in the beadlet sea anemone, Actinia equina. Both winners and losers showed significant repeatability of pre-fight startle-response durations but mean pre-fight startle-response durations were greater for eventual losers than for eventual winners, indicating that RHP varies with boldness. In particular, individuals with short startle responses inflicted more attacks on their opponent. Both repeatability and mean-level responses were changed by the experience of fighting, and these changes varied with outcome. In losers, repeatability was disrupted to a greater extent and the mean startle-response durations were subject to a greater increase than in winners. Thus, following a fight, this behavioural correlate of RHP behaves in a way similar to post-fight changes in physiological status, which can also vary between winners and losers. Understanding the links between aggression and boldness therefore has the potential to enhance our understanding of both the evolution of animal personality and the 'winner and loser effects' of post-fight changes in RHP.

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

PubMed

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

2015-01-01

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

Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.

PubMed

Nelson, Flavia; Akhtar, Mohammad A; Zúñiga, Edward; Perez, Carlos A; Hasan, Khader M; Wilken, Jeffrey; Wolinsky, Jerry S; Narayana, Ponnada A; Steinberg, Joel L

2017-05-01

Cognitive impairment (CI) cannot be diagnosed by magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) paradigms, such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory (WM). Preliminary findings using I/DMT showed differences in blood oxygenation level dependent (BOLD) activation between impaired (MSCI, n = 12) and non-impaired (MSNI, n = 9) multiple sclerosis (MS) patients. The aim of the study was to confirm CI detection based on I/DMT BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and Expanded Disability Status Scale (EDSS) in magnitude of BOLD signal was also sought. A total of 50 patients (EDSS mean ( m) = 3.2, disease duration (DD) m = 12 years, and age m = 40 years) underwent the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and I/DMT. Working memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS. A total of 10 MSNI, 30 MSCI, and 4 borderline patients were included in the analyses. Analysis of variance (ANOVA) showed MSNI had significantly greater WMa than MSCI, in the left prefrontal cortex and left supplementary motor area ( p = 0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas ( p = 0.005, 0.004, respectively). I/DMT-based BOLD activation detects CI in MS. Larger studies are needed to confirm these findings.

Functional Laterality of Task-Evoked Activation in Sensorimotor Cortex of Preterm Infants: An Optimized 3 T fMRI Study Employing a Customized Neonatal Head Coil.

PubMed

Scheef, Lukas; Nordmeyer-Massner, Jurek A; Smith-Collins, Adam Pr; Müller, Nicole; Stegmann-Woessner, Gaby; Jankowski, Jacob; Gieseke, Jürgen; Born, Mark; Seitz, Hermann; Bartmann, Peter; Schild, Hans H; Pruessmann, Klaas P; Heep, Axel; Boecker, Henning

2017-01-01

Functional magnetic resonance imaging (fMRI) in neonates has been introduced as a non-invasive method for studying sensorimotor processing in the developing brain. However, previous neonatal studies have delivered conflicting results regarding localization, lateralization, and directionality of blood oxygenation level dependent (BOLD) responses in sensorimotor cortex (SMC). Amongst the confounding factors in interpreting neonatal fMRI studies include the use of standard adult MR-coils providing insufficient signal to noise, and liberal statistical thresholds, compromising clinical interpretation at the single subject level. Here, we employed a custom-designed neonatal MR-coil adapted and optimized to the head size of a newborn in order to improve robustness, reliability and validity of neonatal sensorimotor fMRI. Thirteen preterm infants with a median gestational age of 26 weeks were scanned at term-corrected age using a prototype 8-channel neonatal head coil at 3T (Achieva, Philips, Best, NL). Sensorimotor stimulation was elicited by passive extension/flexion of the elbow at 1 Hz in a block design. Analysis of temporal signal to noise ratio (tSNR) was performed on the whole brain and the SMC, and was compared to data acquired with an 'adult' 8 channel head coil published previously. Task-evoked activation was determined by single-subject SPM8 analyses, thresholded at p < 0.05, whole-brain FWE-corrected. Using a custom-designed neonatal MR-coil, we found significant positive BOLD responses in contralateral SMC after unilateral passive sensorimotor stimulation in all neonates (analyses restricted to artifact-free data sets = 8/13). Improved imaging characteristics of the neonatal MR-coil were evidenced by additional phantom and in vivo tSNR measurements: phantom studies revealed a 240% global increase in tSNR; in vivo studies revealed a 73% global and a 55% local (SMC) increase in tSNR, as compared to the 'adult' MR-coil. Our findings strengthen the importance of

Task-dependent V1 responses in human retinitis pigmentosa.

PubMed

Masuda, Yoichiro; Horiguchi, Hiroshi; Dumoulin, Serge O; Furuta, Ayumu; Miyauchi, Satoru; Nakadomari, Satoshi; Wandell, Brian A

2010-10-01

During measurement with functional MRI (fMRI) during passive viewing, subjects with macular degeneration (MD) have a large unresponsive lesion projection zone (LPZ) in V1. fMRI responses can be evoked from the LPZ when subjects engage in a stimulus-related task. The authors report fMRI measurements on a different class of subjects, those with retinitis pigmentosa (RP), who have intact foveal vision but peripheral visual field loss. The authors measured three RP subjects and two control subjects. fMRI was performed while the subjects viewed drifting contrast pattern stimuli. The subjects passively viewed the stimuli or performed a stimulus-related task. During passive viewing, the BOLD response in the posterior calcarine cortex of all RP subjects was in phase with the stimulus. A bordering, anterior LPZ could be identified by responses that were in opposite phase to the stimulus. When the RP subjects made stimulus-related judgments, however, the LPZ responses changed: the responses modulated in phase with the stimulus and task. In control subjects, the responses in a simulated V1 LPZ were unchanged between the passive and the stimulus-related judgment conditions. Task-dependent LPZ responses are present in RP subjects, similar to responses measured in MD subjects. The results are consistent with the hypothesis that deleting the retinal input to the LPZ unmasks preexisting extrastriate feedback signals that are present across V1. The authors discuss the implications of this hypothesis for visual therapy designed to replace the missing V1 LPZ inputs and to restore vision.

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

Human protein status modulates brain reward responses to food cues.

PubMed

Griffioen-Roose, Sanne; Smeets, Paul Am; van den Heuvel, Emmy; Boesveldt, Sanne; Finlayson, Graham; de Graaf, Cees

2014-07-01

Protein is indispensable in the human diet, and its intake appears tightly regulated. The role of sensory attributes of foods in protein intake regulation is far from clear. We investigated the effect of human protein status on neural responses to different food cues with the use of functional magnetic resonance imaging (fMRI). The food cues varied by taste category (sweet compared with savory) and protein content (low compared with high). In addition, food preferences and intakes were measured. We used a randomized crossover design whereby 23 healthy women [mean ± SD age: 22 ± 2 y; mean ± SD body mass index (in kg/m(2)): 22.5 ± 1.8] followed two 16-d fully controlled dietary interventions involving consumption of either a low-protein diet (0.6 g protein · kg body weight(-1) · d(-1), ~7% of energy derived from protein, approximately half the normal protein intake) or a high-protein diet (2.2 g protein · kg body weight(-1) · d(-1), ~25% of energy, approximately twice the normal intake). On the last day of the interventions, blood oxygen level-dependent (BOLD) responses to odor and visual food cues were measured by using fMRI. The 2 interventions were followed by a 1-d ad libitum phase, during which a large array of food items was available and preference and intake were measured. When exposed to food cues (relative to the control condition), the BOLD response was higher in reward-related areas (orbitofrontal cortex, striatum) in a low-protein state than in a high-protein state. Specifically, BOLD was higher in the inferior orbitofrontal cortex in response to savory food cues. In contrast, the protein content of the food cues did not modulate the BOLD response. A low protein state also increased preferences for savory food cues and increased protein intake in the ad libitum phase as compared with a high-protein state. Protein status modulates brain responses in reward regions to savory food cues. These novel findings suggest that dietary protein status

Influence of DARPP-32 genetic variation on BOLD activation to happy faces.

PubMed

Persson, Ninni; Lavebratt, Catarina; Ebner, Natalie C; Fischer, Håkan

2017-10-01

Dopaminergic pathways play a crucial role in reward processing, and advanced age can modulate its efficiency. DARPP-32 controls dopaminergic function and is a chemical nexus of reward processing. In 61 younger (20-30 years) and older adults (54% ♀) (65-74 years), we examined how blood-oxygen-level dependent (BOLD) activation to emotional faces, vary over genotypes at three single nucleotide polymorphism (SNPs), coding for DARPP-32 (rs879606; rs907094; 3764352). We also assessed age-magnification of DARPP-32 effects on BOLD activation. We found that major homozygote G, T or A genotypes, with higher cortical expression of DARPP-32, higher dopamine receptor efficacy, and greater bias toward positive cues, had increased functional connectivity in cortical-subcortical circuits in response to happy faces, engaging the dorsal prefrontal cortex (DLPFC), fusiform gyrus (FG) and the midbrain (MB). Local BOLD response to happy faces in FG, and MB was age-dependent, so that older carriers of the major G, T or A alleles showed lesser activation than minor genotypes. These genetic variants of DARPP-32 did not modulate BOLD response to angry faces, or engagement of the inferior occipital gyrus, to happy or angry faces. Taken together our results lend support for a potential role of DARPP-32 genetic variants in neural response to potential reward triggering cues. © The Author (2017). Published by Oxford University Press.

To boldly go: individual differences in boldness influence migratory tendency.

PubMed

Chapman, Ben B; Hulthén, Kaj; Blomqvist, David R; Hansson, Lars-Anders; Nilsson, Jan-Åke; Brodersen, Jakob; Anders Nilsson, P; Skov, Christian; Brönmark, Christer

2011-09-01

Partial migration, whereby only a fraction of the population migrates, is thought to be the most common type of migration in the animal kingdom, and can have important ecological and evolutionary consequences. Despite this, the factors that influence which individuals migrate and which remain resident are poorly understood. Recent work has shown that consistent individual differences in personality traits in animals can be ecologically important, but field studies integrating personality traits with migratory behaviour are extremely rare. In this study, we investigate the influence of individual boldness, an important personality trait, upon the migratory propensity of roach, a freshwater fish, over two consecutive migration seasons. We assay and individually tag 460 roach and show that boldness influences migratory propensity, with bold individuals being more likely to migrate than shy fish. Our data suggest that an extremely widespread personality trait in animals can have significant ecological consequences via influencing individual-level migratory behaviour. © 2011 Blackwell Publishing Ltd/CNRS.

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.

Express yourself: bold individuals induce enhanced morphological defences

PubMed Central

Hulthén, Kaj; Chapman, Ben B.; Nilsson, P. Anders; Hollander, Johan; Brönmark, Christer

2014-01-01

Organisms display an impressive array of defence strategies in nature. Inducible defences (changes in morphology and/or behaviour within a prey's lifetime) allow prey to decrease vulnerability to predators and avoid unnecessary costs of expression. Many studies report considerable interindividual variation in the degree to which inducible defences are expressed, yet what underlies this variation is poorly understood. Here, we show that individuals differing in a key personality trait also differ in the magnitude of morphological defence expression. Crucian carp showing risky behaviours (bold individuals) expressed a significantly greater morphological defence response when exposed to a natural enemy when compared with shy individuals. Furthermore, we show that fish of different personality types differ in their behavioural plasticity, with shy fish exhibiting greater absolute plasticity than bold fish. Our data suggest that individuals with bold personalities may be able to compensate for their risk-prone behavioural type by expressing enhanced morphological defences. PMID:24335987

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.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.

PubMed

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.

Influence of Acoustic Overstimulation on the Central Auditory System: An Functional Magnetic Resonance Imaging (fMRI) Study.

PubMed

Wolak, Tomasz; Cieśla, Katarzyna; Rusiniak, Mateusz; Piłka, Adam; Lewandowska, Monika; Pluta, Agnieszka; Skarżyński, Henryk; Skarżyński, Piotr H

2016-11-28

BACKGROUND The goal of the fMRI experiment was to explore the involvement of central auditory structures in pathomechanisms of a behaviorally manifested auditory temporary threshold shift in humans. MATERIAL AND METHODS The material included 18 healthy volunteers with normal hearing. Subjects in the exposure group were presented with 15 min of binaural acoustic overstimulation of narrowband noise (3 kHz central frequency) at 95 dB(A). The control group was not exposed to noise but instead relaxed in silence. Auditory fMRI was performed in 1 session before and 3 sessions after acoustic overstimulation and involved 3.5-4.5 kHz sweeps. RESULTS The outcomes of the study indicate a possible effect of acoustic overstimulation on central processing, with decreased brain responses to auditory stimulation up to 20 min after exposure to noise. The effect can be seen already in the primary auditory cortex. Decreased BOLD signal change can be due to increased excitation thresholds and/or increased spontaneous activity of auditory neurons throughout the auditory system. CONCLUSIONS The trial shows that fMRI can be a valuable tool in acoustic overstimulation studies but has to be used with caution and considered complimentary to audiological measures. Further methodological improvements are needed to distinguish the effects of TTS and neuronal habituation to repetitive stimulation.

Influence of Acoustic Overstimulation on the Central Auditory System: An Functional Magnetic Resonance Imaging (fMRI) Study

PubMed Central

Wolak, Tomasz; Cieśla, Katarzyna; Rusiniak, Mateusz; Piłka, Adam; Lewandowska, Monika; Pluta, Agnieszka; Skarżyński, Henryk; Skarżyński, Piotr H.

2016-01-01

Background The goal of the fMRI experiment was to explore the involvement of central auditory structures in pathomechanisms of a behaviorally manifested auditory temporary threshold shift in humans. Material/Methods The material included 18 healthy volunteers with normal hearing. Subjects in the exposure group were presented with 15 min of binaural acoustic overstimulation of narrowband noise (3 kHz central frequency) at 95 dB(A). The control group was not exposed to noise but instead relaxed in silence. Auditory fMRI was performed in 1 session before and 3 sessions after acoustic overstimulation and involved 3.5–4.5 kHz sweeps. Results The outcomes of the study indicate a possible effect of acoustic overstimulation on central processing, with decreased brain responses to auditory stimulation up to 20 min after exposure to noise. The effect can be seen already in the primary auditory cortex. Decreased BOLD signal change can be due to increased excitation thresholds and/or increased spontaneous activity of auditory neurons throughout the auditory system. Conclusions The trial shows that fMRI can be a valuable tool in acoustic overstimulation studies but has to be used with caution and considered complimentary to audiological measures. Further methodological improvements are needed to distinguish the effects of TTS and neuronal habituation to repetitive stimulation. PMID:27893698

Calibrated fMRI in the Medial Temporal Lobe During a Memory Encoding Task

PubMed Central

Restom, Khaled; Perthen, Joanna E.; Liu, Thomas T.

2008-01-01

Prior measures of the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) responses to a memory encoding task within the medial temporal lobe have suggested that the coupling between functional changes in CBF and changes in the cerebral metabolic rate of oxgyen (CMRO2) may be tighter in the medial temporal lobe as compared to the primary sensory areas. In this study, we used a calibrated functional magnetic resonance imaging (fMRI) approach to directly estimate memory-encoding-related changes in CMRO2 and to assess the coupling between CBF and CMRO2 in the medial temporal lobe. The CBF-CMRO2 coupling ratio was estimated using a linear fit to the flow and metabolism changes observed across subjects. In addition, we examined the effect of region-of-interest (ROI) selection on the estimates. In response to the memory encoding task, CMRO2 increased by 23.1% ± 8.8 to 25.3% ± 5.7 (depending upon ROI), with an estimated CBF-CMRO2 coupling ratio of 1.66 ± 0.07 to 1.75± 0.16. There was not a significant effect of ROI selection on either the CMRO2 or coupling ratio estimates. The observed coupling ratios were significantly lower than the values (2 to 4.5) that have been reported in previous calibrated fMRI studies of the visual and motor cortices. In addition, the estimated coupling ratio was found to be less sensitive to the calibration procedure for functional responses in the medial temporal lobe as compared to the primary sensory areas. PMID:18329291

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

PubMed

Hu, Yanbo; Walker, Robin

2011-11-01

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

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. Published by Elsevier Inc.

fMRI responses to Jung's Word Association Test: implications for theory, treatment and research.

PubMed

Petchkovsky, Leon; Petchkovsky, Michael; Morris, Philip; Dickson, Paul; Montgomery, Danielle; Dwyer, Jonathan; Burnett, Patrick

2013-06-01

Jung's Word Association Test was performed under fMRI conditions by 12 normal subjects. Pooled complexed responses were contrasted against pooled neutral ones. The fMRI activation pattern of this generic 'complexed response' was very strong (corrected Z scores ranging from 4.90 to 5.69). The activation pattern in each hemisphere includes mirror neurone areas that track 'otherness' (perspectival empathy), anterior insula (both self-awareness and emotional empathy), and cingulated gyrus (self-awareness and conflict-monitoring). These are the sites described by Siegel and colleagues as the 'resonance circuitry' in the brain which is central to mindfulness (awareness of self) and empathy (sense of the other), negotiations between self awareness and the 'internal other'. But there is also an interhemispheric dialogue. Within 3 seconds, the left hemisphere over-rides the right (at least in our normal subjects). Mindfulness and empathy are central to good psychotherapy, and complexes can be windows of opportunity if left-brain hegemony is resisted. This study sets foundations for further research: (i) QEEG studies (with their finer temporal resolution) of complexed responses in normal subjects (ii) QEEG and fMRI studies of complexed responses in other conditions, like schizophrenia, PTSD, disorders of self organization. © 2013, The Society of Analytical Psychology.

Increased fMRI Sensitivity at Equal Data Burden Using Averaged Shifted Echo Acquisition

PubMed Central

Witt, Suzanne T.; Warntjes, Marcel; Engström, Maria

2016-01-01

There is growing evidence as to the benefits of collecting BOLD fMRI data with increased sampling rates. However, many of the newly developed acquisition techniques developed to collect BOLD data with ultra-short TRs require hardware, software, and non-standard analytic pipelines that may not be accessible to all researchers. We propose to incorporate the method of shifted echo into a standard multi-slice, gradient echo EPI sequence to achieve a higher sampling rate with a TR of <1 s with acceptable spatial resolution. We further propose to incorporate temporal averaging of consecutively acquired EPI volumes to both ameliorate the reduced temporal signal-to-noise inherent in ultra-fast EPI sequences and reduce the data burden. BOLD data were collected from 11 healthy subjects performing a simple, event-related visual-motor task with four different EPI sequences: (1) reference EPI sequence with TR = 1440 ms, (2) shifted echo EPI sequence with TR = 700 ms, (3) shifted echo EPI sequence with every two consecutively acquired EPI volumes averaged and effective TR = 1400 ms, and (4) shifted echo EPI sequence with every four consecutively acquired EPI volumes averaged and effective TR = 2800 ms. Both the temporally averaged sequences exhibited increased temporal signal-to-noise over the shifted echo EPI sequence. The shifted echo sequence with every two EPI volumes averaged also had significantly increased BOLD signal change compared with the other three sequences, while the shifted echo sequence with every four EPI volumes averaged had significantly decreased BOLD signal change compared with the other three sequences. The results indicated that incorporating the method of shifted echo into a standard multi-slice EPI sequence is a viable method for achieving increased sampling rate for collecting event-related BOLD data. Further, consecutively averaging every two consecutively acquired EPI volumes significantly increased the measured BOLD signal change and the

Wavelet entropy of BOLD time series: An application to Rolandic epilepsy.

PubMed

Gupta, Lalit; Jansen, Jacobus F A; Hofman, Paul A M; Besseling, René M H; de Louw, Anton J A; Aldenkamp, Albert P; Backes, Walter H

2017-12-01

To assess the wavelet entropy for the characterization of intrinsic aberrant temporal irregularities in the time series of resting-state blood-oxygen-level-dependent (BOLD) signal fluctuations. Further, to evaluate the temporal irregularities (disorder/order) on a voxel-by-voxel basis in the brains of children with Rolandic epilepsy. The BOLD time series was decomposed using the discrete wavelet transform and the wavelet entropy was calculated. Using a model time series consisting of multiple harmonics and nonstationary components, the wavelet entropy was compared with Shannon and spectral (Fourier-based) entropy. As an application, the wavelet entropy in 22 children with Rolandic epilepsy was compared to 22 age-matched healthy controls. The images were obtained by performing resting-state functional magnetic resonance imaging (fMRI) using a 3T system, an 8-element receive-only head coil, and an echo planar imaging pulse sequence ( T2*-weighted). The wavelet entropy was also compared to spectral entropy, regional homogeneity, and Shannon entropy. Wavelet entropy was found to identify the nonstationary components of the model time series. In Rolandic epilepsy patients, a significantly elevated wavelet entropy was observed relative to controls for the whole cerebrum (P = 0.03). Spectral entropy (P = 0.41), regional homogeneity (P = 0.52), and Shannon entropy (P = 0.32) did not reveal significant differences. The wavelet entropy measure appeared more sensitive to detect abnormalities in cerebral fluctuations represented by nonstationary effects in the BOLD time series than more conventional measures. This effect was observed in the model time series as well as in Rolandic epilepsy. These observations suggest that the brains of children with Rolandic epilepsy exhibit stronger nonstationary temporal signal fluctuations than controls. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1728-1737. © 2017 International Society for Magnetic

MULTISCALE ADAPTIVE SMOOTHING MODELS FOR THE HEMODYNAMIC RESPONSE FUNCTION IN FMRI*

PubMed Central

Wang, Jiaping; Zhu, Hongtu; Fan, Jianqing; Giovanello, Kelly; Lin, Weili

2012-01-01

In the event-related functional magnetic resonance imaging (fMRI) data analysis, there is an extensive interest in accurately and robustly estimating the hemodynamic response function (HRF) and its associated statistics (e.g., the magnitude and duration of the activation). Most methods to date are developed in the time domain and they have utilized almost exclusively the temporal information of fMRI data without accounting for the spatial information. The aim of this paper is to develop a multiscale adaptive smoothing model (MASM) in the frequency domain by integrating the spatial and temporal information to adaptively and accurately estimate HRFs pertaining to each stimulus sequence across all voxels in a three-dimensional (3D) volume. We use two sets of simulation studies and a real data set to examine the finite sample performance of MASM in estimating HRFs. Our real and simulated data analyses confirm that MASM outperforms several other state-of-art methods, such as the smooth finite impulse response (sFIR) model. PMID:24533041

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

PubMed

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

2016-01-01

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.

Regional homogeneity changes in prelingually deafened patients: a resting-state fMRI study

NASA Astrophysics Data System (ADS)

Li, Wenjing; He, Huiguang; Xian, Junfang; Lv, Bin; Li, Meng; Li, Yong; Liu, Zhaohui; Wang, Zhenchang

2010-03-01

Resting-state functional magnetic resonance imaging (fMRI) is a technique that measures the intrinsic function of brain and has some advantages over task-induced fMRI. Regional homogeneity (ReHo) assesses the similarity of the time series of a given voxel with its nearest neighbors on a voxel-by-voxel basis, which reflects the temporal homogeneity of the regional BOLD signal. In the present study, we used the resting state fMRI data to investigate the ReHo changes of the whole brain in the prelingually deafened patients relative to normal controls. 18 deaf patients and 22 healthy subjects were scanned. Kendall's coefficient of concordance (KCC) was calculated to measure the degree of regional coherence of fMRI time courses. We found that regional coherence significantly decreased in the left frontal lobe, bilateral temporal lobes and right thalamus, and increased in the postcentral gyrus, cingulate gyrus, left temporal lobe, left thalamus and cerebellum in deaf patients compared with controls. These results show that the prelingually deafened patients have higher degree of regional coherence in the paleocortex, and lower degree in neocortex. Since neocortex plays an important role in the development of auditory, these evidences may suggest that the deaf persons reorganize the paleocortex to offset the loss of auditory.

Sewer pipe, wire, epoxy, and finger tapping: The start of fMRI at the Medical College of Wisconsin

PubMed Central

Bandettini, Peter A.

2011-01-01

In 1991, the Biophysics Research Institute at the Medical College of Wisconsin was among the first groups to develop functional Magnetic Resonance Imaging (fMRI). Our story is unique on a few levels: We didn’t have knowledge of the ability to image human brain activation with MRI using blood oxygenation dependent (BOLD) contrast until early August of 1991 when we attended the Society for Magnetic Resonance in Medicine (SMRM) meeting in San Francisco, yet we produced our first BOLD-based maps of motor cortex activation about a month later. The effort started with two graduate students, Eric Wong and myself. Only a few days prior to that extremely important SMRM meeting, we had developed human echo planar imaging (EPI) capability in-house. Wong designed, built, and interfaced a head gradient coil made out of sewer pipe, wire, and epoxy to a standard GE 1.5 T MRI scanner. Also, a few months prior to building this human head gradient coil he developed the EPI pulse sequences and image reconstruction. All of these efforts were towards a different goal – for demonstration of Wong’s novel approach to perfusion imaging in the human brain. Following SMRM, where a plenary lecture by Tom Brady from MGH opened our eyes to human brain activation imaging using BOLD contrast, and where we learned that EPI was extremely helpful if not critical to its success, we worked quickly to achieve our first results on September 14, 1991. The story is also unique in that Jim Hyde had set up the Biophysics Research Institute to be optimal for just this type of rapidly advancing basic technology research. It was well equipped for hardware development, had open and dynamic collaborative relationships with other departments, hospitals on campus, and GE, and had a relatively flat hierarchy and relaxed, flexible, collegial atmosphere internally. Since these first brain activation results, MCW Biophysics has continued to be at the forefront of functional MRI innovation, having helped to

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

PubMed Central

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

2015-01-01

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

Motor and non-motor circuitry activation induced by subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson’s disease patients: Intraoperative fMRI for DBS

PubMed Central

Knight, Emily J.; Testini, Paola; Min, Hoon-Ki; Gibson, William S.; Gorny, Krzysztof R.; Favazza, Christopher P.; Felmlee, Joel P.; Kim, Inyong; Welker, Kirk M.; Clayton, Daniel A.; Klassen, Bryan T.; Chang, Su-youne; Lee, Kendall H.

2015-01-01

Objective To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with PD would affect the activity of both motor and non-motor networks, we applied intraoperative fMRI to patients receiving DBS. Patients and Methods Ten patients receiving STN DBS for PD underwent intraoperative 1.5T fMRI during high frequency stimulation delivered via an external pulse generator. The study was conducted between the dates of January 1, 2013 and September 30, 2014. Results We observed blood oxygen level dependent (BOLD) signal changes (FDR<.001) in the motor circuitry, including primary motor, premotor, and supplementary motor cortices, thalamus, pedunculopontine nucleus (PPN), and cerebellum, as well as in the limbic circuitry, including cingulate and insular cortices. Activation of the motor network was observed also after applying a Bonferroni correction (p<.001) to our dataset, suggesting that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. Conclusions These findings support the modulatory role of STN DBS on the activity of motor and non-motor networks, and suggest complex mechanisms at the basis of the efficacy of this treatment modality. Furthermore, these results suggest that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. With further studies combining the use of real time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning, but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. PMID:26046412

A novel approach to calibrate the hemodynamic model using functional Magnetic Resonance Imaging (fMRI) measurements.

PubMed

Khoram, Nafiseh; Zayane, Chadia; Djellouli, Rabia; Laleg-Kirati, Taous-Meriem

2016-03-15

The calibration of the hemodynamic model that describes changes in blood flow and blood oxygenation during brain activation is a crucial step for successfully monitoring and possibly predicting brain activity. This in turn has the potential to provide diagnosis and treatment of brain diseases in early stages. We propose an efficient numerical procedure for calibrating the hemodynamic model using some fMRI measurements. The proposed solution methodology is a regularized iterative method equipped with a Kalman filtering-type procedure. The Newton component of the proposed method addresses the nonlinear aspect of the problem. The regularization feature is used to ensure the stability of the algorithm. The Kalman filter procedure is incorporated here to address the noise in the data. Numerical results obtained with synthetic data as well as with real fMRI measurements are presented to illustrate the accuracy, robustness to the noise, and the cost-effectiveness of the proposed method. We present numerical results that clearly demonstrate that the proposed method outperforms the Cubature Kalman Filter (CKF), one of the most prominent existing numerical methods. We have designed an iterative numerical technique, called the TNM-CKF algorithm, for calibrating the mathematical model that describes the single-event related brain response when fMRI measurements are given. The method appears to be highly accurate and effective in reconstructing the BOLD signal even when the measurements are tainted with high noise level (as high as 30%). Published by Elsevier B.V.

Assessment of unconstrained cerebrovascular reactivity marker for large age-range FMRI studies.

PubMed

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

2014-01-01

Breath hold (BH), a commonly used task to measure cerebrovascular reactivity (CVR) in fMRI studies varies in outcome among individuals due to subject-physiology and/or BH-inspiration/expiration differences (i.e., performance). In prior age-related fMRI studies, smaller task-related BOLD response variability is observed among younger than older individuals. Also, a linear CVR versus task relationship exists in younger individuals which maybe useful to test the accuracy of CVR responses in older groups. Hence we hypothesized that subject-related physiological and/or BH differences, if present, may compromise CVR versus task linearity in older individuals. To test the hypothesis, empirical BH versus task relationships from motor and cognitive areas were obtained in younger (mean age = 26 years) and older (mean age = 58 years) human subjects. BH versus task linearity was observed only in the younger group, confirming our hypothesis. Further analysis indicated BH responses and its variability to be similar in both younger and older groups, suggesting that BH may not accurately represent CVR in a large age range. Using the resting state fluctuation of amplitude (RSFA) as an unconstrained alternative to BH, subject-wise correspondence between BH and RSFA was tested. Correlation between BH versus RSFA was significant within the motor but was not significant in the cognitive areas in the younger and was completely disrupted in both areas in the older subjects indicating that BH responses are constrained by subject-related physiology and/or performance-related differences. Contrasting BH to task, RSFA-task relationships were independent of age accompanied by age-related increases in CVR variability as measured by RSFA, not observed with BH. Together the results obtained indicate that RSFA accurately represents CVR in any age range avoiding multiple and yet unknown physiologic and task-related pitfalls of BH.

Vascular-metabolic and GABAergic Inhibitory Correlates of Neural Variability Modulation. A Combined fMRI and PET Study.

PubMed

Qin, Pengmin; Duncan, Niall W; Chen, David Yen-Ting; Chen, Chi-Jen; Huang, Li-Kai; Huang, Zirui; Lin, Chien-Yuan E; Wiebking, Christine; Yang, Che-Ming; Northoff, Georg; Lane, Timothy J

2018-05-21

Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [ 18 F]-fluoro-deoxyglucose PET in a group of healthy participants (n = 15), along with BOLD fMRI and [ 18 F]-flumazenil PET in a separate group (n = 19). Focusing on an EO- vs EC-sensitive region in the occipital cortex (identified in an independent sample), we show that TV is constrained in the EO condition compared to EC. This reduction is correlated with an increase in energy consumption and with regional GABA A receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Long-latency reductions in gamma power predict hemodynamic changes that underlie the negative BOLD signal.

PubMed

Boorman, Luke; Harris, Samuel; Bruyns-Haylett, Michael; Kennerley, Aneurin; Zheng, Ying; Martin, Chris; Jones, Myles; Redgrave, Peter; Berwick, Jason

2015-03-18

Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to "negative" hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30-80 Hz) in the middle-superficial cortical layers in regions surrounding the activated whisker barrel cortex. This reduction in gamma frequency activity was associated with corresponding decreases in the hemodynamic responses that drive the negative BOLD signal. These findings suggest a close relationship between BOLD responses and neural events that operate over time scales that outlast the initiating sensory stimulus, and provide important insights into the neurophysiological basis of negative neuroimaging signals. Copyright © 2015 Boorman et al.

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

PubMed Central

Harris, Samuel; Bruyns-Haylett, Michael; Kennerley, Aneurin; Zheng, Ying; Martin, Chris; Jones, Myles; Redgrave, Peter; Berwick, Jason

2015-01-01

Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to “negative” hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30–80 Hz) in the middle-superficial cortical layers in regions surrounding the activated whisker barrel cortex. This reduction in gamma frequency activity was associated with corresponding decreases in the hemodynamic responses that drive the negative BOLD signal. These findings suggest a close relationship between BOLD responses and neural events that operate over time scales that outlast the initiating sensory stimulus, and provide important insights into the neurophysiological basis of negative neuroimaging signals. PMID:25788681

Evolutionary dynamics of fearfulness and boldness.

PubMed

Ji, Ting; Zhang, Boyu; Sun, Yuehua; Tao, Yi

2009-02-21

A negative relationship between reproductive effort and survival is consistent with life-history. Evolutionary dynamics and evolutionarily stable strategy (ESS) for the trade-off between survival and reproduction are investigated using a simple model with two phenotypes, fearfulness and boldness. The dynamical stability of the pure strategy model and analysis of ESS conditions reveal that: (i) the simple coexistence of fearfulness and boldness is impossible; (ii) a small population size is favorable to fearfulness, but a large population size is favorable to boldness, i.e., neither fearfulness, nor boldness is always favored by natural selection; and (iii) the dynamics of population density is crucial for a proper understanding of the strategy dynamics.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

PubMed Central

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods.

PubMed

Byrne, Claire S; Chambers, Edward S; Alhabeeb, Habeeb; Chhina, Navpreet; Morrison, Douglas J; Preston, Tom; Tedford, Catriona; Fitzpatrick, Julie; Irani, Cherag; Busza, Albert; Garcia-Perez, Isabel; Fountana, Sofia; Holmes, Elaine; Goldstone, Anthony P; Frost, Gary S

2016-07-01

Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable. We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level-dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data). Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations. Our results suggest that colonic propionate production may play an important role in attenuating reward-based eating

Analysis of fMRI data using noise-diffusion network models: a new covariance-coding perspective.

PubMed

Gilson, Matthieu

2018-04-01

Since the middle of the 1990s, studies of resting-state fMRI/BOLD data have explored the correlation patterns of activity across the whole brain, which is referred to as functional connectivity (FC). Among the many methods that have been developed to interpret FC, a recently proposed model-based approach describes the propagation of fluctuating BOLD activity within the recurrently connected brain network by inferring the effective connectivity (EC). In this model, EC quantifies the strengths of directional interactions between brain regions, viewed from the proxy of BOLD activity. In addition, the tuning procedure for the model provides estimates for the local variability (input variances) to explain how the observed FC is generated. Generalizing, the network dynamics can be studied in the context of an input-output mapping-determined by EC-for the second-order statistics of fluctuating nodal activities. The present paper focuses on the following detection paradigm: observing output covariances, how discriminative is the (estimated) network model with respect to various input covariance patterns? An application with the model fitted to experimental fMRI data-movie viewing versus resting state-illustrates that changes in local variability and changes in brain coordination go hand in hand.

Functional magnetic resonance imaging in chronic ischaemic stroke.

PubMed

Lake, Evelyn M R; Bazzigaluppi, Paolo; Stefanovic, Bojana

2016-10-05

Ischaemic stroke is the leading cause of adult disability worldwide. Effective rehabilitation is hindered by uncertainty surrounding the underlying mechanisms that govern long-term ischaemic injury progression. Despite its potential as a sensitive non-invasive in vivo marker of brain function that may aid in the development of new treatments, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has found limited application in the clinical research on chronic stage stroke progression. Stroke affects each of the physiological parameters underlying the BOLD contrast, markedly complicating the interpretation of BOLD fMRI data. This review summarizes current progress on application of BOLD fMRI in the chronic stage of ischaemic injury progression and discusses means by which more information may be gained from such BOLD fMRI measurements. Concomitant measurements of vascular reactivity, neuronal activity and metabolism in preclinical models of stroke are reviewed along with illustrative examples of post-ischaemic evolution in neuronal, glial and vascular function. The realization of the BOLD fMRI potential to propel stroke research is predicated on the carefully designed preclinical research establishing an ischaemia-specific quantitative model of BOLD signal contrast to provide the framework for interpretation of fMRI findings in clinical populations.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Author(s).

Altered affective response in marijuana smokers: an FMRI study.

PubMed

Gruber, Staci A; Rogowska, Jadwiga; Yurgelun-Todd, Deborah A

2009-11-01

More than 94 million Americans have tried marijuana, and it remains the most widely used illicit drug in the nation. Investigations of the cognitive effects of marijuana report alterations in brain function during tasks requiring executive control, including inhibition and decision-making. Endogenous cannabinoids regulate a variety of emotional responses, including anxiety, mood control, and aggression; nevertheless, little is known about smokers' responses to affective stimuli. The anterior cingulate and amygdala play key roles in the inhibition of impulsive behavior and affective regulation, and studies using PET and fMRI have demonstrated changes within these regions in marijuana smokers. Given alterations in mood and perception often observed in smokers, we hypothesized altered fMRI patterns of response in 15 chronic heavy marijuana smokers relative to 15 non-marijuana smoking control subjects during the viewing of masked happy and fearful faces. Despite no between-group differences on clinical or demographic measures, smokers demonstrated a relative decrease in both anterior cingulate and amygdalar activity during masked affective stimuli compared to controls, who showed relative increases in activation within these regions during the viewing of masked faces. Findings indicate that chronic heavy marijuana smokers demonstrate altered activation of frontal and limbic systems while viewing masked faces, consistent with autoradiographic studies reporting high CB-1 receptor density in these regions. These data suggest differences in affective processing in chronic smokers, even when stimuli are presented below the level of conscious processing, and underscore the likelihood that marijuana smokers process emotional information differently from those who do not smoke, which may result in negative consequences.

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

NASA Astrophysics Data System (ADS)

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

2002-04-01

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

Association Between Brain Activation and Functional Connectivity.

PubMed

Tomasi, Dardo; Volkow, Nora D

2018-04-13

The origin of the "resting-state" brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response. This association was significantly attenuated by a novel task signal regression (TSR) procedure, indicating that task performance enhances lFCD and ALFF in activated regions. We also show that lFCD predicts BOLD activation patterns, as was recently shown for other functional connectivity metrics, which corroborates that resting functional connectivity architecture impacts brain activation responses. Thus, our findings indicate a common source for BOLD responses, ALFF and lFCD, which is consistent with the neurovascular origin of local hemodynamic synchrony presumably reflecting coordinated fluctuations in neuronal activity. This study also supports the development of task-evoked functional connectivity density mapping.

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

Physiological and genetic correlates of boldness: characterising the mechanisms of behavioural variation in rainbow trout, Oncorhynchus mykiss.

PubMed

Thomson, Jack S; Watts, Phillip C; Pottinger, Tom G; Sneddon, Lynne U

2011-01-01

Bold, risk-taking animals have previously been putatively linked with a proactive stress coping style whereas it is suggested shyer, risk-averse animals exhibit a reactive coping style. The aim of this study was to investigate whether differences in the expression of bold-type behaviour were evident within and between two lines of rainbow trout, Oncorhynchus mykiss, selectively bred for a low (LR) or high (HR) endocrine response to stress, and to link boldness and stress responsiveness with the expression of related candidate genes. Boldness was determined in individual fish over two trials by measuring the latency to approach a novel object. Differences in plasma cortisol concentrations and the expression of eight novel candidate genes previously identified as being linked with divergent behaviours or stress were determined. Bold and shy individuals, approaching the object within 180 s or not approaching within 300 s respectively, were evident within each line, and this was linked with activity levels in the HR line. Post-stress plasma cortisol concentrations were significantly greater in the HR line compared with the LR line, and six of the eight tested genes were upregulated in the brains of LR fish compared with HR fish. However, no direct relationship between boldness and either stress responsiveness or gene expression was found, although clear differences in stress physiology and, for the first time, gene expression could be identified between the lines. This lack of correlation between physiological and molecular responses and behavioural variation within both lines highlights the complexity of the behavioural-physiological complex. Copyright © 2010 Elsevier Inc. All rights reserved.

Analysis of task-evoked systemic interference in fNIRS measurements: insights from fMRI.

PubMed

Erdoğan, Sinem B; Yücel, Meryem A; Akın, Ata

2014-02-15

Functional near infrared spectroscopy (fNIRS) is a promising method for monitoring cerebral hemodynamics with a wide range of clinical applications. fNIRS signals are contaminated with systemic physiological interferences from both the brain and superficial tissues, resulting in a poor estimation of the task related neuronal activation. In this study, we use the anatomical resolution of functional magnetic resonance imaging (fMRI) to extract scalp and brain vascular signals separately and construct an optically weighted spatial average of the fMRI blood oxygen level-dependent (BOLD) signal for characterizing the scalp signal contribution to fNIRS measurements. We introduce an extended superficial signal regression (ESSR) method for canceling physiology-based systemic interference where the effects of cerebral and superficial systemic interference are treated separately. We apply and validate our method on the optically weighted BOLD signals, which are obtained by projecting the fMRI image onto optical measurement space by use of the optical forward problem. The performance of ESSR method in removing physiological artifacts is compared to i) a global signal regression (GSR) method and ii) a superficial signal regression (SSR) method. The retrieved signals from each method are compared with the neural signals that represent the 'ground truth' brain activation cleaned from cerebral systemic fluctuations. We report significant improvements in the recovery of task induced neural activation with the ESSR method when compared to the other two methods as reflected in the Pearson R(2) coefficient and mean square error (MSE) metrics (two tailed paired t-tests, p<0.05). The signal quality is enhanced most when ESSR method is applied with higher spatial localization, lower inter-trial variability, a clear canonical waveform and higher contrast-to-noise (CNR) improvement (60%). Our findings suggest that, during a cognitive task i) superficial scalp signal contribution to f

fMRI response to spatial working memory in adolescents with comorbid marijuana and alcohol use disorders☆

PubMed Central

Schweinsburg, Alecia D.; Schweinsburg, Brian C.; Cheung, Erick H.; Brown, Gregory G.; Brown, Sandra A.; Tapert, Susan F.

2008-01-01

Alcohol and marijuana use are prevalent in adolescence, yet the neural impact of concomitant use remains unclear. We previously demonstrated functional magnetic resonance imaging (fMRI) response to spatial working memory (SWM) among teens with alcohol use disorders (AUD) compared to controls, and predicted that adolescents with marijuana and alcohol use disorders would show additional abnormalities. Participants were three groups of 15−17-year-olds: 19 non-abusing controls, 15 AUD teens with limited exposure to drugs, and 15 teens with comorbid marijuana and alcohol use disorders (MAUD) and minimal other drug experience. After >2 days’ abstinence, participants performed a SWM task during fMRI acquisition. fMRI brain response patterns differed between groups, despite similar performance on the task. MAUD youths showed less activation in inferior frontal and temporal regions than controls, and more response in other prefrontal regions. Compared to AUD teens, MAUD youths also showed less inferior frontal and temporal activation, but more medial frontal response. Overall, MAUD youths showed different brain response abnormalities than teens with AUD alone, despite relatively short histories of substance involvement. This pattern could suggest compensation for marijuana-related attention and working memory deficits. However, relatively recent use and premorbid features may influence results, and should be examined in future studies. PMID:16002029

Voxel-wise motion artifacts in population-level whole-brain connectivity analysis of resting-state FMRI.

PubMed

Spisák, Tamás; Jakab, András; Kis, Sándor A; Opposits, Gábor; Aranyi, Csaba; Berényi, Ervin; Emri, Miklós

2014-01-01

Functional Magnetic Resonance Imaging (fMRI) based brain connectivity analysis maps the functional networks of the brain by estimating the degree of synchronous neuronal activity between brain regions. Recent studies have demonstrated that "resting-state" fMRI-based brain connectivity conclusions may be erroneous when motion artifacts have a differential effect on fMRI BOLD signals for between group comparisons. A potential explanation could be that in-scanner displacement, due to rotational components, is not spatially constant in the whole brain. However, this localized nature of motion artifacts is poorly understood and is rarely considered in brain connectivity studies. In this study, we initially demonstrate the local correspondence between head displacement and the changes in the resting-state fMRI BOLD signal. Than, we investigate how connectivity strength is affected by the population-level variation in the spatial pattern of regional displacement. We introduce Regional Displacement Interaction (RDI), a new covariate parameter set for second-level connectivity analysis and demonstrate its effectiveness in reducing motion related confounds in comparisons of groups with different voxel-vise displacement pattern and preprocessed using various nuisance regression methods. The effect of using RDI as second-level covariate is than demonstrated in autism-related group comparisons. The relationship between the proposed method and some of the prevailing subject-level nuisance regression techniques is evaluated. Our results show that, depending on experimental design, treating in-scanner head motion as a global confound may not be appropriate. The degree of displacement is highly variable among various brain regions, both within and between subjects. These regional differences bias correlation-based measures of brain connectivity. The inclusion of the proposed second-level covariate into the analysis successfully reduces artifactual motion-related group differences

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

PubMed Central

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

2014-01-01

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

Assessment of Unconstrained Cerebrovascular Reactivity Marker for Large Age-Range fMRI Studies

PubMed Central

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

2014-01-01

Breath hold (BH), a commonly used task to measure cerebrovascular reactivity (CVR) in fMRI studies varies in outcome among individuals due to subject-physiology and/or BH-inspiration/expiration differences (i.e., performance). In prior age-related fMRI studies, smaller task-related BOLD response variability is observed among younger than older individuals. Also, a linear CVR versus task relationship exists in younger individuals which maybe useful to test the accuracy of CVR responses in older groups. Hence we hypothesized that subject-related physiological and/or BH differences, if present, may compromise CVR versus task linearity in older individuals. To test the hypothesis, empirical BH versus task relationships from motor and cognitive areas were obtained in younger (mean age = 26 years) and older (mean age = 58 years) human subjects. BH versus task linearity was observed only in the younger group, confirming our hypothesis. Further analysis indicated BH responses and its variability to be similar in both younger and older groups, suggesting that BH may not accurately represent CVR in a large age range. Using the resting state fluctuation of amplitude (RSFA) as an unconstrained alternative to BH, subject-wise correspondence between BH and RSFA was tested. Correlation between BH versus RSFA was significant within the motor but was not significant in the cognitive areas in the younger and was completely disrupted in both areas in the older subjects indicating that BH responses are constrained by subject-related physiology and/or performance-related differences. Contrasting BH to task, RSFA-task relationships were independent of age accompanied by age-related increases in CVR variability as measured by RSFA, not observed with BH. Together the results obtained indicate that RSFA accurately represents CVR in any age range avoiding multiple and yet unknown physiologic and task-related pitfalls of BH. PMID:24551151

How restful is it with all that noise? Comparison of Interleaved silent steady state (ISSS) and conventional imaging in resting-state fMRI.

PubMed

Andoh, J; Ferreira, M; Leppert, I R; Matsushita, R; Pike, B; Zatorre, R J

2017-02-15

Resting-state fMRI studies have become very important in cognitive neuroscience because they are able to identify BOLD fluctuations in brain circuits involved in motor, cognitive, or perceptual processes without the use of an explicit task. Such approaches have been fruitful when applied to various disordered populations, or to children or the elderly. However, insufficient attention has been paid to the consequences of the loud acoustic scanner noise associated with conventional fMRI acquisition, which could be an important confounding factor affecting auditory and/or cognitive networks in resting-state fMRI. Several approaches have been developed to mitigate the effects of acoustic noise on fMRI signals, including sparse sampling protocols and interleaved silent steady state (ISSS) acquisition methods, the latter being used only for task-based fMRI. Here, we developed an ISSS protocol for resting-state fMRI (rs-ISSS) consisting of rapid acquisition of a set of echo planar imaging volumes following each silent period, during which the steady state longitudinal magnetization was maintained with a train of relatively silent slice-selective excitation pulses. We evaluated the test-retest reliability of intensity and spatial extent of connectivity networks of fMRI BOLD signal across three different days for rs-ISSS and compared it with a standard resting-state fMRI (rs-STD). We also compared the strength and distribution of connectivity networks between rs-ISSS and rs-STD. We found that both rs-ISSS and rs-STD showed high reproducibility of fMRI signal across days. In addition, rs-ISSS showed a more robust pattern of functional connectivity within the somatosensory and motor networks, as well as an auditory network compared with rs-STD. An increased connectivity between the default mode network and the language network and with the anterior cingulate cortex (ACC) network was also found for rs-ISSS compared with rs-STD. Finally, region of interest analysis showed

Simultaneous ERP and fMRI of the auditory cortex in a passive oddball paradigm.

PubMed

Liebenthal, Einat; Ellingson, Michael L; Spanaki, Marianna V; Prieto, Thomas E; Ropella, Kristina M; Binder, Jeffrey R

2003-08-01

Infrequent occurrences of a deviant sound within a sequence of repetitive standard sounds elicit the automatic mismatch negativity (MMN) event-related potential (ERP). The main MMN generators are located in the superior temporal cortex, but their number, precise location, and temporal sequence of activation remain unclear. In this study, ERP and functional magnetic resonance imaging (fMRI) data were obtained simultaneously during a passive frequency oddball paradigm. There were three conditions, a STANDARD, a SMALL deviant, and a LARGE deviant. A clustered image acquisition technique was applied to prevent contamination of the fMRI data by the acoustic noise of the scanner and to limit contamination of the electroencephalogram (EEG) by the gradient-switching artifact. The ERP data were used to identify areas in which the blood oxygenation (BOLD) signal varied with the magnitude of the negativity in each condition. A significant ERP MMN was obtained, with larger peaks to LARGE deviants and with frontocentral scalp distribution, consistent with the MMN reported outside the magnetic field. This result validates the experimental procedures for simultaneous ERP/fMRI of the auditory cortex. Main foci of increased BOLD signal were observed in the right superior temporal gyrus [STG; Brodmann area (BA) 22] and right superior temporal plane (STP; BA 41 and 42). The imaging results provide new information supporting the idea that generators in the right lateral aspect of the STG are implicated in processes of frequency deviant detection, in addition to generators in the right and left STP.

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

PubMed

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

2013-03-01

Patients with Alzheimer's disease have category-specific semantic memory difficulty for natural relative to manufactured objects. We assessed the basis for this deficit by asking healthy adults and patients to judge whether pairs of words share a feature (e.g. "banana:lemon-COLOR"). In an fMRI study, healthy adults showed gray matter (GM) activation of temporal-occipital cortex (TOC) where visual-perceptual features may be represented, and prefrontal cortex (PFC) which may contribute to feature selection. Tractography revealed dorsal and ventral stream white matter (WM) projections between PFC and TOC. Patients had greater difficulty with natural than manufactured objects. This was associated with greater overlap between diseased GM areas correlated with natural kinds in patients and fMRI activation in healthy adults for natural kinds. The dorsal WM projection between PFC and TOC in patients correlated only with judgments of natural kinds. Patients thus remained dependent on the same neural network as controls during judgments of natural kinds, despite disease in these areas. For manufactured objects, patients' judgments showed limited correlations with PFC and TOC GM areas activated by controls, and did not correlate with the PFC-TOC dorsal WM tract. Regions outside of the PFC-TOC network thus may help support patients' judgments of manufactured objects. We conclude that a large-scale neural network for semantic memory implicates both feature knowledge representations in modality-specific association cortex and heteromodal regions important for accessing this knowledge, and that patients' relative deficit for natural kinds is due in part to their dependence on this network despite disease in these areas. Copyright © 2012 Elsevier Inc. All rights reserved.

Convergence of EEG and fMRI measures of reward anticipation.

PubMed

Gorka, Stephanie M; Phan, K Luan; Shankman, Stewart A

2015-12-01

Deficits in reward anticipation are putative mechanisms for multiple psychopathologies. Research indicates that these deficits are characterized by reduced left (relative to right) frontal electroencephalogram (EEG) activity and blood oxygenation level-dependent (BOLD) signal abnormalities in mesolimbic and prefrontal neural regions during reward anticipation. Although it is often assumed that these two measures capture similar mechanisms, no study to our knowledge has directly examined the convergence between frontal EEG alpha asymmetry and functional magnetic resonance imaging (fMRI) during reward anticipation in the same sample. Therefore, the aim of the current study was to investigate if and where in the brain frontal EEG alpha asymmetry and fMRI measures were correlated in a sample of 40 adults. All participants completed two analogous reward anticipation tasks--once during EEG data collection and the other during fMRI data collection. Results indicated that the two measures do converge and that during reward anticipation, increased relative left frontal activity is associated with increased left anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC) and left orbitofrontal cortex (OFC) activation. This suggests that the two measures may similarly capture PFC functioning, which is noteworthy given the role of these regions in reward processing and the pathophysiology of disorders such as depression and schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Modulation by EEG features of BOLD responses to interictal epileptiform discharges

PubMed Central

LeVan, Pierre; Tyvaert, Louise; Gotman, Jean

2013-01-01

Introduction EEG-fMRI of interictal epileptiform discharges (IEDs) usually assumes a fixed hemodynamic response function (HRF). This study investigates HRF variability with respect to IED amplitude fluctuations using independent component analysis (ICA), with the goal of improving the specificity of EEG-fMRI analyses. Methods We selected EEG-fMRI data from 10 focal epilepsy patients with a good quality EEG. IED amplitudes were calculated in an average reference montage. The fMRI data were decomposed by ICA and a deconvolution method identified IED-related components by detecting time courses with a significant HRF time-locked to the IEDs (F-test, p<0.05). Individual HRF amplitudes were then calculated for each IED. Components with a significant HRF/IED amplitude correlation (Spearman test, p< 0.05) were compared to the presumed epileptogenic focus and to results of a general linear model (GLM) analysis. Results In 7 patients, at least one IED-related component was concordant with the focus, but many IED-related components were at distant locations. When considering only components with a significant HRF/IED amplitude correlation, distant components could be discarded, significantly increasing the relative proportion of activated voxels in the focus (p=0.02). In the 3 patients without concordant IED-related components, no HRF/IED amplitude correlations were detected inside the brain. Integrating IED-related amplitudes in the GLM significantly improved fMRI signal modeling in the epileptogenic focus in 4 patients (p< 0.05). Conclusion Activations in the epileptogenic focus appear to show significant correlations between HRF and IED amplitudes, unlike distant responses. These correlations could be integrated in the analysis to increase the specificity of EEG-fMRI studies in epilepsy. PMID:20026222

Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network

PubMed Central

Boettiger, Charlotte A.; Kelley, Elizabeth A.; Mitchell, Jennifer M.; D’Esposito, Mark; Fields, Howard L.

2009-01-01

Previously, we found that distinct brain areas predict individual selection bias in decisions between small immediate (“Now”) and larger delayed rewards (“Later”). Furthermore, such selection bias can be manipulated by endogenous opioid blockade. To test whether blocking endogenous opioids with Naltrexone (NTX) alters brain activity during decision-making in areas predicting individual bias, we compared fMRI BOLD signal correlated with Now versus Later decision-making after acute administration of NTX (50 mg) or placebo. We tested abstinent alcoholics and control subjects in a double-blind two-session design. We defined regions of interest (ROI) centered on activation peaks predicting Now versus Later selection bias. NTX administration significantly increased BOLD signal during decision-making in the right lateral orbital gyrus ROI, an area where enhanced activity during decision-making predicts Later bias. Exploratory analyses identified additional loci where BOLD signal during decision-making was enhanced (left orbitofrontal cortex, left inferior temporal gyrus, and cerebellum) or reduced (right superior temporal pole) by NTX. Additional analyses identified sites, including the right lateral orbital gyrus, in which NTX effects on BOLD signal predicted NTX effects on selection bias. These data agree with opioid receptor expression in human frontal and temporal cortices, and suggest possible mechanisms of NTX’s therapeutic effects. PMID:19258022

Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study.

PubMed

Moeller, Scott J; Konova, Anna B; Tomasi, Dardo; Parvaz, Muhammad A; Goldstein, Rita Z

2016-07-01

The indirect dopamine agonist methylphenidate remediates cognitive deficits in psychopathology, but the individual characteristics that determine its effects on the brain are not known. We aimed to determine whether targeted dopaminergically modulated traits and individual differences could predict neural response to methylphenidate across multiple functional magnetic resonance imaging (fMRI) procedures. We combined neural measures from three separate procedures (two inhibitory control tasks differing in their degree of emotional salience and resting-state functional connectivity) during methylphenidate (20 mg oral, versus randomized and counterbalanced placebo) and correlated these aggregated responses with cocaine use disorder diagnosis (22 cocaine abusers, 21 controls), symptoms of attention deficit hyperactivity disorder, and working memory capacity. Cocaine abusers, relative to controls, had a lower response in the dorsolateral prefrontal cortex to methylphenidate across all three procedures, driven by responses to the two inhibitory control tasks; reduced methylphenidate fMRI response in this region further correlated with more frequent cocaine use. Cocaine abuse (and its frequency), associated with lower tonic dopamine levels, correlated with a reduction in activation to methylphenidate (versus placebo). These initial results provide feasibility to the idea that multimodal fMRI tasks can be meaningfully aggregated, and that these aggregated procedures show a common disruption in addiction in a highly anticipated region relevant to cognitive control. Results also suggest that drug use frequency may represent an important modulatory variable in interpreting the efficacy of pharmacologically enhanced cognitive interventions in addiction.

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

PubMed

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

2011-01-01

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

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

Adaptation of a haptic robot in a 3T fMRI.

PubMed

Snider, Joseph; Plank, Markus; May, Larry; Liu, Thomas T; Poizner, Howard

2011-10-04

Functional magnetic resonance imaging (fMRI) provides excellent functional brain imaging via the BOLD signal with advantages including non-ionizing radiation, millimeter spatial accuracy of anatomical and functional data, and nearly real-time analyses. Haptic robots provide precise measurement and control of position and force of a cursor in a reasonably confined space. Here we combine these two technologies to allow precision experiments involving motor control with haptic/tactile environment interaction such as reaching or grasping. The basic idea is to attach an 8 foot end effecter supported in the center to the robot allowing the subject to use the robot, but shielding it and keeping it out of the most extreme part of the magnetic field from the fMRI machine (Figure 1). The Phantom Premium 3.0, 6DoF, high-force robot (SensAble Technologies, Inc.) is an excellent choice for providing force-feedback in virtual reality experiments, but it is inherently non-MR safe, introduces significant noise to the sensitive fMRI equipment, and its electric motors may be affected by the fMRI's strongly varying magnetic field. We have constructed a table and shielding system that allows the robot to be safely introduced into the fMRI environment and limits both the degradation of the fMRI signal by the electrically noisy motors and the degradation of the electric motor performance by the strongly varying magnetic field of the fMRI. With the shield, the signal to noise ratio (SNR: mean signal/noise standard deviation) of the fMRI goes from a baseline of ~380 to ~330, and ~250 without the shielding. The remaining noise appears to be uncorrelated and does not add artifacts to the fMRI of a test sphere (Figure 2). The long, stiff handle allows placement of the robot out of range of the most strongly varying parts of the magnetic field so there is no significant effect of the fMRI on the robot. The effect of the handle on the robot's kinematics is minimal since it is lightweight (~2

Arterial Spin Labeling (ASL) fMRI: advantages, theoretical constrains, and experimental challenges in neurosciences.

PubMed

Borogovac, Ajna; Asllani, Iris

2012-01-01

Cerebral blood flow (CBF) is a well-established correlate of brain function and therefore an essential parameter for studying the brain at both normal and diseased states. Arterial spin labeling (ASL) is a noninvasive fMRI technique that uses arterial water as an endogenous tracer to measure CBF. ASL provides reliable absolute quantification of CBF with higher spatial and temporal resolution than other techniques. And yet, the routine application of ASL has been somewhat limited. In this review, we start by highlighting theoretical complexities and technical challenges of ASL fMRI for basic and clinical research. While underscoring the main advantages of ASL versus other techniques such as BOLD, we also expound on inherent challenges and confounds in ASL perfusion imaging. In closing, we expound on several exciting developments in the field that we believe will make ASL reach its full potential in neuroscience research.

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

PubMed

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

2014-11-01

Response inhibition is commonly thought to rely on voluntary, reactive, selective, and relatively slow prefrontal mechanisms. In contrast, we suggest here that response inhibition is achieved automatically, nonselectively, within very short delays in uncertain environments. We modified a classical go/nogo protocol to probe context-dependent inhibitory mechanisms. Because no single neuroimaging method can definitely disentangle neural excitation and inhibition, we combined fMRI and EEG recordings in healthy humans. Any stimulus (go or nogo) presented in an uncertain context requiring action restraint was found to evoke activity changes in the supplementary motor complex (SMC) with respect to a control condition in which no response inhibition was required. These changes included: (1) An increase in event-related BOLD activity, (2) an attenuation of the early (170 ms) event related potential generated by a single, consistent source isolated by advanced blind source separation, and (3) an increase in the evoked-EEG Alpha power of this source. Considered together, these results suggest that the BOLD signal evoked by any stimulus in the SMC when the situation is unpredictable can be driven by automatic, nonselective, context-dependent inhibitory activities. This finding reveals the paradoxical mechanisms by which voluntary control of action may be achieved. The ability to provide controlled responses in unpredictable environments would require setting-up the automatic self-inhibitory circuitry within the SMC. Conversely, enabling automatic behavior when the environment becomes predictable would require top-down control to deactivate anticipatorily and temporarily the inhibitory set. Copyright © 2014 Wiley Periodicals, Inc.

Influences of Dietary Added Sugar Consumption on Striatal Food-Cue Reactivity and Postprandial GLP-1 Response

PubMed Central

Dorton, Hilary M.; Luo, Shan; Monterosso, John R.; Page, Kathleen A.

2018-01-01

Sugar consumption in the United States exceeds recommendations from the American Heart Association. Overconsumption of sugar is linked to risk for obesity and metabolic disease. Animal studies suggest that high-sugar diets alter functions in brain regions associated with reward processing, including the dorsal and ventral striatum. Human neuroimaging studies have shown that these regions are responsive to food cues, and that the gut-derived satiety hormones, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY), suppress striatal food-cue responsivity. We aimed to determine the associations between dietary added sugar intake, striatal responsivity to food cues, and postprandial GLP-1 and PYY levels. Twenty-two lean volunteers underwent a functional magnetic resonance imaging (fMRI) scan during which they viewed pictures of food and non-food items after a 12-h fast. Before scanning, participants consumed a glucose drink. A subset of 19 participants underwent an additional fMRI session in which they consumed water as a control condition. Blood was sampled for GLP-1, and PYY levels and hunger ratings were assessed before and ~75 min after drink consumption. In-person 24-h dietary recalls were collected from each participant on three to six separate occasions over a 2-month period. Average percent calories from added sugar were calculated using information from 24-h dietary recalls. A region-of-interest analysis was performed to compare the blood oxygen level-dependent (BOLD) response to food vs. non-food cues in the bilateral dorsal striatum (caudate/putamen) and ventral striatum (nucleus accumbens). The relationships between added sugar, striatal responses, and hormone changes after drink consumption were assessed using Spearman’s correlations. We observed a positive correlation between added sugar intake and BOLD response to food cues in the dorsal striatum and a similar trend in the nucleus accumbens after glucose, but not water, consumption. Added sugar intake

Influences of Dietary Added Sugar Consumption on Striatal Food-Cue Reactivity and Postprandial GLP-1 Response.

PubMed

Dorton, Hilary M; Luo, Shan; Monterosso, John R; Page, Kathleen A

2017-01-01

Sugar consumption in the United States exceeds recommendations from the American Heart Association. Overconsumption of sugar is linked to risk for obesity and metabolic disease. Animal studies suggest that high-sugar diets alter functions in brain regions associated with reward processing, including the dorsal and ventral striatum. Human neuroimaging studies have shown that these regions are responsive to food cues, and that the gut-derived satiety hormones, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY), suppress striatal food-cue responsivity. We aimed to determine the associations between dietary added sugar intake, striatal responsivity to food cues, and postprandial GLP-1 and PYY levels. Twenty-two lean volunteers underwent a functional magnetic resonance imaging (fMRI) scan during which they viewed pictures of food and non-food items after a 12-h fast. Before scanning, participants consumed a glucose drink. A subset of 19 participants underwent an additional fMRI session in which they consumed water as a control condition. Blood was sampled for GLP-1, and PYY levels and hunger ratings were assessed before and ~75 min after drink consumption. In-person 24-h dietary recalls were collected from each participant on three to six separate occasions over a 2-month period. Average percent calories from added sugar were calculated using information from 24-h dietary recalls. A region-of-interest analysis was performed to compare the blood oxygen level-dependent (BOLD) response to food vs. non-food cues in the bilateral dorsal striatum (caudate/putamen) and ventral striatum (nucleus accumbens). The relationships between added sugar, striatal responses, and hormone changes after drink consumption were assessed using Spearman's correlations. We observed a positive correlation between added sugar intake and BOLD response to food cues in the dorsal striatum and a similar trend in the nucleus accumbens after glucose, but not water, consumption. Added sugar intake

Overweight adolescents' brain response to sweetened beverages mirrors addiction pathways.

PubMed

Feldstein Ewing, Sarah W; Claus, Eric D; Hudson, Karen A; Filbey, Francesca M; Yakes Jimenez, Elizabeth; Lisdahl, Krista M; Kong, Alberta S

2017-08-01

Many adolescents struggle with overweight/obesity, which exponentially increases in the transition to adulthood. Overweight/obesity places youth at risk for serious health conditions, including type 2 diabetes. In adults, neural substrates implicated in addiction (e.g., orbitofrontal cortex (OFC), striatum, amygdala, and ventral tegmental area) have been found to be relevant to risk for overweight/obesity. In this study, we examined three hypotheses to disentangle the potential overlap between addiction and overweight/obesity processing by examining (1) brain response to high vs. low calorie beverages, (2) the strength of correspondence between biometrics, including body mass index (BMI) and insulin resistance, and brain response and (3) the relationship between a measure of food addiction and brain response using an established fMRI gustatory cue exposure task with a sample of overweight/obese youth (M age = 16.46; M BMI = 33.1). Greater BOLD response was observed across the OFC, inferior frontal gyrus (IFG), nucleus accumbens, right amygdala, and additional frontoparietal and temporal regions in neural processing of high vs. low calorie beverages. Further, BMI scores positively correlated with BOLD activation in the high calorie > low calorie contrast in the right postcentral gyrus and central operculum. Insulin resistance positively correlated with BOLD activation across the bilateral middle/superior temporal gyrus, left OFC, and superior parietal lobe. No relationships were observed between measures of food addiction and brain response. These findings support the activation of parallel addiction-related neural pathways in adolescents' high calorie processing, while also suggesting the importance of refining conceptual and neurocognitive models to fit this developmental period.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity.

PubMed

Drew Sayer, R; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

2016-10-01

The brain's reward system influences ingestive behavior and subsequently obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. This study sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n = 16) and men (n = 12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the two testing days. Mean fasting-state brain responses on day 2 were reduced compared with day 1 in the left insula and right amygdala, but mean day 1 and day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. © 2016 The Obesity Society.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity

PubMed Central

Sayer, R Drew; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

2016-01-01

Objective The brain’s reward system influences ingestive behavior and subsequently, obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. We sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. Methods A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n=16) and men (n=12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the 2 testing days. Results Mean fasting-state brain responses on Day 2 were reduced compared to Day 1 in the left insula and right amygdala, but mean Day 1 and Day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. Conclusion fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility, but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. PMID:27542906

Mapping cerebrovascular reactivity using concurrent fMRI and near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Tong, Yunjie; Bergethon, Peter R.; Frederick, Blaise d.

2011-02-01

Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral vasculature to a dilatory stimulus and is an important indicator of brain vascular reserve. fMRI has been proven to be an effective imaging technique to obtain the CVR map when the subjects perform CO2 inhalation or the breath holding task (BH). However, the traditional data analysis inaccurately models the BOLD using a boxcar function with fixed time delay. We propose a novel way to process the fMRI data obtained during a blocked BH by using the simultaneously collected near infrared spectroscopy (NIRS) data as regressor1. In this concurrent NIRS and fMRI study, 6 healthy subjects performed a blocked BH (5 breath holds with 20s durations intermitted by 40s of regular breathing). A NIRS probe of two sources and two detectors separated by 3 cm was placed on the right side of prefrontal area of the subjects. The time course of changes in oxy-hemoglobin (Δ[HbO]) was calculated from NIRS data and shifted in time by various amounts, and resampled to the fMRI acquisition rate. Each shifted time course was used as regressor in FEAT (the analysis tool in FSL). The resulting z-statistic maps were concatenated in time and the maximal value was taken along the time for all the voxels to generate a 3-D CVR map. The new method produces more accurate and thorough CVR maps; moreover, it enables us to produce a comparable baseline cerebral vascular map if applied to resting state (RS) data.

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

PubMed

Raut, Savita V; Yadav, Dinkar M

2018-03-28

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.

Functional MRI of human pancreas using BOLD contrast: Responses following glucose ingestion.

PubMed

Chen, Bozhu; Chen, Weibo; Chan, Queenie; Zhou, Nan; He, Jian; Zhou, Zhengyang

2017-09-01

To evaluate the response of the pancreas to glucose ingestion in healthy volunteers by blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). This study was approved by the local Ethics Committee, and informed consent was obtained from all subjects. A multiple gradient recalled echo (mGRE) sequence was performed on a 3.0T MR scanner in 12 healthy volunteers before and after glucose or water ingestion. Pancreatic T2* values were calculated from it at each timepoint, and changes following stimulation were analyzed using summary measures. The valley values and times were compared between the glucose and water ingestion by paired samples t-test. The repeatability of the pancreatic T2* measurements was assessed by calculating the intraclass correlation coefficient (ICC) and coefficient of variation (CV). Pancreatic T2* measurements showed good repeatability (all ICC >0.75). CV for the six baseline acquisitions was 2.74 ± 0.97%, indicating a 5.37% measurement error. A transient but significant decrease (-6.88 ± 1.01%, P value, 0.0005-0.0467) in the pancreatic T2* values was observed within 5 minutes after glucose ingestion, rather than water consumption. Compared to water, glucose ingestion induced earlier (valley times: 3.46 ± 3.22 vs. 7.75 ± 4.09 min, P = 0.0006) and remarkable pancreatic T2* decrease (valley values: -15.33 ± 5.90% vs. -6.88 ± 3.11%, P = 0.0006). BOLD MRI enabled noninvasive quantification of pancreatic T2* changes during glucose stimulation. Glucose ingestion resulted in a rapid and significant pancreatic T2* decrease in healthy young volunteers. 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:831-836. © 2017 International Society for Magnetic Resonance in Medicine.

Neural correlates of the emotional Stroop task in panic disorder patients: an event-related fMRI study.

PubMed

Dresler, Thomas; Hindi Attar, Catherine; Spitzer, Carsten; Löwe, Bernd; Deckert, Jürgen; Büchel, Christian; Ehlis, Ann-Christine; Fallgatter, Andreas J

2012-12-01

Although being a standard tool to assess interference effects of disorder-specific words in clinical samples, the neural underpinnings of the emotional Stroop task are still not well understood and have hardly been investigated in experimental case-control studies. We therefore used functional magnetic resonance imaging (fMRI) to examine the attentional bias toward panic-related words in panic disorder (PD) patients and healthy controls. Twenty PD patients (with or without agoraphobia) and 23 healthy controls matched for age and gender performed an event-related emotional Stroop task with panic-related and neutral words while undergoing 3 Tesla fMRI. On the behavioral level, PD patients showed a significant emotional Stroop effect, i.e. color-naming of panic-related words was prolonged compared to neutral words. This effect was not observed in the control group. PD patients further differed from controls on the neural level in showing increased BOLD activity in the left inferior frontal gyrus in response to panic-related relative to neutral words. PD patients showed the expected attentional bias, i.e. an altered processing of disorder-specific stimuli. This emotional Stroop effect was paralleled by increased activation in the left prefrontal cortex which may indicate altered processing of emotional stimulus material. Copyright © 2012 Elsevier Ltd. All rights reserved.

Does Right-Sided Language Lateralization on BOLD-fMRI Affect Postoperative Language Outcome for AVM Patients?

PubMed

Liu, Zhi; Deng, Xiaofeng; Cao, Yong; Zhao, Yuanli; Zhao, Jizong; Wang, Shuo

2017-01-01

For cerebral arteriovenous malformations (AVMs) involving language areas, right-sided language lateralization on functional magnetic resonance imaging (fMRI) has been reported, which is regarded as language cortex reorganization. The authors attempted to study if this right-sided language lateralization affects postoperative language outcome. Clinical and imaging data of 43 right-handed AVM patients who underwent preoperative fMRI were retrospectively reviewed. All lesions involved the language cortex, with the Broca area involved in 13 patients and the Wernicke area involved in 30 patients. Lateralization indices (LI) of BOLD signal activations were calculated to determine language lateralization. All patients underwent craniotomy and total resection. Western aphasia battery (WAB) was used to evaluate language functions preoperatively, 1-2 weeks after surgery and 6-30 months after surgery. On preoperative fMRI, right-sided lateralization was observed in 18 patients (41.9%, R Group), including 3 with rightsided lateralization in the Broca area alone, 14 in the Wernicke area alone, and 1 in both areas. The other 25 patients were non-rightsided lateralized (NR Group). One week after surgery, 7 patients in the R Group (38.9%) and 11 patients in the NR Group (44.0%) had language function deterioration, and no significant difference was found (p=0.983). At long-term follow-up, 3 patients in the R Group (16.7%) and 4 patients in the NR Group (16.0%) still had aphasia, and no significant difference was observed (p=1.000). Although right-sided lateralization on fMRI might suggest language cortex reorganization, it is not a factor predicting better postoperative language outcome for AVM patients.

Multivariate analysis of fMRI time series: classification and regression of brain responses using machine learning.

PubMed

Formisano, Elia; De Martino, Federico; Valente, Giancarlo

2008-09-01

Machine learning and pattern recognition techniques are being increasingly employed in functional magnetic resonance imaging (fMRI) data analysis. By taking into account the full spatial pattern of brain activity measured simultaneously at many locations, these methods allow detecting subtle, non-strictly localized effects that may remain invisible to the conventional analysis with univariate statistical methods. In typical fMRI applications, pattern recognition algorithms "learn" a functional relationship between brain response patterns and a perceptual, cognitive or behavioral state of a subject expressed in terms of a label, which may assume discrete (classification) or continuous (regression) values. This learned functional relationship is then used to predict the unseen labels from a new data set ("brain reading"). In this article, we describe the mathematical foundations of machine learning applications in fMRI. We focus on two methods, support vector machines and relevance vector machines, which are respectively suited for the classification and regression of fMRI patterns. Furthermore, by means of several examples and applications, we illustrate and discuss the methodological challenges of using machine learning algorithms in the context of fMRI data analysis.

Effect of surrounding vasculature on intravoxel BOLD signal.

PubMed

Chen, Zikuan; Caprihan, Arvind; Calhoun, Vince

2010-04-01

The nonlocal influence from distant magnetization will affect the magnetic field at a voxel in question. Existing reports on BOLD simulation only consider vasculature inside a single voxel, thus omitting the contribution from the surrounding regions. In this article, the authors study the effect of the surrounding vasculature on the magnetic field and the BOLD signal at a cortical voxel by numerical simulation. A cortical voxel is generated as a cubic bin filled with randomly networked capillary vessels. First, the authors generate a cortical voxel with a random vessel network and embed it in a greater voxel by filling its surrounding region with vasculatures by different strategies. Next, they calculate the blood-susceptibility-induced magnetic field (BOLD field) at the voxel of interest (VOI) by a Fourier transform technique for different surrounding scenarios and varying surrounding extent. The BOLD field inhomogeneity is described by a radial distribution with a collection of cubic shell masks. The surrounding extent is defined by a collection of concentric cubes, which encase the VOI. Given a BOLD field in the presence of surrounding vasculature, they calculate BOLD signals by intravoxel dephasing. The influence from the surroundings on the BOLD field at a voxel in question mainly happens at the boundary. The most influence to the BOLD signal is from the inner surroundings. For a 160 x 160 x 160 microm3 voxel embedded in a 480 x 480 x 480 microm3 greater region, the surroundings could disturb the magnetic field by an amount in the range of [-0.002, 0.010] ppmT and could change the BOLD signal ratio in the range of [2.5%, 10%]. (These results were generated from the setting of delta(chi b)B0 = 3 ppmT, capillary = {2.5,6,9} microm, and relaxation time = 60 ms). The surrounding vasculature will impose a magnetic field disturbance at the voxel in question due to the nonlocal influence of magnetization. Simulation results show that the surrounding vasculature

Hippocampal activations in mesial temporal lobe epilepsy due to hippocampal sclerosis- an observational study on intramural encoding-delayed recall paradigms using task-based memory fMRI.

PubMed

Rajesh, P G; Thomas, Bejoy; Pammi, V S Chandrasekhar; Kesavadas, C; Alexander, Aley; Radhakrishnan, Ashalatha; Thomas, S V; Menon, R N

2018-05-26

To validate concurrent utility of within-scanner encoding and delayed recognition-memory paradigms to ascertain hippocampal activations during task-based memory fMRI. Memory paradigms were designed for faces, word-pairs and abstract designs. A deep-encoding task was designed comprising of a total of 9 cycles run within a 1.5T MRI scanner. A recall session was performed after 1 h within the scanner using an event-related design. Group analysis was done with 'correct-incorrect' responses applied as parametric modulators in Statistical Parametric Mapping version 8 using boot-strap method to enable estimation of laterality indices (LI) using custom anatomical masks involving the medio-basal temporal structures. Twenty seven subjects with drug-resistant mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE-HS) [17 patients of left-MTLE and 10 patients of right-MTLE] and 21 right handed age-matched healthy controls (HC) were recruited. For the encoding paradigm blood oxygen level dependent (BOLD) responses in HC demonstrated right laterality for faces, left laterality for word pairs, and bilaterality for design encoding over the regions of interest. Both right and left MTLE-HS groups revealed left lateralisation for word-pair encoding, bilateral activation for face encoding, with design encoding in right MTLE-HS demonstrating a left shift. As opposed to lateralization shown in controls, group analysis of cued-recall BOLD signals acquired within scanner in left MTLE-HS demonstrated right lateralization for word-pairs with bilaterality for faces and designs. The right MTLE-HS group demonstrated bilateral activations for faces, word-pairs and designs. Recall-based fMRI paradigms indicate hippocampal plasticity in MTLE-HS, maximal for word-pair associate recall tasks. Copyright © 2018 Elsevier B.V. All rights reserved.

Effective Connectivity of Cortical Sensorimotor Networks During Finger Movement Tasks: A Simultaneous fNIRS, fMRI, EEG Study.

PubMed

Anwar, A R; Muthalib, M; Perrey, S; Galka, A; Granert, O; Wolff, S; Heute, U; Deuschl, G; Raethjen, J; Muthuraman, Muthuraman

2016-09-01

Recently, interest has been growing to understand the underlying dynamic directional relationship between simultaneously activated regions of the brain during motor task performance. Such directionality analysis (or effective connectivity analysis), based on non-invasive electrophysiological (electroencephalography-EEG) and hemodynamic (functional near infrared spectroscopy-fNIRS; and functional magnetic resonance imaging-fMRI) neuroimaging modalities can provide an estimate of the motor task-related information flow from one brain region to another. Since EEG, fNIRS and fMRI modalities achieve different spatial and temporal resolutions of motor-task related activation in the brain, the aim of this study was to determine the effective connectivity of cortico-cortical sensorimotor networks during finger movement tasks measured by each neuroimaging modality. Nine healthy subjects performed right hand finger movement tasks of different complexity (simple finger tapping-FT, simple finger sequence-SFS, and complex finger sequence-CFS). We focused our observations on three cortical regions of interest (ROIs), namely the contralateral sensorimotor cortex (SMC), the contralateral premotor cortex (PMC) and the contralateral dorsolateral prefrontal cortex (DLPFC). We estimated the effective connectivity between these ROIs using conditional Granger causality (GC) analysis determined from the time series signals measured by fMRI (blood oxygenation level-dependent-BOLD), fNIRS (oxygenated-O2Hb and deoxygenated-HHb hemoglobin), and EEG (scalp and source level analysis) neuroimaging modalities. The effective connectivity analysis showed significant bi-directional information flow between the SMC, PMC, and DLPFC as determined by the EEG (scalp and source), fMRI (BOLD) and fNIRS (O2Hb and HHb) modalities for all three motor tasks. However the source level EEG GC values were significantly greater than the other modalities. In addition, only the source level EEG showed a

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

USGS Publications Warehouse

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

2008-01-01

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

Ecological consequences of the bold-shy continuum: the effect of predator boldness on prey risk.

PubMed

Ioannou, C C; Payne, M; Krause, J

2008-08-01

Although the existence of different personality traits within and between animal populations has been relatively well established, the ecological implications of this variation remain neglected. In this study we tested whether differences in the boldness of pairs of three-spined sticklebacks led to differential predation risk in their prey, Chironomidae larvae. Bolder pairs, those that left a refuge and crossed the tank mid-line sooner, ate a greater proportion of prey in 10 min than less bold fish (therefore prey were at a greater per capita risk). Fish crossed the mid-line more rapidly when a larger number of prey were presented, suggesting they accepted greater risk in return for a larger foraging reward. Perception of predation risk also affected the differences between fish in boldness, as larger fish crossed the mid-line sooner after leaving the refuge (larger fish are less at risk from predation). Hence, an interesting trophic interaction occurs, where the risk experienced by the chironomid larvae is determined by the risk perceived by their predators. Through the variation generated by boldness, a form of behaviourally mediated trophic cascade can occur within (as well as between) communities.

Increased ventral striatal BOLD activity during non-drug reward anticipation in cannabis users.

PubMed

Nestor, Liam; Hester, Robert; Garavan, Hugh

2010-01-01

Despite an increased understanding of the pharmacology and long-term cognitive effects of cannabis in humans, there has been no research to date examining its chronic effects upon reward processing in the brain. Motivational theories regarding long-term drug use posit contrasting predictions with respect to how drug users are likely to process non-drug incentives. The reward deficiency syndrome (RDS) of addiction posits that there are deficits in dopamine (DA) motivational circuitry for non-drug rewards, such that only drugs of abuse are capable of normalizing DA in the ventral striatum (VS). Alternatively, the opponent process theory (OPT) holds that in individuals prone to drug use, there exists some form of mesolimbic hyperactivity, in which there is a bias towards reward-centred behaviour concomitant with impulsivity. The current study examined BOLD responses during reward and loss anticipation and their outcome deliveries in 14 chronic cannabis users and 14 drug-naive controls during a monetary incentive delay (MID) task. Despite no significant behavioural differences between the two groups, cannabis users had significantly more right VS BOLD activity during reward anticipation. Correlation analyses demonstrated that this right VS BOLD response was significantly correlated with life-time use and reported life-time cannabis joints consumed. No correlations between cannabis abstinence and BOLD responses were observed. We also observed a number of group differences following outcome deliveries, most notably hypoactivity in the left insula cortex in response to loss and loss avoidance outcome notifications in the cannabis group. These results may suggest hypersensitivity during instrumental response anticipation for non-drug rewards and a hyposensitivity to loss outcomes in chronic cannabis users; the implications of which are discussed with respect to the potentially sensitizing effects of cannabis for other rewards.

Interleaved EPI based fMRI improved by multiplexed sensitivity encoding (MUSE) and simultaneous multi-band imaging.

PubMed

Chang, Hing-Chiu; Gaur, Pooja; Chou, Ying-hui; Chu, Mei-Lan; Chen, Nan-kuei

2014-01-01

Functional magnetic resonance imaging (fMRI) is a non-invasive and powerful imaging tool for detecting brain activities. The majority of fMRI studies are performed with single-shot echo-planar imaging (EPI) due to its high temporal resolution. Recent studies have demonstrated that, by increasing the spatial-resolution of fMRI, previously unidentified neuronal networks can be measured. However, it is challenging to improve the spatial resolution of conventional single-shot EPI based fMRI. Although multi-shot interleaved EPI is superior to single-shot EPI in terms of the improved spatial-resolution, reduced geometric distortions, and sharper point spread function (PSF), interleaved EPI based fMRI has two main limitations: 1) the imaging throughput is lower in interleaved EPI; 2) the magnitude and phase signal variations among EPI segments (due to physiological noise, subject motion, and B0 drift) are translated to significant in-plane aliasing artifact across the field of view (FOV). Here we report a method that integrates multiple approaches to address the technical limitations of interleaved EPI-based fMRI. Firstly, the multiplexed sensitivity-encoding (MUSE) post-processing algorithm is used to suppress in-plane aliasing artifacts resulting from time-domain signal instabilities during dynamic scans. Secondly, a simultaneous multi-band interleaved EPI pulse sequence, with a controlled aliasing scheme incorporated, is implemented to increase the imaging throughput. Thirdly, the MUSE algorithm is then generalized to accommodate fMRI data obtained with our multi-band interleaved EPI pulse sequence, suppressing both in-plane and through-plane aliasing artifacts. The blood-oxygenation-level-dependent (BOLD) signal detectability and the scan throughput can be significantly improved for interleaved EPI-based fMRI. Our human fMRI data obtained from 3 Tesla systems demonstrate the effectiveness of the developed methods. It is expected that future fMRI studies requiring high

Visual Sexual Stimulation and Erection, a Brief Review with New fMRI Data.

PubMed

Wu, Sharon L; Chow, Maggie S M; L, Jiang Y; Yang, Jingjin; Zhou, Hao; Yew, David T

2017-05-31

This review examines brain sites involved in sexual stimulation. New data on brain activation sites in individuals having erections concomitant with visual erotic stimulation were documented. The activation was chiefly at the midbrain around the cerebral peduncle, and in the pons centering on the tegmentum, they are indicated by blood oxygenation level dependent (BOLD) images captured by functional magnetic resonance imaging (fMRI). The cerebellum and inferior temporal lobe were activated more extensively in individuals viewing pornographic movie with a concomitant erection than those without. Similarly, individuals with erection had activations in the midbrain and pons, while drug addicts had neither erections nor any of these brainstem active sites. From our observation in the new data, we deduced three possible transmitters might be involved in erection: i) cholinergic neurons forming descending pathways and associated with motor activity ii) gamma-aminobutyric acid (GABA), directly or indirectly via decreasing pathways, modulating autonomic vascular responses in the penile vasculature causing the filling of blood iii) GABA decreases to stimulate dopamine increase in ventral tegmentum of the brain, leading to euphoric responses. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Neural correlates of text-based emoticons: a preliminary fMRI study.

PubMed

Kim, Ko Woon; Lee, Sang Won; Choi, Jeewook; Kim, Tae Min; Jeong, Bumseok

2016-08-01

Like nonverbal cues in oral interactions, text-based emoticons, which are textual portrayals of a writer's facial expressions, are commonly used in electronic device-mediated communication. Little is known, however, about how text-based emoticons are processed in the human brain. With this study, we investigated whether the text-based emoticons are processed as face expressions using fMRI. During fMRI scan, subjects were asked to respond by pressing a button, indicating whether text-based emoticons represented positive or negative emotions. Voxel-wise analyses were performed to compare the responses and contrasted with emotional versus scrambled emoticons and among emoticons with different emotions. To explore processing strategies for text-based emoticons, brain activity in the bilateral occipital and fusiform face areas were compared. In the voxel-wise analysis, both emotional and scrambled emoticons were processed mainly in the bilateral fusiform gyri, inferior division of lateral occipital cortex, inferior frontal gyri, dorsolateral prefrontal cortex (DLPFC), dorsal anterior cingulate cortex (dACC), and parietal cortex. In a percent signal change analysis, the right occipital and fusiform face areas showed significantly higher activation than left ones. In comparisons among emoticons, sad one showed significant BOLD signal decrease in the dACC, the left AIC, the bilateral thalamus, and the precuneus as compared with other conditions. The results of this study imply that people recognize text-based emoticons as pictures representing face expressions. Even though text-based emoticons contain emotional meaning, they are not associated with the amygdala while previous studies using emotional stimuli documented amygdala activation.

PyMVPA: A python toolbox for multivariate pattern analysis of fMRI data.

PubMed

Hanke, Michael; Halchenko, Yaroslav O; Sederberg, Per B; Hanson, Stephen José; Haxby, James V; Pollmann, Stefan

2009-01-01

Decoding patterns of neural activity onto cognitive states is one of the central goals of functional brain imaging. Standard univariate fMRI analysis methods, which correlate cognitive and perceptual function with the blood oxygenation-level dependent (BOLD) signal, have proven successful in identifying anatomical regions based on signal increases during cognitive and perceptual tasks. Recently, researchers have begun to explore new multivariate techniques that have proven to be more flexible, more reliable, and more sensitive than standard univariate analysis. Drawing on the field of statistical learning theory, these new classifier-based analysis techniques possess explanatory power that could provide new insights into the functional properties of the brain. However, unlike the wealth of software packages for univariate analyses, there are few packages that facilitate multivariate pattern classification analyses of fMRI data. Here we introduce a Python-based, cross-platform, and open-source software toolbox, called PyMVPA, for the application of classifier-based analysis techniques to fMRI datasets. PyMVPA makes use of Python's ability to access libraries written in a large variety of programming languages and computing environments to interface with the wealth of existing machine learning packages. We present the framework in this paper and provide illustrative examples on its usage, features, and programmability.

PyMVPA: A Python toolbox for multivariate pattern analysis of fMRI data

PubMed Central

Hanke, Michael; Halchenko, Yaroslav O.; Sederberg, Per B.; Hanson, Stephen José; Haxby, James V.; Pollmann, Stefan

2009-01-01

Decoding patterns of neural activity onto cognitive states is one of the central goals of functional brain imaging. Standard univariate fMRI analysis methods, which correlate cognitive and perceptual function with the blood oxygenation-level dependent (BOLD) signal, have proven successful in identifying anatomical regions based on signal increases during cognitive and perceptual tasks. Recently, researchers have begun to explore new multivariate techniques that have proven to be more flexible, more reliable, and more sensitive than standard univariate analysis. Drawing on the field of statistical learning theory, these new classifier-based analysis techniques possess explanatory power that could provide new insights into the functional properties of the brain. However, unlike the wealth of software packages for univariate analyses, there are few packages that facilitate multivariate pattern classification analyses of fMRI data. Here we introduce a Python-based, cross-platform, and open-source software toolbox, called PyMVPA, for the application of classifier-based analysis techniques to fMRI datasets. PyMVPA makes use of Python's ability to access libraries written in a large variety of programming languages and computing environments to interface with the wealth of existing machine-learning packages. We present the framework in this paper and provide illustrative examples on its usage, features, and programmability. PMID:19184561

Cortical processing of pitch: Model-based encoding and decoding of auditory fMRI responses to real-life sounds.

PubMed

De Angelis, Vittoria; De Martino, Federico; Moerel, Michelle; Santoro, Roberta; Hausfeld, Lars; Formisano, Elia

2017-11-13

Pitch is a perceptual attribute related to the fundamental frequency (or periodicity) of a sound. So far, the cortical processing of pitch has been investigated mostly using synthetic sounds. However, the complex harmonic structure of natural sounds may require different mechanisms for the extraction and analysis of pitch. This study investigated the neural representation of pitch in human auditory cortex using model-based encoding and decoding analyses of high field (7 T) functional magnetic resonance imaging (fMRI) data collected while participants listened to a wide range of real-life sounds. Specifically, we modeled the fMRI responses as a function of the sounds' perceived pitch height and salience (related to the fundamental frequency and the harmonic structure respectively), which we estimated with a computational algorithm of pitch extraction (de Cheveigné and Kawahara, 2002). First, using single-voxel fMRI encoding, we identified a pitch-coding region in the antero-lateral Heschl's gyrus (HG) and adjacent superior temporal gyrus (STG). In these regions, the pitch representation model combining height and salience predicted the fMRI responses comparatively better than other models of acoustic processing and, in the right hemisphere, better than pitch representations based on height/salience alone. Second, we assessed with model-based decoding that multi-voxel response patterns of the identified regions are more informative of perceived pitch than the remainder of the auditory cortex. Further multivariate analyses showed that complementing a multi-resolution spectro-temporal sound representation with pitch produces a small but significant improvement to the decoding of complex sounds from fMRI response patterns. In sum, this work extends model-based fMRI encoding and decoding methods - previously employed to examine the representation and processing of acoustic sound features in the human auditory system - to the representation and processing of a relevant

Is brain response to food rewards related to overeating? A test of the reward surfeit model of overeating in children.

PubMed

Adise, Shana; Geier, Charles F; Roberts, Nicole J; White, Corey N; Keller, Kathleen L

2018-06-08

The reward surfeit model of overeating suggests that heightened brain response to rewards contributes to overeating and subsequent weight gain. However, previous studies have not tested whether brain response to reward is associated with food intake, particularly during childhood, a period of dynamic development in reward and inhibitory control neurocircuitry. We conducted functional magnetic resonance imaging (fMRI) with 7-11-year-old children (n = 59; healthy weight, n = 31; overweight, n = 28; 54% female) while they played a modified card-guessing paradigm to examine blood-oxygen-level-dependent (BOLD) response to anticipating and winning rewards (food, money, neutral). Food intake was assessed at three separate meals that measured different facets of eating behavior: 1) typical consumption (baseline), 2) overindulgence (palatable buffet), and 3) eating in the absence of hunger (EAH). A priori regions of interest included regions implicated in both reward processing and inhibitory control. Multiple stepwise regressions were conducted to examine the relationship between intake and BOLD response to rewards. Corrected results showed that a greater BOLD response in the medial prefrontal cortex for anticipating food compared to money positively correlated with how much children ate at the baseline and palatable buffet meals. BOLD response in the dorsolateral prefrontal cortex for winning food compared to money was positively correlated with intake at the palatable buffet meal and EAH. All aforementioned relationships were independent of child weight status. Findings support the reward surfeit model by showing that increased brain response to food compared to money rewards positively correlates with laboratory measures of food intake in children. Copyright © 2018. Published by Elsevier Ltd.

Feedback to distal dendrites links fMRI signals to neural receptive fields in a spiking network model of the visual cortex.

PubMed

Heikkinen, Hanna; Sharifian, Fariba; Vigario, Ricardo; Vanni, Simo

2015-07-01

The blood oxygenation level-dependent (BOLD) response has been strongly associated with neuronal activity in the brain. However, some neuronal tuning properties are consistently different from the BOLD response. We studied the spatial extent of neural and hemodynamic responses in the primary visual cortex, where the BOLD responses spread and interact over much longer distances than the small receptive fields of individual neurons would predict. Our model shows that a feedforward-feedback loop between V1 and a higher visual area can account for the observed spread of the BOLD response. In particular, anisotropic landing of inputs to compartmental neurons were necessary to account for the BOLD signal spread, while retaining realistic spiking responses. Our work shows that simple dendrites can separate tuning at the synapses and at the action potential output, thus bridging the BOLD signal to the neural receptive fields with high fidelity. Copyright © 2015 the American Physiological Society.

CATEGORY-SPECIFIC SEMANTIC MEMORY: CONVERGING EVIDENCE FROM BOLD fMRI AND ALZHEIMER’S DISEASE

PubMed Central

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

2012-01-01

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

Fluoxetine exposure impacts boldness in female Siamese fighting fish, Betta splendens.

PubMed

Dzieweczynski, Teresa L; Kane, Jessica L; Campbell, Brennah A; Lavin, Lindsey E

2016-01-01

The present study examined the effects of the selective serotonin reuptake inhibitor, fluoxetine, on the behavior of female Siamese fighting fish, Betta splendens, in three different boldness assays (Empty Tank, Novel Environment, Social Tendency). When females were unexposed to fluoxetine, boldness was consistent within a context and correlated across assays. Fluoxetine exposure affected behavior within and among individuals on multiple levels. Exposure reduced overall boldness levels, made females behave in a less consistent manner, and significantly reduced correlations over time and across contexts. Fluoxetine exerted its effects on female Betta splendens behavior in a dose-dependent fashion and these effects persisted even after females were housed in clean water. If fluoxetine exposure impacts behaviors such as exploration that are necessary to an individual’s success, this may yield evolutionary consequences. In conclusion, the results show that fluoxetine exposure alters behavior beyond the level of overall response and highlights the importance of studying the behavioral effects of inadvertent pharmaceutical exposure in multiple contexts and with different dosing regimes.

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

PubMed

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

2009-08-01

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

Role of mitochondrial calcium uptake homeostasis in resting state fMRI brain networks.

PubMed

Kannurpatti, Sridhar S; Sanganahalli, Basavaraju G; Herman, Peter; Hyder, Fahmeed

2015-11-01

Mitochondrial Ca(2+) uptake influences both brain energy metabolism and neural signaling. Given that brain mitochondrial organelles are distributed in relation to vascular density, which varies considerably across brain regions, we hypothesized different physiological impacts of mitochondrial Ca(2+) uptake across brain regions. We tested the hypothesis by monitoring brain "intrinsic activity" derived from the resting state functional MRI (fMRI) blood oxygen level dependent (BOLD) fluctuations in different functional networks spanning the somatosensory cortex, caudate putamen, hippocampus and thalamus, in normal and perturbed mitochondrial Ca(2+) uptake states. In anesthetized rats at 11.7 T, mitochondrial Ca(2+) uptake was inhibited or enhanced respectively by treatments with Ru360 or kaempferol. Surprisingly, mitochondrial Ca(2+) uptake inhibition by Ru360 and enhancement by kaempferol led to similar dose-dependent decreases in brain-wide intrinsic activities in both the frequency domain (spectral amplitude) and temporal domain (resting state functional connectivity; RSFC). The fact that there were similar dose-dependent decreases in the frequency and temporal domains of the resting state fMRI-BOLD fluctuations during mitochondrial Ca(2+) uptake inhibition or enhancement indicated that mitochondrial Ca(2+) uptake and its homeostasis may strongly influence the brain's functional organization at rest. Interestingly, the resting state fMRI-derived intrinsic activities in the caudate putamen and thalamic regions saturated much faster with increasing dosage of either drug treatment than the drug-induced trends observed in cortical and hippocampal regions. Regional differences in how the spectral amplitude and RSFC changed with treatment indicate distinct mitochondrion-mediated spontaneous neuronal activity coupling within the various RSFC networks determined by resting state fMRI. Copyright © 2015 John Wiley & Sons, Ltd.

Neural correlates of nature stimuli: an FMRI study.

PubMed

Pati, Debajyoti; O'Boyle, Michael; Amor, Cherif; Hou, Jiancheng; Valipoor, Shabboo; Fang, Dan

2014-01-01

Examine whether there are unique patterns of brain activation associated with exposure to photographic sky compositions (representing nature stimuli) as compared with other positive, negative, and neutral images. The positive impact of nature images on health outcomes traditionally has been measured using behavioral and physiological indicators. However, there is a lack of understanding of the underlying neural mechanism that explains this positive influence. A combination of behavioral responses and functional magnetic resonance imaging (fMRI) technology was used to address research questions. Ten participants belonging to five age groups were subjected to short (25 seconds) exposures of 32 images while their brain activation was monitored via the BOLD response. In a separate run, participants were subjected to extended exposures (12 minutes) of a sky composition and an image of a traditional ceiling. The results show that the activation patterns produced by sky compositions and positive images were quite similar as compared to negative or neutral images. However, sky compositions also produced some unique areas of activation, including those associated with spatial cognition, the expanse of space, circadian rhythm, and perceived motion. In the extended exposure condition, sky compositions tended to activate regions associated with dreaming, while traditional ceiling images activated regions that are related to face processing and potentially visual hallucinations. Nature stimuli, with a combination of vegetation and sky, may produce unique beneficial effects not present in general positive stimuli. Evidence-based design, hospital, healing environments, outcomes, patient-centered care.

"Extreme Bold" in the Faculty Ranks

ERIC Educational Resources Information Center

Kuusisto, Stephen

2013-01-01

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