Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals.
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
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
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.
Blockley, Nicholas P.; Griffeth, Valerie E. M.; Simon, Aaron B.; Buxton, Richard B.
2013-01-01
The dynamics of the blood oxygenation level-dependent (BOLD) response are dependent on changes in cerebral blood flow, cerebral blood volume and the cerebral metabolic rate of oxygen consumption. Furthermore, the amplitude of the response is dependent on the baseline physiological state, defined by the haematocrit, oxygen extraction fraction and cerebral blood volume. As a result of this complex dependence, the accurate interpretation of BOLD data and robust intersubject comparisons when the baseline physiology is varied are difficult. The calibrated BOLD technique was developed to address these issues. However, the methodology is complex and its full promise has not yet been realised. In this review, the theoretical underpinnings of calibrated BOLD, and issues regarding this theory that are still to be resolved, are discussed. Important aspects of practical implementation are reviewed and reported applications of this methodology are presented. PMID:22945365
Non-neural BOLD variability in block and event-related paradigms.
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.
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
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.
The BOLD signal and neurovascular coupling in autism.
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.
The BOLD signal and neurovascular coupling in autism
Reynell, Clare; Harris, Julia J.
2013-01-01
BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging) is commonly used to study differences in neuronal activity between human populations. As the BOLD response is an indirect measure of neuronal activity, meaningful interpretation of differences in BOLD responses between groups relies upon a stable relationship existing between neuronal activity and the BOLD response across these groups. However, this relationship can be altered by changes in neurovascular coupling or energy consumption, which would lead to problems in identifying differences in neuronal activity. In this review, we focus on fMRI studies of people with autism, and comparisons that are made of their BOLD responses with those of control groups. We examine neurophysiological differences in autism that may alter neurovascular coupling or energy use, discuss recent studies that have used fMRI to identify differences between participants with autism and control participants, and explore experimental approaches that could help attribute between-group differences in BOLD signals to either neuronal or neurovascular factors. PMID:23917518
BOLD repetition decreases in object-responsive ventral visual areas depend on spatial attention.
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.
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.
The role of beta-arrestin2 in shaping fMRI BOLD responses to dopaminergic stimulation.
Sahlholm, Kristoffer; Ielacqua, Giovanna D; Xu, Jinbin; Jones, Lynne A; Schlegel, Felix; Mach, Robert H; Rudin, Markus; Schroeter, Aileen
2017-07-01
The dopamine D 2 receptor (D 2 R) couples to inhibitory G i/o proteins and is targeted by antipsychotic and antiparkinsonian drugs. Beta-arrestin2 binds to the intracellular regions of the agonist-occupied D 2 R to terminate G protein activation and promote internalization, but also to initiate downstream signaling cascades which have been implicated in psychosis. Functional magnetic resonance imaging (fMRI) has proven valuable for measuring dopamine receptor-mediated changes in neuronal activity, and might enable beta-arrestin2 function to be studied in vivo. The present study examined fMRI blood oxygenation level dependent (BOLD) signal changes elicited by a dopamine agonist in wild-type (WT) and beta-arrestin2 knockout (KO) mice, to investigate whether genetic deletion of beta-arrestin2 prolongs or otherwise modifies D 2 R-dependent responses. fMRI BOLD data were acquired on a 9.4 T system. During scans, animals received 0.2 mg/kg apomorphine, i.v. In a subset of experiments, animals were pretreated with 2 mg/kg of the D 2 R antagonist, eticlopride. Following apomorphine administration, BOLD signal decreases were observed in caudate/putamen of WT and KO animals. The time course of response decay in caudate/putamen was significantly slower in KO vs. WT animals. In cingulate cortex, an initial BOLD signal decrease was followed by a positive response component in WT but not in KO animals. Eticlopride pretreatment significantly reduced apomorphine-induced BOLD signal changes. The prolonged striatal response decay rates in KO animals might reflect impaired D 2 R desensitization, consistent with the known function of beta-arrestin2. Furthermore, the apomorphine-induced positive response component in cingulate cortex may depend on beta-arrestin2 signaling downstream of D 2 R.
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.
Mapping glucose-mediated gut-to-brain signalling pathways in humans.
Little, Tanya J; McKie, Shane; Jones, Richard B; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G; McLaughlin, John T
2014-08-01
Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250ml) of: 1M glucose+predosing with dexloxiglumide (CCK1 receptor antagonist), 1M glucose+placebo, or 0.9% saline (control)+placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose+dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. Copyright © 2014. Published by Elsevier Inc.
Altered reward expectancy in individuals with recent methamphetamine dependence.
Bischoff-Grethe, Amanda; Connolly, Colm G; Jordan, Stephan J; Brown, Gregory G; Paulus, Martin P; Tapert, Susan F; Heaton, Robert K; Woods, Steven P; Grant, Igor
2017-01-01
Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine-dependent individuals show heightened reactivity to positively valenced stimuli (i.e. positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e. driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH-) histories of methamphetamine dependence. Participants (17 METH+; 23 METH-) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes. METH+ had less BOLD response to loss anticipation than METH- in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH- did not show differential responses to the valence of outcomes. METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior.
Altered reward expectancy in individuals with recent methamphetamine dependence
Bischoff-Grethe, Amanda; Connolly, Colm G; Jordan, Stephan J; Brown, Gregory G; Paulus, Martin P; Tapert, Susan F; Heaton, Robert K; Woods, Steven P; Grant, Igor
2016-01-01
Background Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine dependent individuals show heightened reactivity to positively valenced stimuli (i.e., positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e., driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH−) histories of methamphetamine dependence. Methods Participants (17 METH+; 23 METH−) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes. Results METH+ had less BOLD response to loss anticipation than METH− in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH− did not show differential responses to the valence of outcomes. Discussion METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior. PMID:27649775
Common neural correlates of intertemporal choices and intelligence in adolescents.
Ripke, Stephan; Hübner, Thomas; Mennigen, Eva; Müller, Kathrin U; Li, Shu-Chen; Smolka, Michael N
2015-02-01
Converging behavioral evidence indicates that temporal discounting, measured by intertemporal choice tasks, is inversely related to intelligence. At the neural level, the parieto-frontal network is pivotal for complex, higher-order cognitive processes. Relatedly, underrecruitment of the pFC during a working memory task has been found to be associated with steeper temporal discounting. Furthermore, this network has also been shown to be related to the consistency of intertemporal choices. Here we report an fMRI study that directly investigated the association of neural correlates of intertemporal choice behavior with intelligence in an adolescent sample (n = 206; age 13.7-15.5 years). After identifying brain regions where the BOLD response during intertemporal choice was correlated with individual differences in intelligence, we further tested whether BOLD responses in these areas would mediate the associations between intelligence, the discounting rate, and choice consistency. We found positive correlations between BOLD response in a value-independent decision network (i.e., dorsolateral pFC, precuneus, and occipital areas) and intelligence. Furthermore, BOLD response in a value-dependent decision network (i.e., perigenual ACC, inferior frontal gyrus, ventromedial pFC, ventral striatum) was positively correlated with intelligence. The mediation analysis revealed that BOLD responses in the value-independent network mediated the association between intelligence and choice consistency, whereas BOLD responses in the value-dependent network mediated the association between intelligence and the discounting rate. In summary, our findings provide evidence for common neural correlates of intertemporal choice and intelligence, possibly linked by valuation as well as executive functions.
Controlled inspiration depth reduces variance in breath-holding-induced BOLD signal.
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.
Caffeine Increases the Linearity of the Visual BOLD Response
Liu, Thomas T.; Liau, Joy
2009-01-01
Although the blood oxygenation level dependent (BOLD) signal used in most functional magnetic resonance imaging (fMRI) studies has been shown to exhibit nonlinear characteristics, most analyses assume that the BOLD signal responds in a linear fashion to stimulus. This assumption of linearity can lead to errors in the estimation of the BOLD response, especially for rapid event-related fMRI studies. In this study, we used a rapid event-related design and Volterra kernel analysis to assess the effect of a 200 mg oral dose of caffeine on the linearity of the visual BOLD response. The caffeine dose significantly (p < 0.02) increased the linearity of the BOLD response in a sample of 11 healthy volunteers studied on a 3 Tesla MRI system. In addition, the agreement between nonlinear and linear estimates of the hemodynamic response function was significantly increased (p= 0.013) with the caffeine dose. These findings indicate that differences in caffeine usage should be considered as a potential source of bias in the analysis of rapid event-related fMRI studies. PMID:19854278
From blood oxygenation level dependent (BOLD) signals to brain temperature maps.
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.
Placental baseline conditions modulate the hyperoxic BOLD-MRI response.
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.
Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.
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.
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 Alcoholism.
Caffeine reduces resting-state BOLD functional connectivity in the motor cortex.
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.
Mapping glucose-mediated gut-to-brain signalling pathways in humans☆
Little, Tanya J.; McKie, Shane; Jones, Richard B.; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G.; McLaughlin, John T.
2014-01-01
Objectives Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Experimental design Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250 ml) of: 1 M glucose + predosing with dexloxiglumide (CCK1 receptor antagonist), 1 M glucose + placebo, or 0.9% saline (control) + placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Principal observations Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose + dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Conclusions Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. PMID:24685436
Longitudinal decrease in blood oxygenation level dependent response in cerebral amyloid angiopathy.
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.
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.
ERIC Educational Resources Information Center
Karten, Ariel; Hirsch, Joy
2015-01-01
Neural mechanisms that underlie language disability in autism spectrum disorder (ASD) have been associated with reduced excitatory processes observed as positive blood oxygen level dependent (BOLD) responses. However, negative BOLD responses (NBR) associated with language and inhibitory processes have been less studied in ASD. In this study,…
Song, Yinchen; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Lin, Wei-Chiang; Riera, Jorge J.
2015-01-01
Alterations in the connectivity patterns of the fMRI-based resting-state networks (RSNs) have been reported in several types of epilepsies. Evidence pointed out these alterations might be associated with the genesis and propagation of interictal epileptiform discharges (IEDs). IEDs also evoke blood-oxygen-level dependent (BOLD) responses, which have been used to delineate irritative zones during preoperative work-up. Therefore, one may expect a relationship between the topology of the IED-evoked BOLD response network and the altered spatial patterns of the RSNs. In this study, we used EEG recordings and fMRI data obtained simultaneously from a chronic model of focal epilepsy in Wistar rats to verify our hypothesis. We found that IED-evoked BOLD response networks comprise both cortical and subcortical structures with a rat-dependent topology. In all rats, IEDs evoke both activation and deactivation types of BOLD responses. Using a Granger causality method, we found that in many cases areas with BOLD deactivation have directed influences on areas with activation (p<0.05). We were able to predict topological properties (i.e., focal/diffused, unilateral/bilateral) of the IED-evoked BOLD response network by performing hierarchical clustering analysis on major spatial features of the RSNs. All these results suggest that IEDs and disruptions in the RSNs found previously in humans may be different manifestations of the same transient events, probably reflecting altered consciousness. In our opinion, the shutdown of specific nodes of the default mode network may cause uncontrollable excitability in other functionally connected brain areas. We conclude that IED-evoked BOLD responses (i.e., activation and deactivation) and alterations of RSNs are intrinsically related, and speculate that an understanding of their interplay is necessary to discriminate focal epileptogenesis and network propagation phenomena across different brain modules via hub-based connectivity. PMID:26226628
Influence of DARPP-32 genetic variation on BOLD activation to happy faces.
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.
Anatomical and functional assemblies of brain BOLD oscillations
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
Atabaki, A; Marciniak, K; Dicke, P W; Karnath, H-O; Thier, P
2014-03-01
Distinguishing a target from distractors during visual search is crucial for goal-directed behaviour. The more distractors that are presented with the target, the larger is the subject's error rate. This observation defines the set-size effect in visual search. Neurons in areas related to attention and eye movements, like the lateral intraparietal area (LIP) and frontal eye field (FEF), diminish their firing rates when the number of distractors increases, in line with the behavioural set-size effect. Furthermore, human imaging studies that have tried to delineate cortical areas modulating their blood oxygenation level-dependent (BOLD) response with set size have yielded contradictory results. In order to test whether BOLD imaging of the rhesus monkey cortex yields results consistent with the electrophysiological findings and, moreover, to clarify if additional other cortical regions beyond the two hitherto implicated are involved in this process, we studied monkeys while performing a covert visual search task. When varying the number of distractors in the search task, we observed a monotonic increase in error rates when search time was kept constant as was expected if monkeys resorted to a serial search strategy. Visual search consistently evoked robust BOLD activity in the monkey FEF and a region in the intraparietal sulcus in its lateral and middle part, probably involving area LIP. Whereas the BOLD response in the FEF did not depend on set size, the LIP signal increased in parallel with set size. These results demonstrate the virtue of BOLD imaging in monkeys when trying to delineate cortical areas underlying a cognitive process like visual search. However, they also demonstrate the caution needed when inferring neural activity from BOLD activity. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Task-evoked BOLD responses are normal in areas of diaschisis after stroke.
Fair, Damien A; Snyder, Abraham Z; Connor, Lisa Tabor; Nardos, Binyam; Corbetta, Maurizio
2009-01-01
Cerebral infarction can cause diaschisis, a reduction of blood flow and metabolism in areas of the cortex distant from the site of the lesion. Although the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal is increasingly used to examine the neural correlates of recovery in stroke, its reliability in areas of diaschisis is uncertain. The effect of chronic diaschisis as measured by resting positron emission tomography on task-evoked BOLD responses during word-stem completion in a block design fMRI study was examined in 3 patients, 6 months after a single left hemisphere stroke involving the inferior frontal gyrus and operculum. The BOLD responses were minimally affected in areas of chronic diaschisis. Within the confines of this study, the mechanism underlying the BOLD signal, which includes a mismatch between neuronally driven increases in blood flow and a corresponding increase in oxygen use, appears to be intact in areas of chronic diaschisis.
Stecker, G Christopher; McLaughlin, Susan A; Higgins, Nathan C
2015-10-15
Whole-brain functional magnetic resonance imaging was used to measure blood-oxygenation-level-dependent (BOLD) responses in human auditory cortex (AC) to sounds with intensity varying independently in the left and right ears. Echoplanar images were acquired at 3 Tesla with sparse image acquisition once per 12-second block of sound stimulation. Combinations of binaural intensity and stimulus presentation rate were varied between blocks, and selected to allow measurement of response-intensity functions in three configurations: monaural 55-85 dB SPL, binaural 55-85 dB SPL with intensity equal in both ears, and binaural with average binaural level of 70 dB SPL and interaural level differences (ILD) ranging ±30 dB (i.e., favoring the left or right ear). Comparison of response functions equated for contralateral intensity revealed that BOLD-response magnitudes (1) generally increased with contralateral intensity, consistent with positive drive of the BOLD response by the contralateral ear, (2) were larger for contralateral monaural stimulation than for binaural stimulation, consistent with negative effects (e.g., inhibition) of ipsilateral input, which were strongest in the left hemisphere, and (3) also increased with ipsilateral intensity when contralateral input was weak, consistent with additional, positive, effects of ipsilateral stimulation. Hemispheric asymmetries in the spatial extent and overall magnitude of BOLD responses were generally consistent with previous studies demonstrating greater bilaterality of responses in the right hemisphere and stricter contralaterality in the left hemisphere. Finally, comparison of responses to fast (40/s) and slow (5/s) stimulus presentation rates revealed significant rate-dependent adaptation of the BOLD response that varied across ILD values. Copyright © 2015. Published by Elsevier Inc.
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
Negative blood oxygen level dependent signals during speech comprehension.
Rodriguez Moreno, Diana; Schiff, Nicholas D; Hirsch, Joy
2015-05-01
Speech comprehension studies have generally focused on the isolation and function of regions with positive blood oxygen level dependent (BOLD) signals with respect to a resting baseline. Although regions with negative BOLD signals in comparison to a resting baseline have been reported in language-related tasks, their relationship to regions of positive signals is not fully appreciated. Based on the emerging notion that the negative signals may represent an active function in language tasks, the authors test the hypothesis that negative BOLD signals during receptive language are more associated with comprehension than content-free versions of the same stimuli. Regions associated with comprehension of speech were isolated by comparing responses to passive listening to natural speech to two incomprehensible versions of the same speech: one that was digitally time reversed and one that was muffled by removal of high frequencies. The signal polarity was determined by comparing the BOLD signal during each speech condition to the BOLD signal during a resting baseline. As expected, stimulation-induced positive signals relative to resting baseline were observed in the canonical language areas with varying signal amplitudes for each condition. Negative BOLD responses relative to resting baseline were observed primarily in frontoparietal regions and were specific to the natural speech condition. However, the BOLD signal remained indistinguishable from baseline for the unintelligible speech conditions. Variations in connectivity between brain regions with positive and negative signals were also specifically related to the comprehension of natural speech. These observations of anticorrelated signals related to speech comprehension are consistent with emerging models of cooperative roles represented by BOLD signals of opposite polarity.
Negative Blood Oxygen Level Dependent Signals During Speech Comprehension
Rodriguez Moreno, Diana; Schiff, Nicholas D.
2015-01-01
Abstract Speech comprehension studies have generally focused on the isolation and function of regions with positive blood oxygen level dependent (BOLD) signals with respect to a resting baseline. Although regions with negative BOLD signals in comparison to a resting baseline have been reported in language-related tasks, their relationship to regions of positive signals is not fully appreciated. Based on the emerging notion that the negative signals may represent an active function in language tasks, the authors test the hypothesis that negative BOLD signals during receptive language are more associated with comprehension than content-free versions of the same stimuli. Regions associated with comprehension of speech were isolated by comparing responses to passive listening to natural speech to two incomprehensible versions of the same speech: one that was digitally time reversed and one that was muffled by removal of high frequencies. The signal polarity was determined by comparing the BOLD signal during each speech condition to the BOLD signal during a resting baseline. As expected, stimulation-induced positive signals relative to resting baseline were observed in the canonical language areas with varying signal amplitudes for each condition. Negative BOLD responses relative to resting baseline were observed primarily in frontoparietal regions and were specific to the natural speech condition. However, the BOLD signal remained indistinguishable from baseline for the unintelligible speech conditions. Variations in connectivity between brain regions with positive and negative signals were also specifically related to the comprehension of natural speech. These observations of anticorrelated signals related to speech comprehension are consistent with emerging models of cooperative roles represented by BOLD signals of opposite polarity. PMID:25412406
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
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.
Locating the cortical bottleneck for slow reading in peripheral vision
Yu, Deyue; Jiang, Yi; Legge, Gordon E.; He, Sheng
2015-01-01
Yu, Legge, Park, Gage, and Chung (2010) suggested that the neural bottleneck for slow peripheral reading is located in nonretinotopic areas. We investigated the potential rate-limiting neural site for peripheral reading using fMRI, and contrasted peripheral reading with recognition of peripherally presented line drawings of common objects. We measured the BOLD responses to both text (three-letter words/nonwords) and line-drawing objects presented either in foveal or peripheral vision (10° lower right visual field) at three presentation rates (2, 4, and 8/second). The statistically significant interaction effect of visual field × presentation rate on the BOLD response for text but not for line drawings provides evidence for distinctive processing of peripheral text. This pattern of results was obtained in all five regions of interest (ROIs). At the early retinotopic cortical areas, the BOLD signal slightly increased with increasing presentation rate for foveal text, and remained fairly constant for peripheral text. In the Occipital Word-Responsive Area (OWRA), Visual Word Form Area (VWFA), and object sensitive areas (LO and PHA), the BOLD responses to text decreased with increasing presentation rate for peripheral but not foveal presentation. In contrast, there was no rate-dependent reduction in BOLD response for line-drawing objects in all the ROIs for either foveal or peripheral presentation. Only peripherally presented text showed a distinctive rate-dependence pattern. Although it is possible that the differentiation starts to emerge at the early retinotopic cortical representation, the neural bottleneck for slower reading of peripherally presented text may be a special property of peripheral text processing in object category selective cortex. PMID:26237299
BOLD response to semantic and syntactic processing during hypoglycemia is load-dependent.
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.
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.
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.
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
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…
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
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
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.
Reduced BOLD response to periodic visual stimulation.
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.
Inferring neural activity from BOLD signals through nonlinear optimization.
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.
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:25477775
Simon, Aaron B.; Griffeth, Valerie E. M.; Wong, Eric C.; Buxton, Richard B.
2013-01-01
Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged. PMID:23382977
fMRI BOLD response to the eyes task in offspring from multiplex alcohol dependence families.
Hill, Shirley Y; Kostelnik, Bryan; Holmes, Brian; Goradia, Dhruman; McDermott, Michael; Diwadkar, Vaibhav; Keshavan, Matcheri
2007-12-01
Increased susceptibility for developing alcohol dependence (AD) may be related to structural and functional differences in brain circuits that influence social cognition and more specifically, theory of mind (ToM). Alcohol dependent individuals have a greater likelihood of having deficits in social skills and greater social alienation. These characteristics may be related to inherited differences in the neuroanatomical network that comprises the social brain. Adolescent/young adult participants from multiplex AD families and controls (n = 16) were matched for gender, age, IQ, education, and handedness and administered the Eyes Task of Baron-Cohen during functional magnetic resonance imaging (fMRI). High-risk (HR) subjects showed significantly diminished blood oxygen level dependent (BOLD) response in comparison with low-risk control young adults in the right middle temporal gyrus (RMTG) and the left inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM tasks. Offspring from multiplex families for AD may manifest one aspect of their genetic susceptibility by having a diminished BOLD response in brain regions associated with performance of ToM tasks. These results suggest that those at risk for developing AD may have reduced ability to empathize with others' state of mind, possibly resulting in diminished social skill.
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.
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
Spatio-Temporal Information Analysis of Event-Related BOLD Responses
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
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 signature that should, in the future, be compared to other μ opioid agonists. PMID:27857679
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
Quelch, Darren R; Mick, Inge; McGonigle, John; Ramos, Anna C; Flechais, Remy S A; Bolstridge, Mark; Rabiner, Eugenii; Wall, Matthew B; Newbould, Rexford D; Steiniger-Brach, Björn; van den Berg, Franz; Boyce, Malcolm; Østergaard Nilausen, Dorrit; Breuning Sluth, Lasse; Meulien, Didier; von der Goltz, Christoph; Nutt, David; Lingford-Hughes, Anne
2017-06-01
Nalmefene is a µ and δ opioid receptor antagonist, κ opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol-dependent individuals with "high-risk drinking levels" to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level-dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge. Twenty-two currently heavy-drinking, non-treatment-seeking alcohol-dependent males were recruited. The effect of single dose nalmefene (18 mg) on changes in a priori defined striatal region of interest BOLD signal change during reward anticipation compared with placebo was investigated using functional magnetic resonance imaging. Both conditions were performed under intravenous alcohol administration (6% vol/vol infusion to achieve a target level of 80 mg/dL). Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal region of interest compared with placebo. Nalmefene did not alter brain perfusion. Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene's actions on opioid receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Heinen, Klaartje; Feredoes, Eva; Weiskopf, Nikolaus; Ruff, Christian C; Driver, Jon
2014-11-01
Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for "spatial" attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level-dependent (BOLD) signals in visual areas processing "target feature" but not in "distracter feature"-processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial "feature"-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property. © The Author 2013. Published by Oxford University Press.
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
NASA Astrophysics Data System (ADS)
DiNuzzo, Mauro; Mascali, Daniele; Moraschi, Marta; Bussu, Giorgia; Maraviglia, Bruno; Mangia, Silvia; Giove, Federico
2017-02-01
Time-domain analysis of blood-oxygenation level-dependent (BOLD) signals allows the identification of clusters of voxels responding to photic stimulation in primary visual cortex (V1). However, the characterization of information encoding into temporal properties of the BOLD signals of an activated cluster is poorly investigated. Here, we used Shannon entropy to determine spatial and temporal information encoding in the BOLD signal within the most strongly activated area of the human visual cortex during a hemifield photic stimulation. We determined the distribution profile of BOLD signals during epochs at rest and under stimulation within small (19-121 voxels) clusters designed to include only voxels driven by the stimulus as highly and uniformly as possible. We found consistent and significant increases (2-4% on average) in temporal information entropy during activation in contralateral but not ipsilateral V1, which was mirrored by an expected loss of spatial information entropy. These opposite changes coexisted with increases in both spatial and temporal mutual information (i.e. dependence) in contralateral V1. Thus, we showed that the first cortical stage of visual processing is characterized by a specific spatiotemporal rearrangement of intracluster BOLD responses. Our results indicate that while in the space domain BOLD maps may be incapable of capturing the functional specialization of small neuronal populations due to relatively low spatial resolution, some information encoding may still be revealed in the temporal domain by an increase of temporal information entropy.
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.
Neural and vascular variability and the fMRI-BOLD response in normal aging.
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 rights reserved.
Hare, Hannah V; Germuska, Michael; Kelly, Michael E; Bulte, Daniel P
2013-11-01
Measurement of cerebrovascular reactivity (CVR) can give valuable information about existing pathology and the risk of adverse events, such as stroke. A common method of obtaining regional CVR values is by measuring the blood flow response to carbon dioxide (CO2)-enriched air using arterial spin labeling (ASL) or blood oxygen level-dependent (BOLD) imaging. Recently, several studies have used carbogen gas (containing only CO2 and oxygen) as an alternative stimulus. A direct comparison was performed between CVR values acquired by ASL and BOLD imaging using stimuli of (1) 5% CO2 in air and (2) 5% CO2 in oxygen (carbogen-5). Although BOLD and ASL CVR values are shown to be correlated for CO2 in air (mean response 0.11±0.03% BOLD, 4.46±1.80% ASL, n=16 hemispheres), this correlation disappears during a carbogen stimulus (0.36±0.06% BOLD, 4.97±1.30% ASL). It is concluded that BOLD imaging should generally not be used in conjunction with a carbogen stimulus when measuring CVR, and that care must be taken when interpreting CVR as measured by ASL, as values obtained from different stimuli (CO2 in air versus carbogen) are not directly comparable.
Association Between Brain Activation and Functional Connectivity.
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.
Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD
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
The spatio-temporal mapping of epileptic networks: Combination of EEG–fMRI and EEG source imaging
Vulliemoz, S.; Thornton, R.; Rodionov, R.; Carmichael, D.W.; Guye, M.; Lhatoo, S.; McEvoy, A.W.; Spinelli, L.; Michel, C.M.; Duncan, J.S.; Lemieux, L.
2009-01-01
Simultaneous EEG–fMRI acquisitions in patients with epilepsy often reveal distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated with epileptiform discharges. We investigated if electrical source imaging (ESI) performed on the interictal epileptiform discharges (IED) acquired during fMRI acquisition could be used to study the dynamics of the networks identified by the BOLD effect, thereby avoiding the limitations of combining results from separate recordings. Nine selected patients (13 IED types identified) with focal epilepsy underwent EEG–fMRI. Statistical analysis was performed using SPM5 to create BOLD maps. ESI was performed on the IED recorded during fMRI acquisition using a realistic head model (SMAC) and a distributed linear inverse solution (LAURA). ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was closest to the positive BOLD cluster with maximal statistical significance in only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small BOLD clusters could also have clinical relevance in some cases. ESI at later time frame (ESIp) showed propagation to remote sources co-localised with other BOLD clusters in half of cases. In concordant cases, the distance between maxima of ESI and the closest EEG–fMRI cluster was less than 33 mm, in agreement with previous studies. We conclude that simultaneous ESI and EEG–fMRI analysis may be able to distinguish areas of BOLD response related to initiation of IED from propagation areas. This combination provides new opportunities for investigating epileptic networks. PMID:19408351
Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.
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.
Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain
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
NASA Astrophysics Data System (ADS)
Wallace, Tess E.; Manavaki, Roido; Graves, Martin J.; Patterson, Andrew J.; Gilbert, Fiona J.
2017-01-01
Physiological fluctuations are expected to be a dominant source of noise in blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) experiments to assess tumour oxygenation and angiogenesis. This work investigates the impact of various physiological noise regressors: retrospective image correction (RETROICOR), heart rate (HR) and respiratory volume per unit time (RVT), on signal variance and the detection of BOLD contrast in the breast in response to a modulated respiratory stimulus. BOLD MRI was performed at 3 T in ten volunteers at rest and during cycles of oxygen and carbogen gas breathing. RETROICOR was optimized using F-tests to determine which cardiac and respiratory phase terms accounted for a significant amount of signal variance. A nested regression analysis was performed to assess the effect of RETROICOR, HR and RVT on the model fit residuals, temporal signal-to-noise ratio, and BOLD activation parameters. The optimized RETROICOR model accounted for the largest amount of signal variance ( Δ R\\text{adj}2 = 3.3 ± 2.1%) and improved the detection of BOLD activation (P = 0.002). Inclusion of HR and RVT regressors explained additional signal variance, but had a negative impact on activation parameter estimation (P < 0.001). Fluctuations in HR and RVT appeared to be correlated with the stimulus and may contribute to apparent BOLD signal reactivity.
Kallioniemi, Elisa; Pitkänen, Minna; Könönen, Mervi; Vanninen, Ritva; Julkunen, Petro
2016-11-01
Although the relationship between neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) has been widely studied in motor mapping, it is unknown how the motor response type or the choice of motor task affect this relationship. Centers of gravity (CoGs) and response maxima were measured with blood-oxygen-level dependent (BOLD) and arterial spin labeling (ASL) fMRI during motor tasks against nTMS CoGs and response maxima, which were mapped with motor evoked potentials (MEPs) and silent periods (SPs). No differences in motor representations (CoGs and response maxima) were observed in lateral-medial direction (p=0.265). fMRI methods localized the motor representation more posterior than nTMS (p<0.001). This was not affected by the BOLD fMRI motor task (p>0.999) nor nTMS response type (p>0.999). ASL fMRI maxima did not differ from the nTMS nor BOLD fMRI CoGs (p≥0.070), but the ASL CoG was deeper in comparison to other methods (p≤0.042). The BOLD fMRI motor task did not influence the depth of the motor representation (p≥0.745). The median Euclidean distances between the nTMS and fMRI motor representations varied between 7.7mm and 14.5mm and did not differ between the methods (F≤1.23, p≥0.318). The relationship between fMRI and nTMS mapped excitatory (MEP) and inhibitory (SP) responses, and whether the choice of motor task affects this relationship, have not been studied before. The congruence between fMRI and nTMS is good. The choice of nTMS motor response type nor BOLD fMRI motor task had no effect on this relationship. Copyright © 2016 Elsevier B.V. All rights reserved.
Febo, Marcelo; Pira, Ashley S.
2011-01-01
Amphetamine, which is known to cause sensitization, potentiates the hormonal and neurobiological signatures of stress and may also increase sensitivity to stress-inducing stimuli in limbic areas. Trimethylthiazoline (5 μL TMT) is a chemical constituent of fox feces that evokes innate fear and activates the neuronal and hormonal signatures of stress in rats. We used blood oxygen level dependent (BOLD) MRI to test whether amphetamine sensitization (1 mg/kg, i.p. X 3 days) in female rats has a lasting effect on the neural response to a stress-evoking stimulus, the scent of a predator, during the postpartum period. The subiculum and dopamine-enriched midbrain VTA/SN of amphetamine-sensitized, but not control mothers showed a greater BOLD signal response to predator odor than a control putrid scent. The greater responsiveness of these two brain regions following stimulant sensitization might impact neural processing in response to stressors in the maternal brain. PMID:21134359
Febo, Marcelo; Pira, Ashley S
2011-03-25
Amphetamine, which is known to cause sensitization, potentiates the hormonal and neurobiological signatures of stress and may also increase sensitivity to stress-inducing stimuli in limbic areas. Trimethylthiazoline (5μL TMT) is a chemical constituent of fox feces that evokes innate fear and activates the neuronal and hormonal signatures of stress in rats. We used blood oxygen level dependent (BOLD) MRI to test whether amphetamine sensitization (1mg/kg, i.p. ×3days) in female rats has a lasting effect on the neural response to a stress-evoking stimulus, the scent of a predator, during the postpartum period. The subiculum and dopamine-enriched midbrain VTA/SN of amphetamine-sensitized but not control mothers showed a greater BOLD signal response to predator odor than a control putrid scent. The greater responsiveness of these two brain regions following stimulant sensitization might impact neural processing in response to stressors in the maternal brain. Copyright © 2010 Elsevier B.V. All rights reserved.
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.
The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults
Cortese, Bernadette M.; Uhde, Thomas W.; Brady, Kathleen T.; McClernon, F. Joseph; Yang, Qing X.; Collins, Heather R.; LeMatty, Todd; Hartwell, Karen J.
2015-01-01
Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor + picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multi-sensory, but not unisensory cues, was significantly related to participants’ level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. PMID:26475784
The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults.
Cortese, Bernadette M; Uhde, Thomas W; Brady, Kathleen T; McClernon, F Joseph; Yang, Qing X; Collins, Heather R; LeMatty, Todd; Hartwell, Karen J
2015-12-30
Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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.
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
Mechanisms of migraine aura revealed by functional MRI in human visual cortex
Hadjikhani, Nouchine; Sanchez del Rio, Margarita; Wu, Ona; Schwartz, Denis; Bakker, Dick; Fischl, Bruce; Kwong, Kenneth K.; Cutrer, F. Michael; Rosen, Bruce R.; Tootell, Roger B. H.; Sorensen, A. Gregory; Moskowitz, Michael A.
2001-01-01
Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 ± 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex. PMID:11287655
Negative BOLD with Large Increases in Neuronal Activity
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
Shock-like haemodynamic responses induced in the primary visual cortex by moving visual stimuli
Robinson, P. A.
2016-01-01
It is shown that recently discovered haemodynamic waves can form shock-like fronts when driven by stimuli that excite the cortex in a patch that moves faster than the haemodynamic wave velocity. If stimuli are chosen in order to induce shock-like behaviour, the resulting blood oxygen level-dependent (BOLD) response is enhanced, thereby improving the signal to noise ratio of measurements made with functional magnetic resonance imaging. A spatio-temporal haemodynamic model is extended to calculate the BOLD response and determine the main properties of waves induced by moving stimuli. From this, the optimal conditions for stimulating shock-like responses are determined, and ways of inducing these responses in experiments are demonstrated in a pilot study. PMID:27974572
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.
Gonzalez-Castillo, Javier; Hoy, Colin W.; Handwerker, Daniel A.; Roopchansingh, Vinai; Inati, Souheil J.; Saad, Ziad S.; Cox, Robert W.; Bandettini, Peter A.
2015-01-01
It was recently shown that when large amounts of task-based blood oxygen level–dependent (BOLD) data are combined to increase contrast- and temporal signal-to-noise ratios, the majority of the brain shows significant hemodynamic responses time-locked with the experimental paradigm. Here, we investigate the biological significance of such widespread activations. First, the relationship between activation extent and task demands was investigated by varying cognitive load across participants. Second, the tissue specificity of responses was probed using the better BOLD signal localization capabilities of a 7T scanner. Finally, the spatial distribution of 3 primary response types—namely positively sustained (pSUS), negatively sustained (nSUS), and transient—was evaluated using a newly defined voxel-wise waveshape index that permits separation of responses based on their temporal signature. About 86% of gray matter (GM) became significantly active when all data entered the analysis for the most complex task. Activation extent scaled with task load and largely followed the GM contour. The most common response type was nSUS BOLD, irrespective of the task. Our results suggest that widespread activations associated with extremely large single-subject functional magnetic resonance imaging datasets can provide valuable information about the functional organization of the brain that goes undetected in smaller sample sizes. PMID:25405938
Comparison of block and event-related experimental designs in diffusion-weighted functional MRI.
Williams, Rebecca J; McMahon, Katie L; Hocking, Julia; Reutens, David C
2014-08-01
To compare diffusion-weighted functional magnetic resonance imaging (DfMRI), a novel alternative to the blood oxygenation level-dependent (BOLD) contrast, in a functional MRI experiment. Nine participants viewed contrast reversing (7.5 Hz) black-and-white checkerboard stimuli using block and event-related paradigms. DfMRI (b = 1800 mm/s(2)) and BOLD sequences were acquired. Four parameters describing the observed signal were assessed: percent signal change, spatial extent of the activation, the Euclidean distance between peak voxel locations, and the time-to-peak of the best fitting impulse response for different paradigms and sequences. The BOLD conditions showed a higher percent signal change relative to DfMRI; however, event-related DfMRI showed the strongest group activation (t = 21.23, P < 0.0005). Activation was more diffuse and spatially closer to the BOLD response for DfMRI when the block design was used. DfMRIevent showed the shortest TTP (4.4 ± 0.88 sec). The hemodynamic contribution to DfMRI may increase with the use of block designs. © 2013 Wiley Periodicals, Inc.
Neural correlates of value, risk, and risk aversion contributing to decision making under risk.
Christopoulos, George I; Tobler, Philippe N; Bossaerts, Peter; Dolan, Raymond J; Schultz, Wolfram
2009-10-07
Decision making under risk is central to human behavior. Economic decision theory suggests that value, risk, and risk aversion influence choice behavior. Although previous studies identified neural correlates of decision parameters, the contribution of these correlates to actual choices is unknown. In two different experiments, participants chose between risky and safe options. We identified discrete blood oxygen level-dependent (BOLD) correlates of value and risk in the ventral striatum and anterior cingulate, respectively. Notably, increasing inferior frontal gyrus activity to low risk and safe options correlated with higher risk aversion. Importantly, the combination of these BOLD responses effectively decoded the behavioral choice. Striatal value and cingulate risk responses increased the probability of a risky choice, whereas inferior frontal gyrus responses showed the inverse relationship. These findings suggest that the BOLD correlates of decision factors are appropriate for an ideal observer to detect behavioral choices. More generally, these biological data contribute to the validity of the theoretical decision parameters for actual decisions under risk.
Simon, Aaron B.; Dubowitz, David J.; Blockley, Nicholas P.; Buxton, Richard B.
2016-01-01
Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2′ as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2′, we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2′-based estimate of the metabolic response to CO2 of 1.4%, and R2′- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2′-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. PMID:26790354
Simon, Aaron B; Dubowitz, David J; Blockley, Nicholas P; Buxton, Richard B
2016-04-01
Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2' as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2', we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2'-based estimate of the metabolic response to CO2 of 1.4%, and R2'- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2'-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. Copyright © 2016 Elsevier Inc. All rights reserved.
Kenkel, W M; Yee, J R; Moore, K; Madularu, D; Kulkarni, P; Gamber, K; Nedelman, M; Ferris, C F
2016-03-22
Anxiety and social deficits, often involving communication impairment, are fundamental clinical features of fragile X syndrome. There is growing evidence that dysregulation in reward processing is a contributing factor to the social deficits observed in many psychiatric disorders. Hence, we hypothesized that transgenic fragile X mental retardation 1 gene (fmr1) KO (FX) rats would display alterations in reward processing. To this end, awake control and FX rats were imaged for changes in blood oxygen level dependent (BOLD) signal intensity in response to the odor of almond, a stimulus to elicit the innate reward response. Subjects were 'odor naive' to this evolutionarily conserved stimulus. The resulting changes in brain activity were registered to a three-dimensional segmented, annotated rat atlas delineating 171 brain regions. Both wild-type (WT) and FX rats showed robust brain activation to a rewarding almond odor, though FX rats showed an altered temporal pattern and tended to have a higher number of voxels with negative BOLD signal change from baseline. This pattern of greater negative BOLD was especially apparent in the Papez circuit, critical to emotional processing and the mesolimbic/habenular reward circuit. WT rats showed greater positive BOLD response in the supramammillary area, whereas FX rats showed greater positive BOLD response in the dorsal lateral striatum, and greater negative BOLD response in the retrosplenial cortices, the core of the accumbens and the lateral preoptic area. When tested in a freely behaving odor-investigation paradigm, FX rats failed to show the preference for almond odor which typifies WT rats. However, FX rats showed investigation profiles similar to WT when presented with social odors. These data speak to an altered processing of this highly salient novel odor in the FX phenotype and lend further support to the notion that altered reward systems in the brain may contribute to fragile X syndrome symptomology.
Noncanonical spike-related BOLD responses in focal epilepsy
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
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.
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
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.
Brain atrophy can introduce age-related differences in BOLD response.
Liu, Xueqing; Gerraty, Raphael T; Grinband, Jack; Parker, David; Razlighi, Qolamreza R
2017-04-11
Use of functional magnetic resonance imaging (fMRI) in studies of aging is often hampered by uncertainty about age-related differences in the amplitude and timing of the blood oxygenation level dependent (BOLD) response (i.e., hemodynamic impulse response function (HRF)). Such uncertainty introduces a significant challenge in the interpretation of the fMRI results. Even though this issue has been extensively investigated in the field of neuroimaging, there is currently no consensus about the existence and potential sources of age-related hemodynamic alterations. Using an event-related fMRI experiment with two robust and well-studied stimuli (visual and auditory), we detected a significant age-related difference in the amplitude of response to auditory stimulus. Accounting for brain atrophy by circumventing spatial normalization and processing the data in subjects' native space eliminated these observed differences. In addition, we simulated fMRI data using age differences in brain morphology while controlling HRF shape. Analyzing these simulated fMRI data using standard image processing resulted in differences in HRF amplitude, which were eliminated when the data were analyzed in subjects' native space. Our results indicate that age-related atrophy introduces inaccuracy in co-registration to standard space, which subsequently appears as attenuation in BOLD response amplitude. Our finding could explain some of the existing contradictory reports regarding age-related differences in the fMRI BOLD responses. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
The apéritif effect: alcohol's effects on the brain's response to food aromas in women
Eiler, William J.A.; Džemidžić, Mario; Case, K. Rose; Soeurt, Christina M.; Armstrong, Cheryl L.H.; Mattes, Richard D.; O'Connor, Sean J.; Harezlak, Jaroslaw; Acton, Anthony J.; Considine, Robert V.; Kareken, David A.
2015-01-01
Objective Consuming alcohol prior to a meal (an apéritif) increases food consumption. This greater food consumption may result from increased activity in brain regions that mediate reward and regulate feeding behavior. Using functional magnetic resonance imaging, we evaluated the blood oxygenation level dependent (BOLD) response to the food aromas of either roast beef or Italian meat sauce following pharmacokinetically controlled intravenous infusion of alcohol. Methods BOLD activation to food aromas in non-obese women (n=35) was evaluated once during intravenous infusion of 6% v/v EtOH, clamped at a steady-state breath alcohol concentration of 50 mg/dL, and once during infusion of saline using matching pump rates. Ad libitum intake of roast beef with noodles or Italian meat sauce with pasta following imaging was recorded. Results BOLD activation to food relative to non-food odors in the hypothalamic area was increased during alcohol pre-load when compared to saline. Food consumption was significantly greater, and levels of ghrelin were reduced, following alcohol. Conclusions An alcohol pre-load increased food consumption and potentiated differences between food and non-food BOLD responses in the region of the hypothalamus. The hypothalamus may mediate the interplay of alcohol and responses to food cues, thus playing a role in the apéritif phenomenon. PMID:26110891
Jacobs, Julia; Hawco, Colin; Kobayashi, Eliane; Boor, Rainer; LeVan, Pierre; Stephani, Ulrich; Siniatchkin, Michael; Gotman, Jean
2008-04-01
EEG-fMRI is a non-invasive tool to investigate epileptogenic networks in patients with epilepsy. Different patterns of BOLD responses have been observed in children as compared to adults. A high intra- and intersubject variability of the hemodynamic response function (HRF) to epileptic discharges has been observed in adults. The actual HRF to epileptic discharges in children and its dependence on age are unknown. We analyzed 64 EEG-fMRI event types in 37 children (3 months to 18 years), 92% showing a significant BOLD response. HRFs were calculated for each BOLD cluster using a Fourier basis set. After excluding HRFs with a low signal-to-noise ratio, 126 positive and 98 negative HRFs were analyzed. We evaluated age-dependent changes as well as the effect of increasing numbers of spikes. Peak time, amplitude and signal-to-noise ratio of the HRF and the t-statistic score of the cluster were used as dependent variables. We observed significantly longer peak times of the HRF in the youngest children (0 to 2 years), suggesting that the use of multiple HRFs might be important in this group. A different coupling between neuronal activity and metabolism or blood flow in young children may cause this phenomenon. Even if the t-value increased with frequent spikes, the amplitude of the HRF decreased significantly with spike frequency. This reflects a violation of the assumptions of the General Linear Model and therefore the use of alternative analysis techniques may be more appropriate with high spiking rates, a common situation in children.
Jacobs, Julia; Hawco, Colin; Kobayashi, Eliane; Boor, Rainer; LeVan, Pierre; Stephani, Ulrich; Siniatchkin, Michael; Gotman, Jean
2013-01-01
EEG-fMRI is a non-invasive tool to investigate epileptogenic networks in patients with epilepsy. Different patterns of BOLD responses have been observed in children as compared to adults. A high intra- and intersubject variability of the hemodynamic response function (HRF) to epileptic discharges has been observed in adults. The actual HRF to epileptic discharges in children and its dependence on age are unknown. We analyzed 64 EEG-fMRI event types in 37 children (3 months to 18 years), 92% showing a significant BOLD response. HRFs were calculated for each BOLD cluster using a Fourier basis set. After excluding HRFs with a low signal-to-noise ratio, 126 positive and 98 negative HRFs were analyzed. We evaluated age-dependent changes as well as the effect of increasing numbers of spikes. Peak time, amplitude and signal-to-noise ratio of the HRF and the t-statistic score of the cluster were used as dependent variables. We observed significantly longer peak times of the HRF in the youngest children (0 to 2 years), suggesting that the use of multiple HRFs might be important in this group. A different coupling between neuronal activity and metabolism or blood flow in young children may cause this phenomenon. Even if the t-value increased with frequent spikes, the amplitude of the HRF decreased significantly with spike frequency. This reflects a violation of the assumptions of the General Linear Model and therefore the use of alternative analysis techniques may be more appropriate with high spiking rates, a common situation in children. PMID:18221891
Contrasting neural effects of aging on proactive and reactive response inhibition.
Bloemendaal, Mirjam; Zandbelt, Bram; Wegman, Joost; van de Rest, Ondine; Cools, Roshan; Aarts, Esther
2016-10-01
Two distinct forms of response inhibition may underlie observed deficits in response inhibition in aging. We assessed whether age-related neurocognitive impairments in response inhibition reflect deficient reactive inhibition (outright stopping) or also deficient proactive inhibition (anticipatory response slowing), which might be particularly evident with high information load. We used functional magnetic resonance imaging in young (n = 25, age range 18-32) and older adults (n = 23, 61-74) with a stop-signal task. Relative to young adults, older adults exhibited impaired reactive inhibition (i.e., longer stop-signal reaction time) and increased blood oxygen level-dependent (BOLD) signal for successful versus unsuccessful inhibition in the left frontal cortex and cerebellum. Furthermore, older adults also exhibited impaired proactive slowing, but only as a function of information load. This load-dependent behavioral deficit was accompanied by a failure to increase blood oxygen level-dependent (BOLD) signal under high information load in lateral frontal cortex, presupplementary motor area and striatum. Our findings suggest that inhibitory deficits in older adults are caused both by reduced stopping abilities and by diminished preparation capacity during information overload. Copyright © 2016 Elsevier Inc. All rights reserved.
Cortical lamina-dependent blood volume changes in human brain at 7 T.
Huber, Laurentius; Goense, Jozien; Kennerley, Aneurin J; Trampel, Robert; Guidi, Maria; Reimer, Enrico; Ivanov, Dimo; Neef, Nicole; Gauthier, Claudine J; Turner, Robert; Möller, Harald E
2015-02-15
Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8-1.6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans. Copyright © 2014 Elsevier Inc. All rights reserved.
Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers
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
Physiologic underpinnings of negative BOLD cerebrovascular reactivity in brain ventricles.
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 CVR in brain ventricles. © 2013.
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
The study of pain with blood oxygen level dependent functional magnetic resonance imaging
NASA Astrophysics Data System (ADS)
Ibinson, James W.
Using blood oxygen level dependent functional magnetic resonance imaging (BOLD FMRI), the brain areas activated by pain were studied. These initial studies led to interesting new findings about the body's response to pain and to the refinement of one method used in FMRI analysis for correction of physiologic noise (signal fluctuations caused by the cyclic and non-cyclic changes in the cardiovascular and respiratory status of the body). In the first study, evidence was provided suggesting that the multiple painful stimulations used in typical pain FMRI block designs may cause attenuation over time of the BOLD signal within activated areas. The effect this may have on pain investigations using multiple tasks has not been previously investigated. The demonstrated BOLD attenuation seems unique to pain studies. Several possible explanations exist, but two of the most likely are neural activity modulation by descending pain inhibitory mechanisms and changing hemodynamics caused by a physiologic response to pain. The second study began the investigation of hemodynamics by monitoring the physiologic response to pain for eight subjects in two phases. Phase one used a combination of standard operating suite monitors and research equipment to characterizing the physiologic response to pain. Phase two collected magnetic resonance quantitative flow images during painful nerve stimulation to test for changes in global cerebral blood flow. It is well established that changes in respiration and global blood flow can affect the BOLD response, leading to the final investigation of this dissertation. The brain activation induced by pain for the same eight subjects used in the physiologic response experiments described above was then studied by BOLD FMRI. By including the respiration signal and end-tidal carbon dioxide levels in the analysis of the images, the quantification and removal of image intensity variations correlated to breathing and end-tidal carbon dioxide changes could be performed. The technique generally accepted for this analysis, however, uses respiration signals averaged over a 3 second period. Because normal respiratory rate is approximately one breath every 3 to 5 seconds, it was hypothesized that performing the correction using the average breathing data set would miss much of the actual respiration induced variation in each image. Therefore, a new technique for removing signal that covaries with the actual breathing values present during the collection of each image was introduced. (Abstract shortened by UMI.)
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
Brown, Trecia A; Joanisse, Marc F; Gati, Joseph S; Hughes, Sarah M; Nixon, Pam L; Menon, Ravi S; Lomber, Stephen G
2013-01-01
Much of what is known about the cortical organization for audition in humans draws from studies of auditory cortex in the cat. However, these data build largely on electrophysiological recordings that are both highly invasive and provide less evidence concerning macroscopic patterns of brain activation. Optical imaging, using intrinsic signals or dyes, allows visualization of surface-based activity but is also quite invasive. Functional magnetic resonance imaging (fMRI) overcomes these limitations by providing a large-scale perspective of distributed activity across the brain in a non-invasive manner. The present study used fMRI to characterize stimulus-evoked activity in auditory cortex of an anesthetized (ketamine/isoflurane) cat, focusing specifically on the blood-oxygen-level-dependent (BOLD) signal time course. Functional images were acquired for adult cats in a 7 T MRI scanner. To determine the BOLD signal time course, we presented 1s broadband noise bursts between widely spaced scan acquisitions at randomized delays (1-12 s in 1s increments) prior to each scan. Baseline trials in which no stimulus was presented were also acquired. Our results indicate that the BOLD response peaks at about 3.5s in primary auditory cortex (AI) and at about 4.5 s in non-primary areas (AII, PAF) of cat auditory cortex. The observed peak latency is within the range reported for humans and non-human primates (3-4 s). The time course of hemodynamic activity in cat auditory cortex also occurs on a comparatively shorter scale than in cat visual cortex. The results of this study will provide a foundation for future auditory fMRI studies in the cat to incorporate these hemodynamic response properties into appropriate analyses of cat auditory cortex. Copyright © 2012 Elsevier Inc. All rights reserved.
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
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.
Heo, Hye-Young; Wemmie, John A; Johnson, Casey P; Thedens, Daniel R; Magnotta, Vincent A
2015-07-01
Recent experiments suggest that T1 relaxation in the rotating frame (T(1ρ)) is sensitive to metabolism and can detect localized activity-dependent changes in the human visual cortex. Current functional magnetic resonance imaging (fMRI) methods have poor temporal resolution due to delays in the hemodynamic response resulting from neurovascular coupling. Because T(1ρ) is sensitive to factors that can be derived from tissue metabolism, such as pH and glucose concentration via proton exchange, we hypothesized that activity-evoked T(1ρ) changes in visual cortex may occur before the hemodynamic response measured by blood oxygenation level-dependent (BOLD) and arterial spin labeling (ASL) contrast. To test this hypothesis, functional imaging was performed using T(1ρ), BOLD, and ASL in human participants viewing an expanding ring stimulus. We calculated eccentricity phase maps across the occipital cortex for each functional signal and compared the temporal dynamics of T(1ρ) versus BOLD and ASL. The results suggest that T(1ρ) changes precede changes in the two blood flow-dependent measures. These observations indicate that T(1ρ) detects a signal distinct from traditional fMRI contrast methods. In addition, these findings support previous evidence that T(1ρ) is sensitive to factors other than blood flow, volume, or oxygenation. Furthermore, they suggest that tissue metabolism may be driving activity-evoked T(1ρ) changes.
A functional MRI study of happy and sad affective states induced by classical music.
Mitterschiffthaler, Martina T; Fu, Cynthia H Y; Dalton, Jeffrey A; Andrew, Christopher M; Williams, Steven C R
2007-11-01
The present study investigated the functional neuroanatomy of transient mood changes in response to Western classical music. In a pilot experiment, 53 healthy volunteers (mean age: 32.0; SD = 9.6) evaluated their emotional responses to 60 classical musical pieces using a visual analogue scale (VAS) ranging from 0 (sad) through 50 (neutral) to 100 (happy). Twenty pieces were found to accurately induce the intended emotional states with good reliability, consisting of 5 happy, 5 sad, and 10 emotionally unevocative, neutral musical pieces. In a subsequent functional magnetic resonance imaging (fMRI) study, the blood oxygenation level dependent (BOLD) signal contrast was measured in response to the mood state induced by each musical stimulus in a separate group of 16 healthy participants (mean age: 29.5; SD = 5.5). Mood state ratings during scanning were made by a VAS, which confirmed the emotional valence of the selected stimuli. Increased BOLD signal contrast during presentation of happy music was found in the ventral and dorsal striatum, anterior cingulate, parahippocampal gyrus, and auditory association areas. With sad music, increased BOLD signal responses were noted in the hippocampus/amygdala and auditory association areas. Presentation of neutral music was associated with increased BOLD signal responses in the insula and auditory association areas. Our findings suggest that an emotion processing network in response to music integrates the ventral and dorsal striatum, areas involved in reward experience and movement; the anterior cingulate, which is important for targeting attention; and medial temporal areas, traditionally found in the appraisal and processing of emotions. Copyright 2006 Wiley-Liss, Inc.
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 problematic drinking. © 2013 Society for the Study of Addiction.
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.
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.
Fourier modeling of the BOLD response to a breath-hold task: Optimization and reproducibility.
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 based on a BH task with preparatory inspiration, yielding robust estimates of this important physiological parameter. Copyright © 2016 Elsevier Inc. All rights reserved.
Using novel control groups to dissect the amygdala's role in Williams syndrome.
Thornton-Wells, Tricia A; Avery, Suzanne N; Blackford, Jennifer Urbano
2011-07-01
Williams syndrome is a neurodevelopmental disorder with an intriguing behavioral phenotype-hypersociability combined with significant non-social fears. Previous studies have demonstrated abnormalities in amygdala function in individuals with Williams syndrome compared to typically-developing controls. However, it remains unclear whether the findings are related to the atypical neurodevelopment of Williams syndrome, or are also associated with behavioral traits at the extreme end of a normal continuum. We used functional magnetic resonance imaging (fMRI) to compare amygdala blood-oxygenation-level-dependent (BOLD) responses to non-social and social images in individuals with Williams syndrome compared to either individuals with inhibited temperament (high non-social fear) or individuals with uninhibited temperament (high sociability). Individuals with Williams syndrome had larger amygdala BOLD responses when viewing the non-social fear images than the inhibited temperament control group. In contrast, when viewing both fear and neutral social images, individuals with Williams syndrome did not show smaller amygdala BOLD responses relative to the uninhibited temperament control group, but instead had amygdala responses proportionate to their sociability. These results suggest heightened amygdala response to non-social fear images is characteristic of WS, whereas, variability in amygdala response to social fear images is proportionate to, and might be explained by, levels of trait sociability.
Fluoxetine exposure impacts boldness in female Siamese fighting fish, Betta splendens.
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.
Walitt, Brian; Čeko, Marta; Khatiwada, Manish; Gracely, John L.; Rayhan, Rakib; VanMeter, John W.; Gracely, Richard H.
2016-01-01
The subjective experience of cognitive dysfunction (“fibrofog”) is common in fibromyalgia. This study investigated the relation between subjective appraisal of cognitive function, objective cognitive task performance, and brain activity during a cognitive task using functional magnetic resonance imaging (fMRI). Sixteen fibromyalgia patients and 13 healthy pain-free controls completed a battery of questionnaires, including the Multiple Ability Self-Report Questionnaire (MASQ), a measure of self-perceived cognitive difficulties. Participants were evaluated for working memory performance using a modified N-back working memory task while undergoing Blood Oxygen Level Dependent (BOLD) fMRI measurements. Fibromyalgia patients and controls did not differ in working memory performance. Subjective appraisal of cognitive function was associated with better performance (accuracy) on the working memory task in healthy controls but not in fibromyalgia patients. In fibromyalgia patients, increased perceived cognitive difficulty was positively correlated with the severity of their symptoms. BOLD response during the working memory task did not differ between the groups. BOLD response correlated with task accuracy in control subjects but not in fibromyalgia patients. Increased subjective cognitive impairment correlated with decreased BOLD response in both groups but in different anatomic regions. In conclusion, “fibrofog” appears to be better characterized by subjective rather than objective impairment. Neurologic correlates of this subjective experience of impairment might be separate from those involved in the performance of cognitive tasks. PMID:26955513
Walitt, Brian; Čeko, Marta; Khatiwada, Manish; Gracely, John L; Rayhan, Rakib; VanMeter, John W; Gracely, Richard H
2016-01-01
The subjective experience of cognitive dysfunction ("fibrofog") is common in fibromyalgia. This study investigated the relation between subjective appraisal of cognitive function, objective cognitive task performance, and brain activity during a cognitive task using functional magnetic resonance imaging (fMRI). Sixteen fibromyalgia patients and 13 healthy pain-free controls completed a battery of questionnaires, including the Multiple Ability Self-Report Questionnaire (MASQ), a measure of self-perceived cognitive difficulties. Participants were evaluated for working memory performance using a modified N-back working memory task while undergoing Blood Oxygen Level Dependent (BOLD) fMRI measurements. Fibromyalgia patients and controls did not differ in working memory performance. Subjective appraisal of cognitive function was associated with better performance (accuracy) on the working memory task in healthy controls but not in fibromyalgia patients. In fibromyalgia patients, increased perceived cognitive difficulty was positively correlated with the severity of their symptoms. BOLD response during the working memory task did not differ between the groups. BOLD response correlated with task accuracy in control subjects but not in fibromyalgia patients. Increased subjective cognitive impairment correlated with decreased BOLD response in both groups but in different anatomic regions. In conclusion, "fibrofog" appears to be better characterized by subjective rather than objective impairment. Neurologic correlates of this subjective experience of impairment might be separate from those involved in the performance of cognitive tasks.
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.
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.
Brumback, Ty; Squeglia, Lindsay M; Jacobus, Joanna; Pulido, Carmen; Tapert, Susan F; Brown, Sandra A
2015-07-01
Heavy drinking during adolescence is associated with increased reactivity to alcohol related stimuli and to differential neural development. Alcohol cue reactivity has been widely studied among adults with alcohol use disorders, but little is known about the neural substrates of cue reactivity in adolescent drinkers. The current study aimed to identify changes in blood-oxygen level dependent (BOLD) signal during a cue reactivity task pre- and post-monitored abstinence from alcohol. Demographically matched adolescents (16.0-18.9 years, 54% female) with histories of heavy episodic drinking (HD; n=22) and light or non-drinking control teens (CON; n=16) were recruited to participate in a month-long study. All participants completed a functional Magnetic Resonance Imaging (fMRI) scan with an alcohol cue reactivity task and substance use assessments at baseline and after 28 days of monitored abstinence from alcohol and drugs (i.e., urine toxicology testing every 48-72 h). Repeated-measure analysis of variance (ANOVA) examined main effects of group, time, and group×time interactions on BOLD signal response in regions of interest defined by functional differences at baseline. The HD group exhibited greater (p<.01) BOLD activation than CON to alcohol cues relative to neutral cues in all regions of interest (ROIs; bilateral striatum/globus pallidus, left anterior cingulate, bilateral cerebellum, and parahippocampal gyrus extending to the thalamus/substantia nigra) across time points. Group×time effects showed that HD exhibited greater BOLD activation to alcohol cues than CON at baseline in left anterior cingulate cortex and in the right cerebellar region, but these decreased to non-significance after one month of monitored abstinence. In all ROIs examined, HD exhibited greater BOLD response than CON to alcohol relative to neutral beverage picture cues at baseline, indicating heightened cue reactivity to alcohol cues in heavy drinking adolescents prior to the onset of any alcohol use diagnosis. Across the majority of these brain regions, differences in BOLD response were no longer apparent following a month of abstinence, suggesting a decrease in alcohol cue reactivity among adolescent non-dependent heavy drinkers as a consequence of abstaining from alcohol. These results highlight the malleability of adolescent brain function despite no formal intervention targeting cue reactivity. Increased understanding of the neural underpinnings of cue reactivity could have implications for prevention and intervention strategies in adolescent heavy alcohol users. Copyright © 2015 Elsevier Ltd. All rights reserved.
Rodrigues Barreto, Felipe; Mangia, Silvia; Garrido Salmon, Carlos Ernesto
2017-07-01
To identify the impact of reduced oxygen availability on the evoked vascular response upon visual stimulation in the healthy human brain by magnetic resonance imaging (MRI). Functional MRI techniques based on arterial spin labeling (ASL), blood oxygenation level-dependent (BOLD), and vascular space occupancy (VASO)-dependent contrasts were utilized to quantify the BOLD signal, cerebral blood flow (CBF), and volume (CBV) from nine subjects at 3T (7M/2F, 27.3 ± 3.6 years old) during normoxia and mild hypoxia. Changes in visual stimulus-induced oxygen consumption rates were also estimated with mathematical modeling. Significant reductions in the extension of activated areas during mild hypoxia were observed in all three imaging contrasts: by 42.7 ± 25.2% for BOLD (n = 9, P = 0.002), 33.1 ± 24.0% for ASL (n = 9, P = 0.01), and 31.9 ± 15.6% for VASO images (n = 7, P = 0.02). Activated areas during mild hypoxia showed responses with similar amplitude for CBF (58.4 ± 18.7% hypoxia vs. 61.7 ± 16.1% normoxia, P = 0.61) and CBV (33.5 ± 17.5% vs. 25.2 ± 13.0%, P = 0.27), but not for BOLD (2.5 ± 0.8% vs. 4.1 ± 0.6%, P = 0.009). The estimated stimulus-induced increases of oxygen consumption were smaller during mild hypoxia as compared to normoxia (3.1 ± 5.0% vs. 15.5 ± 15.1%, P = 0.04). Our results demonstrate an altered vascular and metabolic response during mild hypoxia upon visual stimulation. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:142-149. © 2016 International Society for Magnetic Resonance in Medicine.
Williams, Rebecca J; Reutens, David C; Hocking, Julia
2015-11-01
Decreased water displacement following increased neural activity has been observed using diffusion-weighted functional MRI (DfMRI) at high b-values. The physiological mechanisms underlying the diffusion signal change may be unique from the standard blood oxygenation level-dependent (BOLD) contrast and closer to the source of neural activity. Whether DfMRI reflects neural activity more directly than BOLD outside the primary cerebral regions remains unclear. Colored and achromatic Mondrian visual stimuli were statistically contrasted to functionally localize the human color center Area V4 in neurologically intact adults. Spatial and temporal properties of DfMRI and BOLD activation were examined across regions of the visual cortex. At the individual level, DfMRI activation patterns showed greater spatial specificity to V4 than BOLD. The BOLD activation patterns were more prominent in the primary visual cortex than DfMRI, where activation was localized to the ventral temporal lobe. Temporally, the diffusion signal change in V4 and V1 both preceded the corresponding hemodynamic response, however the early diffusion signal change was more evident in V1. DfMRI may be of use in imaging applications implementing cognitive subtraction paradigms, and where highly precise individual functional localization is required.
Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.
Kim, Jinho; Jeong, Yong
2013-01-01
Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic AβPP(SWE)/PS1ΔE9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.
Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome.
Mutch, W Alan C; Ellis, Michael J; Ryner, Lawrence N; Ruth Graham, M; Dufault, Brenden; Gregson, Brian; Hall, Thomas; Bunge, Martin; Essig, Marco; Fisher, Joseph A; Duffin, James; Mikulis, David J
2016-09-01
OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.
Weafer, Jessica; Dzemidzic, Mario; Eiler, William; Oberlin, Brandon G.; Wang, Yang; Kareken, David A.
2015-01-01
Trait impulsivity and poor inhibitory control are well-established risk factors for alcohol misuse, yet little is known about the associated neurobiological endophenotypes. Here we examined correlations among brain physiology and self-reported trait impulsive behavior, impaired control over drinking, and a behavioral measure of response inhibition. A sample of healthy drinkers (n=117) completed a pulsed arterial spin labeling (PASL) scan to quantify resting regional cerebral blood flow (rCBF), and measures of self-reported impulsivity (Eysenck I7 Impulsivity scale) and impaired control over drinking. A subset of subjects (n=40) performed a stop signal task during blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess brain regions involved in response inhibition. Eysenck I7 scores were inversely related to blood flow in the right precentral gyrus. Significant BOLD activation during response inhibition occurred in an overlapping right frontal motor/premotor region. Moreover, impaired control over drinking was associated with reduced BOLD response in the same region. These findings suggest that impulsive personality and impaired control over drinking are associated with brain physiology in areas implicated in response inhibition. This is consistent with the idea that difficulty controlling behavior is due in part to impairment in motor restraint systems. PMID:26065376
The time-course of cortico-limbic neural responses to air hunger.
Binks, Andrew P; Evans, Karleyton C; Reed, Jeffrey D; Moosavi, Shakeeb H; Banzett, Robert B
2014-12-01
Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼ 45 mm Hg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V(T)) was alternated every 90 s between high VT (0.96 ± 0.23 L) that provided respiratory comfort (12 ± 6% full scale) and low V(T) (0.48 ± 0.08 L) which evoked air hunger (56 ± 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak <30s and (2) slow, BOLD signal peak >40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research. Copyright © 2014 Elsevier B.V. All rights reserved.
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.
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.
Rusu, Cristian; Morisi, Rita; Boschetto, Davide; Dharmakumar, Rohan; Tsaftaris, Sotirios A.
2014-01-01
This paper aims to identify approaches that generate appropriate synthetic data (computer generated) for Cardiac Phase-resolved Blood-Oxygen-Level-Dependent (CP–BOLD) MRI. CP–BOLD MRI is a new contrast agent- and stress-free approach for examining changes in myocardial oxygenation in response to coronary artery disease. However, since signal intensity changes are subtle, rapid visualization is not possible with the naked eye. Quantifying and visualizing the extent of disease relies on myocardial segmentation and registration to isolate the myocardium and establish temporal correspondences and ischemia detection algorithms to identify temporal differences in BOLD signal intensity patterns. If transmurality of the defect is of interest pixel-level analysis is necessary and thus a higher precision in registration is required. Such precision is currently not available affecting the design and performance of the ischemia detection algorithms. In this work, to enable algorithmic developments of ischemia detection irrespective to registration accuracy, we propose an approach that generates synthetic pixel-level myocardial time series. We do this by (a) modeling the temporal changes in BOLD signal intensity based on sparse multi-component dictionary learning, whereby segmentally derived myocardial time series are extracted from canine experimental data to learn the model; and (b) demonstrating the resemblance between real and synthetic time series for validation purposes. We envision that the proposed approach has the capacity to accelerate development of tools for ischemia detection while markedly reducing experimental costs so that cardiac BOLD MRI can be rapidly translated into the clinical arena for the noninvasive assessment of ischemic heart disease. PMID:24691119
Rusu, Cristian; Morisi, Rita; Boschetto, Davide; Dharmakumar, Rohan; Tsaftaris, Sotirios A
2014-07-01
This paper aims to identify approaches that generate appropriate synthetic data (computer generated) for cardiac phase-resolved blood-oxygen-level-dependent (CP-BOLD) MRI. CP-BOLD MRI is a new contrast agent- and stress-free approach for examining changes in myocardial oxygenation in response to coronary artery disease. However, since signal intensity changes are subtle, rapid visualization is not possible with the naked eye. Quantifying and visualizing the extent of disease relies on myocardial segmentation and registration to isolate the myocardium and establish temporal correspondences and ischemia detection algorithms to identify temporal differences in BOLD signal intensity patterns. If transmurality of the defect is of interest pixel-level analysis is necessary and thus a higher precision in registration is required. Such precision is currently not available affecting the design and performance of the ischemia detection algorithms. In this work, to enable algorithmic developments of ischemia detection irrespective to registration accuracy, we propose an approach that generates synthetic pixel-level myocardial time series. We do this by 1) modeling the temporal changes in BOLD signal intensity based on sparse multi-component dictionary learning, whereby segmentally derived myocardial time series are extracted from canine experimental data to learn the model; and 2) demonstrating the resemblance between real and synthetic time series for validation purposes. We envision that the proposed approach has the capacity to accelerate development of tools for ischemia detection while markedly reducing experimental costs so that cardiac BOLD MRI can be rapidly translated into the clinical arena for the noninvasive assessment of ischemic heart disease.
Error processing in current and former cocaine users
Castelluccio, Brian C.; Meda, Shashwath A.; Muska, Christine E.; Stevens, Michael C.; Pearlson, Godfrey D.
2013-01-01
Deficits in response inhibition and error processing can result in maladaptive behavior, including failure to use past mistakes to inform present decisions. A specific deficit in inhibiting a prepotent response represents one aspect of impulsivity and is a prominent feature of addictive behaviors in general, including cocaine abuse/dependence. Brain regions implicated in cognitive control exhibit reduced activation in cocaine abusers. The purposes of the present investigation were (1) to identify neural differences associated with error processing in current and former cocaine-dependent individuals compared to healthy controls and (2) to determine whether former, long-term abstinent cocaine users showed similar differences compared with current users. The present study used an fMRI Go/No-Go task to investigate differences in BOLD response to correct rejections and false alarms between current cocaine users (n=30), former cocaine users (n=29), and healthy controls (n=35). Impulsivity trait measures were also assessed and compared with BOLD activity. Nineteen regions of interest previously implicated in errors of disinhibition were queried. There were no group differences in the correct rejections condition, but both current and former users exhibited increased BOLD response relative to controls for false alarms. In current users, the pregenual cingulate gyrus and left angular/supramarginal gyri overactivated. In former users, the right middle frontal/precentral gyri, right inferior parietal lobule, and left angular/supramarginal gyri overactivated. Overall, our results support a hypothesis that neural activity in former users differs more from healthy controls than that of current users due to cognitive compensation that facilitates abstinence. PMID:23949893
Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience.
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).
Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies
Bernal-Casas, David; Fang, Zhongnan; Lee, Jin Hyung
2017-01-01
A large number of fMRI studies have shown that the temporal dynamics of evoked BOLD responses can be highly heterogeneous. Failing to model heterogeneous responses in statistical analysis can lead to significant errors in signal detection and characterization and alter the neurobiological interpretation. However, to date it is not clear that, out of a large number of options, which methods are robust against variability in the temporal dynamics of BOLD responses in block-design studies. Here, we used rodent optogenetic fMRI data with heterogeneous BOLD responses and simulations guided by experimental data as a means to investigate different analysis methods’ performance against heterogeneous BOLD responses. Evaluations are carried out within the general linear model (GLM) framework and consist of standard basis sets as well as independent component analysis (ICA). Analyses show that, in the presence of heterogeneous BOLD responses, conventionally used GLM with a canonical basis set leads to considerable errors in the detection and characterization of BOLD responses. Our results suggest that the 3rd and 4th order gamma basis sets, the 7th to 9th order finite impulse response (FIR) basis sets, the 5th to 9th order B-spline basis sets, and the 2nd to 5th order Fourier basis sets are optimal for good balance between detection and characterization, while the 1st order Fourier basis set (coherence analysis) used in our earlier studies show good detection capability. ICA has mostly good detection and characterization capabilities, but detects a large volume of spurious activation with the control fMRI data. PMID:27993672
Nicolas, R; Gros-Dagnac, H; Aubry, F; Celsis, P
2017-06-01
The blood oxygen level-dependent (BOLD) effect is extensively used for functional MRI (fMRI) but presents some limitations. Diffusion-weighted fMRI (DfMRI) has been proposed as a method more tightly linked to neuronal activity. This work proposes a protocol of DfMRI acquired for several b-values and diffusion directions that is compared to gradient-echo BOLD (GE-BOLD) and to repeated spin-echo BOLD (SE-BOLD, acquisitions performed with b=0s/mm 2 ), which was also used to ensure the reproducibility of the response. A block stimulation paradigm of the primary visual system (V1) was performed in 12 healthy subjects with checkerboard alternations (2Hz frequency). DfMRI was performed at 3T with 5 b-values (b=1500, 1000, 500, 250, 0s/mm 2 ) with TR/TE=1004/93ms, Δ/δ=45.4ms/30ms, and 6 spatial directions for diffusion measures. GE-BOLD was performed with a similar block stimulation design timing. Apparent Diffusion Coefficient (ADC)-fMRI was computed with all b-values used. An identical Z-score level was used for all fMRI modalities for the comparison of volumes of activation. ADC-fMRI and SE-BOLD fMRI activation locations were compared in a voxel-based analysis to a cytoarchitectural probability map of V1. SE-BOLD activation volumes represented only 55% of the GE-BOLD activation volumes (P<0.0001). DfMRI activation volumes averaged for all b-values acquired represented only 12% of GE-BOLD (P<0.0001) and only 22% of SE-BOLD activation volumes (P<0.005). Compared to SE-BOLD-fMRI, ADC-fMRI activations showed fewer pixels outside of V1 and a higher average probability of belonging to V1. DfMRI and ADC-fMRI acquisition at 3T could be easily post-processed with common neuro-imaging software. DfMRI and ADC-fMRI activation volumes were significantly smaller than those obtained with SE-BOLD. ADC-fMRI activations were more precisely localized in V1 than those of SE-BOLD-fMRI. This validated the increased capability of ADC-fMRI compared to BOLD to enhance the precision of localizing an fMRI activation in the cyto-architectural zone V1, thereby justifying the use of ADC-fMRI for neuro-scientific studies. Copyright © 2017 Elsevier Inc. All rights reserved.
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
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.
van Opstal, Anna M; van den Berg-Huysmans, Annette A; Hoeksma, Marco; Blonk, Cor; Pijl, Hanno; Rombouts, Serge A R B; van der Grond, Jeroen
2018-01-01
Excessive consumption of sugar-sweetened beverages (SSBs) has been associated with obesity and related diseases. SSBs are often consumed cold, and both the energy content and temperature might influence the consumption behavior for SSBs. The main aim of this study was to elucidate whether consumption temperature and energy (i.e., glucose) content modulate homeostatic (hypothalamus) and reward [ventral tegmental area (VTA)] responses. Sixteen healthy men participated in our study [aged 18-25 y; body mass index (kg/m2): 20-23]. High-resolution functional magnetic resonance imaging data were collected after ingestion of 4 different study stimuli: plain tap water at room temperature (22°C), plain tap water at 0°C, a glucose-containing beverage (75 g glucose dissolved in 300 mL water) at 22°C, and a similar glucose drink at 0°C. Blood oxygen level-dependent (BOLD) changes from baseline (7 min preingestion) were analyzed over time in the hypothalamus and VTA for individual stimulus effects and for effects between stimuli. In the hypothalamus, water at 22°C led to a significantly increased BOLD response; all other stimuli resulted in a direct, significant decrease in BOLD response compared with baseline. In the VTA, a significantly decreased BOLD response compared with baseline was found after the ingestion of stimuli containing glucose at 0°C and 22°C. These responses were not significantly modulated by consumption temperature. The consumption of plain water did not have a significant VTA BOLD effect. Our data show that glucose at 22°C, glucose at 0°C, and water at 0°C lowered hypothalamic activity, which is associated with increased satiation. On the contrary, the consumption of water at room temperature increased activity. All stimuli led to a similar VTA response, which suggests that all drinks elicited a similar hedonic response. Our results indicate that, in addition to glucose, the low temperature at which SSBs are often consumed also leads to a response from the hypothalamus and might strengthen the response of the VTA. This trial was registered at www.clinicaltrials.gov as NCT03181217. © 2018 American Society for Nutrition. All rights reserved.
Schindler, Andreas; Bartels, Andreas
2017-05-01
Superimposed on the visual feed-forward pathway, feedback connections convey higher level information to cortical areas lower in the hierarchy. A prominent framework for these connections is the theory of predictive coding where high-level areas send stimulus interpretations to lower level areas that compare them with sensory input. Along these lines, a growing body of neuroimaging studies shows that predictable stimuli lead to reduced blood oxygen level-dependent (BOLD) responses compared with matched nonpredictable counterparts, especially in early visual cortex (EVC) including areas V1-V3. The sources of these modulatory feedback signals are largely unknown. Here, we re-examined the robust finding of relative BOLD suppression in EVC evident during processing of coherent compared with random motion. Using functional connectivity analysis, we show an optic flow-dependent increase of functional connectivity between BOLD suppressed EVC and a network of visual motion areas including MST, V3A, V6, the cingulate sulcus visual area (CSv), and precuneus (Pc). Connectivity decreased between EVC and 2 areas known to encode heading direction: entorhinal cortex (EC) and retrosplenial cortex (RSC). Our results provide first evidence that BOLD suppression in EVC for predictable stimuli is indeed mediated by specific high-level areas, in accord with the theory of predictive coding. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Visual BOLD Response in Late Blind Subjects with Argus II Retinal Prosthesis
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
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.
Cortical functional anatomy of voluntary saccades in Parkinson disease.
Rieger, Jochem W; Kim, Aleander; Argyelan, Miklos; Farber, Mark; Glazman, Sofya; Liebeskind, Marc; Meyer, Thomas; Bodis-Wollner, Ivan
2008-10-01
In Parkinson Disease (PD) several aspects of saccades are affected. The saccade-generating brainstem neurons are spared, however, the signals they receive may be flawed. In particular voluntary saccades suffer, but the functional anatomy of the impairment of saccade-related cortical control is unknown. We measured blood-oxygenation-level-dependent (BOLD) activation with functional Magnetic Resonance Imaging (fMRI) while healthy participants and patients with PD performed horizontal voluntary saccades between peripheral visual targets or fixated centrally. We compared saccade-related BOLD-activity vs. fixation in patients with PD and in healthy controls and correlated perisaccadic BOLD-activity in PD patients with saccade kinetics (multistep saccades). Saccade related BOLD-activation was found in both PD and healthy participants in the superior parietal cortex (PEF) and the occipital cortex. Our results suggest remarkable hypoactivity of the frontal and supplementary eye fields (FEF and SEF) in PD patients. On the other hand, PD patients showed a statistically more reliable BOLD modulation than healthy participants in the posterior cingulate gyrus, the parahippocampal gyrus, inferior parietal lobule, precuneus and in the middle temporal gyrus. Given abnormal frontal and normal PEF responses, our results suggest that in PD a frontal cortical circuitry, known to be associated with saccade planning, selection, and predicting a metric error of the saccade, is deficient.
Early anti-correlated BOLD signal changes of physiologic origin.
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
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
Furlan, Michele; Smith, Andrew T.; Walker, Robin
2016-01-01
Previous studies have identified several cortical regions that show larger BOLD responses during preparation and execution of anti-saccades than pro-saccades. We confirmed this finding with a greater BOLD response for anti-saccades than pro-saccades during the preparation phase in the FEF, IPS and DLPFC and in the FEF and IPS in the execution phase. We then applied multi-voxel pattern analysis (MVPA) to establish whether different neural populations are involved in the two types of saccade. Pro-saccades and anti-saccades were reliably decoded during saccade execution in all three cortical regions (FEF, DLPFC and IPS) and in IPS during saccade preparation. This indicates neural specialization, for programming the desired response depending on the task rule, in these regions. In a further study tailored for imaging the superior colliculus in the midbrain a similar magnitude BOLD response was observed for pro-saccades and anti-saccades and the two saccade types could not be decoded with MVPA. This was the case both for activity related to the preparation phase and also for that elicited during the execution phase. We conclude that separate cortical neural populations are involved in the task-specific programming of a saccade while in contrast, the SC has a role in response preparation but may be less involved in high-level, task-specific aspects of the control of saccades. PMID:27391390
Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies.
Liu, Jia; Duffy, Ben A; Bernal-Casas, David; Fang, Zhongnan; Lee, Jin Hyung
2017-02-15
A large number of fMRI studies have shown that the temporal dynamics of evoked BOLD responses can be highly heterogeneous. Failing to model heterogeneous responses in statistical analysis can lead to significant errors in signal detection and characterization and alter the neurobiological interpretation. However, to date it is not clear that, out of a large number of options, which methods are robust against variability in the temporal dynamics of BOLD responses in block-design studies. Here, we used rodent optogenetic fMRI data with heterogeneous BOLD responses and simulations guided by experimental data as a means to investigate different analysis methods' performance against heterogeneous BOLD responses. Evaluations are carried out within the general linear model (GLM) framework and consist of standard basis sets as well as independent component analysis (ICA). Analyses show that, in the presence of heterogeneous BOLD responses, conventionally used GLM with a canonical basis set leads to considerable errors in the detection and characterization of BOLD responses. Our results suggest that the 3rd and 4th order gamma basis sets, the 7th to 9th order finite impulse response (FIR) basis sets, the 5th to 9th order B-spline basis sets, and the 2nd to 5th order Fourier basis sets are optimal for good balance between detection and characterization, while the 1st order Fourier basis set (coherence analysis) used in our earlier studies show good detection capability. ICA has mostly good detection and characterization capabilities, but detects a large volume of spurious activation with the control fMRI data. Copyright © 2016 Elsevier Inc. All rights reserved.
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 interpretation of reward-related human fMRI data. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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.
Campbell, Darren W; Wallace, Marc G; Modirrousta, Mandana; Polimeni, Joseph O; McKeen, Nancy A; Reiss, Jeffrey P
2015-12-01
Psychological well-being and social acumen benefit from the recognition of humourous intent and its enjoyment. The enjoyment of humour requires recognition, but humour recognition is not necessarily accompanied by humour enjoyment. Humour recognition is crucial during social interactions, while the associated enjoyment is less critical. Few neuroimaging studies have explicitly differentiated between the neural foundations of humour comprehension and humour appreciation. Among such studies, design limitations have obscured the specification of neural correlates to humour comprehension or appreciation. We implemented a trichotomous response option to address these design limitations. Twenty-four participants rated 120 comics (90 unaltered with humourous intent and 30 caption-altered without humourous intent) as either funny jokes (FJ), not funny jokes but intended to be funny (NFJ), or not intended to be funny or non-jokes (NJ). We defined humour comprehension by NFJ minus NJ and humour appreciation by FJ minus NFJ. We measured localized blood oxygen level dependent (BOLD) neural responses with a 3T MRI scanner. We tested for BOLD responses in humour comprehension brain regions of interest (ROIs), humour appreciation ROIs, and across the whole-brain. We found significant NFJ-NJ BOLD responses in our humour comprehension ROIs and significant FJ-NFJ BOLD responses in select humour appreciation ROIs. One key finding is that comprehension accuracy levels correlated with humour-comprehension responses in the left temporo-parietal junction (TPJ). This finding represents a novel and precise neural linkage to humour comprehension. A second key finding is that the superior frontal gyrus (SFG) was uniquely associated with humour-appreciation. The SFG response suggests that complex cognitive processing underlies humour appreciation and that current models of humour appreciation be revised. Finally, our research design provides an operational distinction between humour comprehension and appreciation and a sensitive measure of individual differences in humour comprehension accuracy. Copyright © 2015 Elsevier Ltd. All rights reserved.
Jin, Guangwei; Li, Kuncheng; Hu, Yingying; Qin, Yulin; Wang, Xiangqing; Xiang, Jie; Yang, Yanhui; Lu, Jie; Zhong, Ning
2011-11-01
To compare the blood oxygen level-dependent (BOLD) response, measured with functional magnetic resonance (MR) imaging, in the posterior cingulate cortex (PCC) and adjacent precuneus regions between healthy control subjects and patients with amnestic mild cognitive impairment (MCI) during problem-solving tasks. This study was approved by the institutional review board. Each subject provided written informed consent. Thirteen patients with amnestic MCI and 13 age- and sex-matched healthy control subjects participated in the study. The functional magnetic resonance (MR) imaging tasks were simplified 4 × 4-grid number placement puzzles that were divided into a simple task (using the row rule or the column rule to solve the puzzle) and a complex task (using both the row and column rules to solve the puzzle). Behavioral results and functional imaging results between the healthy control group and the amnestic MCI group were analyzed. The accuracy for the complex task in the healthy control group was significantly higher than that in the amnestic MCI group (P < .05). The healthy control group exhibited a deactivated BOLD signal intensity (SI) change in the bilateral PCC and adjacent precuneus regions during the complex task, whereas the amnestic MCI group showed activation. The positive linear correlations between the BOLD SI change in bilateral PCC and adjacent precuneus regions and in bilateral hippocampi in the amnestic MCI group were significant (P < .001), while in the healthy control group, they were not (P ≥ .23). These findings suggest that an altered BOLD response in amnestic MCI patients during complex tasks might be related to a decline in problem-solving ability and to memory impairment and, thus, may indicate a compensatory response to memory impairment. RSNA, 2011
Global Brain Blood-Oxygen Level Responses to Autonomic Challenges in Obstructive Sleep Apnea
Macey, Paul M.; Kumar, Rajesh; Ogren, Jennifer A.; Woo, Mary A.; Harper, Ronald M.
2014-01-01
Obstructive sleep apnea (OSA) is accompanied by brain injury, perhaps resulting from apnea-related hypoxia or periods of impaired cerebral perfusion. Perfusion changes can be determined indirectly by evaluation of cerebral blood volume and oxygenation alterations, which can be measured rapidly and non-invasively with the global blood oxygen level dependent (BOLD) signal, a magnetic resonance imaging procedure. We assessed acute BOLD responses in OSA subjects to pressor challenges that elicit cerebral blood flow changes, using a two-group comparative design with healthy subjects as a reference. We separately assessed female and male patterns, since OSA characteristics and brain injury differ between sexes. We studied 94 subjects, 37 with newly-diagnosed, untreated OSA (6 female (age mean ± std: 52.1±8.1 yrs; apnea/hypopnea index [AHI]: 27.7±15.6 events/hr and 31 male 54.3±8.4 yrs; AHI: 37.4±19.6 events/hr), and 20 female (age 50.5±8.1 yrs) and 37 male (age 45.6±9.2 yrs) healthy control subjects. We measured brain BOLD responses every 2 s while subjects underwent cold pressor, hand grip, and Valsalva maneuver challenges. The global BOLD signal rapidly changed after the first 2 s of each challenge, and differed in magnitude between groups to two challenges (cold pressor, hand grip), but not to the Valsalva maneuver (repeated measures ANOVA, p<0.05). OSA females showed greater differences from males in response magnitude and pattern, relative to healthy counterparts. Cold pressor BOLD signal increases (mean ± adjusted standard error) at the 8 s peak were: OSA 0.14±0.08% vs. Control 0.31±0.06%, and hand grip at 6 s were: OSA 0.08±0.03% vs. Control at 0.30±0.02%. These findings, indicative of reduced cerebral blood flow changes to autonomic challenges in OSA, complement earlier reports of altered resting blood flow and reduced cerebral artery responsiveness. Females are more affected than males, an outcome which may contribute to the sex-specific brain injury in the syndrome. PMID:25166862
Plasticity in animal personality traits: does prior experience alter the degree of boldness?
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.
Test-retest reliability of evoked heat stimulation BOLD fMRI.
Upadhyay, Jaymin; Lemme, Jordan; Anderson, Julie; Bleakman, David; Large, Thomas; Evelhoch, Jeffrey L; Hargreaves, Richard; Borsook, David; Becerra, Lino
2015-09-30
To date, the blood oxygenated-level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique has enabled an objective and deeper understanding of pain processing mechanisms embedded within the human central nervous system (CNS). In order to further comprehend the benefits and limitations of BOLD fMRI in the context of pain as well as the corresponding subjective pain ratings, we evaluated the univariate response, test-retest reliability and confidence intervals (CIs) at the 95% level of both data types collected during evoked stimulation of 40°C (non-noxious), 44°C (mildly noxious) and a subject-specific temperature eliciting a 7/10 pain rating. The test-retest reliability between two scanning sessions was determined by calculating group-level interclass correlation coefficients (ICCs) and at the single-subject level. Across the three stimuli, we initially observed a graded response of increasing magnitude for both VAS (visual analog score) pain ratings and fMRI data. Test-retest reliability was observed to be highest for VAS pain ratings obtained during the 7/10 pain stimulation (ICC=0.938), while ICC values of pain fMRI data for a distribution of CNS structures ranged from 0.5 to 0.859 (p<0.05). Importantly, the upper and lower confidence interval CI bounds reported herein could be utilized in subsequent trials involving healthy volunteers to hypothesize the magnitude of effect required to overcome inherent variability of either VAS pain ratings or BOLD responses evoked during innocuous or noxious thermal stimulation. Copyright © 2015 Elsevier B.V. All rights reserved.
The cumulative influence of hyperoxia and hypercapnia on blood oxygenation and R2*
Faraco, Carlos C; Strother, Megan K; Siero, Jeroen CW; Arteaga, Daniel F; Scott, Allison O; Jordan, Lori C; Donahue, Manus J
2015-01-01
Cerebrovascular reactivity (CVR)-weighted blood-oxygenation-level-dependent magnetic resonance imaging (BOLD-MRI) experiments are frequently used in conjunction with hyperoxia. Owing to complex interactions between hyperoxia and hypercapnia, quantitative effects of these gas mixtures on BOLD responses, blood and tissue R2*, and blood oxygenation are incompletely understood. Here we performed BOLD imaging (3 T; TE/TR=35/2,000 ms; spatial resolution=3 × 3 × 3.5 mm3) in healthy volunteers (n=12; age=29±4.1 years) breathing (i) room air (RA), (ii) normocapnic–hyperoxia (95% O2/5% N2, HO), (iii) hypercapnic–normoxia (5% CO2/21% O2/74% N2, HC-NO), and (iv) hypercapnic–hyperoxia (5% CO2/95% O2, HC-HO). For HC-HO, experiments were performed with separate RA and HO baselines to control for changes in O2. T2-relaxation-under-spin-tagging MRI was used to calculate basal venous oxygenation. Signal changes were quantified and established hemodynamic models were applied to quantify vasoactive blood oxygenation, blood–water R2*, and tissue–water R2*. In the cortex, fractional BOLD changes (stimulus/baseline) were HO/RA=0.011±0.007; HC-NO/RA=0.014±0.004; HC-HO/HO=0.020±0.008; and HC-HO/RA=0.035±0.010; for the measured basal venous oxygenation level of 0.632, this led to venous blood oxygenation levels of 0.660 (HO), 0.665 (HC-NO), and 0.712 (HC-HO). Interleaving a HC-HO stimulus with HO baseline provided a smaller but significantly elevated BOLD response compared with a HC-NO stimulus. Results provide an outline for how blood oxygenation differs for several gas stimuli and provides quantitative information on how hypercapnic BOLD CVR and R2* are altered during hyperoxia. PMID:26174329
Wang, Xinmei; Cui, Dongmei; Zheng, Ling; Yang, Xiao; Yang, Hui
2012-01-01
Purpose To elucidate the different neuromechanisms of subjects with strabismic and anisometropic amblyopia compared with normal vision subjects using blood oxygen level–dependent functional magnetic resonance imaging (BOLD-fMRI) and pattern-reversal visual evoked potential (PR-VEP). Methods Fifty-three subjects, age range seven to 12 years, diagnosed with strabismic amblyopia (17 cases), anisometropic amblyopia (20 cases), and normal vision (16 cases), were examined using the BOLD-fMRI and PR-VEP of UTAS-E3000 techniques. Cortical activation by binocular viewing of reversal checkerboard patterns was examined in terms of the calcarine region of interest (ROI)-based and spatial frequency–dependent analysis. The correlation of cortical activation in fMRI and the P100 amplitude in VEP were analyzed using the SPSS 12.0 software package. Results In the BOLD-fMRI procedure, reduced areas and decreased activation levels were found in Brodmann area (BA) 17 and other extrastriate areas in subjects with amblyopia compared with the normal vision group. In general, the reduced areas mainly resided in the striate visual cortex in subjects with anisometropic amblyopia. In subjects with strabismic amblyopia, a more significant cortical impairment was found in bilateral BA 18 and BA 19 than that in subjects with anisometropic amblyopia. The activation by high-spatial-frequency stimuli was reduced in bilateral BA 18 and 19 as well as BA 17 in subjects with anisometropic amblyopia, whereas the activation was mainly reduced in BA 18 and BA 19 in subjects with strabismic amblyopia. These findings were further confirmed by the ROI-based analysis of BA 17. During spatial frequency–dependent VEP detection, subjects with anisometropic amblyopia had reduced sensitivity for high spatial frequency compared to subjects with strabismic amblyopia. The cortical activation in fMRI with the calcarine ROI-based analysis of BA 17 was significantly correlated with the P100 amplitude in VEP recording. Conclusions This study suggested that different types of amblyopia had different cortical responses and combinations of spatial frequency–dependent BOLD-fMRI with PR-VEP could differentiate among various kinds of amblyopia according to the different cortical responses. This study can supply new methods for amblyopia neurology study. PMID:22539870
Metabolic demands of neural-hemodynamic associated and disassociated areas in brain.
Sanganahalli, Basavaraju G; Herman, Peter; Rothman, Douglas L; Blumenfeld, Hal; Hyder, Fahmeed
2016-10-01
Interpretation of regional blood oxygenation level-dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is contingent on whether local field potential (LFP) and multi-unit activity (MUA) is either dissociated or associated. To examine whether neural-hemodynamic associated and dissociated areas have different metabolic demands, we recorded sensory-evoked responses of BOLD signal, blood flow (CBF), and blood volume (CBV), which with calibrated fMRI provided oxidative metabolism (CMR O2 ) from rat's ventral posterolateral thalamic nucleus (VPL) and somatosensory forelimb cortex (S1 FL ) and compared these neuroimaging signals to neurophysiological recordings. MUA faithfully recorded evoked latency differences between VPL and S1 FL because evoked MUA in these regions were similar in magnitude. Since evoked LFP was significantly attenuated in VPL, we extracted the time courses of the weaker thalamic LFP to compare with the stronger cortical LFP using wavelet transform. BOLD and CBV responses were greater in S1 FL than in VPL, similar to LFP regional differences. CBF and CMR O2 responses were both comparably larger in S1 FL and VPL. Despite different levels of CBF-CMR O2 and LFP-MUA couplings in VPL and S1 FL , the CMR O2 was well matched with MUA in both regions. These results suggest that neural-hemodynamic associated and dissociated areas in VPL and S1 FL can have similar metabolic demands. © The Author(s) 2016.
Dose-dependent fluoxetine effects on boldness in male Siamese fighting fish.
Dzieweczynski, Teresa L; Campbell, Brennah A; Kane, Jessica L
2016-03-01
As the use of pharmaceuticals and personal care products (PPCPs) continues to rise, these compounds enter the environment in increasing frequency. One such PPCP, fluoxetine, has been found in detectable amounts in aquatic ecosystems worldwide, where it may interfere with the behavior of exposed organisms. Fluoxetine exposure has been found to influence boldness and exploration in a range of fish species; however, how it might alter behavior in multiple contexts or over time is rarely examined. To this end, the effects of fluoxetine on boldness over time were studied in male Siamese fighting fish. Three different groups of males (0, 0.5 and 5 µg l(-1) fluoxetine) were tested in multiple boldness assays (empty tank, novel environment and shoal) once a week for 3 weeks to collect baseline measures and then at three different time points post-exposure. The effects of these varying exposure amounts on behavior were then examined for overall response, consistency and across-context correlations. Unexposed males were bolder in all contexts, were more consistent within a context, and had stronger between-context correlations than exposed males. Fluoxetine had dose-dependent effects on behavior, as males that received the higher dose exhibited greater behavioral effects. This study stresses the potential fitness consequences of fluoxetine exposure and suggests that examining behavioral effects of PPCPs under different dosing regimens and in multiple contexts is important to gain an increased understanding of how exposure affects behavior. © 2016. Published by The Company of Biologists Ltd.
The influence of monetary punishment on cognitive control in abstinent cocaine-users*
Hester, Robert; Bell, Ryan P.; Foxe, John J.; Garavan, Hugh
2013-01-01
Background Dependent drug users show a diminished neural response to punishment, in both limbic and cortical regions, though it remains unclear how such changes influence cognitive processes critical to addiction. To assess this relationship, we examined the influence of monetary punishment on inhibitory control and adaptive post-error behaviour in abstinent cocaine dependent (CD) participants. Methods 15 abstinent CD and 15 matched control participants performed a Go/No-go response inhibition task, which administered monetary fines for failed response inhibition, during collection of fMRI data. Results CD participants showed reduced inhibitory control and significantly less adaptive post-error slowing in response to punishment, when compared to controls. The diminished behavioural punishment sensitivity shown by CD participants was associated with significant hypoactive error-related BOLD responses in the dorsal anterior cingulate cortex (ACC), right insula and right prefrontal regions. Specifically, CD participants’ error-related response in these regions was not modulated by the presence of punishment, whereas control participants’ response showed a significant BOLD increase during punished errors. Conclusions CD participants showed a blunted response to failed control (errors) that was not modulated by punishment. Consistent with previous findings of reduced sensitivity to monetary loss in cocaine users, we further demonstrate that such insensitivity is associated with an inability to increase cognitive control in the face of negative consequences, a core symptom of addiction. The pattern of deficits in the CD group may have implications for interventions that attempt to improve cognitive control in drug dependent groups via positive/negative incentives. PMID:23791040
The influence of monetary punishment on cognitive control in abstinent cocaine-users.
Hester, Robert; Bell, Ryan P; Foxe, John J; Garavan, Hugh
2013-11-01
Dependent drug users show a diminished neural response to punishment, in both limbic and cortical regions, though it remains unclear how such changes influence cognitive processes critical to addiction. To assess this relationship, we examined the influence of monetary punishment on inhibitory control and adaptive post-error behavior in abstinent cocaine dependent (CD) participants. 15 abstinent CD and 15 matched control participants performed a Go/No-go response inhibition task, which administered monetary fines for failed response inhibition, during collection of fMRI data. CD participants showed reduced inhibitory control and significantly less adaptive post-error slowing in response to punishment, when compared to controls. The diminished behavioral punishment sensitivity shown by CD participants was associated with significant hypoactive error-related BOLD responses in the dorsal anterior cingulate cortex (ACC), right insula and right prefrontal regions. Specifically, CD participants' error-related response in these regions was not modulated by the presence of punishment, whereas control participants' response showed a significant BOLD increase during punished errors. CD participants showed a blunted response to failed control (errors) that was not modulated by punishment. Consistent with previous findings of reduced sensitivity to monetary loss in cocaine users, we further demonstrate that such insensitivity is associated with an inability to increase cognitive control in the face of negative consequences, a core symptom of addiction. The pattern of deficits in the CD group may have implications for interventions that attempt to improve cognitive control in drug dependent groups via positive/negative incentives. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.
Using High Spatial Resolution to Improve BOLD fMRI Detection at 3T
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
Large enhancement of perfusion contribution on fMRI signal
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
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.
Roy, Tamal; Bhat, Anuradha
2018-01-01
This study (1) investigated variation among populations and the effects of sex and body size on boldness, activity and shoal-association tendency among wild zebrafish, and (2) tested for existence of correlations between behaviours, controlling for sex and body size. Individuals across four natural populations were tested for general activity in a novel situation, number of predator inspections undertaken and tendency to associate with a conspecific shoal in the presence of predators. Results showed a significant effect of population on boldness with a population from high-predation habitat being bolder than populations from low-predation habitats. Males showed significantly higher tendencies than females to associate with a conspecific shoal in the presence of predators. Further, a negative relationship was found between activity and boldness only within two low-predation populations. Individual body size had a strong effect on the activity-boldness relationship within the low-predation population from flowing water habitat. Smaller fish were bolder and less active while larger fish were more cautious and active. Overall, the results indicated that while population-level behavioural responses might be shaped by predation pressure, state-dependent factors could determine behavioural correlations among individuals within populations.
Roy, Tamal
2018-01-01
This study (1) investigated variation among populations and the effects of sex and body size on boldness, activity and shoal-association tendency among wild zebrafish, and (2) tested for existence of correlations between behaviours, controlling for sex and body size. Individuals across four natural populations were tested for general activity in a novel situation, number of predator inspections undertaken and tendency to associate with a conspecific shoal in the presence of predators. Results showed a significant effect of population on boldness with a population from high-predation habitat being bolder than populations from low-predation habitats. Males showed significantly higher tendencies than females to associate with a conspecific shoal in the presence of predators. Further, a negative relationship was found between activity and boldness only within two low-predation populations. Individual body size had a strong effect on the activity–boldness relationship within the low-predation population from flowing water habitat. Smaller fish were bolder and less active while larger fish were more cautious and active. Overall, the results indicated that while population-level behavioural responses might be shaped by predation pressure, state-dependent factors could determine behavioural correlations among individuals within populations. PMID:29410809
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.
MEG and fMRI Fusion for Non-Linear Estimation of Neural and BOLD Signal Changes
Plis, Sergey M.; Calhoun, Vince D.; Weisend, Michael P.; Eichele, Tom; Lane, Terran
2010-01-01
The combined analysis of magnetoencephalography (MEG)/electroencephalography and functional magnetic resonance imaging (fMRI) measurements can lead to improvement in the description of the dynamical and spatial properties of brain activity. In this paper we empirically demonstrate this improvement using simulated and recorded task related MEG and fMRI activity. Neural activity estimates were derived using a dynamic Bayesian network with continuous real valued parameters by means of a sequential Monte Carlo technique. In synthetic data, we show that MEG and fMRI fusion improves estimation of the indirectly observed neural activity and smooths tracking of the blood oxygenation level dependent (BOLD) response. In recordings of task related neural activity the combination of MEG and fMRI produces a result with greater signal-to-noise ratio, that confirms the expectation arising from the nature of the experiment. The highly non-linear model of the BOLD response poses a difficult inference problem for neural activity estimation; computational requirements are also high due to the time and space complexity. We show that joint analysis of the data improves the system's behavior by stabilizing the differential equations system and by requiring fewer computational resources. PMID:21120141
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.
Simultaneous GCaMP6-based fiber photometry and fMRI in rats.
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.
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
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.
Edmiston, E. Kale; McHugo, Maureen; Dukic, Mildred S.; Smith, Stephen D.; Abou-Khalil, Bassel; Eggers, Erica
2013-01-01
Emotionally arousing pictures induce increased activation of visual pathways relative to emotionally neutral images. A predominant model for the preferential processing and attention to emotional stimuli posits that the amygdala modulates sensory pathways through its projections to visual cortices. However, recent behavioral studies have found intact perceptual facilitation of emotional stimuli in individuals with amygdala damage. To determine the importance of the amygdala to modulations in visual processing, we used functional magnetic resonance imaging to examine visual cortical blood oxygenation level-dependent (BOLD) signal in response to emotionally salient and neutral images in a sample of human patients with unilateral medial temporal lobe resection that included the amygdala. Adults with right (n = 13) or left (n = 5) medial temporal lobe resections were compared with demographically matched healthy control participants (n = 16). In the control participants, both aversive and erotic images produced robust BOLD signal increases in bilateral primary and secondary visual cortices relative to neutral images. Similarly, all patients with amygdala resections showed enhanced visual cortical activations to erotic images both ipsilateral and contralateral to the lesion site. All but one of the amygdala resection patients showed similar enhancements to aversive stimuli and there were no significant group differences in visual cortex BOLD responses in patients compared with controls for either aversive or erotic images. Our results indicate that neither the right nor left amygdala is necessary for the heightened visual cortex BOLD responses observed during emotional stimulus presentation. These data challenge an amygdalo-centric model of emotional modulation and suggest that non-amygdalar processes contribute to the emotional modulation of sensory pathways. PMID:23825407
Response of neural reward regions to food cues in autism spectrum disorders
2012-01-01
Background One hypothesis for the social deficits that characterize autism spectrum disorders (ASD) is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. Method We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD) signal in response to the food images Results We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. Conclusion These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD. PMID:22958533
Cho, Junghun; Kee, Youngwook; Spincemaille, Pascal; Nguyen, Thanh D; Zhang, Jingwei; Gupta, Ajay; Zhang, Shun; Wang, Yi
2018-03-07
To map the cerebral metabolic rate of oxygen (CMRO 2 ) by estimating the oxygen extraction fraction (OEF) from gradient echo imaging (GRE) using phase and magnitude of the GRE data. 3D multi-echo gradient echo imaging and perfusion imaging with arterial spin labeling were performed in 11 healthy subjects. CMRO 2 and OEF maps were reconstructed by joint quantitative susceptibility mapping (QSM) to process GRE phases and quantitative blood oxygen level-dependent (qBOLD) modeling to process GRE magnitudes. Comparisons with QSM and qBOLD alone were performed using ROI analysis, paired t-tests, and Bland-Altman plot. The average CMRO 2 value in cortical gray matter across subjects were 140.4 ± 14.9, 134.1 ± 12.5, and 184.6 ± 17.9 μmol/100 g/min, with corresponding OEFs of 30.9 ± 3.4%, 30.0 ± 1.8%, and 40.9 ± 2.4% for methods based on QSM, qBOLD, and QSM+qBOLD, respectively. QSM+qBOLD provided the highest CMRO 2 contrast between gray and white matter, more uniform OEF than QSM, and less noisy OEF than qBOLD. Quantitative CMRO 2 mapping that fits the entire complex GRE data is feasible by combining QSM analysis of phase and qBOLD analysis of magnitude. © 2018 International Society for Magnetic Resonance in Medicine.
Mayhew, S D; Mullinger, K J; Ostwald, D; Porcaro, C; Bowtell, R; Bagshaw, A P; Francis, S T
2016-06-01
In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR-NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of average responses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Baird, Abigail A; Colvin, Mary K; Vanhorn, John D; Inati, Souheil; Gazzaniga, Michael S
2005-04-01
In the present study, we combined 2 types of magnetic resonance technology to explore individual differences on a task that required the recognition of objects presented from unusual viewpoints. This task was chosen based on previous work that has established the necessity of information transfer from the right parietal cortex to the left inferior cortex for its successful completion. We used reaction times (RTs) to localize regions of cortical activity in the superior parietal and inferior frontal regions (blood oxygen level-dependent [BOLD] response) that were more active with longer response times. These regions were then sampled, and their signal change used to predict individual differences in structural integrity of white matter in the corpus callosum (using diffusion tensor imaging). Results show that shorter RTs (and associated increases in BOLD response) are associated with increased organization in the splenium of the corpus callosum, whereas longer RTs are associated with increased organization in the genu.
2013-01-01
Background Social anxiety disorder (SAD) is thought to involve deficits in emotion regulation, and more specifically, deficits in cognitive reappraisal. However, evidence for such deficits is mixed. Methods Using functional magnetic resonance imaging (fMRI) of blood oxygen-level dependent (BOLD) signal, we examined reappraisal-related behavioral and neural responses in 27 participants with generalized SAD and 27 healthy controls (HC) during three socio-emotional tasks: (1) looming harsh faces (Faces); (2) videotaped actors delivering social criticism (Criticism); and (3) written autobiographical negative self-beliefs (Beliefs). Results Behaviorally, compared to HC, participants with SAD had lesser reappraisal-related reduction in negative emotion in the Beliefs task. Neurally, compared to HC, participants with SAD had lesser BOLD responses in reappraisal-related brain regions when reappraising faces, in visual and attention related regions when reappraising criticism, and in the left superior temporal gyrus when reappraising beliefs. Examination of the temporal dynamics of BOLD responses revealed late reappraisal-related increased responses in HC, compared to SAD. In addition, the dorsomedial prefrontal cortex (DMPFC), which showed reappraisal-related increased activity in both groups, had similar temporal dynamics in SAD and HC during the Faces and Criticism tasks, but greater late response increases in HC, compared to SAD, during the Beliefs task. Reappraisal-related greater late DMPFC responses were associated with greater percent reduction in negative emotion ratings in SAD patients. Conclusions These results suggest a dysfunction of cognitive reappraisal in SAD patients, with overall reduced late brain responses in prefrontal regions, particularly when reappraising faces. Decreased late activity in the DMPFC might be associated with deficient reappraisal and greater negative reactivity. Trial registration ClinicalTrials.gov identifier: NCT00380731 PMID:24517388
Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina
2017-05-01
A sound of interest may be tracked amid other salient sounds by focusing attention on its characteristic features including its frequency. Functional magnetic resonance imaging findings have indicated that frequency representations in human primary auditory cortex (AC) contribute to this feat. However, attentional modulations were examined at relatively low spatial and spectral resolutions, and frequency-selective contributions outside the primary AC could not be established. To address these issues, we compared blood oxygenation level-dependent (BOLD) responses in the superior temporal cortex of human listeners while they identified single frequencies versus listened selectively for various frequencies within a multifrequency scene. Using best-frequency mapping, we observed that the detailed spatial layout of attention-induced BOLD response enhancements in primary AC follows the tonotopy of stimulus-driven frequency representations-analogous to the "spotlight" of attention enhancing visuospatial representations in retinotopic visual cortex. Moreover, using an algorithm trained to discriminate stimulus-driven frequency representations, we could successfully decode the focus of frequency-selective attention from listeners' BOLD response patterns in nonprimary AC. Our results indicate that the human brain facilitates selective listening to a frequency of interest in a scene by reinforcing the fine-grained activity pattern throughout the entire superior temporal cortex that would be evoked if that frequency was present alone. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence.
Fierstra, Jorn; van Niftrik, Bas; Piccirelli, Marco; Burkhardt, Jan Karl; Pangalu, Athina; Kocian, Roman; Valavanis, Antonios; Weller, Michael; Regli, Luca; Bozinov, Oliver
2016-07-01
Current MRI sequences are limited in identifying brain areas at risk for high grade glioma recurrence. We employed intraoperative 3-Tesla functional MRI to assess cerebrovascular reactivity (CVR) after high-grade glioma resection and analyzed regional CVR responses in areas of tumor recurrence on clinical follow-up imaging. Five subjects with high-grade glioma that underwent an intraoperative Blood Oxygen-Level Dependent (BOLD) MRI CVR examination and had a clinical follow-up of at least 18months were selected from a prospective database. For this study, location of tumor recurrence was spatially matched to the intraoperative imaging to assess CVR response in that particular area. CVR is defined as the percent BOLD signal change during repeated cycles of apnea. Of the 5 subjects (mean age 44, 2 females), 4 were diagnosed with a WHO grade III and 1 subject with a WHO grade IV glioma. Three subjects exhibited a tumor recurrence on clinical follow-up MRI (mean: 15months). BOLD CVR measured in the spatially matched area of tumor recurrence was on average 94% increased (range-32% to 183%) as compared to contralateral hemisphere CVR response, 1.50±0.81 versus 1.03±0.46 respectively (p=0.31). For this first analysis in a small cohort, we found altered intraoperative CVR in brain areas exhibiting high grade glioma recurrence on clinical follow-up imaging. Copyright © 2016 Elsevier Inc. All rights reserved.
Multisite Reliability of Cognitive BOLD Data
Brown, Gregory G.; Mathalon, Daniel H.; Stern, Hal; Ford, Judith; Mueller, Bryon; Greve, Douglas N.; McCarthy, Gregory; Voyvodic, Jim; Glover, Gary; Diaz, Michele; Yetter, Elizabeth; Burak Ozyurt, I.; Jorgensen, Kasper W.; Wible, Cynthia G.; Turner, Jessica A.; Thompson, Wesley K.; Potkin, Steven G.
2010-01-01
Investigators perform multi-site functional magnetic resonance imaging studies to increase statistical power, to enhance generalizability, and to improve the likelihood of sampling relevant subgroups. Yet undesired site variation in imaging methods could off-set these potential advantages. We used variance components analysis to investigate sources of variation in the blood oxygen level dependent (BOLD) signal across four 3T magnets in voxelwise and region of interest (ROI) analyses. Eighteen participants traveled to four magnet sites to complete eight runs of a working memory task involving emotional or neutral distraction. Person variance was more than 10 times larger than site variance for five of six ROIs studied. Person-by-site interactions, however, contributed sizable unwanted variance to the total. Averaging over runs increased between-site reliability, with many voxels showing good to excellent between-site reliability when eight runs were averaged and regions of interest showing fair to good reliability. Between-site reliability depended on the specific functional contrast analyzed in addition to the number of runs averaged. Although median effect size was correlated with between-site reliability, dissociations were observed for many voxels. Brain regions where the pooled effect size was large but between-site reliability was poor were associated with reduced individual differences. Brain regions where the pooled effect size was small but between-site reliability was excellent were associated with a balance of participants who displayed consistently positive or consistently negative BOLD responses. Although between-site reliability of BOLD data can be good to excellent, acquiring highly reliable data requires robust activation paradigms, ongoing quality assurance, and careful experimental control. PMID:20932915
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.
Simultaneous EEG/fMRI analysis of the resonance phenomena in steady-state visual evoked responses.
Bayram, Ali; Bayraktaroglu, Zubeyir; Karahan, Esin; Erdogan, Basri; Bilgic, Basar; Ozker, Muge; Kasikci, Itir; Duru, Adil D; Ademoglu, Ahmet; Oztürk, Cengizhan; Arikan, Kemal; Tarhan, Nevzat; Demiralp, Tamer
2011-04-01
The stability of the steady-state visual evoked potentials (SSVEPs) across trials and subjects makes them a suitable tool for the investigation of the visual system. The reproducible pattern of the frequency characteristics of SSVEPs shows a global amplitude maximum around 10 Hz and additional local maxima around 20 and 40 Hz, which have been argued to represent resonant behavior of damped neuronal oscillators. Simultaneous electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) measurement allows testing of the resonance hypothesis about the frequency-selective increases in SSVEP amplitudes in human subjects, because the total synaptic activity that is represented in the fMRI-Blood Oxygen Level Dependent (fMRI-BOLD) response would not increase but get synchronized at the resonance frequency. For this purpose, 40 healthy volunteers were visually stimulated with flickering light at systematically varying frequencies between 6 and 46 Hz, and the correlations between SSVEP amplitudes and the BOLD responses were computed. The SSVEP frequency characteristics of all subjects showed 3 frequency ranges with an amplitude maximum in each of them, which roughly correspond to alpha, beta and gamma bands of the EEG. The correlation maps between BOLD responses and SSVEP amplitude changes across the different stimulation frequencies within each frequency band showed no significant correlation in the alpha range, while significant correlations were obtained in the primary visual area for the beta and gamma bands. This non-linear relationship between the surface recorded SSVEP amplitudes and the BOLD responses of the visual cortex at stimulation frequencies around the alpha band supports the view that a resonance at the tuning frequency of the thalamo-cortical alpha oscillator in the visual system is responsible for the global amplitude maximum of the SSVEP around 10 Hz. Information gained from the SSVEP/fMRI analyses in the present study might be extrapolated to the EEG/fMRI analysis of the transient event-related potentials (ERPs) in terms of expecting more reliable and consistent correlations between EEG and fMRI responses, when the analyses are carried out on evoked or induced oscillations (spectral perturbations) in separate frequency bands instead of the time-domain ERP peaks.
Miller, Jennifer L; James, G Andrew; Goldstone, Anthony P; Couch, Jessica A; He, Guojun; Driscoll, Daniel J; Liu, Yijun
2007-06-01
Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.
Differential responses in dorsal visual cortex to motion and disparity depth cues
Arnoldussen, David M.; Goossens, Jeroen; van den Berg, Albert V.
2013-01-01
We investigated how interactions between monocular motion parallax and binocular cues to depth vary in human motion areas for wide-field visual motion stimuli (110 × 100°). We used fMRI with an extensive 2 × 3 × 2 factorial blocked design in which we combined two types of self-motion (translational motion and translational + rotational motion), with three categories of motion inflicted by the degree of noise (self-motion, distorted self-motion, and multiple object-motion), and two different view modes of the flow patterns (stereo and synoptic viewing). Interactions between disparity and motion category revealed distinct contributions to self- and object-motion processing in 3D. For cortical areas V6 and CSv, but not the anterior part of MT+ with bilateral visual responsiveness (MT+/b), we found a disparity-dependent effect of rotational flow and noise: When self-motion perception was degraded by adding rotational flow and moderate levels of noise, the BOLD responses were reduced compared with translational self-motion alone, but this reduction was cancelled by adding stereo information which also rescued the subject's self-motion percept. At high noise levels, when the self-motion percept gave way to a swarm of moving objects, the BOLD signal strongly increased compared to self-motion in areas MT+/b and V6, but only for stereo in the latter. BOLD response did not increase for either view mode in CSv. These different response patterns indicate different contributions of areas V6, MT+/b, and CSv to the processing of self-motion perception and the processing of multiple independent motions. PMID:24339808
Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.
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.
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.
Anderson, Ian M; Juhasz, Gabriella; Thomas, Emma; Downey, Darragh; McKie, Shane; Deakin, J F William; Elliott, Rebecca
2011-01-01
Both reduced serotonergic (5-HT) function and negative emotional biases have been associated with vulnerability to depression. In order to investigate whether these might be related we examined 5-HT modulation of affective processing in 14 remitted depressed subjects compared with 12 never depressed controls matched for age and sex. Participants underwent function magnetic resonance imaging (fMRI) during a covert face emotion task with and without intravenous citalopram (7.5mg) pretreatment. Compared with viewing neutral faces, and irrespective of group, citalopram enhanced left anterior cingulate blood oxygen level dependent (BOLD) response to happy faces, right posterior insula and right lateral orbitofrontal responses to sad faces, and reduced amygdala responses bilaterally to fearful faces. In controls, relative to remitted depressed subjects, citalopram increased bilateral hippocampal responses to happy faces and increased right anterior insula response to sad faces. These findings were not accounted for by changes in BOLD responses to viewing neutral faces. These results are consistent with previous findings showing 5-HT modulation of affective processing; differences found in previously depressed participants compared with controls may contribute to emotional processing biases underlying vulnerability to depressive relapse. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.
Neural and vascular variability and the fMRI-BOLD response in normal aging
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
Anderson, Jeffrey S; Zielinski, Brandon A; Nielsen, Jared A; Ferguson, Michael A
2014-04-01
Very low-frequency blood oxygen level-dependent (BOLD) fluctuations have emerged as a valuable tool for describing brain anatomy, neuropathology, and development. Such fluctuations exhibit power law frequency dynamics, with largest amplitude at lowest frequencies. The biophysical mechanisms generating such fluctuations are poorly understood. Using publicly available data from 1,019 subjects of age 7-30, we show that BOLD fluctuations exhibit temporal complexity that is linearly related to local connectivity (regional homogeneity), consistently and significantly covarying across subjects and across gray matter regions. This relationship persisted independently of covariance with gray matter density or standard deviation of BOLD signal. During late neurodevelopment, BOLD fluctuations were unchanged with age in association cortex while becoming more random throughout the rest of the brain. These data suggest that local interconnectivity may play a key role in establishing the complexity of low-frequency BOLD fluctuations underlying functional magnetic resonance imaging connectivity. Stable low-frequency power dynamics may emerge through segmentation and integration of connectivity during development of distributed large-scale brain networks. Copyright © 2013 Wiley Periodicals, Inc.
Preliminary evidence for genetic overlap between body mass index and striatal reward response.
Lancaster, T M; Ihssen, I; Brindley, L M; Linden, D E
2018-01-10
The reward-processing network is implicated in the aetiology of obesity. Several lines of evidence suggest obesity-linked genetic risk loci (such as DRD2 and FTO) may influence individual variation in body mass index (BMI) through neuropsychological processes reflected in alterations in activation of the striatum during reward processing. However, no study has tested the broader hypotheses that (a) the relationship between BMI and reward-related brain activation (measured through the blood oxygenation-dependent (BOLD) signal) may be observed in a large population study and (b) the overall genetic architecture of these phenotypes overlap, an assumption critical for the progression of imaging genetic studies in obesity research. Using data from the Human Connectome Project (N = 1055 healthy, young individuals: average BMI = 26.4), we first establish a phenotypic relationship between BMI and ventral striatal (VS) BOLD during the processing of rewarding (monetary) stimuli (β = 0.44, P = 0.013), accounting for potential confounds. BMI and VS BOLD were both significantly influenced by additive genetic factors (H2r = 0.57; 0.12, respectively). Further decomposition of this variance suggested that the relationship was driven by shared genetic (ρ g = 0.47, P = 0.011), but not environmental (ρ E = -0.07, P = 0.29) factors. To validate the assumption of genetic pleiotropy between BMI and VS BOLD, we further show that polygenic risk for higher BMI is also associated with increased VS BOLD response to appetitive stimuli (calorically high food images), in an independent sample (N = 81; P FWE-ROI < 0.005). Together, these observations suggest that the genetic factors link risk to obesity to alterations within key nodes of the brain's reward circuity. These observations provide a basis for future work exploring the mechanistic role of genetic loci that confer risk for obesity using the imaging genetics approach.
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.
Sex differences in stress response circuitry activation dependent on female hormonal cycle.
Goldstein, Jill M; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos
2010-01-13
Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this functional magnetic resonance imaging study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry [amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and anterior cingulate gyrus (ACG)]. Women were scanned twice based on normal variation in menstrual cycle hormones [i.e., early follicular (EF) compared with late follicular-midcycle (LF/MC) menstrual phases]. Using SPM8b, there were few significant differences in blood oxygenation level-dependent (BOLD) signal changes in men compared to EF women, except ventromedial nucleus (VMN), lateral hypothalamic area (LHA), left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males.
Littlefield, Melissa M; Dietz, Martin J; Fitzgerald, Des; Knudsen, Kasper J; Tonks, James
2015-01-01
"Truth" has been used as a baseline condition in several functional magnetic resonance imaging (fMRI) studies of deception. However, like deception, telling the truth is an inherently social construct, which requires consideration of another person's mental state, a phenomenon known as Theory of Mind. Using a novel ecological paradigm, we examined blood oxygenation level dependent (BOLD) responses during social and simple truth telling. Participants (n = 27) were randomly divided into two competing teams. Post-competition, each participant was scanned while evaluating performances from in-group and out-group members. Participants were asked to be honest and were told that their evaluations would be made public. We found increased BOLD responses in the medial prefrontal cortex, bilateral anterior insula and precuneus when participants were asked to tell social truths compared to simple truths about another person. At the behavioral level, participants were slower at responding to social compared to simple questions about another person. These findings suggest that telling the truth is a nuanced cognitive operation that is dependent on the degree of mentalizing. Importantly, we show that the cortical regions engaged by truth telling show a distinct pattern when the task requires social reasoning.
Littlefield, Melissa M.; Dietz, Martin J.; Fitzgerald, Des; Knudsen, Kasper J.; Tonks, James
2015-01-01
“Truth” has been used as a baseline condition in several functional magnetic resonance imaging (fMRI) studies of deception. However, like deception, telling the truth is an inherently social construct, which requires consideration of another person's mental state, a phenomenon known as Theory of Mind. Using a novel ecological paradigm, we examined blood oxygenation level dependent (BOLD) responses during social and simple truth telling. Participants (n = 27) were randomly divided into two competing teams. Post-competition, each participant was scanned while evaluating performances from in-group and out-group members. Participants were asked to be honest and were told that their evaluations would be made public. We found increased BOLD responses in the medial prefrontal cortex, bilateral anterior insula and precuneus when participants were asked to tell social truths compared to simple truths about another person. At the behavioral level, participants were slower at responding to social compared to simple questions about another person. These findings suggest that telling the truth is a nuanced cognitive operation that is dependent on the degree of mentalizing. Importantly, we show that the cortical regions engaged by truth telling show a distinct pattern when the task requires social reasoning. PMID:26539094
Normothermic Mouse Functional MRI of Acute Focal Thermostimulation for Probing Nociception
Reimann, Henning Matthias; Hentschel, Jan; Marek, Jaroslav; Huelnhagen, Till; Todiras, Mihail; Kox, Stefanie; Waiczies, Sonia; Hodge, Russ; Bader, Michael; Pohlmann, Andreas; Niendorf, Thoralf
2016-01-01
Combining mouse genomics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. Here we report on the reproducible application of acute noxious heat stimuli to examine the feasibility and limitations of functional brain mapping for central pain processing in mice. Recent technical and procedural advances were applied for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying mild noxious heat stimuli to wildtype mice resulted in highly significant BOLD patterns in anatomical brain structures forming the pain matrix, which comprise temporal signal intensity changes of up to 6% magnitude. We also observed sub-threshold correlation patterns in large areas of the brain, as well as alterations in mean arterial blood pressure (MABP) in response to the applied stimulus. PMID:26821826
Normothermic Mouse Functional MRI of Acute Focal Thermostimulation for Probing Nociception
NASA Astrophysics Data System (ADS)
Reimann, Henning Matthias; Hentschel, Jan; Marek, Jaroslav; Huelnhagen, Till; Todiras, Mihail; Kox, Stefanie; Waiczies, Sonia; Hodge, Russ; Bader, Michael; Pohlmann, Andreas; Niendorf, Thoralf
2016-01-01
Combining mouse genomics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. Here we report on the reproducible application of acute noxious heat stimuli to examine the feasibility and limitations of functional brain mapping for central pain processing in mice. Recent technical and procedural advances were applied for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying mild noxious heat stimuli to wildtype mice resulted in highly significant BOLD patterns in anatomical brain structures forming the pain matrix, which comprise temporal signal intensity changes of up to 6% magnitude. We also observed sub-threshold correlation patterns in large areas of the brain, as well as alterations in mean arterial blood pressure (MABP) in response to the applied stimulus.
Decoupling of reaction time-related default mode network activity with cognitive demand.
Barber, Anita D; Caffo, Brian S; Pekar, James J; Mostofsky, Stewart H
2017-06-01
Reaction Time (RT) is associated with increased amplitude of the Blood Oxygen-Level Dependent (BOLD) response in task positive regions. Few studies have focused on whether opposing RT-related suppression of task activity also occurs. The current study used two Go/No-go tasks with different cognitive demands to examine regions that showed greater BOLD suppression for longer RT trials. These RT-related suppression effects occurred within the DMN and were task-specific, localizing to separate regions for the two tasks. In the task requiring working memory, RT-related de-coupling of the DMN occurred. This was reflected by opposing RT-BOLD effects for different DMN regions, as well as by reduced positive RT-related Psycho-Physiological Interaction (PPI) connectivity within the DMN and a lack of negative RT-related PPI connectivity between DMN and task positive regions. The results suggest that RT-related DMN suppression is task-specific. RT-related de-coupling of the DMN with more complex task demands may contribute to lapses of attention and performance decrements that occur during cognitively-demanding tasks.
Neurochemical responses to chromatic and achromatic stimuli in the human visual cortex.
Bednařík, Petr; Tkáč, Ivan; Giove, Federico; Eberly, Lynn E; Deelchand, Dinesh K; Barreto, Felipe R; Mangia, Silvia
2018-02-01
In the present study, we aimed at determining the metabolic responses of the human visual cortex during the presentation of chromatic and achromatic stimuli, known to preferentially activate two separate clusters of neuronal populations (called "blobs" and "interblobs") with distinct sensitivity to color or luminance features. Since blobs and interblobs have different cytochrome-oxidase (COX) content and micro-vascularization level (i.e., different capacities for glucose oxidation), different functional metabolic responses during chromatic vs. achromatic stimuli may be expected. The stimuli were optimized to evoke a similar load of neuronal activation as measured by the bold oxygenation level dependent (BOLD) contrast. Metabolic responses were assessed using functional 1 H MRS at 7 T in 12 subjects. During both chromatic and achromatic stimuli, we observed the typical increases in glutamate and lactate concentration, and decreases in aspartate and glucose concentration, that are indicative of increased glucose oxidation. However, within the detection sensitivity limits, we did not observe any difference between metabolic responses elicited by chromatic and achromatic stimuli. We conclude that the higher energy demands of activated blobs and interblobs are supported by similar increases in oxidative metabolism despite the different capacities of these neuronal populations.
Alarcón, Gabriela; Ray, Siddharth; Nagel, Bonnie J.
2017-01-01
Objectives Elevated body mass index (BMI) is associated with deficits in working memory, reduced gray matter volume in frontal and parietal lobes, as well as changes in white matter (WM) microstructure. The current study examined whether BMI was related to working memory performance and blood oxygen level dependent (BOLD) activity, as well as WM microstructure during adolescence. Methods Linear regressions with BMI and (1) verbal working memory BOLD signal, (2) spatial working memory BOLD signal, and (3) fractional anisotropy (FA), a measure of WM microstructure, were conducted in a sample of 152 healthy adolescents ranging in BMI. Results BMI was inversely related to IQ and verbal and spatial working memory accuracy; however, there was no significant relationship between BMI and BOLD response for either verbal or spatial working memory. Furthermore, BMI was negatively correlated with FA in the left superior longitudinal fasciculus (SLF) and left inferior longitudinal fasciculus (ILF). ILF FA and IQ significantly mediated the relationship between BMI and verbal working memory performance, whereas SLF FA, but not IQ, significantly mediated the relationship between BMI and accuracy of both verbal and spatial working memory. Conclusions These findings indicate that higher BMI is associated with decreased FA in WM fibers connecting brain regions that support working memory, and that WM microstructural deficits may underlie inferior working memory performance in youth with higher BMI. Of interest, BMI did not show the same relationship with working memory BOLD activity, which may indicate that changes in brain structure precede changes in function. PMID:26708324
Cocaine and methamphetamine induce opposing changes in BOLD signal response in rats.
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
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
Caffrey, Martha K; Febo, Marcelo
2014-01-01
Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and -Cue). The BOLD response to +Cue and -Cue was measured in dams on postpartum days 2-4. Odor cues were delivered to dams in the absence and then the presence of pups. Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus -Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Caffrey, Martha K.; Febo, Marcelo
2013-01-01
BACKGROUND Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. METHODS Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and −Cue). The BOLD response to +Cue and −Cue was measured in dams on postpartum days 2–4. Odor cues were delivered to dams in the absence and then the presence of pups. RESULTS Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus −Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. CONCLUSIONS Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. PMID:24183499
Brain functional BOLD perturbation modelling for forward fMRI and inverse mapping
Robinson, Jennifer; Calhoun, Vince
2018-01-01
Purpose To computationally separate dynamic brain functional BOLD responses from static background in a brain functional activity for forward fMRI signal analysis and inverse mapping. Methods A brain functional activity is represented in terms of magnetic source by a perturbation model: χ = χ0 +δχ, with δχ for BOLD magnetic perturbations and χ0 for background. A brain fMRI experiment produces a timeseries of complex-valued images (T2* images), whereby we extract the BOLD phase signals (denoted by δP) by a complex division. By solving an inverse problem, we reconstruct the BOLD δχ dataset from the δP dataset, and the brain χ distribution from a (unwrapped) T2* phase image. Given a 4D dataset of task BOLD fMRI, we implement brain functional mapping by temporal correlation analysis. Results Through a high-field (7T) and high-resolution (0.5mm in plane) task fMRI experiment, we demonstrated in detail the BOLD perturbation model for fMRI phase signal separation (P + δP) and reconstructing intrinsic brain magnetic source (χ and δχ). We also provided to a low-field (3T) and low-resolution (2mm) task fMRI experiment in support of single-subject fMRI study. Our experiments show that the δχ-depicted functional map reveals bidirectional BOLD χ perturbations during the task performance. Conclusions The BOLD perturbation model allows us to separate fMRI phase signal (by complex division) and to perform inverse mapping for pure BOLD δχ reconstruction for intrinsic functional χ mapping. The full brain χ reconstruction (from unwrapped fMRI phase) provides a new brain tissue image that allows to scrutinize the brain tissue idiosyncrasy for the pure BOLD δχ response through an automatic function/structure co-localization. PMID:29351339
Cole, Ella F.; Quinn, John L.
2014-01-01
Despite a growing body of evidence linking personality to life-history variation and fitness, the behavioural mechanisms underlying these relationships remain poorly understood. One mechanism thought to play a key role is how individuals respond to risk. Relatively reactive and proactive (or shy and bold) personality types are expected to differ in how they manage the inherent trade-off between productivity and survival, with bold individuals being more risk-prone with lower survival probability, and shy individuals adopting a more risk-averse strategy. In the great tit (Parus major), the shy–bold personality axis has been well characterized in captivity and linked to fitness. Here, we tested whether ‘exploration behaviour’, a captive assay of the shy–bold axis, can predict risk responsiveness during reproduction in wild great tits. Relatively slow-exploring (shy) females took longer than fast-exploring (bold) birds to resume incubation after a novel object, representing an unknown threat, was attached to their nest-box, with some shy individuals not returning within the 40 min trial period. Risk responsiveness was consistent within individuals over days. These findings provide rare, field-based experimental evidence that shy individuals prioritize survival over reproductive investment, supporting the hypothesis that personality reflects life-history variation through links with risk responsiveness. PMID:24829251
Sustained negative BOLD response in human fMRI finger tapping task.
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."
Impact of task-related changes in heart rate on estimation of hemodynamic response and model fit.
Hillenbrand, Sarah F; Ivry, Richard B; Schlerf, John E
2016-05-15
The blood oxygen level dependent (BOLD) signal, as measured using functional magnetic resonance imaging (fMRI), is widely used as a proxy for changes in neural activity in the brain. Physiological variables such as heart rate (HR) and respiratory variation (RV) affect the BOLD signal in a way that may interfere with the estimation and detection of true task-related neural activity. This interference is of particular concern when these variables themselves show task-related modulations. We first establish that a simple movement task reliably induces a change in HR but not RV. In group data, the effect of HR on the BOLD response was larger and more widespread throughout the brain than were the effects of RV or phase regressors. The inclusion of HR regressors, but not RV or phase regressors, had a small but reliable effect on the estimated hemodynamic response function (HRF) in M1 and the cerebellum. We next asked whether the inclusion of a nested set of physiological regressors combining phase, RV, and HR significantly improved the model fit in individual participants' data sets. There was a significant improvement from HR correction in M1 for the greatest number of participants, followed by RV and phase correction. These improvements were more modest in the cerebellum. These results indicate that accounting for task-related modulation of physiological variables can improve the detection and estimation of true neural effects of interest. Copyright © 2016 Elsevier Inc. All rights reserved.
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 limbic structures and the brain stem during electrical stimulation of the left anterior auditory canal. BOLD signal decreases in the area of the nuclei of the vagus nerve may indicate an effective stimulation of vagal afferences. In contrast, stimulation at the posterior wall seems to lead to unspecific changes of the BOLD signal within the solitary tract, which is a key relay station of vagal neurotransmission. The results of the study show promise for a specific novel method of cranial nerve stimulation and provide a basis for further developments and applications of non-invasive transcutaneous vagus stimulation in psychiatric patients. Copyright © 2013 Elsevier Inc. All rights reserved.
Mark, Clarisse I; Mazerolle, Erin L; Chen, J Jean
2015-08-01
The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes in blood oxygenation resulting from the relative balance between cerebral oxygen metabolism (through neural activity) and oxygen supply (through cerebral blood flow and volume). As such, there are cases in which BOLD signals might be dissociated from neural activity, leading to misleading results. The emphasis of this review is to develop a critical perspective for interpreting BOLD results, through a comprehensive consideration of BOLD's metabolic and vascular underpinnings. We demonstrate that such an understanding is especially important under disease or resting conditions. We also describe state-of-the-art acquisition and analytical techniques to reveal physiological information on the mechanisms underlying measured BOLD signals. With these goals in mind, this review is structured to provide a fundamental understanding of: 1) the physiological and physical sources of the BOLD contrast; 2) the extraction of information regarding oxidative metabolism and cerebrovascular reactivity from the BOLD signal, critical to investigating neuropathology; and 3) the fundamental importance of metabolic and vascular mechanisms for interpreting resting-state BOLD measurements. © 2015 Wiley Periodicals, Inc.
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.
Food portion size and energy density evoke different patterns of brain activation in children12
Fearnbach, S Nicole; Wilson, Stephen J; Fisher, Jennifer O; Savage, Jennifer S; Rolls, Barbara J; Keller, Kathleen L
2017-01-01
Background: Large portions of food promote intake, but the mechanisms that drive this effect are unclear. Previous neuroimaging studies have identified the brain-reward and decision-making systems that are involved in the response to the energy density (ED) (kilocalories per gram) of foods, but few studies have examined the brain response to the food portion size (PS). Objective: We used functional MRI (fMRI) to determine the brain response to food images that differed in PSs (large and small) and ED (high and low). Design: Block-design fMRI was used to assess the blood oxygen level–dependent (BOLD) response to images in 36 children (7–10 y old; girls: 50%), which was tested after a 2-h fast. Pre-fMRI fullness and liking were rated on visual analog scales. A whole-brain cluster-corrected analysis was used to compare BOLD activation for main effects of the PS, ED, and their interaction. Secondary analyses were used to associate BOLD contrast values with appetitive traits and laboratory intake from meals for which the portions of all foods were increased. Results: Compared with small-PS cues, large-PS cues were associated with decreased activation in the inferior frontal gyrus (P < 0.01). Compared with low-ED cues, high-ED cues were associated with increased activation in multiple regions (e.g., in the caudate, cingulate, and precentral gyrus) and decreased activation in the insula and superior temporal gyrus (P < 0.01 for all). A PS × ED interaction was shown in the superior temporal gyrus (P < 0.01). BOLD contrast values for high-ED cues compared with low-ED cues in the insula, declive, and precentral gyrus were negatively related to appetitive traits (P < 0.05). There were no associations between the brain response to the PS and either appetitive traits or intake. Conclusions: Cues regarding food PS may be processed in the lateral prefrontal cortex, which is a region that is implicated in cognitive control, whereas ED activates multiple areas involved in sensory and reward processing. Possible implications include the development of interventions that target decision-making and reward systems differently to moderate overeating. PMID:27881393
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.
Detecting agency from the biological motion of veridical vs animated agents
Kelley, William M.; Heatherton, Todd F.; Macrae, C. Neil
2007-01-01
The ability to detect agency is fundamental for understanding the social world. Underlying this capacity are neural circuits that respond to patterns of intentional biological motion in the superior temporal sulcus and temporoparietal junction. Here we show that the brain's blood oxygenation level dependent (BOLD) response to such motion is modulated by the representation of the actor. Dynamic social interactions were portrayed by either live-action agents or computer-animated agents, enacting the exact same patterns of biological motion. Using an event-related design, we found that the BOLD response associated with the perception and interpretation of agency was greater when identical physical movements were performed by real rather than animated agents. This finding has important implications for previous work on biological motion that has relied upon computer-animated stimuli and demonstrates that the neural substrates of social perception are finely tuned toward real-world agents. In addition, the response in lateral temporal areas was observed in the absence of instructions to make mental inferences, thus demonstrating the spontaneous implementation of the intentional stance. PMID:18985141
van Leeuwen, Tessa M; Petersson, Karl Magnus; Hagoort, Peter
2010-08-10
In synaesthesia, sensations in a particular modality cause additional experiences in a second, unstimulated modality (e.g., letters elicit colour). Understanding how synaesthesia is mediated in the brain can help to understand normal processes of perceptual awareness and multisensory integration. In several neuroimaging studies, enhanced brain activity for grapheme-colour synaesthesia has been found in ventral-occipital areas that are also involved in real colour processing. Our question was whether the neural correlates of synaesthetically induced colour and real colour experience are truly shared. First, in a free viewing functional magnetic resonance imaging (fMRI) experiment, we located main effects of synaesthesia in left superior parietal lobule and in colour related areas. In the left superior parietal lobe, individual differences between synaesthetes (projector-associator distinction) also influenced brain activity, confirming the importance of the left superior parietal lobe for synaesthesia. Next, we applied a repetition suppression paradigm in fMRI, in which a decrease in the BOLD (blood-oxygenated-level-dependent) response is generally observed for repeated stimuli. We hypothesized that synaesthetically induced colours would lead to a reduction in BOLD response for subsequently presented real colours, if the neural correlates were overlapping. We did find BOLD suppression effects induced by synaesthesia, but not within the colour areas. Because synaesthetically induced colours were not able to suppress BOLD effects for real colour, we conclude that the neural correlates of synaesthetic colour experience and real colour experience are not fully shared. We propose that synaesthetic colour experiences are mediated by higher-order visual pathways that lie beyond the scope of classical, ventral-occipital visual areas. Feedback from these areas, in which the left parietal cortex is likely to play an important role, may induce V4 activation and the percept of synaesthetic colour.
The Not-So-Global Blood Oxygen Level-Dependent Signal.
Billings, Jacob; Keilholz, Shella
2018-04-01
Global signal regression is a controversial processing step for resting-state functional magnetic resonance imaging, partly because the source of the global blood oxygen level-dependent (BOLD) signal remains unclear. On the one hand, nuisance factors such as motion can readily introduce coherent BOLD changes across the whole brain. On the other hand, the global signal has been linked to neural activity and vigilance levels, suggesting that it contains important neurophysiological information and should not be discarded. Any widespread pattern of coordinated activity is likely to contribute appreciably to the global signal. Such patterns may include large-scale quasiperiodic spatiotemporal patterns, known also to be tied to performance on vigilance tasks. This uncertainty surrounding the separability of the global BOLD signal from concurrent neurological processes motivated an examination of the global BOLD signal's spatial distribution. The results clarify that although the global signal collects information from all tissue classes, a diverse subset of the BOLD signal's independent components contribute the most to the global signal. Further, the timing of each network's contribution to the global signal is not consistent across volunteers, confirming the independence of a constituent process that comprises the global signal.
Shyness and boldness in pumpkinseed sunfish: individual differences are context-specific.
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.
Human protein status modulates brain reward responses to food cues.
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 affects taste category preferences, which could play an important role in the regulation of protein intake in humans. This trial was registered at www.trialregister.nl/trialreg/admin/rctview.asp?TC=3288 as NTR3288. © 2014 American Society for Nutrition.
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.
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
Wilson, Stephen M; Isenberg, Anna Lisette; Hickok, Gregory
2009-11-01
Word production is a complex multistage process linking conceptual representations, lexical entries, phonological forms and articulation. Previous studies have revealed a network of predominantly left-lateralized brain regions supporting this process, but many details regarding the precise functions of different nodes in this network remain unclear. To better delineate the functions of regions involved in word production, we used event-related functional magnetic resonance imaging (fMRI) to identify brain areas where blood oxygen level-dependent (BOLD) responses to overt picture naming were modulated by three psycholinguistic variables: concept familiarity, word frequency, and word length, and one behavioral variable: reaction time. Each of these variables has been suggested by prior studies to be associated with different aspects of word production. Processing of less familiar concepts was associated with greater BOLD responses in bilateral occipitotemporal regions, reflecting visual processing and conceptual preparation. Lower frequency words produced greater BOLD signal in left inferior temporal cortex and the left temporoparietal junction, suggesting involvement of these regions in lexical selection and retrieval and encoding of phonological codes. Word length was positively correlated with signal intensity in Heschl's gyrus bilaterally, extending into the mid-superior temporal gyrus (STG) and sulcus (STS) in the left hemisphere. The left mid-STS site was also modulated by reaction time, suggesting a role in the storage of lexical phonological codes.
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
Sex Differences in Stress Response Circuitry Activation Dependent on Female Hormonal Cycle
Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos
2010-01-01
Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this fMRI study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right-handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry (amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal and medial prefrontal cortices (OFC and mPFC), and anterior cingulate gyrus (ACG). Women were scanned twice based on normal variation in menstrual cycle hormones (i.e., early follicular (EF) compared with late follicular-midcycle menstrual phases (LF/MC)). Using SPM8b, there were few significant differences in BOLD signal changes in men compared to EF women, except ventromedial (VMN) and lateral (LHA) hypothalamus, left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males. PMID:20071507
MRI measurement of the temporal evolution of relative CMRO(2) during rat forepaw stimulation.
Mandeville, J B; Marota, J J; Ayata, C; Moskowitz, M A; Weisskoff, R M; Rosen, B R
1999-11-01
This study reports the first measurement of the relative cerebral metabolic rate of oxygen utilization (rCMRO(2)) during functional brain activation with sufficient temporal resolution to address the dynamics of blood oxygen level-dependent (BOLD) MRI signal. During rat forepaw stimulation, rCMRO(2) was determined in somatosensory cortex at 3-sec intervals, using a model of BOLD signal and measurements of the change in BOLD transverse relaxation rate, the resting state BOLD transverse relaxation rate, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV). Average percentage changes from 10 to 30 sec after onset of forepaw stimulation for rCBF, rCBV, rCMRO(2), and BOLD relaxation rate were 62 +/- 16, 17 +/- 2, 19 +/- 17, and -26 +/- 12, respectively. A poststimulus undershoot in BOLD signal was quantitatively attributed to the temporal mismatch between changes in blood flow and volume, and not to the role of oxygen metabolism. Magn Reson Med 42:944-951, 1999. Copyright 1999 Wiley-Liss, Inc.
Retinotopic mapping with Spin Echo BOLD at 7 Tesla
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
Le Galliard, J-F; Paquet, M; Mugabo, M
2015-05-01
Temperament traits are seen in many animal species, and recent evolutionary models predict that they could be maintained by heterogeneous selection. We tested this prediction by examining density-dependent selection in juvenile common lizards Zootoca vivipara scored for activity, boldness and sociability at birth and at the age of 1 year. We measured three key life-history traits (juvenile survival, body growth rate and reproduction) and quantified selection in experimental populations at five density levels ranging from low to high values. We observed consistent individual differences for all behaviours on the short term, but only for activity and one boldness measure across the first year of life. At low density, growth selection favoured more sociable lizards, whereas viability selection favoured less active individuals. A significant negative correlational selection on activity and boldness existed for body growth rate irrespective of density. Thus, behavioural traits were characterized by limited ontogenic consistency, and natural selection was heterogeneous between density treatments and fitness traits. This confirms that density-dependent selection plays an important role in the maintenance of individual differences in exploration-activity and sociability. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.
Crosslinking EEG time-frequency decomposition and fMRI in error monitoring.
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.
Dona, Olga; Noseworthy, Michael D; DeMatteo, Carol; Connolly, John F
2017-01-01
Conventional imaging techniques are unable to detect abnormalities in the brain following mild traumatic brain injury (mTBI). Yet patients with mTBI typically show delayed response on neuropsychological evaluation. Because fractal geometry represents complexity, we explored its utility in measuring temporal fluctuations of brain resting state blood oxygen level dependent (rs-BOLD) signal. We hypothesized that there could be a detectable difference in rs-BOLD signal complexity between healthy subjects and mTBI patients based on previous studies that associated reduction in signal complexity with disease. Fifteen subjects (13.4 ± 2.3 y/o) and 56 age-matched (13.5 ± 2.34 y/o) healthy controls were scanned using a GE Discovery MR750 3T MRI and 32-channel RF-coil. Axial FSPGR-3D images were used to prescribe rs-BOLD (TE/TR = 35/2000ms), acquired over 6 minutes. Motion correction was performed and anatomical and functional images were aligned and spatially warped to the N27 standard atlas. Fractal analysis, performed on grey matter, was done by estimating the Hurst exponent using de-trended fluctuation analysis and signal summation conversion methods. Voxel-wise fractal dimension (FD) was calculated for every subject in the control group to generate mean and standard deviation maps for regional Z-score analysis. Voxel-wise validation of FD normality across controls was confirmed, and non-Gaussian voxels (3.05% over the brain) were eliminated from subsequent analysis. For each mTBI patient, regions where Z-score values were at least 2 standard deviations away from the mean (i.e. where |Z| > 2.0) were identified. In individual patients the frequently affected regions were amygdala (p = 0.02), vermis(p = 0.03), caudate head (p = 0.04), hippocampus(p = 0.03), and hypothalamus(p = 0.04), all previously reported as dysfunctional after mTBI, but based on group analysis. It is well known that the brain is best modeled as a complex system. Therefore a measure of complexity using rs-BOLD signal FD could provide an additional method to grade and monitor mTBI. Furthermore, this approach can be personalized thus providing unique patient specific assessment.
Windischberger, Christian; Lanzenberger, Rupert; Holik, Alexander; Spindelegger, Christoph; Stein, Patrycja; Moser, Ulrike; Gerstl, Florian; Fink, Martin; Moser, Ewald; Kasper, Siegfried
2010-01-15
Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.
Georgiou-Karistianis, Nellie; Stout, Julie C; Domínguez D, Juan F; Carron, Sarah P; Ando, Ayaka; Churchyard, Andrew; Chua, Phyllis; Bohanna, India; Dymowski, Alicia R; Poudel, Govinda; Egan, Gary F
2014-05-01
We used functional magnetic resonance imaging (fMRI) to investigate spatial working memory (WM) in an N-BACK task (0, 1, and 2-BACK) in premanifest Huntington's disease (pre-HD, n = 35), early symptomatic Huntington's disease (symp-HD, n = 23), and control (n = 32) individuals. Overall, both WM conditions (1-BACK and 2-BACK) activated a large network of regions throughout the brain, common to all groups. However, voxel-wise and time-course analyses revealed significant functional group differences, despite no significant behavioral performance differences. During 1-BACK, voxel-wise blood-oxygen-level-dependent (BOLD) signal activity was significantly reduced in a number of regions from the WM network (inferior frontal gyrus, anterior insula, caudate, putamen, and cerebellum) in pre-HD and symp-HD groups, compared with controls; however, time-course analysis of the BOLD response in the dorsolateral prefrontal cortex (DLPFC) showed increased activation in symp-HD, compared with pre-HD and controls. The pattern of reduced voxel-wise BOLD activity in pre-HD and symp-HD, relative to controls, became more pervasive during 2-BACK affecting the same structures as in 1-BACK, but also incorporated further WM regions (anterior cingulate gyrus, parietal lobe and thalamus). The DLPFC BOLD time-course for 2-BACK showed a reversed pattern to that observed in 1-BACK, with a significantly diminished signal in symp-HD, relative to pre-HD and controls. Our findings provide support for functional brain reorganisation in cortical and subcortical regions in both pre-HD and symp-HD, which are modulated by task difficulty. Moreover, the lack of a robust striatal BOLD signal in pre-HD may represent a very early signature of change observed up to 15 years prior to clinical diagnosis. Copyright © 2013 Wiley Periodicals, Inc.
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 Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Jacquin, L; Reader, S M; Boniface, A; Mateluna, J; Patalas, I; Pérez-Jvostov, F; Hendry, A P
2016-07-01
Natural enemies such as predators and parasites are known to shape intraspecific variability of behaviour and personality in natural populations, yet several key questions remain: (i) What is the relative importance of predation vs. parasitism in shaping intraspecific variation of behaviour across generations? (ii) What are the contributions of genetic and plastic effects to this behavioural divergence? (iii) And to what extent are responses to predation and parasitism repeatable across independent evolutionary lineages? We addressed these questions using Trinidadian guppies (Poecilia reticulata) (i) varying in their exposure to dangerous fish predators and Gyrodactylus ectoparasites for (ii) both wild-caught F0 and laboratory-reared F2 individuals and coming from (iii) multiple independent evolutionary lineages (i.e. independent drainages). Several key findings emerged. First, a population's history of predation and parasitism influenced behavioural profiles, but to different extent depending on the behaviour considered (activity, shoaling or boldness). Second, we had evidence for some genetic effects of predation regime on behaviour, with differences in activity of F2 laboratory-reared individuals, but not for parasitism, which had only plastic effects on the boldness of wild-caught F0 individuals. Third, the two lineages showed a mixture of parallel and nonparallel responses to predation/parasitism, with parallel responses being stronger for predation than for parasitism and for activity and boldness than for shoaling. These findings suggest that different sets of behaviours provide different pay-offs in alternative predation/parasitism environments and that parasitism has more transient effects in shaping intraspecific variation of behaviour than does predation. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.
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.
Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy.
Lindberg, Ulrich; Witting, Nanna; Jørgensen, Stine Lundgaard; Vissing, John; Rostrup, Egill; Larsson, Henrik Bo Wiberg; Kruuse, Christina
2017-01-01
Patients suffering from Becker muscular dystrophy (BMD) have dysfunctional dystrophin proteins and are deficient in neuronal nitric oxide synthase (nNOS) in muscles. This causes functional ischemia and contributes to muscle wasting. Similar functional ischemia may be present in brains of patients with BMD, who often have mild cognitive impairment, and nNOS may be important for the regulation of the microvascular circulation in the brain. We hypothesized that treatment with sildenafil, a phosphodiesterase type 5 inhibitor that potentiates nitric oxide responses, would augment both the blood oxygen level-dependent (BOLD) response and cerebral blood flow (CBF) in patients with BMD. Seventeen patients (mean ± SD age 38.5 ± 10.8 years) with BMD were included in this randomized, double-blind, placebo-controlled, crossover trial. Twelve patients completed the entire study. Effects of sildenafil were assessed by 3 T magnetic resonance (MR) scanning, evoked potentials, somatosensory task-induced BOLD functional MR imaging, regional and global perfusion, and angiography before and after 4 weeks of sildenafil, 20 mg (Revatio in gelatine capsules, oral, 3 times daily), or placebo treatment. Sildenafil increased the event-related sensory and visual BOLD response compared with placebo (p < 0.01). However, sildenafil did not alter CBF, measured by MR phase contrast mapping, or the arterial diameter of the middle cerebral artery, measured by MR angiography. We conclude that nNOS may play a role in event-related neurovascular responses. Further studies in patients with BMD may help clarify the roles of dystrophin and nNOS in neurovascular coupling in general, and in patients with BMD in particular.
Parada, Mayte; Gérard, Marina; Larcher, Kevin; Dagher, Alain; Binik, Yitzchak M
2018-02-01
The few studies that have examined the neural correlates of genital arousal have focused on men and are methodologically hard to compare. To investigate the neural correlates of peripheral physiologic sexual arousal using identical methodology for men and women. 2 groups (20 men, 20 women) viewed movie clips (erotic, humor) while genital temperature was continuously measured using infrared thermal imaging. Participants also continuously evaluated changes in their subjective arousal and answered discrete questions about liking the movies and wanting sexual stimulation. Brain activity, indicated by blood oxygen level-dependent (BOLD) response, was measured using functional magnetic resonance imaging. BOLD responses, genital temperature, and subjective sexual arousal. BOLD activity in a number of brain regions was correlated with changes in genital temperature in men and women; however, activation in women appeared to be more extensive than in men, including the anterior and posterior cingulate cortex, right cerebellum, insula, frontal operculum, and paracingulate gyrus. Examination of the strength of the correlation between BOLD response and genital temperature showed that women had a stronger brain-genital relation compared with men in a number of regions. There were no brain regions in men with stronger brain-genital correlations than in women. Our findings shed light on the neurophysiologic processes involved in genital arousal for men and women. Further research examining the specific brain regions that mediate our findings is necessary to pave the way for clinical application. A strength of the study is the use of thermography, which allows for a direct comparison of the neural correlates of genital arousal in men and women. This study has the common limitations of most laboratory-based sexual arousal research, including sampling bias, lack of ecologic validity, and equipment limitations, and those common to neuroimaging research, including BOLD signal interpretation and neuroimaging analysis issues. Our findings provide direct sex comparisons of the neural correlates of genital arousal in men and women and suggest that brain-genital correlations could be stronger in women. Parada M, Gérard M, Larcher K, et al. How Hot Are They? Neural Correlates of Genital Arousal: An Infrared Thermographic and Functional Magnetic Resonance Imaging Study of Sexual Arousal in Men and Women. J Sex Med 2018;15:217-229. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
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.
Månsson, K N T; Frick, A; Boraxbekk, C-J; Marquand, A F; Williams, S C R; Carlbring, P; Andersson, G; Furmark, T
2015-03-17
Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52% (12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2-97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale-Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC-amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC-amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.
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.
Chen, Li M; Turner, Gregory H; Friedman, Robert M; Zhang, Na; Gore, John C; Roe, Anna W; Avison, Malcolm J
2007-08-22
Although blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to explore human brain function, questions remain regarding the ultimate spatial resolution of positive BOLD fMRI, and indeed the extent to which functional maps revealed by positive BOLD correlate spatially with maps obtained with other high-spatial-resolution mapping techniques commonly used in animals, such as optical imaging of intrinsic signal (OIS) and single-unit electrophysiology. Here, we demonstrate that the positive BOLD signal at 9.4T can reveal the fine topography of individual fingerpads in single-condition activation maps in nonhuman primates. These digit maps are similar to maps obtained from the same animal using intrinsic optical imaging. Furthermore, BOLD fMRI reliably resolved submillimeter spatial shifts in activation in area 3b previously identified with OIS (Chen et al., 2003) as neural correlates of the "funneling illusion." These data demonstrate that at high field, high-spatial-resolution topographic maps can be achieved using the positive BOLD signal, weakening previous notions regarding the spatial specificity of the positive BOLD signal.
Focal BOLD-fMRI changes in bicuculline-induced tonic-clonic seizures in the rat
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
Task-Related Modulations of BOLD Low-Frequency Fluctuations within the Default Mode Network
Tommasin, Silvia; Mascali, Daniele; Gili, Tommaso; Assan, Ibrahim Eid; Moraschi, Marta; Fratini, Michela; Wise, Richard G.; Macaluso, Emiliano; Mangia, Silvia; Giove, Federico
2017-01-01
Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33 ± 6 years, 8 F/12 M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the continuous execution of a working memory n-back task. We found that task execution impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to continuous task execution, can contribute to a better understanding of how brain networks rearrange themselves in response to a task. PMID:28845420
Bartolo, M J; Gieselmann, M A; Vuksanovic, V; Hunter, D; Sun, L; Chen, X; Delicato, L S; Thiele, A
2011-01-01
The functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) signal is regularly used to assign neuronal activity to cognitive function. Recent analyses have shown that the local field potential (LFP) gamma power is a better predictor of the fMRI BOLD signal than spiking activity. However, LFP gamma power and spiking activity are usually correlated, clouding the analysis of the neural basis of the BOLD signal. We show that changes in LFP gamma power and spiking activity in the primary visual cortex (V1) of the awake primate can be dissociated by using grating and plaid pattern stimuli, which differentially engage surround suppression and cross-orientation inhibition/facilitation within and between cortical columns. Grating presentation yielded substantial V1 LFP gamma frequency oscillations and significant multi-unit activity. Plaid pattern presentation significantly reduced the LFP gamma power while increasing population multi-unit activity. The fMRI BOLD activity followed the LFP gamma power changes, not the multi-unit activity. Inference of neuronal activity from the fMRI BOLD signal thus requires detailed a priori knowledge of how different stimuli or tasks activate the cortical network. PMID:22081989
Merlanti, R; Gallina, G; Capolongo, F; Contiero, L; Biancotto, G; Dacasto, M; Montesissa, C
2007-03-14
17Beta-boldenone (17beta-BOLD) and Boldione (ADD) are steroid compounds with androgenic activity, likely to be used as growth promoters in cattle. Different studies still on-going aiming to distinguish between "natural" occurrence or illegal BOLD source had already indicated that their metabolism in cattle is of relevant significance. To identify metabolites as in vivo markers to support the thesis of exogenous administration, a further approach to the in vitro biotransformation of 17beta-BOLD and ADD was performed using different subcellular fractions obtained from both liver and kidney of untreated cattle. Polar and non-polar metabolites obtained from incubated parent compounds were formerly separated by high performance liquid chromatography (HPLC) elution and successively identified by liquid chromatography tandem mass spectrometry (LC-MS/MS) detection. The bovine liver was the target tissue of the main metabolic reaction transforming 17beta-BOLD to ADD and vice versa. The presence of 6beta-hydroxy-17beta-BOLD, produced from both compounds when NADPH was added as cofactors to liver post mitochondrial and microsomal fractions suggests that cytochrome P450-dependent enzymes could be involved in the biotransformation, as it occurs for 6beta-hydroxylation of 17beta-testosterone. The results indicated that the urinary excretion profile in vivo of 6beta-hydroxy-17beta-BOLD and 16alpha-hydroxy-17beta-BOLD could be studied together with 17alpha- and 17beta-BOLD as putative markers of BOLD treatment in cattle.
Blood oxygenation level-dependent MRI for assessment of renal oxygenation
Neugarten, Joel; Golestaneh, Ladan
2014-01-01
Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) has recently emerged as an important noninvasive technique to assess intrarenal oxygenation under physiologic and pathophysiologic conditions. Although this tool represents a major addition to our armamentarium of methodologies to investigate the role of hypoxia in the pathogenesis of acute kidney injury and progressive chronic kidney disease, numerous technical limitations confound interpretation of data derived from this approach. BOLD MRI has been utilized to assess intrarenal oxygenation in numerous experimental models of kidney disease and in human subjects with diabetic and nondiabetic chronic kidney disease, acute kidney injury, renal allograft rejection, contrast-associated nephropathy, and obstructive uropathy. However, confidence in conclusions based on data derived from BOLD MRI measurements will require continuing advances and technical refinements in the use of this technique. PMID:25473304
Amphetamine sensitization alters reward processing in the human striatum and amygdala.
O'Daly, Owen G; Joyce, Daniel; Tracy, Derek K; Azim, Adnan; Stephan, Klaas E; Murray, Robin M; Shergill, Sukhwinder S
2014-01-01
Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS) has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD) signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.
Does boldness explain vulnerability to angling in Eurasian perch Perca fluviatilis?
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?
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
Functional magnetic resonance imaging in chronic ischaemic stroke.
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).
An Introduction to Normalization and Calibration Methods in Functional MRI
ERIC Educational Resources Information Center
Liu, Thomas T.; Glover, Gary H.; Mueller, Bryon A.; Greve, Douglas N.; Brown, Gregory G.
2013-01-01
In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes…
The Target Selective Neural Response — Similarity, Ambiguity, and Learning Effects
Hampshire, Adam; Thompson, Russell; Duncan, John; Owen, Adrian M.
2008-01-01
A network of frontal and parietal brain regions is commonly recruited during tasks that require the deliberate ‘top-down’ control of thought and action. Previously, using simple target detection, we have demonstrated that within this frontoparietal network, the right ventrolateral prefrontal cortex (VLPFC) in particular is sensitive to the presentation of target objects. Here, we use a range of target/non-target morphs to plot the target selective response within distinct frontoparietal sub-regions in greater detail. The increased resolution allows us to examine the extent to which different cognitive factors can predict the blood oxygenation level dependent (BOLD) response to targets. Our results reveal that both probability of positive identification (similarity to target) and proximity to the 50% decision boundary (ambiguity) are significant predictors of BOLD signal change, particularly in the right VLPFC. Furthermore, the profile of target related signal change is not static, with the degree of selectivity increasing as the task becomes familiar. These findings demonstrate that frontoparietal sub-regions are recruited under increased cognitive demand and that when recruited, they adapt, using both fast and slow mechanisms, to selectively respond to those items that are of the most relevance to current intentions. PMID:18575585
Development of visual cortical function in infant macaques: A BOLD fMRI study
Meeson, Alan; Munk, Matthias H. J.; Kourtzi, Zoe; Movshon, J. Anthony; Logothetis, Nikos K.; Kiorpes, Lynne
2017-01-01
Functional brain development is not well understood. In the visual system, neurophysiological studies in nonhuman primates show quite mature neuronal properties near birth although visual function is itself quite immature and continues to develop over many months or years after birth. Our goal was to assess the relative development of two main visual processing streams, dorsal and ventral, using BOLD fMRI in an attempt to understand the global mechanisms that support the maturation of visual behavior. Seven infant macaque monkeys (Macaca mulatta) were repeatedly scanned, while anesthetized, over an age range of 102 to 1431 days. Large rotating checkerboard stimuli induced BOLD activation in visual cortices at early ages. Additionally we used static and dynamic Glass pattern stimuli to probe BOLD responses in primary visual cortex and two extrastriate areas: V4 and MT-V5. The resulting activations were analyzed with standard GLM and multivoxel pattern analysis (MVPA) approaches. We analyzed three contrasts: Glass pattern present/absent, static/dynamic Glass pattern presentation, and structured/random Glass pattern form. For both GLM and MVPA approaches, robust coherent BOLD activation appeared relatively late in comparison to the maturation of known neuronal properties and the development of behavioral sensitivity to Glass patterns. Robust differential activity to Glass pattern present/absent and dynamic/static stimulus presentation appeared first in V1, followed by V4 and MT-V5 at older ages; there was no reliable distinction between the two extrastriate areas. A similar pattern of results was obtained with the two analysis methods, although MVPA analysis showed reliable differential responses emerging at later ages than GLM. Although BOLD responses to large visual stimuli are detectable, our results with more refined stimuli indicate that global BOLD activity changes as behavioral performance matures. This reflects an hierarchical development of the visual pathways. Since fMRI BOLD reflects neural activity on a population level, our results indicate that, although individual neurons might be adult-like, a longer maturation process takes place on a population level. PMID:29145469
2015-01-01
Pain-related anxiety and fear are associated with increased difficulties in attention, increased awareness of pain, impaired disengagement from pain, and can moderate the effects of attentional coping attempts. Accurately assessing the direct impact of pain-related anxiety and fear on pain behavior has proved difficult. Studies have demonstrated no or limited influence of pain-related fear and anxiety on behavior but this may be due to inherent problems with the scales used. Neuroimaging has improved the understanding of neural processes underlying the factors that influence pain perception. This study aimed to establish if a Picture and Imagination Task (PIT), largely developed from the Photographs of Daily Activity (PHODA) assessment tool, could help explore how people living with chronic pain process information about daily activities. Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to compare brain responses in patients with chronic musculoskeletal pain (CMSKP) (n = 15) and healthy controls (n = 15). Subjects were asked to imagine how they would feel mentally and physically if asked to perform daily activities illustrated in PIT. The results found that a number of regions involved in pain processing saw increased BOLD activation in patients compared with controls when undertaking the task and included the insula, anterior cingulate cortex, thalamus and inferior and superior parietal cortices. Similarly, increased BOLD responses in patients compared to controls in the frontal pole, paracingulate and the supplementary motor cortex may be suggestive of a memory component to the responses The amygdala, orbitofrontal cortex, substantia nigra/ventral tegmentum, putamen, thalamus, pallidum, inferior parietal (supramarginal and angular gyrus) and cingulate cortex were also seen to have greater differences in BOLD signal changes in patients compared with controls and many of these regions are also associated with general phobic responses. Therefore, we suggest that PIT is a useful task to explore pain- and movement-related anxiety and fear in fMRI studies. Regions in the Default Mode Network remained active or were less deactivated during the PIT task in patients with CMSKP compared to healthy controls supporting the contention that the DMN is abnormal in patients with CMSKP. PMID:26496709
Tan, Ao; Hu, Li; Tu, Yiheng; Chen, Rui; Hung, Yeung Sam; Zhang, Zhiguo
2016-07-01
N1 component of auditory evoked potentials is extensively used to investigate the propagation and processing of auditory inputs. However, the substantial interindividual variability of N1 could be a possible confounding factor when comparing different individuals or groups. Therefore, identifying the neuronal mechanism and origin of the interindividual variability of N1 is crucial in basic research and clinical applications. This study is aimed to use simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data to investigate the coupling between N1 and spontaneous functional connectivity (FC). EEG and fMRI data were simultaneously collected from a group of healthy individuals during a pure-tone listening task. Spontaneous FC was estimated from spontaneous blood oxygenation level-dependent (BOLD) signals that were isolated by regressing out task evoked BOLD signals from raw BOLD signals and then was correlated to N1 magnitude across individuals. It was observed that spontaneous FC between bilateral Heschl's gyrus was significantly and positively correlated with N1 magnitude across individuals (Spearman's R = 0.829, p < 0.001). The specificity of this observation was further confirmed by two whole-brain voxelwise analyses (voxel-mirrored homotopic connectivity analysis and seed-based connectivity analysis). These results enriched our understanding of the functional significance of the coupling between event-related brain responses and spontaneous brain connectivity, and hold the potential to increase the applicability of brain responses as a probe to the mechanism underlying pathophysiological conditions.
Brain activity and connectivity changes in response to glucose ingestion.
van Opstal, A M; Hafkemeijer, A; van den Berg-Huysmans, A A; Hoeksma, M; Blonk, C; Pijl, H; Rombouts, S A R B; van der Grond, J
2018-05-27
The regulatory role of the brain in directing eating behavior becomes increasingly recognized. Although many areas in the brain have been found to respond to food cues, very little data is available after actual caloric intake. The aim of this study was to determine normal whole brain functional responses to ingestion of glucose after an overnight fast. Twenty-five normal weight, adult males underwent functional MRI on two separate visits. In a single-blind randomized study setup, participants received either glucose solution (50 g/300 ml of water) or plain water. We studied changes in Blood Oxygen Level Dependent (BOLD) signal, voxel-based connectivity by Eigenvector Centrality Mapping, and functional network connectivity. Ingestion of glucose led to increased centrality in the thalamus and to decreases in BOLD signal in various brain areas. Decreases in connectivity in the sensory-motor and dorsal visual stream networks were found. Ingestion of water resulted in increased centrality across the brain, and increases in connectivity in the medial and lateral visual cortex network. Increased BOLD intensity was found in the intracalcarine and cingulate cortex. Our data show that ingestion of glucose leads to decreased activity and connectivity in brain areas and networks linked to energy seeking and satiation. In contrast, drinking plain water leads to increased connectivity probably associated with continued food seeking and unfulfilled reward. Trail registration: This study combines data of two studies registered at clinicaltrails.gov under numbers NCT03202342 and NCT03247114.
Wu, Jinglong; Wang, Bin; Yan, Tianyi; Li, Xiujun; Bao, Xuexiang; Guo, Qiyong
2012-01-11
In the present study, we used event-related functional magnetic resonance imaging (fMRI) to explore the different roles of the posterior inferior frontal gyrus (pIFG) in Chinese character form judgment between literate and illiterate subjects. Using event-related fMRI, 24 healthy right-handed Chinese subjects (12 literates and 12 illiterates) were asked to perform Chinese character and figure form judgment tasks. The blood oxygen level-dependent (BOLD) differences in pIFG were examined with general linear modeling (GLM). We found differences in reaction times and accuracy between subjects as they performed these tasks. These behavioral differences reflect the different cognitive demands of character form judgment for literate and illiterate individuals. The results showed differences in the BOLD response patterns in the pIFG between the two discrimination tasks and the two subject groups. A comparison of the character and figure tasks showed that literate and illiterate subjects had similar BOLD responses in the inferior frontal gyrus. However, differences in behavioral performance suggest that the pIFG plays a different role in Chinese character form judgment for each subject group. In literate subjects, the left pIFG mediated access to phonology in achieving Chinese character form judgment, whereas the right pIFG participated in the processing of the orthography of Chinese characters. In illiterate subjects, the bilateral frontal gyrus participated in the visual-spatial processing of Chinese characters to achieve form judgment. Copyright © 2011 Elsevier B.V. All rights reserved.
Quantifying Trust, Distrust, and Suspicion in Human-System Interactions
2015-10-26
devices which require subjects to lie in restricted positions ( fMRI ), or to drink hazardous materials (PET), EEG and fNIRS can non-invasively measure... fMRI . Since fNIRS and fMRI both measure elements of the Blood Oxygen Level Dependent (BOLD) signal. Researchers have recently explored the...response inhibition load, verbal working memory load, and spatial working memory load [1, 7]. We have also successfully localized brain regions such as
DOE Office of Scientific and Technical Information (OSTI.GOV)
Adamson, J; Chang, Z; Cai, J
Purpose: To develop a robust MRI sequence to measure BOLD breath hold induced contrast in context of breast radiotherapy. Methods: Two sequences were selected from prior studies as candidates to measure BOLD contrast attributable to breath holding within the breast: (1) T2* based Gradient Echo EPI (TR/TE = 500/41ms, flip angle = 60°), and (2) T2 based Single Shot Fast Spin Echo (SSFSE) (TR/TE = 3000/60ms). We enrolled ten women post-lumpectomy for breast cancer who were undergoing treatment planning for whole breast radiotherapy. Each session utilized a 1.5T GE MRI and 4 channel breast coil with the subject immobilized pronemore » on a custom board. For each sequence, 1–3 planes of the lumpectomy breast were imaged continuously during a background measurement (1min) and intermittent breath holds (20–40s per breath hold, 3–5 holds per sequence). BOLD contrast was quantified as correlation of changes in per-pixel intensity with the breath hold schedule convolved with a hemodynamic response function. Subtle motion was corrected using a deformable registration algorithm. Correlation with breath-holding was considered significant if p<0.001. Results: The percentage of the breast ROI with positive BOLD contrast measured by the two sequences were in agreement with a correlation coefficient of R=0.72 (p=0.02). While both sequences demonstrated areas with strong BOLD response, the response was more systematic throughout the breast for the SSFSE (T2) sequence (% breast with response in the same direction: 51.2%±0.7% for T2* vs. 68.1%±16% for T2). In addition, the T2 sequence was less prone to magnetic susceptibility artifacts, especially in presence of seroma, and provided a more robust image with little distortion or artifacts. Conclusion: A T2 SSFSE sequence shows promise for measuring BOLD contrast in the context of breast radiotherapy utilizing a breath hold technique. Further study in a larger patient cohort is warranted to better refine this novel technique.« less
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.
Shi, Hong-Jian; Li, Yan-Feng; Ji, Wen-Jie; Lin, Zhi-Chun; Cai, Wei; Chen, Tao; Yuan, Bin; Niu, Xiu-Long; Li, Han-Ying; Shu, Wen; Li, Yu-Ming; Yuan, Fei; Zhou, Xin; Zhang, Zhuoli
2018-06-01
This study aimed to investigate the feasibility of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate visceral adipose tissue (VAT) oxygenation in Zucker diabetic fatty (ZDF) rats and its associations with systemic metaflammation. Five-week-old ZDF rats and Zucker lean (ZL) rats were fed a high-fat diet (HFD) for 18 weeks. A baseline BOLD-MRI scan of perirenal adipose tissue was performed after 8 weeks of HFD feeding, and then the rats were randomized to receive pioglitazone or a vehicle for the following 10 weeks. At sacrifice, BOLD-MRI scan, Hypoxyprobe-1 injection, and circulating T helper 17 (Th17), regulatory T (Treg) cells, and monocyte subtype flow cytometry analysis were performed. HFD feeding led to a significant increase in VAT BOLD-MRI R2* signals (20.14 ± 0.23 per second vs. 21.53 ± 0.20 per second; P = 0.012), an indicator for decreased oxygenation. R2* signal was significantly correlated with VAT pimonidazole adduct-positive area, insulin resistance, Th17 and Treg cells, CD43 + and CD43+ + monocyte subtypes, and VAT macrophage infiltration. Pioglitazone treatment improved the insulin resistance and was associated with a delayed progression of VAT oxygenation. This work demonstrated the feasibility of BOLD-MRI for detecting the VAT oxygenation status in ZDF rats, and the BOLD-MRI signals were associated with insulin resistance and systemic metaflammation in ZDF rats during the development of obesity. © 2018 The Obesity Society.
Reproducibility of EEG-fMRI results in a patient with fixation-off sensitivity.
Formaggio, Emanuela; Storti, Silvia Francesca; Galazzo, Ilaria Boscolo; Bongiovanni, Luigi Giuseppe; Cerini, Roberto; Fiaschi, Antonio; Manganotti, Paolo
2014-07-01
Blood oxygenation level-dependent (BOLD) activation associated with interictal epileptiform discharges in a patient with fixation-off sensitivity (FOS) was studied using a combined electroencephalography-functional magnetic resonance imaging (EEG-fMRI) technique. An automatic approach for combined EEG-fMRI analysis and a subject-specific hemodynamic response function was used to improve general linear model analysis of the fMRI data. The EEG showed the typical features of FOS, with continuous epileptiform discharges during elimination of central vision by eye opening and closing and fixation; modification of this pattern was clearly visible and recognizable. During all 3 recording sessions EEG-fMRI activations indicated a BOLD signal decrease related to epileptiform activity in the parietal areas. This study can further our understanding of this EEG phenomenon and can provide some insight into the reliability of the EEG-fMRI technique in localizing the irritative zone.
Functional MRI of inhibitory processing in abstinent adolescent marijuana users.
Tapert, Susan F; Schweinsburg, Alecia D; Drummond, Sean P A; Paulus, Martin P; Brown, Sandra A; Yang, Tony T; Frank, Lawrence R
2007-10-01
Marijuana intoxication appears to impair response inhibition, but it is unclear if impaired inhibition and associated brain abnormalities persist after prolonged abstinence among adolescent users. We hypothesized that brain activation during a go/no-go task would show persistent abnormalities in adolescent marijuana users after 28 days of abstinence. Adolescents with (n = 16) and without (n = 17) histories of marijuana use were compared on blood oxygen level dependent (BOLD) response to a go/no-go task during functional magnetic resonance imaging (fMRI) after 28 days of monitored abstinence. Participants had no neurological problems or Axis I diagnoses other than cannabis abuse/dependence. Marijuana users did not differ from non-users on task performance but showed more BOLD response than non-users during inhibition trials in right dorsolateral prefrontal, bilateral medial frontal, bilateral inferior and superior parietal lobules, and right occipital gyri, as well as during "go" trials in right prefrontal, insular, and parietal cortices (p < 0.05, clusters > 943 microl). Differences remained significant even after controlling for lifetime and recent alcohol use. Adolescent marijuana users relative to non-users showed increased brain processing effort during an inhibition task in the presence of similar task performance, even after 28 days of abstinence. Thus, increased brain processing effort to achieve inhibition may predate the onset of regular use or result from it. Future investigations will need to determine whether increased brain processing effort is associated with risk to use.
Fechner, Hanna B; Pachur, Thorsten; Schooler, Lael J; Mehlhorn, Katja; Battal, Ceren; Volz, Kirsten G; Borst, Jelmer P
2016-12-01
How do people use memories to make inferences about real-world objects? We tested three strategies based on predicted patterns of response times and blood-oxygen-level-dependent (BOLD) responses: one strategy that relies solely on recognition memory, a second that retrieves additional knowledge, and a third, lexicographic (i.e., sequential) strategy, that considers knowledge conditionally on the evidence obtained from recognition memory. We implemented the strategies as computational models within the Adaptive Control of Thought-Rational (ACT-R) cognitive architecture, which allowed us to derive behavioral and neural predictions that we then compared to the results of a functional magnetic resonance imaging (fMRI) study in which participants inferred which of two cities is larger. Overall, versions of the lexicographic strategy, according to which knowledge about many but not all alternatives is searched, provided the best account of the joint patterns of response times and BOLD responses. These results provide insights into the interplay between recognition and additional knowledge in memory, hinting at an adaptive use of these two sources of information in decision making. The results highlight the usefulness of implementing models of decision making within a cognitive architecture to derive predictions on the behavioral and neural level. Copyright © 2016 Elsevier B.V. All rights reserved.
Evolutionary Dynamics of Fearfulness and Boldness: A Stochastic Simulation Model
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.
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.
Brain magnetic resonance imaging with contrast dependent on blood oxygenation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ogawa, S.; Lee, T.M.; Kay, A.R.
1990-12-01
Paramagnetic deoxyhemoglobin in venous blood is a naturally occurring contrast agent for magnetic resonance imaging (MRI). By accentuating the effects of this agent through the use of gradient-echo techniques in high yields, the authors demonstrate in vivo images of brain microvasculature with image contrast reflecting the blood oxygen level. This blood oxygenation level-dependent (BOLD) contrast follows blood oxygen changes induced by anesthetics, by insulin-induced hypoglycemia, and by inhaled gas mixtures that alter metabolic demand or blood flow. The results suggest that BOLD contrast can be used to provide in vivo real-time maps of blood oxygenation in the brain under normalmore » physiological conditions. BOLD contrast adds an additional feature to magnetic resonance imaging and complement other techniques that are attempting to provide position emission tomography-like measurements related to regional neural activity.« less
Brain Magnetic Resonance Imaging with Contrast Dependent on Blood Oxygenation
NASA Astrophysics Data System (ADS)
Ogawa, S.; Lee, T. M.; Kay, A. R.; Tank, D. W.
1990-12-01
Paramagnetic deoxyhemoglobin in venous blood is a naturally occurring contrast agent for magnetic resonance imaging (MRI). By accentuating the effects of this agent through the use of gradient-echo techniques in high fields, we demonstrate in vivo images of brain microvasculature with image contrast reflecting the blood oxygen level. This blood oxygenation level-dependent (BOLD) contrast follows blood oxygen changes induced by anesthetics, by insulin-induced hypoglycemia, and by inhaled gas mixtures that alter metabolic demand or blood flow. The results suggest that BOLD contrast can be used to provide in vivo real-time maps of blood oxygenation in the brain under normal physiological conditions. BOLD contrast adds an additional feature to magnetic resonance imaging and complements other techniques that are attempting to provide positron emission tomography-like measurements related to regional neural activity.
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.
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% reduction over grey matter). We were able to identify vascular effects and hence altered neurovascular coupling through the alteration of low-level task FMRI responses in the face of a preserved visual evoked potential. However, our data also suggest a cognitive effect of caffeine through its positive effect on the frontal BOLD signal consistent with the shortening of oddball EEG response latency. The combined use of EEG–FMRI is a promising methodology for investigating alterations in brain function in drug and disease studies where neurovascular coupling may be altered on a regional basis. PMID:22561357
Increased ventral striatal BOLD activity during non-drug reward anticipation in cannabis users.
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.
Changing body temperature affects the T2* signal in the rat brain and reveals hypothalamic activity.
Vanhoutte, G; Verhoye, M; Van der Linden, A
2006-05-01
This study was designed to determine brain activity in the hypothalamus-in particular the thermoregulatory function of the hypothalamic preoptic area (PO). We experimentally changed the body temperature in rats within the physiological range (37-39 degrees C) and monitored changes in blood oxygenation level-dependent (BOLD) MR signal. To explore PO activity we had to deal with general signal changes caused by temperature-dependent alterations in the affinity of oxygen for hemoglobin, which contributes to BOLD contrast because it is partly sensitive to the amount of paramagnetic deoxyhemoglobin in the voxel. To reduce these overall temperature-induced effects, we corrected the BOLD data using brain-specific correction algorithms. The results showed activity of the PO during body warming from 38 degrees C to 39 degrees C, supported by an increased BOLD signal after correction. This is the first fMRI study on the autonomous nervous system in which hypothalamic activity elicited by changes in the internal environment (body temperature) was monitored. In this study we also demonstrate 1) that any fMRI study of anesthetized small animals should guard against background BOLD signal drift, since animals are vulnerable to body temperature fluctuations; and 2) the existence of a link between PO activity and the sympathetically-mediated opening of the arteriovenous anastomoses in a parallel study on the rat tail, a peripheral thermoregulatory organ.
NASA Astrophysics Data System (ADS)
Hadi, Shamil; Siadat, Mohamad R.; Babajani-Feremi, Abbas
2012-03-01
Emotional tasks may result in a strong blood oxygen level-dependent (BOLD) signal in the amygdala in 5- HTTLRP short-allele. Reduced anterior cingulate cortex (ACC)-amygdala connectivity in short-allele provides a potential mechanistic account for the observed increase in amygdala activity. In our study, fearful and threatening facial expressions were presented to two groups of 12 subjects with long- and short-allele carriers. The BOLD signals of the left amygdala of each group were averaged to increase the signal-to-noise ratio. A Bayesian approach was used to estimate the model parameters to elucidate the underlying hemodynamic mechanism. Our results showed a positive BOLD signal in the left amygdala for short-allele individuals, and a negative BOLD signal in the same region for long-allele individuals. This is due to the fact that short-allele is associated with lower availability of serotonin transporter (5-HTT) and this leads to an increase of serotonin (5-HT) concentration in the cACC-amygdala synapse.
Zeuner, Kirsten E; Knutzen, Arne; Granert, Oliver; Sablowsky, Simone; Götz, Julia; Wolff, Stephan; Jansen, Olav; Dressler, Dirk; Schneider, Susanne A; Klein, Christine; Deuschl, Günther; van Eimeren, Thilo; Witt, Karsten
2016-01-01
Previous receptor binding studies suggest dopamine function is altered in the basal ganglia circuitry in task-specific dystonia, a condition characterized by contraction of agonist and antagonist muscles while performing specific tasks. Dopamine plays a role in reward-based learning. Using fMRI, this study compared 31 right-handed writer's cramp patients to 35 controls in reward-based learning of a probabilistic reversal-learning task. All subjects chose between two stimuli and indicated their response with their left or right index finger. One stimulus response was rewarded 80%, the other 20%. After contingencies reversal, the second stimulus response was rewarded in 80%. We further linked the DRD2/ANKK1-TaqIa polymorphism, which is associated with 30% reduction of the striatal dopamine receptor density with reward-based learning and assumed impaired reversal learning in A + subjects. Feedback learning in patients was normal. Blood-oxygen level dependent (BOLD) signal in controls increased with negative feedback in the insula, rostral cingulate cortex, middle frontal gyrus and parietal cortex (pFWE < 0.05). In comparison to controls, patients showed greater increase in BOLD activity following negative feedback in the dorsal anterior cingulate cortex (BA32). The genetic status was not correlated with the BOLD activity. The Brodmann area 32 (BA32) is part of the dorsal anterior cingulate cortex (dACC) that plays an important role in coordinating and integrating information to guide behavior and in reward-based learning. The dACC is connected with the basal ganglia-thalamo-loop modulated by dopaminergic signaling. This finding suggests disturbed integration of reinforcement history in decision making and implicate that the reward system might contribute to the pathogenesis in writer's cramp.
The balanced mind: the variability of task-unrelated thoughts predicts error monitoring
Allen, Micah; Smallwood, Jonathan; Christensen, Joanna; Gramm, Daniel; Rasmussen, Beinta; Jensen, Christian Gaden; Roepstorff, Andreas; Lutz, Antoine
2013-01-01
Self-generated thoughts unrelated to ongoing activities, also known as “mind-wandering,” make up a substantial portion of our daily lives. Reports of such task-unrelated thoughts (TUTs) predict both poor performance on demanding cognitive tasks and blood-oxygen-level-dependent (BOLD) activity in the default mode network (DMN). However, recent findings suggest that TUTs and the DMN can also facilitate metacognitive abilities and related behaviors. To further understand these relationships, we examined the influence of subjective intensity, ruminative quality, and variability of mind-wandering on response inhibition and monitoring, using the Error Awareness Task (EAT). We expected to replicate links between TUT and reduced inhibition, and explored whether variance in TUT would predict improved error monitoring, reflecting a capacity to balance between internal and external cognition. By analyzing BOLD responses to subjective probes and the EAT, we dissociated contributions of the DMN, executive, and salience networks to task performance. While both response inhibition and online TUT ratings modulated BOLD activity in the medial prefrontal cortex (mPFC) of the DMN, the former recruited a more dorsal area implying functional segregation. We further found that individual differences in mean TUTs strongly predicted EAT stop accuracy, while TUT variability specifically predicted levels of error awareness. Interestingly, we also observed co-activation of salience and default mode regions during error awareness, supporting a link between monitoring and TUTs. Altogether our results suggest that although TUT is detrimental to task performance, fluctuations in attention between self-generated and external task-related thought is a characteristic of individuals with greater metacognitive monitoring capacity. Achieving a balance between internally and externally oriented thought may thus aid individuals in optimizing their task performance. PMID:24223545
Prospective MR image alignment between breath-holds: Application to renal BOLD MRI.
Kalis, Inge M; Pilutti, David; Krafft, Axel J; Hennig, Jürgen; Bock, Michael
2017-04-01
To present an image registration method for renal blood oxygen level-dependent (BOLD) measurements that enables semiautomatic assessment of parenchymal and medullary R2* changes under a functional challenge. In a series of breath-hold acquisitions, three-dimensional data were acquired initially for prospective image registration of subsequent BOLD measurements. An algorithm for kidney alignment for BOLD renal imaging (KALIBRI) was implemented to detect the positions of the left and right kidney so that the kidneys were acquired in the subsequent BOLD measurement at consistent anatomical locations. Residual in-plane distortions were corrected retrospectively so that semiautomatic dynamic R2* measurements of the renal cortex and medulla become feasible. KALIBRI was tested in six healthy volunteers during a series of BOLD experiments, which included a 600- to 1000-mL water challenge. Prospective image registration and BOLD imaging of each kidney was achieved within a total measurement time of about 17 s, enabling its execution within a single breath-hold. KALIBRI improved the registration by up to 35% as found with mutual information measures. In four volunteers, a medullary R2* decrease of up to 40% was observed after water ingestion. KALIBRI improves the quality of two-dimensional time-resolved renal BOLD MRI by aligning local renal anatomy, which allows for consistent R2* measurements over many breath-holds. Magn Reson Med 77:1573-1582, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.
McKenzie, David J; Belão, Thiago C; Killen, Shaun S; Rantin, F Tadeu
2015-12-01
The African sharptooth catfish Clarias gariepinus has bimodal respiration, it has a suprabranchial air-breathing organ alongside substantial gills. We used automated bimodal respirometry to reveal that undisturbed juvenile catfish (N=29) breathed air continuously in normoxia, with a marked diurnal cycle. Air breathing and routine metabolic rate (RMR) increased in darkness when, in the wild, this nocturnal predator forages. Aquatic hypoxia (20% air saturation) greatly increased overall reliance on air breathing. We investigated whether two measures of risk taking to breathe air, namely absolute rates of aerial O2 uptake (ṀO2,air) and the percentage of RMR obtained from air (%ṀO2,air), were influenced by individual standard metabolic rate (SMR) and boldness. In particular, whether any influence varied with resource availability (normoxia versus hypoxia) or relative fear of predation (day versus night). Individual SMR, derived from respirometry, had an overall positive influence on ṀO2,air across all contexts but a positive influence on %ṀO2,air only in hypoxia. Thus, a pervasive effect of SMR on air breathing became most acute in hypoxia, when individuals with higher O2 demand took proportionally more risks. Boldness was estimated as time required to resume air breathing after a fearful stimulus in daylight normoxia (Tres). Although Tres had no overall influence on ṀO2,air or %ṀO2,air, there was a negative relationship between Tres and %ṀO2,air in daylight, in normoxia and hypoxia. There were two Tres response groups, 'bold' phenotypes with Tres below 75 min (N=13) which, in daylight, breathed proportionally more air than 'shy' phenotypes with Tres above 115 min (N=16). Therefore, individual boldness influenced air breathing when fear of predation was high. Thus, individual energy demand and personality did not have parallel influences on the emergent tendency to take risks to obtain a resource; their influences varied in strength with context. © 2015. Published by The Company of Biologists Ltd.
Morrell, Glen; Rusinek, Henry; Warner, Lizette; Vivier, Pierre-Hugues; Cheung, Alfred K.; Lerman, Lilach O.; Lee, Vivian S.
2014-01-01
Blood oxygen level-dependent (BOLD) MRI data of kidney, while indicative of tissue oxygenation level (Po2), is in fact influenced by multiple confounding factors, such as R2, perfusion, oxygen permeability, and hematocrit. We aim to explore the feasibility of extracting tissue Po2 from renal BOLD data. A method of two steps was proposed: first, a Monte Carlo simulation to estimate blood oxygen saturation (SHb) from BOLD signals, and second, an oxygen transit model to convert SHb to tissue Po2. The proposed method was calibrated and validated with 20 pigs (12 before and after furosemide injection) in which BOLD-derived tissue Po2 was compared with microprobe-measured values. The method was then applied to nine healthy human subjects (age: 25.7 ± 3.0 yr) in whom BOLD was performed before and after furosemide. For the 12 pigs before furosemide injection, the proposed model estimated renal tissue Po2 with errors of 2.3 ± 5.2 mmHg (5.8 ± 13.4%) in cortex and −0.1 ± 4.5 mmHg (1.7 ± 18.1%) in medulla, compared with microprobe measurements. After injection of furosemide, the estimation errors were 6.9 ± 3.9 mmHg (14.2 ± 8.4%) for cortex and 2.6 ± 4.0 mmHg (7.7 ± 11.5%) for medulla. In the human subjects, BOLD-derived medullary Po2 increased from 16.0 ± 4.9 mmHg (SHb: 31 ± 11%) at baseline to 26.2 ± 3.1 mmHg (SHb: 53 ± 6%) at 5 min after furosemide injection, while cortical Po2 did not change significantly at ∼58 mmHg (SHb: 92 ± 1%). Our proposed method, validated with a porcine model, appears promising for estimating tissue Po2 from renal BOLD MRI data in human subjects. PMID:24452640
fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease
Bondi, Mark W.; Houston, Wes S.; Eyler, Lisa T.; Brown, Gregory G.
2006-01-01
Objective To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults. Methods Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE ε4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions. Results Nondemented older adults with an APOE ε4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched ε3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated. Conclusions The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE ε4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding. PMID:15699382
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.
Task-dependent and task-independent neurovascular responses to syntactic processing⋆
Caplan, David; Chen, Evan; Waters, Gloria
2008-01-01
The neural basis for syntactic processing was studied using event-related fMRI to determine the locations of BOLD signal increases in the contrast of syntactically complex sentences with center-embedded, object-extracted relative clauses and syntactically simple sentences with right-branching, subject-extracted relative clauses in a group of 15 participants in three tasks. In a sentence verification task, participants saw a target sentence in one of these two syntactic forms, followed by a probe in a simple active form, and determined whether the probe expressed a proposition in the target. In a plausibility judgment task, participants determined whether a sentence in one of these two syntactic forms was plausible or implausible. Finally, in a non-word detection task, participants determined whether a sentence in one of these two syntactic forms contained only real words or a non-word. BOLD signal associated with the syntactic contrast increased in the left posterior inferior frontal gyrus in non-word detection and in a widespread set of areas in the other two tasks. We conclude that the BOLD activity in the left posterior inferior frontal gyrus reflects syntactic processing independent of concurrent cognitive operations and the more widespread areas of activation reflect the use of strategies and the use of the products of syntactic processing to accomplish tasks. PMID:18387556
Task-related modulations of BOLD low-frequency fluctuations within the default mode network
NASA Astrophysics Data System (ADS)
Tommasin, Silvia; Mascali, Daniele; Gili, Tommaso; Eid Assan, Ibrahim; Moraschi, Marta; Fratini, Michela; Wise, Richard G.; Macaluso, Emiliano; Mangia, Silvia; Giove, Federico
2017-07-01
Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33±6 years, 8F/12M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the steady-state execution of a sustained working memory n-back task. We found that the steady state execution of such a task impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to steady-state task execution, can contribute to a better understanding of how brain networks rearrange themselves in response of a task.
Inter-subject phase synchronization for exploratory analysis of task-fMRI.
Bolt, Taylor; Nomi, Jason S; Vij, Shruti G; Chang, Catie; Uddin, Lucina Q
2018-08-01
Analysis of task-based fMRI data is conventionally carried out using a hypothesis-driven approach, where blood-oxygen-level dependent (BOLD) time courses are correlated with a hypothesized temporal structure. In some experimental designs, this temporal structure can be difficult to define. In other cases, experimenters may wish to take a more exploratory, data-driven approach to detecting task-driven BOLD activity. In this study, we demonstrate the efficiency and power of an inter-subject synchronization approach for exploratory analysis of task-based fMRI data. Combining the tools of instantaneous phase synchronization and independent component analysis, we characterize whole-brain task-driven responses in terms of group-wise similarity in temporal signal dynamics of brain networks. We applied this framework to fMRI data collected during performance of a simple motor task and a social cognitive task. Analyses using an inter-subject phase synchronization approach revealed a large number of brain networks that dynamically synchronized to various features of the task, often not predicted by the hypothesized temporal structure of the task. We suggest that this methodological framework, along with readily available tools in the fMRI community, provides a powerful exploratory, data-driven approach for analysis of task-driven BOLD activity. Copyright © 2018 Elsevier Inc. All rights reserved.
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.
Amphetamine modulates brain signal variability and working memory in younger and older adults.
Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman
2015-06-16
Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.
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.
Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation
Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.
2011-01-01
Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 minutes after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20 mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem’s modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABAA receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. PMID:21640782
Chiacchiaretta, Piero; Cerritelli, Francesco; Bubbico, Giovanna; Perrucci, Mauro Gianni; Ferretti, Antonio
2018-01-01
Measurement of the dynamic coupling between spontaneous Blood Oxygenation Level Dependent (BOLD) and cerebral blood flow (CBF) fluctuations has been recently proposed as a method to probe resting-state brain physiology. Here we investigated how the dynamic BOLD-CBF coupling during resting-state is affected by aging. Fifteen young subjects and 17 healthy elderlies were studied using a dual-echo pCASL sequence. We found that the dynamic BOLD-CBF coupling was markedly reduced in elderlies, in particular in the left supramarginal gyrus, an area known to be involved in verbal working memory and episodic memory. Moreover, correcting for temporal shift between BOLD and CBF timecourses resulted in an increased correlation of the two signals for both groups, but with a larger increase for elderlies. However, even after temporal shift correction, a significantly decreased correlation was still observed for elderlies in the left supramarginal gyrus, indicating that the age-related dynamic BOLD-CBF uncoupling in this region is more pronounced and can be only partially explained with a simple time-shift between the two signals. Interestingly, these results were observed in a group of elderlies with normal cognitive functions, suggesting that the study of dynamic BOLD-CBF coupling during resting-state is a promising technique, potentially able to provide early biomarkers of functional changes in the aging brain.
The cortical response to the oral perception of fat emulsions and the effect of taster status
Eldeghaidy, Sally; Marciani, Luca; McGlone, Francis; Hollowood, Tracey; Hort, Joanne; Head, Kay; Taylor, Andrew J.; Busch, Johanneke; Spiller, Robin C.; Gowland, Penny A.
2011-01-01
The rewarding attributes of foods containing fat are associated with the increase in fat consumption, but little is known of how the complex physical and chemical properties of orally ingested fats are represented and decoded in the brain nor how this impacts feeding behavior within the population. Here, functional MRI (fMRI) is used to assess the brain response to isoviscous, isosweet fat emulsions of increasing fat concentration and to investigate the correlation of behavioral and neuroimaging responses with taster status (TS). Cortical areas activated in response to fat, and those areas positively correlated with fat concentration, were identified. Significant responses that positively correlated with increasing fat concentration were found in the anterior insula, frontal operculum and secondary somatosensory cortex (SII), anterior cingulate cortex, and amygdala. Assessing the effect of TS revealed a strong correlation with self-reported preference of the samples and with cortical response in somatosensory areas [primary somatosensory cortex (SI), SII, and midinsula] and the primary taste area (anterior insula) and a trend in reward areas (amygdala and orbitofrontal cortex). This finding of a strong correlation with TS in somatosensory areas supports the theory of increased mechanosensory trigeminal innervation in high 6-n-propyl-2-thiouracil (PROP) tasters and has been linked to a higher risk of obesity. The interindividual differences in blood oxygenation level-dependent (BOLD) amplitude with TS indicates that segmenting populations by TS will reduce the heterogeneity of BOLD responses, improving signal detection power. PMID:21389303
FRONTO-STRIATAL FUNCTIONAL CONNECTIVITY DURING RESPONSE INHIBITION IN ALCOHOL DEPENDENCE
Courtney, Kelly E.; Ghahremani, Dara G.; Ray, Lara A.
2013-01-01
Poor response inhibition has been implicated in the development of alcohol dependence, yet little is known about how neural pathways underlying cognitive control are affected in this disorder. Moreover, endogenous opioid levels may impact the functionality of inhibitory control pathways. This study investigated the relationship between alcohol dependence severity and functional connectivity of fronto-striatal networks during response inhibition in an alcohol dependent sample. A secondary aim of this study was to test the moderating effect of a functional polymorphism (A118G) of the µ-opioid receptor (OPRM1) gene. Twenty individuals with alcohol dependence (6 females; 90% Caucasian; mean age = 29.4) who were prospectively genotyped on the OPRM1 gene underwent blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) while performing a Stop Signal Task (SST). The relationship between alcohol dependence severity and functional connectivity within fronto-striatal networks important for response inhibition was assessed using psychophysiological interaction (PPI) analyses. Analyses revealed greater alcohol dependence severity associated with weaker functional connectivity between the putamen and prefrontal regions (e.g., the anterior insula, anterior cingulate, and medial prefrontal cortex) during response inhibition. Further, the OPRM1 genotype was associated with differential response inhibition-related functional connectivity. This study demonstrates that individuals with more severe alcohol dependence exhibit less frontal connectivity with the striatum, a component of cognitive control networks important for response inhibition. These findings suggest that the fronto-striatal pathway underlying response inhibition is weakened as alcoholism progresses. PMID:23240858
Alarcón, Gabriela; Cservenka, Anita; Fair, Damien A.; Nagel, Bonnie J.
2014-01-01
Adolescence is a developmental period characterized by notable changes in behavior, physical attributes, and an increase in endogenous sex steroid hormones, which may impact cognitive functioning. Moreover, sex differences in brain structure are present, leading to differences in neural function and cognition. Here, we examine sex differences in performance and blood oxygen level-dependent (BOLD) activation in a sample of adolescents during a spatial working memory (SWM) task. We also examine whether endogenous testosterone levels mediate differential brain activity between the sexes. Adolescents between ages 10 and 16 completed a SWM functional magnetic resonance imaging (fMRI) task, and serum hormone levels were assessed within seven days of scanning. While there were no sex differences in task performance (accuracy and reaction time), differences in BOLD response between girls and boys emerged, with girls deactivating brain regions in the default mode network and boys showing increased response in SWM-related brain regions of the frontal cortex. These results suggest that adolescent boys and girls adopted distinct neural strategies, while maintaining spatial cognitive strategies that facilitated comparable cognitive performance of a SWM task. A nonparametric bootstrapping procedure revealed that testosterone did not mediate sex-specific brain activity, suggesting that sex differences in BOLD activation during SWM may be better explained by other factors, such as early organizational effects of sex steroids or environmental influences. Elucidating sex differences in neural function and the influence of gonadal hormones can serve as a basis of comparison for understanding sexually dimorphic neurodevelopment and inform sex-specific psychopathology that emerges in adolescence. PMID:25312831
Abnormal GABAergic function and face processing in schizophrenia: A pharmacologic-fMRI study.
Tso, Ivy F; Fang, Yu; Phan, K Luan; Welsh, Robert C; Taylor, Stephan F
2015-10-01
The involvement of the gamma-aminobutyric acid (GABA) system in schizophrenia is suggested by postmortem studies and the common use of GABA receptor-potentiating agents in treatment. In a recent study, we used a benzodiazepine challenge to demonstrate abnormal GABAergic function during processing of negative visual stimuli in schizophrenia. This study extended this investigation by mapping GABAergic mechanisms associated with face processing and social appraisal in schizophrenia using a benzodiazepine challenge. Fourteen stable, medicated schizophrenia/schizoaffective patients (SZ) and 13 healthy controls (HC) underwent functional MRI using the blood oxygenation level-dependent (BOLD) technique while they performed the Socio-emotional Preference Task (SePT) on emotional face stimuli ("Do you like this face?"). Participants received single-blinded intravenous saline and lorazepam (LRZ) in two separate sessions separated by 1-3weeks. Both SZ and HC recruited medial prefrontal cortex/anterior cingulate during the SePT, relative to gender identification. A significant drug by group interaction was observed in the medial occipital cortex, such that SZ showed increased BOLD signal to LRZ challenge, while HC showed an expected decrease of signal; the interaction did not vary by task. The altered BOLD response to LRZ challenge in SZ was significantly correlated with increased negative affect across multiple measures. The altered response to LRZ challenge suggests that abnormal face processing and negative affect in SZ are associated with altered GABAergic function in the visual cortex, underscoring the role of impaired visual processing in socio-emotional deficits in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.
Abnormal GABAergic function and negative affect in schizophrenia.
Taylor, Stephan F; Demeter, Elise; Phan, K Luan; Tso, Ivy F; Welsh, Robert C
2014-03-01
Deficits in the γ-aminobutyric acid (GABA) system have been reported in postmortem studies of schizophrenia, and therapeutic interventions in schizophrenia often involve potentiation of GABA receptors (GABAR) to augment antipsychotic therapy and treat negative affect such as anxiety. To map GABAergic mechanisms associated with processing affect, we used a benzodiazepine challenge while subjects viewed salient visual stimuli. Fourteen stable, medicated schizophrenia/schizoaffective patients and 13 healthy comparison subjects underwent functional magnetic resonance imaging using the blood oxygenation level-dependent (BOLD) technique while they viewed salient emotional images. Subjects received intravenous lorazepam (LRZ; 0.01 mg/kg) or saline in a single-blinded, cross-over design (two sessions separated by 1-3 weeks). A predicted group by drug interaction was noted in the dorsal medial prefrontal cortex (dmPFC) as well as right superior frontal gyrus and left and right occipital regions, such that psychosis patients showed an increased BOLD signal to LRZ challenge, rather than the decreased signal exhibited by the comparison group. A main effect of reduced BOLD signal in bilateral occipital areas was noted across groups. Consistent with the role of the dmPFC in processing emotion, state negative affect positively correlated with the response to the LRZ challenge in the dmPFC for the patients and comparison subjects. The altered response to LRZ challenge is consistent with altered inhibition predicted by postmortem findings of altered GABAR in schizophrenia. These results also suggest that negative affect in schizophrenia/schizoaffective disorder is associated-directly or indirectly-with GABAergic function on a continuum with normal behavior.
Yang, Albert C; Hong, Chen-Jee; Liou, Yin-Jay; Huang, Kai-Lin; Huang, Chu-Chung; Liu, Mu-En; Lo, Men-Tzung; Huang, Norden E; Peng, Chung-Kang; Lin, Ching-Po; Tsai, Shih-Jen
2015-06-01
Schizophrenia is characterized by heterogeneous pathophysiology. Using multiscale entropy (MSE) analysis, which enables capturing complex dynamics of time series, we characterized MSE patterns of blood-oxygen-level-dependent (BOLD) signals across different time scales and determined whether BOLD activity in patients with schizophrenia exhibits increased complexity (increased entropy in all time scales), decreased complexity toward regularity (decreased entropy in all time scales), or decreased complexity toward uncorrelated randomness (high entropy in short time scales followed by decayed entropy as the time scale increases). We recruited 105 patients with schizophrenia with an age of onset between 18 and 35 years and 210 age- and sex-matched healthy volunteers. Results showed that MSE of BOLD signals in patients with schizophrenia exhibited two routes of decreased BOLD complexity toward either regular or random patterns. Reduced BOLD complexity toward regular patterns was observed in the cerebellum and temporal, middle, and superior frontal regions, and reduced BOLD complexity toward randomness was observed extensively in the inferior frontal, occipital, and postcentral cortices as well as in the insula and middle cingulum. Furthermore, we determined that the two types of complexity change were associated differently with psychopathology; specifically, the regular type of BOLD complexity change was associated with positive symptoms of schizophrenia, whereas the randomness type of BOLD complexity was associated with negative symptoms of the illness. These results collectively suggested that resting-state dynamics in schizophrenia exhibit two routes of pathologic change toward regular or random patterns, which contribute to the differences in syndrome domains of psychosis in patients with schizophrenia. © 2015 Wiley Periodicals, Inc.
Oxygen-induced frequency shifts in hyperoxia: a significant component of BOLD signal.
Song, Youngkyu; Cho, Gyunggoo; Chun, Song-I; Baek, Jin Hee; Cho, HyungJoon; Kim, Young Ro; Park, Sung Bin; Kim, Jeong Kon
2014-07-01
In comparison to the well-documented significance of intravascular deoxyhemoglobin (deoxyHgb), the effects of dissolved oxygen on the blood-oxygen-level-dependent (BOLD) signal have not been widely reported. Based on the fact that the prolonged inspiration of high oxygen fraction gas can result in up to a sixfold increase of the baseline tissue oxygenation, the current study focused on the influence of dissolved oxygen on the BOLD signal during hyperoxia. As results, our in vitro study revealed that the r1 and r2 (relaxivities) of the oxygen-treated serum were 0.22 mM(-1) · s(-1) and 0.19 mM(-1) · s(-1) , respectively. In an in vivo experiment, hyperoxic respiration induced negative BOLD contrast (i.e. signal decrease) in 18-42% of measured brain regions, voxels with accompanying significant decreases in both the T(*)2 (-12.1% to -19.4%) and T1 (-5.8% to -3.3%) relaxation times. In contrast, the T(*)2 relaxation time significantly increased (11.2% to 14.0%) for the voxels displaying positive BOLD contrast (in 41-50% of the measured brain), which reflected a hyperoxygenation-induced reduction in tissue deoxyHgb concentration. These data imply that hyperoxia-driven BOLD signal changes are primarily determined by the counteracting effects of extravascular oxygen and intravascular deoxyHgb. Oxygen-induced magnetic susceptibility was further demonstrated by the study of 1 min hypoxia, which induced BOLD signal changes opposite to those under hyperoxia. Vasoconstriction was more common in voxels with negative BOLD contrast than in voxels with positive contrast (% change of blood volume, -9.8% to -12.8% versus 2.0% to 2.2%), which further suggests that negative BOLD contrast is mainly evoked by an increase in extravascular oxygen concentration. Conclusively, frequency shifts, which are induced by the accumulation of oxygen molecules and associated magnetic field inhomogeneity, are a significant source of the negative BOLD contrast during hyperoxia. Copyright © 2014 John Wiley & Sons, Ltd.
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 behavior via striatal pathways, independent of changes in plasma PYY and GLP-1. This trial was registered at clinicaltrials.gov as NCT00750438.
Differential reward responses during competition against in- and out-of-network others.
Fareri, Dominic S; Delgado, Mauricio R
2014-04-01
Social interactions occur within a variety of different contexts--cooperative/competitive--and often involve members of our social network. Here, we investigated whether social network modulated the value placed on positive outcomes during a competitive context. Eighteen human participants played a simple card-guessing game with three different competitors: a close friend (in-network), a confederate (out-of-network) and a random number generator (non-social condition) while undergoing functional magnetic resonance imaging. Neuroimaging results at the time of outcome receipt demonstrated a significant main effect of competitor across multiple regions of medial prefrontal cortex, with Blood Oxygen Level Dependent (BOLD) responses strongest when competing against one's friend compared with all other conditions. Striatal BOLD responses demonstrated a more general sensitivity to positive compared with negative monetary outcomes, which an exploratory analysis revealed to be stronger when interacting with social, compared with non-social, competitors. Interestingly, a Granger causality analysis indicated directed influences sent from an medial prefrontal cortex (mPFC) region, which shows social network differentiation of outcomes, and the ventral striatum bilaterally. Our results suggest that when competing against others of varying degrees of social network, mPFC differentially values these outcomes, perhaps treating in-network outcomes as more informative, leaving the striatum to more general value computations.
Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Latorre, Valeria; Sambataro, Fabio; Popolizio, Teresa; Nardini, Marcello; Mattay, Venkata S; Weinberger, Daniel R; Bertolino, Alessandro
2010-04-01
Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.
Differential reward responses during competition against in- and out-of-network others
Fareri, Dominic S.
2014-01-01
Social interactions occur within a variety of different contexts––cooperative/competitive––and often involve members of our social network. Here, we investigated whether social network modulated the value placed on positive outcomes during a competitive context. Eighteen human participants played a simple card-guessing game with three different competitors: a close friend (in-network), a confederate (out-of-network) and a random number generator (non-social condition) while undergoing functional magnetic resonance imaging. Neuroimaging results at the time of outcome receipt demonstrated a significant main effect of competitor across multiple regions of medial prefrontal cortex, with Blood Oxygen Level Dependent (BOLD) responses strongest when competing against one’s friend compared with all other conditions. Striatal BOLD responses demonstrated a more general sensitivity to positive compared with negative monetary outcomes, which an exploratory analysis revealed to be stronger when interacting with social, compared with non-social, competitors. Interestingly, a Granger causality analysis indicated directed influences sent from an medial prefrontal cortex (mPFC) region, which shows social network differentiation of outcomes, and the ventral striatum bilaterally. Our results suggest that when competing against others of varying degrees of social network, mPFC differentially values these outcomes, perhaps treating in-network outcomes as more informative, leaving the striatum to more general value computations. PMID:23314007
PARTICLE FILTERING WITH SEQUENTIAL PARAMETER LEARNING FOR NONLINEAR BOLD fMRI SIGNALS.
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.
Dissociation between unconscious motor response facilitation and conflict in medial frontal areas.
D'Ostilio, Kevin; Garraux, Gaëtan
2012-01-01
Masked prime tasks have shown that sensory information that has not been consciously perceived can nevertheless modulate behavior. The neuronal correlates of behavioral manifestations of visuomotor priming remain debated, particularly with respect to the distribution and direction (i.e. increase or decrease) of activity changes in medial frontal areas. Here, we predicted that these discrepant results could be accounted for by two automatic and unconscious processes embedded in this task: response conflict and facilitation. We used event-related functional magnetic resonance imaging (fMRI), as 24 healthy participants had to respond, as fast as possible, to a target arrow presented immediately after a subliminal masked prime arrow. There were three experimental conditions defined by the prime-target relationship: compatible, incompatible, and neutral. The classical visuomotor priming effect was reproduced, with relatively longer reaction times (RTs) in incompatible trials. Longer RTs in incompatible than in neutral trials were specifically associated with stronger blood oxygen level-dependent (BOLD) activity in a conflict-related network comprising the anterior cingulate cortex and right frontal associative areas. Motor response facilitation as shown by shorter RTs in compatible than in neutral trials was associated with reduced activation in a motor preparation network including the medial and lateral premotor cortices, as a result of the repetition suppression of the fMRI BOLD signal. The present results provide new insights into automatic and unconscious visuomotor priming processes, suggesting an involvement of either a cognitive or motor network, depending on the prime-target relationship. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
Infraslow Electroencephalographic and Dynamic Resting State Network Activity.
Grooms, Joshua K; Thompson, Garth J; Pan, Wen-Ju; Billings, Jacob; Schumacher, Eric H; Epstein, Charles M; Keilholz, Shella D
2017-06-01
A number of studies have linked the blood oxygenation level dependent (BOLD) signal to electroencephalographic (EEG) signals in traditional frequency bands (δ, θ, α, β, and γ), but the relationship between BOLD and its direct frequency correlates in the infraslow band (<1 Hz) has been little studied. Previously, work in rodents showed that infraslow local field potentials play a role in functional connectivity, particularly in the dynamic organization of large-scale networks. To examine the relationship between infraslow activity and network dynamics in humans, direct current (DC) EEG and resting state magnetic resonance imaging data were acquired simultaneously. The DC EEG signals were correlated with the BOLD signal in patterns that resembled resting state networks. Subsequent dynamic analysis showed that the correlation between DC EEG and the BOLD signal varied substantially over time, even within individual subjects. The variation in DC EEG appears to reflect the time-varying contribution of different resting state networks. Furthermore, some of the patterns of DC EEG and BOLD correlation are consistent with previous work demonstrating quasiperiodic spatiotemporal patterns of large-scale network activity in resting state. These findings demonstrate that infraslow electrical activity is linked to BOLD fluctuations in humans and that it may provide a basis for large-scale organization comparable to that observed in animal studies.
Infraslow Electroencephalographic and Dynamic Resting State Network Activity
Grooms, Joshua K.; Thompson, Garth J.; Pan, Wen-Ju; Billings, Jacob; Schumacher, Eric H.; Epstein, Charles M.
2017-01-01
Abstract A number of studies have linked the blood oxygenation level dependent (BOLD) signal to electroencephalographic (EEG) signals in traditional frequency bands (δ, θ, α, β, and γ), but the relationship between BOLD and its direct frequency correlates in the infraslow band (<1 Hz) has been little studied. Previously, work in rodents showed that infraslow local field potentials play a role in functional connectivity, particularly in the dynamic organization of large-scale networks. To examine the relationship between infraslow activity and network dynamics in humans, direct current (DC) EEG and resting state magnetic resonance imaging data were acquired simultaneously. The DC EEG signals were correlated with the BOLD signal in patterns that resembled resting state networks. Subsequent dynamic analysis showed that the correlation between DC EEG and the BOLD signal varied substantially over time, even within individual subjects. The variation in DC EEG appears to reflect the time-varying contribution of different resting state networks. Furthermore, some of the patterns of DC EEG and BOLD correlation are consistent with previous work demonstrating quasiperiodic spatiotemporal patterns of large-scale network activity in resting state. These findings demonstrate that infraslow electrical activity is linked to BOLD fluctuations in humans and that it may provide a basis for large-scale organization comparable to that observed in animal studies. PMID:28462586
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 was negatively associated with GLP-1 response to glucose. Post hoc analysis revealed a negative correlation between GLP-1 response to glucose and BOLD response to food cues in the dorsal striatum. Our findings suggest that habitual added sugar intake is related to increased striatal response to food cues and decreased GLP-1 release following glucose intake, which could contribute to susceptibility to overeating. PMID:29403396
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 was negatively associated with GLP-1 response to glucose. Post hoc analysis revealed a negative correlation between GLP-1 response to glucose and BOLD response to food cues in the dorsal striatum. Our findings suggest that habitual added sugar intake is related to increased striatal response to food cues and decreased GLP-1 release following glucose intake, which could contribute to susceptibility to overeating.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gu, Z.; Ching, W.Y.
Based on the Sterne-Inkson model for the self-energy correction to the single-particle energy in the local-density approximation (LDA), we have implemented an approximate energy-dependent and [bold k]-dependent [ital GW] correction scheme to the orthogonalized linear combination of atomic orbital-based local-density calculation for insulators. In contrast to the approach of Jenkins, Srivastava, and Inkson, we evaluate the on-site exchange integrals using the LDA Bloch functions throughout the Brillouin zone. By using a [bold k]-weighted band gap [ital E][sub [ital g
Kannurpatti, Sridhar S; Motes, Michael A; Rypma, Bart; Biswal, Bharat B
2011-07-01
In this report we demonstrate a hemodynamic scaling method with resting-state fluctuation of amplitude (RSFA) in healthy adult younger and older subject groups. We show that RSFA correlated with breath hold (BH) responses throughout the brain in groups of younger and older subjects which RSFA and BH performed comparably in accounting for age-related hemodynamic coupling changes, and yielded more veridical estimates of age-related differences in task-related neural activity. BOLD data from younger and older adults performing motor and cognitive tasks were scaled using RSFA and BH related signal changes. Scaling with RSFA and BH reduced the skew of the BOLD response amplitude distribution in each subject and reduced mean BOLD amplitude and variability in both age groups. Statistically significant differences in intrasubject amplitude variation across regions of activated cortex, and intersubject amplitude variation in regions of activated cortex were observed between younger and older subject groups. Intra- and intersubject variability differences were mitigated after scaling. RSFA, though similar to BH in minimizing skew in the unscaled BOLD amplitude distribution, attenuated the neural activity-related BOLD amplitude significantly less than BH. The amplitude and spatial extent of group activation were lower in the older than in the younger group before and after scaling. After accounting for vascular variability differences through scaling, age-related decreases in activation volume were observed during the motor and cognitive tasks. The results suggest that RSFA-scaled data yield age-related neural activity differences during task performance with negligible effects from non-neural (i.e., vascular) sources. Copyright © 2010 Wiley-Liss, Inc.
Oxytocin modulates hemodynamic responses to monetary incentives in humans
Mickey, Brian J.; Heffernan, Joseph; Heisel, Curtis; Peciña, Marta; Hsu, David T.; Zubieta, Jon-Kar; Love, Tiffany M.
2016-01-01
Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. Here we examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin’s effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans – even in a non-social context – and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry. PMID:27614896
Computational advances towards linking BOLD and behavior.
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.
Barrett, Frederick S; Preller, Katrin H; Herdener, Marcus; Janata, Petr; Vollenweider, Franz X
2017-09-28
Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves.
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
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
Jahnke, Cosima; Gebker, Rolf; Manka, Robert; Schnackenburg, Bernhard; Fleck, Eckart; Paetsch, Ingo
2010-04-01
This study determined the value of navigator-gated 3-dimensional blood oxygen level-dependent (BOLD) cardiac magnetic resonance (CMR) at 3.0-T for the detection of stress-induced myocardial ischemic reactions. Although BOLD CMR has been introduced for characterization of myocardial oxygenation status, previously reported CMR approaches suffered from a low signal-to-noise ratio and motion-related artifacts with impaired image quality and a limited diagnostic value in initial patient studies. Fifty patients with suspected or known coronary artery disease underwent CMR at 3.0-T followed by invasive X-ray angiography within 48 h. Three-dimensional BOLD images were acquired during free breathing with full coverage of the left ventricle in a short-axis orientation. The BOLD imaging was performed at rest and under adenosine stress, followed by stress and rest first-pass perfusion and delayed enhancement imaging. Quantitative coronary X-ray angiography (QCA) was used for coronary stenosis definition (diameter reduction > or =50%). The BOLD and first-pass perfusion images were semiquantitatively evaluated (for BOLD imaging, signal intensity differences between stress and rest [DeltaSI]; for perfusion imaging, myocardial perfusion reserve index [MPRI]). The image quality of BOLD CMR at rest and during adenosine stress was considered good to excellent in 90% and 84% of the patients, respectively. The DeltaSI measurements differed significantly between normal myocardium, myocardium supplied by a stenotic coronary artery, and infarcted myocardium (p < 0.001). The receiver-operator characteristic analysis identified a cutoff value of DeltaSI = 2.7% for the detection of coronary stenosis, resulting in a sensitivity and specificity of 85.0% and 80.5%, respectively. An MPRI cutoff value of 1.35 yielded a sensitivity and specificity of 89.5% and 85.8%, respectively. The DeltaSI significantly correlated with the degree of coronary stenosis (r = -0.65, p < 0.001). Additionally, DeltaSI and MPRI showed substantial agreement (kappa value 0.66). Navigator-gated 3-dimensional BOLD imaging at 3.0-T reliably detected stress-induced myocardial ischemic reactions and may be considered a valid alternative to first-pass exogenous contrast-enhancement studies. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Personality-dependent dispersal cancelled under predation risk
Cote, Julien; Fogarty, Sean; Tymen, Blaise; Sih, Andrew; Brodin, Tomas
2013-01-01
Dispersal is a fundamental life-history trait for many ecological processes. Recent studies suggest that dispersers, in comparison to residents, display various phenotypic specializations increasing their dispersal inclination or success. Among them, dispersers are believed to be consistently more bold, exploratory, asocial or aggressive than residents. These links between behavioural types and dispersal should vary with the cause of dispersal. However, with the exception of one study, personality-dependent dispersal has not been studied in contrasting environments. Here, we used mosquitofish (Gambusia affinis) to test whether personality-dependent dispersal varies with predation risk, a factor that should induce boldness or sociability-dependent dispersal. Corroborating previous studies, we found that dispersing mosquitofish are less social than non-dispersing fish when there was no predation risk. However, personality-dependent dispersal is negated under predation risk, dispersers having similar personality types to residents. Our results suggest that adaptive dispersal decisions could commonly depend on interactions between phenotypes and ecological contexts. PMID:24197414
Alavash, Mohsen; Lim, Sung-Joo; Thiel, Christiane; Sehm, Bernhard; Deserno, Lorenz; Obleser, Jonas
2018-05-15
Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. However, how dopamine modulates the large-scale cortical dynamics during cognitive performance has remained elusive. Using functional MRI during a working memory task in healthy young human listeners, we investigated the effect of levodopa (l-dopa) on two aspects of cortical dynamics, blood oxygen-level-dependent (BOLD) signal variability and the functional connectome of large-scale cortical networks. We here show that enhanced dopaminergic signaling modulates the two potentially interrelated aspects of large-scale cortical dynamics during cognitive performance, and the degree of these modulations is able to explain inter-individual differences in l-dopa-induced behavioral benefits. Relative to placebo, l-dopa increased BOLD signal variability in task-relevant temporal, inferior frontal, parietal and cingulate regions. On the connectome level, however, l-dopa diminished functional integration across temporal and cingulo-opercular regions. This hypo-integration was expressed as a reduction in network efficiency and modularity in more than two thirds of the participants and to different degrees. Hypo-integration co-occurred with relative hyper-connectivity in paracentral lobule and precuneus, as well as posterior putamen. Both, l-dopa-induced BOLD signal variability modulation and functional connectome modulations proved predictive of an individual's l-dopa-induced benefits in behavioral performance, namely response speed and perceptual sensitivity. Lastly, l-dopa-induced modulations of BOLD signal variability were correlated with l-dopa-induced modulation of nodal connectivity and network efficiency. Our findings underline the role of dopamine in maintaining the dynamic range of, and communication between, cortical systems, and their explanatory power for inter-individual differences in benefits from dopamine during cognitive performance. Copyright © 2018 Elsevier Inc. All rights reserved.
Tousseyn, Simon; Dupont, Patrick; Goffin, Karolien; Sunaert, Stefan; Van Paesschen, Wim
2014-01-01
There is currently a lack of knowledge about electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) specificity. Our aim was to define sensitivity and specificity of blood oxygen level dependent (BOLD) responses to interictal epileptic spikes during EEG-fMRI for detecting the ictal onset zone (IOZ). We studied 21 refractory focal epilepsy patients who had a well-defined IOZ after a full presurgical evaluation and interictal spikes during EEG-fMRI. Areas of spike-related BOLD changes overlapping the IOZ in patients were considered as true positives; if no overlap was found, they were treated as false-negatives. Matched healthy case-controls had undergone similar EEG-fMRI in order to determine true-negative and false-positive fractions. The spike-related regressor of the patient was used in the design matrix of the healthy case-control. Suprathreshold BOLD changes in the brain of controls were considered as false positives, absence of these changes as true negatives. Sensitivity and specificity were calculated for different statistical thresholds at the voxel level combined with different cluster size thresholds and represented in receiver operating characteristic (ROC)-curves. Additionally, we calculated the ROC-curves based on the cluster containing the maximal significant activation. We achieved a combination of 100% specificity and 62% sensitivity, using a Z-threshold in the interval 3.4–3.5 and cluster size threshold of 350 voxels. We could obtain higher sensitivity at the expense of specificity. Similar performance was found when using the cluster containing the maximal significant activation. Our data provide a guideline for different EEG-fMRI settings with their respective sensitivity and specificity for detecting the IOZ. The unique cluster containing the maximal significant BOLD activation was a sensitive and specific marker of the IOZ. PMID:25101049
The Effect of Opioid Receptor Blockade on the Neural Processing of Thermal Stimuli
Schoell, Eszter D.; Bingel, Ulrike; Eippert, Falk; Yacubian, Juliana; Christiansen, Kerrin; Andresen, Hilke; May, Arne; Buechel, Christian
2010-01-01
The endogenous opioid system represents one of the principal systems in the modulation of pain. This has been demonstrated in studies of placebo analgesia and stress-induced analgesia, where anti-nociceptive activity triggered by pain itself or by cognitive states is blocked by opioid antagonists. The aim of this study was to characterize the effect of opioid receptor blockade on the physiological processing of painful thermal stimulation in the absence of cognitive manipulation. We therefore measured BOLD (blood oxygen level dependent) signal responses and intensity ratings to non-painful and painful thermal stimuli in a double-blind, cross-over design using the opioid receptor antagonist naloxone. On the behavioral level, we observed an increase in intensity ratings under naloxone due mainly to a difference in the non-painful stimuli. On the neural level, painful thermal stimulation was associated with a negative BOLD signal within the pregenual anterior cingulate cortex, and this deactivation was abolished by naloxone. PMID:20811582
Cohen, Alexander D; Nencka, Andrew S; Lebel, R Marc; Wang, Yang
2017-01-01
A novel sequence has been introduced that combines multiband imaging with a multi-echo acquisition for simultaneous high spatial resolution pseudo-continuous arterial spin labeling (ASL) and blood-oxygenation-level dependent (BOLD) echo-planar imaging (MBME ASL/BOLD). Resting-state connectivity in healthy adult subjects was assessed using this sequence. Four echoes were acquired with a multiband acceleration of four, in order to increase spatial resolution, shorten repetition time, and reduce slice-timing effects on the ASL signal. In addition, by acquiring four echoes, advanced multi-echo independent component analysis (ME-ICA) denoising could be employed to increase the signal-to-noise ratio (SNR) and BOLD sensitivity. Seed-based and dual-regression approaches were utilized to analyze functional connectivity. Cerebral blood flow (CBF) and BOLD coupling was also evaluated by correlating the perfusion-weighted timeseries with the BOLD timeseries. These metrics were compared between single echo (E2), multi-echo combined (MEC), multi-echo combined and denoised (MECDN), and perfusion-weighted (PW) timeseries. Temporal SNR increased for the MECDN data compared to the MEC and E2 data. Connectivity also increased, in terms of correlation strength and network size, for the MECDN compared to the MEC and E2 datasets. CBF and BOLD coupling was increased in major resting-state networks, and that correlation was strongest for the MECDN datasets. These results indicate our novel MBME ASL/BOLD sequence, which collects simultaneous high-resolution ASL/BOLD data, could be a powerful tool for detecting functional connectivity and dynamic neurovascular coupling during the resting state. The collection of more than two echoes facilitates the use of ME-ICA denoising to greatly improve the quality of resting state functional connectivity MRI.
Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation.
Licata, Stephanie C; Lowen, Steven B; Trksak, George H; Maclean, Robert R; Lukas, Scott E
2011-08-15
Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABA(A) receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem's modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABA(A) receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. Copyright © 2011 Elsevier Inc. All rights reserved.
Effect of sound intensity on tonotopic fMRI maps in the unanesthetized monkey.
Tanji, Kazuyo; Leopold, David A; Ye, Frank Q; Zhu, Charles; Malloy, Megan; Saunders, Richard C; Mishkin, Mortimer
2010-01-01
The monkey's auditory cortex includes a core region on the supratemporal plane (STP) made up of the tonotopically organized areas A1, R, and RT, together with a surrounding belt and a lateral parabelt region. The functional studies that yielded the tonotopic maps and corroborated the anatomical division into core, belt, and parabelt typically used low-amplitude pure tones that were often restricted to threshold-level intensities. Here we used functional magnetic resonance imaging in awake rhesus monkeys to determine whether, and if so how, the tonotopic maps and the pattern of activation in core, belt, and parabelt are affected by systematic changes in sound intensity. Blood oxygenation level-dependent (BOLD) responses to groups of low- and high-frequency pure tones 3-4 octaves apart were measured at multiple sound intensity levels. The results revealed tonotopic maps in the auditory core that reversed at the putative areal boundaries between A1 and R and between R and RT. Although these reversals of the tonotopic representations were present at all intensity levels, the lateral spread of activation depended on sound amplitude, with increasing recruitment of the adjacent belt areas as the intensities increased. Tonotopic organization along the STP was also evident in frequency-specific deactivation (i.e. "negative BOLD"), an effect that was intensity-specific as well. Regions of positive and negative BOLD were spatially interleaved, possibly reflecting lateral inhibition of high-frequency areas during activation of adjacent low-frequency areas, and vice versa. These results, which demonstrate the strong influence of tonal amplitude on activation levels, identify sound intensity as an important adjunct parameter for mapping the functional architecture of auditory cortex.
Jerome, Neil P; Boult, Jessica K R; Orton, Matthew R; d'Arcy, James; Collins, David J; Leach, Martin O; Koh, Dow-Mu; Robinson, Simon P
2016-10-03
To investigate the combined use of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) and blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) to assess rat renal function using a 1.5T clinical platform. Multiple b-value DW and BOLD MR images were acquired from adult rats using a parallel clinical coil arrangement, enabling quantitation of the apparent diffusion coefficient (ADC), IVIM-derived diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f), and the transverse relaxation time T 2 *, for whole kidney, renal cortex, and medulla. Following the acquisition of two baseline datasets to assess measurement repeatability, images were acquired following i.v. administration of hydralazine, furosemide, or angiotensin II for up to 40 min. Excellent repeatability (CoV <10 %) was observed for ADC, D, f and T 2 * measured over the whole kidney. Hydralazine induced a marked and significant (p < 0.05) reduction in whole kidney ADC, D, and T 2 *, and a significant (p < 0.05) increase in D* and f. Furosemide significantly (p < 0.05) increased whole kidney ADC, D, and T 2 *. A more variable response to angiotensin II was determined, with a significant (p < 0.05) increase in medulla D* and significant (p < 0.05) reduction in whole kidney T 2 * established. Multiparametric MRI, incorporating quantitation of IVIM DWI and BOLD biomarkers and performed on a clinical platform, can be used to monitor the acute effects of vascular and tubular modulating drugs on rat kidney function in vivo. Clinical adoption of such functional imaging biomarkers can potentially inform on treatment effects in patients with renal dysfunction.
van der Bel, René; Coolen, Bram F; Nederveen, Aart J; Potters, Wouter V; Verberne, Hein J; Vogt, Liffert; Stroes, Erik S G; Krediet, C T Paul
2016-03-28
The role of kidney hypoxia is considered pivotal in the progression of chronic kidney disease. A widely used method to assess kidney oxygenation is blood oxygen level dependent (BOLD)-magnetic resonance imaging (MRI), but its interpretation remains problematic. The BOLD-MRI signal is the result of kidney oxygen consumption (a proxy of glomerular filtration) and supply (ie, glomerular perfusion). Therefore, we hypothesized that with pharmacological modulation of kidney blood flow, renal oxygenation, as assessed by BOLD-MRI, correlates to filtration fraction (ie, glomerular filtration rate/effective renal plasma flow) in healthy humans. Eight healthy volunteers were subjected to continuous angiotensin-II infusion at 0.3, 0.9, and 3.0 ng/kg per minute. At each dose, renal oxygenation and blood flow were assessed using BOLD and phase-contrast MRI. Subsequently, "gold standard" glomerular filtration rate/effective renal plasma flow measurements were performed under the same conditions. Renal plasma flow decreased dose dependently from 660±146 to 467±103 mL/min per 1.73 m(2) (F[3, 21]=33.3, P<0.001). Glomerular filtration rate decreased from 121±23 to 110±18 mL/min per 1.73 m(2) (F[1.8, 2.4]=6.4, P=0.013). Cortical transverse relaxation rate (R2*; increases in R2* represent decreases in oxygenation) increased by 7.2±3.8% (F[3, 21]=7.37, P=0.001); medullar R2* did not change. Cortical R2* related to filtration fraction (R(2) 0.46, P<0.001). By direct comparison between "gold standard" kidney function measurements and BOLD MRI, we showed that cortical oxygenation measured by BOLD MRI relates poorly to glomerular filtration rate but is associated with filtration fraction. For future studies, there may be a need to include renal plasma flow measurements when employing renal BOLD-MRI. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Notohamiprodjo, Mike; Staehler, Michael; Steiner, Nicole; Schwab, Felix; Sourbron, Steven P; Michaely, Henrik J; Helck, Andreas D; Reiser, Maximilian F; Nikolaou, Konstantin
2013-06-01
To investigate a multiparametric magnetic resonance imaging (MRI) approach comprising diffusion-weighted imaging (DWI), blood oxygen-dependent (BOLD), and dynamic contrast-enhanced (DCE) MRI for characterization and differentiation of primary renal cell carcinoma (RCC). Fourteen patients with clear-cell carcinoma and four patients with papillary RCC were examined with DWI, BOLD MRI, and DCE MRI at 1.5T. The apparent diffusion coefficient (ADC) was calculated with a monoexponential decay. The spin-dephasing rate R2* was derived from parametric R2* maps. DCE-MRI was analyzed using a two-compartment exchange model allowing separation of perfusion (plasma flow [FP] and plasma volume [VP]), permeability (permeability surface area product [PS]), and extravascular extracellular volume (VE). Statistical analysis was performed with Wilcoxon signed-rank test, Pearson's correlation coefficient, and receiver operating characteristic curve analysis. Clear-cell RCC showed higher ADC and lower R2* compared to papillary subtypes, but differences were not significant. FP of clear-cell subtypes was significantly higher than in papillary RCC. Perfusion parameters showed moderate but significant inverse correlation with R2*. VE showed moderate inverse correlation with ADC. Fp and Vp showed best sensitivity for histological differentiation. Multiparametric MRI comprising DWI, BOLD, and DCE MRI is feasible for assessment of primary RCC. BOLD moderately correlates to DCE MRI-derived perfusion. ADC shows moderate correlation to the extracellular volume, but does not correlate to tumor oxygenation or perfusion. In this preliminary study DCE-MRI appeared superior to BOLD and DWI for histological differentiation. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.
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.
Talanow, Tobias; Kasparbauer, Anna-Maria; Steffens, Maria; Meyhöfer, Inga; Weber, Bernd; Smyrnis, Nikolaos; Ettinger, Ulrich
2016-08-01
The antisaccade task is a prominent tool to investigate the response inhibition component of cognitive control. Recent theoretical accounts explain performance in terms of parallel programming of exogenous and endogenous saccades, linked to the horse race metaphor. Previous studies have tested the hypothesis of competing saccade signals at the behavioral level by selectively slowing the programming of endogenous or exogenous processes e.g. by manipulating the probability of antisaccades in an experimental block. To gain a better understanding of inhibitory control processes in parallel saccade programming, we analyzed task-related eye movements and blood oxygenation level dependent (BOLD) responses obtained using functional magnetic resonance imaging (fMRI) at 3T from 16 healthy participants in a mixed antisaccade and prosaccade task. The frequency of antisaccade trials was manipulated across blocks of high (75%) and low (25%) antisaccade frequency. In blocks with high antisaccade frequency, antisaccade latencies were shorter and error rates lower whilst prosaccade latencies were longer and error rates were higher. At the level of BOLD, activations in the task-related saccade network (left inferior parietal lobe, right inferior parietal sulcus, left precentral gyrus reaching into left middle frontal gyrus and inferior frontal junction) and deactivations in components of the default mode network (bilateral temporal cortex, ventromedial prefrontal cortex) compensated increased cognitive control demands. These findings illustrate context dependent mechanisms underlying the coordination of competing decision signals in volitional gaze control. Copyright © 2016 Elsevier Inc. All rights reserved.
Dual-echo ASL based assessment of motor networks: a feasibility study
NASA Astrophysics Data System (ADS)
Storti, Silvia Francesca; Boscolo Galazzo, Ilaria; Pizzini, Francesca B.; Menegaz, Gloria
2018-04-01
Objective. Dual-echo arterial spin labeling (DE-ASL) technique has been recently proposed for the simultaneous acquisition of ASL and blood-oxygenation-level-dependent (BOLD)-functional magnetic resonance imaging (fMRI) data. The assessment of this technique in detecting functional connectivity at rest or during motor and motor imagery tasks is still unexplored both per-se and in comparison with conventional methods. The purpose is to quantify the sensitivity of the DE-ASL sequence with respect to the conventional fMRI sequence (cvBOLD) in detecting brain activations, and to assess and compare the relevance of node features in decoding the network structure. Approach. Thirteen volunteers were scanned acquiring a pseudo-continuous DE-ASL sequence from which the concomitant BOLD (ccBOLD) simultaneously to the ASL can be extracted. The approach consists of two steps: (i) model-based analyses for assessing brain activations at individual and group levels, followed by statistical analysis for comparing the activation elicited by the three sequences under two conditions (motor and motor imagery), respectively; (ii) brain connectivity graph-theoretical analysis for assessing and comparing the network models properties. Main results. Our results suggest that cvBOLD and ccBOLD have comparable sensitivity in detecting the regions involved in the active task, whereas ASL offers a higher degree of co-localization with smaller activation volumes. The connectivity results and the comparative analysis of node features across sequences revealed that there are no strong changes between rest and tasks and that the differences between the sequences are limited to few connections. Significance. Considering the comparable sensitivity of the ccBOLD and cvBOLD sequences in detecting activated brain regions, the results demonstrate that DE-ASL can be successfully applied in functional studies allowing to obtain both ASL and BOLD information within a single sequence. Further, DE-ASL is a powerful technique for research and clinical applications allowing to perform quantitative comparisons as well as to characterize functional connectivity.
Murphy, Matthew C; Poplawsky, Alexander J; Vazquez, Alberto L; Chan, Kevin C; Kim, Seong-Gi; Fukuda, Mitsuhiro
2016-08-15
Functional MRI (fMRI) is a popular and important tool for noninvasive mapping of neural activity. As fMRI measures the hemodynamic response, the resulting activation maps do not perfectly reflect the underlying neural activity. The purpose of this work was to design a data-driven model to improve the spatial accuracy of fMRI maps in the rat olfactory bulb. This system is an ideal choice for this investigation since the bulb circuit is well characterized, allowing for an accurate definition of activity patterns in order to train the model. We generated models for both cerebral blood volume weighted (CBVw) and blood oxygen level dependent (BOLD) fMRI data. The results indicate that the spatial accuracy of the activation maps is either significantly improved or at worst not significantly different when using the learned models compared to a conventional general linear model approach, particularly for BOLD images and activity patterns involving deep layers of the bulb. Furthermore, the activation maps computed by CBVw and BOLD data show increased agreement when using the learned models, lending more confidence to their accuracy. The models presented here could have an immediate impact on studies of the olfactory bulb, but perhaps more importantly, demonstrate the potential for similar flexible, data-driven models to improve the quality of activation maps calculated using fMRI data. Copyright © 2016 Elsevier Inc. All rights reserved.
Tommasin, Silvia; Mascali, Daniele; Moraschi, Marta; Gili, Tommaso; Assan, Ibrahim Eid; Fratini, Michela; DiNuzzo, Mauro; Wise, Richard G; Mangia, Silvia; Macaluso, Emiliano; Giove, Federico
2018-06-14
Brain activity at rest is characterized by widely distributed and spatially specific patterns of synchronized low-frequency blood-oxygenation level-dependent (BOLD) fluctuations, which correspond to physiologically relevant brain networks. This network behaviour is known to persist also during task execution, yet the details underlying task-associated modulations of within- and between-network connectivity are largely unknown. In this study we exploited a multi-parametric and multi-scale approach to investigate how low-frequency fluctuations adapt to a sustained n-back working memory task. We found that the transition from the resting state to the task state involves a behaviourally relevant and scale-invariant modulation of synchronization patterns within both task-positive and default mode networks. Specifically, decreases of connectivity within networks are accompanied by increases of connectivity between networks. In spite of large and widespread changes of connectivity strength, the overall topology of brain networks is remarkably preserved. We show that these findings are strongly influenced by connectivity at rest, suggesting that the absolute change of connectivity (i.e., disregarding the baseline) may be not the most suitable metric to study dynamic modulations of functional connectivity. Our results indicate that a task can evoke scale-invariant, distributed changes of BOLD fluctuations, further confirming that low frequency BOLD oscillations show a specialized response and are tightly bound to task-evoked activation. Copyright © 2018. Published by Elsevier Inc.
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 and consequences for behavioural interactions. Copyright © 2017 Elsevier B.V. All rights reserved.
How does experience modulate auditory spatial processing in individuals with blindness?
Tao, Qian; Chan, Chetwyn C H; Luo, Yue-jia; Li, Jian-jun; Ting, Kin-hung; Wang, Jun; Lee, Tatia M C
2015-05-01
Comparing early- and late-onset blindness in individuals offers a unique model for studying the influence of visual experience on neural processing. This study investigated how prior visual experience would modulate auditory spatial processing among blind individuals. BOLD responses of early- and late-onset blind participants were captured while performing a sound localization task. The task required participants to listen to novel "Bat-ears" sounds, analyze the spatial information embedded in the sounds, and specify out of 15 locations where the sound would have been emitted. In addition to sound localization, participants were assessed on visuospatial working memory and general intellectual abilities. The results revealed common increases in BOLD responses in the middle occipital gyrus, superior frontal gyrus, precuneus, and precentral gyrus during sound localization for both groups. Between-group dissociations, however, were found in the right middle occipital gyrus and left superior frontal gyrus. The BOLD responses in the left superior frontal gyrus were significantly correlated with accuracy on sound localization and visuospatial working memory abilities among the late-onset blind participants. In contrast, the accuracy on sound localization only correlated with BOLD responses in the right middle occipital gyrus among the early-onset counterpart. The findings support the notion that early-onset blind individuals rely more on the occipital areas as a result of cross-modal plasticity for auditory spatial processing, while late-onset blind individuals rely more on the prefrontal areas which subserve visuospatial working memory.
Kannurpatti, Sridhar S.; Motes, Michael A.; Rypma, Bart; Biswal, Bharat B.
2012-01-01
In this report we demonstrate a hemodynamic scaling method with resting-state fluctuation of amplitude (RSFA) in healthy adult younger and older subject groups. We show that RSFA correlated with breath hold (BH) responses throughout the brain in groups of younger and older subjects, that RSFA and BH performed comparably in accounting for age-related hemodynamic coupling changes, and yielded more veridical estimates of age-related differences in task-related neural activity. BOLD data from younger and older adults performing motor and cognitive tasks were scaled using RSFA and BH related signal changes. Scaling with RSFA and BH reduced the skew of the BOLD response amplitude distribution in each subject and reduced mean BOLD amplitude and variability in both age groups. Statistically significant differences in intra-subject amplitude variation across regions of activated cortex, and inter-subject amplitude variation in regions of activated cortex were observed between younger and older subject groups. Intra- and inter-subject variability differences were mitigated after scaling. RSFA, though similar to BH in minimizing skew in the un-scaled BOLD amplitude distribution, attenuated the neural activity related BOLD amplitude significantly less than BH. The amplitude and spatial extent of group activation were lower in the older than in the younger group prior to and after scaling. After accounting for vascular variability differences through scaling, age-related decreases in activation volume were observed during the motor and cognitive tasks. The results suggest that RSFA-scaled data yield age-related neural activity differences during task performance with negligible effects from non-neural (i.e., vascular) sources. PMID:20665721
Congruence of happy and sad emotion in music and faces modifies cortical audiovisual activation.
Jeong, Jeong-Won; Diwadkar, Vaibhav A; Chugani, Carla D; Sinsoongsud, Piti; Muzik, Otto; Behen, Michael E; Chugani, Harry T; Chugani, Diane C
2011-02-14
The powerful emotion inducing properties of music are well-known, yet music may convey differing emotional responses depending on environmental factors. We hypothesized that neural mechanisms involved in listening to music may differ when presented together with visual stimuli that conveyed the same emotion as the music when compared to visual stimuli with incongruent emotional content. We designed this study to determine the effect of auditory (happy and sad instrumental music) and visual stimuli (happy and sad faces) congruent or incongruent for emotional content on audiovisual processing using fMRI blood oxygenation level-dependent (BOLD) signal contrast. The experiment was conducted in the context of a conventional block-design experiment. A block consisted of three emotional ON periods, music alone (happy or sad music), face alone (happy or sad faces), and music combined with faces where the music excerpt was played while presenting either congruent emotional faces or incongruent emotional faces. We found activity in the superior temporal gyrus (STG) and fusiform gyrus (FG) to be differentially modulated by music and faces depending on the congruence of emotional content. There was a greater BOLD response in STG when the emotion signaled by the music and faces was congruent. Furthermore, the magnitude of these changes differed for happy congruence and sad congruence, i.e., the activation of STG when happy music was presented with happy faces was greater than the activation seen when sad music was presented with sad faces. In contrast, incongruent stimuli diminished the BOLD response in STG and elicited greater signal change in bilateral FG. Behavioral testing supplemented these findings by showing that subject ratings of emotion in faces were influenced by emotion in music. When presented with happy music, happy faces were rated as more happy (p=0.051) and sad faces were rated as less sad (p=0.030). When presented with sad music, happy faces were rated as less happy (p=0.008) and sad faces were rated as sadder (p=0.002). Happy-sad congruence across modalities may enhance activity in auditory regions while incongruence appears to impact the perception of visual affect, leading to increased activation in face processing regions such as the FG. We suggest that greater understanding of the neural bases of happy-sad congruence across modalities can shed light on basic mechanisms of affective perception and experience and may lead to novel insights in the study of emotion regulation and therapeutic use of music. Copyright © 2010 Elsevier Inc. All rights reserved.
Englander, Zachary K; Horenstein, Craig I; Bowden, Stephen G; Chow, Daniel S; Otten, Marc L; Lignelli, Angela; Bruce, Jeffrey N; Canoll, Peter; Grinband, Jack
2018-06-01
Purpose To determine the effect that R132H mutation status of diffuse glioma has on extent of vascular dysregulation and extent of residual blood oxygen level-dependent (BOLD) abnormality after surgical resection. Materials and Methods This study was an institutional review board-approved retrospective analysis of an institutional database of patients, and informed consent was waived. From 2010 to 2017, 39 treatment-naïve patients with diffuse glioma underwent preoperative echo-planar imaging and BOLD functional magnetic resonance imaging. BOLD vascular dysregulation maps were made by identifying voxels with time series similar to tumor and dissimilar to healthy brain. The spatial overlap between tumor and vascular dysregulation was characterized by using the Dice coefficient, and areas of BOLD abnormality outside the tumor margins were quantified as BOLD-only fraction (BOF). Linear regression was used to assess effects of R132H status on the Dice coefficient, BOF, and residual BOLD abnormality after surgical resection. Results When compared with R132H wild-type (R132H-) gliomas, R132H-mutated (R132H+) gliomas showed greater spatial overlap between BOLD abnormality and tumor (mean Dice coefficient, 0.659 ± 0.02 [standard error] for R132H+ and 0.327 ± 0.04 for R132H-; P < .001), less BOLD abnormality beyond the tumor margin (mean BOF, 0.255 ± 0.03 for R132H+ and 0.728 ± 0.04 for R132H-; P < .001), and less postoperative BOLD abnormality (residual fraction, 0.046 ± 0.0047 for R132H+ and 0.397 ± 0.045 for R132H-; P < .001). Receiver operating characteristic curve analysis showed high sensitivity and specificity in the discrimination of R132H+ tumors from R132H- tumors with calculation of both Dice coefficient and BOF (area under the receiver operating characteristic curve, 0.967 and 0.977, respectively). Conclusion R132H mutation status is an important variable affecting the extent of tumor-associated vascular dysregulation and the residual vascular dysregulation after surgical resection. © RSNA, 2018 Online supplemental material is available for this article.
Neural substrate of the late positive potential in emotional processing
Liu, Yuelu; Huang, Haiqing; McGinnis, Menton; Keil, Andreas; Ding, Mingzhou
2012-01-01
The late positive potential (LPP) is a reliable electrophysiological index of emotional perception in humans. Despite years of research the brain structures that contribute to the generation and modulation of LPP are not well understood. Recording EEG and fMRI simultaneously, and applying a recently proposed single-trial ERP analysis method, we addressed the problem by correlating the single-trial LPP amplitude evoked by affective pictures with the blood-oxygen-level-dependent (BOLD) activity. Three results were found. First, relative to neutral pictures, pleasant and unpleasant pictures elicited enhanced LPP, as well as heightened BOLD activity in both visual cortices and emotion-processing structures such as amygdala and prefrontal cortex, consistent with previous findings. Second, the LPP amplitude across three picture categories was significantly correlated with BOLD activity in visual cortices, temporal cortices, amygdala, orbitofrontal cortex, and insula. Third, within each picture category, LPP-BOLD coupling revealed category-specific differences. For pleasant pictures, the LPP amplitude was coupled with BOLD in occipitotemporal junction, medial prefrontal cortex, amygdala, and precuneus, whereas for unpleasant pictures, significant LPP-BOLD correlation was observed in ventrolateral prefrontal cortex, insula, and posterior cingulate cortex. These results suggest that LPP is generated and modulated by an extensive brain network comprised of both cortical and subcortical structures associated with visual and emotional processing and the degree of contribution by each of these structures to the LPP modulation is valence-specific. PMID:23077042
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.
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
The human brain representation of odor identification.
Kjelvik, Grete; Evensmoen, Hallvard R; Brezova, Veronika; Håberg, Asta K
2012-07-01
Odor identification (OI) tests are increasingly used clinically as biomarkers for Alzheimer's disease and schizophrenia. The aim of this study was to directly compare the neuronal correlates to identified odors vs. nonidentified odors. Seventeen females with normal olfactory function underwent a functional magnetic resonance imaging (fMRI) experiment with postscanning assessment of spontaneous uncued OI. An event-related analysis was performed to compare within-subject activity to spontaneously identified vs. nonidentified odors at the whole brain level, and in anatomic and functional regions of interest (ROIs) in the medial temporal lobe (MTL). Parameter estimate values and blood oxygenated level-dependent (BOLD) signal curves for correctly identified and nonidentified odors were derived from functional ROIs in hippocampus, entorhinal, piriform, and orbitofrontal cortices. Number of activated voxels and max parameter estimate values were obtained from anatomic ROIs in the hippocampus and the entorhinal cortex. At the whole brain level the correct OI gave rise to increased activity in the left entorhinal cortex and secondary olfactory structures, including the orbitofrontal cortex. Increased activation was also observed in fusiform, primary visual, and auditory cortices, inferior frontal plus inferior temporal gyri. The anatomic MTL ROI analysis showed increased activation in the left entorhinal cortex, right hippocampus, and posterior parahippocampal gyri in correct OI. In the entorhinal cortex and hippocampus the BOLD signal increased specifically in response to identified odors and decreased for nonidentified odors. In orbitofrontal and piriform cortices both identified and nonidentified odors gave rise to an increased BOLD signal, but the response to identified odors was significantly greater than that for nonidentified odors. These results support a specific role for entorhinal cortex and hippocampus in OI, whereas piriform and orbitofrontal cortices are active in both smelling and OI. Moreover, episodic as well as semantic memory systems appeared to support OI.
Alarcón, Gabriela; Cservenka, Anita; Fair, Damien A; Nagel, Bonnie J
2014-12-17
Adolescence is a developmental period characterized by notable changes in behavior, physical attributes, and an increase in endogenous sex steroid hormones, which may impact cognitive functioning. Moreover, sex differences in brain structure are present, leading to differences in neural function and cognition. Here, we examine sex differences in performance and blood oxygen level-dependent (BOLD) activation in a sample of adolescents during a spatial working memory (SWM) task. We also examine whether endogenous testosterone levels mediate differential brain activity between the sexes. Adolescents between ages 10 and 16 years completed a SWM functional magnetic resonance imaging (fMRI) task, and serum hormone levels were assessed within seven days of scanning. While there were no sex differences in task performance (accuracy and reaction time), differences in BOLD response between girls and boys emerged, with girls deactivating brain regions in the default mode network and boys showing increased response in SWM-related brain regions of the frontal cortex. These results suggest that adolescent boys and girls adopted distinct neural strategies, while maintaining spatial cognitive strategies that facilitated comparable cognitive performance of a SWM task. A nonparametric bootstrapping procedure revealed that testosterone did not mediate sex-specific brain activity, suggesting that sex differences in BOLD activation during SWM may be better explained by other factors, such as early organizational effects of sex steroids or environmental influences. Elucidating sex differences in neural function and the influence of gonadal hormones can serve as a basis of comparison for understanding sexually dimorphic neurodevelopment and inform sex-specific psychopathology that emerges in adolescence. Copyright © 2014 Elsevier B.V. All rights reserved.
The effect of boldness on decision-making in barnacle geese is group-size-dependent
Kurvers, Ralf H. J. M.; Adamczyk, Vena M. A. P.; van Wieren, Sipke E.; Prins, Herbert H. T.
2011-01-01
In group-living species, decisions made by individuals may result in collective behaviours. A central question in understanding collective behaviours is how individual variation in phenotype affects collective behaviours. However, how the personality of individuals affects collective decisions in groups remains poorly understood. Here, we investigated the role of boldness on the decision-making process in different-sized groups of barnacle geese. Naive barnacle geese, differing in boldness score, were introduced in a labyrinth in groups with either one or three informed demonstrators. The demonstrators possessed information about the route through the labyrinth. In pairs, the probability of choosing a route prior to the informed demonstrator increased with increasing boldness score: bolder individuals decided more often for themselves where to go compared with shyer individuals, whereas shyer individuals waited more often for the demonstrators to decide and followed this information. In groups of four individuals, however, there was no effect of boldness on decision-making, suggesting that individual differences were less important with increasing group size. Our experimental results show that personality is important in collective decisions in pairs of barnacle geese, and suggest that bolder individuals have a greater influence over the outcome of decisions in groups. PMID:21123271
The effect of boldness on decision-making in barnacle geese is group-size-dependent.
Kurvers, Ralf H J M; Adamczyk, Vena M A P; van Wieren, Sipke E; Prins, Herbert H T
2011-07-07
In group-living species, decisions made by individuals may result in collective behaviours. A central question in understanding collective behaviours is how individual variation in phenotype affects collective behaviours. However, how the personality of individuals affects collective decisions in groups remains poorly understood. Here, we investigated the role of boldness on the decision-making process in different-sized groups of barnacle geese. Naive barnacle geese, differing in boldness score, were introduced in a labyrinth in groups with either one or three informed demonstrators. The demonstrators possessed information about the route through the labyrinth. In pairs, the probability of choosing a route prior to the informed demonstrator increased with increasing boldness score: bolder individuals decided more often for themselves where to go compared with shyer individuals, whereas shyer individuals waited more often for the demonstrators to decide and followed this information. In groups of four individuals, however, there was no effect of boldness on decision-making, suggesting that individual differences were less important with increasing group size. Our experimental results show that personality is important in collective decisions in pairs of barnacle geese, and suggest that bolder individuals have a greater influence over the outcome of decisions in groups.
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
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.
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.
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.
Generalization of value in reinforcement learning by humans.
Wimmer, G Elliott; Daw, Nathaniel D; Shohamy, Daphna
2012-04-01
Research in decision-making has focused on the role of dopamine and its striatal targets in guiding choices via learned stimulus-reward or stimulus-response associations, behavior that is well described by reinforcement learning theories. However, basic reinforcement learning is relatively limited in scope and does not explain how learning about stimulus regularities or relations may guide decision-making. A candidate mechanism for this type of learning comes from the domain of memory, which has highlighted a role for the hippocampus in learning of stimulus-stimulus relations, typically dissociated from the role of the striatum in stimulus-response learning. Here, we used functional magnetic resonance imaging and computational model-based analyses to examine the joint contributions of these mechanisms to reinforcement learning. Humans performed a reinforcement learning task with added relational structure, modeled after tasks used to isolate hippocampal contributions to memory. On each trial participants chose one of four options, but the reward probabilities for pairs of options were correlated across trials. This (uninstructed) relationship between pairs of options potentially enabled an observer to learn about option values based on experience with the other options and to generalize across them. We observed blood oxygen level-dependent (BOLD) activity related to learning in the striatum and also in the hippocampus. By comparing a basic reinforcement learning model to one augmented to allow feedback to generalize between correlated options, we tested whether choice behavior and BOLD activity were influenced by the opportunity to generalize across correlated options. Although such generalization goes beyond standard computational accounts of reinforcement learning and striatal BOLD, both choices and striatal BOLD activity were better explained by the augmented model. Consistent with the hypothesized role for the hippocampus in this generalization, functional connectivity between the ventral striatum and hippocampus was modulated, across participants, by the ability of the augmented model to capture participants' choice. Our results thus point toward an interactive model in which striatal reinforcement learning systems may employ relational representations typically associated with the hippocampus. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
NASA Astrophysics Data System (ADS)
Cao, Jianbo; An, Hengqing; Huang, Xinglu; Fu, Guifeng; Zhuang, Rongqiang; Zhu, Lei; Xie, Jin; Zhang, Fan
2016-05-01
Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities. Because each modality has its own set of advantages and limitations, there has been interest in developing methods that can co-deliver the two regimens for enhanced tumor treatment. Among the efforts, nano-graphene oxide-mediated phototherapies have recently attracted much attention. Nano-graphene oxide has a broad absorbance spectrum and can be loaded with photosensitizers, such as chlorin e6, with high efficiency. Chlorin e6-loaded and PEGylated nano-graphene (GO-PEG-Ce6) can be excited at 660 nm, 808 nm, or both, to induce PDT, PTT, or PDT/PTT combination. Despite the potential of the treatments, there is a lack of a diagnostic tool which can monitor their therapeutic response in a non-invasive and prognostic manner; such an ability is urgently needed for the transformation and translation of the technologies. In this study, we performed diffusion-weighted and blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) after GO-PEG-Ce6-mediated PTT, PDT, or PTT/PDT. We found that after efficient PTT, there is a significant increase of the tumor apparent diffusion coefficient (ADC) value in diffusion-weighted imaging (DWI) maps; meanwhile, an efficient PDT led to an increase of in BOLD images. In both the cases, the amplitude of the increase was correlated with the treatment outcomes. More interestingly, a synergistic treatment efficacy was observed when the PTT/PDT combination was applied, and the combination was associated with a greater ADC and increase than when either modality was used alone. In particular, the PTT/PDT condition that induced the most dramatic short-term increase of the ADC value (>70%) caused the most effective tumor control in the long-run, with 60% of the treated animals being tumor-free after 60 days. These results suggest the great promise of the combination of DWI and BOLD MRI as a tool for accurate monitoring and prognosis of phototherapies, which is of great value to the future developments of the methodologies.
Clinical utility of BOLD fMRI in preoperative work-up of epilepsy
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
BOLD magnetic resonance imaging in nephrology
Hall, Michael E; Jordan, Jennifer H; Juncos, Luis A; Hundley, W Gregory; Hall, John E
2018-01-01
Magnetic resonance (MR) imaging, a non-invasive modality that provides anatomic and physiologic information, is increasingly used for diagnosis of pathophysiologic conditions and for understanding renal physiology in humans. Although functional MR imaging methods were pioneered to investigate the brain, they also offer powerful techniques for investigation of other organ systems such as the kidneys. However, imaging the kidneys provides unique challenges due to potential complications from contrast agents. Therefore, development of non-contrast techniques to study kidney anatomy and physiology is important. Blood oxygen level-dependent (BOLD) MR is a non-contrast imaging technique that provides functional information related to renal tissue oxygenation in various pathophysiologic conditions. Here we discuss technical considerations, clinical uses and future directions for use of BOLD MR as well as complementary MR techniques to better understand renal pathophysiology. Our intent is to summarize kidney BOLD MR applications for the clinician rather than focusing on the complex physical challenges that functional MR imaging encompasses; however, we briefly discuss some of those issues. PMID:29559807
NASA Astrophysics Data System (ADS)
Amor, T. A.; Russo, R.; Diez, I.; Bharath, P.; Zirovich, M.; Stramaglia, S.; Cortes, J. M.; de Arcangelis, L.; Chialvo, D. R.
2015-09-01
The brain exhibits a wide variety of spatiotemporal patterns of neuronal activity recorded using functional magnetic resonance imaging as the so-called blood-oxygenated-level-dependent (BOLD) signal. An active area of work includes efforts to best describe the plethora of these patterns evolving continuously in the brain. Here we explore the third-moment statistics of the brain BOLD signals in the resting state as a proxy to capture extreme BOLD events. We find that the brain signal exhibits typically nonzero skewness, with positive values for cortical regions and negative values for subcortical regions. Furthermore, the combined analysis of structural and functional connectivity demonstrates that relatively more connected regions exhibit activity with high negative skewness. Overall, these results highlight the relevance of recent results emphasizing that the spatiotemporal location of the relatively large-amplitude events in the BOLD time series contains relevant information to reproduce a number of features of the brain dynamics during resting state in health and disease.
Heritability of boldness and aggressiveness in the zebrafish.
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.
Individual personality differences in Port Jackson sharks Heterodontus portusjacksoni.
Byrnes, E E; Brown, C
2016-08-01
This study examined interindividual personality differences between Port Jackson sharks Heterodontus portusjacksoni utilizing a standard boldness assay. Additionally, the correlation between differences in individual boldness and stress reactivity was examined, exploring indications of individual coping styles. Heterodontus portusjacksoni demonstrated highly repeatable individual differences in boldness and stress reactivity. Individual boldness scores were highly repeatable across four trials such that individuals that were the fastest to emerge in the first trial were also the fastest to emerge in subsequent trials. Additionally, individuals that were the most reactive to a handling stressor in the first trial were also the most reactive in a second trial. The strong link between boldness and stress response commonly found in teleosts was also evident in this study, providing evidence of proactive-reactive coping styles in H. portusjacksoni. These results demonstrate the presence of individual personality differences in sharks for the first time. Understanding how personality influences variation in elasmobranch behaviour such as prey choice, habitat use and activity levels is critical to better managing these top predators which play important ecological roles in marine ecosystems. © 2016 The Fisheries Society of the British Isles.
Victor, Teresa A; Furey, Maura L; Fromm, Stephen J; Bellgowan, Patrick S F; Öhman, Arne; Drevets, Wayne C
2012-01-01
Major depressive disorder (MDD) is associated with a mood-congruent processing bias in the amygdala toward face stimuli portraying sad expressions that is evident even when such stimuli are presented below the level of conscious awareness. The extended functional anatomical network that maintains this response bias has not been established, however. To identify neural network differences in the hemodynamic response to implicitly presented facial expressions between depressed and healthy control participants. Unmedicated-depressed participants with MDD (n=22) and healthy controls (HC; n=25) underwent functional MRI as they viewed face stimuli showing sad, happy or neutral face expressions, presented using a backward masking design. The blood-oxygen-level dependent (BOLD) signal was measured to identify regions where the hemodynamic response to the emotionally valenced stimuli differed between groups. The MDD subjects showed greater BOLD responses than the controls to masked-sad versus masked-happy faces in the hippocampus, amygdala and anterior inferotemporal cortex. While viewing both masked-sad and masked-happy faces relative to masked-neutral faces, the depressed subjects showed greater hemodynamic responses than the controls in a network that included the medial and orbital prefrontal cortices and anterior temporal cortex. Depressed and healthy participants showed distinct hemodynamic responses to masked-sad and masked-happy faces in neural circuits known to support the processing of emotionally valenced stimuli and to integrate the sensory and visceromotor aspects of emotional behavior. Altered function within these networks in MDD may establish and maintain illness-associated differences in the salience of sensory/social stimuli, such that attention is biased toward negative and away from positive stimuli.
Effects of acute alcohol intoxication on saccadic conflict and error processing.
Marinkovic, Ksenija; Rickenbacher, Elizabeth; Azma, Sheeva; Artsy, Elinor; Lee, Adrian K C
2013-12-01
Flexible behavior optimization relies on cognitive control which includes the ability to suppress automatic responses interfering with relevant goals. Extensive evidence suggests that the anterior cingulate cortex (ACC) is the central node in a predominantly frontal cortical network subserving executive tasks. Neuroimaging studies indicate that the ACC is sensitive to acute intoxication during conflict, but such evidence is limited to tasks using manual responses with arbitrary response contingencies. The present study was designed to examine whether alcohol's effects on top-down cognitive control would generalize to the oculomotor system during inhibition of hardwired saccadic responses. Healthy social drinkers (N = 22) underwent functional magnetic resonance imaging (fMRI) scanning and eye movement tracking during alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. They performed visually guided prosaccades (PS) towards a target and volitional antisaccades (AS) away from it. To mitigate possible vasoactive effects of alcohol on the BOLD (blood oxygenation level-dependent) signal, resting perfusion was quantified with arterial spin labeling (ASL) and used as a covariate in the BOLD analysis. Saccadic conflict was subserved by a distributed frontoparietal network. However, alcohol intoxication selectively attenuated activity only in the ACC to volitional AS and erroneous responses. This study provides converging evidence for the selective ACC vulnerability to alcohol intoxication during conflict across different response modalities and executive tasks, confirming its supramodal, high-level role in cognitive control. Alcohol intoxication may impair top-down regulative functions by attenuating the ACC activity, resulting in behavioral disinhibition and decreased self-control.
Functional MR imaging assessment of a non-responsive brain injured patient.
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.
Lipp, Ilona; Murphy, Kevin; Caseras, Xavier; Wise, Richard G
2015-06-01
FMRI BOLD responses to changes in neural activity are influenced by the reactivity of the vasculature. By complementing a task-related BOLD acquisition with a vascular reactivity measure obtained through breath-holding or hypercapnia, this unwanted variance can be statistically reduced in the BOLD responses of interest. Recently, it has been suggested that vascular reactivity can also be estimated using a resting state scan. This study aimed to compare three breath-hold based analysis approaches (block design, sine-cosine regressor and CO2 regressor) and a resting state approach (CO2 regressor) to measure vascular reactivity. We tested BOLD variance explained by the model and repeatability of the measures. Fifteen healthy participants underwent a breath-hold task and a resting state scan with end-tidal CO2 being recorded during both. Vascular reactivity was defined as CO2-related BOLD percent signal change/mmHg change in CO2. Maps and regional vascular reactivity estimates showed high repeatability when the breath-hold task was used. Repeatability and variance explained by the CO2 trace regressor were lower for the resting state data based approach, which resulted in highly variable measures of vascular reactivity. We conclude that breath-hold based vascular reactivity estimations are more repeatable than resting-based estimates, and that there are limitations with replacing breath-hold scans by resting state scans for vascular reactivity assessment. Copyright © 2015. Published by Elsevier Inc.
Activation of Neural Pathways Associated with Sexual Arousal in Non-Human Primates
Ferris, Craig F.; Snowdon, Charles T.; King, Jean A.; Sullivan, John M.; Ziegler, Toni E.; Olson, David P.; Schultz-Darken, Nancy J.; Tannenbaum, Pamela L.; Ludwig, Reinhold; Wu, Ziji; Einspanier, Almuth; Vaughan, J. Thomas; Duong, Timothy Q.
2006-01-01
Purpose To evaluate brain activity associated with sexual arousal, fully conscious male marmoset monkeys were imaged during presentation of odors that naturally elicit high levels of sexual activity and sexual motivation. Material and Methods Male monkeys were lightly anesthetized, secured in a head and body restrainer with a built-in birdcage resonator and positioned in a 9.4-Tesla spectrometer. When fully conscious, monkeys were presented with the odors of a novel receptive female or an ovariectomized monkey. Both odors were presented during an imaging trial and the presentation of odors was counterbalanced. Significant changes in both positive and negative BOLD signal were mapped and averaged. Results Periovulatory odors significantly increased positive BOLD signal in several cortical areas: the striatum, hippocampus, septum, periaqueductal gray, and cerebellum, in comparison with odors from ovariectomized monkeys. Conversely, negative BOLD signal was significantly increased in the temporal cortex, cingulate cortex, putamen, hippocampus, substantia nigra, medial preoptic area, and cerebellum with presentation of odors from ovariectomized marmosets as compared to periovulatory odors. A common neural circuit comprising the temporal and cingulate cortices, putamen, hippocampus, medial preoptic area, and cerebellum shared both the positive BOLD response to periovulatory odors and the negative BOLD response to odors of ovariectomized females. Conclusion These data suggest the odor-driven enhancement and suppression of sexual arousal affect neuronal activity in many of the same general brain areas. These areas included not only those associated with sexual activity, but also areas involved in emotional processing and reward. PMID:14745749
Lipp, Ilona; Murphy, Kevin; Caseras, Xavier; Wise, Richard G.
2015-01-01
FMRI BOLD responses to changes in neural activity are influenced by the reactivity of the vasculature. By complementing a task-related BOLD acquisition with a vascular reactivity measure obtained through breath-holding or hypercapnia, this unwanted variance can be statistically reduced in the BOLD responses of interest. Recently, it has been suggested that vascular reactivity can also be estimated using a resting state scan. This study aimed to compare three breath-hold based analysis approaches (block design, sine–cosine regressor and CO2 regressor) and a resting state approach (CO2 regressor) to measure vascular reactivity. We tested BOLD variance explained by the model and repeatability of the measures. Fifteen healthy participants underwent a breath-hold task and a resting state scan with end-tidal CO2 being recorded during both. Vascular reactivity was defined as CO2-related BOLD percent signal change/mm Hg change in CO2. Maps and regional vascular reactivity estimates showed high repeatability when the breath-hold task was used. Repeatability and variance explained by the CO2 trace regressor were lower for the resting state data based approach, which resulted in highly variable measures of vascular reactivity. We conclude that breath-hold based vascular reactivity estimations are more repeatable than resting-based estimates, and that there are limitations with replacing breath-hold scans by resting state scans for vascular reactivity assessment. PMID:25795342
Safford, Ashley S; Hussey, Elizabeth A; Parasuraman, Raja; Thompson, James C
2010-07-07
Although it is well documented that the ability to perceive biological motion is mediated by the lateral temporal cortex, whether and when neural activity in this brain region is modulated by attention is unknown. In particular, it is unclear whether the processing of biological motion requires attention or whether such stimuli are processed preattentively. Here, we used functional magnetic resonance imaging, high-density electroencephalography, and cortically constrained source estimation methods to investigate the spatiotemporal effects of attention on the processing of biological motion. Directing attention to tool motion in overlapping movies of biological motion and tool motion suppressed the blood oxygenation level-dependent (BOLD) response of the right superior temporal sulcus (STS)/middle temporal gyrus (MTG), while directing attention to biological motion suppressed the BOLD response of the left inferior temporal sulcus (ITS)/MTG. Similarly, category-based modulation of the cortical current source density estimates from the right STS/MTG and left ITS was observed beginning at approximately 450 ms following stimulus onset. Our results indicate that the cortical processing of biological motion is strongly modulated by attention. These findings argue against preattentive processing of biological motion in the presence of stimuli that compete for attention. Our findings also suggest that the attention-based segregation of motion category-specific responses only emerges relatively late (several hundred milliseconds) in processing.
Express yourself: bold individuals induce enhanced morphological defences
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
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.
Investigating the dependence of BOLD contrast on oxidative metabolism.
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.
Fierstra, Jorn; Burkhardt, Jan-Karl; van Niftrik, Christiaan Hendrik Bas; Piccirelli, Marco; Pangalu, Athina; Kocian, Roman; Neidert, Marian Christoph; Valavanis, Antonios; Regli, Luca; Bozinov, Oliver
2017-02-01
To assess the feasibility of functional blood oxygen-level dependent (BOLD) MRI to evaluate intraoperative cerebrovascular reactivity (CVR) at 3 Tesla field strength. Ten consecutive neurosurgical subjects scheduled for a clinical intraoperative MRI examination were enrolled in this study. In addition to the clinical protocol a BOLD sequence was implemented with three cycles of 44 s apnea to calculate CVR values on a voxel-by-voxel basis throughout the brain. The CVR range was then color-coded and superimposed on an anatomical volume to create high spatial resolution CVR maps. Ten subjects (mean age 34.8 ± 13.4; 2 females) uneventfully underwent the intraoperative BOLD protocol, with no complications occurring. Whole-brain CVR for all subjects was (mean ± SD) 0.69 ± 0.42, whereas CVR was markedly higher for tumor subjects as compared to vascular subjects, 0.81 ± 0.44 versus 0.33 ± 0.10, respectively. Furthermore, color-coded functional maps could be robustly interpreted for a whole-brain assessment of CVR. We demonstrate that intraoperative BOLD MRI is feasible in creating functional maps to assess cerebrovascular reactivity throughout the brain in subjects undergoing a neurosurgical procedure. Magn Reson Med 77:806-813, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.
Influence of Alcohol Use on Neural Response to Go/No-Go Task in College Drinkers
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
Semantic processing and response inhibition.
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.
Szczepanik, Joanna; Nugent, Allison C; Drevets, Wayne C; Khanna, Ashish; Zarate, Carlos A; Furey, Maura L
2016-08-30
The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Boldness in two perch populations - long-term differences and the effect of predation pressure.
Magnhagen, Carin; Hellström, Gustav; Borcherding, Jost; Heynen, Martina
2012-11-01
1. Populations of the same species often display different behaviours, for example, in their response to predators. The question is whether this difference is developed as part of a divergent selection caused by differences in predation pressure, or as a result of phenotypic responses to current environmental conditions. 2. Two populations of Eurasian perch were investigated over a time span of 6 years to see whether risk-taking behaviour in young-of-the-year perch were consistent across cohorts, or if behaviour varied over time with changes in predation regime. 3. Boldness was estimated in aquarium studies by looking at how the fish made trade-offs between foraging in a risky area and staying in shelter. Predation risk of each year and lake was estimated from fishing surveys, using an individual-based model calculating attack rates for cannibalistic perch. 4. The average boldness scores were consistently lower in perch from Fisksjön compared with those in Ängersjön, although the magnitude of the difference varied among years. Variance component analyses showed that differences between lakes in boldness scores only explained 12 per cent of the total variation. Differences between years were contributing at least similarly or more to the total variance, and the variation was higher in Fisksjön than in Ängersjön. 5. The observed risk-taking behaviour of young-of-the-year perch, compared across cohorts, was significantly correlated with the year-specific estimates of cannibalistic attack rates, with lower boldness scores in years with higher predation pressure. In Fisksjön, with significant changes over the years in population structure, the range of both predation risk and boldness scores was wider than in Ängersjön. 6. By following the two perch populations over several years, we have been able to show that the differences in risk-taking behaviour mainly are due to direct phenotypic responses to recent experience of predation risk. Long-term differences in behaviour among perch populations thus reflect consistent differences in predation regime rather than diverging inherent traits. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.
Generate the scale-free brain music from BOLD signals
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
Generate the scale-free brain music from BOLD signals.
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.
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.
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.
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
Aviram-Friedman, Roni; Astbury, Nerys; Ochner, Christopher N; Contento, Isobel; Geliebter, Allan
2018-02-01
To refine the biobehavioral markers of binge eating disorder (BED). We conducted fMRI brain scans using images of high energy processed food (HEPF), low energy unprocessed food (LEUF), or non-foods (NF) in 42 adults (obese with BED [obese -BED; n=13] and obese with no BED [obese non-BED; n=29]) selected via ads. Two blood oxygenated level dependent (BOLD) signal contrast maps were examined: food versus nonfood, and HEPF versus LEUF. In addition, score differences on the disinhibition scale were correlated with BOLD signals. food versus nonfood showed greater BOLD activity for BED in emotional, motivational and somatosensory brain areas: insula, anterior cingulate cortex (ACC), Brodmann areas (BA) 19 & 32, inferior parietal lobule (IPL), posterior cingulate cortex (PCC), and lingual, postcentral, middle temporal and cuneate gyri (p≤0.005; k≥88). HEPF versus LEUF showed greater BOLD activity for BED in inhibitory brain regions: BA 6, middle and superior frontal gyri (p<0.01; k≥119). The groups also differed in the relationships between disinhibition and BOLD activity in the postcentral gyrus (PCG; p=0.04) and ACC-BA 32 (p=0.02). For all participants jointly, PCG BOLD amplitude predicted greater disinhibition (p=0.04). Food images elicited neural activity indicating attention bias (cuneate & PCG), emotion dysregulation (BA 19 & 32), and disinhibition (MFG, BA6 & SFG) in obese with BED. These may help tailor a treatment for the obesity with BED phenotype. Copyright © 2017. Published by Elsevier Inc.
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.
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.
The activity in the anterior insulae is modulated by perceptual decision-making difficulty.
Lamichhane, Bidhan; Adhikari, Bhim M; Dhamala, Mukesh
2016-07-07
Previous neuroimaging studies provide evidence for the involvement of the anterior insulae (INSs) in perceptual decision-making processes. However, how the insular cortex is involved in integration of degraded sensory information to create a conscious percept of environment and to drive our behaviors still remains a mystery. In this study, using functional magnetic resonance imaging (fMRI) and four different perceptual categorization tasks in visual and audio-visual domains, we measured blood oxygen level dependent (BOLD) signals and examined the roles of INSs in easy and difficult perceptual decision-making. We created a varying degree of degraded stimuli by manipulating the task-specific stimuli in these four experiments to examine the effects of task difficulty on insular cortex response. We hypothesized that significantly higher BOLD response would be associated with the ambiguity of the sensory information and decision-making difficulty. In all of our experimental tasks, we found the INS activity consistently increased with task difficulty and participants' behavioral performance changed with the ambiguity of the presented sensory information. These findings support the hypothesis that the anterior insulae are involved in sensory-guided, goal-directed behaviors and their activities can predict perceptual load and task difficulty. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
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.
Fischer, Sarah; Breithaupt, Lauren; Wonderlich, Joseph; Westwater, Margaret L; Crosby, Ross D; Engel, Scott G; Thompson, James; Lavender, Jason; Wonderlich, Stephen
2017-09-01
Women with symptoms of bulimia nervosa (BN) exhibit decreased response to visual food cues in several limbic and frontal regions compared to controls. Stress causes decreased blood oxygenation level dependent (BOLD) response in these regions in non-clinical samples; there is a lack of data on this topic in BN. This study examined the impact of individual differences in neural reactivity to palatable food cues following acute stress on stress-binge trajectories in everyday life. 16 women with BN symptoms viewed palatable food cues prior to and immediately following an acute stress induction in the scanner. Participants then responded to a series of prompts assessing daily ratings of stress and binge episodes for a period of two weeks. Decreased BOLD signal was observed in response to food cues pre to post stress in the anterior cingulate cortex (ACC), amygdala, and ventromedial prefrontal cortex (vmPFC). Ecological momentary assessment data collection demonstrated that stress increased prior to binge episodes in the natural environment, and decreased following. Changes in activation in the ACC, precuneus, and dorsolateral prefrontal cortex (dlPFC) significantly moderated the relationship of stress to binge eating in daily life, such that women who exhibited decreased response reported significantly increasing stress prior to binges, while women who did not exhibit decreases reported no significant change in stress prior to binges. Individual differences in neural response to food cues under stress appear to underlie distinct antecedants to binge eating. Copyright © 2017 Elsevier Ltd. All rights reserved.
Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.
Snel, Marieke; Wijngaarden, Marjolein A; Bizino, Maurice B; van der Grond, Jeroen; Teeuwisse, Wouter M; van Buchem, Mark A; Jazet, Ingrid M; Pijl, Hanno
2012-01-01
Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation. Copyright © 2012 S. Karger AG, Basel.
Novel fMRI working memory paradigm accurately detects cognitive impairment in Multiple Sclerosis
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
Neural correlates of human body perception.
Aleong, Rosanne; Paus, Tomás
2010-03-01
The objective of this study was to investigate potential sex differences in the neural response to human bodies using fMRI carried out in healthy young adults. We presented human bodies in a block-design experiment to identify body-responsive regions of the brain, namely, extrastriate body area (EBA) and fusiform body area (FBA). In a separate event-related "adaptation" experiment, carried out in the same group of subjects, we presented sets of four human bodies of varying body size and shape. Varying levels of body morphing were introduced to assess the degree of morphing required for adaptation release. Analysis of BOLD signal in the block-design experiment revealed significant Sex x Hemisphere interactions in the EBA and the FBA responses to human bodies. Only women showed greater BOLD response to bodies in the right hemisphere compared with the left hemisphere for both EBA and FBA. The BOLD response in right EBA was higher in women compared with men. In the adaptation experiment, greater right versus left hemisphere response for EBA and FBA was also identified among women but not men. These findings are particularly novel in that they address potential sex differences in the lateralization of EBA and FBA responses to human body images. Although previous studies have found some degree of right hemisphere dominance in body perception, our results suggest that such a functional lateralization may differ between men and women.
Age-Dependent Relationships between Prefrontal Cortex Activation and Processing Efficiency
Motes, Michael A.; Biswal, Bharat B.; Rypma, Bart
2012-01-01
fMRI was used in the present study to examine the neural basis for age-related differences in processing efficiency, particularly targeting prefrontal cortex (PFC). During scanning, older and younger participants completed a processing efficiency task in which they determined on each trial whether a symbol-number pair appeared in a simultaneously presented array of nine symbol-number pairs. Estimates of task-related BOLD signal-change were obtained for each participant. These estimates were then correlated with the participants’ performance on the task. For younger participants, BOLD signal-change within PFC decreased with better performance, but for older participants, BOLD signal-change within PFC increased with better performance. The results support the hypothesis that the availability and use of PFC resources mediates age-related changes in processing efficiency. PMID:22792129
Age-Dependent Relationships between Prefrontal Cortex Activation and Processing Efficiency.
Motes, Michael A; Biswal, Bharat B; Rypma, Bart
2011-01-01
fMRI was used in the present study to examine the neural basis for age-related differences in processing efficiency, particularly targeting prefrontal cortex (PFC). During scanning, older and younger participants completed a processing efficiency task in which they determined on each trial whether a symbol-number pair appeared in a simultaneously presented array of nine symbol-number pairs. Estimates of task-related BOLD signal-change were obtained for each participant. These estimates were then correlated with the participants' performance on the task. For younger participants, BOLD signal-change within PFC decreased with better performance, but for older participants, BOLD signal-change within PFC increased with better performance. The results support the hypothesis that the availability and use of PFC resources mediates age-related changes in processing efficiency.
The pathology of social phobia is independent of developmental changes in face processing.
Blair, Karina S; Geraci, Marilla; Korelitz, Katherine; Otero, Marcela; Towbin, Ken; Ernst, Monique; Leibenluft, Ellen; Blair, R J R; Pine, Daniel S
2011-11-01
While social phobia in adolescence predicts the illness in adulthood, no study has directly compared the neural responses in social phobia in adults and adolescents. The authors examined neural responses to facial expressions in adults and adolescents with social phobia to determine whether the neural correlates of adult social phobia during face processing also manifest in adolescent social phobia. Blood-oxygen-level-dependent (BOLD) responses were compared in 39 medication-free participants with social phobia (25 adults and 14 adolescents) and 39 healthy comparison subjects (23 adults and 16 adolescents) matched on age, IQ, and gender. During fMRI scans, participants saw angry, fearful, and neutral expression stimuli while making a gender judgment. Significant diagnosis-by-emotion interactions were observed within the amygdala and the rostral anterior cingulate cortex, as has previously been hypothesized. In these regions, both the adolescent and adult social phobia patients showed significantly increased BOLD responses relative to their respective age-matched comparison subjects, and there was no evidence of age-related modulation of between-group differences. These enhanced responses occurred specifically when viewing angry (rostral anterior cingulate cortex) and fearful (amygdala and rostral anterior cingulate cortex) expressions but not when viewing neutral expressions. In addition, the severity of social phobia was significantly correlated with the enhanced rostral anterior cingulate cortex response in the adults. The neural correlates of adult social phobia during face processing also manifest in adolescents. Neural correlates that are observed in adult social phobia may represent the persistence of profiles established earlier in life rather than adaptive responses to such earlier perturbations or maturational changes. These cross-sectional observations might encourage longitudinal fMRI studies of adolescent social phobia.
Dynamics of brain responses to phobic-related stimulation in specific phobia subtypes.
Caseras, Xavier; Mataix-Cols, David; Trasovares, Maria Victoria; López-Solà, Marina; Ortriz, Hector; Pujol, Jesus; Soriano-Mas, Carles; Giampietro, Vincent; Brammer, Michael J; Torrubia, Rafael
2010-10-01
Very few studies have investigated to what extent different subtypes of specific phobia share the same underlying functional neuroanatomy. This study aims to investigate the potential differences in the anatomy and dynamics of the blood oxygen level-dependent (BOLD) responses associated with spider and blood-injection-injury phobias. We used an event-related paradigm in 14 untreated spider phobics, 15 untreated blood-injection-injury phobics and 17 controls. Phobic images successfully induced distress only in phobic participants. Both phobic groups showed a similar pattern of heart rate increase following the presentation of phobic stimuli, this being different from controls. The presentation of phobic images induced activity within the same brain network in all participants, although the intensity of brain responses was significantly higher in phobics. Only blood-injection-injury phobics showed greater activity in the ventral prefrontal cortex compared with controls. This phobia group also presented a lower activity peak in the left amygdala compared with spider phobics. Importantly, looking at the dynamics of BOLD responses, both phobia groups showed a quicker time-to-peak in the right amygdala than controls, but only spider phobics also differed from controls in this parameter within the left amygdala. Considering these and previous findings, both phobia subtypes show very similar responses regarding their immediate reaction to phobia-related images, but critical differences in their sustained responses to these stimuli. These results highlight the importance of considering complex mental processes potentially associated with coping and emotion regulation processes, rather than exclusively focusing on primary neural responses to threat, when investigating fear and phobias. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
Silvetti, Massimo; Lasaponara, Stefano; Lecce, Francesca; Dragone, Alessio; Macaluso, Emiliano; Doricchi, Fabrizio
2016-12-01
In humans, invalid visual targets that mismatch spatial expectations induced by attentional cues are considered to selectively engage a right hemispheric "reorienting" network that includes the temporal parietal junction (TPJ), the inferior frontal gyrus (IFG), and the medial frontal gyrus (MFG). However, recent findings suggest that this hemispheric dominance is not absolute and that it is rather observed because the TPJ and IFG areas in the left hemisphere are engaged both by invalid and valid cued targets. Because of this, the BOLD response of the left hemisphere to invalid targets is usually cancelled out by the standard "invalid versus valid" contrast used in functional magnetic resonance imaging investigations of spatial attention. Here, we used multivariate pattern recognition analysis (MVPA) to gain finer insight into the role played by the left TPJ and IFG in reorienting to invalid targets. We found that in left TPJ and IFG blood oxygen level-dependent (BOLD) responses to invalid and valid targets were associated to different patterns of neural activity, possibly reflecting the presence of functionally distinct neuronal populations. Pattern segregation was significant at group level, it was present in almost all of the participants to the study and was observed both for targets in the left and right side of space. A control whole-brain MVPA ("Searchlight" analysis) confirmed the results obtained in predefined regions of interest and highlighted that also other areas, that is, superior parietal and frontal-polar cortex, show different patterns of BOLD response to valid and invalid targets. These results confirm and expand previous evidence highlighting the involvement of the left hemisphere in reorienting of visual attention (Doricchi et al. 2010; Dragone et al. 2015). These findings suggest that asymmetrical reorienting deficits suffered by right brain damaged patients with left spatial neglect, who have severe impairments in contralesional reorienting and less severe impairments in ipsilesional reorienting, are due to preserved reorienting abilities in the intact left hemisphere. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Neural correlates of working memory in first episode and recurrent depression: An fMRI study.
Yüksel, Dilara; Dietsche, Bruno; Konrad, Carsten; Dannlowski, Udo; Kircher, Tilo; Krug, Axel
2018-06-08
Patients suffering from major depressive disorder (MDD) show deficits in working memory (WM) performance accompanied by bilateral fronto-parietal BOLD signal changes. It is unclear whether patients with a first depressive episode (FDE) exhibit the same signal changes as patients with recurrent depressive episodes (RDE). We investigated seventy-four MDD inpatients (48 RDE, 26 FDE) and 74 healthy control (HC) subjects performing an n-back WM task (0-back, 2-back, 3-back condition) in a 3T-fMRI. FMRI analyses revealed deviating BOLD signal in MDD in the thalamus (0-back vs. 2-back), the angular gyrus (0-back vs. 3-back), and the superior frontal gyrus (2-back vs. 3-back). Further effects were observed between RDE vs. FDE. Thus, RDE displayed differing neural activation in the middle frontal gyrus (2-back vs. 3-back), the inferior frontal gyrus, and the precentral gyrus (0-back vs. 2-back). In addition, both HC and FDE indicated a linear activation trend depending on task complexity. Although we failed to find behavioral differences between the groups, results suggest differing BOLD signal in fronto-parietal brain regions in MDD vs. HC, and in RDE vs. FDE. Moreover, both HC and FDE show similar trends in activation shapes. This indicates a link between levels of complexity-dependent activation in fronto-parietal brain regions and the stage of MDD. We therefore assume that load-dependent BOLD signal during WM is impaired in MDD, and that it is particularly affected in RDE. We also suspect neurobiological compensatory mechanisms of the reported brain regions in (working) memory functioning. Copyright © 2018 Elsevier Inc. All rights reserved.
Habitat quality mediates personality through differences in social context.
Belgrad, Benjamin A; Griffen, Blaine D
2017-06-01
Assessing the stability of animal personalities has become a major goal of behavioral ecologists. Most personality studies have utilized solitary individuals, but little is known on the extent that individuals retain their personality across ecologically relevant group settings. We conducted a field survey which determined that mud crabs, Panopeus herbstii, remain scattered as isolated individuals on degraded oyster reefs while high quality reefs can sustain high crab densities (>10 m -2 ). We examined the impact of these differences in social context on personality by quantifying the boldness of the same individual crabs when in isolation and in natural cohorts. Crabs were also exposed to either a treatment of predator cues or a control of no cue throughout the experiment to assess the strength of this behavioral reaction norm. Crabs were significantly bolder when in groups than as solitary individuals with predator cue treatments exhibiting severally reduced crab activity levels in comparison to corresponding treatments with no predator cues. Behavioral plasticity depended on the individual and was strongest in the presence of predator cues. While bold crabs largely maintained their personality in isolation and group settings, shy crabs would become substantially bolder when among conspecifics. These results imply that the shifts in crab boldness were a response to changes in perceived predation risk, and provide a mechanism for explaining variation in behavioral plasticity. Such findings suggest that habitat degradation may produce subpopulations with different behavioral patterns because of differing social interactions between individual animals.
Neural correlates of the popular music phenomenon: evidence from functional MRI and PET imaging.
Chen, Qiaozhen; Zhang, Ying; Hou, Haifeng; Du, Fenglei; Wu, Shuang; Chen, Lin; Shen, Yehua; Chao, Fangfang; Chung, June-Key; Zhang, Hong; Tian, Mei
2017-06-01
Music can induce different emotions. However, its neural mechanism remains unknown. The aim of this study was to use functional magnetic resonance imaging (fMRI) and position emission tomography (PET) imaging for mapping of neural changes under the most popular music in healthy volunteers. Blood-oxygen-level-dependent (BOLD) fMRI and monoamine receptor PET imaging with 11 C-N-methylspiperone ( 11 C-NMSP) were conducted under the popular music Gangnam Style and light music A Comme Amour in healthy subjects. PET and fMRI images were analyzed by using the Statistical Parametric Mapping software (SPM). Significantly increased fMRI BOLD signals were found in the bilateral superior temporal cortices, left cerebellum, left putamen and right thalamus cortex. Monoamine receptor availability was increased significantly in the left superior temporal gyrus and left putamen, but decreased in the bilateral superior occipital cortices under the Gangnam Style compared with the light music condition. Significant positive correlation was found between 11 C-NMSP binding and fMRI BOLD signals in the left temporal cortex. Furthermore, increased 11 C-NMSP binding in the left putamen was positively correlated with the mood arousal level score under the Gangnam Style condition. Popular music Gangnam Style can arouse pleasure experience and strong emotional response. The left putamen is positively correlated with the mood arousal level score under the Gangnam Style condition. Our results revealed characteristic patterns of brain activity associated with Gangnam Style, and may also provide more general insights into the music-induced emotional processing.
Villalobos, Michele E.; Mizuno, Akiko; Dahl, Branelle C.; Kemmotsu, Nobuko; Müller, Ralph-Axel
2010-01-01
Some recent evidence has suggested abnormalities of the dorsal stream and possibly the mirror neuron system in autism, which may be responsible for impairments of joint attention, imitation, and secondarily for language delays. The current study investigates functional connectivity along the dorsal stream in autism, examining interregional blood oxygenation level dependent (BOLD) signal cross-correlation during visuomotor coordination. Eight high-functioning autistic men and 8 handedness and age-matched controls were included. Visually prompted button presses were performed with the preferred hand. For each subject, functional connectivity was computed in terms of BOLD signal correlation with the mean time series in bilateral visual area 17. Our hypothesis of reduced dorsal stream connectivity in autism was only in part confirmed. Functional connectivity with superior parietal areas was not significantly reduced. However, the autism group showed significantly reduced connectivity with bilateral inferior frontal area 44, which is compatible with the hypothesis of mirror neuron defects in autism. More generally, our findings suggest that dorsal stream connectivity in autism may not be fully functional. PMID:15808991
Villalobos, Michele E; Mizuno, Akiko; Dahl, Branelle C; Kemmotsu, Nobuko; Müller, Ralph-Axel
2005-04-15
Some recent evidence has suggested abnormalities of the dorsal stream and possibly the mirror neuron system in autism, which may be responsible for impairments of joint attention, imitation, and secondarily for language delays. The current study investigates functional connectivity along the dorsal stream in autism, examining interregional blood oxygenation level dependent (BOLD) signal cross-correlation during visuomotor coordination. Eight high-functioning autistic men and eight handedness and age-matched controls were included. Visually prompted button presses were performed with the preferred hand. For each subject, functional connectivity was computed in terms of BOLD signal correlation with the mean time series in bilateral visual area 17. Our hypothesis of reduced dorsal stream connectivity in autism was only in part confirmed. Functional connectivity with superior parietal areas was not significantly reduced. However, the autism group showed significantly reduced connectivity with bilateral inferior frontal area 44, which is compatible with the hypothesis of mirror neuron defects in autism. More generally, our findings suggest that dorsal stream connectivity in autism may not be fully functional.
fMRI mapping of the visual system in the mouse brain with interleaved snapshot GE-EPI.
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.
Differences in boldness are repeatable and heritable in a long-lived marine predator
Patrick, Samantha C; Charmantier, Anne; Weimerskirch, Henri
2013-01-01
Animal personalities, composed of axes of consistent individual behaviors, are widely reported and can have important fitness consequences. However, despite theoretical predictions that life-history trade-offs may cause and maintain personality differences, our understanding of the evolutionary ecology of personality remains poor, especially in long-lived species where trade-offs and senescence have been shown to be stronger. Furthermore, although much theoretical and empirical work assumes selection shapes variation in personalities, studies exploring the genetic underpinnings of personality traits are rare. Here we study one standard axis of personality, the shy–bold continuum, in a long-lived marine species, the wandering albatross from Possession Island, Crozet, by measuring the behavioral response to a human approach. Using generalized linear mixed models in a Bayesian framework, we show that boldness is highly repeatable and heritable. We also find strong differences in boldness between breeding colonies, which vary in size and density, suggesting birds are shyer in more dense colonies. These results demonstrate that in this seabird population, boldness is both heritable and repeatable and highlights the potential for ecological and evolutionary processes to shape personality traits in species with varying life-history strategies. PMID:24340172
Differences in boldness are repeatable and heritable in a long-lived marine predator.
Patrick, Samantha C; Charmantier, Anne; Weimerskirch, Henri
2013-11-01
Animal personalities, composed of axes of consistent individual behaviors, are widely reported and can have important fitness consequences. However, despite theoretical predictions that life-history trade-offs may cause and maintain personality differences, our understanding of the evolutionary ecology of personality remains poor, especially in long-lived species where trade-offs and senescence have been shown to be stronger. Furthermore, although much theoretical and empirical work assumes selection shapes variation in personalities, studies exploring the genetic underpinnings of personality traits are rare. Here we study one standard axis of personality, the shy-bold continuum, in a long-lived marine species, the wandering albatross from Possession Island, Crozet, by measuring the behavioral response to a human approach. Using generalized linear mixed models in a Bayesian framework, we show that boldness is highly repeatable and heritable. We also find strong differences in boldness between breeding colonies, which vary in size and density, suggesting birds are shyer in more dense colonies. These results demonstrate that in this seabird population, boldness is both heritable and repeatable and highlights the potential for ecological and evolutionary processes to shape personality traits in species with varying life-history strategies.
Shi, Huilan; Jia, Junya; Li, Dong; Wei, Li; Shang, Wenya; Zheng, Zhenfeng
2018-02-09
Precise renal histopathological diagnosis will guide therapy strategy in patients with lupus nephritis. Blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) has been applicable noninvasive technique in renal disease. This current study was performed to explore whether BOLD MRI could contribute to diagnose renal pathological pattern. Adult patients with lupus nephritis renal pathological diagnosis were recruited for this study. Renal biopsy tissues were assessed based on the lupus nephritis ISN/RPS 2003 classification. The Blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) was used to obtain functional magnetic resonance parameter, R2* values. Several functions of R2* values were calculated and used to construct algorithmic models for renal pathological patterns. In addition, the algorithmic models were compared as to their diagnostic capability. Both Histopathology and BOLD MRI were used to examine a total of twelve patients. Renal pathological patterns included five classes III (including 3 as class III + V) and seven classes IV (including 4 as class IV + V). Three algorithmic models, including decision tree, line discriminant, and logistic regression, were constructed to distinguish the renal pathological pattern of class III and class IV. The sensitivity of the decision tree model was better than that of the line discriminant model (71.87% vs 59.48%, P < 0.001) and inferior to that of the Logistic regression model (71.87% vs 78.71%, P < 0.001). The specificity of decision tree model was equivalent to that of the line discriminant model (63.87% vs 63.73%, P = 0.939) and higher than that of the logistic regression model (63.87% vs 38.0%, P < 0.001). The Area under the ROC curve (AUROCC) of the decision tree model was greater than that of the line discriminant model (0.765 vs 0.629, P < 0.001) and logistic regression model (0.765 vs 0.662, P < 0.001). BOLD MRI is a useful non-invasive imaging technique for the evaluation of lupus nephritis. Decision tree models constructed using functions of R2* values may facilitate the prediction of renal pathological patterns.
2016-01-01
When blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) was discovered in the early 1990s, it provoked an explosion of interest in exploring human cognition, using brain mapping techniques based on MRI. Standards for data acquisition and analysis were rapidly put in place, in order to assist comparison of results across laboratories. Recently, MRI data acquisition capabilities have improved dramatically, inviting a rethink of strategies for relating functional brain activity at the systems level with its neuronal substrates and functional connections. This paper reviews the established capabilities of BOLD contrast fMRI, the perceived weaknesses of major methods of analysis, and current results that may provide insights into improved brain modelling. These results have inspired the use of in vivo myeloarchitecture for localizing brain activity, individual subject analysis without spatial smoothing and mapping of changes in cerebral blood volume instead of BOLD activation changes. The apparent fundamental limitations of all methods based on nuclear magnetic resonance are also discussed. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574303
Implicit Race Bias Decreases the Similarity of Neural Representations of Black and White Faces
Brosch, Tobias; Bar-David, Eyal; Phelps, Elizabeth A.
2013-01-01
Implicit race bias has been shown to affect decisions and behaviors. It may also change perceptual experience by increasing perceived differences between social groups. We investigated how this phenomenon may be expressed at the neural level by testing whether the distributed blood-oxygenation-level-dependent (BOLD) patterns representing Black and White faces are more dissimilar in participants with higher implicit race bias. We used multivoxel pattern analysis to predict the race of faces participants were viewing. We successfully predicted the race of the faces on the basis of BOLD activation patterns in early occipital visual cortex, occipital face area, and fusiform face area (FFA). Whereas BOLD activation patterns in early visual regions, likely reflecting different perceptual features, allowed successful prediction for all participants, successful prediction on the basis of BOLD activation patterns in FFA, a high-level face-processing region, was restricted to participants with high pro-White bias. These findings suggest that stronger implicit pro-White bias decreases the similarity of neural representations of Black and White faces. PMID:23300228
Turner, Robert
2016-10-05
When blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) was discovered in the early 1990s, it provoked an explosion of interest in exploring human cognition, using brain mapping techniques based on MRI. Standards for data acquisition and analysis were rapidly put in place, in order to assist comparison of results across laboratories. Recently, MRI data acquisition capabilities have improved dramatically, inviting a rethink of strategies for relating functional brain activity at the systems level with its neuronal substrates and functional connections. This paper reviews the established capabilities of BOLD contrast fMRI, the perceived weaknesses of major methods of analysis, and current results that may provide insights into improved brain modelling. These results have inspired the use of in vivo myeloarchitecture for localizing brain activity, individual subject analysis without spatial smoothing and mapping of changes in cerebral blood volume instead of BOLD activation changes. The apparent fundamental limitations of all methods based on nuclear magnetic resonance are also discussed.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Authors.
Spatial band-pass filtering aids decoding musical genres from auditory cortex 7T fMRI.
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.
Effects of covert and overt paradigms in clinical language fMRI.
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 lateralization of essential language centers for scans performed on the same and different days. Their overt counterparts achieved confirmatory localization but lower lateralization capabilities. Reference data for presurgical application are provided. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.
Tseng, Angela; Wang, Zhishun; Huo, Yuankai; Goh, Suzanne; Russell, James A; Peterson, Bradley S
2016-02-01
Individuals with autism spectrum disorders (ASD) often have difficulty recognizing and interpreting facial expressions of emotion, which may impair their ability to navigate and communicate successfully in their social, interpersonal environments. Characterizing specific differences between individuals with ASD and their typically developing (TD) counterparts in the neural activity subserving their experience of emotional faces may provide distinct targets for ASD interventions. Thus we used functional magnetic resonance imaging (fMRI) and a parametric experimental design to identify brain regions in which neural activity correlated with ratings of arousal and valence for a broad range of emotional faces. Participants (51 ASD, 84 TD) were group-matched by age, sex, IQ, race, and socioeconomic status. Using task-related change in blood-oxygen-level-dependent (BOLD) fMRI signal as a measure, and covarying for age, sex, FSIQ, and ADOS scores, we detected significant differences across diagnostic groups in the neural activity subserving the dimension of arousal but not valence. BOLD-signal in TD participants correlated inversely with ratings of arousal in regions associated primarily with attentional functions, whereas BOLD-signal in ASD participants correlated positively with arousal ratings in regions commonly associated with impulse control and default-mode activity. Only minor differences were detected between groups in the BOLD signal correlates of valence ratings. Our findings provide unique insight into the emotional experiences of individuals with ASD. Although behavioral responses to face-stimuli were comparable across diagnostic groups, the corresponding neural activity for our ASD and TD groups differed dramatically. The near absence of group differences for valence correlates and the presence of strong group differences for arousal correlates suggest that individuals with ASD are not atypical in all aspects of emotion-processing. Studying these similarities and differences may help us to understand the origins of divergent interpersonal emotional experience in persons with ASD. Hum Brain Mapp 37:443-461, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
Tseng, Angela; Wang, Zhishun; Huo, Yuankai; Goh, Suzanne; Russell, James A.; Peterson, Bradley S.
2016-01-01
Individuals with autism spectrum disorders (ASD) often have difficulty recognizing and interpreting facial expressions of emotion, which may impair their ability to navigate and communicate successfully in their social, interpersonal environments. Characterizing specific differences between individuals with ASD and their typically-developing (TD) counterparts in the neural activity subserving their experience of emotional faces may provide distinct targets for ASD interventions. Thus we used functional magnetic resonance imaging (fMRI) and a parametric experimental design to identify brain regions in which neural activity correlated with ratings of arousal and valence for a broad range of emotional faces. Participants (51 ASD, 84 TD) were group-matched by age, sex, IQ, race, and socioeconomic status. Using task-related change in blood-oxygen-level-dependent (BOLD) fMRI signal as a measure, and covarying for age, sex, FSIQ, and ADOS scores, we detected significant differences across diagnostic groups in the neural activity subserving the dimension of arousal but not valence. BOLD-signal in TD participants correlated inversely with ratings of arousal in regions associated primarily with attentional functions, whereas BOLD-signal in ASD participants correlated positively with arousal ratings in regions commonly associated with impulse control and default-mode activity. Only minor differences were detected between groups in the BOLD signal correlates of valence ratings. Our findings provide unique insight into the emotional experiences of individuals with ASD. Although behavioral responses to face-stimuli were comparable across diagnostic groups, the corresponding neural activity for our ASD and TD groups differed dramatically. The near absence of group differences for valence correlates and the presence of strong group differences for arousal correlates suggest that individuals with ASD are not atypical in all aspects of emotion-processing. Studying these similarities and differences may help us to understand the origins of divergent interpersonal emotional experience in persons with ASD. PMID:26526072
Self-Regulation of Amygdala Activation Using Real-Time fMRI Neurofeedback
Phillips, Raquel; Alvarez, Ruben P.; Simmons, W. Kyle; Bellgowan, Patrick; Drevets, Wayne C.; Bodurka, Jerzy
2011-01-01
Real-time functional magnetic resonance imaging (rtfMRI) with neurofeedback allows investigation of human brain neuroplastic changes that arise as subjects learn to modulate neurophysiological function using real-time feedback regarding their own hemodynamic responses to stimuli. We investigated the feasibility of training healthy humans to self-regulate the hemodynamic activity of the amygdala, which plays major roles in emotional processing. Participants in the experimental group were provided with ongoing information about the blood oxygen level dependent (BOLD) activity in the left amygdala (LA) and were instructed to raise the BOLD rtfMRI signal by contemplating positive autobiographical memories. A control group was assigned the same task but was instead provided with sham feedback from the left horizontal segment of the intraparietal sulcus (HIPS) region. In the LA, we found a significant BOLD signal increase due to rtfMRI neurofeedback training in the experimental group versus the control group. This effect persisted during the Transfer run without neurofeedback. For the individual subjects in the experimental group the training effect on the LA BOLD activity correlated inversely with scores on the Difficulty Identifying Feelings subscale of the Toronto Alexithymia Scale. The whole brain data analysis revealed significant differences for Happy Memories versus Rest condition between the experimental and control groups. Functional connectivity analysis of the amygdala network revealed significant widespread correlations in a fronto-temporo-limbic network. Additionally, we identified six regions — right medial frontal polar cortex, bilateral dorsomedial prefrontal cortex, left anterior cingulate cortex, and bilateral superior frontal gyrus — where the functional connectivity with the LA increased significantly across the rtfMRI neurofeedback runs and the Transfer run. The findings demonstrate that healthy subjects can learn to regulate their amygdala activation using rtfMRI neurofeedback, suggesting possible applications of rtfMRI neurofeedback training in the treatment of patients with neuropsychiatric disorders. PMID:21931738
Deficient aversive-potentiated startle and the triarchic model of psychopathy: The role of boldness.
Esteller, Àngels; Poy, Rosario; Moltó, Javier
2016-05-01
This study examined the contribution of the phenotypic domains of boldness, meanness, and disinhibition of the triarchic conceptualization of psychopathy (Patrick, Fowles, & Krueger, 2009) to deficient aversive-potentiated startle in a mixed-gender sample of 180 undergraduates. Eyeblink responses to noise probes were recorded during a passive picture-viewing task (erotica, neutral, threat, and mutilation). Deficient threat vs. neutral potentiation was uniquely related to increased boldness scores, thus suggesting that the diminished defensive reaction to aversive stimulation is specifically linked to the charm, social potency and venturesomeness features of psychopathy (boldness), but not to features such as callousness, coldheartedness and cruelty traits (meanness), even though both phenotypes theoretically share the same underlying low-fear disposition. Our findings provide further evidence of the differential association between distinct psychopathy components and deficits in defensive reactivity and strongly support the validity of the triarchic model of psychopathy in disentangling the etiology of this personality disorder. Copyright © 2016 Elsevier B.V. All rights reserved.
Ma, Yuhan; Berman, Avery J L; Pike, G Bruce
2016-12-01
To determine the contribution of paramagnetic dissolved oxygen in blood plasma to blood-oxygenation-level-dependent (BOLD) signal changes in hyperoxic calibrated BOLD studies. Bovine blood plasma samples were prepared with partial pressures of oxygen (pO 2 ) ranging from 110 to 600 mmHg. R 1 , R 2 , and R 2 * of the plasma with dissolved oxygen were measured using quantitative MRI sequences at 3 Tesla. Simulations were performed to predict the relative effects of dissolved oxygen and deoxyhemoglobin changes in hyperoxia calibrated BOLD. The relaxivities of dissolved oxygen in plasma were found to be r 1, O2 =1.97 ± 0.09 ×10 -4 s -1 mmHg -1 , r 2, O2 =2.3 ± 0.7 ×10 -4 s -1 mmHg -1 , and r 2, O2 * = 2.3 ± 0.7 ×10 -4 s -1 mmHg -1 . Simulations predict that neither the transverse nor longitudinal relaxation rates of dissolved oxygen contribute significantly to the BOLD signal during hyperoxia. During hyperoxia, the increases in R 2 and R 2 * of blood from dissolved oxygen in plasma are considerably less than the decreases in R 2 and R 2 * from venous deoxyhemoglobin. R 1 effects due to dissolved oxygen are also predicted to be negligible. As a result, dissolved oxygen in arteries should not contribute significantly to the hyperoxic calibrated BOLD signal. Magn Reson Med 76:1905-1911, 2016. © 2015 International Society for Magnetic Resonance in Medicine. © 2015 International Society for Magnetic Resonance in Medicine.
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.
Does social context affect boldness in juveniles?
Loftus, Siobhan; Borcherding, Jost
2017-12-01
Differences in boldness are common between populations or between related species and are discussed as part of individual coping style, personality, or behavioral syndrome. Boldness has been found to be dependent on experience, social, and environmental contexts. The major aim of the present study was to establish an experimental environment that would allow analyzing the risk-taking behavior of 2 competing invasive goby species. Neogobius melanostomus was more active in the absence of a predator Sander lucioperca than N. fluviatilis and clearly spent more time "swimming" and "feeding" than N. fluviatilis . In addition, N. melanostomus was always faster than N. fluviatilis both when leaving the shelter and reaching offered food. Based on the different behaviors recorded, species-specific boldness scores were established using a principal component analysis. Although there was no overall difference in boldness scores between the 2 species, both competitive conditions and the effect of the predator played significant roles as factors influencing boldness. Neogobius melanostomus was more affected by the presence/absence of the predator than the social circumstances. Neogobius fluviatilis , on the other hand, was more active and bolder in competitive situations. However, when alone, N. fluviatilis was rather inactive and displayed altogether shy behavior, independent of the presence/absence of the predator. Thus, the study confirms the prediction that there are differences in behavior and behavioral plasticity, and therein predator-avoidance strategies, between ecologically similar species of goby living in sympatry. We argue that these differences may be related to differential habitat use of both invasive species that presently dominate the fish community in the Lower Rhine.
Does social context affect boldness in juveniles?
Borcherding, Jost
2017-01-01
Abstract Differences in boldness are common between populations or between related species and are discussed as part of individual coping style, personality, or behavioral syndrome. Boldness has been found to be dependent on experience, social, and environmental contexts. The major aim of the present study was to establish an experimental environment that would allow analyzing the risk-taking behavior of 2 competing invasive goby species. Neogobius melanostomus was more active in the absence of a predator Sander lucioperca than N. fluviatilis and clearly spent more time “swimming” and “feeding” than N. fluviatilis. In addition, N. melanostomus was always faster than N. fluviatilis both when leaving the shelter and reaching offered food. Based on the different behaviors recorded, species-specific boldness scores were established using a principal component analysis. Although there was no overall difference in boldness scores between the 2 species, both competitive conditions and the effect of the predator played significant roles as factors influencing boldness. Neogobius melanostomus was more affected by the presence/absence of the predator than the social circumstances. Neogobius fluviatilis, on the other hand, was more active and bolder in competitive situations. However, when alone, N. fluviatilis was rather inactive and displayed altogether shy behavior, independent of the presence/absence of the predator. Thus, the study confirms the prediction that there are differences in behavior and behavioral plasticity, and therein predator-avoidance strategies, between ecologically similar species of goby living in sympatry. We argue that these differences may be related to differential habitat use of both invasive species that presently dominate the fish community in the Lower Rhine. PMID:29492025
Gompf, Florian; Pflug, Anja; Laufs, Helmut; Kell, Christian A
2017-01-01
Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region.
Leadership, personality and social feedback
Ang, Tzo Zen; Sweetman, Gemma; Johnstone, Rufus A; Manica, Andrea
2009-01-01
In a recent paper, we showed that leadership arises from individual behavioral differences in pairs of foraging stickleback (Gasterosteus aculeatus). Foraging data from randomly combined pairs of fish were analyzed using Markov Chain models to infer the individual movement rules underlying joint behavior. While both fish responded to partner movement, bolder individuals were the least responsive and showed greater individual initiative. Shy partners were more faithful followers and were also found to bring about greater leadership tendencies in their bold partners. The ability of such followers to inspire bolder fish suggests that leadership may be dependent on individual temperament differences, reinforced by social feedback. PMID:19721883
Li, Chiang-Shan Ray; Milivojevic, Verica; Constable, R Todd; Sinha, Rajita
2005-12-30
Previous neuroimaging studies showed that use of marijuana can alter patterns of cortical activation during rest or a task challenge. We used functional magnetic resonance imaging to examine whether recent cannabis abuse contributed to stress-induced blood-oxygen-level-dependent (BOLD) contrast in a group of cocaine-dependent individuals. Emotional stress was induced using the script-guided imagery paradigm, in which subjects imagined being in a real-life stressful situation and, as a control, in a neutral situation, while BOLD signals of their brain were acquired with a 1.5 T scanner. Abstinent cocaine-dependent subjects with recent marijuana abuse (n=8) were compared with abstinent cocaine-dependent subjects who had not abused marijuana recently (n=18). The two groups were otherwise matched in their demographic characteristics and drug use history. All subjects were abstinent for at least 15 days and drug free as confirmed by urine drug screening before the imaging session. Recent cannabis abusers demonstrated hypo-activation in frontal cortical areas including the perigenual anterior cingulate during increased emotional stress. In contrast, at the same statistical threshold, no brain regions showed increased activation in recent cannabis abusers compared with non-abusers. The group difference in the perigenual anterior cingulate remained even when lifetime cocaine and alcohol consumption was accounted for in covariance analysis. These results provide evidence that recent cannabis abuse is associated with decreased activation in the frontal cortex during an emotional stress task. The results suggest an abnormal cognitive control mechanism during affective processing in association with heavy cannabis use.
Kareken, David A.; Dzemidzic, Mario; Oberlin, Brandon G.; Eiler, William J.A.
2014-01-01
Background A preference for sweet tastes has been repeatedly shown to be associated with alcohol preference in both animals and humans. In this study, we tested the extent to which recent drinking is related to blood oxygen dependent (BOLD) activation from an intensely sweet solution in orbitofrontal areas known to respond to primary rewards. Methods Sixteen right-handed, non-treatment seeking, healthy volunteers (mean age 26 years; 75% male) were recruited from the community. All underwent a taste test using a range of sucrose concentrations, as well as functional magnetic resonance imaging (fMRI) during pseudorandom, event-driven stimulation with water and a 0.83M concentration of sucrose in water. Results [Sucrose > Water] provoked significant BOLD activation in primary gustatory cortex and amygdala, as well as in the right ventral striatum and in bilateral orbitofrontal cortex. Drinks/drinking day correlated significantly with the activation as extracted from the left orbital area (r = 0.52, p = 0.04 after correcting for a bilateral comparison). Using stepwise multiple regression, the addition of rated sucrose-liking accounted for significantly more variance in drinks/drinking day than did left orbital activation alone (multiple R= 0.79, p = 0.002). Conclusions Both the orbitofrontal response to an intensely sweet taste, as well as rated liking of that taste, accounted for significant variance in drinking behavior. The brain response to sweet tastes may be an important phenotype of alcoholism risk. PMID:23841808
Multisensory speech perception without the left superior temporal sulcus.
Baum, Sarah H; Martin, Randi C; Hamilton, A Cris; Beauchamp, Michael S
2012-09-01
Converging evidence suggests that the left superior temporal sulcus (STS) is a critical site for multisensory integration of auditory and visual information during speech perception. We report a patient, SJ, who suffered a stroke that damaged the left tempo-parietal area, resulting in mild anomic aphasia. Structural MRI showed complete destruction of the left middle and posterior STS, as well as damage to adjacent areas in the temporal and parietal lobes. Surprisingly, SJ demonstrated preserved multisensory integration measured with two independent tests. First, she perceived the McGurk effect, an illusion that requires integration of auditory and visual speech. Second, her perception of morphed audiovisual speech with ambiguous auditory or visual information was significantly influenced by the opposing modality. To understand the neural basis for this preserved multisensory integration, blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine brain responses to audiovisual speech in SJ and 23 healthy age-matched controls. In controls, bilateral STS activity was observed. In SJ, no activity was observed in the damaged left STS but in the right STS, more cortex was active in SJ than in any of the normal controls. Further, the amplitude of the BOLD response in right STS response to McGurk stimuli was significantly greater in SJ than in controls. The simplest explanation of these results is a reorganization of SJ's cortical language networks such that the right STS now subserves multisensory integration of speech. Copyright © 2012 Elsevier Inc. All rights reserved.
Evidence for unlimited capacity processing of simple features in visual cortex
White, Alex L.; Runeson, Erik; Palmer, John; Ernst, Zachary R.; Boynton, Geoffrey M.
2017-01-01
Performance in many visual tasks is impaired when observers attempt to divide spatial attention across multiple visual field locations. Correspondingly, neuronal response magnitudes in visual cortex are often reduced during divided compared with focused spatial attention. This suggests that early visual cortex is the site of capacity limits, where finite processing resources must be divided among attended stimuli. However, behavioral research demonstrates that not all visual tasks suffer such capacity limits: The costs of divided attention are minimal when the task and stimulus are simple, such as when searching for a target defined by orientation or contrast. To date, however, every neuroimaging study of divided attention has used more complex tasks and found large reductions in response magnitude. We bridged that gap by using functional magnetic resonance imaging to measure responses in the human visual cortex during simple feature detection. The first experiment used a visual search task: Observers detected a low-contrast Gabor patch within one or four potentially relevant locations. The second experiment used a dual-task design, in which observers made independent judgments of Gabor presence in patches of dynamic noise at two locations. In both experiments, blood-oxygen level–dependent (BOLD) signals in the retinotopic cortex were significantly lower for ignored than attended stimuli. However, when observers divided attention between multiple stimuli, BOLD signals were not reliably reduced and behavioral performance was unimpaired. These results suggest that processing of simple features in early visual cortex has unlimited capacity. PMID:28654964
NASA Astrophysics Data System (ADS)
Fukami, Tadanori; Shimada, Takamasa; Akatsuka, Takao; Saito, Yoichi
In audiometry, ABR (Auditory Brainstem Response) is widely used. However, it shows low accuracy in low frequency band. Meanwhile, AMFR (Amplitude-Modulation-Following Response), the response during hearing an amplitude-modulated tone, has high frequency specificity and is brought to attention. As the first step to clinical application of AMFR, we investigated the activated areas in a brain when the subjects hear SAM tone (Sinusoidally Amplitude-Modulated tone) with both ears. We measured following two signals. One is the difference of BOLD (Blood Oxygenation Level Dependent) signal between hearing SAM tone vs. silence, the other is the difference of BOLD signal between hearing SAM tone vs. unmodulated tone. As a result, in the case of SAM vs. silence, the bilaterally auditory cortex (Broadmann Area 41, 42), the biratelally BA 10, left superior frontal gyrus and right superior temporal gyrus were activated (p<0.0037, uncorrected). In the case of SAM vs. unmodulated tone, the bilaterally superior frontal gyrus (BA 6) and precuneus (BA 7), neighboring area including the bilaterally inferior parietal lobule (BA 40), the bilaterally medial frontal gyrus and superior frontal gyrus were activated (p<0.021, uncorrected). Activations of visual perception due to eye-opened state were detected in some parts of activations. As a result, we inferred that modulated tone was recognized in the medial frontal gyrus and inferior parietal lobule was the part related to perception of amplitude-modulation.
Multisensory Speech Perception Without the Left Superior Temporal Sulcus
Baum, Sarah H.; Martin, Randi C.; Hamilton, A. Cris; Beauchamp, Michael S.
2012-01-01
Converging evidence suggests that the left superior temporal sulcus (STS) is a critical site for multisensory integration of auditory and visual information during speech perception. We report a patient, SJ, who suffered a stroke that damaged the left tempo-parietal area, resulting in mild anomic aphasia. Structural MRI showed complete destruction of the left middle and posterior STS, as well as damage to adjacent areas in the temporal and parietal lobes. Surprisingly, SJ demonstrated preserved multisensory integration measured with two independent tests. First, she perceived the McGurk effect, an illusion that requires integration of auditory and visual speech. Second, her perception of morphed audiovisual speech with ambiguous auditory or visual information was significantly influenced by the opposing modality. To understand the neural basis for this preserved multisensory integration, blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine brain responses to audiovisual speech in SJ and 23 healthy age-matched controls. In controls, bilateral STS activity was observed. In SJ, no activity was observed in the damaged left STS but in the right STS, more cortex was active in SJ than in any of the normal controls. Further, the amplitude of the BOLD response in right STS response to McGurk stimuli was significantly greater in SJ than in controls. The simplest explanation of these results is a reorganization of SJ's cortical language networks such that the right STS now subserves multisensory integration of speech. PMID:22634292
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.
Adolescent neural response to reward is related to participant sex and task motivation
Alarcón, Gabriela; Cservenka, Anita; Nagel, Bonnie J.
2017-01-01
Risky decision making is prominent during adolescence, perhaps contributed to by heightened sensation seeking and ongoing maturation of reward and dopamine systems in the brain, which are, in part, modulated by sex hormones. In this study, we examined sex differences in the neural substrates of reward sensitivity during a risky decision-making task and hypothesized that compared with girls, boys would show heightened brain activation in reward-relevant regions, particularly the nucleus accumbens, during reward receipt. Further, we hypothesized that testosterone and estradiol levels would mediate this sex difference. Moreover, we predicted boys would make more risky choices on the task. While boys showed increased nucleus accumbens blood oxygen level-dependent (BOLD) response relative to girls, sex hormones did not mediate this effect. As predicted, boys made a higher percentage of risky decisions during the task. Interestingly, boys also self-reported more motivation to perform well and earn money on the task, while girls self-reported higher state anxiety prior to the scan session. Motivation to earn money partially mediated the effect of sex on nucleus accumbens activity during reward. Previous research shows that increased motivation and salience of reinforcers is linked with more robust striatal BOLD response, therefore psychosocial factors, in addition to sex, may play an important role in reward sensitivity. Elucidating neurobiological mechanisms that support adolescent sex differences in risky decision making has important implications for understanding individual differences that lead to advantageous and adverse behaviors that affect health outcomes. PMID:27816780
Bangen, Katherine J; Restom, Khaled; Liu, Thomas T; Wierenga, Christina E; Jak, Amy J; Salmon, David P; Bondi, Mark W
2012-01-01
Functional magnetic resonance imaging (fMRI) of older adults at risk for Alzheimer's disease (AD) by virtue of their cognitive (i.e., mild cognitive impairment [MCI]) and/or genetic (i.e., apolipoprotein E [APOE] ε4 allele) status demonstrate divergent brain response patterns during memory encoding across studies. Using arterial spin labeling MRI, we examined the influence of AD risk on resting cerebral blood flow (CBF) as well as the CBF and blood oxygenation level dependent (BOLD) signal response to memory encoding in the medial temporal lobes (MTL) in 45 older adults (29 cognitively normal [14 APOE ε4 carriers and 15 noncarriers]; 16 MCI [8 APOE ε4 carriers, 8 noncarriers]). Risk groups were comparable in terms of mean age, years of education, gender distribution, and vascular risk burden. Individuals at genetic risk for AD by virtue of the APOE ε4 allele demonstrated increased MTL resting state CBF relative to ε4 noncarriers, whereas individuals characterized as MCI showed decreased MTL resting state CBF relative to their cognitively normal peers. For percent change CBF, there was a trend toward a cognitive status by genotype interaction. In the cognitively normal group, there was no difference in percent change CBF based on APOE genotype. In contrast, in the MCI group, APOE ε4 carriers demonstrated significantly greater percent change in CBF relative to ε4 noncarriers. No group differences were found for BOLD response. Findings suggest that abnormal resting state CBF and CBF response to memory encoding may be early indicators of brain dysfunction in individuals at risk for developing AD.
Torres, Isabela F Araújo; Júlio, Gustavo S da C; Figueiredo, Luis Gustavo; de Lima, Natália L C; Soares, Ana Paula N; Luz, Ronald K
2017-12-01
Considering that each personality type in animals presents distinct physiological and behavioural responses, this study evaluated the efficiency of the Novel Environment test to classify larvae of Lophiosilurus alexandri into bold and shy individuals, which were then investigated for growth, cannibalism and mortality in larviculture of pure and mixed groups. Larvae with an average weight of 24.0±1.7mg and length of 14.1±0.4mm, were subjected to a Novel Environment test to classify their personality type (bold and shy larvae). After the larvae were classified according to personality type, they were subjected to larviculture for 15days. Three treatments were tested: only bold larvae, only shy larvae, and a mixed treatment (bold larvae+shy larvae) at a density for 16 larvae/L, which were fed 3 times a day with Artemia nauplii. After larviculture, there were no differences in the final lengths of larvae of the bold, shy, and mixed treatments (26.9±0.76mm, 26.7±1.00mm, and 26.8±1.24mm, respectively); however, shy larvae possessed weighed less (0.22±0.01g) than the bold and mixed treatments, which did not differ significantly (0.25±0.02g and 0.27±0.02g, respectively). The bold and mixed treatments had the highest cannibalism rate (11.2±5.1% and 23.1±12.3%, respectively). Overall survival was lowest in the mixed treatment (62.5±13.0%), while that of the bold and shy treatments were similar (82.5±9.2% and 86.2±9.2%, respectively). The separation of L. alexandri larvae by traits can ensure a decrease in cannibalism and hence, more productive larviculture. Copyright © 2017 Elsevier B.V. All rights reserved.
Dengel, Donald R; Evanoff, Nicholas G; Marlatt, Kara L; Geijer, Justin R; Mueller, Bryon A; Lim, Kelvin O
2017-11-01
Hypercapnia has been utilized as a stimulus to elicit changes in cerebral blood flow (CBF). However, in many instances it has been delivered in a non-controlled method that is often difficult to reproduce. The purpose of this study was to examine the within- and between-visit reproducibility of blood oxygen level-dependent (BOLD) signal changes to an iso-oxic square wave alteration in end-tidal carbon dioxide partial pressure (P et CO 2 ). Two 3-Tesla (3T) MRI scans were performed on the same visit, with two square wave alterations administered per scan. The protocol was repeated on a separate visit with minimum of 3 days between scanning sessions. P et CO 2 was altered to stimulate changes in cerebral vascular reactivity (CVR), while P et O 2 was held constant. Eleven subjects (six females; mean age 26·5 ± 5·7 years) completed the full testing protocol. Excellent within-visit square wave reproducibility (ICC > 0·75) was observed. Similarly, square waves were reproducible between scanning sessions (ICC > 0·7). This study demonstrates BOLD signal changes in response to alterations in P et CO 2 are reproducible both within- and between-visit MRI scans. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.
Neurovascular coupling is brain region-dependent.
Devonshire, Ian M; Papadakis, Nikos G; Port, Michael; Berwick, Jason; Kennerley, Aneurin J; Mayhew, John E W; Overton, Paul G
2012-02-01
Despite recent advances in alternative brain imaging technologies, functional magnetic resonance imaging (fMRI) remains the workhorse for both medical diagnosis and primary research. Indeed, the number of research articles that utilise fMRI have continued to rise unabated since its conception in 1991, despite the limitation that recorded signals originate from the cerebral vasculature rather than neural tissue. Consequently, understanding the relationship between brain activity and the resultant changes in metabolism and blood flow (neurovascular coupling) remains a vital area of research. In the past, technical constraints have restricted investigations of neurovascular coupling to cortical sites and have led to the assumption that coupling in non-cortical structures is the same as in the cortex, despite the lack of any evidence. The current study investigated neurovascular coupling in the rat using whole-brain blood oxygenation level-dependent (BOLD) fMRI and multi-channel electrophysiological recordings and measured the response to a sensory stimulus as it proceeded through brainstem, thalamic and cortical processing sites - the so-called whisker-to-barrel pathway. We found marked regional differences in the amplitude of BOLD activation in the pathway and non-linear neurovascular coupling relationships in non-cortical sites. The findings have important implications for studies that use functional brain imaging to investigate sub-cortical function and caution against the use of simple, linear mapping of imaging signals onto neural activity. Copyright © 2011 Elsevier Inc. All rights reserved.
Klefoth, Thomas; Skov, Christian; Kuparinen, Anna; Arlinghaus, Robert
2017-12-01
In passively operated fishing gear, boldness-related behaviors should fundamentally affect the vulnerability of individual fish and thus be under fisheries selection. To test this hypothesis, we used juvenile common-garden reared carp ( Cyprinus carpio ) within a narrow size range to investigate the mechanistic basis of behavioral selection caused by angling. We focused on one key personality trait (i.e., boldness), measured in groups within ponds, two morphological traits (body shape and head shape), and one life-history trait (juvenile growth capacity) and studied mean standardized selection gradients caused by angling. Carp behavior was highly repeatable within ponds. In the short term, over seven days of fishing, total length, not boldness, was the main predictor of angling vulnerability. However, after 20 days of fishing, boldness turned out to be the main trait under selection, followed by juvenile growth rate, while morphological traits were only weakly related to angling vulnerability. In addition, we found juvenile growth rate to be moderately correlated with boldness. Hence, direct selection on boldness will also induce indirect selection on juvenile growth and vice versa, but given that the two traits are not perfectly correlated, independent evolution of both traits is also possible. Our study is among the first to mechanistically reveal that energy-acquisition-related behaviors, and not growth rate per se, are key factors determining the probability of capture, and hence, behavioral traits appear to be the prime targets of angling selection. We predict an evolutionary response toward increased shyness in intensively angling-exploited fish stocks, possibly causing the emergence of a timidity syndrome.
Ellis, Jennifer D; Schroder, Hans S; Patrick, Christopher J; Moser, Jason S
2017-10-01
Individuals with psychopathic traits often demonstrate blunted reactivity to negative emotional stimuli. However, it is not yet clear whether these individuals also have difficulty regulating their emotional responses to negative stimuli. To address this question, participants with varying levels of psychopathic traits (indexed by the Triarchic Measure of Psychopathy; Patrick, 2010) completed a task in which they passively viewed, increased, or decreased their emotions to negative picture stimuli while electrocortical activity was recorded. During passive viewing of negative images, higher boldness, but not higher disinhibition or meanness, was associated with reduced amplitude of the late positive potential (LPP), an ERP that indexes reactivity to emotionally relevant stimuli. However, all participants demonstrated expected enhancement of the LPP when asked to increase their emotional response. Participants did not show expected suppression of the LPP when asked to decrease their emotional response. Contrary to the electrophysiological data, individuals with higher boldness did not self-report experiencing blunted emotional response during passive viewing trials, and they reported experiencing greater emotional reactivity relative to other participants when regulating (e.g., both increasing and decreasing) their emotions. Results suggest inconsistency between physiological and self-report indices of emotion among high-bold individuals during both affective processing and regulation. © 2017 Society for Psychophysiological Research.
Outcome dependency alters the neural substrates of impression formation
Ames, Daniel L.; Fiske, Susan T.
2015-01-01
How do people maintain consistent impressions of other people when other people are often inconsistent? The present research addresses this question by combining recent neuroscientific insights with ecologically meaningful behavioral methods. Participants formed impressions of real people whom they met in a personally involving situation. fMRI and supporting behavioral data revealed that outcome dependency (i.e., depending on another person for a desired outcome) alters previously identified neural dynamics of impression formation. Consistent with past research, a functional localizer identified a region of dorsomedial PFC previously linked to social impression formation. In the main task, this ROI revealed the predicted patterns of activity across outcome dependency conditions: greater BOLD response when information confirmed (vs. violated) social expectations if participants were outcome-independent and the reverse pattern if participants were outcome-dependent. We suggest that, although social perceivers often discount expectancy-disconfirming information as noise, being dependent on another person for a desired outcome focuses impression-formation processing on the most diagnostic information, rather than on the most tractable information. PMID:23850465
Wu, Xi; Yang, Zhipeng; Bailey, Stephen K; Zhou, Jiliu; Cutting, Laurie E; Gore, John C; Ding, Zhaohua
2017-05-15
Functional MRI has proven to be effective in detecting neural activity in brain cortices on the basis of blood oxygenation level dependent (BOLD) contrast, but has relatively poor sensitivity for detecting neural activity in white matter. To demonstrate that BOLD signals in white matter are detectable and contain information on neural activity, we stimulated the somatosensory system and examined distributions of BOLD signals in related white matter pathways. The temporal correlation profiles and frequency contents of BOLD signals were compared between stimulation and resting conditions, and between relevant white matter fibers and background regions, as well as between left and right side stimulations. Quantitative analyses show that, overall, MR signals from white matter fiber bundles in the somatosensory system exhibited significantly greater temporal correlations with the primary sensory cortex and greater signal power during tactile stimulations than in a resting state, and were stronger than corresponding measurements for background white matter both during stimulations and in a resting state. The temporal correlation and signal power under stimulation were found to be twice those observed from the same bundle in a resting state, and bore clear relations with the side of stimuli. These indicate that BOLD signals in white matter fibers encode neural activity related to their functional roles connecting cortical volumes, which are detectable with appropriate methods. Copyright © 2017 Elsevier Inc. All rights reserved.
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.
Implications of oxidative stress in the brain plasticity originated by fasting: a BOLD-fMRI study.
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 and the maximum intensity of BOLD signal in the activated area M1 was determined for all studied volunteers. The current study allowed measuring regional brain volumes and neural network activity before and during an extended period of fasting using BOLD-fMRI. This demonstrated and confirmed the impact of fasting on human brain structure and function. Further studies are required to elucidate mechanisms and enable direct inference of a diet-induced OS effect on the brain.
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 results extend our understanding of the electrophysiological signature of BOLD RSNs and demonstrate the intrinsic connection between the fast neuronal activity and slow hemodynamic fluctuations. Copyright © 2012 Elsevier Inc. All rights reserved.
Brightness and transparency in the early visual cortex.
Salmela, Viljami R; Vanni, Simo
2013-06-24
Several psychophysical studies have shown that transparency can have drastic effects on brightness and lightness. However, the neural processes generating these effects have remained unresolved. Several lines of evidence suggest that the early visual cortex is important for brightness perception. While single cell recordings suggest that surface brightness is represented in the primary visual cortex, the results of functional magnetic resonance imaging (fMRI) studies have been discrepant. In addition, the location of the neural representation of transparency is not yet known. We investigated whether the fMRI responses in areas V1, V2, and V3 correlate with brightness and transparency. To dissociate the blood oxygen level-dependent (BOLD) response to brightness from the response to local border contrast and mean luminance, we used variants of White's brightness illusion, both opaque and transparent, in which luminance increments and decrements cancel each other out. The stimuli consisted of a target surface and a surround. The surround luminance was always sinusoidally modulated at 0.5 Hz to induce brightness modulation to the target. The target luminance was constant or modulated in counterphase to null brightness modulation. The mean signal changes were calculated from the voxels in V1, V2, and V3 corresponding to the retinotopic location of the target surface. The BOLD responses were significantly stronger for modulating brightness than for stimuli with constant brightness. In addition, the responses were stronger for transparent than for opaque stimuli, but there was more individual variation. No interaction between brightness and transparency was found. The results show that the early visual areas V1-V3 are sensitive to surface brightness and transparency and suggest that brightness and transparency are represented separately.
Van Vugt, Dean A; Krzemien, Alicja; Alsaadi, Hanin; Frank, Tamar C; Reid, Robert L
2014-04-16
We postulate that insulin regulation of food intake is compromised when insulin resistance is present. In order to investigate the effect of insulin sensitivity on appetitive brain responses, we conducted functional magnetic resonance imaging studies in a group of women diagnosed with polycystic ovary syndrome (PCOS) in which insulin sensitivity ranged from normal to resistant. Subjects (n=19) were imaged while viewing pictures of high calorie (HC) foods and low calorie (LC) foods after ingesting either 75 g glucose or an equivalent volume of water. The insulin sensitive group showed reduced blood oxygen level dependent (BOLD) signal in response to food pictures following glucose ingestion in numerous corticolimbic brain regions, whereas the insulin resistant group did not. There was a significant interaction between insulin sensitivity (sensitive vs resistant) and condition (water vs glucose). The largest clusters identified included the left insula, bilateral limbic/parahippocampal gyrus/culmen/midbrain, bilateral limbic lobe/precuneus, and left superior/mid temporal gyrus/parietal for HC and LC stimuli combined, the left parahippocampal gyrus/fusiform/pulvinar/midbrain for HC pictures, and the left superior/mid temporal gyrus/parietal and middle/inferior frontal gyrus/orbitofrontal cortex for LC pictures. Furthermore, BOLD signal in the anterior cingulate, medial frontal gyrus, posterior cingulate/precuneus, and parietal cortex during a glucose challenge correlated negatively with insulin sensitivity. We conclude the PCOS women with insulin resistance have an impaired brain response to a glucose challenge. The inability of postprandial hyperinsulinemia to inhibit brain responsiveness to food cues in insulin resistant subjects may lead to greater non-homeostatic eating. Copyright © 2014 Elsevier B.V. All rights reserved.
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.
High efficiency multishot interleaved spiral-in/out: acquisition for high-resolution BOLD fMRI.
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 high spatial resolution BOLD functional magnetic resonance imaging applications. © 2012 Wiley Periodicals, Inc.
Functional MRI of human pancreas using BOLD contrast: Responses following glucose ingestion.
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.
Slobounov, Semyon M.; Zhang, K.; Pennell, D.; Ray, W.; Johnson, B.; Sebastianelli, W.
2010-01-01
Memory problems are one of the most common symptoms of sport-related mild traumatic brain injury (MTBI), known as concussion. Surprisingly, little research has examined spatial memory in concussed athletes given its importance in athletic environments. Here, we combine functional magnetic resonance imaging (fMRI) with a virtual reality (VR) paradigm designed to investigate the possibility of residual functional deficits in recently concussed but asymptomatic individuals. Specifically, we report performance of spatial memory navigation tasks in a VR environment and fMRI data in 15 athletes suffering from MTBI and 15 neurologically normal, athletically active age matched controls. No differences in performance were observed between these two groups of subjects in terms of success rate (94 and 92%) and time to complete the spatial memory navigation tasks (mean = 19.5 and 19.7 s). Whole brain analysis revealed that similar brain activation patterns were observed during both encoding and retrieval among the groups. However, concussed athletes showed larger cortical networks with additional increases in activity outside of the shared region of interest (ROI) during encoding. Quantitative analysis of blood oxygen level dependent (BOLD) signal revealed that concussed individuals had a significantly larger cluster size during encoding at parietal cortex, right dorsolateral prefrontal cortex, and right hippocampus. In addition, there was a significantly larger BOLD signal percent change at the right hippocampus. Neither cluster size nor BOLD signal percent change at shared ROIs was different between groups during retrieval. These major findings are discussed with respect to current hypotheses regarding the neural mechanism responsible for alteration of brain functions in a clinical setting. PMID:20039023
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
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
The Effect of Passive Movement for Paretic Ankle-Foot and Brain Activity in Post-Stroke Patients.
Vér, Csilla; Emri, Miklós; Spisák, Tamás; Berényi, Ervin; Kovács, Kázmér; Katona, Péter; Balkay, László; Menyhárt, László; Kardos, László; Csiba, László
2016-01-01
This study aims at investigating the short-term efficacy of the continuous passive motion (CPM) device developed for the therapy of ankle-foot paresis and to investigate by fMRI the blood oxygen level-dependent responses (BOLD) during ankle passive movement (PM). Sixty-four stroke patients were investigated. Patients were assigned into 2 groups: 49 patients received both 15 min manual and 30 min device therapy (M + D), while the other group (n = 15) received only 15 min manual therapy (M). A third group of stroke patients (n = 12) was investigated by fMRI before and immediately after 30 min CPM device therapy. There was no direct relation between the fMRI group and the other 2 groups. All subjects were assessed using the Modified Ashworth Scale (MAS) and a goniometer. Mean MAS decreased, the ankle's mean plantar flexion and dorsiflexion passive range of motion (PROM) increased and the equinovalgus improved significantly in the M + D group. In the fMRI group, the PM of the paretic ankle increased BOLD responses; this was observed in the contralateral pre- and postcentral gyrus, superior temporal gyrus, central opercular cortex, and in the ipsilateral postcentral gyrus, frontal operculum cortex and cerebellum. Manual therapy with CPM device therapy improved the ankle PROM, equinovalgus and severity of spasticity. The ankle PM increased ipsi- and contralateral cortical activation. © 2016 S. Karger AG, Basel.
Labudda, Kirsten; Woermann, Friedrich G; Mertens, Markus; Pohlmann-Eden, Bernd; Markowitsch, Hans J; Brand, Matthias
2008-06-01
Recent functional neuroimaging and lesion studies demonstrate the involvement of the orbitofrontal/ventromedial prefrontal cortex as a key structure in decision making processes. This region seems to be particularly crucial when contingencies between options and consequences are unknown but have to be learned by the use of feedback following previous decisions (decision making under ambiguity). However, little is known about the neural correlates of decision making under risk conditions in which information about probabilities and potential outcomes is given. In the present study, we used functional magnetic resonance imaging to measure blood-oxygenation-level-dependent (BOLD) responses in 12 subjects during a decision making task. This task provided explicit information about probabilities and associated potential incentives. The responses were compared to BOLD signals in a control condition without information about incentives. In contrast to previous decision making studies, we completely removed the outcome phase following a decision to exclude the potential influence of feedback previously received on current decisions. The results indicate that the integration of information about probabilities and incentives leads to activations within the dorsolateral prefrontal cortex, the posterior parietal lobe, the anterior cingulate and the right lingual gyrus. We assume that this pattern of activation is due to the involvement of executive functions, conflict detection mechanisms and arithmetic operations during the deliberation phase of decisional processes that are based on explicit information.
Ganesh, Shanti; van Schie, Hein T; Cross, Emily S; de Lange, Floris P; Wigboldus, Daniël H J
2015-08-01
Mental imagery of one's body moving through space is important for imagining changing visuospatial perspectives, as well as for determining how we might appear to other people. Previous neuroimaging research has implicated the temporoparietal junction (TPJ) in this process. It is unclear, however, how neural activity in the TPJ relates to the rotation perspectives from which mental spatial transformation (MST) of one's own body can take place, i.e. from an egocentric or an allocentric perspective. It is also unclear whether TPJ involvement in MST is self-specific or whether the TPJ may also be involved in MST of other human bodies. The aim of the current study was to disentangle neural processes involved in egocentric versus allocentric MSTs of human bodies representing self and other. We measured functional brain activity of healthy participants while they performed egocentric and allocentric MSTs in relation to whole-body photographs of themselves and a same-sex stranger. Findings indicated higher blood oxygen level-dependent (BOLD) response in bilateral TPJ during egocentric versus allocentric MST. Moreover, BOLD response in the TPJ during egocentric MST correlated positively with self-report scores indicating how awkward participants felt while viewing whole-body photos of themselves. These findings considerably advance our understanding of TPJ involvement in MST and its interplay with self-awareness. Copyright © 2015 Elsevier Inc. All rights reserved.
Barrett, Frederick S; Janata, Petr
2016-10-01
Nostalgia is an emotion that is most commonly associated with personally and socially relevant memories. It is primarily positive in valence and is readily evoked by music. It is also an idiosyncratic experience that varies between individuals based on affective traits. We identified frontal, limbic, paralimbic, and midbrain brain regions in which the strength of the relationship between ratings of nostalgia evoked by music and blood-oxygen-level-dependent (BOLD) signal was predicted by affective personality measures (nostalgia proneness and the sadness scale of the Affective Neuroscience Personality Scales) that are known to modulate the strength of nostalgic experiences. We also identified brain areas including the inferior frontal gyrus, substantia nigra, cerebellum, and insula in which time-varying BOLD activity correlated more strongly with the time-varying tonal structure of nostalgia-evoking music than with music that evoked no or little nostalgia. These findings illustrate one way in which the reward and emotion regulation networks of the brain are recruited during the experiencing of complex emotional experiences triggered by music. These findings also highlight the importance of considering individual differences when examining the neural responses to strong and idiosyncratic emotional experiences. Finally, these findings provide a further demonstration of the use of time-varying stimulus-specific information in the investigation of music-evoked experiences. Copyright © 2016 Elsevier Ltd. All rights reserved.
Fera, Francesco; Passamonti, Luca; Herzallah, Mohammad M; Myers, Catherine E; Veltri, Pierangelo; Morganti, Giuseppina; Quattrone, Aldo; Gluck, Mark A
2014-07-01
To test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands. Copyright © 2013 Wiley Periodicals, Inc.
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.
Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation
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
El-Hage, W; Zelaya, F; Radua, J; Gohier, B; Alsop, D C; Phillips, M L; Surguladze, S A
2013-08-01
Serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with modulation of resting-state amygdala level, which was considered to underlie a risk for mood and anxiety disorders. The findings however have been inconsistent which could be related to interactions of the genotype with other factors e.g. sex or personality characteristics. Therefore, the aim of the present study was to explore the modulation of the amygdala perfusion in the resting-state by sex and 5-HTTLPR/rs25531 genotype, controlled for personality dimensions assessed by Temperament and Character Inventory (Cloninger et al., 1994). The resting-state cerebral blood flow (rCBF) was examined using an arterial spin labelling technique. All participants were genotyped for the 5-HTTLPR/rs25531 genotype (L/L-L/S-S/S genotypes and LA-LG variants). The study group comprised 81 right-handed Caucasian healthy volunteers (42 females) aged 19-55 years. We measured rCBF in the amygdala and in the whole-brain grey matter. The data of blood-oxygen-level-dependent (BOLD) response in amygdala to fearful dynamic faces in the same sample were also analysed. There was a significant main effect of sex in both the left and right amygdalae, with higher rCBF in males. Main effect of 5-HTTLPR/rs25531 genotype which was significant in the right amygdala only, was accounted for by higher rCBF in S/S vs. L/L homozygotes. An interaction between sex and 5-HTTLPR/rs25531 genotype was observed in rCBF in the right amygdala. This was accounted for by higher values of rCBF in the right amygdala in males' S allele carriers compared with females. In females, there was a significant negative correlation between the rCBF and BOLD response in the right amygdala, and more so in S carriers. In males, there was no significant correlation between rCBF and BOLD response in the right amygdala. The novelty of our results lies in the demonstration of gene by sex interaction with resting blood flow in the amygdala that elucidates sex-related differences in emotional reactivity. Copyright © 2013 Elsevier Inc. All rights reserved.
Nasrallah, Fatima A; Lew, Si Kang; Low, Amanda Si-Min; Chuang, Kai-Hsiang
2014-01-01
Correlative fluctuations in functional MRI (fMRI) signals across the brain at rest have been taken as a measure of functional connectivity, but the neural basis of this resting-state MRI (rsMRI) signal is not clear. Previously, we found that the α2 adrenergic agonist, medetomidine, suppressed the rsMRI correlation dose-dependently but not the stimulus evoked activation. To understand the underlying electrophysiology and neurovascular coupling, which might be altered due to the vasoconstrictive nature of medetomidine, somatosensory evoked potential (SEP) and resting electroencephalography (EEG) were measured and correlated with corresponding BOLD signals in rat brains under three dosages of medetomidine. The SEP elicited by electrical stimulation to both forepaws was unchanged regardless of medetomidine dosage, which was consistent with the BOLD activation. Identical relationship between the SEP and BOLD signal under different medetomidine dosages indicates that the neurovascular coupling was not affected. Under resting state, EEG power was the same but a depression of inter-hemispheric EEG coherence in the gamma band was observed at higher medetomidine dosage. Different from medetomidine, both resting EEG power and BOLD power and coherence were significantly suppressed with increased isoflurane level. Such reduction was likely due to suppressed neural activity as shown by diminished SEP and BOLD activation under isoflurane, suggesting different mechanisms of losing synchrony at resting-state. Even though, similarity between electrophysiology and BOLD under stimulation and resting-state implicates a tight neurovascular coupling in both medetomidine and isoflurane. Our results confirm that medetomidine does not suppress neural activity but dissociates connectivity in the somatosensory cortex. The differential effect of medetomidine and its receptor specific action supports the neuronal origin of functional connectivity and implicates the mechanism of its sedative effect. © 2013. Published by Elsevier Inc. All rights reserved.
Dzieweczynski, Teresa L; Portrais, Kelley B; Stevens, Megan A; Kane, Jessica L; Lawrence, Jaslynn M
2018-04-01
Components of boldness, such as activity level and locomotion, influence an individual's ability to avoid predators and acquire resources, generating fitness consequences. The presence of endocrine disrupting chemicals (EDCs) in the aquatic environment may affect fitness by changing morphology or altering behaviors like courtship and exploration. Most research on EDC-generated behavioral effects has focused on estrogen mimics and reproductive endpoints. Far fewer studies have examined the effects of other types of EDCs or measured non-reproductive behaviors. EDCs with antiandrogenic properties are present in waterways yet we know little about their effects on exposed individuals although they may produce effects similar to those caused by estrogen mimics because they act on the same hormonal pathway. To examine the effects of antiandrogens on boldness, this study exposed male Siamese fighting fish, Betta splendens, to a high or low dose of one of two antiandrogens, vinclozolin or flutamide, and observed behavior in three boldness assays, both before and after exposure. Overall, antiandrogen exposure increased boldness behavior, especially following exposure to the higher dose. Whether or not antiandrogen exposure influenced boldness, as well as the nature and intensity of the effect, was assay-dependent. This demonstrates the importance of studying EDC effects in a range of contexts and, at least within this species, suggests that antiandrogenic compounds may generate distinct physiological effects in different situations. How and why the behavioral effects differ from those caused by exposure to an estrogen mimic, as well as the potential consequences of increased activity levels, are discussed. Exposure to an antiandrogen, regardless of dose, produced elevated activity levels and altered shoaling and exploration in male Siamese fighting fish. These modifications may have fitness consequences. Copyright © 2018 Elsevier Ltd. All rights reserved.
Gompf, Florian; Pflug, Anja; Laufs, Helmut; Kell, Christian A.
2017-01-01
Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region. PMID:29249950
Gould van Praag, Cassandra D; Garfinkel, Sarah; Ward, Jamie; Bor, Daniel; Seth, Anil K
2016-07-29
In grapheme-colour synaesthesia (GCS), the presentation of letters or numbers induces an additional 'concurrent' experience of colour. Early functional MRI (fMRI) investigations of GCS reported activation in colour-selective area V4 during the concurrent experience. However, others have failed to replicate this key finding. We reasoned that individual differences in synaesthetic phenomenology might explain this inconsistency in the literature. To test this hypothesis, we examined fMRI BOLD responses in a group of grapheme-colour synaesthetes (n=20) and matched controls (n=20) while characterising the individual phenomenology of the synaesthetes along dimensions of 'automaticity' and 'localisation'. We used an independent functional localiser to identify colour-selective areas in both groups. Activations in these areas were then assessed during achromatic synaesthesia-inducing, and non-inducing conditions; we also explored whole brain activations, where we sought to replicate the existing literature regarding synaesthesia effects. Controls showed no significant activations in the contrast of inducing > non-inducing synaesthetic stimuli, in colour-selective ROIs or at the whole brain level. In the synaesthete group, we correlated activation within colour-selective ROIs with individual differences in phenomenology using the Coloured Letters and Numbers (CLaN) questionnaire which measures, amongst other attributes, the subjective automaticity/attention in synaesthetic concurrents, and their spatial localisation. Supporting our hypothesis, we found significant correlations between individual measures of synaesthetic phenomenology and BOLD responses in colour-selective areas, when contrasting inducing against non-inducing stimuli. Specifically, left-hemisphere colour area responses were stronger for synaesthetes scoring high on phenomenological localisation and automaticity/attention, while right-hemisphere colour area responses showed a relationship with localisation only. In exploratory whole brain analyses, the BOLD response within several other areas was also correlated with these phenomenological factors, including the intra-parietal sulcus, insula, precentral and supplementary motor areas. Our findings reveal a network of regions underlying synaesthetic phenomenology and they help reconcile the diversity of previous results regarding colour-selective BOLD responses during synaesthesia, by establishing a bridge between neural responses and individual synaesthetic phenomenology. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
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.
GPS baseline configuration design based on robustness analysis
NASA Astrophysics Data System (ADS)
Yetkin, M.; Berber, M.
2012-11-01
The robustness analysis results obtained from a Global Positioning System (GPS) network are dramatically influenced by the configuration
NASA Astrophysics Data System (ADS)
Tuccari, G.; Bezrukovs, Vl.; Nechaeva, M.
2012-12-01
A digital base band converter (DBBC) system has been developed by the Istituto di Radioastronomia (Noto, Italy) for increasing the sensitivity of European VLBI Network (EVN) by expanding the full observed bandwidth using numerical methods. The output data rate of this VLBI-backend is raised from 1 to 4 Gbps for each radiotelescope. All operations related to the signal processing (frequency translation, amplification, frequency generation with local oscillators, etc.) are transferred to the digital domain, which allows - in addition to well-known advantages coming from digital technologies - achieving better repeatability, precision, simplicity, etc. The maximum input band of DBBC system is 3.5 GHz, and the instantaneous bandwidth is up to 1 GHz for each radio frequency/intermediate frequency (RF/IF) out of the eight possible. This backend is a highly powerful platform for other radioastronomy applications, and a number of additional so-called personalities have been developed and used. This includes PFB (polyphase filter bank) receivers and Spectra for high resolution spectroscopy. An additional new development with the same aim - to use the DBBC system as a multi-purpose backend - is related to the bi-static radar observations including Radar VLBI. In such observations it is possible to study the population of space debris, with detection of even centimetre class fragments. A powerful transmitter is used to illuminate the sky region to be analyzed, and the echoes coming from known or unknown objects are reflected to one or more groundbased telescopes thus producing a single-dish or interferometric detection. The DBBC Radar VLBI personality is able to realize a high-resolution spectrum analysis, maintaining in the central area the echo signal at the expected frequency including the Doppler shift of frequency. For extremely weak signals a very large integration time is needed, so for this personality different input parameters are provided. The realtime information can then allow exploring easily the desired range of search for unknown or not fully determined orbit objects. These features make Radar VLBI personality most useful in the space debris measurements. DBBC sistēma izstrādāta Noto Radioastronomijas institūtā. Sistēmas galvenais
The Shape of Things to Come: The Military Benefits of the Brain-Computer Interface in 2040
2015-04-01
blood flow using a method referred to as blood-oxygen-level contrast (BOLD).20, 21 The hemodynamic responses are an indication of increased demand...both human and animal studies. One key disadvantage to fMRI/BOLD is that since the basis of measurement is the indirect detection of blood flow ...analytical tool to assess brain injury, BCIs enhance a patient’s quality of life. For example, the cochlear implant, developed in 1976, can be seen as an
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gilmore, R.; Pei, X.; Moss, F.
We show how a topological model which describes the stretching and squeezing mechanisms responsible for creating chaotic behavior can be extracted from the neural spike train data. The mechanism we have identified is the same one ([open quotes]gateau roul[acute e],[close quotes] or jelly-roll) which has previously been identified in the Duffing oscillator [Gilmore and McCallum, Phys. Rev. E [bold 51], 935 (1995)] and in a YAG laser [Boulant [ital et al.], Phys. Rev. E [bold 55], 5082 (1997)]. [copyright] [ital 1999 American Institute of Physics.
Fierstra, Jorn; van Niftrik, Christiaan; Warnock, Geoffrey; Wegener, Susanne; Piccirelli, Marco; Pangalu, Athina; Esposito, Giuseppe; Valavanis, Antonios; Buck, Alfred; Luft, Andreas; Bozinov, Oliver; Regli, Luca
2018-03-01
Increased stroke risk correlates with hemodynamic failure, which can be assessed with ( 15 O-)H 2 O positron emission tomography (PET) cerebral blood flow (CBF) measurements. This gold standard technique, however, is not established for routine clinical imaging. Standardized blood oxygen-level-dependent (BOLD) functional magnetic resonance imaging+CO 2 is a noninvasive and potentially widely applicable tool to assess whole-brain quantitative cerebrovascular reactivity (CVR). We examined the agreement between the 2 imaging modalities and hypothesized that quantitative CVR can be a surrogate imaging marker to assess hemodynamic failure. Nineteen data sets of subjects with chronic cerebrovascular steno-occlusive disease (age, 60±11 years; 4 women) and unilaterally impaired perfusion reserve on Diamox-challenged ( 15 O-)H 2 O PET were studied and compared with a standardized BOLD functional magnetic resonance imaging+CO 2 examination within 6 weeks (8±19 days). Agreement between quantitative CBF- and CVR-based perfusion reserve was assessed. Hemodynamic failure was staged according to PET findings: stage 0: normal CBF, normal perfusion reserve; stage I: normal CBF, decreased perfusion reserve; and stage II: decreased CBF, decreased perfusion reserve. The BOLD CVR data set of the same subjects was then matched to the corresponding stage of hemodynamic failure. PET-based stage I versus stage II could also be clearly separated with BOLD CVR measurements (CVR for stage I 0.11 versus CVR for stage II -0.03; P <0.01). Hemispheric and middle cerebral artery territory difference analyses (ie, affected versus unaffected side) showed a significant correlation for CVR impairment in the affected hemisphere and middle cerebral artery territory ( P <0.01, R 2 =0.47 and P =0.02, R 2 = 0.25, respectively). BOLD CVR corresponded well to CBF perfusion reserve measurements obtained with ( 15 O-)H 2 O-PET, especially for detecting hemodynamic failure in the affected hemisphere and middle cerebral artery territory and for identifying hemodynamic failure stage II. BOLD CVR may, therefore, be considered for prospective studies assessing stroke risk in patients with chronic cerebrovascular steno-occlusive disease, in particular because it can potentially be implemented in routine clinical imaging. © 2018 American Heart Association, Inc.
Eddy correlation measurements of size-dependent cloud droplet turbulent fluxes to complex terrain
NASA Astrophysics Data System (ADS)
Vong, Richard J.; Kowalski, Andrew S.
1995-07-01
An eddy correlation technique was used to measure the turbulent flux of cloud droplets to complex, forested terrain near the coast of Washington State during the spring of 1993. Excellent agreement was achieved for cloud liquid water content measured by two instruments. Substantial downward liquid water fluxes of
1mm per 24 h were measured at night during "steady and continuous" cloud events, about twice the magnitude of those measured by Beswick etal. in Scotland. Cloud water chemical fluxes were estimated to represent up to 50% of the chemical deposition associated with precipitation at the site. An observed size-dependence in the turbulent liquid water fluxes suggested that both droplet impaction, which leads to downward fluxes, and phase change processes, which can lead to upward fluxes, consistently are important contributors to the eddy correlation results. The diameter below which phase change processes were important to observed fluxes was shown to depend upon σL
, the relative standard deviation of the liquid water content (LWC) within a 30-min averaging period. The crossover from upward to downward LW flux occurs at 8µm for steady and continuous cloud events but at
13µm for events with a larger degree of LWC variability. This comparison of the two types of cloud events suggested that evaporation was the most likely cause of upward droplet fluxes for the smaller droplets (dia<13µm) during cloud with variable LWC (σL
>0.3).
Investigation of BOLD fMRI Resonance Frequency Shifts and Quantitative Susceptibility Changes at 7 T
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
Kimberley, Teresa J; Pickett, Kristen A
2012-01-01
The pathophysiology of focal hand dystonia (FHD) is not clearly understood. Previous studies have reported increased and decreased cortical activity associated with motor tasks. The aim of this study was to investigate blood oxygen level dependent (BOLD) signal changes in functional magnetic resonance imaging within the hand area of primary motor cortex during cued movement of individual digits. Eight healthy individuals and five individuals with right hand FHD participated. Beta weight contrasts were examined within the hand area of the motor cortex. In both groups, BOLD signal changes in the hemisphere contralateral to the moving hand were greater in the left hemisphere than the right. Between groups, no difference was found during control of the left hand, but a significant difference was seen during right hand movement; specifically, individuals with dystonia showed increased contralateral and decreased ipsilateral cortical response associated with the affected hand as compared to healthy individuals. This suggests a similar, albeit exaggerated pattern of activation in individuals with FHD on the affected side. These results suggest different levels of ipsilateral and contralateral activation between healthy and dystonic individuals but also show a relative difference between symptomatic and asymptomatic control within the patient population.
Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation.
Johnstone, Tom; Salomons, Tim V; Backonja, Miroslav Misha; Davidson, Richard J
2012-01-16
The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49°C) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid-cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum. Copyright © 2011 Elsevier Inc. All rights reserved.
Assessment of sexual orientation using the hemodynamic brain response to visual sexual stimuli.
Ponseti, Jorge; Granert, Oliver; Jansen, Olav; Wolff, Stephan; Mehdorn, Hubertus; Bosinski, Hartmut; Siebner, Hartwig
2009-06-01
The assessment of sexual orientation is of importance to the diagnosis and treatment of sex offenders and paraphilic disorders. Phallometry is considered gold standard in objectifying sexual orientation, yet this measurement has been criticized because of its intrusiveness and limited reliability. To evaluate whether the spatial response pattern to sexual stimuli as revealed by a change in blood oxygen level-dependent (BOLD) signal can be used for individual classification of sexual orientation. We used a preexisting functional MRI (fMRI) data set that had been acquired in a nonclinical sample of 12 heterosexual men and 14 homosexual men. During fMRI, participants were briefly exposed to pictures of same-sex and opposite-sex genitals. Data analysis involved four steps: (i) differences in the BOLD response to female and male sexual stimuli were calculated for each subject; (ii) these contrast images were entered into a group analysis to calculate whole-brain difference maps between homosexual and heterosexual participants; (iii) a single expression value was computed for each subject expressing its correspondence to the group result; and (iv) based on these expression values, Fisher's linear discriminant analysis and the kappa-nearest neighbor classification method were used to predict the sexual orientation of each subject. Sensitivity and specificity of the two classification methods in predicting individual sexual orientation. Both classification methods performed well in predicting individual sexual orientation with a mean accuracy of >85% (Fisher's linear discriminant analysis: 92% sensitivity, 85% specificity; kappa-nearest neighbor classification: 88% sensitivity, 92% specificity). Despite the small sample size, the functional response patterns of the brain to sexual stimuli contained sufficient information to predict individual sexual orientation with high accuracy. These results suggest that fMRI-based classification methods hold promise for the diagnosis of paraphilic disorders (e.g., pedophilia).
Zhang, Myron; Avitsian, Rafi; Bhattacharyya, Pallab; Bulacio, Juan; Cendes, Fernando; Enatsu, Rei; Lowe, Mark; Najm, Imad; Nair, Dileep; Phillips, Michael; Gonzalez-Martinez, Jorge
2014-01-01
Abstract Patients with medically intractable epilepsy often undergo invasive evaluation and surgery, with a 50% success rate. The low success rate is likely due to poor identification of the epileptogenic zone (EZ), the brain area causing seizures. This work introduces a new method using functional magnetic resonance imaging (fMRI) with simultaneous direct electrical stimulation of the brain that could help localize the EZ, performed in five patients with medically intractable epilepsy undergoing invasive evaluation with intracranial depth electrodes. Stimulation occurred in a location near the hypothesized EZ and a location away. Electrical recordings in response to stimulation were recorded and compared to fMRI. Multiple stimulation parameters were varied, like current and frequency. The brain areas showing fMRI response were compared with the areas resected and the success of surgery. Robust fMRI maps of activation networks were easily produced, which also showed a significant but weak positive correlation between quantitative measures of blood-oxygen-level-dependent (BOLD) activity and measures of electrical activity in response to direct electrical stimulation (mean correlation coefficient of 0.38 for all acquisitions that produced a strong BOLD response). For four patients with outcome data at 6 months, successful surgical outcome is consistent with the resection of brain areas containing high local fMRI activity. In conclusion, this method demonstrates the feasibility of simultaneous direct electrical stimulation and fMRI in humans, which allows the study of brain connectivity with high resolution and full spatial coverage. This innovative technique could be used to better define the localization and extension of the EZ in intractable epilepsies, as well as for other functional neurosurgical procedures. PMID:24735069
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.
Crowley, Thomas J; Dalwani, Manish S; Mikulich-Gilbertson, Susan K; Du, Yiping P; Lejuez, Carl W; Raymond, Kristen M; Banich, Marie T
2010-09-22
Adolescents with conduct and substance problems ("Antisocial Substance Disorder" (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys. We compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere. Adolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders.
Ries, Michele L.; Jabbar, Britta M.; Schmitz, Taylor W.; Trivedi, Mehul A.; Gleason, Carey E.; Carlsson, Cynthia M.; Rowley, Howard A.; Asthana, Sanjay; Johnson, Sterling C.
2009-01-01
Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer’s disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants’ activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly-significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD. PMID:17445294
Månsson, Kristoffer N T; Salami, Alireza; Carlbring, Per; Boraxbekk, C-J; Andersson, Gerhard; Furmark, Tomas
2017-02-01
Effective psychiatric treatments ameliorate excessive anxiety and induce neuroplasticity immediately after the intervention, indicating that emotional components in the human brain are rapidly adaptable. Still, the interplay between structural and functional neuroplasticity is poorly understood, and studies of treatment-induced long-term neuroplasticity are rare. Functional and structural magnetic resonance imaging (using 3T MRI) was performed in 13 subjects with social anxiety disorder on 3 occasions over 1year. All subjects underwent 9 weeks of Internet-delivered cognitive behaviour therapy in a randomized cross-over design and independent assessors used the Clinically Global Impression-Improvement (CGI-I) scale to determine treatment response. Gray matter (GM) volume, assessed with voxel-based morphometry, and functional blood-oxygen level-dependent (BOLD) responsivity to self-referential criticism were compared between treatment responders and non-responders using 2×2 (group×time; pretreatment to follow-up) ANOVA. At 1-year follow-up, 7 (54%) subjects were classified as CGI-I responders. Left amygdala GM volume was more reduced in responders relative to non-responders from pretreatment to 1-year follow-up (Z=3.67, Family-Wise Error corrected p=0.02). In contrast to previous short-term effects, altered BOLD activations to self-referential criticism did not separate responder groups at follow-up. The structure and function of the amygdala changes immediately after effective psychological treatment of social anxiety disorder, but only reduced amygdala GM volume, and not functional activity, is associated with a clinical response 1year after CBT. Copyright © 2016 Elsevier B.V. All rights reserved.
Dynamic physiological modeling for functional diffuse optical tomography
Diamond, Solomon Gilbert; Huppert, Theodore J.; Kolehmainen, Ville; Franceschini, Maria Angela; Kaipio, Jari P.; Arridge, Simon R.; Boas, David A.
2009-01-01
Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. The diffuse nature of near-infrared photon migration in tissue and the multitude of physiological systems that affect hemodynamics motivate the use of anatomical and physiological models to improve estimates of the functional hemodynamic response. In this paper, we present a linear state-space model for DOT analysis that models the physiological fluctuations present in the data with either static or dynamic estimation. We demonstrate the approach by using auxiliary measurements of blood pressure variability and heart rate variability as inputs to model the background physiology in DOT data. We evaluate the improvements accorded by modeling this physiology on ten human subjects with simulated functional hemodynamic responses added to the baseline physiology. Adding physiological modeling with a static estimator significantly improved estimates of the simulated functional response, and further significant improvements were achieved with a dynamic Kalman filter estimator (paired t tests, n = 10, P < 0.05). These results suggest that physiological modeling can improve DOT analysis. The further improvement with the Kalman filter encourages continued research into dynamic linear modeling of the physiology present in DOT. Cardiovascular dynamics also affect the blood-oxygen-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This state-space approach to DOT analysis could be extended to BOLD fMRI analysis, multimodal studies and real-time analysis. PMID:16242967
Intracranial microprobe for evaluating neuro-hemodynamic coupling in unanesthetized human neocortex
Keller, Corey J.; Cash, Sydney S.; Narayanan, Suresh; Wang, Chunmao; Kuzniecky, Ruben; Carlson, Chad; Devinsky, Orrin; Thesen, Thomas; Doyle, Werner; Sassaroli, Angelo; Boas, David A.; Ulbert, Istvan; Halgren, Eric
2009-01-01
Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a “laminar optode,” a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans. PMID:19428529
Intracranial microprobe for evaluating neuro-hemodynamic coupling in unanesthetized human neocortex.
Keller, Corey J; Cash, Sydney S; Narayanan, Suresh; Wang, Chunmao; Kuzniecky, Ruben; Carlson, Chad; Devinsky, Orrin; Thesen, Thomas; Doyle, Werner; Sassaroli, Angelo; Boas, David A; Ulbert, Istvan; Halgren, Eric
2009-05-15
Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a "laminar optode," a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans.
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.
Adolescent neural response to reward is related to participant sex and task motivation.
Alarcón, Gabriela; Cservenka, Anita; Nagel, Bonnie J
2017-02-01
Risky decision making is prominent during adolescence, perhaps contributed to by heightened sensation seeking and ongoing maturation of reward and dopamine systems in the brain, which are, in part, modulated by sex hormones. In this study, we examined sex differences in the neural substrates of reward sensitivity during a risky decision-making task and hypothesized that compared with girls, boys would show heightened brain activation in reward-relevant regions, particularly the nucleus accumbens, during reward receipt. Further, we hypothesized that testosterone and estradiol levels would mediate this sex difference. Moreover, we predicted boys would make more risky choices on the task. While boys showed increased nucleus accumbens blood oxygen level-dependent (BOLD) response relative to girls, sex hormones did not mediate this effect. As predicted, boys made a higher percentage of risky decisions during the task. Interestingly, boys also self-reported more motivation to perform well and earn money on the task, while girls self-reported higher state anxiety prior to the scan session. Motivation to earn money partially mediated the effect of sex on nucleus accumbens activity during reward. Previous research shows that increased motivation and salience of reinforcers is linked with more robust striatal BOLD response, therefore psychosocial factors, in addition to sex, may play an important role in reward sensitivity. Elucidating neurobiological mechanisms that support adolescent sex differences in risky decision making has important implications for understanding individual differences that lead to advantageous and adverse behaviors that affect health outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.
Latencies in BOLD response during visual attention processes.
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.
Champagne, Allen A; Bhogal, Alex A; Coverdale, Nicole S; Mark, Clarisse I; Cook, Douglas J
2017-12-05
Redistribution of blood flow across different brain regions, arising from the vasoactive nature of hypercapnia, can introduce errors when examining cerebrovascular reactivity (CVR) response delays. In this study, we propose a novel analysis method to characterize hemodynamic delays in the blood oxygen level dependent (BOLD) response to hypercapnia, and hyperoxia, as a way to provide insight into transient differences in vascular reactivity between cortical regions, and across tissue depths. A pseudo-continuous arterial spin labeling sequence was used to acquire BOLD and cerebral blood flow simultaneously in 19 healthy adults (12 F; 20 ± 2 years) during boxcar CO 2 and O 2 gas inhalation paradigms. Despite showing distinct differences in hypercapnia-induced response delay times (P < 0.05; Bonferroni corrected), grey matter regions showed homogenous hemodynamic latencies (P > 0.05) once calibrated for bolus arrival time derived using non-vasoactive hyperoxic gas challenges. Longer hypercapnic temporal delays were observed as the depth of the white matter tissue increased, although no significant differences in response lag were found during hyperoxia across tissue depth, or between grey and white matter. Furthermore, calibration of hypercapnic delays using hyperoxia revealed that deeper white matter layers may be more prone to dynamic redistribution of blood flow, which introduces response lag times ranging between 1 and 3 s in healthy subjects. These findings suggest that the combination of hypercapnic and hyperoxic gas-inhalation MRI can be used to distinguish between differences in CVR that arise as a result of delayed stimulus arrival time (due to the local architecture of the cerebrovasculature), or preferential blood flow distribution. Calibrated response delays to hypercapnia provide important insights into cerebrovascular physiology, and may be used to correct response delays associated with vascular impairment. Copyright © 2017. Published by Elsevier Inc.
Zhang, Sheng; Li, Chiang-Shan Ray
2010-01-15
Brain imaging has provided a useful tool to examine the neural processes underlying human cognition. A critical question is whether and how task engagement influences the observed regional brain activations. Here we highlighted this issue and derived a neural measure of task engagement from the task-residual low-frequency blood oxygenation level-dependent (BOLD) activity in the precuneus. Using independent component analysis, we identified brain regions in the default circuit - including the precuneus and medial prefrontal cortex (mPFC) - showing greater activation during resting as compared to task residuals in 33 individuals. Time series correlations with the posterior cingulate cortex as the seed region showed that connectivity with the precuneus was significantly stronger during resting as compared to task residuals. We hypothesized that if the task-residual BOLD activity in the precuneus reflects engagement, it should account for a certain amount of variance in task-related regional brain activation. In an additional experiment of 59 individuals performing a stop signal task, we observed that the fractional amplitude of low-frequency fluctuation (fALFF) of the precuneus but not the mPFC accounted for approximately 10% of the variance in prefrontal activation related to attentional monitoring and response inhibition. Taken together, these results suggest that task-residual fALFF in the precuneus may be a potential indicator of task engagement. This measurement may serve as a useful covariate in identifying motivation-independent neural processes that underlie the pathogenesis of a psychiatric or neurological condition.
Overweight adolescents' brain response to sweetened beverages mirrors addiction pathways.
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.
Metabolism study of boldenone in human urine by gas chromatography-tandem mass spectrometry.
Wu, Xinchen; Gao, Feng; Zhang, Wenxin; Ni, Jian
2015-11-10
Boldenone (BOLD), an anabolic steroid, is likely to be abused in livestock breeding and in sports. Although some of BOLD metabolites in human urine, such as 5β-adrost-1-en-17β-ol-3-one (BM1), have been detected, investigations on their excretion patterns for both genders are insufficient. Moreover, little research on 17α-BOLD glucuronide as a metabolite in human urine has been reported. The aim of this study is to make a contribution to the knowledge of 17β-BOLD metabolism in humans. Three male and three female volunteers were orally administrated with 30mg 17β-BOLD. Urine samples were collected and analyzed with gas chromatography-tandem mass spectrometry. The data proved that 17β-BOLD, BM1, and 17α-BOLD were excreted in urine in both free and glucuronic conjugated forms after administration of 17β-BOLD. For most subjects, the urinary concentrations of BM1 were higher than that of 17β-BOLD. 17α-BOLD was excreted in small amounts. 17α-BOLD, 17β-BOLD, and BM1 were present naturally in urine with low concentrations. Administration of 30mg 17β-BOLD could not influence the excretion profiles of urinary androsterone, etiocholanolone, and testosterone/epitestosterone ratio. There were no differences in BOLD metabolic patterns between man and woman. Copyright © 2015 Elsevier B.V. All rights reserved.
Brechmann, André; Baumgart, Frank; Scheich, Henning
2002-01-01
Recognition of sound patterns must be largely independent of level and of masking or jamming background sounds. Auditory patterns of relevance in numerous environmental sounds, species-specific vocalizations and speech are frequency modulations (FM). Level-dependent activation of the human auditory cortex (AC) in response to a large set of upward and downward FM tones was studied with low-noise (48 dB) functional magnetic resonance imaging at 3 Tesla. Separate analysis in four territories of AC was performed in each individual brain using a combination of anatomical landmarks and spatial activation criteria for their distinction. Activation of territory T1b (including primary AC) showed the most robust level dependence over the large range of 48-102 dB in terms of activated volume and blood oxygen level dependent contrast (BOLD) signal intensity. The left nonprimary territory T2 also showed a good correlation of level with activated volume but, in contrast to T1b, not with BOLD signal intensity. These findings are compatible with level coding mechanisms observed in animal AC. A systematic increase of activation with level was not observed for T1a (anterior of Heschl's gyrus) and T3 (on the planum temporale). Thus these areas might not be specifically involved in processing of the overall intensity of FM. The rostral territory T1a of the left hemisphere exhibited highest activation when the FM sound level fell 12 dB below scanner noise. This supports the previously suggested special involvement of this territory in foreground-background decomposition tasks. Overall, AC of the left hemisphere showed a stronger level-dependence of signal intensity and activated volume than the right hemisphere. But any side differences of signal intensity at given levels were lateralized to right AC. This might point to an involvement of the right hemisphere in more specific aspects of FM processing than level coding.
Rao, Neena K.; Motes, Michael A.; Rypma, Bart
2014-01-01
Several fMRI studies have examined brain regions mediating inter-subject variability in cognitive efficiency, but none have examined regions mediating intra-subject variability in efficiency. Thus, the present study was designed to identify brain regions involved in intra-subject variability in cognitive efficiency via participant-level correlations between trial-level reaction time (RT) and trial-level fMRI BOLD percent signal change on a processing speed task. On each trial, participants indicated whether a digit-symbol probe-pair was present or absent in an array of nine digit-symbol probe-pairs while fMRI data were collected. Deconvolution analyses, using RT time-series models (derived from the proportional scaling of an event-related hemodynamic response function model by trial-level RT), were used to evaluate relationships between trial-level RTs and BOLD percent signal change. Although task-related patterns of activation and deactivation were observed in regions including bilateral occipital, bilateral parietal, portions of the medial wall such as the precuneus, default mode network regions including anterior cingulate, posterior cingulate, bilateral temporal, right cerebellum, and right cuneus, RT-BOLD correlations were observed in a more circumscribed set of regions. Positive RT-BOLD correlations, where fast RTs were associated with lower BOLD percent signal change, were observed in regions including bilateral occipital, bilateral parietal, and the precuneus. RT-BOLD correlations were not observed in the default mode network indicating a smaller set of regions associated with intra-subject variability in cognitive efficiency. The results are discussed in terms of a distributed area of regions that mediate variability in the cognitive efficiency that might underlie processing speed differences between individuals. PMID:25374527
Rao, Neena K; Motes, Michael A; Rypma, Bart
2014-01-01
Several fMRI studies have examined brain regions mediating inter-subject variability in cognitive efficiency, but none have examined regions mediating intra-subject variability in efficiency. Thus, the present study was designed to identify brain regions involved in intra-subject variability in cognitive efficiency via participant-level correlations between trial-level reaction time (RT) and trial-level fMRI BOLD percent signal change on a processing speed task. On each trial, participants indicated whether a digit-symbol probe-pair was present or absent in an array of nine digit-symbol probe-pairs while fMRI data were collected. Deconvolution analyses, using RT time-series models (derived from the proportional scaling of an event-related hemodynamic response function model by trial-level RT), were used to evaluate relationships between trial-level RTs and BOLD percent signal change. Although task-related patterns of activation and deactivation were observed in regions including bilateral occipital, bilateral parietal, portions of the medial wall such as the precuneus, default mode network regions including anterior cingulate, posterior cingulate, bilateral temporal, right cerebellum, and right cuneus, RT-BOLD correlations were observed in a more circumscribed set of regions. Positive RT-BOLD correlations, where fast RTs were associated with lower BOLD percent signal change, were observed in regions including bilateral occipital, bilateral parietal, and the precuneus. RT-BOLD correlations were not observed in the default mode network indicating a smaller set of regions associated with intra-subject variability in cognitive efficiency. The results are discussed in terms of a distributed area of regions that mediate variability in the cognitive efficiency that might underlie processing speed differences between individuals.
Xiao, Xiao; Dupuis-Roy, Nicolas; Jiang, Jun; Du, Xue; Zhang, Mingmin; Zhang, Qinglin
2018-02-21
The functional magnetic resonance imaging (fMRI) technique was used to investigate brain activations related to conflict control in a taste-visual cross-modal pairing task. On each trial, participants had to decide whether the taste of a gustatory stimulus matched or did not match the expected taste of the food item depicted in an image. There were four conditions: Negative match (NM; sour gustatory stimulus and image of sour food), negative mismatch (NMM; sour gustatory stimulus and image of sweet food), positive match (PM; sweet gustatory stimulus and image of sweet food), positive mismatch (PMM; sweet gustatory stimulus and image of sour food). Blood oxygenation level-dependent (BOLD) contrasts between the NMM and the NM conditions revealed an increased activity in the middle frontal gyrus (MFG) (BA 6), the lingual gyrus (LG) (BA 18), and the postcentral gyrus. Furthermore, the NMM minus NM BOLD differences observed in the MFG were correlated with the NMM minus NM differences in response time. These activations were specifically associated with conflict control during the aversive gustatory stimulation. BOLD contrasts between the PMM and the PM condition revealed no significant positive activation, which supported the hypothesis that the human brain is especially sensitive to aversive stimuli. Altogether, these results suggest that the MFG is associated with the taste-visual cross-modal conflict control. A possible role of the LG as an information conflict detector at an early perceptual stage is further discussed, along with a possible involvement of the postcentral gyrus in the processing of the taste-visual cross-modal sensory contrast. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
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.
Radar studies of midlatitude ionospheric plasma drifts
NASA Astrophysics Data System (ADS)
Scherliess, L.; Fejer, B. G.; Holt, J.; Goncharenko, L.; Amory-Mazaudier, C.; Buonsanto, M. J.
2001-02-01
We use incoherent scatter radar measurements from Millstone Hill and Saint Santin to study the midlatitude F region electrodynamic plasma drifts during geomagnetically quiet and active periods. We present initially a local time, season, and solar flux dependent analytical model of the quiet time zonal and meridional
Functional magnetic resonance imaging.
Buchbinder, Bradley R
2016-01-01
Functional magnetic resonance imaging (fMRI) maps the spatiotemporal distribution of neural activity in the brain under varying cognitive conditions. Since its inception in 1991, blood oxygen level-dependent (BOLD) fMRI has rapidly become a vital methodology in basic and applied neuroscience research. In the clinical realm, it has become an established tool for presurgical functional brain mapping. This chapter has three principal aims. First, we review key physiologic, biophysical, and methodologic principles that underlie BOLD fMRI, regardless of its particular area of application. These principles inform a nuanced interpretation of the BOLD fMRI signal, along with its neurophysiologic significance and pitfalls. Second, we illustrate the clinical application of task-based fMRI to presurgical motor, language, and memory mapping in patients with lesions near eloquent brain areas. Integration of BOLD fMRI and diffusion tensor white-matter tractography provides a road map for presurgical planning and intraoperative navigation that helps to maximize the extent of lesion resection while minimizing the risk of postoperative neurologic deficits. Finally, we highlight several basic principles of resting-state fMRI and its emerging translational clinical applications. Resting-state fMRI represents an important paradigm shift, focusing attention on functional connectivity within intrinsic cognitive networks. © 2016 Elsevier B.V. All rights reserved.
Storti, Silvia F; Del Felice, Alessandra; Formaggio, Emanuela; Boscolo Galazzo, Ilaria; Bongiovanni, Luigi G; Cerini, Roberto; Fiaschi, Antonio; Manganotti, Paolo
2015-07-01
The combined use of electroencephalography (EEG) and functional magnetic resonance imaging (EEG-fMRI) in epilepsy allows the noninvasive hemodynamic characterization of epileptic discharge-related neuronal activations. The aim of this study was to investigate pathophysiologic mechanisms underlying epileptic activity by exploring the spatial and temporal distribution of fMRI signal modifications during seizure in a single patient with posttraumatic epilepsy. EEG and fMRI data were acquired during two scanning sessions: a spontaneous critical episode was observed during the first, and interictal events were recorded during the second. The EEG-fMRI data were analyzed using the general linear model (GLM). Blood oxygenation level-dependent (BOLD) localization derived from the preictal and artifact-free postictal phase was concordant with the BOLD localization of the interictal epileptiform discharges identified in the second session, pointing to a left perilesional mesiofrontal area. Of note, BOLD signal modifications were already visible several seconds before seizure onset. In brief, BOLD activations from the preictal, postictal, and interictal epileptiform discharge analysis appear to be concordant with the clinically driven localization hypothesis, whereas a widespread network of activations is detected during the ictal phase in a partial seizure. © EEG and Clinical Neuroscience Society (ECNS) 2014.
Direct estimation of evoked hemoglobin changes by multimodality fusion imaging
Huppert, Theodore J.; Diamond, Solomon G.; Boas, David A.
2009-01-01
In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI signals. Using numerical simulations, we demonstrate that concurrent optical and BOLD measurements can be used to create cross-calibrated estimates of absolute micromolar deoxyhemoglobin changes. We apply this new analysis tool to experimental data acquired simultaneously with both DOT and BOLD imaging during a motor task, demonstrate the ability to more robustly estimate hemoglobin changes in comparison to DOT alone, and show how this approach can provide cross-calibrated estimates of hemoglobin changes. Using this multimodal method, we estimate the calibration of the 3 tesla BOLD signal to be −0.55% ± 0.40% signal change per micromolar change of deoxyhemoglobin. PMID:19021411
Post-stroke aphasia recovery assessed with fMRI and a picture identification task
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 of the picture identification task for post-stroke language recovery evaluation. Study data suggest that adult stroke patients utilize functional peri-stroke areas to perform language functions. PMID:20719532
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.
Affective neural response to restricted interests in Autism Spectrum Disorders
Cascio, Carissa J.; Foss-Feig, Jennifer H.; Heacock, Jessica; Schauder, Kimberly B.; Loring, Whitney A.; Rogers, Baxter P.; Pryweller, Jennifer R.; Newsom, Cassandra R.; Cockhren, Jurnell; Cao, Aize; Bolton, Scott
2013-01-01
Background Restricted interests are a class of repetitive behavior in autism spectrum disorders (ASD) whose intensity and narrow focus often contribute to significant interference with daily functioning. While numerous neuroimaging studies have investigated executive circuits as putative neural substrates of repetitive behavior, recent work implicates affective neural circuits in restricted interests. We sought to explore the role of affective neural circuits and determine how restricted interests are distinguished from hobbies or interests in typical development. Methods We compared a group of children with ASD to a typically developing (TD) group of children with strong interests or hobbies, employing parent report, an operant behavioral task, and functional imaging with personalized stimuli based on individual interests. Results While performance on the operant task was similar between the two groups, parent report of intensity and interference of interests was significantly higher in the ASD group. Both the ASD and TD groups showed increased BOLD response in widespread affective neural regions to pictures of their own interest. When viewing pictures of other children's interests, the TD group showed a similar pattern, whereas BOLD response in the ASD group was much more limited. Increased BOLD response in the insula and anterior cingulate cortex distinguished the ASD from the TD group, and parent report of the intensity and interference with daily life of the child's restricted interest predicted insula response. Conclusions While affective neural network response and operant behavior are comparable in typical and restricted interests, the narrowness of focus that clinically distinguishes restricted interests in ASD is reflected in more interference in daily life and aberrantly enhanced insula and anterior cingulate response to individuals’ own interests in the ASD group. These results further support the involvement of affective neural networks in repetitive behaviors in ASD. PMID:24117668
Xu, Nan; Spreng, R Nathan; Doerschuk, Peter C
2017-01-01
Resting-state functional MRI (rs-fMRI) is widely used to noninvasively study human brain networks. Network functional connectivity is often estimated by calculating the timeseries correlation between blood-oxygen-level dependent (BOLD) signal from different regions of interest (ROIs). However, standard correlation cannot characterize the direction of information flow between regions. In this paper, we introduce and test a new concept, prediction correlation, to estimate effective connectivity in functional brain networks from rs-fMRI. In this approach, the correlation between two BOLD signals is replaced by a correlation between one BOLD signal and a prediction of this signal via a causal system driven by another BOLD signal. Three validations are described: (1) Prediction correlation performed well on simulated data where the ground truth was known, and outperformed four other methods. (2) On simulated data designed to display the "common driver" problem, prediction correlation did not introduce false connections between non-interacting driven ROIs. (3) On experimental data, prediction correlation recovered the previously identified network organization of human brain. Prediction correlation scales well to work with hundreds of ROIs, enabling it to assess whole brain interregional connectivity at the single subject level. These results provide an initial validation that prediction correlation can capture the direction of information flow and estimate the duration of extended temporal delays in information flow between regions of interest ROIs based on BOLD signal. This approach not only maintains the high sensitivity to network connectivity provided by the correlation analysis, but also performs well in the estimation of causal information flow in the brain.
Functional magnetic resonance imaging (FMRI) with auditory stimulation in songbirds.
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.
Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.
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 MRI evidence for a role of ventral prefrontal cortex in tinnitus
Seydell-Greenwald, Anna; Leaver, Amber M.; Turesky, Ted K.; Morgan, Susan; Kim, Hung J.; Rauschecker, Josef P.
2012-01-01
It has long been known that subjective tinnitus, a constant or intermittent phantom sound perceived by 10 to 15 % of the adult population, is not a purely auditory phenomenon but is also tied to limbic-related brain regions. Supporting evidence comes from data indicating that stress and emotion can modulate tinnitus, and from brain imaging studies showing functional and anatomical differences in limbic-related brain regions of tinnitus patients and controls. Recent studies from our lab revealed altered blood oxygen level-dependent (BOLD) responses to stimulation at the tinnitus frequency in the ventral striatum (specifically, the nucleus accumbens) and gray-matter reductions (i.e. anatomical changes) in ventromedial prefrontal cortex (vmPFC), of tinnitus patients compared to controls. The present study extended these findings by demonstrating functional differences in vmPFC between 20 tinnitus patients and 20 age-matched controls. Importantly, the observed BOLD response in vmPFC was positively correlated with tinnitus characteristics such as subjective loudness and the percent of time during which the tinnitus was perceived, whereas correlations with Tinnitus Handicap Inventory scores and other variables known to be affected in tinnitus (e.g. depression, anxiety, noise sensitivity, hearing loss) were weaker or absent. This suggests that the observed group differences are indeed related to the tinnitus percept and not to an affective reaction to tinnitus. The results further corroborate vmPFC as a region of high interest for tinnitus research. PMID:22982009
Bolo, Nicolas R; Musen, Gail; Jacobson, Alan M; Weinger, Katie; McCartney, Richard L; Flores, Veronica; Renshaw, Perry F; Simonson, Donald C
2011-12-01
To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes. Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging during euglycemic (5.0 mmol/L) and hypoglycemic (2.8 mmol/L) hyperinsulinemic clamps, we compared brain activation response to a working-memory task (WMT) in type 1 diabetic subjects (n = 16) with that in age-matched nondiabetic control subjects (n = 16). Behavioral performance was assessed by percent correct responses. During euglycemia, the WMT activated the bilateral frontal and parietal cortices, insula, thalamus, and cerebellum in both groups. During hypoglycemia, activation decreased in both groups but remained 80% larger in type 1 diabetic versus control subjects (P < 0.05). In type 1 diabetic subjects, higher HbA(1c) was associated with lower activation in the right parahippocampal gyrus and amygdala (R(2) = 0.45, P < 0.002). Deactivation of the default-mode network (DMN) also was seen in both groups during euglycemia. However, during hypoglycemia, type 1 diabetic patients deactivated the DMN 70% less than control subjects (P < 0.05). Behavioral performance did not differ between glycemic conditions or groups. BOLD activation was increased and deactivation was decreased in type 1 diabetic versus control subjects during hypoglycemia. This higher level of brain activation required by type 1 diabetic subjects to attain the same level of cognitive performance as control subjects suggests reduced cerebral efficiency in type 1 diabetes.
Left fusiform BOLD responses are inversely related to word-likeness in a one-back task.
Wang, Xiaojuan; Yang, Jianfeng; Shu, Hua; Zevin, Jason D
2011-04-01
Although its precise functional contribution to reading remains unclear, there is broad consensus that an activity in the left mid-fusiform gyrus is highly sensitive to written words and word-like stimuli. In the current study, we take advantage of a particularity of the Chinese writing system in order to manipulate word-likeness parametrically, from real characters, to pseudo-characters that vary in whether they contain phonological and semantic cues, to artificial stimuli with varying surface similarity to real characters. In a one-back task, BOLD activity in the left mid-fusiform was inversely related to word-likeness, such that the least activity was observed in response to real characters, and the greatest to artificial stimuli that violate the orthotactic constraints of the writing system. One possible explanation for this surprising result is that the short-term memory demands of the one-back task put more pressure on the visual system when other sources of information cannot be used to aid in detecting repeated stimuli. For real characters and, to a lesser extent for pseudo-characters, information about meaning and pronunciation can contribute to performance, whereas artificial stimuli are entirely dependent on visual information. Consistent with this view, functional connectivity analyses revealed a strong positive relationship between left mid-fusiform and other visual areas, whereas areas typically involved in phonological and semantic processing for text were negatively correlated with this region. Copyright © 2011 Elsevier Inc. All rights reserved.
fMRI reveals two distinct cerebral networks subserving speech motor control.
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.
Biro, Peter A; Beckmann, Christa; Stamps, Judy A
2010-01-07
Consistent individual differences in behaviour, termed personality, are common in animal populations and can constrain their responses to ecological and environmental variation, such as temperature. Here, we show for the first time that normal within-daytime fluctuations in temperature of less than 3 degrees C have large effects on personality for two species of juvenile coral reef fish in both observational and manipulative experiments. On average, individual scores on three personality traits (PTs), activity, boldness and aggressiveness, increased from 2.5- to sixfold as a function of temperature. However, whereas most individuals became more active, aggressive and bold across temperature contexts (were plastic), others did not; this changed the individual rank order across temperatures and thus altered personality. In addition, correlations between PTs were consistent across temperature contexts, e.g. fish that were active at a given temperature also tended to be both bold and aggressive. These results (i) highlight the importance of very carefully controlling for temperature when studying behavioural variation among and within individuals and (ii) suggest that individual differences in energy metabolism may contribute to animal personality, given that temperature has large direct effects on metabolic rates in ectotherms.
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 and assessment of working and pet dogs. PMID:25289182
Evidence accumulation detected in BOLD signal using slow perceptual decision making.
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.
Zumer, Johanna M.; Scheeringa, René; Schoffelen, Jan-Mathijs; Norris, David G.; Jensen, Ole
2014-01-01
Given the limited processing capabilities of the sensory system, it is essential that attended information is gated to downstream areas, whereas unattended information is blocked. While it has been proposed that alpha band (8–13 Hz) activity serves to route information to downstream regions by inhibiting neuronal processing in task-irrelevant regions, this hypothesis remains untested. Here we investigate how neuronal oscillations detected by electroencephalography in visual areas during working memory encoding serve to gate information reflected in the simultaneously recorded blood-oxygenation-level-dependent (BOLD) signals recorded by functional magnetic resonance imaging in downstream ventral regions. We used a paradigm in which 16 participants were presented with faces and landscapes in the right and left hemifields; one hemifield was attended and the other unattended. We observed that decreased alpha power contralateral to the attended object predicted the BOLD signal representing the attended object in ventral object-selective regions. Furthermore, increased alpha power ipsilateral to the attended object predicted a decrease in the BOLD signal representing the unattended object. We also found that the BOLD signal in the dorsal attention network inversely correlated with visual alpha power. This is the first demonstration, to our knowledge, that oscillations in the alpha band are implicated in the gating of information from the visual cortex to the ventral stream, as reflected in the representationally specific BOLD signal. This link of sensory alpha to downstream activity provides a neurophysiological substrate for the mechanism of selective attention during stimulus processing, which not only boosts the attended information but also suppresses distraction. Although previous studies have shown a relation between the BOLD signal from the dorsal attention network and the alpha band at rest, we demonstrate such a relation during a visuospatial task, indicating that the dorsal attention network exercises top-down control of visual alpha activity. PMID:25333286
Vink, E E; Boer, A; Verloop, W L; Spiering, W; Voskuil, M; Vonken, E; Hoogduin, J M; Leiner, T; Bots, M L; Blankestijn, P J
2015-07-01
Renal denervation (RDN) is a promising therapy for resistant hypertension. RDN is assumed to decrease sympathetic activity. Consequently, RDN can potentially increase renal oxygenation. Blood oxygen level-dependent MRI (BOLD-MRI) provides a non-invasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the effect of RDN on renal oxygenation as determined by BOLD-MRI. Patients with resistant hypertension or the inability to follow a stable drug regimen due to unacceptable side effects were included. BOLD-MRI was performed before and 12 months after RDN. Twenty-seven patients were imaged on 3 T and 19 on 1.5 T clinical MRI systems. Fifty-four patients were included, 46 patients (23 men, mean age 57 years) completed the study. Mean 24-h BP changed from 163(±20)/98(±14) mmHg to 154(±22)/92(±13) mmHg (p = 0.001 and p < 0.001). eGFR did not change after RDN [77(±18) vs. 79(±20) mL/min/1.73 m(2); p = 0.13]. RDN did not affect renal oxygenation [1.5 T: cortical R2*: 12.5(±0.9) vs. 12.5(±0.9), p = 0.94; medullary R2*: 19.6(±1.7) vs. 19.3(1.4), p = 0.40; 3 T: cortical R2*: 18.1(±0.8) vs. 17.8(±1.2), p = 0.47; medullary R2*: 27.4(±1.9) vs. 26.7(±1.8), p = 0.19]. The current study shows that RDN does not lead to changes in renal oxygenation 1 year after RDN as determined by BOLD-MRI. • Renal denervation significantly decreased ambulatory blood pressure. • Renal denervation did not change renal oxygenation as determined by BOLD-MRI. • Absence of a change in renal oxygenation might be explained by autoregulation.
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.
Motes, Michael A; Rao, Neena K; Shokri-Kojori, Ehsan; Chiang, Hsueh-Sheng; Kraut, Michael A; Hart, John
2017-01-01
Computer-based assessment of many cognitive processes (eg, anticipatory and response readiness processes) requires the use of invariant stimulus display times (SDT) and intertrial intervals (ITI). Although designs with invariant SDTs and ITIs have been used in functional magnetic resonance imaging (fMRI) research, such designs are problematic for fMRI studies because of collinearity issues. This study examined regressor modulation with trial-level reaction times (RT) as a method for improving signal detection in a go/no-go task with invariant SDTs and ITIs. The effects of modulating the go regressor were evaluated with respect to the detection of BOLD signal-change for the no-go condition. BOLD signal-change to no-go stimuli was examined when the go regressor was based on a (a) canonical hemodynamic response function (HRF), (b) RT-based amplitude-modulated (AM) HRF, and (c) RT-based amplitude and duration modulated (A&DM) HRF. Reaction time–based modulation reduced the collinearity between the go and no-go regressors, with A&DM producing the greatest reductions in correlations between the regressors, and greater reductions in the correlations between regressors were associated with longer mean RTs and greater RT variability. Reaction time–based modulation increased statistical power for detecting group-level no-go BOLD signal-change across a broad set of brain regions. The findings show the efficacy of using regressor modulation to increase power in detecting BOLD signal-change in fMRI studies in which circumstances dictate the use of temporally invariant stimulus presentations. PMID:29276390
Motes, Michael A; Rao, Neena K; Shokri-Kojori, Ehsan; Chiang, Hsueh-Sheng; Kraut, Michael A; Hart, John
2017-01-01
Computer-based assessment of many cognitive processes (eg, anticipatory and response readiness processes) requires the use of invariant stimulus display times (SDT) and intertrial intervals (ITI). Although designs with invariant SDTs and ITIs have been used in functional magnetic resonance imaging (fMRI) research, such designs are problematic for fMRI studies because of collinearity issues. This study examined regressor modulation with trial-level reaction times (RT) as a method for improving signal detection in a go / no-go task with invariant SDTs and ITIs. The effects of modulating the go regressor were evaluated with respect to the detection of BOLD signal-change for the no-go condition. BOLD signal-change to no-go stimuli was examined when the go regressor was based on a (a) canonical hemodynamic response function (HRF), (b) RT-based amplitude-modulated (AM) HRF, and (c) RT-based amplitude and duration modulated (A&DM) HRF. Reaction time-based modulation reduced the collinearity between the go and no-go regressors, with A&DM producing the greatest reductions in correlations between the regressors, and greater reductions in the correlations between regressors were associated with longer mean RTs and greater RT variability. Reaction time-based modulation increased statistical power for detecting group-level no-go BOLD signal-change across a broad set of brain regions. The findings show the efficacy of using regressor modulation to increase power in detecting BOLD signal-change in fMRI studies in which circumstances dictate the use of temporally invariant stimulus presentations.
Fast fMRI provides high statistical power in the analysis of epileptic networks.
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 modeling of physiological noise, temporal analysis of the BOLD signal and defining appropriate thresholds is required to fully profit from its high temporal resolution. © 2013.
Striatal-Limbic Activation is Associated with Intensity of Anticipatory Anxiety
Yang, Hongyu; Spence, Jeffrey S.; Devous, Michael D.; Briggs, Richard W.; Goyal, Aman; Xiao, Hong; Yadav, Hardik; Adinoff, Bryon
2013-01-01
Anxiety experienced in anticipation of impending aversive events induces striatal-limbic activation. However, previous functional magnetic imaging (fMRI) studies of anticipatory anxiety have utilized post-test measures of anxiety, making a direct association between neural activation and distress problematic. This paradigm was designed to assess the BOLD response to an aversive conditioned stimulus while simultaneously measuring subjective anxiety. Fifteen male healthy subjects (45.5±8.5 years old) were studied. A high threat conditioned stimulus (CS) was paired with either an unpredictable, highly aversive (painful) or a non-aversive (non-painful) unconditioned stimulus and compared to a low threat CS paired with a predictable, non-aversive stimulus. Neural response was assessed with fMRI, and subjective anxiety (1 to 4) was recorded upon the presentation of each CS. High subjective ratings of real-time anticipatory anxiety (2, 3, and 4), relative to low anticipatory anxiety (1), elicited increased activation in the bilateral striatum, bilateral orbital frontal cortex, left anterior insula, and anterior cingulate cortex (ACC) and decreased activation in the posterior cingulate cortex (PCC). The amplitude of BOLD signal change generally paralleled the subjective rating of anxiety. Real-time measures of anticipatory anxiety confirm previous reports, using post-test measures of anxiety, of striatal-limbic activation during anticipatory anxiety while simultaneously demonstrating an increase in BOLD response in parallel with heightened anxiety. PMID:23137803
High Field Small Animal Magnetic Resonance Oncology Studies
Bokacheva, Louisa; Ackerstaff, Ellen; LeKaye, H. Carl; Zakian, Kristen; Koutcher, Jason A.
2014-01-01
This review focuses on the applications of high magnetic field magnetic resonance imaging (MRI) and spectroscopy (MRS) to cancer studies in small animals. High field MRI can provide information about tumor physiology, the microenvironment, metabolism, vascularity and cellularity. Such studies are invaluable for understanding tumor growth and proliferation, response to treatment and drug development. The MR techniques reviewed here include 1H, 31P, Chemical Exchange Saturation Transfer (CEST) imaging, and hyperpolarized 13C MR spectroscopy as well as diffusion-weighted, Blood Oxygen Level Dependent (BOLD) contrast imaging, and dynamic contrast-enhanced MR imaging. These methods have been proven effective in animal studies and are highly relevant to human clinical studies. PMID:24374985
Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli
Cunningham-Bussel, Amy C.; Root, James C.; Butler, Tracy; Tuescher, Oliver; Pan, Hong; Epstein, Jane; Weisholtz, Daniel S.; Pavony, Michelle; Silverman, Michael E.; Goldstein, Martin S.; Altemus, Margaret; Cloitre, Marylene; LeDoux, Joseph; McEwen, Bruce; Stern, Emily; Silbersweig, David
2014-01-01
Summary The development and exacerbation of many psychiatric and neurologic conditions are associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis as measured by aberrant levels of cortisol secretion. Here we report on the relationship between the amplitude of diurnal cortisol secretion, measured across 3 typical days in 18 healthy individuals, and blood oxygen level dependant (BOLD) response in limbic fear/stress circuits, elicited by in-scanner presentation of emotionally negative stimuli, specifically, images of the World Trade Center (WTC) attack. Results indicate that subjects who secrete a greater amplitude of cortisol diurnally demonstrate less brain activation in limbic regions, including the amygdala and hippocampus/parahippocampus, and hypothalamus during exposure to traumatic WTC-related images. Such initial findings can begin to link our understanding, in humans, of the relationship between the diurnal amplitude of a hormone integral to the stress response, and those neuroanatomical regions that are implicated as both modulating and being modulated by that response. PMID:19135805