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Sample records for predict task-induced bold

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2011-02-01

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

  3. Boldness predicts social status in zebrafish (Danio rerio).

    PubMed

    Dahlbom, S Josefin; Lagman, David; Lundstedt-Enkel, Katrin; Sundström, L Fredrik; Winberg, Svante

    2011-01-01

    This study explored if boldness could be used to predict social status. First, boldness was assessed by monitoring individual zebrafish behaviour in (1) an unfamiliar barren environment with no shelter (open field), (2) the same environment when a roof was introduced as a shelter, and (3) when the roof was removed and an unfamiliar object (Lego® brick) was introduced. Next, after a resting period of minimum one week, social status of the fish was determined in a dyadic contest and dominant/subordinate individuals were determined as the winner/loser of two consecutive contests. Multivariate data analyses showed that males were bolder than females and that the behaviours expressed by the fish during the boldness tests could be used to predict which fish would later become dominant and subordinate in the ensuing dyadic contest. We conclude that bold behaviour is positively correlated to dominance in zebrafish and that boldness is not solely a consequence of social dominance.

  4. Boldness Predicts Social Status in Zebrafish (Danio rerio)

    PubMed Central

    Dahlbom, S. Josefin; Lagman, David; Lundstedt-Enkel, Katrin; Sundström, L. Fredrik; Winberg, Svante

    2011-01-01

    This study explored if boldness could be used to predict social status. First, boldness was assessed by monitoring individual zebrafish behaviour in (1) an unfamiliar barren environment with no shelter (open field), (2) the same environment when a roof was introduced as a shelter, and (3) when the roof was removed and an unfamiliar object (Lego® brick) was introduced. Next, after a resting period of minimum one week, social status of the fish was determined in a dyadic contest and dominant/subordinate individuals were determined as the winner/loser of two consecutive contests. Multivariate data analyses showed that males were bolder than females and that the behaviours expressed by the fish during the boldness tests could be used to predict which fish would later become dominant and subordinate in the ensuing dyadic contest. We conclude that bold behaviour is positively correlated to dominance in zebrafish and that boldness is not solely a consequence of social dominance. PMID:21858168

  5. A review of calibrated blood oxygenation level-dependent (BOLD) methods for the measurement of task-induced changes in brain oxygen metabolism.

    PubMed

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

    2013-08-01

    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. Copyright © 2012 John Wiley & Sons, Ltd.

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

    PubMed Central

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

    2013-01-01

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

  7. The synchronization of spontaneous BOLD activity predicts extraversion and neuroticism.

    PubMed

    Wei, Luqing; Duan, Xujun; Yang, Yang; Liao, Wei; Gao, Qing; Ding, Ju-rong; Zhang, Zhiqiang; Zeng, Weixi; Li, Yuan; Lu, Guangming; Chen, Huafu

    2011-10-24

    There is an increasing body of evidence pointing to a relationship between personality and brain markers. The purpose of this study was to identify the associations between personality dimensions of extraversion and neuroticism and the local synchronization of spontaneous blood oxygen level-dependent (BOLD) activity assessed by regional homogeneity (ReHo) approach. Our results revealed the significant negative correlation between neuroticism and ReHo in the left middle frontal gyrus, providing evidence for the left frontal activation involved in pleasant emotion. ReHo was correlated negatively with extraversion in the medial prefrontal cortex (MPFC), an important portion of the default mode network (DMN), thus further indicating the relationship between DMN and personality. In addition, ReHo in the insula, cerebellum and cingulate gyrus was correlated positively with extraversion, suggesting the associations between individual difference in extraversion and specific brain regions involved in affective processing. These findings shed light on the important relationship between the synchronization of spontaneous fluctuations and personality dimensions of extraversion and neuroticism, which provide further evidence for the neural underpinning of individual difference in personality traits.

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Predicting the Multisensory Consequences of One’s Own Action: BOLD Suppression in Auditory and Visual Cortices

    PubMed Central

    van Kemenade, Bianca M.; Arikan, B. Ezgi; Fiehler, Katja; Leube, Dirk T.; Harris, Laurence R.; Kircher, Tilo

    2017-01-01

    Predictive mechanisms are essential to successfully interact with the environment and to compensate for delays in the transmission of neural signals. However, whether and how we predict multisensory action outcomes remains largely unknown. Here we investigated the existence of multisensory predictive mechanisms in a context where actions have outcomes in different modalities. During fMRI data acquisition auditory, visual and auditory-visual stimuli were presented in active and passive conditions. In the active condition, a self-initiated button press elicited the stimuli with variable short delays (0-417ms) between action and outcome, and participants had to detect the presence of a delay for auditory or visual outcome (task modality). In the passive condition, stimuli appeared automatically, and participants had to detect the number of stimulus modalities (unimodal/bimodal). For action consequences compared to identical but unpredictable control stimuli we observed suppression of the blood oxygen level depended (BOLD) response in a broad network including bilateral auditory and visual cortices. This effect was independent of task modality or stimulus modality and strongest for trials where no delay was detected (undetectedpredictive mechanisms lead to BOLD suppression in multiple sensory brain regions. These findings support the hypothesis of multisensory predictive mechanisms, which are probably conducted in the left cerebellum. PMID:28060861

  11. Boldness predicts an individual's position along an exploration-exploitation foraging trade-off.

    PubMed

    Patrick, Samantha C; Pinaud, David; Weimerskirch, Henri

    2017-09-01

    Individuals do not have complete information about the environment and therefore they face a trade-off between gathering information (exploration) and gathering resources (exploitation). Studies have shown individual differences in components of this trade-off but how stable these strategies are in a population and the intrinsic drivers of these differences is not well understood. Top marine predators are expected to experience a particularly strong trade-off as many species have large foraging ranges and their prey often have a patchy distribution. This environment leads these species to exhibit pronounced exploration and exploitation phases but differences between individuals are poorly resolved. Personality differences are known to be important in foraging behaviour but also in the trade-off between exploration and exploitation. Here we test whether personality predicts an individual exploration-exploitation strategy using wide ranging wandering albatrosses (Diomedea exulans) as a model system. Using GPS tracking data from 276 wandering albatrosses, we extract foraging parameters indicative of exploration (searching) and exploitation (foraging) and show that foraging effort, time in patch and size of patch are strongly correlated, demonstrating these are indicative of an exploration-exploitation (EE) strategy. Furthermore, we show these are consistent within individuals and appear stable in the population, with no reproductive advantage. The searching and foraging behaviour of bolder birds placed them towards the exploration end of the trade-off, whereas shy birds showed greater exploitation. This result provides a mechanism through which individual foraging strategies may emerge. Age and sex affected components of the trade-off, but not the trade-off itself, suggesting these factors may drive behavioural compensation to maintain resource acquisition and this was supported by the evidence that there were no fitness consequence of any EE trait nor the trade

  12. Boldness psychopathic traits predict reduced gaze toward fearful eyes in men with a history of violence.

    PubMed

    Gillespie, Steven M; Rotshtein, Pia; Beech, Anthony R; Mitchell, Ian J

    2017-09-01

    Research with developmental and adult samples has shown a relationship of psychopathic traits with reduced eye gaze. However, these relationships remained to be investigated among forensic samples. Here we examined the eye movements of male violent offenders during an emotion recognition task. Violent offenders performed similar to non-offending controls, and their eye movements varied with the emotion and intensity of the facial expression. In the violent offender group Boldness psychopathic traits, but not Meanness or Disinhibition, were associated with reduced dwell time and fixation counts, and slower first fixation latencies, on the eyes compared with the mouth. These results are the first to show a relationship of psychopathic traits with reduced attention to the eyes in a forensic sample, and suggest that Boldness is associated with difficulties in orienting attention toward emotionally salient aspects of the face. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  13. Cerebellar BOLD signal during the acquisition of a new lexicon predicts its early consolidation.

    PubMed

    Lesage, Elise; Nailer, Emma L; Miall, R Chris

    2016-10-01

    Cerebellar contributions to language are presently poorly understood, but it has been argued that the cerebellar role in motor learning can be extended to learning in cognitive and linguistic domains. Here, we used fMRI to investigate whether the cerebellum is recruited in mapping novel words onto existing semantic concepts. On separate days, participants performed a Basque vocabulary learning task and a control English synonym task in the MRI scanner. Learning-related BOLD activity was found in left inferior frontal gyrus, bilateral insula, pre-SMA, left superior parietal cortex, right caudate, the right cerebellar vermis and right cerebellar Crus II. The extent to which the cerebellar regions, but not the cerebral areas, were recruited during learning correlated positively with participants' off-line improvement in performance after the learning task. These data provide evidence for a cerebellar role in lexical learning, and suggest that the right cerebellum may contribute toward consolidation of lexico-semantic associations in the language network. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Resting-state BOLD oscillation frequency predicts vigilance task performance at both normal and high environmental temperatures.

    PubMed

    Song, Xiaopeng; Qian, Shaowen; Liu, Kai; Zhou, Shuqin; Zhu, Huaiqiu; Zou, Qihong; Liu, Yijun; Sun, Gang; Gao, Jia-Hong

    2017-06-09

    Hyperthermia may impair vigilance functions and lead to slower reaction times (RTs) in the psychomotor vigilance task (PVT) and possibly disturbing cerebral hemodynamic rhythms. To test these hypotheses, we acquired the resting-state BOLD and cerebral blood flow (CBF) data, as well as PVTRTs from 15 participants in two simulated environmental thermal conditions (50 °C/25 °C). We adopted a data-driven method, frequency component analysis, to quantify the mean frequency of the BOLD series of each voxel. Across-subject correlation analysis was employed to detect the brain areas whose BOLD oscillation frequency was correlated with the RTs. Significant changes of BOLD frequency and CBF within these areas were compared between hyperthermia and normothermia conditions. Spatial correlations between BOLD frequency and CBF were calculated within different brain areas for each subject under both thermal conditions. Results showed that, under both thermal conditions, the RTs correlated with the BOLD frequency positively in the default mode network (DMN) and negatively in the sensorimotor network (SMN). The increase of BOLD frequency in the thalamus and ventral medial prefrontal cortex was correlated with the increase of RTs in hyperthermia compared with normothermia. Hyperthermia decreased BOLD frequency and CBF in the SMN, while it increased CBF in the thalamus and posterior cingulate. In both thermal conditions, the spatial distribution of CBF negatively correlated with the spatial distribution of BOLD oscillation frequency in most cortical areas, especially in cingulate cortices, precuneus, and primary visual cortex. These results suggest that hyperthermia might deteriorate task performance by interfering with the resting-state CBF, and with BOLD rhythms. The overlapping of the thermoregulatory and vigilance functions in the SMN and DMN might underlie the neural mechanisms of the cognitive-behavioral impairments induced by hyperthermia.

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

    PubMed

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

    2014-11-01

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

  16. Choice from non-choice: Predicting consumer preferences from BOLD signals obtained during passive viewing

    PubMed Central

    Levy, Ifat; Lazzaro, Stephanie C.; Rutledge, Robb B.; Glimcher, Paul W.

    2011-01-01

    Decision-making is often viewed as a two-stage process, where subjective values are first assigned to each option and then the option of the highest value is selected. Converging evidence suggests that these subjective values are represented in the striatum and medial prefrontal cortex (MPFC). A separate line of evidence suggests that activation in the same areas represents the values of rewards even when choice is not required, as in classical conditioning tasks. However, it is unclear whether the same neural mechanism is engaged in both cases. To address this question we measured brain activation with fMRI while human subjects passively viewed individual consumer goods. We then sampled activation from predefined regions of interest and used it to predict subsequent choices between the same items made outside of the scanner. Our results show that activation in the striatum and MPFC in the absence of choice predicts subsequent choices, suggesting that these brain areas represent value in a similar manner whether or not choice is required. PMID:21209196

  17. Emotional Intelligence, Personality, and Task-Induced Stress

    ERIC Educational Resources Information Center

    Matthews, Gerald; Emo, Amanda K.; Funke, Gregory; Zeidner, Moshe; Roberts, Richard D.; Costa, Paul T.; Schulze, Ralf

    2006-01-01

    Emotional intelligence (EI) may predict stress responses and coping strategies in a variety of applied settings. This study compares EI and the personality factors of the Five Factor Model (FFM) as predictors of task-induced stress responses. Participants (N = 200) were randomly assigned to 1 of 4 task conditions, 3 of which were designed to be…

  18. Emotional intelligence, personality, and task-induced stress.

    PubMed

    Matthews, Gerald; Emo, Amanda K; Funke, Gregory; Zeidner, Moshe; Roberts, Richard D; Costa, Paul T; Schulze, Ralf

    2006-06-01

    Emotional intelligence (EI) may predict stress responses and coping strategies in a variety of applied settings. This study compares EI and the personality factors of the Five Factor Model (FFM) as predictors of task-induced stress responses. Participants (N = 200) were randomly assigned to 1 of 4 task conditions, 3 of which were designed to be stressful. Results confirmed that low EI was related to worry states and avoidance coping, even with the FFM statistically controlled. However, EI was not specifically related to task-induced changes in stress state. Results also confirmed that Neuroticism related to distress, worry, and emotion-focused coping, and Conscientiousness predicted use of task-focused coping. The applied utility of EI and personality measures is discussed.

  19. Comparison of BOLD cerebrovascular reactivity mapping and DSC MR perfusion imaging for prediction of neurovascular uncoupling potential in brain tumors.

    PubMed

    Pillai, Jay J; Zacà, Domenico

    2012-08-01

    The coupling mechanism between neuronal firing and cerebrovascular dilatation can be significantly compromised in cerebral diseases, making it difficult to identify eloquent cortical areas near or within resectable lesions by using Blood Oxygen Level Dependent (BOLD) fMRI. Several metabolic and vascular factors have been considered to account for this lesion-induced neurovascular uncoupling (NVU), but no imaging gold standard exists currently for the detection of NVU. However, it is critical in clinical fMRI studies to evaluate the risk of NVU because the presence of NVU may result in false negative activation that may result in inadvertent resection of eloquent cortex, resulting in permanent postoperative neurologic deficits. Although NVU results from a disruption of one or more components of a complex cellular and chemical neurovascular coupling cascade (NCC) MR imaging is only able to evaluate the final step in this NCC involving the ultimate cerebrovascular response. Since anything that impairs cerebrovascular reactivity (CVR) will necessarily result in NVU, regardless of its effect more proximally along the NCC, we can consider mapping of CVR as a surrogate marker of NVU potential. We hypothesized that BOLD breath-hold (BH) CVR mapping can serve as a better marker of NVU potential than T2* Dynamic Susceptibility Contrast gadolinium perfusion MR imaging, because the latter is known to only reflect NVU risk associated with high grade gliomas by determining elevated relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) related to tumor angiogenesis. However, since low and intermediate grade gliomas are not associated with such tumoral hyperperfusion, BOLD BH CVR mapping may be able to detect such NVU potential even in lower grade gliomas without angiogenesis, which is the hallmark of glioblastomas. However, it is also known that glioblastomas are associated with variable NVU, since angiogenesis may not always result in NVU. Perfusion

  20. BOLD-fMRI with median nerve electrical stimulation predict hemodynamic improvement after revascularization in patients with moyamoya disease.

    PubMed

    Qiao, Peng-Gang; Han, Cong; Qian, Tianyi; Li, Gong-Jie; Yin, Hong

    2017-10-01

    To assess the severity of cerebral hemodynamic impairment and hemodynamic improvements, after revascularization in moyamoya disease (MMD) by means of blood-oxygen-level dependent functional magnetic resonance imaging (BOLD-fMRI). BOLD-fMRI with median nerve electrical stimulation based on echo planar imaging was performed in 73 volunteers with MMD and 15 healthy volunteers using a 3.0 Tesla MRI scanner. Twenty-four MMD patients were reexamined after encephaloduroarteriosynangiosis. Time-signal intensity curves of the activated area of the contralateral primary somatosensory cortex were computed. Negative response time (Tnr) and peak (Pnr), positive response time (Tpr) and peak (Ppr), and time to negative peak (TTPn) and positive peak (TTPp) were measured. Compared with nonparesthesia group and the asymptomatic side of paresthesia group, the patients with paresthesia showed extended Tnr (22.04 ± 3.34 s versus 9.57 ± 2.27 s and 12.67 ± 2.69 s, P = 0.0096), decreased Pnr (-0.47 ± 0.06 versus -0.30 ± 0.09 and -0.33 ± 0.09, P = 0.010), delayed TTPn (9.04 ± 1.39 s versus 3.66 ± 0.79 s and 4.88 ± 1.10 s, P = 0.0064), shortened Tpr (22.75 ± 2.30 s versus 36.85 ± 2.68 s and 33 ± 2.49 s, P = 0.0010), and decreased Ppr (0.62 ± 0.08 versus 0.99 ± 0.15 and 0.97 ± 0.11, P = 0.0149) when subjected to median nerve electrical stimulation in the symptomatic side. After surgery, the patients with paresthesia showed shorter Tnr (1.53 ± 1.66 s versus 17.88 ± 22.61 s, P = 0.0002), increased Pnr (-0.14 ± 0.17 versus -0.44 ± 0.53, P = 0.0178), advanced TTPn (1.29 ± 1.21 s versus 7.29 ± 8.21 s, P = 0.0005), extended Tpr (36.94 ± 6.41 s versus 25.18 ± 15.51 s, P = 0.0091), increased Ppr (1.21 ± 0.87 versus 0.77 ± 0.60, P = 0.0201), and advanced TTPp (11.18 ± 4.70 s versus 27.29 ± 20.00 s, P = 0.0046). Bold-fMRI is

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

    PubMed Central

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

    2013-01-01

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

  2. Bold Books for Teenagers

    ERIC Educational Resources Information Center

    Gallo, Don

    2005-01-01

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

  3. Bold Books for Teenagers

    ERIC Educational Resources Information Center

    Gallo, Don

    2005-01-01

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

  4. Age-related reduction of BOLD modulation to cognitive difficulty predicts poorer task accuracy and poorer fluid reasoning ability.

    PubMed

    Rieck, Jenny R; Rodrigue, Karen M; Boylan, Maria A; Kennedy, Kristen M

    2017-02-15

    Aging is associated with reduced resources needed to perform difficult cognitive tasks, but the neural underpinnings are not well understood, especially as there is scant evidence linking functional brain differences to aging cognition. Therefore, the current study examined modulation of fMRI activation from easier to harder spatial distance judgments across a large lifespan sample (N=161; ages 20-94) to identify when in the lifespan modulation to difficulty begins to show deficits and if age-related modulation predicts cognition. Analyses revealed two sets of regions in which modulation increased with difficulty due to either more activation (positive modulation) or more deactivation (negative modulation) to difficulty. These two networks evidenced differential aging trajectories: a right-lateralized fronto-parietal network that decreased in modulation to difficulty between middle- and older-age, and a network of regions in ventromedial prefrontal cortex, posterior cingulate, left angular and middle frontal gyri that showed decreased modulation at the transition from younger to middle-age. Critically, older adults who maintained negative modulation to difficulty showed higher task accuracy. Further, individuals who showed greater coupling between positive and negative modulation performed better on a fluid reasoning task. Age-related preservation of coupled modulation in both cognitive control regions and regions typically associated with default network may be a salient marker of how the brain adapts to maintain cognitive function as we age. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed Central

    Lages, Martin; Jaworska, Katarzyna

    2012-01-01

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

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

    PubMed

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

    2014-08-15

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

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

    PubMed Central

    Mandeville, Joseph B.

    2014-01-01

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

  8. Task-induced deactivation and the "resting" state.

    PubMed

    Binder, Jeffrey R

    2012-08-15

    Task-induced decreases in blood flow and the widespread use of "resting" baselines produced unexpected and discrepant results in early cognitive imaging studies, especially in language comprehension experiments. Here I describe from a personal perspective some of the events and thought processes leading to the first hypothesis-driven fMRI study of the "resting" state.

  9. Reading Rate, Readability and Variations in Task-Induced Processing.

    ERIC Educational Resources Information Center

    Coke, Esther U.

    This study examined the adaptability of reading rate to passage difficulty under different conditions of task-induced processing. Sixteen experimental passages varying in subject matter and ranging from 85 to 171 words were selected from a set of 32 texts rated for comprehensibility. The eight easiest and eight hardest texts were selected. Another…

  10. BOLD Granger causality reflects vascular anatomy.

    PubMed

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

    2013-01-01

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

  11. BOLD Granger Causality Reflects Vascular Anatomy

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-03-01

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

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

    PubMed Central

    Chen, Yufen; Parrish, Todd B.

    2009-01-01

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

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

    PubMed

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

    2017-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-25

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

  17. "Extreme Bold" in the Faculty Ranks

    ERIC Educational Resources Information Center

    Kuusisto, Stephen

    2013-01-01

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

  18. BOLD Frequency Power Indexes Working Memory Performance.

    PubMed

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

    2013-01-01

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

  19. "Extreme Bold" in the Faculty Ranks

    ERIC Educational Resources Information Center

    Kuusisto, Stephen

    2013-01-01

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

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

    PubMed

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

    2017-09-01

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

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

    PubMed Central

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

    2006-01-01

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

  2. Quantum theory with bold operator tensors.

    PubMed

    Hardy, Lucien

    2015-08-06

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

  3. Decreased BOLD responses in audiovisual processing.

    PubMed

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

    2010-12-29

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

  4. The Need for Bold Thinking.

    PubMed

    Lowi-Young, Mimi; DuBois-Wing, Gwen

    2016-01-01

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

  5. Absence of a Significant Extravascular Contribution to the Skeletal Muscle BOLD Effect at 3T

    PubMed Central

    Sanchez, Otto A.; Copenhaver, Elizabeth A.; Elder, Christopher P.; Damon, Bruce M.

    2010-01-01

    Blood oxygenation-level dependent (BOLD) contrast in skeletal may reflect the contributions of both intravascular and extravascular relaxation effects. The purpose of this study was to determine the significance of the extravascular BOLD effect in skeletal muscle at 3T. In experiments, R2* was measured before and during arterial occlusion under the following conditions: 1) the leg extended and rotated (to vary the capillary orientation with respect to B0) and 2) with the blood’s signal nulled using a multi-echo vascular space occupancy experiment. In the leg rotation protocol, 3 minutes of arterial occlusion decreased %HbO2 from 67% to 45% and increased R2* from 34.2 to 36.6 s-1, but there was no difference in the R2* response to occlusion between the extended and rotated positions. Numerical simulations of intra- and extravascular BOLD effects corresponding to these conditions predicted that the intravascular BOLD contribution to the R2* change was always >50 times larger than the extravascular BOLD contribution. Blood signal nulling eliminated the change in R2* caused by arterial occlusion. These data indicate that under these experimental conditions, the contribution of the extravascular BOLD effect to skeletal muscle R2* was too small to be practically important. PMID:20665796

  6. Absence of a significant extravascular contribution to the skeletal muscle BOLD effect at 3 T.

    PubMed

    Sanchez, Otto A; Copenhaver, Elizabeth A; Elder, Christopher P; Damon, Bruce M

    2010-08-01

    Blood oxygenation level dependent (BOLD) contrast in skeletal may reflect the contributions of both intravascular and extravascular relaxation effects. The purpose of this study was to determine the significance of the extravascular BOLD effect in skeletal muscle at 3 T. In experiments, R(2)* was measured before and during arterial occlusion under the following conditions: (1) the leg extended and rotated (to vary the capillary orientation with respect to the amplitude of static field) and (2) with the blood's signal nulled using a multiecho vascular space occupancy experiment. In the leg rotation protocol, 3 min of arterial occlusion decreased oxyhemoglobin saturation from 67% to 45% and increased R(2)* from 34.2 to 36.6 sec(-1), but there was no difference in the R(2)* response to occlusion between the extended and rotated positions. Numerical simulations of intra- and extravascular BOLD effects corresponding to these conditions predicted that the intravascular BOLD contribution to the R(2)* change was always > 50 times larger than the extravascular BOLD contribution. Blood signal nulling eliminated the change in R(2)* caused by arterial occlusion. These data indicate that under these experimental conditions, the contribution of the extravascular BOLD effect to skeletal muscle R(2)* was too small to be practically important.

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

    USGS Publications Warehouse

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

    2008-01-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2016-09-09

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

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

    PubMed Central

    Lohrenz, Terry; Kishida, Kenneth T.

    2016-01-01

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

  11. Caffeine increases the temporal variability of resting-state BOLD connectivity in the motor cortex.

    PubMed

    Rack-Gomer, Anna Leigh; Liu, Thomas T

    2012-02-01

    Correlations between spontaneous fluctuations in the blood oxygenation level dependent (BOLD) signal measured with functional MRI are finding increasing use as measures of functional connectivity in the brain, where differences can potentially predict cognitive performance and diagnose disease. Caffeine, which is a widely consumed neural stimulant and vasoactive agent, has been found to decrease the amplitude and correlation of resting-state BOLD fluctuations, and hence is an important factor to consider in functional connectivity studies. However, because the BOLD signal is sensitive to neural and vascular factors, the physiological mechanisms by which caffeine alters spontaneous BOLD fluctuations remain unclear. Resting-state functional connectivity has traditionally been assessed using stationary measures, such as the correlation coefficient between BOLD signals measured across the length of a scan. However, recent work has shown that the correlation of resting-state networks can vary considerably over time, with periods as short as 10 s. In this study, we used a sliding window correlation analysis to assess temporal variations in resting-state functional connectivity of the motor cortex before and after caffeine ingestion. We found that the temporal variability of BOLD correlation was significantly higher following a caffeine dose, with transient periods of strong correlation alternating with periods of low or negative correlation. This phenomenon was primarily due to increased variability in the phase difference between BOLD time courses in the left and right motor cortices. These results indicate that caffeine may cause underlying spontaneous neural fluctuations to go in and out of coherence more frequently, and emphasizes the need to consider non-stationary measures when studying changes in functional connectivity.

  12. Boldness and its relation to psychopathic personality: Prototypicality analyses among forensic mental health, criminal justice, and layperson raters.

    PubMed

    Sörman, Karolina; Edens, John F; Smith, Shannon Toney; Clark, John W; Kristiansson, Marianne; Svensson, Olof

    2016-06-01

    Research on psychopathic personality has been dominated by a focus on criminality and social deviance, but some theoretical models argue that certain putatively adaptive features are important components of this construct. In 3 samples (forensic mental health practitioners, probation officers and a layperson community sample), we investigated adaptive traits as conceptualized in the Triarchic model of psychopathy (Patrick et al., 2009), specifically the relevance of boldness to construals of psychopathic personality. Participants completed prototypicality ratings of psychopathic traits, including 3 items created to tap components of boldness (Socially bold, Adventurous, Emotionally stable), and they also rated a series of attitudinal statements (e.g., perceived correlates of being psychopathic, moral judgments about psychopaths). The composite Boldness scale was rated as moderately to highly prototypical among forensic mental health practitioners and probation officers and positively associated with other theoretically relevant domains of psychopathy. Across samples, higher composite Boldness ratings predicted greater endorsement of adaptive traits (e.g., social skills) as characteristic of psychopathy. For the individual items, Socially bold was rated as highly prototypical and was associated with theoretically relevant correlates. Adventurous also was seen as prototypical, though to a lesser degree. Only forensic mental health practitioners endorsed Emotionally stable as characteristic of psychopathy. Our results provide partial support for the contention that the boldness concept is viewed as an important component of psychopathy, particularly among professionals who work directly with offender populations. (PsycINFO Database Record

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

    PubMed

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

    2010-02-01

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

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

    PubMed

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

    2002-03-01

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

  15. BOLD subjective value signals exhibit robust range adaptation.

    PubMed

    Cox, Karin M; Kable, Joseph W

    2014-12-03

    Many theories of decision making assume that choice options are assessed along a common subjective value (SV) scale. The neural correlates of SV are widespread and reliable, despite the wide variation in the range of values over which decisions are made (e.g., between goods worth a few dollars, in some cases, or hundreds of dollars, in others). According to adaptive coding theories (Barlow, 1961), an efficient value signal should exhibit range adaptation, such that neural activity maintains a fixed dynamic range, and the slope of the value response varies inversely with the range of values within the local context. Although monkey data have demonstrated range adaptation in single-unit correlates of value (Padoa-Schioppa, 2009; Kobayashi et al., 2010), whether BOLD value signals exhibit similar range adaptation is unknown. To test for this possibility, we presented human participants with choices between a fixed immediate and variable delayed payment options. Across two conditions, the delayed options' SVs spanned either a narrow or wide range. SV-tracking activity emerged in the posterior cingulate, ventral striatum, anterior cingulate, and ventromedial prefrontal cortex. Throughout this network, we observed evidence consistent with the predictions of range adaptation: the SV response slope increased in the narrow versus wide range, with statistically significant slope changes confirmed for the posterior cingulate and ventral striatum. No regions exhibited a reliably increased BOLD activity range in the wide versus narrow condition. Our observations of range adaptation present implications for the interpretation of BOLD SV responses that are measured across different contexts or individuals.

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

    PubMed

    Jung, Kwan-Jin

    2009-09-01

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

  17. A protocol for use of medetomidine anesthesia in rats for extended studies using task-induced BOLD contrast and resting-state functional connectivity

    PubMed Central

    Pawela, Christopher P.; Biswal, Bharat B.; Hudetz, Anthony G.; Schulte, Marie L.; Li, Rupeng; Jones, Seth R.; Cho, Younghoon R.; Matloub, Hani S.; Hyde, James S.

    2009-01-01

    The α2-adrenoreceptor agonist, medetomidine, which exhibits dose-dependent sedative effects and is gaining acceptance in small-animal functional magnetic resonance imaging (fMRI), has been studied. Rats were examined on the bench using the classic tail-pinch method with three infusion sequences: 100 μg/kg/hr, 300 μg/kg/hr, or 100 μg/kg/hr followed by 300 μg/kg/hr. Stepping the infusion rate from 100 to 300 μg/kg/hr after 2.5 hours resulted in a prolonged period of approximately level sedation that cannot be achieved by a constant infusion of either 100 or 300 μg/kg/hr. By stepping the infusion dosage, experiments as long as six hours are possible. Functional MRI experiments were carried out on rats using a frequency dependent electrical stimulation protocol—namely, forepaw stimulation at 3, 5, 7, and 10 Hz. Each rat was studied for a four-hour period, divided into two equal portions. During the first portion, rats were started at a 100 μg/kg/hr constant infusion. During the second portion, four secondary levels of infusion were used: 100, 150, 200, and 300 μg/kg/hr. The fMRI response to stimulation frequency was used as an indirect measure of modulation of neuronal activity through pharmacological manipulation. The frequency response to stimulus was attenuated at the lower secondary infusion dosages 100 or 150 μg/kg/hr but not at the higher secondary infusion dosages 200 or 300 μg/kg/hr. Parallel experiments with the animal at rest were carried out using both electroencephalogram (EEG) and functional connectivity MRI (fcMRI) methods with consistent results. In the secondary infusion period using 300 μg/kg/hr, resting-state functional connectivity is enhanced. PMID:19285560

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

    PubMed Central

    Ekstrom, Arne

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

    The functional magnetic resonance (fMRI) baseline is known to drift over the course of an experiment and is often attributed to hardware instability. These ultraslow fMRI fluctuations are inseparable from blood oxygenation level dependent (BOLD) changes in standard single echo fMRI and they are therefore typically removed before further analysis in both resting-state and task paradigms. However, some part of these fluctuations may be of neuronal origin, as neural activity can indeed fluctuate at the scale of several minutes or even longer, such as after the administration of drugs or during the ultradian rhythms. Here, we show that it is possible to separate the slow BOLD and non-BOLD drifts automatically using multi-echo fMRI and multi-echo independent components analysis (ME-ICA) denoising by demonstrating the detection of a visual signal evoked from a flickering checkerboard with slowly changing contrast. PMID:25449746

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

    PubMed Central

    Leontiev, Oleg; Buxton, Richard B.

    2007-01-01

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

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

    PubMed

    Leontiev, Oleg; Buxton, Richard B

    2007-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. Multisite Reliability of Cognitive BOLD Data

    PubMed Central

    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

  4. Differences in boldness are repeatable and heritable in a long-lived marine predator

    PubMed Central

    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

  5. The Relationship between Task-Induced Involvement Load and Learning New Words from Context

    ERIC Educational Resources Information Center

    Nassaji, Hossein; Hu, Hsueh-chao Marcella

    2012-01-01

    This study investigated the relationship between task-induced involvement load and ESL learners' inferencing and learning word meanings from context. Thirty-two ESL learners were randomly assigned to one of three groups, with each group receiving a different version of a text that was assumed to differ from one another in terms of the degree of…

  6. Nonlinear estimation of the BOLD signal.

    PubMed

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

    2008-04-01

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

  7. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Bold face type. 232.307 Section 232.307 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION REGULATION S-T... face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied in...

  8. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Bold face type. 232.307 Section 232.307 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION REGULATION S-T... face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied in...

  9. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Bold face type. 232.307 Section 232.307 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION REGULATION S-T... face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied in...

  10. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Bold face type. 232.307 Section 232.307 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION REGULATION S-T... face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied in...

  11. 17 CFR 232.307 - Bold face type.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Bold face type. 232.307 Section 232.307 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION REGULATION S-T... face type. (a) Provisions requiring presentation of information in bold face type shall be satisfied in...

  12. Pre-ictal BOLD alterations: Two cases of patients with focal epilepsy.

    PubMed

    Vinette, Sarah A; Premji, Shahleen; Beers, Craig A; Gaxiola-Valdez, Ismael; Pittman, Daniel J; Slone, Edward G; Goodyear, Bradley G; Federico, Paolo

    2016-11-01

    The pre-ictal state is of interest for better understanding pathophysiological processes leading up to seizures and for identifying potential biomarkers for the prediction of these events. We present two cases of patients with focal epilepsy (occipital, insular) who had seizures during functional magnetic resonance imaging (fMRI) scans. Interictal (>30min pre-seizure) control data was available for one participant. The location and timing of pre-ictal blood oxygenation-level dependent (BOLD) signal alterations were examined along with changes in pre-ictal functional connectivity. BOLD signal increases were seen at/close to the seizure onset zone and in/near a contralateral homologous region for both patients. In one patient, BOLD signal decreases were also observed distant from the seizure onset zone. The BOLD signal changes began 11 to 3min prior to seizure onset. These findings add to a growing number of cases of pre-ictal hemodynamic alterations. The significant BOLD signal increases seen in/near the homologous region contralateral to the seizure onset zone in both patients suggests that this area may play a critical role in the pre-ictal state, perhaps functioning to inhibit the seizure onset zone, or alternatively, to be directly involved in seizure generation. Pre-ictal functional connectivity, using a seed at the presumed seizure onset zone, demonstrated increases in connectivity with regions near the contralateral homologous region prior to seizures. Alterations in connectivity were also observed and characterized in interictal data, highlighting the importance of future research in determining if the observed pre-ictal changes are specific indicators for impending seizures.

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

    NASA Astrophysics Data System (ADS)

    Renvall, Ville; Nangini, Cathy; Hari, Riitta

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  16. Identifying Childhood Characteristics that Underlie Pre-Morbid Risk for Substance Use Disorders: Socialization and Boldness

    PubMed Central

    Hicks, Brian M.; Iacono, William G.; McGue, Matt

    2013-01-01

    Utilizing a longitudinal twin study (N = 2510), we identified the child characteristics present prior to initiation of substance use that best predicted later substance use disorders. Two independent traits accounted for the majority of pre-morbid risk: socialization (conformity to rules and conventional values) and boldness (sociability and social assurance, stress resilience, and thrill seeking). Low socialization was associated with disruptive behavior disorders, parental externalizing disorders, and environmental adversity, and exhibited moderate genetic (.45) and shared environmental influences (.30). Boldness was highly heritable (.71) and associated with less internalizing distress and environmental adversity. Together, these traits exhibited robust associations with adolescent and young adult substance use disorders (R = .48 and .50, respectively), and incremental prediction over disruptive behavior disorders, parental externalizing disorders, and environmental adversity. Results were replicated in an independent sample. Socialization and boldness offer a novel conceptualization of underlying risk for substance use disorders that has the potential to improve prediction and theory with implications for basic research, prevention, and intervention. PMID:24280373

  17. Identifying childhood characteristics that underlie premorbid risk for substance use disorders: socialization and boldness.

    PubMed

    Hicks, Brian M; Iacono, William G; McGue, Matt

    2014-02-01

    We utilized a longitudinal twin study (N = 2,510) to identify the child characteristics present prior to initiation of substance use that best predicted later substance use disorders. Two independent traits accounted for the majority of premorbid risk: socialization (conformity to rules and conventional values) and boldness (sociability and social assurance, stress resilience, and thrill seeking). Low socialization was associated with disruptive behavior disorders, parental externalizing disorders, and environmental adversity and exhibited moderate genetic (0.45) and shared environmental influences (0.30). Boldness was highly heritable (0.71) and associated with less internalizing distress and environmental adversity. In combination, these traits exhibited robust associations with adolescent and young adult substance use disorders (R = .48 and .50, respectively) and incremental prediction over disruptive behavior disorders, parental externalizing disorders, and environmental adversity. The results were replicated in an independent sample. Socialization and boldness offer a novel conceptualization of underlying risk for substance use disorders that has the potential to improve prediction and theory with implications for basic research, prevention, and intervention.

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

    PubMed

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

    2012-04-15

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

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

    PubMed

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

    2013-01-01

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

  20. Task-induced frequency modulation features for brain-computer interfacing

    NASA Astrophysics Data System (ADS)

    Jayaram, Vinay; Hohmann, Matthias; Just, Jennifer; Schölkopf, Bernhard; Grosse-Wentrup, Moritz

    2017-10-01

    Objective. Task-induced amplitude modulation of neural oscillations is routinely used in brain-computer interfaces (BCIs) for decoding subjects’ intents, and underlies some of the most robust and common methods in the field, such as common spatial patterns and Riemannian geometry. While there has been some interest in phase-related features for classification, both techniques usually presuppose that the frequencies of neural oscillations remain stable across various tasks. We investigate here whether features based on task-induced modulation of the frequency of neural oscillations enable decoding of subjects’ intents with an accuracy comparable to task-induced amplitude modulation. Approach. We compare cross-validated classification accuracies using the amplitude and frequency modulated features, as well as a joint feature space, across subjects in various paradigms and pre-processing conditions. We show results with a motor imagery task, a cognitive task, and also preliminary results in patients with amyotrophic lateral sclerosis (ALS), as well as using common spatial patterns and Laplacian filtering. Main results. The frequency features alone do not significantly out-perform traditional amplitude modulation features, and in some cases perform significantly worse. However, across both tasks and pre-processing in healthy subjects the joint space significantly out-performs either the frequency or amplitude features alone. This result only does not hold for ALS patients, for whom the dataset is of insufficient size to draw any statistically significant conclusions. Significance. Task-induced frequency modulation is robust and straight forward to compute, and increases performance when added to standard amplitude modulation features across paradigms. This allows more information to be extracted from the EEG signal cheaply and can be used throughout the field of BCIs.

  1. On the Stability of BOLD fMRI Correlations.

    PubMed

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

    2016-09-02

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

  2. Fitness Consequences of Boldness in Juvenile and Adult Largemouth Bass.

    PubMed

    Ballew, Nicholas G; Mittelbach, Gary G; Scribner, Kim T

    2017-04-01

    To date, most studies investigating the relationship between personality traits and fitness have focused on a single measure of fitness (such as survival) at a specific life stage. However, many personality traits likely have multiple effects on fitness, potentially operating across different functional contexts and stages of development. Here, we address the fitness consequences of boldness, under seminatural conditions, across life stages and functional contexts in largemouth bass (Micropterus salmoides). Specifically, we report the effect of boldness on (1) juvenile survivorship in an outdoor pond containing natural prey and predators and (2) adult reproductive success in three outdoor ponds across three reproductive seasons (years). Juvenile survival was negatively affected by boldness, with bolder juveniles having a lower probability of survival than shyer juveniles. In contrast, bolder adult male bass had greater reproductive success than their shyer male counterparts. Female reproductive success was not affected by boldness. These findings demonstrate that boldness can affect fitness differently across life stages. Further, boldness was highly consistent across years and significantly heritable, which suggests that boldness has a genetic component. Thus, our results support theory suggesting that fitness trade-offs across life stages may contribute to the maintenance of personality variation within populations.

  3. An experimental test of density-dependent selection on temperament traits of activity, boldness and sociability.

    PubMed

    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.

  4. Age, sex and reproductive status affect boldness in dogs.

    PubMed

    Starling, Melissa J; Branson, Nicholas; Thomson, Peter C; McGreevy, Paul D

    2013-09-01

    Boldness in dogs is believed to be one end of the shy-bold axis, representing a super-trait. Several personality traits fall under the influence of this super-trait. Previous studies have found that boldness is affected by breed and breed groups, influences performance in sporting dogs, and is affected in some cases by the sex of the dogs. This study investigated the effects of dog age, sex and reproductive status on boldness in dogs by way of a dog personality survey circulated amongst Australian dog owners. Age had a significant effect on boldness (F=4.476; DF=16,758; P<0.001), with boldness decreasing with age in years. Males were bolder than females (F=19.219; DF=1,758; P<0.001) and entire dogs were bolder than neutered dogs (F=4.330; DF=1,758; P<0.038). The study indicates how behaviour may change in adult dogs as they age and adds to the literature on how sex and reproductive status may affect personality in dogs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. The BOLD signal and neurovascular coupling in autism.

    PubMed

    Reynell, Clare; Harris, Julia J

    2013-10-01

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

  6. The BOLD signal and neurovascular coupling in autism

    PubMed Central

    Reynell, Clare; Harris, Julia J.

    2013-01-01

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

  7. Sex and boldness explain individual differences in spatial learning in a lizard

    PubMed Central

    Carazo, Pau; Noble, Daniel W. A.; Chandrasoma, Dani; Whiting, Martin J.

    2014-01-01

    Understanding individual differences in cognitive performance is a major challenge to animal behaviour and cognition studies. We used the Eastern water skink (Eulamprus quoyii) to examine associations between exploration, boldness and individual variability in spatial learning, a dimension of lizard cognition with important bearing on fitness. We show that males perform better than females in a biologically relevant spatial learning task. This is the first evidence for sex differences in learning in a reptile, and we argue that it is probably owing to sex-specific selective pressures that may be widespread in lizards. Across the sexes, we found a clear association between boldness after a simulated predatory attack and the probability of learning the spatial task. In contrast to previous studies, we found a nonlinear association between boldness and learning: both ‘bold’ and ‘shy’ behavioural types were more successful learners than intermediate males. Our results do not fit with recent predictions suggesting that individual differences in learning may be linked with behavioural types via high–low-risk/reward trade-offs. We suggest the possibility that differences in spatial cognitive performance may arise in lizards as a consequence of the distinct environmental variability and complexity experienced by individuals as a result of their sex and social tactics. PMID:24619443

  8. Predictors of dyspnea prevalence: Results from the BOLD study

    PubMed Central

    Grønseth, Rune; Vollmer, William M.; Hardie, Jon A.; Ólafsdóttir, Inga Sif; Lamprecht, Bernd; Buist, A. Sonia; Gnatiuc, Louisa; Gulsvik, Amund; Johannessen, Ane; Enright, Paul

    2014-01-01

    Dyspnea is a cardinal symptom for cardiorespiratory diseases. No study has assessed worldwide variation in dyspnea prevalence or predictors of dyspnea. We used cross-sectional data from population-based samples in 15 countries of the BOLD study to estimate prevalence of dyspnea in the full sample as well as in an a priori defined low-risk group (few risk factors or dyspnea-associated diseases). Dyspnea was defined by the modified Medical Research Council questions. We used ordered logistic regression analysis to study the association of dyspnea with site, sex, age, education, smoking habits, low/high BMI, self-reported disease, and spirometry results. Of the 9,484 participants, 27% reported any dyspnea. In the low-risk subsample (N=4,329), 16% reported some dyspnea. In multivariate analyses, all covariates were correlated to dyspnea, but only 13% of dyspnea variation was explained. Women reported more dyspnea than men (odds ratio ≈ 2.1). When forced vital capacity (FVC) fell below 60% of predicted, dyspnea was much more likely. There was considerable geographical variation in dyspnea, even when we adjusted for known risk factors and spirometry results. We were only able to explain 13% of dyspnea variation. PMID:24176991

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Nestor, Liam; Hester, Robert; Garavan, Hugh

    2010-01-01

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

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

    PubMed Central

    Nestor, Liam; Hester, Robert; Garavan, Hugh

    2009-01-01

    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-naïve 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. PMID:19631753

  12. Hemodynamic Nonlinearities Affect BOLD fMRI Response Timing and Amplitude

    PubMed Central

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

    2009-01-01

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

  13. Drinfeld constructions of the quantum affine superalgebra U{sub q}{bold (}gl({cflx m}/n){bold )}

    SciTech Connect

    Fan, H.; Hou, B.; Shi, K.

    1997-01-01

    We apply the method of the central extensions introduced by Reshetikhin and Semenov{endash}Tian{endash}Shansky to the case of the Perk{endash}Shultz model. By using the method proposed by Frenkel{endash}Ding, we establish the Drinfeld constructions of the quantum affine superalgebra U{sub q}{bold (}gl({cflx m}/n){bold )}. {copyright} {ital 1997 American Institute of Physics.}

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

    PubMed

    Sousa, I; Vilela, P; Figueiredo, P

    2014-09-01

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

  15. The effect of dissolved oxygen on the relaxation rates of blood plasma: Implications for hyperoxia calibrated BOLD.

    PubMed

    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 (pO2 ) ranging from 110 to 600 mmHg. R1 , R2 , and R2(*) 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 r1,O2 =1.97 ± 0.09 ×10(-4) s(-1) mmHg(-1) , r2,O2 =2.3 ± 0.7 ×10(-4) s(-1) mmHg(-1) , and r2,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 R2 and R2(*) of blood from dissolved oxygen in plasma are considerably less than the decreases in R2 and R2(*) from venous deoxyhemoglobin. R1 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.

  16. Plasticity varies with boldness in a weakly-electric fish.

    PubMed

    Kareklas, Kyriacos; Arnott, Gareth; Elwood, Robert W; Holland, Richard A

    2016-01-01

    The expression of animal personality is indicated by patterns of consistency in individual behaviour. Often, the differences exhibited between individuals are consistent across situations. However, between some situations, this can be biased by variable levels of individual plasticity. The interaction between individual plasticity and animal personality can be illustrated by examining situation-sensitive personality traits such as boldness (i.e. risk-taking and exploration tendency). For the weakly electric fish Gnathonemus petersii, light condition is a major factor influencing behaviour. Adapted to navigate in low-light conditions, this species chooses to be more active in dark environments where risk from visual predators is lower. However, G. petersii also exhibit individual differences in their degree of behavioural change from light to dark. The present study, therefore, aims to examine if an increase of motivation to explore in the safety of the dark, not only affects mean levels of boldness, but also the variation between individuals, as a result of differences in individual plasticity. Boldness was consistent between a novel-object and a novel-environment situation in bright light. However, no consistency in boldness was noted between a bright (risky) and a dark (safe) novel environment. Furthermore, there was a negative association between boldness and the degree of change across novel environments, with shier individuals exhibiting greater behavioural plasticity. This study highlights that individual plasticity can vary with personality. In addition, the effect of light suggests that variation in boldness is situation specific. Finally, there appears to be a trade-off between personality and individual plasticity with shy but plastic individuals minimizing costs when perceiving risk and bold but stable individuals consistently maximizing rewards, which can be maladaptive.

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

    PubMed

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

    2016-05-01

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

  18. Magnitude and phase behavior of multiresolution BOLD signal

    PubMed Central

    Chen, Zikuan; Calhoun, Vince D.

    2010-01-01

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

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

    PubMed

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

    2012-11-15

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

  20. Hypoxia in Prostate Cancer: Correlation of BOLD-MRI With Pimonidazole Immunohistochemistry-Initial Observations

    SciTech Connect

    Hoskin, Peter J. . E-mail: peterhoskin@nhs.net; Carnell, Dawn M.; Taylor, N. Jane; Smith, Rowena E.; Stirling, J. James; Daley, Frances M.; Saunders, Michele I.; Bentzen, Soren M.; Collins, David J.; D'Arcy, James A.; Padhani, Anwar P.

    2007-07-15

    Purpose: To investigate the ability of blood oxygen level-dependent (BOLD) MRI to depict clinically significant prostate tumor hypoxia. Methods and Materials: Thirty-three patients with prostate carcinoma undergoing radical prostatectomy were studied preoperatively, using gradient echo sequences without and with contrast medium enhancement, to map relative tissue oxygenation according to relaxivity rates and relative blood volume (rBV). Pimonidazole was administered preoperatively, and whole-mount sections of selected tumor-bearing slices were stained for pimonidazole fixation and tumor and nontumor localization. Histologic and imaging parameters were independently mapped onto patient prostate outlines. Using 5-mm grids, 861 nontumor grid locations were compared with 237 tumor grids (with >50% tumor per location) using contingency table analysis with respect to the ability of imaging to predict pimonidazole staining. Results: Twenty patients completed the imaging and histologic protocols. Pimonidazole staining was found in 33% of nontumor and in 70% of tumor grids. The sensitivity of the MR relaxivity parameter R{sub 2}* in depicting tumor hypoxia was high (88%), improving with the addition of low rBV information (95%) without changing specificity (36% and 29%, respectively). High R{sub 2}* increased the positive predictive value for hypoxia by 6% (70% to 76%); conversely, low R{sub 2}* decreased the likelihood of hypoxia being present by 26% (70% to 44%) and by 41% (71% to 30%) when combined with rBV information. Conclusion: R{sub 2}* maps from BOLD-MRI have high sensitivity but low specificity for defining intraprostatic tumor hypoxia. This together with the negative predictive value of 70% when combined with blood volume information makes BOLD-MRI a potential noninvasive technique for mapping prostatic tumor hypoxia.

  1. Task-Induced Symmetry and Reduction in Kinematic Systems with Application to Needle Steering

    PubMed Central

    Kallem, Vinutha; Chang, Dong Eui; Cowan, Noah J.

    2010-01-01

    Lie group symmetry in a mechanical system can lead to a dimensional reduction in its dynamical equations. Typically, the symmetries that one exploits are intrinsic to the mechanical system at hand, e.g. invariance of the system’s Lagrangian to some group of motions. In the present work we consider symmetries that arise from an extrinsic control task, rather than the intrinsic structure of configuration space, constraints, or system dynamics. We illustrate this technique with several examples. In the examples, the reduction enables us to design essentially global feedback controllers on the reduced systems. We apply task-induced symmetry and reduction to a recently developed 6 DOF kinematic model of steerable bevel-tip needles. The resulting controllers cause the needle tip to track a subspace of its configuration space. We envision that the methodology presented in this paper will form the basis for a new planning and control framework for needle steering. PMID:20664750

  2. Task-Induced Symmetry and Reduction in Kinematic Systems with Application to Needle Steering.

    PubMed

    Kallem, Vinutha; Chang, Dong Eui; Cowan, Noah J

    2007-10-29

    Lie group symmetry in a mechanical system can lead to a dimensional reduction in its dynamical equations. Typically, the symmetries that one exploits are intrinsic to the mechanical system at hand, e.g. invariance of the system's Lagrangian to some group of motions. In the present work we consider symmetries that arise from an extrinsic control task, rather than the intrinsic structure of configuration space, constraints, or system dynamics. We illustrate this technique with several examples. In the examples, the reduction enables us to design essentially global feedback controllers on the reduced systems.We apply task-induced symmetry and reduction to a recently developed 6 DOF kinematic model of steerable bevel-tip needles. The resulting controllers cause the needle tip to track a subspace of its configuration space. We envision that the methodology presented in this paper will form the basis for a new planning and control framework for needle steering.

  3. Bold Diagrammatic Monte Carlo for Fermionic and Fermionized Systems

    NASA Astrophysics Data System (ADS)

    Svistunov, Boris

    2013-03-01

    In three different fermionic cases--repulsive Hubbard model, resonant fermions, and fermionized spins-1/2 (on triangular lattice)--we observe the phenomenon of sign blessing: Feynman diagrammatic series features finite convergence radius despite factorial growth of the number of diagrams with diagram order. Bold diagrammatic Monte Carlo technique allows us to sample millions of skeleton Feynman diagrams. With the universal fermionization trick we can fermionize essentially any (bosonic, spin, mixed, etc.) lattice system. The combination of fermionization and Bold diagrammatic Monte Carlo yields a universal first-principle approach to strongly correlated lattice systems, provided the sign blessing is a generic fermionic phenomenon. Supported by NSF and DARPA

  4. How bold is blood oxygenation level-dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions.

    PubMed

    Niendorf, T; Pohlmann, A; Arakelyan, K; Flemming, B; Cantow, K; Hentschel, J; Grosenick, D; Ladwig, M; Reimann, H; Klix, S; Waiczies, S; Seeliger, E

    2015-01-01

    Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD-MRI is non-invasive and indicative of renal tissue oxygenation. Nonetheless, recent (pre-) clinical studies revived the question as to how bold renal BOLD-MRI really is. This review aimed to deliver some answers. It is designed to inspire the renal physiology, nephrology and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose, the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD-MRI are summarized. The link between tissue oxygenation and the oxygenation-sensitive MR biomarker T2∗ is outlined. The merits and limitations of renal BOLD-MRI in animal and human studies are surveyed together with their clinical implications. Explorations into detailing the relation between renal T2∗ and renal tissue partial pressure of oxygen (pO2 ) are discussed with a focus on factors confounding the T2∗ vs. tissue pO2 relation. Multi-modality in vivo approaches suitable for detailing the role of the confounding factors that govern T2∗ are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal T2∗ is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.

  5. Task effects on BOLD signal correlates of implicit syntactic processing

    PubMed Central

    Caplan, David

    2010-01-01

    BOLD signal was measured in sixteen participants who made timed font change detection judgments in visually presented sentences that varied in syntactic structure and the order of animate and inanimate nouns. Behavioral data indicated that sentences were processed to the level of syntactic structure. BOLD signal increased in visual association areas bilaterally and left supramarginal gyrus in the contrast of sentences with object- and subject-extracted relative clauses without font changes in which the animacy order of the nouns biased against the syntactically determined meaning of the sentence. This result differs from the findings in a non-word detection task (Caplan et al, 2008a), in which the same contrast led to increased BOLD signal in the left inferior frontal gyrus. The difference in areas of activation indicates that the sentences were processed differently in the two tasks. These differences were further explored in an eye tracking study using the materials in the two tasks. Issues pertaining to how parsing and interpretive operations are affected by a task that is being performed, and how this might affect BOLD signal correlates of syntactic contrasts, are discussed. PMID:20671983

  6. The Boldest New Idea? An End to Bold Ideas

    ERIC Educational Resources Information Center

    Rothstein, Richard

    2011-01-01

    The past two decades have proven that bold, single-factor reform ideas have little power to change the face of education. Pundits and policymakers would have schools and school systems make grand changes to accommodate the reform idea du jour--and then profess the incompetence of schools and teachers when those changes prove less than effective.…

  7. FY 2011 Federal Budget Process Begins with Bold Proposal

    ERIC Educational Resources Information Center

    Karolak, Eric

    2010-01-01

    The federal government's annual budget process was kick-started this year with a bold proposal that has implications for anyone who provides child care. But keeping child care front and center in Washington will take a lot of effort in 2010. On February 1, the Administration released the Budget Proposal for Federal Fiscal Year 2011. It calls for…

  8. FY 2011 Federal Budget Process Begins with Bold Proposal

    ERIC Educational Resources Information Center

    Karolak, Eric

    2010-01-01

    The federal government's annual budget process was kick-started this year with a bold proposal that has implications for anyone who provides child care. But keeping child care front and center in Washington will take a lot of effort in 2010. On February 1, the Administration released the Budget Proposal for Federal Fiscal Year 2011. It calls for…

  9. BOLD-Perfusion Coupling during Monocular and Binocular Stimulation

    PubMed Central

    Gauthier, Claudine; Hoge, Richard D.

    2008-01-01

    Previous studies have suggested that during selective activation of a subset of the zones comprising a columnar system in visual cortex, perfusion increases uniformly in all columns of the system, while increases in oxidative metabolism occur predominantly in the activated columns. This could lead to disproportionately large blood oxygenation level-dependent (BOLD) signal increases for a given flow increase during monocular (relative to binocular) stimulation, due to contributions from columns which undergo large increases in perfusion with little or no change in oxidative metabolism. In the present study, we sought to test this hypothesis by measuring BOLD-perfusion coupling ratios in spatially averaged signals over V1 during monocular and binocular visual stimulation. It was found that, although withholding input to one eye resulted in statistically significant decreases in BOLD and perfusion signals in primary visual cortex, the ratio between BOLD and perfusion increases did not change significantly. These results do not support a gross mismatch between spatial patterns of flow and metabolism response during monocular stimulation. PMID:18350120

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

    PubMed

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

    2013-01-01

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

  11. Task-Induced Symmetry and Reduction with Application to Needle Steering

    PubMed Central

    Kallem, Vinutha; Chang, Dong Eui; Cowan, Noah J.

    2010-01-01

    Lie group symmetry in a mechanical system can lead to a dimensional reduction in its dynamical equations. Typically, the symmetries that one exploits are intrinsic to the mechanical system at hand, e.g. invariance of the system’s Lagrangian to some group of motions. In the present work we consider symmetries that arise from an extrinsic control task, rather than the intrinsic structure of the configuration space, constraints, or system dynamics. We illustrate this technique with several examples. In the examples, the reduction enables us to design essentially global feedback controllers on the reduced systems. We also demonstrate how the proposed technique dovetails with Lagrangian reduction. We apply task-induced symmetry and reduction to a recently developed 6 DOF kinematic model of steerable bevel-tip needles. The resulting controllers cause the needle tip to track a subspace of its configuration space. We envision that the methodology presented in this paper will form the basis for a new planning and control framework for needle steering. PMID:20485454

  12. [Analysis of surface electromyography on repetitive lifting task-induced fatigue of back muscles].

    PubMed

    Chen, Jing; Ding, Jia-Shun; Wang, Zheng-Lun; Yang, Lei

    2004-12-01

    Using surface electromyography (SEMG) technique to evaluate repetitive lifting task-induced fatigue of back muscles. Thirteen volunteers lifted and lowered an 8 kg weight from floor to waist level for 100 times. Fatigue in the erector spinae muscles was quantified by comparing the frequency content of the EMG signal during static contractions performed before, and immediately after the 100 lifts. EMG average amplitude rose gradually during 100 lifts, the difference was significant at T10 right (P < 0.05) and L3 left (P < 0.01), the difference was not significant at T10 left and L3 right (P > 0.05). The median frequency intercept at T10 right, T10 left, L3 right, L3 left erector spinae muscles decreased by 2.0% (P > 0.05) 10.9% and 29.9% (P < 0.05), 27.9% (P < 0.01), respectively. The mean power frequency intercept decreased by 9% at L3 left erector spinae muscle (P < 0.05), the decrease was not statistically significant at other sites (P > 0.05). Repetitive lifting may induce measurable fatigue in the erector spinae muscles. Erector spinae muscle at L3 is more easily fatigued than at T10. Using the median frequency intercept to assess muscle fatigue is more sensitive than using mean power frequency intercept.

  13. Age association of language task induced deactivation induced in a pediatric population.

    PubMed

    Sun, Binjian; Berl, Madison M; Burns, Thomas G; Gaillard, William D; Hayes, Laura; Adjouadi, Malek; Jones, Richard A

    2013-01-15

    Task-induced deactivation (TID) potentially reflects the interactions between the default mode and task specific networks, which are assumed to be age dependent. The study of the age association of such interactions provides insight about the maturation of neural networks, and lays out the groundwork for evaluating abnormal development of neural networks in neurological disorders. The current study analyzed the deactivations induced by language tasks in 45 right-handed normal controls aging from 6 to 22 years of age. Converging results from GLM, dual regression and ROI analyses showed a gradual reduction in both the spatial extent and the strength of the TID in the DMN cortices as the brain matured from kindergarten to early adulthood in the absence of any significant change in task performance. The results may be ascribed to maturation leading to either improved multi-tasking (i.e. reduced deactivation) or reduced cognitive demands due to greater experience (affects both control and active tasks but leads to reduced overall difference). However, other effects, such as changes in the DMN connectivity that were not included in this study may also have influenced the results. In light of this, researchers should be cautious when investigating the maturation of DMN using TID. With a GLM analysis using the concatenated fMRI data from several paradigms, this study additionally identified an age associated increase of TID in the STG (bilateral), possibly reflecting the role of this area in speech perception and phonological processing.

  14. Task-Induced Symmetry and Reduction with Application to Needle Steering.

    PubMed

    Kallem, Vinutha; Chang, Dong Eui; Cowan, Noah J

    2010-01-01

    Lie group symmetry in a mechanical system can lead to a dimensional reduction in its dynamical equations. Typically, the symmetries that one exploits are intrinsic to the mechanical system at hand, e.g. invariance of the system's Lagrangian to some group of motions. In the present work we consider symmetries that arise from an extrinsic control task, rather than the intrinsic structure of the configuration space, constraints, or system dynamics. We illustrate this technique with several examples. In the examples, the reduction enables us to design essentially global feedback controllers on the reduced systems. We also demonstrate how the proposed technique dovetails with Lagrangian reduction.We apply task-induced symmetry and reduction to a recently developed 6 DOF kinematic model of steerable bevel-tip needles. The resulting controllers cause the needle tip to track a subspace of its configuration space. We envision that the methodology presented in this paper will form the basis for a new planning and control framework for needle steering.

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

    PubMed Central

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

    2010-01-01

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

  16. Electrophysiological low-frequency coherence and cross-frequency coupling contribute to BOLD connectivity.

    PubMed

    Wang, Liang; Saalmann, Yuri B; Pinsk, Mark A; Arcaro, Michael J; Kastner, Sabine

    2012-12-06

    Brain networks are commonly defined using correlations between blood oxygen level-dependent (BOLD) signals in different brain areas. Although evidence suggests that gamma-band (30-100 Hz) neural activity contributes to local BOLD signals, the neural basis of interareal BOLD correlations is unclear. We first defined a visual network in monkeys based on converging evidence from interareal BOLD correlations during a fixation task, task-free state, and anesthesia, and then simultaneously recorded local field potentials (LFPs) from the same four network areas in the task-free state. Low-frequency oscillations (<20 Hz), and not gamma activity, predominantly contributed to interareal BOLD correlations. The low-frequency oscillations also influenced local processing by modulating gamma activity within individual areas. We suggest that such cross-frequency coupling links local BOLD signals to BOLD correlations across distributed networks.

  17. Electrophysiological low-frequency coherence and cross-frequency coupling contributes to BOLD connectivity

    PubMed Central

    Wang, Liang; Saalmann, Yuri B.; Pinsk, Mark A.; Arcaro, Michael J.; Kastner, Sabine

    2012-01-01

    SUMMARY Brain networks are commonly defined using correlations between blood oxygen level-dependent (BOLD) signals in different brain areas. Although evidence suggests that gamma band (30–100 Hz) neural activity contributes to local BOLD signals, the neural basis of inter-areal BOLD correlations is unclear. We first defined a visual network in monkeys based on converging evidence from inter-areal BOLD correlations during a fixation task, task-free state and anesthesia, and then simultaneously recorded local field potentials (LFPs) from the same four network areas in the task-free state. Low frequency oscillations (< 20 Hz), and not gamma activity, predominantly contributed to inter-areal BOLD correlations. The low frequency oscillations also influenced local processing by modulating gamma activity within individual areas. We suggest that such cross-frequency coupling links local BOLD signals to BOLD correlations across distributed networks. PMID:23217748

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Churchill, Nathan W; Strother, Stephen C

    2013-11-15

    The presence of physiological noise in functional MRI can greatly limit the sensitivity and accuracy of BOLD signal measurements, and produce significant false positives. There are two main types of physiological confounds: (1) high-variance signal in non-neuronal tissues of the brain including vascular tracts, sinuses and ventricles, and (2) physiological noise components which extend into gray matter tissue. These physiological effects may also be partially coupled with stimuli (and thus the BOLD response). To address these issues, we have developed PHYCAA+, a significantly improved version of the PHYCAA algorithm (Churchill et al., 2011) that (1) down-weights the variance of voxels in probable non-neuronal tissue, and (2) identifies the multivariate physiological noise subspace in gray matter that is linked to non-neuronal tissue. This model estimates physiological noise directly from EPI data, without requiring external measures of heartbeat and respiration, or manual selection of physiological components. The PHYCAA+ model significantly improves the prediction accuracy and reproducibility of single-subject analyses, compared to PHYCAA and a number of commonly-used physiological correction algorithms. Individual subject denoising with PHYCAA+ is independently validated by showing that it consistently increased between-subject activation overlap, and minimized false-positive signal in non gray-matter loci. The results are demonstrated for both block and fast single-event task designs, applied to standard univariate and adaptive multivariate analysis models. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Archimedes: a bold step into the future.

    PubMed

    Lumpkin, John R

    2007-01-01

    The increasing adoption of electronic health records (EHRs) enables the development of new tools to guide clinical research, clinical protocol development, and national policy formulation. Archimedes is an example of a new generation of tools that go beyond identifying past problems with medical devices and pharmaceuticals or failures with health care delivery to predicting potential problems and identifying new treatments and approaches that can improve care. Although the arrival of this new generation of tools raises some concerns, the tools' great potential for improving care must be carefully considered.

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

    PubMed

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

    2010-10-15

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

  2. Matched-filter acquisition for BOLD fMRI.

    PubMed

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

    2014-10-15

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  4. Does “Task Difficulty” Explain “Task-Induced Deactivation?”

    PubMed Central

    Gilbert, Sam J.; Bird, Geoffrey; Frith, Chris D.; Burgess, Paul W.

    2012-01-01

    The “default mode network” is commonly described as a set of brain regions in which activity is suppressed during relatively demanding, or difficult, tasks. But what sort of tasks are these? We review some of the contrasting ways in which a task might be assessed as being difficult, such as error rate, response time, propensity to interfere with performance of other tasks, and requirement for transformation of internal representations versus accumulation of perceptual information. We then describe a fMRI study in which 18 participants performed two “stimulus-oriented” tasks, where responses were directly cued by visual stimuli, alongside a “stimulus-independent” task, with a greater reliance on internally generated information. When indexed by response time and error rate, the stimulus-independent task was intermediate in difficulty between the two stimulus-oriented tasks. Nevertheless, BOLD signal in medial rostral prefrontal cortex (MPFC) – a prominent part of the default mode network – was reduced in the stimulus-independent condition in comparison with both the more difficult and the less difficult stimulus-oriented conditions. By contrast, other regions of the default mode network showed greatest deactivation in the difficult stimulus-oriented condition. There was therefore significant functional heterogeneity between different default mode regions. We conclude that task difficulty – as measured by response time and error rate – does not provide an adequate account of signal change in MPFC. At least in some circumstances, a better predictor of MPFC activity is the requirement of a task for transformation and manipulation of internally represented information, with greatest MPFC activity in situations predominantly requiring attention to perceptual information. PMID:22539930

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2011-09-01

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

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

    PubMed

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

    2008-06-01

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

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

    PubMed

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

    2012-10-01

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

  9. Resting states affect spontaneous BOLD oscillations in sensory and paralimbic cortex.

    PubMed

    McAvoy, Mark; Larson-Prior, Linda; Nolan, Tracy S; Vaishnavi, S Neil; Raichle, Marcus E; d'Avossa, Giovanni

    2008-08-01

    The brain exhibits spontaneous neural activity that depends on the behavioral state of the organism. We asked whether the blood oxygenation level-dependent (BOLD) signal reflects these modulations. BOLD was measured under three steady-state conditions: while subjects kept their eyes closed, kept their eyes open, or while fixating. The BOLD spectral density was calculated across brain voxels and subjects. Visual, sensory-motor, auditory, and retrosplenial cortex showed modulations of the BOLD spectral density by resting state type. All modulated regions showed greater spontaneous BOLD oscillations in the eyes closed than the eyes open or fixation conditions, suggesting that the differences were endogenously driven. Next, we examined the pattern of correlations between regions whose ongoing BOLD signal was modulated by resting state type. Regional neuronal correlations were estimated using an analytic procedure from the comparison of BOLD-BOLD covariances in the fixation and eyes closed conditions. Most regions were highly correlated with one another, with the exception of the primary visual cortices, which showed low correlations with the other regions. In conclusion, changes in resting state were associated with synchronous modulations of spontaneous BOLD oscillations in cortical sensory areas driven by two spatially overlapping, but temporally uncorrelated signals.

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

    PubMed

    Sotero, Roberto C; Iturria-Medina, Yasser

    2011-11-01

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

  11. Trade-off between frequency and precision during stepping movements: Kinematic and BOLD brain activation patterns.

    PubMed

    Martínez, Martin; Valencia, Miguel; Vidorreta, Marta; Luis, Elkin O; Castellanos, Gabriel; Villagra, Federico; Fernández-Seara, Maria A; Pastor, Maria A

    2016-05-01

    The central nervous system has the ability to adapt our locomotor pattern to produce a wide range of gait modalities and velocities. In reacting to external pacing stimuli, deviations from an individual preferred cadence provoke a concurrent decrease in accuracy that suggests the existence of a trade-off between frequency and precision; a compromise that could result from the specialization within the control centers of locomotion to ensure a stable transition and optimal adaptation to changing environment. Here, we explore the neural correlates of such adaptive mechanisms by visually guiding a group of healthy subjects to follow three comfortable stepping frequencies while simultaneously recording their BOLD responses and lower limb kinematics with the use of a custom-built treadmill device. In following the visual stimuli, subjects adopt a common pattern of symmetric and anti-phase movements across pace conditions. However, when increasing the stimulus frequency, an improvement in motor performance (precision and stability) was found, which suggests a change in the control mode from reactive to predictive schemes. Brain activity patterns showed similar BOLD responses across pace conditions though significant differences were observed in parietal and cerebellar regions. Neural correlates of stepping precision were found in the insula, cerebellum, dorsolateral pons and inferior olivary nucleus, whereas neural correlates of stepping stability were found in a distributed network, suggesting a transition in the control strategy across the stimulated range of frequencies: from unstable/reactive at lower paces (i.e., stepping stability managed by subcortical regions) to stable/predictive at higher paces (i.e., stability managed by cortical regions). Hum Brain Mapp 37:1722-1737, 2016. © 2016 Wiley Periodicals, Inc.

  12. Advances in the hydrodynamics solver of CO5BOLD

    NASA Astrophysics Data System (ADS)

    Freytag, Bernd

    Many features of the Roe solver used in the hydrodynamics module of CO5BOLD have recently been added or overhauled, including the reconstruction methods (by adding the new second-order ``Frankenstein's method''), the treatment of transversal velocities, energy-flux averaging and entropy-wave treatment at small Mach numbers, the CTU scheme to combine the one-dimensional fluxes, and additional safety measures. All this results in a significantly better behavior at low Mach number flows, and an improved stability at larger Mach numbers requiring less (or no) additional tensor viscosity, which then leads to a noticeable increase in effective resolution.

  13. The Effect of Letter-stroke Boldness on Reading Speed in Central and Peripheral Vision

    PubMed Central

    Bernard, Jean-Baptiste; Kumar, Girish; Junge, Jasmine; Chung, Susana T.L.

    2013-01-01

    People with central vision loss often prefer boldface print over normal print for reading. However, little is known about how reading speed is influenced by the letter-stroke boldness of font. In this study, we examined the reliance of reading speed on stroke boldness, and determined whether this reliance differs between the normal central and peripheral vision. Reading speed was measured using the rapid serial visual presentation paradigm, where observers with normal vision read aloud short single sentences presented on a computer monitor, one word at a time. Text was rendered in Courier at six levels of boldness, defined as the stroke-width normalized to that of the standard Courier font: 0.27, 0.72, 1, 1.48, 1.89 and 3.04× the standard. Testings were conducted at the fovea and 10° in the inferior visual field. Print sizes used were 0.8× and 1.4× the critical print size (smallest print size that can be read at the maximum reading speed). At the fovea, reading speed was invariant for the middle four levels of boldness, but dropped by 23.3% for the least and the most bold text. At 10° eccentricity, reading speed was virtually the same for all boldness <1, but showed a poorer tolerance to bolder text, dropping by 21.5% for 1.89x boldness and 51% for the most bold (3.04x) text. These results could not be accounted for by the changes in print size or the RMS contrast of text associated with changes in stroke boldness. Our results suggest that contrary to the popular belief, reading speed does not benefit from bold text in the normal fovea and periphery. Excessive increase in stroke boldness may even impair reading speed, especially in the periphery. PMID:23523572

  14. Bold coloration and the evolution of aposematism in terrestrial carnivores.

    PubMed

    Stankowich, Theodore; Caro, Tim; Cox, Matthew

    2011-11-01

    Several species of terrestrial carnivores (Mammalia: Carnivora) have bold contrasting color patterns that, in some species, apparently signal possession of noxious anal gland secretions, or even physical strength and great ferocity; yet the evolutionary drivers of both placement and patterning of these contrasting pelage colors on the body, and the ecological selection pressures underlying them, have yet to be systematically examined. Here we explore these issues and find not only that both boldly colored and dichromatic species do indeed often use anal gland secretions for defense, but also that such species are stockier, and live in more exposed habitats where other forms of antipredator defense are limited. We also show that white dorsa are found in sprayers that are primarily nocturnal; that horizontal stripes are found in species that have an ability to spray anal secretions accurately; and that facial stripes are found in burrowing species that typically leave only their heads exposed to attack. Our phylogenetic reconstructions suggest that aposematic coloration has evolved more than once in terrestrial carnivores. We finish by outlining five evolutionary routes for patterns of pelage coloration in this taxon.

  15. Crossing the implementation chasm: a proposal for bold action.

    PubMed

    Lorenzi, Nancy M; Novak, Laurie L; Weiss, Jacob B; Gadd, Cynthia S; Unertl, Kim M

    2008-01-01

    As health care organizations dramatically increase investment in information technology (IT) and the scope of their IT projects, implementation failures become critical events. Implementation failures cause stress on clinical units, increase risk to patients, and result in massive costs that are often not recoverable. At an estimated 28% success rate, the current level of investment defies management logic. This paper asserts that there are "chasms" in IT implementations that represent risky stages in the process. Contributors to the chasms are classified into four categories: design, management, organization, and assessment. The American College of Medical Informatics symposium participants recommend bold action to better understand problems and challenges in implementation and to improve the ability of organizations to bridge these implementation chasms. The bold action includes the creation of a Team Science for Implementation strategy that allows for participation from multiple institutions to address the long standing and costly implementation issues. The outcomes of this endeavor will include a new focus on interdisciplinary research and an inter-organizational knowledge base of strategies and methods to optimize implementations and subsequent achievement of organizational objectives.

  16. Pupil diameter covaries with BOLD activity in human locus coeruleus.

    PubMed

    Murphy, Peter R; O'Connell, Redmond G; O'Sullivan, Michael; Robertson, Ian H; Balsters, Joshua H

    2014-08-01

    The locus coeruleus-noradrenergic (LC-NA) neuromodulatory system has been implicated in a broad array of cognitive processes, yet scope for investigating this system's function in humans is currently limited by an absence of reliable non-invasive measures of LC activity. Although pupil diameter has been employed as a proxy measure of LC activity in numerous studies, empirical evidence for a relationship between the two is lacking. In the present study, we sought to rigorously probe the relationship between pupil diameter and BOLD activity localized to the human LC. Simultaneous pupillometry and fMRI revealed a relationship between continuous pupil diameter and BOLD activity in a dorsal pontine cluster overlapping with the LC, as localized via neuromelanin-sensitive structural imaging and an LC atlas. This relationship was present both at rest and during performance of a two-stimulus oddball task, with and without spatial smoothing of the fMRI data, and survived retrospective image correction for physiological noise. Furthermore, the spatial extent of this pupil/LC relationship guided a volume-of-interest analysis in which we provide the first demonstration in humans of a fundamental characteristic of animal LC activity: phasic modulation by oddball stimulus relevance. Taken together, these findings highlight the potential for utilizing pupil diameter to achieve a more comprehensive understanding of the role of the LC-NA system in human cognition.

  17. Correlation between BOLD-MRI and HIF expression level in renal carcinoma.

    PubMed

    Li, Dong; Wang, Xingming; Wang, Shuai; Cheng, Jie

    2015-01-01

    Occupying about 2%~3% of all malignant tumors, renal carcinoma is the most common primary cancer in kidney. The oxidative level of tumor cells is of vital role for optimizing treatment plan, evaluating efficacy and predicting prognosis. This study thus investigated the R2(*) value in mouse renal carcinoma model and the correlation between tumor hypoxia and expression level of hypoxia inducible factor-1 (HIF-1). A total of 20 BALB/C nude mice (4~6 weeks old) were inoculated with human ACHN renal carcinoma cells to generate renal cancer model. After the tumor diameter reached 0.5 cm, all animals were examined by BOLD-MRI, both under normal inhalation (R2a(*)) and carbogen treatment (R2b(*)). The alternation of R2(*) values (ΔR2(*)=R2a(*) - R2b(*)) was calculated. Mice were then sacrificed for Immunohistochemical (IHC) staining targeting HIF-1α and HIF-2α. The positive score of HIF was then analyzed for its correlation with R2(*) value. In 18 mice finished both experiments, Pearson correlation analysis revealed significant negative correlation between R2a(*) and ΔR2(*) (r=-0.48, P<0.05) and positive relationship between ΔR2(*) and HIF-2α (r=0.38, P<0.05). HIF-1α level, however, did not correlated with tumor R(*) values. The positive correlation between ΔR2(*) and HIF-2α, but not HIF-1α, suggested potential role of combined BOLD-MRI technique and HIF-1α staining in clinical diagnosis of renal carcinoma. HIF-2α may work as biological marker for renal cancer.

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

    NASA Astrophysics Data System (ADS)

    Alonso, Benito De Celis

    2012-10-01

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

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

    PubMed

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

    2007-01-01

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

  20. Assessing Vascular Oxygen Dynamics for Breast Tumor Prognosis: Comparison Between MR BOLD and Near Infrared Method

    DTIC Science & Technology

    2005-09-01

    treat- ments, such as chemotherapy and radiotherapy (37). In summary, changes in breast tumor temperature and vascular oxygenation have been... Breast Tumor Prognosis: Comparison Between MR BOLD and Near Infrared Method PRINCIPAL INVESTIGATOR: Hanli Liu, Ph.D...CONTRACT NUMBER Assessing Vascular Oxygen Dynamics for Breast Tumor Prognosis: Comparison Between MR BOLD and Near Infrared Method

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

    PubMed

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

    2016-11-01

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

  2. BOLD signal and functional connectivity associated with loving kindness meditation.

    PubMed

    Garrison, Kathleen A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2014-05-01

    Loving kindness is a form of meditation involving directed well-wishing, typically supported by the silent repetition of phrases such as "may all beings be happy," to foster a feeling of selfless love. Here we used functional magnetic resonance imaging to assess the neural substrate of loving kindness meditation in experienced meditators and novices. We first assessed group differences in blood oxygen level-dependent (BOLD) signal during loving kindness meditation. We next used a relatively novel approach, the intrinsic connectivity distribution of functional connectivity, to identify regions that differ in intrinsic connectivity between groups, and then used a data-driven approach to seed-based connectivity analysis to identify which connections differ between groups. Our findings suggest group differences in brain regions involved in self-related processing and mind wandering, emotional processing, inner speech, and memory. Meditators showed overall reduced BOLD signal and intrinsic connectivity during loving kindness as compared to novices, more specifically in the posterior cingulate cortex/precuneus (PCC/PCu), a finding that is consistent with our prior work and other recent neuroimaging studies of meditation. Furthermore, meditators showed greater functional connectivity during loving kindness between the PCC/PCu and the left inferior frontal gyrus, whereas novices showed greater functional connectivity during loving kindness between the PCC/PCu and other cortical midline regions of the default mode network, the bilateral posterior insula lobe, and the bilateral parahippocampus/hippocampus. These novel findings suggest that loving kindness meditation involves a present-centered, selfless focus for meditators as compared to novices.

  3. Frontal cortex BOLD signal changes in premanifest Huntington disease

    PubMed Central

    Ferraro, Stefania; Piacentini, Sylvie; Mandelli, Maria L.; Bertolino, Nicola; Ghielmetti, Francesco; Epifani, Francesca; Nigri, Anna; Taroni, Franco; Bruzzone, Maria G.; Donato, Stefano Di; Savoiardo, Mario; Mariotti, Caterina; Grisoli, Marina

    2014-01-01

    Objective: To identify a possible functional imaging biomarker sensitive to the earliest neural changes in premanifest Huntington disease (preHD), allowing early therapeutic approaches aimed at preventing or delaying clinical onset. Methods: Sixteen preHD and 18 healthy participants were submitted to anatomical acquisitions and functional MRI (fMRI) acquisitions during the execution of the exogenous covert orienting of attention task. Due to strong a priori hypothesis, all fMRI correlation analyses were restricted to the following: (1) the frontal oculomotor cortex identified by the means of a prosaccadic task, comprising frontal eye fields and supplementary frontal eye fields; and (2) the data collected during inhibition of return, a phenomenon occurring during the executed task. In preHD, multiple regression analysis was performed between fMRI data and the probability to develop the disease in the next 5 years (p5HD). Moreover, mean blood oxygen level–dependent (BOLD) signal changes in the frontal oculomotor cortex and striatal volumes were linearly correlated with p5HD. Results: In preHD, multiple regression analysis showed that clusters of activity strongly correlated with p5HD in the right frontal oculomotor cortex. Importantly, mean BOLD signal changes of this region correlated with p5HD (r2 = 0.52). Among the considered striatal volumes, a modest correlation (r2 = 0.29) was observed in the right putamen and p5HD. Conclusion: fMRI activations in the right-frontal oculomotor cortex during inhibition of return can be considered a possible functional imaging biomarker in preHD. PMID:24898924

  4. BOLD signal and functional connectivity associated with loving kindness meditation

    PubMed Central

    Garrison, Kathleen A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2014-01-01

    Loving kindness is a form of meditation involving directed well-wishing, typically supported by the silent repetition of phrases such as “may all beings be happy,” to foster a feeling of selfless love. Here we used functional magnetic resonance imaging to assess the neural substrate of loving kindness meditation in experienced meditators and novices. We first assessed group differences in blood oxygen level-dependent (BOLD) signal during loving kindness meditation. We next used a relatively novel approach, the intrinsic connectivity distribution of functional connectivity, to identify regions that differ in intrinsic connectivity between groups, and then used a data-driven approach to seed-based connectivity analysis to identify which connections differ between groups. Our findings suggest group differences in brain regions involved in self-related processing and mind wandering, emotional processing, inner speech, and memory. Meditators showed overall reduced BOLD signal and intrinsic connectivity during loving kindness as compared to novices, more specifically in the posterior cingulate cortex/precuneus (PCC/PCu), a finding that is consistent with our prior work and other recent neuroimaging studies of meditation. Furthermore, meditators showed greater functional connectivity during loving kindness between the PCC/PCu and the left inferior frontal gyrus, whereas novices showed greater functional connectivity during loving kindness between the PCC/PCu and other cortical midline regions of the default mode network, the bilateral posterior insula lobe, and the bilateral parahippocampus/hippocampus. These novel findings suggest that loving kindness meditation involves a present-centered, selfless focus for meditators as compared to novices. PMID:24944863

  5. Spatiotemporal alignment of in utero BOLD-MRI series.

    PubMed

    Turk, Esra Abaci; Luo, Jie; Gagoski, Borjan; Pascau, Javier; Bibbo, Carolina; Robinson, Julian N; Grant, P Ellen; Adalsteinsson, Elfar; Golland, Polina; Malpica, Norberto

    2017-08-01

    To present a method for spatiotemporal alignment of in-utero magnetic resonance imaging (MRI) time series acquired during maternal hyperoxia for enabling improved quantitative tracking of blood oxygen level-dependent (BOLD) signal changes that characterize oxygen transport through the placenta to fetal organs. The proposed pipeline for spatiotemporal alignment of images acquired with a single-shot gradient echo echo-planar imaging includes 1) signal nonuniformity correction, 2) intravolume motion correction based on nonrigid registration, 3) correction of motion and nonrigid deformations across volumes, and 4) detection of the outlier volumes to be discarded from subsequent analysis. BOLD MRI time series collected from 10 pregnant women during 3T scans were analyzed using this pipeline. To assess pipeline performance, signal fluctuations between consecutive timepoints were examined. In addition, volume overlap and distance between manual region of interest (ROI) delineations in a subset of frames and the delineations obtained through propagation of the ROIs from the reference frame were used to quantify alignment accuracy. A previously demonstrated rigid registration approach was used for comparison. The proposed pipeline improved anatomical alignment of placenta and fetal organs over the state-of-the-art rigid motion correction methods. In particular, unexpected temporal signal fluctuations during the first normoxia period were significantly decreased (P < 0.01) and volume overlap and distance between region boundaries measures were significantly improved (P < 0.01). The proposed approach to align MRI time series enables more accurate quantitative studies of placental function by improving spatiotemporal alignment across placenta and fetal organs. 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:403-412. © 2017 International Society for Magnetic Resonance in Medicine.

  6. Chronic obstructive pulmonary disease mortality and prevalence: the associations with smoking and poverty--a BOLD analysis.

    PubMed

    Burney, Peter; Jithoo, Anamika; Kato, Bernet; Janson, Christer; Mannino, David; Nizankowska-Mogilnicka, Ewa; Studnicka, Michael; Tan, Wan; Bateman, Eric; Koçabas, Ali; Vollmer, William M; Gislason, Thorarrin; Marks, Guy; Koul, Parvaiz A; Harrabi, Imed; Gnatiuc, Louisa; Buist, Sonia

    2014-05-01

    Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking. However, COPD mortality is high in poor countries with low smoking rates. Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD. We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI). National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence. The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked. National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33). Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000. Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000. Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high 'COPD' mortality in poor countries.

  7. Chronic obstructive pulmonary disease mortality and prevalence: the associations with smoking and poverty—a BOLD analysis

    PubMed Central

    Burney, Peter; Jithoo, Anamika; Kato, Bernet; Janson, Christer; Mannino, David; Niżankowska-Mogilnicka, Ewa; Studnicka, Michael; Tan, Wan; Bateman, Eric; Koçabas, Ali; Vollmer, William M; Gislason, Thorarrin; Marks, Guy; Koul, Parvaiz A; Harrabi, Imed; Gnatiuc, Louisa; Buist, Sonia

    2014-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking. However, COPD mortality is high in poor countries with low smoking rates. Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD. We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI). Methods National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence. The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked. Results National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33). Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000. Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000. Conclusions Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. PMID:24353008

  8. Use of spin echo T(2) BOLD in assessment of cerebral misery perfusion at 1.5 T.

    PubMed

    Kavec, M; Gröhn, O H; Kettunen, M I; Silvennoinen, M J; Penttonen, M; Kauppinen, R A

    2001-03-01

    Inadequate blood supply relative to metabolic demand, a haemodynamic condition termed as misery perfusion, often occurs in conjunction with acute ischaemic stroke. Misery perfusion results in adaptive changes in cerebral physiology including increased cerebral blood volume (CBV) and oxygen extraction ratio (OER) to secure substrate supply for the brain. It has been suggested that the presence of misery perfusion may be an indication of reversible ischaemia, thus detection of this condition may have clinical impact in acute stroke imaging. The ability of single spin echo T(2) to detect misery perfusion in the rat brain at 1.5 T owing to its sensitivity to blood oxygenation level dependent (BOLD) contrast was studied both theoretically and experimentally. Based on the known physiology of misery perfusion, tissue morphometry and blood relaxation data, T(2) behaviour in misery perfusion was simulated. The interpretation of these computations was experimentally assessed by quantifying T(2) in a rat model for cerebral misery perfusion. CBF was quantified with the H(2) clearance method. A drop of CBF from 58+/-8 to 17+/-3 ml/100 g/min in the parieto-frontal cortex caused shortening of T(2) from 66.9+/-0.4 to 64.6+/-0.5 ms. Under these conditions, no change in diffusion MRI was detected. In contrast, the cortex with CBF of 42+/-7 ml/100 g/min showed no change in T(2). Computer simulations accurately predicted these T(2) responses. The present study shows that the acute drop of CBF by 70% causes a negative BOLD that is readily detectable by T(2) MRI at 1.5 T. Thus BOLD may serve as an index of misery perfusion thus revealing viable tissue with increased OER.

  9. Distinct effects of isoflurane on basal BOLD signals in tissue/vascular microstructures in rats

    PubMed Central

    Tsurugizawa, Tomokazu; Takahashi, Yukari; Kato, Fusao

    2016-01-01

    Isoflurane is a well-known volatile anesthetic. However, it remains equivocal whether its effects on BOLD signal differ depending on the types of intracranial structures, such as capillaries and large blood vessels. We compared dose-dependent effect of isoflurane on the basal BOLD signals in distinct cerebral structures (tissue structure or large vessels) using high resolution T2*-images at 9.4 T MRI system in rat somatosensory cortex. The local field potential (LFP) in the somatosensory cortex and mean arterial pressure (MAP) were also investigated. Isoflurane induced inverted U-shaped dose-dependent change in BOLD signal in large vessels and tissue regions: BOLD signal under 2.0% and 2.5% isoflurane significantly increased from the maintenance dose (1.5%) and that under 3.0% was similar to maintenance dose. Remarkably, BOLD signal increase in tissue regions under 2.5% was significantly smaller than that in large vessels. The MAP decreased monotonically due to the dose of isoflurane and the LFP was strongly suppressed under high dose (2.5% and 3.0%). These results indicate that isoflurane-induced alteration of MAP and neuronal activity affected BOLD signal and, especially, BOLD signal in the tissue regions was more affected by the neuronal activity. PMID:27976678

  10. Resolution and reproducibility of BOLD and perfusion functional MRI at 3.0 Tesla.

    PubMed

    van Gelderen, Peter; W H Wu, Carolyn; de Zwart, Jacco A; Cohen, Leonardo; Hallett, Mark; Duyn, Jeff H

    2005-09-01

    Visual and somatosensory activation studies were performed on normal subjects to compare the spatial discrimination and reproducibility between functional MRI (fMRI) methods based on blood oxygen level-dependent (BOLD) and perfusion contrast. To allow simultaneous measurement of BOLD and perfusion contrast, a dedicated MRI acquisition technique was developed. Repeated experiments of sensory stimulation of single digits of the right hand showed an average variability of activation amplitude of 25% for BOLD data, and a significantly lower variability of 21% for perfusion data. No significant difference in the variability of the locus of activity was observed between the BOLD and perfusion data. In somatotopy experiments, digits II and V were subjected to passive sensory stimulation. Both the BOLD and perfusion data showed substantial overlap in the activation patterns from the two digits. In a retinotopy study, two stimuli were alternated to excite different patches of V1. Again there was substantial overlap between the activation patterns from both stimuli, although the perfusion performed somewhat better than the BOLD method. Particularly for the visual studies, the overlap in activation patterns was more than expected based on the fine-scale retinotopic mapping of cortical activity, suggesting that both BOLD and perfusion contrast mechanisms contribute substantially to the point-spread function (PSF).

  11. A streamlined acquisition for mapping baseline brain oxygenation using quantitative BOLD.

    PubMed

    Stone, Alan J; Blockley, Nicholas P

    2017-02-15

    Quantitative BOLD (qBOLD) is a non-invasive MR technique capable of producing quantitative measurements of the haemodynamic and metabolic properties of the brain. Here we propose a refinement of the qBOLD methodology, dubbed streamlined-qBOLD, in order to provide a clinically feasible method for mapping baseline brain oxygenation. In streamlined-qBOLD confounding signal contributions are minimised during data acquisition through the application of (i) a Fluid Attenuated Inversion Recovery (FLAIR) preparation to remove cerebral spinal fluid (CSF) signal contamination, (ii) a Gradient Echo Slice Excitation Profile Imaging (GESEPI) acquisition to reduce the effect of macroscopic magnetic field gradients and (iii) an Asymmetric Spin Echo (ASE) pulse sequence to directly measure the reversible transverse relaxation rate, R2'. Together these features simplify the application of the qBOLD model, improving the robustness of the resultant parametric maps. A theoretical optimisation framework was used to optimise acquisition parameters in relation to signal to noise ratio. In a healthy subject group (n = 7) apparent elevations in R2' caused by partial volumes of CSF were shown to be reduced with the application of CSF nulling. Significant decreases in R2' (p < 0.001) and deoxygenated blood volume (p < 0.01) were seen in cortical grey matter, across the group, with the application of CSF suppression. Quantitative baseline brain oxygenation parameter maps were calculated using qBOLD modelling and compared with literature values.

  12. Skeletal muscle BOLD MRI: from underlying physiological concepts to its usefulness in clinical conditions.

    PubMed

    Jacobi, Bjoern; Bongartz, Georg; Partovi, Sasan; Schulte, Anja-Carina; Aschwanden, Markus; Lumsden, Alan B; Davies, Mark G; Loebe, Matthias; Noon, Georg P; Karimi, Sasan; Lyo, John K; Staub, Daniel; Huegli, Rolf W; Bilecen, Deniz

    2012-06-01

    Blood oxygenation-level dependent (BOLD) MRI has gained particular attention in functional brain imaging studies, where it can be used to localize areas of brain activation with high temporal resolution. To a higher degree than in the brain, skeletal muscles show extensive but transient alterations of blood flow between resting and activation state. Thus, there has been interest in the application of the BOLD effect in studying the physiology of skeletal muscles (healthy and diseased) and its possible application to clinical practice. This review outlines the potential of skeletal muscle BOLD MRI as a diagnostic tool for the evaluation of physiological and pathological alterations in the peripheral limb perfusion, such as in peripheral arterial occlusive disease. Moreover, current knowledge is summarized regarding the complex mechanisms eliciting BOLD effect in skeletal muscle. We describe technical fundaments of the procedure that should be taken into account when performing skeletal muscle BOLD MRI, including the most often applied paradigms to provoke BOLD signal changes and key parameters of the resulting time courses. Possible confounding effects in muscle BOLD imaging studies, like age, muscle fiber type, training state, and drug effects are also reviewed in detail. Copyright © 2012 Wiley Periodicals, Inc.

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

    PubMed

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

    2007-07-01

    Caffeine ingestion results in increased brain cell metabolism (Nehlig et al. [1992] Brain Res Brain Res Rev 17:139-170) and decreased cerebral blood flow (Field et al. [2003] Radiology 227:129-135; Mulderink et al. [2002] Neuroimage 15:37-44). The current study investigated the effect of caffeine in a word stem completion task using only novel word stems (no repeated stimuli). Resting perfusion was measured with arterial spin labeled perfusion MRI, along with blood oxygenation level-dependent (BOLD) signal before and after ingestion of regular coffee, decaffeinated coffee, and water. Based on previous research (Laurienti et al. [2002] Neuroimage 17:751-757; Mulderink et al. [2002] Neuroimage 15:37-44), we hypothesized that caffeine would result in increased BOLD signal intensity and extent of BOLD activation. As expected, caffeine resulted in a significant decrease in cerebral perfusion. However, both the control and caffeine groups showed an increase in BOLD signal amplitude across two sets of novel word stems. Additionally, the control group showed a 50% reduction in the extent of BOLD activation, while the caffeine group showed no change in activation extent. Neither group showed changes in BOLD baseline signal over time, which had been suggested to mediate caffeine-related BOLD signal changes. The results suggest that caffeine may attenuate general task practice effects that have been described in recent functional MRI studies of word stem completion (Buckner et al. [2000] Brain 123:620-640). Copyright 2007 Wiley-Liss, Inc.

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

    PubMed

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

    2010-01-01

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

  15. Dependence of BOLD signal change on tactile stimulus intensity in SI of primates.

    PubMed

    Zhang, Na; Gore, John C; Chen, Li M; Avison, Malcolm J

    2007-07-01

    Recently, we have demonstrated that the fine-digit topography (millimeter sized) previously identified in the primary somatosensory cortex (SI), using electrophysiology and intrinsic signal optical imaging, can also be mapped with submillimeter resolution using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging at high field. In the present study, we have examined the dependence of BOLD signal response on stimulus intensity in two subregions of SI, Areas 3b and 1. In a region(s)-of-interest (ROI) analysis of Area 3b, BOLD signal amplitude increased linearly with increasing amplitude of an 8-Hz vibrotactile stimulus, and BOLD signal was sustained throughout the stimulation period. In contrast, in Area 1, a significant BOLD signal response was only observed with more intense stimuli, and ROI analysis of the dependence of BOLD response showed no significant dependence on stimulus intensity. In addition, activation was not sustained throughout the period of stimulation. Differing responses of Areas 3b and 1 suggest potentially divergent roles for subregions of SI cortices in vibrotactile intensity encoding. Moreover, this study underscores the importance of imaging at small spatial scales. In this case, such high-resolution imaging allows differentiation between area-specific roles in intensity encoding and identifies anatomic targets for detailed electrophysiological studies of somatosensory neuronal populations with different coding properties. These experiments illustrate the value of nonhuman primates for characterizing the dependence of the BOLD signal response on stimulus parameters and on underlying neural response properties.

  16. Susceptibility-related MR signal dephasing under nonstatic conditions: experimental verification and consequences for qBOLD measurements.

    PubMed

    Sohlin, Maja C; Schad, Lothar R

    2011-02-01

    To experimentally verify a theoretical model describing the MR signal dephasing under nonstatic conditions in a voxel containing a vascular network, and to estimate the stability of the model for qBOLD measurements. Measurement phantoms reflecting the properties of the theoretical model, i.e., statistically distributed and randomly oriented cylinders in a homogeneous medium were constructed by randomly coiled polyamide fibers immersed in a NiSO(4) solution. The resemblance between measured and theoretical signal curves was investigated by calculation of root mean squared error maps. Simulated nonstatic dephasing data were evaluated using the static dephasing model to estimate the stability of the model and the influence of input parameters. The theoretical model describing the MR signal dephasing under nonstatic conditions was experimentally verified in phantom measurements. In simulations, it was found that, by neglecting the effect of diffusion when predicting the MR signal-time course expected in an in vivo measurement of the tissue oxygenation, errors of 10-30% would be introduced into the parameter estimation. The simulations indicate unpredictable results for simultaneous evaluation of blood oxygenation level and blood volume fraction. Neglecting the effects of diffusion in quantitative BOLD measurements could give rise to substantial errors in the parameter estimation. Copyright © 2011 Wiley-Liss, Inc.

  17. The role of social attraction and its link with boldness in the collective movements of three-spined sticklebacks.

    PubMed

    Jolles, Jolle W; Fleetwood-Wilson, Adeline; Nakayama, Shinnosuke; Stumpe, Martin C; Johnstone, Rufus A; Manica, Andrea

    2015-01-01

    Social animals must time and coordinate their behaviour to ensure the benefits of grouping, resulting in collective movements and the potential emergence of leaders and followers. However, individuals often differ consistently from one another in how they cope with their environment, a phenomenon known as animal personality, which may affect how individuals use coordination rules and requiring them to compromise. Here we tracked the movements of pairs of three-spined sticklebacks, Gasterosteus aculeatus, separated by a transparent partition that allowed them to observe and interact with one another in a context containing cover. Individuals differed consistently in their tendency to approach their partner's compartment during collective movements. The strength of this social attraction was positively correlated with the behavioural coordination between members of a pair but was negatively correlated with an individual's tendency to lead. Social attraction may form part of a broader behavioural syndrome as it was predicted by the boldness of an individual, measured in isolation prior to the observation of pairs, and by the boldness of the partner. We found that bolder fish, and those paired with bolder partners, tended to approach their partner's compartment less closely. These findings provide important insights into the mechanisms that govern the dynamics and functioning of social groups and the emergence and maintenance of consistent behavioural differences.

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

    PubMed

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

    2009-01-01

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

  19. Adolfo J. de Bold PhD OC FRSC: a pioneer in cardiovascular medicine.

    PubMed

    Braunwald, Eugene

    2015-11-01

    Eugene Braunwald MD discusses the discovery of the Natriuretic Peptide System by A J de Bold, which as a consequence, made it possible for the Federal Drug Administration to approve the first ARNi on 7 July 2015.

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

    PubMed

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

    2015-01-01

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

  1. Functional connectivity in BOLD and CBF data: Similarity and reliability of resting brain networks

    PubMed Central

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

    2014-01-01

    Resting-state functional connectivity (FC) fMRI (rs-fcMRI) offers an appealing approach to mapping the brain’s intrinsic functional organization. Blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) are the two main rs-fcMRI approaches to assess alterations in brain networks associated with individual differences, behavior and psychopathology. While the BOLD signal is stronger with a higher temporal resolution, ASL provides quantitative, direct measures of the physiology and metabolism of specific networks. This study systematically investigated the similarity and reliability of resting brain networks (RBNs) in BOLD and ASL. A 2 × 2 × 2 factorial design was employed where each subject underwent repeated BOLD and ASL rs-fcMRI scans on two occasions on two MRI scanners respectively. Both independent and joint FC analyses revealed common RBNs in ASL and BOLD rs-fcMRI with a moderate to high level of spatial overlap, verified by Dice Similarity Coefficients. Test–retest analyses indicated more reliable spatial network patterns in BOLD (average modal Intraclass Correlation Coefficients: 0.905 ± 0.033 between-sessions; 0.885 ± 0.052 between-scanners) than ASL (0.545 ± 0.048; 0.575 ± 0.059). Nevertheless, ASL provided highly reproducible (0.955 ± 0.021; 0.970 ± 0.011) network-specific CBF measurements. Moreover, we observed positive correlations between regional CBF and FC in core areas of all RBNs indicating a relationship between network connectivity and its baseline metabolism. Taken together, the combination of ASL and BOLD rs-fcMRI provides a powerful tool for characterizing the spatiotemporal and quantitative properties of RBNs. These findings pave the way for future BOLD and ASL rs-fcMRI studies in clinical populations that are carried out across time and scanners. PMID:25463468

  2. Dissociated mean and functional connectivity BOLD signals in visual cortex during eyes closed and fixation

    PubMed Central

    Larson-Prior, Linda; Ludwikow, Marek; Zhang, Dongyang; Snyder, Abraham Z.; Gusnard, Debra L.; Raichle, Marcus E.; d'Avossa, Giovanni

    2012-01-01

    We investigated the effects of resting state type on blood oxygen level-dependent (BOLD) signal and functional connectivity in two paradigms: participants either alternated between fixation and eyes closed or maintained fixation or eyes closed throughout each scan. The BOLD signal and functional connectivity of lower and higher tiers of the visual cortical hierarchy were found to be differentially modulated during eyes closed versus fixation. Fixation was associated with greater mean BOLD signals in primary visual cortex and lower mean BOLD signals in extrastriate visual areas than periods of eyes closed. In addition, analysis of thalamocortical functional connectivity during scans in which participants maintained fixation showed synchronized BOLD fluctuations between those thalamic nuclei whose mean BOLD signal was systematically modulated during alternating epochs of eyes closed and fixation, primary visual cortex and the attention network, while during eyes closed negatively correlated fluctuations were seen between the same thalamic nuclei and extrastriate visual areas. Finally, in all visual areas the amplitude of spontaneous BOLD fluctuations was greater during eyes closed than during fixation. The dissociation between early and late tiers of visual cortex, which characterizes both mean and functionally connected components of the BOLD signal, may depend on the reorganization of thalamocortical networks. Since dissociated changes in local blood flow also characterize transitions between different stages of sleep and wakefulness (Braun AR, Balkin TJ, Wesenten NJ, Gwadry F, Carson RE, Varga M, Baldwin P, Belenky G, Herscovitch P. Science 279: 91–95, 1998), our results suggest that dissociated endogenous neural activity in primary and extrastriate cortex may represent a general aspect of brain function. PMID:22875902

  3. Test-Retest Stability of Calibrated BOLD-fMRI in HIV− and HIV+ Subjects

    PubMed Central

    Ances, Beau; Vaida, Florin; Ellis, Ronald; Buxton, Richard

    2010-01-01

    Subject performance, scanner hardware, or biological factors can affect single session neuroimaging measures. Stability studies using calibrated blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) have been performed in health but not disease. We utilized calibrated BOLD-fMRI to determine the effects of HIV on neurovascular coupling. 6 clinically stable HIV-infected patients (HIV+) and 10 seronegative controls (HIV−) were scanned at two separate sessions approximately 3 months apart. Both mild hypercapnia (5% CO2) exposure and a visual functional activation task were performed. Intra-class correlation coefficients (ICC) and inter-subject variance were determined for calibrated BOLD-fMRI measures (baseline cerebral blood flow (CBF), functional CBF, BOLD, and cerebral metabolic rate of oxygen consumption (CMRO2) changes) for HIV+ and HIV− subjects. The two groups did not differ in age, sex, or education. HIV+ subjects had lower mean baseline CBF (p <0.04, Cohen’s d=−1.07) and functional BOLD responses (p< 0.001, Cohen’s d=−2.47) and a trend towards a decrease in mean functional CBF responses (p= 0.07, Cohen’s d=−0.92) despite similar mean functional CMRO2 changes (p= 0.71, Cohen’s d=0.19). The stability of each calibrated BOLD-fMRI measure, as assessed by ICC, was significantly lower for HIV+ subjects. In addition, HIV+ participants had greater inter-subject variability for baseline CBF (p <0.02), functional BOLD (p< 0.001), CBF (p< 0.001), and CMRO2 (p< 0.002) responses. Our results demonstrate that calibrated BOLD-fMRI measures have excellent stability within healthy controls. In contrast, these values have greater variability in clinically stable HIV+ subjects and may reflect alterations in coupling between CBF and CMRO2 with disease. PMID:20932922

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

    PubMed Central

    Chen, Jingyuan; Glover, Gary H.

    2014-01-01

    Blood oxygen level dependent (BOLD) spontaneous signals from resting-state (RS) brains have typically been characterized by low-pass filtered timeseries at frequencies ≤ 0.1 Hz, and studies of these low-frequency fluctuations have contributed exceptional understanding of the baseline functions of our brain. Very recently, emerging evidence has demonstrated that spontaneous activities may persist in higher frequency bands (even up to 0.8 Hz), while presenting less variable network patterns across the scan duration. However, as an indirect measure of neuronal activity, BOLD signal results from an inherently slow hemodynamic process, which in fact might be too slow to accommodate the observed high-frequency functional connectivity (FC). To examine whether the observed high-frequency spontaneous FC originates from BOLD contrast, we collected RS data as a function of echo time (TE). Here we focus on two specific resting state networks – the default-mode network (DMN) and executive control network (ECN), and the major findings are fourfold: (1) we observed BOLD-like linear TE-dependence in the spontaneous activity at frequency bands up to 0.5 Hz (the maximum frequency that can be resolved with TR = 1s), supporting neural relevance of the RSFC at higher frequency range; (2) Conventional models of hemodynamic response functions must be modified to support resting state BOLD contrast, especially at higher frequencies; (3) there are increased fractions of non-BOLD-like contributions to the RSFC above the conventional 0.1 Hz (non-BOLD/BOLD contrast at 0.4~0.5 Hz is ~ 4 times that at <0.1 Hz); and (4) the spatial patterns of RSFC are frequency-dependent. Possible mechanisms underlying the present findings and technical concerns regarding RSFC above 0.1 Hz are discussed. PMID:25497686

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

    PubMed Central

    Behrens, Timothy E. J.

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. To Boldly Go: Practical Career Advice for Young Scientists

    NASA Astrophysics Data System (ADS)

    Fiske, P.

    1998-05-01

    Young scientists in nearly every field are finding the job market of the 1990's a confusing and frustrating place. Ph.D. supply is far larger than that needed to fill entry-level positions in "traditional" research careers. More new Ph.D. and Master's degree holders are considering a wider range of careers in and out of science, but feel ill-prepared and uninformed about their options. Some feel their Ph.D. training has led them to a dead-end. I present a thorough and practical overview to the process of career planning and job hunting in the 1990's, from the perspective of a young scientist. I cover specific steps that young scientists can take to broaden their horizons, strengthen their skills, and present their best face to potential employers. An important part of this is the realization that most young scientists possess a range of valuable "transferable skills" that are highly sought after by employers in and out of science. I will summarize the specifics of job hunting in the 90's, including informational interviewing, building your network, developing a compelling CV and resume, cover letters, interviewing, based on my book "To Boldly Go: A Practical Career Guide for Scientists". I will also identify other resources available for young scientists. Finally, I will highlight individual stories of Ph.D.-trained scientists who have found exciting and fulfilling careers outside the "traditional" world of academia.

  8. Boldly going where no one has gone before.

    PubMed

    Lyons, M F

    1998-01-01

    With all the changes occurring in the U.S. health care system come new opportunities for physician executives willing to boldly go where no one has gone before. These positions are being newly created and thus are somewhat undefined and uncharted. Health care organizations want individuals for high-risk positions with unique skill sets and bright, new ideas. Organizations want to find people who can do what has never been done before-for them, at least, if not anywhere in the universe. How does that translate into experiences that you might want to acquire? Most organizations today are looking for individuals with some networking experience, but analogous experience (such as in a multi-site medical group or active involvement in formation of IPAs) is often a good alternative. In addition, true line experience in one or more organizations is a solid credential. Knowledge of where managed health care dollars begin and end is a necessity. As always, executive style and presence are expected.

  9. {ital Q}{sup {bold 2}} Evolution of Chiral-Odd Twist-3 Distributions {ital h{sub L}}({ital x}{bold ,}{ital Q}{sup {bold 2}}) and {ital e}({ital x}{bold ,}{ital Q}{sup {bold 2}}) in Large-{ital N{sub c}} QCD

    SciTech Connect

    Balitsky, I.I.; Braun, V.M.; Koike, Y.; Tanaka, K. |||

    1996-10-01

    We prove that the twist-3 chiral-odd parton distributions obey simple Gribov-Lipatov-Altarelli-Parisi evolution equations in the limit {ital N}{sub {ital c}}{r_arrow}{infinity} and give analytic results for the corresponding anomalous dimensions. To this end we introduce an evolution equation for the corresponding three-particle twist-3 parton correlation functions and find an exact analytic solution. For large values of {ital n} (operator dimension) we are further able to collect all corrections subleading in {ital N}{sub {ital c}}, so our final results are valid to {ital O}{bold (}(1/{ital N}{sup 2}{sub {ital c}})ln({ital n})/{ital n}{bold )} accuracy. {copyright} {ital 1996 The American Physical Society.}

  10. Individual boldness is linked to protective shell shape in aquatic snails

    PubMed Central

    Ahlgren, Johan; Chapman, Ben B.; Nilsson, P. Anders; Brönmark, Christer

    2015-01-01

    The existence of consistent individual differences in behaviour (‘animal personality’) has been well documented in recent years. However, how such individual variation in behaviour is maintained over evolutionary time is an ongoing conundrum. A well-studied axis of animal personality is individual variation along a bold–shy continuum, where individuals differ consistently in their propensity to take risks. A predation-risk cost to boldness is often assumed, but also that the reproductive benefits associated with boldness lead to equivalent fitness outcomes between bold and shy individuals over a lifetime. However, an alternative or complementary explanation may be that bold individuals phenotypically compensate for their risky lifestyle to reduce predation costs, for instance by investing in more pronounced morphological defences. Here, we investigate the ‘phenotypic compensation’ hypothesis, i.e. that bold individuals exhibit more pronounced anti-predator defences than shy individuals, by relating shell shape in the aquatic snail Radix balthica to an index of individual boldness. Our analyses find a strong relationship between risk-taking propensity and shell shape in this species, with bolder individuals exhibiting a more defended shell shape than shy individuals. We suggest that this supports the ‘phenotypic compensation’ hypothesis and sheds light on a previously poorly studied mechanism to promote the maintenance of personality variation among animals. PMID:25904320

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

    PubMed Central

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

    2015-01-01

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

  12. The quantitative genetic architecture of the bold-shy continuum in zebrafish, Danio rerio.

    PubMed

    Oswald, Mary E; Singer, Mathew; Robison, Barrie D

    2013-01-01

    In studies of consistent individual differences (personality) along the bold-shy continuum, a pattern of behavioral correlations frequently emerges: individuals towards the bold end of the continuum are more likely to utilize risky habitat, approach potential predators, and feed under risky conditions. Here, we address the hypothesis that observed phenotypic correlations among component behaviors of the bold-shy continuum are a result of underlying genetic correlations (quantitative genetic architecture). We used a replicated three-generation pedigree of zebrafish (Danio rerio) to study three putative components of the bold-shy continuum: horizontal position, swim level, and feeding latency. We detected significant narrow-sense heritabilities as well as significant genetic and phenotypic correlations among all three behaviors, such that fish selected for swimming at the front of the tank swam closer to the observer, swam higher in the water column, and fed more quickly than fish selected for swimming at the back of the tank. Further, the lines varied in their initial open field behavior (swim level and activity level). The quantitative genetic architecture of the bold-shy continuum indicates that the multivariate behavioral phenotype characteristic of a "bold" personality type may be a result of correlated evolution via underlying genetic correlations.

  13. Midazolam sedation increases fluctuation and synchrony of the resting brain BOLD signal.

    PubMed

    Kiviniemi, Vesa J; Haanpää, Hannu; Kantola, Juha-Heikki; Jauhiainen, Jukka; Vainionpää, Vilho; Alahuhta, Seppo; Tervonen, Osmo

    2005-05-01

    The blood oxygen level-dependent (BOLD) magnetic resonance signal of functional brain cortices is dominated by very low frequency (VLF) fluctuations in anesthetized child patients. The temporal synchrony of the BOLD signal is also higher in anesthetized children compared with awake adults. The origin of the synchronous fluctuations can be related to maturation, pathological status or the anesthesia used in the imaging. Two of the three confounding variables (maturation and pathology) were controlled in this study. The effect of midazolam (4+/-0.8 mg) sedation on the BOLD signal was assessed in 12 healthy adults (aged 24+/-1.5 years) at 1.5 T. The VLF fluctuation power and temporal synchrony of the BOLD signal increased significantly after the sedation in the auditory and visual cortices. The fast Fourier transformation power spectral baseline fit parameters of the BOLD signal were also found to change significantly after sedation. It is concluded that the VLF fluctuation and temporal synchrony of the BOLD signal become increased after sedation in functional brain regions.

  14. Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study

    PubMed Central

    Vollmer, W.M.; Gíslason, þ.; Burney, P.; Enright, P.L.; Gulsvik, A.; Kocabas, A.; Buist, A.S.

    2011-01-01

    Published guidelines recommend spirometry to accurately diagnose chronic obstructive pulmonary disease (COPD). However, even spirometry-based COPD prevalence estimates can vary widely. We compared properties of several spirometry-based COPD definitions using data from the international Burden of Obstructive Lung Disease (BOLD)study. 14 sites recruited population-based samples of adults aged ≥40 yrs. Procedures included standardised questionnaires and post-bronchodilator spirometry. 10,001 individuals provided usable data. Use of the lower limit of normal (LLN) forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio reduced the age-related increases in COPD prevalence that are seen among healthy never-smokers when using the fixed ratio criterion (FEV1/FVC <0.7) recommended by the Global Initiative for Chronic Obstructive Lung Disease. The added requirement of an FEV1 either <80% predicted or below the LLN further reduced age-related increases and also led to the least site-to-site variability in prevalence estimates after adjusting for potential confounders. Use of the FEV1/FEV6 ratio in place of the FEV1/FVC yielded similar prevalence estimates. Use of the FEV1/FVC

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

    PubMed

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

    2014-01-01

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

  16. Boldness behavior and stress physiology in a novel urban environment suggest rapid correlated evolutionary adaptation

    PubMed Central

    Cardoso, Gonçalo C.; Whittaker, Danielle J.; Campbell-Nelson, Samuel; Robertson, Kyle W.; Ketterson, Ellen D.

    2012-01-01

    Novel or changing environments expose animals to diverse stressors that likely require coordinated hormonal and behavioral adaptations. Predicted adaptations to urban environments include attenuated physiological responses to stressors and bolder exploratory behaviors, but few studies to date have evaluated the impact of urban life on codivergence of these hormonal and behavioral traits in natural systems. Here, we demonstrate rapid adaptive shifts in both stress physiology and correlated boldness behaviors in a songbird, the dark-eyed junco, following its colonization of a novel urban environment. We compared elevation in corticosterone (CORT) in response to handling and flight initiation distances in birds from a recently established urban population in San Diego, California to birds from a nearby wildland population in the species' ancestral montane breeding range. We also measured CORT and exploratory behavior in birds raised from early life in a captive common garden study. We found persistent population differences for both reduced CORT responses and bolder exploratory behavior in birds from the colonist population, as well as significant negative covariation between maximum CORT and exploratory behavior. Although early developmental effects cannot be ruled out, these results suggest contemporary adaptive evolution of correlated hormonal and behavioral traits associated with colonization of an urban habitat. PMID:22936840

  17. The Effects of Task-Induced Involvement Load on Word Learning and Confidence Judgments Mediated by Knowledge and Regulation of Cognition

    ERIC Educational Resources Information Center

    Teng, Feng

    2017-01-01

    The relationships between knowledge and regulation of cognition and how they interact to mediate the effects of task-induced involvement load on word learning and confidence judgments were investigated. The participants were 77 undergraduate English majors. They were required to complete a checklist on metacognition. Subsequently, they were…

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

    PubMed

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

    2017-09-22

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

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

    PubMed Central

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

    2013-01-01

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

  20. Finding Thalamic BOLD Correlates to Posterior Alpha EEG

    PubMed Central

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

    2012-01-01

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

  1. "To Boldly Go Where No One Has Gone Before".

    PubMed

    Kelley, Keith W

    2017-08-14

    Americans are suffering from a culture of taking pills. Six out of ten Americans utilize at least one prescription drug, and more than one in ten use five or more prescription medicines. Although this torrent of taking pills is already high, drug use in the USA has not yet crested. Prescription drugs have specific targets, but often they adversely affect other tissues and organs. In keeping with the mission of the recently named National Center for Complementary and Integrative Health (NCCIH), Brain, Behavior, and Immunity searches for the underlying cause and potential efficacy of both drug and non-drug interventions. When the journal was first published in 1987, it challenged the scientific tidal wave that emphasized specialization in a single, specific discipline such as molecular biology, neuroscience or immunology. The focus of the journal was to support and extend biomedical research by publishing cutting edge findings in psychoneuroimmunology. Brain, Behavior, and Immunity began serving as the official journal of the Psychoneuroimmunology Research Society (PNIRS) in 2000. During its first 16 years of existence, Brain, Behavior, and Immunity published 600 papers. During the subsequent 15 years, there has been a steep, linear rise in publications that continues to this day, amounting to the publication of nearly 2,500 articles in psychoneuroimmunology. Some of the current and hottest topics in the field are investigating ancient health practices such as mindfulness-based meditation, Tai Chi, exercise, perinatal health and the gut microbiome. As such, Brain, Behavior, and Immunity continues to advance biomedical research by boldly going forward. Just as it originally challenged the specialization philosophy that is so prevalent in medicine, it is now exploring the integrative physiological events that underlie century-old health practices. This approach has revealed that some age-old interventions are just as efficacious as prescription drugs. A world in which

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

    PubMed

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

    2010-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. Metabolic and vascular origins of the BOLD effect: Implications for imaging pathology and resting-state brain function.

    PubMed

    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.

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

    PubMed

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

    2010-05-01

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

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

    PubMed

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

    2010-04-15

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2010-08-02

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

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

    PubMed

    Mayhew, S D; Bagshaw, A P

    2017-07-15

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

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

    PubMed

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

    2012-01-01

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

  11. Determinations of renal cortical and medullary oxygenation using BOLD Magnetic Resonance Imaging and selective diuretics

    PubMed Central

    Warner, Lizette; Glockner, James F.; Woollard, John; Textor, Stephen C.; Romero, Juan C.; Lerman, Lilach O.

    2010-01-01

    Objective This study was undertaken to test the hypothesis that blood O2 level dependent magnetic resonance imaging (BOLD MRI) can detect changes in cortical proximal tubule (PT) and medullary thick ascending limb of Henle (TAL) oxygenation consequent to successive administration of furosemide and acetazolamide (Az). Assessment of PT and TAL function could be useful to monitor renal disease states in vivo. Therefore, the adjunct use of diuretics that inhibit Na+ reabsorption selectively in PT and TAL, Az and furosemide, respectively, may help discern tubular function by using BOLD MRI to detect changes in tissue oxygenation. Material and Methods BOLD MRI signal R2* (inversely related to oxygenation) and tissue oxygenation with intrarenal O2 probes were measured in pigs that received either furosemide (0.5mg/kg) or Az (15mg/kg) alone, Az sequentially after furosemide (n=6 each, 15-minute intervals), or only saline vehicle (n=3). Results R2* decreased in the cortex of Az-treated and medulla of furosemide-treated kidneys, corresponding to an increase in their tissue O2 assessed with probes. However, BOLD MRI also showed decreased cortical R2* following furosemide that was additive to the Az-induced decrease. Az administration, both alone and after furosemide, also decreased renal blood flow (−26±3.5 and −29.2±3%, respectively, p<0.01). Conclusion These results suggest that an increase in medullary and cortical tissue O2 elicited by selective diuretics is detectable by BOLD MRI, but may be complicated by hemodynamic effects of the drugs. Therefore, the BOLD MRI signal may reflect functional changes additional to oxygenation, and needs to be interpreted cautiously. PMID:20856128

  12. To boldly gulp: standard metabolic rate and boldness have context-dependent influences on risk-taking to breathe air in a catfish.

    PubMed

    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

  13. CO2BOLD assessment of moyamoya syndrome: Validation with single photon emission computed tomography and positron emission tomography imaging

    PubMed Central

    Pellaton, Alain; Bijlenga, Philippe; Bouchez, Laurie; Cuvinciuc, Victor; Barnaure, Isabelle; Garibotto, Valentina; Lövblad, Karl-Olof; Haller, Sven

    2016-01-01

    AIM To compare the assessment of cerebrovascular reserve (CVR) using CO2BOLD magnetic resonance imaging (MRI) vs positron emission tomography (PET) and single photon emission computed tomography (SPECT) as reference standard. METHODS Ten consecutive patients (8 women, mean age of 41 ± 26 years) with moyamoya syndrome underwent 14 pre-surgical evaluations for external-internal carotid artery bypass surgery. CVR was assessed using CO2BOLD and PET (4)/SPECT (11) with a maximum interval of 36 d, and evaluated by two experienced neuroradiologists. RESULTS The inter-rater agreement was 0.81 for SPECT (excellent), 0.43 for PET (fair) and 0.7 for CO2BOLD (good). In 9/14 cases, there was a correspondence between CO2BOLD and PET/SPECT. In 4/14 cases, CVR was over-estimated in CO2BOLD, while in 1/14 case, CVR was underestimated in CO2BOLD. The sensitivity of CO2BOLD was 86% and a specificity of 43%. CONCLUSION CO2BOLD can be used for pre-surgical assessment of CVR in patients with moyamoya syndrome and combines the advantages of absent irradiation, high availability of MRI and assessment of brain parenchyma, cerebral vessels and surrogate CVR in one stop. PMID:27928470

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Chen, Zikuan; Calhoun, Vince D

    2011-08-15

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

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

    PubMed Central

    Simon, Aaron B.; Buxton, Richard B.

    2015-01-01

    Calibrated BOLD imaging, in which traditional measurements of the BOLD signal are combined with measurements of cerebral blood flow (CBF) within a BOLD biophysical model to estimate changes in oxygen metabolism (CMRO2), has been a valuable tool for untangling the physiological processes associated with neural stimulus-induced BOLD activation. However, to date this technique has largely been applied to the study of essentially steady-state physiological changes (baseline to activation) associated with block-design stimuli, and it is unclear whether this approach may be directly extended to the study of more dynamic, naturalistic experimental designs. In this study we tested an assumption underlying this technique whose validity is critical to the application of calibrated BOLD to the study of more dynamic stimuli, that information about fluctuations in venous cerebral blood volume (CBVv) can be captured indirectly by measuring fluctuations in CBF, making the independent measurement of CBVv unnecessary. To accomplish this, simultaneous arterial spin labeling and BOLD imaging was used to measure the CBF and BOLD responses to flickering checkerboards with contrasts that oscillated continuously with frequencies of ~0.02-0.16Hz. The measurements were then fit to a dynamic physiological model of the BOLD response in order to explore the range of consistent CMRO2 and CBVv responses. We found that the BOLD and CBF responses were most consistent with relatively tight dynamic coupling between CBF and CMRO2 and a CBVv response that was an order of magnitude slower than either CBF or CMRO2. This finding suggests that the assumption of tight flow-volume coupling may not be strictly valid, complicating the extension of calibrated BOLD to more naturalistic experimental designs. PMID:25862267

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. Using pulse oximetry to account for high and low frequency physiological artifacts in the BOLD signal.

    PubMed

    Verstynen, Timothy D; Deshpande, Vibhas

    2011-04-15

    The BOLD signal not only reflects changes in local neural activity, but also exhibits variability from physiological processes like cardiac rhythms and breathing. We investigated how both of these physiological sources are reflected in the pulse oximetry (PO) signal, a direct measure of blood oxygenation, and how this information can be used to account for different types of noise in the BOLD response. Measures of heart rate, respiration and PO were simultaneously recorded while neurologically healthy participants performed an eye-movement task in a 3T MRI. PO exhibited power in frequencies that matched those found in the independently recorded cardiac and respiration signals. Using the phasic and aphasic properties of these signals as nuisance regressors, we found that the different frequency components of the PO signal could be used to identify different types of physiological artifacts in the BOLD response. A comparison of different physiological noise models found that a simple, down-sampled version of the PO signal improves the estimation of task-relevant statistics nearly as well as more established noise models that may run the risk of over-parameterization. These findings suggest that the PO signal captures multiple sources of physiological noise in the BOLD response and provides a simple and efficient way of modeling these noise sources in subsequent analysis.

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

    PubMed

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

    2015-03-01

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

  1. The influence of noise on BOLD-mediated vessel size imaging analysis methods

    PubMed Central

    Germuska, Michael A; Meakin, James A; Bulte, Daniel P

    2013-01-01

    Vessel size imaging (VSI) is a magnetic resonance imaging (MRI) technique that aims to provide quantitative measurements of tissue microvasculature. An emerging variation of this technique uses the blood oxygenation level-dependent (BOLD) effect as the source of the imaging contrast. Gas challenges have the advantage over contrast injection techniques in that they are noninvasive and easily repeatable because of the fast washout of the contrast. However, initial results from BOLD-VSI studies are somewhat contradictory, with substantially different estimates of the mean vessel radius. Owing to BOLD-VSI being an emerging technique, there is not yet a standard processing methodology, and different techniques have been used to calculate the mean vessel radius and reject uncertain estimates. In addition, the acquisition methodology and signal modeling vary from group to group. Owing to these differences, it is difficult to determine the source of this variation. Here we use computer modeling to assess the impact of noise on the accuracy and precision of different BOLD-VSI calculations. Our results show both potential overestimates and underestimates of the mean vessel radius, which is confirmed with a validation study at 3T. PMID:23942365

  2. 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…

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

    ERIC Educational Resources Information Center

    Collay, Michelle

    2006-01-01

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

  4. Abnormal functional MRI BOLD contrast in the vegetative state after severe traumatic brain injury.

    PubMed

    Heelmann, Volker; Lippert-Grüner, Marcela; Rommel, Thomas; Wedekind, Christoph

    2010-06-01

    For the rehabilitation process, the treatment of patients surviving brain injury in a vegetative state is still a serious challenge. The aim of this study was to investigate patients exhibiting severely disturbed consciousness using functional magnetic resonance imaging. Five cases of posttraumatic vegetative state and one with minimal consciousness close to the vegetative state were studied clinically, electrophysiologically, and by means of functional magnetic resonance imaging. Visual, sensory, and acoustic paradigms were used for stimulation. In three patients examined less than 2 months after trauma, a consistent decrease in blood oxygen level dependent (BOLD) signal ('negative activation') was observed for visual stimulation; one case even showed a decrease in BOLD activation for all three activation paradigms. In the remaining three cases examined more than 6 months after trauma, visual stimulation yielded positive BOLD contrast or no activation. In all cases, sensory stimulation was followed by a decrease in BOLD signal or no activation, whereas auditory stimulation failed to elicit any activation with the exception of one case. Functional magnetic resonance imaging in the vegetative state indicates retained yet abnormal brain function; this abnormality can be attributed to the impairment of cerebral vascular autoregulation or an increase in the energy consumption of activated neocortex in severe traumatic brain injury.

  5. 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…

  6. Female mating preference for bold males in the guppy, Poecilia reticulata.

    PubMed

    Godin, J G; Dugatkin, L A

    1996-09-17

    Although females prefer to mate with brightly colored males in numerous species, the benefits accruing to such females are virtually unknown. According to one hypothesis of sexual selection theory, if the expression of costly preferred traits in males (such as conspicuous colors) is proportional to the male's overall quality or reveals his quality, a well-developed trait should indicate good condition and/or viability for example. A female choosing such a male would therefore stand to gain direct or indirect fitness benefits, or both. Among potential phenotypic indicators of an individual's quality are the amount and brightness of its carotenoid-based colors and its boldness, as measured by its willingness to risk approaching predators without being killed. Here, we show experimentally that in the Trinidadian guppy (Poecilia reticulata) the visual conspicuousness of the color pattern of males correlates positively with boldness toward, and with escape distance from, a cichlid fish predator. Bold individuals are thus more informed about nearby predators and more likely to survive encounters with them. Mate-choice experiments showed that females prefer colorful males as mates, but prefer bolder males irrespective of their coloration when given the opportunity to observe their behavior toward a potential fish predator. By preferentially mating with colorful males, female guppies are thus choosing on average, relatively bold, and perhaps more viable, individuals. In doing so, and to the extent that viability is heritable, they potentially gain indirect fitness benefits by producing more viable offspring than otherwise.

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

    PubMed Central

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

    2009-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2007-07-15

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

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

    PubMed

    Tong, Yunjie; Frederick, Blaise Deb

    2014-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  15. A Comparison of Measures of Boldness and Their Relationships to Survival in Young Fish

    PubMed Central

    White, James R.; Meekan, Mark G.; McCormick, Mark I.; Ferrari, Maud C. O.

    2013-01-01

    Boldness is the propensity of an animal to engage in risky behavior. Many variations of novel-object or novel-environment tests have been used to quantify the boldness of animals, although the relationship between test outcomes has rarely been investigated. Furthermore, the relationship of outcomes to any ecological aspect of fitness is generally assumed, rather than measured directly. Our study is the first to compare how the outcomes of the same test of boldness differ among observers and how different tests of boldness relate to the survival of individuals in the field. Newly-metamorphosed lemon damselfish, Pomacentrus moluccensis, were placed onto replicate patches of natural habitat. Individual behavior was quantified using four tests (composed of a total of 12 different measures of behavior): latency to enter a novel environment, activity in a novel environment, and reactions to threatening and benign novel objects. After behavior was quantified, survival was monitored for two days during which time fish were exposed to natural predators. Variation among observers was low for most of the 12 measures, except distance moved and the threat test (reaction to probe thrust), which displayed unacceptable amounts of inter-observer variation. Overall, the results of the behavioral tests suggested that novel environment and novel object tests quantified similar behaviors, yet these behavioral measures were not interchangeable. Multiple measures of behavior within the context of novel environment or object tests were the most robust way to assess boldness and these measures have a complex relationship with survivorship of young fish in the field. Body size and distance ventured from shelter were the only variables that had a direct and positive relationship with survival. PMID:23874804

  16. Attention to detail: why considering task demands is essential for single-trial analysis of BOLD correlates of the visual P1 and N1.

    PubMed

    Warbrick, Tracy; Arrubla, Jorge; Boers, Franks; Neuner, Irene; Shah, N Jon

    2014-03-01

    Single-trial fluctuations in the EEG signal have been shown to temporally correlate with the fMRI BOLD response and are valuable for modeling trial-to-trial fluctuations in responses. The P1 and N1 components of the visual ERP are sensitive to different attentional modulations, suggesting that different aspects of stimulus processing can be modeled with these ERP parameters. As such, different patterns of BOLD covariation for P1 and N1 informed regressors would be expected; however, current findings are equivocal. We investigate the effects of variations in attention on P1 and N1 informed BOLD activation in a visual oddball task. Simultaneous EEG-fMRI data were recorded from 13 healthy participants during three conditions of a visual oddball task: Passive, Count, and Respond. We show that the P1 and N1 components of the visual ERP can be used in the integration-by-prediction method of EEG-fMRI data integration to highlight brain regions related to target detection and response production. Our data suggest that the P1 component of the ERP reflects changes in sensory encoding of stimulus features and is more informative for the Passive and Count conditions. The N1, on the other hand, was more informative for the Respond condition, suggesting that it can be used to model the processing of stimulus, meaning specifically discriminating one type of stimulus from another, and processes involved in integrating sensory information with response selection. Our results show that an understanding of the underlying electrophysiology is necessary for a thorough interpretation of EEG-informed fMRI analysis.

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

    PubMed

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

    2012-01-01

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

  18. Inefficient Preparatory fMRI-BOLD Network Activations Predict Working Memory Dysfunctions in Patients with Schizophrenia

    PubMed Central

    Baenninger, Anja; Diaz Hernandez, Laura; Rieger, Kathryn; Ford, Judith M.; Kottlow, Mara; Koenig, Thomas

    2016-01-01

    Patients with schizophrenia show abnormal dynamics and structure of temporally ­coherent networks (TCNs) assessed using fMRI, which undergo adaptive shifts in preparation for a cognitively demanding task. During working memory (WM) tasks, patients with schizophrenia show persistent deficits in TCNs as well as EEG indices of WM. Studying their temporal relationship during WM tasks might provide novel insights into WM performance deficits seen in schizophrenia. Simultaneous EEG-fMRI data were acquired during the performance of a verbal Sternberg WM task with two load levels (load 2 and load 5) in 17 patients with schizophrenia and 17 matched healthy controls. Using covariance mapping, we investigated the relationship of the activity in the TCNs before the memoranda were encoded and EEG spectral power during the retention interval. We assessed four TCNs – default mode network (DMN), dorsal attention network (dAN), left and right working memory networks (WMNs) – and three EEG bands – theta, alpha, and beta. In healthy controls, there was a load-dependent inverse relation between DMN and frontal midline theta power and an anti-correlation between DMN and dAN. Both effects were not significantly detectable in patients. In addition, healthy controls showed a left-lateralized load-dependent recruitment of the WMNs. Activation of the WMNs was bilateral in patients, suggesting more resources were recruited for successful performance on the WM task. Our findings support the notion of schizophrenia patients showing deviations in their neurophysiological responses before the retention of relevant information in a verbal WM task. Thus, treatment strategies as neurofeedback ­targeting prestates could be beneficial as task performance relies on the preparatory state of the brain. PMID:27047395

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  20. Inefficient Preparatory fMRI-BOLD Network Activations Predict Working Memory Dysfunctions in Patients with Schizophrenia.

    PubMed

    Baenninger, Anja; Diaz Hernandez, Laura; Rieger, Kathryn; Ford, Judith M; Kottlow, Mara; Koenig, Thomas

    2016-01-01

    Patients with schizophrenia show abnormal dynamics and structure of temporally -coherent networks (TCNs) assessed using fMRI, which undergo adaptive shifts in preparation for a cognitively demanding task. During working memory (WM) tasks, patients with schizophrenia show persistent deficits in TCNs as well as EEG indices of WM. Studying their temporal relationship during WM tasks might provide novel insights into WM performance deficits seen in schizophrenia. Simultaneous EEG-fMRI data were acquired during the performance of a verbal Sternberg WM task with two load levels (load 2 and load 5) in 17 patients with schizophrenia and 17 matched healthy controls. Using covariance mapping, we investigated the relationship of the activity in the TCNs before the memoranda were encoded and EEG spectral power during the retention interval. We assessed four TCNs - default mode network (DMN), dorsal attention network (dAN), left and right working memory networks (WMNs) - and three EEG bands - theta, alpha, and beta. In healthy controls, there was a load-dependent inverse relation between DMN and frontal midline theta power and an anti-correlation between DMN and dAN. Both effects were not significantly detectable in patients. In addition, healthy controls showed a left-lateralized load-dependent recruitment of the WMNs. Activation of the WMNs was bilateral in patients, suggesting more resources were recruited for successful performance on the WM task. Our findings support the notion of schizophrenia patients showing deviations in their neurophysiological responses before the retention of relevant information in a verbal WM task. Thus, treatment strategies as neurofeedback -targeting prestates could be beneficial as task performance relies on the preparatory state of the brain.

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

    PubMed

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

    2013-05-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2003-01-01

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

  4. Bold-line Monte Carlo and the nonequilibrium physics of strongly correlated many-body systems

    NASA Astrophysics Data System (ADS)

    Cohen, Guy

    2015-03-01

    This talk summarizes real time bold-line diagrammatic Monte-Carlo approaches to quantum impurity models, which make significant headway against the sign problem by summing over corrections to self-consistent diagrammatic expansions rather than a bare diagrammatic series. When the bold-line method is combined with reduced dynamics techniques both local single-time properties and two time correlators such as Green functions can be computed at very long timescales, enabling studies of nonequilibrium steady state behavior of quantum impurity models and creating new solvers for nonequilibrium dynamical mean field theory. This work is supported by NSF DMR 1006282, NSF CHE-1213247, DOE ER 46932, TG-DMR120085 and TG-DMR130036, and the Yad Hanadiv-Rothschild Foundation.

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

    PubMed

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

    2008-10-01

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

  6. BOLD MRI of the human cervical spinal cord at 3 tesla.

    PubMed

    Stroman, P W; Nance, P W; Ryner, L N

    1999-09-01

    The feasibility of functional MRI of the spinal cord was investigated by carrying out blood oxygen-level dependent (BOLD) imaging of the human cervical spinal cord at a field of 3 T. BOLD imaging of the cervical spinal cord showed an average intensity increase of 7.0% during repeated exercise with the dominant hand with a return to baseline during rest periods. The areas of activation were predominantly on the same side of the spinal cord as the hand performing the exercise, between the levels of the sixth cervical and first thoracic spinal cord segments. The direct correspondence between these areas and those involved with the transmission of motor impulses to the hand, and reception of sensory information from the hand, demonstrates that spinal functional magnetic resonance imaging is feasible. Magn Reson Med 42:571-576, 1999. Copyright 1999 Wiley-Liss, Inc.

  7. [Susceptibility weighted magnetic resonance sequences "SWAN, SWI and VenoBOLD": technical aspects and clinical applications].

    PubMed

    Hodel, J; Rodallec, M; Gerber, S; Blanc, R; Maraval, A; Caron, S; Tyvaert, L; Zuber, M; Zins, M

    2012-05-01

    Susceptibility-weighted MR sequences, T2 star weighted angiography (SWAN, General Electric), Susceptibility weighted imaging (SWI, Siemens) and venous blood oxygen level dependant (VenoBOLD, Philips) are 3D spoiled gradient-echo sequence that provide a high sensitivity for the detection of blood degradation products, calcifications, and iron deposits. For all these sequences, an appropriate echo time allows for the visualization of susceptibility differences between adjacent tissues. However, each of these sequences presents a specific technical background. The purpose of this review was to describe 1/the technical aspects of SWAN, VenoBOLD and SWI sequences, 2/the differences observed in term of contrast within the images, 3/the key imaging findings in neuroimaging using susceptibility-weighted MR sequences.

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

    PubMed Central

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

    2015-01-01

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

  9. Effects of anesthesia on resting state BOLD signals in white matter of non-human primates.

    PubMed

    Wu, Tung-Lin; Wang, Feng; Anderson, Adam W; Chen, Li Min; Ding, Zhaohua; Gore, John C

    2016-11-01

    Resting state functional magnetic resonance imaging (rsfMRI) has been widely used to measure functional connectivity between cortical regions of the brain. However, there have been minimal reports of bold oxygenation level dependent (BOLD) signals in white matter, and even fewer attempts to detect resting state connectivity. Recently, there has been growing evidence that suggests that reliable detection of white matter BOLD signals may be possible. We have previously shown that nearest neighbor inter-voxel correlations of resting state BOLD signal fluctuations in white matter are anisotropic and can be represented by a functional correlation tensor, but the biophysical origins of these signal variations are not clear. We aimed to assess whether MRI signal fluctuations in white matter vary for different baseline levels of neural activity. We performed imaging studies on live squirrel monkeys under different levels of isoflurane anesthesia at 9.4T. We found 1) the fractional power (0.01-0.08Hz) in white matter was between 60 to 75% of the level in gray matter; 2) the power in both gray and white matter low frequencies decreased monotonically in similar manner with increasing levels of anesthesia; 3) the distribution of fractional anisotropy values of the functional tensors in white matter were significantly higher than those in gray matter; and 4) the functional tensor eigenvalues decreased with increasing level of anesthesia. Our results suggest that as anesthesia level changes baseline neural activity, white matter signal fluctuations behave similarly to those in gray matter, and functional tensors in white matter are affected in parallel.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2013-12-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. Teacherpreneurs: a bold brand of teacher leadership for 21st-century teaching and learning.

    PubMed

    Berry, Barnett

    2013-04-19

    Challenges facing our public schools demand a bold brand of teacher leadership. Teacherpreneurs, effective teachers who teach students regularly but also incubate and execute the kinds of policies and pedagogies students deserve, represent a new culture of training and ingenuity. Teachers who lead outside the classroom but do not lose their connection to students are best positioned to develop and disseminate best policies and practices for 21st-century teaching and learning.

  15. A Bold 21st Century Strategy for U.S. Airborne ISR

    DTIC Science & Technology

    2007-03-13

    Staff G-2, United States Army , 7 April 2004,14-20. 27 Richard Meinhart , Strategic Planning by the Chairmen, Joint Chiefs of Staff, 1990 to 2005...USAWC STRATEGY RESEARCH PROJECT A BOLD 21ST CENTURY STRATEGY FOR U.S. ARMY AIRBORNE ISR by Mr. Jack L...Kimberly Department of Army Civilian Colonel John H. Schnibben Project Adviser This SRP is submitted in partial fulfillment of

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

    PubMed Central

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

    2010-01-01

    Baboon, with its large brain size and extensive cortical folding compared to other non-human primates, serves as a good model for neuroscience research. This study reports the implementation of a baboon model for blood oxygenation level-dependent (BOLD) fMRI studies (1.5 × 1.5 × 4 mm resolution) on a clinical 3 T-MRI scanner. BOLD fMRI responses to hypercapnic (5% CO2) challenge, 10 Hz flicker visual, and vibrotactile somatosensory–motor stimulations were investigated in baboons anesthetized sequentially with isoflurane and ketamine. Hypercapnia evoked robust BOLD increases. Paralysis was determined to be necessary to achieve reproducible functional activations within and between subjects under our experimental conditions. With optimized anesthetic doses (0.8–1.0% isoflurane or 6–8 mg/kg/h ketamine) and adequate paralysis (vecuronium, 0.2 mg/kg), robust activations were detected in the visual (V), primary (S1) and secondary (S2) somatosensory, primary motor (M cortices), supplementary motor area (SMA), lateral geniculate nucleus (LGN) and thalamus (Th). Data were tabulated for 11 trials under isoflurane and 10 trials under ketamine on 5 baboons. S1, S2, M, and V activations were detected in essentially all trials (90–100% of the time, except 82% for S2 under isoflurane and 70% for M under ketamine). LGN activations were detected 64–70% of the time under both anesthetics. SMA and Th activations were detected 36–45% of the time under isoflurane and 60% of the time under ketamine. BOLD percent changes among different structures were slightly higher under ketamine than isoflurane (0.75% versus 0.58% averaging all structures), but none was statistically different (P>0.05). This baboon model offers an opportunity to non-invasively image brain functions and dysfunctions in large non-human primates. PMID:20471483

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  19. Acute exposure to 17α-ethinylestradiol alters boldness behavioral syndrome in female Siamese fighting fish.

    PubMed

    Dzieweczynski, Teresa L; Campbell, Brennah A; Marks, Jodi M; Logan, Brittney

    2014-09-01

    The role of anthropogenic sources in generating, maintaining, and influencing behavioral syndromes has recently been identified as an important area of future research. Endocrine disrupting chemicals are prevalent and persistent in aquatic ecosystems worldwide. These chemicals are known to have marked effects on the morphology and behavior of exposed individuals and, as such, may serve as a potential influence on behavioral syndromes. However, both the effects of exposure on behaviors beyond courtship and aggression and how exposure might affect behavioral variation at the individual level are understudied. To address this question, we examined boldness behavior in female Siamese fighting fish in three different assays (Novel Environment, Empty Tank, Shoaling) both before and after they were exposed to the estrogen mimic, 17α-ethinylestradiol (EE2). EE2 influences courtship, aggression, and boldness in males of this species but its effects have not been examined in females, to our knowledge. Females were tested multiple times in each assay before and after exposure so that behavioral consistency could be examined. A behavioral syndrome for boldness and activity level occurred across the three assays. The reductions in boldness and loss of the behavioral syndrome that resulted from EE2 exposure were surprising and suggest that the effects of EE2 exposure on female behavior and physiology should be examined more frequently. This study is one of the first to examine the effects of EE2 in females as well as on correlated behaviors and emphasizes the importance of examining the effects of endocrine disrupting chemicals on individual behavioral variation and consistency. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. Effect of hunger level and time of day on boldness and aggression in the zebrafish Danio rerio.

    PubMed

    Ariyomo, T O; Watt, P J

    2015-06-01

    The effect of two environmental variables, hunger level (fed or not fed before behavioural assays) and time of day (morning or afternoon), on the boldness and aggressiveness of male and female zebrafish Danio rerio, was tested. The results showed that neither hunger level nor time of testing influenced boldness in males and females, but hunger level significantly affected aggression in females when compared with males.

  3. Size doesn't matter, sex does: a test for boldness in sister species of Brachyrhaphis fishes

    PubMed Central

    Ingley, Spencer J; Rehm, Jeremy; Johnson, Jerald B

    2014-01-01

    The effect of divergent natural selection on the evolution of behavioral traits has long been a focus of behavioral ecologists. Predation, due to its ubiquity in nature and strength as a selective agent, has been considered an important environmental driver of behavior. Predation is often confounded with other environmental factors that could also play a role in behavioral evolution. For example, environments that contain predators are often more ecologically complex and “risky” (i.e., exposed and dangerous). Previous work shows that individuals from risky environments are often more bold, active, and explorative than those from low-risk environments. To date, most comparative studies of environmentally driven behavioral divergence are limited to comparisons among populations within species that occur in divergent selective environments but neglect comparisons between species following speciation. This limits our understanding of how behavior evolves post-speciation. The Central American live-bearing fish genus Brachyrhaphis provides an ideal system for examining the relationship between selective environments and behavior, within and between species. Here, we test for differences in boldness between sister species B. roseni and B. terrabensis that occur in streams with and without piscivorous predators, respectively. We found that species do differ in boldness, with species that occur with predators being bolder than those that do not. Within each species, we found that sexes differed in boldness, with males being bolder than females. We also tested for a relationship between size (a surrogate for metabolic rate) and boldness, but found no size effects. Therefore, sex, not size, affects boldness. These results are consistent with the hypothesis that complex and risky environments favor individuals with more bold behavioral traits, but they are not consistent with the hypothesis that size (and therefore metabolic rate) drives divergence in boldness. Finally

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

    PubMed

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

    2017-04-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-06-01

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

  8. Effect of median-nerve electrical stimulation on BOLD activity in acute ischemic stroke patients.

    PubMed

    Manganotti, P; Storti, S F; Formaggio, E; Acler, M; Zoccatelli, G; Pizzini, F B; Alessandrini, F; Bertoldo, A; Toffolo, G M; Bovi, P; Beltramello, A; Moretto, G; Fiaschi, A

    2012-01-01

    To investigate blood oxygenation level-dependent (BOLD) activation during somatosensory electrical stimulation of the median nerve in acute stroke patients and to determine its correlation with ischemic damage and clinical recovery over time. Fourteen acute stroke patients underwent functional magnetic resonance imaging (fMRI) during contralesional median-nerve electrical stimulation 12-48 h after stroke. Findings were then validated by diffusion tensor imaging (DTI) and motor evoked potential by transcranial magnetic stimulation (TMS). Poor clinical recovery at three months was noted in four patients with no activation in the early days after stroke, whereas good clinical recovery was observed in eight patients with a normal activation pattern in the primary sensory motor area in the acute phase. In two patients BOLD activation correlated weakly with clinical recovery. Findings from TMS and DTI partially correlated with clinical recovery and functional scores. Clinically relevant insights into the "functional reserve" of stroke patients gained with peripheral nerve stimulation during fMRI may carry prognostic value already in the acute period of a cerebrovascular accident. BOLD activation maps could provide insights into the functional organization of the residual systems and could contribute to medical decision making in neurological and rehabilitative treatment. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

    Ganesan, Karthik; Ursekar, Meher

    2014-01-01

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

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

    PubMed

    Behzadi, Yashar; Liu, Thomas T

    2006-08-01

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

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

    PubMed Central

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

    2009-01-01

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

  12. Context Consistency and Seasonal Variation in Boldness of Male Two-Spotted Gobies

    PubMed Central

    Magnhagen, Carin; Wacker, Sebastian; Forsgren, Elisabet; Cats Myhre, Lise; Espy, Elizabeth; Amundsen, Trond

    2014-01-01

    In order to attribute the behaviour of an animal to its personality it is important to study whether certain behavioural traits show up consistently across a variety of contexts. The aim of this study was to investigate whether breeding state males of the two-spotted goby, Gobiusculus flavescens, showed consistent degree of boldness when tested in four different behaviour assays. We also wanted to investigate whether boldness varied over the breeding season in accordance with changes in male-male competition for matings. We used two standard assays (the emergence test and the open field test), and two simple assays related to threat response. Repeated runs of each of the tests were highly correlated, and we found significant correlations between all four assays. Thus, we have documented both a within and a between-context consistency in risk-taking behaviour. Furthermore, we found that goby males studied during the middle of the breeding season were bolder than males studied at the end of the season. Since male two-spotted gobies face strongly decreasing male-male competition as the season progresses, the benefit of being bold for the mating success of the males may differ over the time of the breeding season. The difference in behaviour found over the season thus corresponds well with the sexual dynamics of this model species. PMID:24671255

  13. Spontaneous BOLD event triggered averages for estimating functional connectivity at resting state

    PubMed Central

    Tagliazucchi, Enzo; Balenzuela, Pablo; Fraiman, Daniel; Montoya, Pedro; Chialvo, Dante R.

    2010-01-01

    Recent neuroimaging studies have demonstrated that the spontaneous brain activity reflects, to a large extent, the same activation patterns measured in response to cognitive and behavioral tasks. This correspondence between activation and rest has been explored with a large repertoire of computational methods, ranging from analysis of pairwise interactions between areas of the brain to the global brain networks yielded by independent component analysis. In this paper we describe an alternative method based on the averaging of the BOLD signal at a region of interest (target) triggered by spontaneous increments in activity at another brain area (seed). The resting BOLD event triggered averages (“rBeta”) can be used to estimate functional connectivity at resting state. Using two simple examples, here we illustrate how the analysis of the average response triggered by spontaneous increases/decreases in the BOLD signal is sufficient to capture the aforementioned correspondence in a variety of circumstances. The computation of the non linear response during rest here described allows for a direct comparison with results obtained during task performance, providing an alternative measure of functional interaction between brain areas. PMID:21078369

  14. The relationship between brain oscillations and BOLD signal during memory formation: a combined EEG-fMRI study.

    PubMed

    Hanslmayr, Simon; Volberg, Gregor; Wimber, Maria; Raabe, Markus; Greenlee, Mark W; Bäuml, Karl-Heinz T

    2011-11-02

    Previous studies demonstrated that increases in the theta frequency band with concomitant decreases in the alpha/beta frequency band indicate successful memory formation. However, little is known about the brain regions and the cognitive processes that underlie these encoding-related oscillatory memory effects. We investigated this relationship using simultaneous EEG-fMRI recordings in humans during long-term memory encoding. In line with prior studies, we demonstrate that a decrease in beta power and an increase in theta power positively predict subsequent recall. In fMRI, stronger activity in the left inferior prefrontal cortex and the right parahippocampal gyrus correlated with successful memory formation. EEG source localization revealed that the subsequent memory effect in the beta band was localized in the left inferior prefrontal cortex, whereas the effect in the theta band was localized in medial temporal lobe regions. Trial-by-trial correlations between EEG and BOLD activity showed that beta power correlated negatively with left inferior prefrontal cortex activity. This correlation was more pronounced for items that could later be successfully recalled compared to items later forgotten. Based on these findings, we suggest that beta oscillations in the left inferior prefrontal cortex indicate semantic encoding processes, whereas theta oscillations in the medial temporal lobe reflect the binding of an item to its spatiotemporal context.

  15. Non-invasive monitoring of renal oxygenation using BOLD-MRI: a reproducibility study.

    PubMed

    Simon-Zoula, Sonia C; Hofmann, Lucie; Giger, Andreas; Vogt, Bruno; Vock, Peter; Frey, Felix J; Boesch, Chris

    2006-02-01

    Blood oxygenation level-dependent (BOLD) MRI was shown to allow non-invasive observation of renal oxygenation in humans. However, clinical applications of this type of functional MRI of the kidney are still limited, most likely because of difficulties in obtaining reproducible and reliable information. The aim of this study was to evaluate the reproducibility and robustness of a BOLD method applied to the kidneys and to identify systematic physiological changes potentially influencing the renal oxygenation of healthy volunteers. To measure the BOLD effect, a modified multi-echo data image combination (MEDIC) sequence was used to acquire 12 T2*-weighted images within a single breath-hold. Three identical measurements were performed on three axial and three coronal slices of right and left kidneys in 18 volunteers. The mean R2* (1/T2*) values determined in medulla and cortex showed no significant differences over three repetitions and low intra-subject coefficients of variation (CV) (3 and 4% in medulla and cortex, respectively). The average R2* values were higher in the medulla (16.15 +/- 0.11) than in the cortex (11.69 +/- 0.18) (P < 0.001). Only a minor influence of slice orientation was observed. Mean R2* values were slightly higher (3%) in the left than in the right kidney (P < 0.001). Differences between volunteers were identified (P < 0.001). Part of these differences was attributable to age-dependent R2* values, since these values increased with age when medulla (P < 0.001, r = 0.67) or cortex (P < 0.020, r = 0.42) were considered. Thus, BOLD measurements in the kidney are highly reproducible and robust. The results allow one to identify the known cortico-medullary gradient of oxygenation evidenced by the gradient of R2* values and suggest that medulla is more hypoxic in older than younger individuals. BOLD-MRI is therefore a useful tool to study sequentially and non-invasively regional oxygenation of human kidneys. 2006 John Wiley & Sons, Ltd.

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

    PubMed

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

    2016-07-15

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

  17. Fractal analysis of spontaneous fluctuations of the BOLD signal in rat brain

    PubMed Central

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

    2013-01-01

    Analysis of task-evoked fMRI data ignores low frequency fluctuations (LFF) of the resting-state the BOLD signal, yet LFF of the spontaneous BOLD signal is crucial for analysis of resting-state connectivity maps. We characterized the LFF of resting-state BOLD signal at 11.7T in α-chloralose and domitor anesthetized rat brain and modeled the spontaneous signal as a scale-free (i.e., fractal) distribution of amplitude power (∣A∣2) across a frequency range (f) compatible with an ∣A(f)∣2 ∝ 1/fβ model where β is the scaling exponent (or spectral index). We compared β values from somatosensory forelimb area (S1FL), cingulate cortex (CG), and caudate putamen (CPu). With α-chloralose, S1FL and CG β values dropped from ~0.7 at in vivo to ~0.1 at post mortem (p<0.0002), whereas CPu β values dropped from ~0.3 at in vivo to ~0.1 at post mortem (p<0.002). With domitor, cortical (S1FL, CG) β values were slightly higher than with α-chloralose, while subcortical (CPu) β values were similar with α-chloralose. Although cortical and subcortical β values with both anesthetics were significantly different in vivo (p<0.002), at post mortem β values in these regions were not significantly different and approached zero (i.e., range of −0.1 to 0.2). Since a water phantom devoid of susceptibility gradients had a β value of zero (i.e., random), we conclude that deoxyhemoglobin present in voxels post-sacrifice still impacts tissue water diffusion. These results suggest that in the anesthetized rat brain the LFF of BOLD signal at 11.7T follow a general 1/fβ model of fractality where β is a variable responding to physiology. We describe typical experimental pitfalls which may elude detection of fractality in the resting-state BOLD signal. PMID:21777682

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

  20. A BOLD Perspective on Age-Related Neurometabolic-Flow Coupling and Neural Efficiency Changes in Human Visual Cortex

    PubMed Central

    Hutchison, Joanna Lynn; Shokri-Kojori, Ehsan; Lu, Hanzhang; Rypma, Bart

    2013-01-01

    Age-related performance declines in visual tasks have been attributed to reductions in processing efficiency. The neural basis of these declines has been explored by comparing the blood-oxygen-level-dependent (BOLD) index of neural activity in older and younger adults during visual task performance. However, neural activity is one of many factors that change with age and lead to BOLD signal differences. We investigated the origin of age-related BOLD changes by comparing blood flow and oxygen metabolic constituents of BOLD signal. Subjects periodically viewed flickering annuli and pressed a button when detecting luminance changes in a central fixation cross. Using magnetic resonance dual-echo arterial spin labeling and CO2 ingestion, we observed age-equivalent (i.e., similar in older and younger groups) fractional cerebral blood flow (ΔCBF) in the presence of age-related increases in fractional cerebral metabolic rate of oxygen (ΔCMRO2). Reductions in ΔCBF responsiveness to increased ΔCMRO2 in elderly led to paradoxical age-related BOLD decreases. Age-related ΔCBF/ΔCMRO2 ratio decreases were associated with reaction times, suggesting that age-related slowing resulted from less efficient neural activity. We hypothesized that reduced vascular responsiveness to neural metabolic demand would lead to a reduction in ΔCBF/ΔCMRO2. A simulation of BOLD relative to ΔCMRO2 for lower and higher neurometabolic-flow coupling ratios (approximating those for old and young, respectively) indicated less BOLD signal change in old than young in relatively lower CMRO2 ranges, as well as greater BOLD signal change in young compared to old in relatively higher CMRO2 ranges. These results suggest that age-comparative studies relying on BOLD signal might be misinterpreted, as age-related BOLD changes do not merely reflect neural activity changes. Age-related declines in neurometabolic-flow coupling might lead to neural efficiency reductions that can adversely affect visual task

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

    PubMed Central

    Bush, Keith; Cisler, Josh

    2013-01-01

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

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

    PubMed

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

    2012-05-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2008-03-01

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

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

    PubMed

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

    2011-02-01

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

  6. Bold ideas shortlisted for future ESA science projects

    NASA Astrophysics Data System (ADS)

    2000-03-01

    nature of empty space. Quantum theory implies that even a perfect vacuum is not really empty but seethes with short-lived particles and forces. Half a century ago, the Dutch physicist Hendrik Casimir predicted that this hidden nature of the vacuum should reveal itself by a novel force between two metal plates. The proposal is to measure the Casimir force between superconducting surfaces a hundredth of a millimetre apart, a million times more accurately than has been done on the ground. Finally, one of the proposed projects is astronomical. EDDINGTON would take up a station far from the Earth and use a 1-metre telescope with a wide field of view to examine stars for oscillations and passing planets. Oscillations due to sound waves have already revealed many features of the Sun's interior, allowing astrophysicists to check their theories about how stars work, in the nearest case. Now astronomers are beginning to use the same method in other stars, and EDDINGTON would apply it to 50,000 stars of many different kinds. It would also check 700,000 stars for the presence of planets, revealed by a dip in the brightness of a star when a planet passes in front of it. In addition to the above mentioned proposals, SSAC recommended to study three proposals for accommodation on the International Space Station (ISS): * EUSO, study of the cosmic neutrinos and extremely high energy cosmic rays, * LOBSTER, an imaging all-sky X-Ray monitor; MOSS, studying the physics of superconducting ultra-stable microwave oscillators. "As is always the case, these exciting proposals give us an embarrassment of riches," comments Roger Bonnet, ESA's director of science. "That's thanks to the vigour and imagination of Europe's space science community".

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2017-03-11

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

  9. Dictionary-driven Ischemia Detection from Cardiac Phase-Resolved Myocardial BOLD MRI at Rest

    PubMed Central

    Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A.

    2016-01-01

    Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP–BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP–BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson’s r = 0.84) w.r.t. infarct size. When advances in automated registration and segmentation of CP–BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique. PMID:26292338

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

    PubMed

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

    2017-02-27

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2017-05-31

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

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

    PubMed Central

    Scherf, Thomas

    2017-01-01

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

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

    PubMed

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

    2007-08-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  17. Imaging brain vasculature with BOLD 3D microscopy: MR detection limits determined by in vivo two-photon microscopy

    PubMed Central

    Park, Sung-Hong; Masamoto, Kazuto; Hendrich, Kristy; Kanno, Iwao; Kim, Seong-Gi

    2008-01-01

    Rat brain vasculature was imaged at 9.4 T with blood oxygenation level dependent (BOLD) microscopy. Data were acquired without exogenous contrast agent in < 35 min using 3D gradient-echo imaging with 78-μm isotropic resolution (N = 6). Detailed vascular patterns including intracortical veins and some branches were observed in simple magnitude-contrast data acquired at an experimentally-optimized echo time. The venous origin of the dark patterns was confirmed by oxygenation-dependent studies, and when the systemic arterial oxygen saturation level was < 80%, BOLD microscopy revealed additional intracortical vessels presumed to be of arterial orgin. Quantification shows a decrease of intracortical venous density with depth. The full width at half-minimum intensity was 90–190 μm for most intracortical venous vessels identifiable by BOLD venography. Since actual diameters are not directly quantifiable by BOLD, we also measured diameter-dependent intracortical venous density in vivo by two-photon excitation fluorescent microscopy (N = 5). Density comparisons between the two modalities, along with computer simulations, show that venous vessels as small as ~16–30 μm diameter are detectable with 9.4-T BOLD microscopy under our experimental conditions. PMID:18383285

  18. Resting state BOLD fMRI for pre-surgical planning

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. BOLD VENTURE COMPUTATION SYSTEM for nuclear reactor core analysis, Version III

    SciTech Connect

    Vondy, D.R.; Fowler, T.B.; Cunningham, G.W. III.

    1981-06-01

    This report is a condensed documentation for VERSION III of the BOLD VENTURE COMPUTATION SYSTEM for nuclear reactor core analysis. An experienced analyst should be able to use this system routinely for solving problems by referring to this document. Individual reports must be referenced for details. This report covers basic input instructions and describes recent extensions to the modules as well as to the interface data file specifications. Some application considerations are discussed and an elaborate sample problem is used as an instruction aid. Instructions for creating the system on IBM computers are also given.

  1. The Rule of Three for Prizes in Science and the Bold Triptychs of Francis Bacon.

    PubMed

    Goldstein, Joseph L

    2016-09-22

    For many scientific awards, such as Nobels and Laskers, the maximum number of recipients is three. This Rule of Three forces selection committees to make difficult decisions that increase the likelihood of singling out those individuals who open a new field and continue to lead it. The Rule of Three is reminiscent of art's three-panel triptych, a form that the modern master Francis Bacon used to distill complex stories in a bold way. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Distinction between Neural and Vascular BOLD Oscillations and Intertwined Heart Rate Oscillations at 0.1 Hz in the Resting State and during Movement

    PubMed Central

    Pfurtscheller, Gert; Schwerdtfeger, Andreas; Brunner, Clemens; Aigner, Christoph; Fink, David; Brito, Joana; Carmo, Marciano P.; Andrade, Alexandre

    2017-01-01

    In the resting state, blood oxygen level-dependent (BOLD) oscillations with a frequency of about 0.1 Hz are conspicuous. Whether their origin is neural or vascular is not yet fully understood. Furthermore, it is not clear whether these BOLD oscillations interact with slow oscillations in heart rate (HR). To address these two questions, we estimated phase-locking (PL) values between precentral gyrus (PCG) and insula in 25 scanner-naïve individuals during rest and stimulus-paced finger movements in both hemispheres. PL was quantified in terms of time delay and duration in the frequency band 0.07 to 0.13 Hz. Results revealed both positive and negative time delays. Positive time delays characterize neural BOLD oscillations leading in the PCG, whereas negative time delays represent vascular BOLD oscillations leading in the insula. About 50% of the participants revealed positive time delays distinctive for neural BOLD oscillations, either with short or long unilateral or bilateral phase-locking episodes. An expected preponderance of neural BOLD oscillations was found in the left hemisphere during right-handed movement and unexpectedly in the right hemisphere during rest. Only neural BOLD oscillations were significantly associated with heart rate variability (HRV) in the 0.1-Hz range in the first resting state. It is well known that participating in magnetic resonance imaging (MRI) studies may be frightening and cause anxiety. In this respect it is important to note that the most significant hemispheric asymmetry (p<0.002) with a right-sided dominance of neural BOLD and a left-sided dominance of vascular BOLD oscillations was found in the first resting session in the scanner-naïve individuals. Whether the enhanced left-sided perfusion (dominance of vascular BOLD) or the right-sided dominance of neural BOLD is related to the increased level of anxiety, attention or stress needs further research. PMID:28052074

  3. Distinction between Neural and Vascular BOLD Oscillations and Intertwined Heart Rate Oscillations at 0.1 Hz in the Resting State and during Movement.

    PubMed

    Pfurtscheller, Gert; Schwerdtfeger, Andreas; Brunner, Clemens; Aigner, Christoph; Fink, David; Brito, Joana; Carmo, Marciano P; Andrade, Alexandre

    2017-01-01

    In the resting state, blood oxygen level-dependent (BOLD) oscillations with a frequency of about 0.1 Hz are conspicuous. Whether their origin is neural or vascular is not yet fully understood. Furthermore, it is not clear whether these BOLD oscillations interact with slow oscillations in heart rate (HR). To address these two questions, we estimated phase-locking (PL) values between precentral gyrus (PCG) and insula in 25 scanner-naïve individuals during rest and stimulus-paced finger movements in both hemispheres. PL was quantified in terms of time delay and duration in the frequency band 0.07 to 0.13 Hz. Results revealed both positive and negative time delays. Positive time delays characterize neural BOLD oscillations leading in the PCG, whereas negative time delays represent vascular BOLD oscillations leading in the insula. About 50% of the participants revealed positive time delays distinctive for neural BOLD oscillations, either with short or long unilateral or bilateral phase-locking episodes. An expected preponderance of neural BOLD oscillations was found in the left hemisphere during right-handed movement and unexpectedly in the right hemisphere during rest. Only neural BOLD oscillations were significantly associated with heart rate variability (HRV) in the 0.1-Hz range in the first resting state. It is well known that participating in magnetic resonance imaging (MRI) studies may be frightening and cause anxiety. In this respect it is important to note that the most significant hemispheric asymmetry (p<0.002) with a right-sided dominance of neural BOLD and a left-sided dominance of vascular BOLD oscillations was found in the first resting session in the scanner-naïve individuals. Whether the enhanced left-sided perfusion (dominance of vascular BOLD) or the right-sided dominance of neural BOLD is related to the increased level of anxiety, attention or stress needs further research.

  4. A Big Five facet analysis of sub-clinical narcissism: understanding boldness in terms of well-known personality traits.

    PubMed

    Furnham, Adrian; Crump, John

    2014-08-01

    This study aimed to examine a Big Five 'bright-side' analysis of a sub-clinical personality disorder, i.e. narcissism. A total of 6957 British adults completed the NEO-PI-R, which measures the Big Five Personality factors at the domain and the facet level, as well as the Hogan Development Survey (HDS), which has a measure of Narcissism called Bold as one of its dysfunctional interpersonal tendencies. Correlation and regression results confirmed many of the associations between the Big Five domains and facets (NEO-PI-R) and sub-clinical narcissism. The Bold (Narcissism) scale from the HDS was the criterion variable in all analyses. Bold individuals are disagreeable extraverts with very low scores on facet Modesty but moderately high scores on Assertiveness, Competence and Achievement Striving. The study confirmed work using different population groups and different measures.

  5. Individual boldness traits influenced by temperature in male Siamese fighting fish.

    PubMed

    Forsatkar, Mohammad Navid; Nematollahi, Mohammad Ali; Biro, Peter A; Beckmann, Christa

    2016-10-15

    Temperature has profound effects on physiology of ectothermic animals. However, the effects on temperature variation on behavioral traits are poorly studied in contrast to physiological endpoints. This may be important as even small differences in temperatures have large effects on physiological rates including overall metabolism, and behavior is known to be linked to metabolism at least in part. The primary aim of this study was to determine the effects of ambient temperature on boldness responses of a species of fish commonly used in behavioral experiments, the Siamese fighting fish (Betta splendens). At 26°C, subjects were first examined for baseline behaviors over three days, using three different (but complementary) 'open field' type assays tested in a fixed order. Those same fish were next exposed to either the same temperature (26°C) or a higher temperature (30°C) for 10days, and then the same behavioral assays were repeated. Those individuals exposed to increased temperatures reduced their latency to leave the release area (area I), spent more time in area III (farthest from release area), and were more active overall; together we infer these behaviors to reflect an increase in general 'boldness' with increased temperature. Our results add to a limited number of studies of temperature effects on behavioral tendencies in ectotherms that are evident even after some considerable acclimation. From a methodological perspective, our results indicate careful temperature control is needed when studying behavior in this and other species of fish. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Octopus visual system: a functional MRI model for detecting neuronal electric currents without a BOLD confound

    PubMed Central

    Jiang, Xia; Lu, Hanbing; Shigeno, Shuichi; Tan, Li-Hai; Yang, Yihong; Ragsdale, Clifton W.; Gao, Jia-Hong

    2014-01-01

    Purpose Despite the efforts that have been devoted to detecting the transient magnetic fields generated by neuronal firing, the conclusion that a functionally relevant signal can be measured with magnetic resonance imaging (MRI) is still controversial. For human studies of neuronal current MRI (nc-MRI), the blood-oxygen-level-dependent (BOLD) effect remains an irresolvable confound. For tissue studies where hemoglobin is removed, natural sensory stimulation is not possible. This study investigates the feasibility of detecting a physiologically induced nc-MRI signal in vivo in a BOLD-free environment. Methods The cephalopod mollusc Octopus bimaculoides has vertebrate-like eyes, large optic lobes (OLs) and blood that does not contain hemoglobin. Visually evoked potentials were measured in the octopus retina and OL by electroretinogram and local field potential. nc-MRI scans were conducted at 9.4 Tesla to capture these activities. Results Electrophysiological recording detected strong responses in the retina and OL in vivo; however, nc-MRI failed to demonstrate any statistically significant signal change with a detection threshold of 0.2° for phase and 0.2% for magnitude. Experiments in a dissected eye-OL preparation yielded similar results. Conclusion These findings in a large hemoglobin-free nervous system suggest that sensory evoked neuronal magnetic fields are too weak for direct detection with current MRI technology. PMID:24301336

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

    PubMed

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

    2008-10-15

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

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

    PubMed Central

    Hillman, Elizabeth M.C.

    2014-01-01

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

  9. Unemployment in chronic airflow obstruction around the world: results from the BOLD study.

    PubMed

    Grønseth, Rune; Erdal, Marta; Tan, Wan C; Obaseki, Daniel O; Amaral, Andre F S; Gislason, Thorarinn; Juvekar, Sanjay K; Koul, Parvaiz A; Studnicka, Michael; Salvi, Sundeep; Burney, Peter; Buist, A Sonia; Vollmer, William M; Johannessen, Ane

    2017-09-01

    We aimed to examine associations between chronic airflow obstruction (CAO) and unemployment across the world.Cross-sectional data from 26 sites in the Burden of Obstructive Lung Disease (BOLD) study were used to analyse effects of CAO on unemployment. Odds ratios for unemployment in subjects aged 40-65 years were estimated using a multilevel mixed-effects generalised linear model with study site as random effect. Site-by-site heterogeneity was assessed using individual participant data meta-analyses.Out of 18 710 participants, 11.3% had CAO. The ratio of unemployed subjects with CAO divided by subjects without CAO showed large site discrepancies, although these were no longer significant after adjusting for age, sex, smoking and education. The site-adjusted odds ratio (95% CI) for unemployment was 1.79 (1.41-2.27) for CAO cases, decreasing to 1.43 (1.14-1.79) after adjusting for sociodemographic factors, comorbidities and forced vital capacity. Of other covariates that were associated with unemployment, age and education were important risk factors in high-income sites (4.02 (3.53-4.57) and 3.86 (2.80-5.30), respectively), while female sex was important in low- to middle-income sites (3.23 (2.66-3.91)).In the global BOLD study, CAO was associated with increased levels of unemployment, even after adjusting for sociodemographic factors, comorbidities and lung function. Copyright ©ERS 2017.

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

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

    2012-01-01

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

  12. Oxygenation in Cervical Cancer and Normal Uterine Cervix assessed using BOLD MRI at 3 T1

    PubMed Central

    Hallac, Rami R.; Ding, Yao; Yuan, Qing; McColl, Roderick W.; Lea, Jayanthi; Sims, Robert D.; Weatherall, Paul T.; Mason, Ralph P.

    2012-01-01

    Hypoxia is reported to be a biomarker for poor prognosis in cervical cancer. However, a practical non-invasive method is needed for routine clinical evaluation of tumor hypoxia. This study examined the potential use of BOLD (Blood Oxygenation Level Dependent) contrast MRI as a non-invasive technique to assess tumor vascular oxygenation at 3 T. Following IRB-approved informed consent and in compliance with HIPAA, successful results were achieved in nine patients with locally advanced cervical cancer (FIGO stage IIA to IVA) and three normal volunteers. In the first four patients, dynamic T2*-weighted MRI was performed in the transaxial plane using a multi-shot EPI sequence while patients breathed room air followed by oxygen (15 dm3/min). Later, a multi-echo gradient echo examination was added to provide quantitative R2* measurements. Baseline T2*-weighted signal intensity was quite stable, but increased to various extents in tumors upon initiation of oxygen breathing. Signal in normal uterus increased significantly, while iliacus muscle did not change. R2* responded significantly in healthy uterus, cervix, and eight cervical tumors. This preliminary study demonstrates that BOLD MRI of cervical cancer at 3 T is feasible. However, more patients must be evaluated and followed clinically before any prognostic value can be determined. PMID:22619091

  13. Nonlinear Bayesian Estimation of BOLD Signal under Non-Gaussian Noise

    PubMed Central

    Khan, Ali Fahim; Younis, Muhammad Shahzad; Bajwa, Khalid Bashir

    2015-01-01

    Modeling the blood oxygenation level dependent (BOLD) signal has been a subject of study for over a decade in the neuroimaging community. Inspired from fluid dynamics, the hemodynamic model provides a plausible yet convincing interpretation of the BOLD signal by amalgamating effects of dynamic physiological changes in blood oxygenation, cerebral blood flow and volume. The nonautonomous, nonlinear set of differential equations of the hemodynamic model constitutes the process model while the weighted nonlinear sum of the physiological variables forms the measurement model. Plagued by various noise sources, the time series fMRI measurement data is mostly assumed to be affected by additive Gaussian noise. Though more feasible, the assumption may cause the designed filter to perform poorly if made to work under non-Gaussian environment. In this paper, we present a data assimilation scheme that assumes additive non-Gaussian noise, namely, the e-mixture noise, affecting the measurements. The proposed filter MAGSF and the celebrated EKF are put to test by performing joint optimal Bayesian filtering to estimate both the states and parameters governing the hemodynamic model under non-Gaussian environment. Analyses using both the synthetic and real data reveal superior performance of the MAGSF as compared to EKF. PMID:25691911

  14. Improved BOLD detection in the medial temporal region using parallel imaging and voxel volume reduction.

    PubMed

    Bellgowan, Patrick S F; Bandettini, Peter A; van Gelderen, Peter; Martin, Alex; Bodurka, Jerzy

    2006-02-15

    Using gradient-echo EPI, signal dropout due to macroscopic off resonance effects can prevent blood-oxygenation-level-dependent (BOLD) signal change detection. The anterior medial temporal lobe (MTL) is located near these susceptibility gradients and therefore shows considerable signal dropout with GE-EPI. Reducing the volume of the image voxel reduces susceptibility-related signal dropout. However, this is accompanied by a prohibitive reduction in signal-to-noise ratio (SNR). To compensate for SNR loss with smaller voxels, we used a multi-channel MRI receiver with an array of receive-only 16-element surface coils at 3 T. We demonstrate that the reduction of susceptibility artifacts, through use of high resolution images, coupled with the gains in image SNR from the array coil improves the temporal signal-to-noise ratio (TSNR) and enhances the contrast-to-noise ratio (CNR). Furthermore, a comparison of 2 mm with 4-mm-thick axial images both with the same in-plane resolution showed that thinner slices enhanced TSNR and CNR throughout the ventral-medial regions of the temporal lobes, with the greatest improvement in the most anterior regions of the MTL. Further improvements were seen when adjacent 2 mm slices were combined to match overall voxel volume. These results demonstrate that BOLD investigation of anterior MTL function can be enhanced by decreasing voxel size but only in combination with the SNR gained by using the 16-channel head coil system.

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

    PubMed

    Pierce, Jordan E; McDowell, Jennifer E

    2017-03-31

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

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

    PubMed Central

    Felix-Ortiz, Ada C.; Febo, Marcelo

    2012-01-01

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

  17. Frequency of Spontaneous BOLD Signal Differences between Moderate and Late Preterm Newborns and Term Newborns.

    PubMed

    Wu, Xiushuang; Wei, Luqing; Wang, Nan; Hu, Zhangxue; Wang, Li; Ma, Juan; Feng, Shuai; Cai, Yue; Song, Xiaopeng; Shi, Yuan

    2016-10-01

    Little is known about the frequency features of spontaneous neural activity in the brains of moderate and late preterm (MLPT) newborns. We used resting-state functional magnetic resonance imaging (rs-fMRI) and the amplitude of low-frequency fluctuation (ALFF) method to investigate the frequency properties of spontaneous blood oxygen level-dependent (BOLD) signals in 26 MLPT and 35 term newborns. Two frequency bands, slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz), were analyzed. Our results showed widespread differences in ALFF between the two bands; differences occurred mainly in the primary sensory and motor cortices and to a lesser extent in association cortices and subcortical areas. Compared with term newborns, MLPT newborns showed significantly altered neural activity predominantly in the primary sensory and motor cortices and in the posterior cingulate gyrus/precuneus. In addition, a significant interaction between frequency bands and groups was observed in the primary somatosensory cortex. Intriguingly, these primary sensory and motor regions have been proven to be the major cortical hubs during the neonatal period. Our results revealed the frequency of spontaneous BOLD signal differences between MLPT and term newborns, which contribute to the understanding of regional development of spontaneous brain rhythms of MLPT newborns.

  18. Abnormal perilesional BOLD signal is not correlated with stroke patients’ behavior

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2003-01-01

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

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

    PubMed

    Bandoh, Hiroshi; Kida, Ikuhiro; Ueda, Hiroshi

    2011-01-17

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

  5. Quantification of oxygen changes in the placenta from BOLD MR image sequences

    NASA Astrophysics Data System (ADS)

    Porras, Antonio R.; Piella, Gemma; You, Wonsang; Limperopoulos, Catherine; Linguraru, Marius George

    2017-03-01

    Functional analysis of the placenta is important to analyze and understand its role in fetal growth and development. BOLD MR is a non-invasive technique that has been extensively used for functional analysis of the brain. During the last years, several studies have shown that this dynamic image modality is also useful to extract functional information of the placenta. We propose in this paper a method to track the placenta from a sequence of BOLD MR images acquired under normoxia and hyperoxia conditions with the goal of quantifying how the placenta adapts to oxygenation changes. The method is based on a spatiotemporal transformation model that ensures temporal coherence of the tracked structures. The method was initially applied to four patients with healthy pregnancies. An average MR signal increase of 16.96+/-8.39% during hyperoxia was observed. These automated results are in line with state-of-the-art reports using time-consuming manual segmentations subject to inter-observer errors.

  6. Task-Related Modulations of BOLD Low-Frequency Fluctuations within the Default Mode Network.

    PubMed

    Tommasin, Silvia; Mascali, Daniele; Gili, Tommaso; Assan, Ibrahim Eid; 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, 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.

  7. Task-Related Modulations of BOLD Low-Frequency Fluctuations within the Default Mode Network

    PubMed Central

    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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  12. Disentangling resting-state BOLD variability and PCC functional connectivity in 22q11.2 deletion syndrome.

    PubMed

    Zöller, Daniela; Schaer, Marie; Scariati, Elisa; Padula, Maria Carmela; Eliez, Stephan; Van De Ville, Dimitri

    2017-04-01

    Although often ignored in fMRI studies, moment-to-moment variability of blood oxygenation level dependent (BOLD) signals reveals important information about brain function. Indeed, higher brain signal variability has been associated with better cognitive performance in young adults compared to children and elderly adults. Functional connectivity, a very common approach in resting-state fMRI analysis, is scaled for variance. Thus, alterations might be confounded or driven by BOLD signal variance alterations. Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurodevelopmental disorder that is associated with a vast cognitive and clinical phenotype. To date, several resting-state fMRI studies reported altered functional connectivity in 22q11.2DS, however BOLD signal variance has not yet been analyzed. Here, we employed PLS correlation analysis to reveal multivariate patterns of diagnosis-related alterations and age-relationship throughout the cortex of 50 patients between 9 and 25 years old and 50 healthy controls in the same age range. To address how functional connectivity in the default mode network is influenced by BOLD signal fluctuations, we conducted the same analysis on seed-to-voxel connectivity of the posterior cingulate cortex (PCC) and compared resulting brain patterns. BOLD signal variance was lower mainly in regions of the default mode network and in the dorsolateral prefrontal cortex, but higher in large parts of the temporal lobes. In those regions, BOLD signal variance was correlated with age in healthy controls, but not in patients, suggesting deviant developmental trajectories from child- to adulthood. Positive connectivity of the PCC within the default mode network as well as negative connectivity towards the frontoparietal network were weaker in patients with 22q11.2DS. We furthermore showed that lower functional connectivity of the PCC was not driven by higher BOLD signal variability. Our results confirm the strong implication of BOLD

  13. Effect of dual-task-induced uncertainty on gait biomechanics in patients with multiple sclerosis with 2-6.5 EDSS grade.

    PubMed

    Gutiérrez Cruz, Carmen; Miangolarra Page, Juan Carlos; Rojas Ruiz, F Javier

    2016-09-01

    The goal of this study was to assess the effect that uncertainty induced by dual task conditions has on reaction-response time parameters and gait patterns of patients with multiple sclerosis (MS) with a 2-6.5 EDSS grade. The study involved eleven patients - nine women and two men - diagnosed with multiple sclerosis (age, 48±10years; height, 1.65±0.1m; weight, 72±22kg) with capacity to walk five meters without any aid or assistance. We employed an intra-group repeated measures design. Each participant was asked to walk with and without task-related uncertainty. Reaction-response and gait cycle times, as well as center of mass (CM) dynamics were measured using three force plates synchronized with a video camera through an electronic device that also controlled the system of uncertainty. The results obtained reveal that uncertainty induced by dual tasking is related to a reduction in the mean stride length and mean displacement and horizontal velocity of the CM in patients with MS. The values obtained for CM parameters indicate that uncertainty affects balance, as compared to no-uncertainty situations. These results confirm the necessity of including controlled dual-task-induced uncertainty in physical training programs for MS patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Repeated practice of a Go/NoGo visuomotor task induces neuroplastic change in the human posterior parietal cortex: an MEG study.

    PubMed

    Sugawara, Kazuhiro; Onishi, Hideaki; Yamashiro, Koya; Soma, Toshio; Oyama, Mineo; Kirimoto, Hikari; Tamaki, Hiroyuki; Murakami, Hiroatsu; Kameyama, Shigeki

    2013-05-01

    The posterior parietal cortex (PPC) is strongly related to task performance by evaluating sensory cues and visually guided movements. Sensorimotor processing is improved by task repetition as indicated by reduced response time. We investigated practice-induced changes in PPC visuomotor processing during a Go/NoGo task in humans using 306-channel magnetoencephalography. Eleven healthy adult males were instructed to extend the right index finger when presented with the Go stimulus (a red circle), but not to react to the NoGo stimulus (a green circle or a red square). Magnetic fields over the visual, posterior parietal, and sensorimotor cortices were measured before and after 3 days of task practice. The first peak of the visual-evoked field (VEF) occurred at approximately 80 ms after presentation of either the Go or NoGo stimulus, while a PPC response, with latency to a peak of 175.8 ± 26.7 ms, occurred only after the Go stimulus. No significant change in the first peak of VEF was measured after 3 days of task practice, but there was a significant reduction in the latency to peak PPC activity (160.1 ± 27.6 ms) and in the time from peak PPC activity to electromyogram onset. In all participants, practice resulted in a significant reduction in reaction time. These results demonstrate that practicing a sensorimotor task induces neuroplastic changes in PPC that accelerate sensorimotor processing and reduce motor response times.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2003-01-01

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

  17. Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia.

    PubMed

    Kuga, Hironori; Onitsuka, Toshiaki; Hirano, Yoji; Nakamura, Itta; Oribe, Naoya; Mizuhara, Hiroaki; Kanai, Ryota; Kanba, Shigenobu; Ueno, Takefumi

    2016-10-01

    Recent MRI studies have shown that schizophrenia is characterized by reductions in brain gray matter, which progress in the acute state of the disease. Cortical circuitry abnormalities in gamma oscillations, such as deficits in the auditory steady state response (ASSR) to gamma frequency (>30-Hz) stimulation, have also been reported in schizophrenia patients. In the current study, we investigated neural responses during click stimulation by BOLD signals. We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ), 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ), and 24 healthy controls (HC), assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

  18. Comparison between subjects with long- and short-allele carriers in the BOLD signal within amygdala during emotional tasks

    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.

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

    PubMed

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

    2017-01-01

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

  20. Red supergiant star studies with CO5BOLD and Optim3D

    NASA Astrophysics Data System (ADS)

    Plez, B.; Chiavassa, A.

    We describe recent work focused towards a better understanding of red supergiant stars using 3D radiative-hydrodynamics (RHD) simulations with CO5BOLD. A small number of simulations now exist that span up to seven years of stellar time, at various numerical resolutions. Our discussion concentrates on interferometric and spectroscopic observations. We point out a number of problems, in particular the line depth and line width that are not well reproduced by simulations. The most recent introduction of a non-grey treatment of the radiation field dramatically improved the match with observations, without solving all difficulties. We also review the newly revived effective temperature scale controversy, and argue that it will only be solved using 3D RHD models.

  1. Pathfinder technologies for bold new missions. [U.S. research and development program for space exploration

    NASA Technical Reports Server (NTRS)

    Sadin, Stanley R.; Rosen, Robert

    1987-01-01

    Project Pathfinder is a proposed U.S. Space Research and Technology program intended to enable bold new missions of space exploration. Pathfinder continues the advancement of technological capabilities and extends the foundation established under the Civil Space Technology Initiative, CSTI. By filling critical technological gaps, CSTI enhances access to Earth orbit and supports effective operations and science missions therein. Pathfinder, with a longer-term horizon, looks to a future that builds on Shuttle and Space Station and addresses technologies that support a range of exploration missions including: a return to the Moon to build an outpost; piloted missions to Mars; and continued scientific exploration of Earth and the other planets. The program's objective is to develop, within reasonable time frames, those emerging and innovative technologies that will make possible both new and enhanced missions and system concepts.

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

    PubMed

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

    2011-09-01

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

  3. Pathfinder technologies for bold new missions. [U.S. research and development program for space exploration

    NASA Technical Reports Server (NTRS)

    Sadin, Stanley R.; Rosen, Robert

    1987-01-01

    Project Pathfinder is a proposed U.S. Space Research and Technology program intended to enable bold new missions of space exploration. Pathfinder continues the advancement of technological capabilities and extends the foundation established under the Civil Space Technology Initiative, CSTI. By filling critical technological gaps, CSTI enhances access to Earth orbit and supports effective operations and science missions therein. Pathfinder, with a longer-term horizon, looks to a future that builds on Shuttle and Space Station and addresses technologies that support a range of exploration missions including: a return to the Moon to build an outpost; piloted missions to Mars; and continued scientific exploration of Earth and the other planets. The program's objective is to develop, within reasonable time frames, those emerging and innovative technologies that will make possible both new and enhanced missions and system concepts.

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

    PubMed

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

    2015-01-01

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

  5. Observation of two distinct spatial-temporal BOLD clusters during sensory stimulation in rats.

    PubMed

    Goelman, Gadi; Pelled, Galit; Dodd, Steve; Koretsky, Alan

    2007-02-01

    Neuronal activity evokes changes in local CBF and CBV, whose spatial differences are not fully known. We use the Radial Correlation Contrast (RCC) analysis method with high spatial resolution 100 x 100 x 1000 microm3 data collected with an 11.7 T magnet to differentiate two spatial-temporal BOLD clusters during sensory rat forepaw stimulation and hypothesize that each corresponds to either the CBF or the CBV processes. One cluster, obtained during the time segment of stimulation onset, is characterized by a high positive BOLD signal whereas the other, obtained during the simulation decline time segment, is characterized by a lower positive signal and strong post stimulus undershoot. The average volume of stimulation onset clusters is embedded in the stimulation decline clusters with the latter significantly larger and shifted towards deeper cortical layers. Comparison of amplitude-RCC and cross-correlation analyses performed on equivalent time segments (30 s, 40 images) revealed no differences in cluster size or location, demonstrating that temporal locality is more important than spatial locality in distinguishing between stimulation onset and stimulation decline clusters. We hypothesize that clusters characterized by stimulation onset are highly weighted by local changes in CBF whereas clusters characterized by stimulation decline are more CBV weighted. Moreover, the data suggest that the locations of the highest CBF changes are distinct from the locations of the highest CBV changes. While the former located within stimulation decline clusters and its weight is gradually reduced towards cluster's periphery (mainly ventrally), the highest changes in CBV occur in the cluster's periphery with only modest changes towards its center.

  6. Consistency in boldness, activity and exploration at different stages of life

    PubMed Central

    2013-01-01

    Background Animals show consistent individual behavioural patterns over time and over situations. This phenomenon has been referred to as animal personality or behavioural syndromes. Little is known about consistency of animal personalities over entire life times. We investigated the repeatability of behaviour in common voles (Microtus arvalis) at different life stages, with different time intervals, and in different situations. Animals were tested using four behavioural tests in three experimental groups: 1. before and after maturation over three months, 2. twice as adults during one week, and 3. twice as adult animals over three months, which resembles a substantial part of their entire adult life span of several months. Results Different behaviours were correlated within and between tests and a cluster analysis showed three possible behavioural syndrome-axes, which we name boldness, exploration and activity. Activity and exploration behaviour in all tests was highly repeatable in adult animals tested over one week. In animals tested over maturation, exploration behaviour was consistent whereas activity was not. Voles that were tested as adults with a three-month interval showed the opposite pattern with stable activity but unstable exploration behaviour. Conclusions The consistency in behaviour over time suggests that common voles do express stable personality over short time. Over longer periods however, behaviour is more flexible and depending on life stage (i.e. tested before/after maturation or as adults) of the tested individual. Level of boldness or activity does not differ between tested groups and maintenance of variation in behavioural traits can therefore not be explained by expected future assets as reported in other studies. PMID:24314274

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

    PubMed Central

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

    2017-01-01

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

  8. Dynamical properties of BOLD activity from the ventral posteromedial cortex associated with meditation and attentional skills.

    PubMed

    Pagnoni, Giuseppe

    2012-04-11

    Neuroimaging data suggest a link between the spontaneous production of thoughts during wakeful rest and slow fluctuations of activity in the default mode network (DMN), a set of brain regions with high basal metabolism and a major neural hub in the ventral posteromedial cortex (vPMC). Meta-awareness and regulation of mind-wandering are core cognitive components of most contemplative practices and to study their impact on DMN activity, we collected functional MRI (fMRI) data from a cohort of experienced Zen meditators and meditation-naive controls engaging in a basic attention-to-breathing protocol. We observed a significant group difference in the skewness of the fMRI BOLD signal from the vPMC, suggesting that the relative incidence of states of elevated vPMC activity was lower in meditators; furthermore, the same parameter was significantly correlated with performance on a rapid visual information processing (RVIP) test for sustained attention conducted outside the scanner. Finally, a functional connectivity analysis with the vPMC seed revealed a significant association of RVIP performance with the degree of temporal correlation between vPMC and the right temporoparietal junction (TPJ), a region strongly implicated in stimulus-triggered reorienting of attention. Together, these findings suggest that the vPMC BOLD signal skewness and the temporal relationship of vPMC and TPJ activities reflect the dynamic tension between mind-wandering, meta-awareness, and directed attention, and may represent a useful endophenotype for studying individual differences in attentional abilities and the impairment of the latter in specific clinical conditions.

  9. Pre-stimulus BOLD-network activation modulates EEG spectral activity during working memory retention.

    PubMed

    Kottlow, Mara; Schlaepfer, Anthony; Baenninger, Anja; Michels, Lars; Brandeis, Daniel; Koenig, Thomas

    2015-01-01

    Working memory (WM) processes depend on our momentary mental state and therefore exhibit considerable fluctuations. Here, we investigate the interplay of task-preparatory and task-related brain activity as represented by pre-stimulus BOLD-fluctuations and spectral EEG from the retention periods of a visual WM task. Visual WM is used to maintain sensory information in the brain enabling the performance of cognitive operations and is associated with mental health. We tested 22 subjects simultaneously with EEG and fMRI while performing a visuo-verbal Sternberg task with two different loads, allowing for the temporal separation of preparation, encoding, retention and retrieval periods. Four temporally coherent networks (TCNs)-the default mode network (DMN), the dorsal attention, the right and the left WM network-were extracted from the continuous BOLD data by means of a group ICA. Subsequently, the modulatory effect of these networks' pre-stimulus activation upon retention-related EEG activity in the theta, alpha, and beta frequencies was analyzed. The obtained results are informative in the context of state-dependent information processing. We were able to replicate two well-known load-dependent effects: the frontal-midline theta increase during the task and the decrease of pre-stimulus DMN activity. As our main finding, these two measures seem to depend on each other as the significant negative correlations at frontal-midline channels suggested. Thus, suppressed pre-stimulus DMN levels facilitated later task related frontal midline theta increases. In general, based on previous findings that neuronal coupling in different frequency bands may underlie distinct functions in WM retention, our results suggest that processes reflected by spectral oscillations during retention seem not only to be "online" synchronized with activity in different attention-related networks but are also modulated by activity in these networks during preparation intervals.

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

    PubMed Central

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

    2011-01-01

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

  11. Optimization of simultaneous multislice EPI for concurrent functional perfusion and BOLD signal measurements at 7T

    PubMed Central

    Poser, Benedikt A; Huber, Laurentius; Pfeuffer, Josef; Uludağ, Kâmil

    2016-01-01

    Purpose To overcome limitations of previous ultra‐high‐field arterial spin labeling (ASL) techniques concerning temporal resolution and brain coverage by utilizing the simultaneous multi‐slice (SMS) approach. Methods An optimized, flow‐alternating inversion recovery quantitative imaging of perfusion using a single subtraction II scheme was developed that tackles the challenges of 7 tesla (T) ASL. The implementation of tailored labeling radiofrequency pulses reduced the effect of transmit field ( B1+) inhomogeneities. The proposed approach utilizes an SMS echo‐planar imaging (EPI) readout to efficiently achieve large brain coverage. Results A pulsed ASL (PASL) technique with large brain coverage is described and optimized that can be applied at temporal resolutions below 2.5 s, similar to those achievable at 1.5 and 3T magnetic field strength. The influences of within‐ and through‐slice acceleration factors and reconstruction parameters on perfusion and blood‐oxygenation‐level‐dependent (BOLD)‐signal image and temporal signal‐to‐noise ratio (SNR) are presented. The proposed approach yielded twice the brain coverage as compared to conventional PASL at 7T, without notable loss in image quality. Conclusion The presented SMS EPI PASL at 7T overcomes current limitations in SNR, temporal resolution, and spatial coverage for functional perfusion and BOLD signal as well as baseline perfusion measurements. Magn Reson Med 78:121–129, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. PMID:27465273

  12. BOLD Magnetic Resonance Imaging identifies cortical hypoxia in severe renovascular disease”

    PubMed Central

    Gloviczki, Monika L; Glockner, James F; Crane, John A; McKusick, Michael A; Misra, Sanjay; Grande, Joseph P; Lerman, Lilach O; Textor, Stephen C

    2014-01-01

    Atherosclerotic renal artery stenosis has a range of manifestations depending upon the severity of vascular occlusion. The aim of this study was to examine whether exceeding the limits of adaptation to reduced blood flow ultimately leads to tissue hypoxia as determined by blood oxygen level dependent (BOLD) MR imaging. We compared three groups of hypertensive patients (24 with essential hypertension [EH]), 13 with “moderate” (Doppler velocities 200-384 cm/sec) and 17 with “severe” atherosclerotic renal artery stenosis ([ARAS]; velocities above 384 cm/sec and loss of functional renal tissue). Cortical and medullary blood flows and volumes were determined by multi-detector CT. Post-stenotic kidney size and blood flow were reduced with ARAS, and tissue perfusion fell in the most severe lesions. Tissue deoxyhemoglobin, as reflected by R2* values, was higher in medulla as compared to cortex for all groups and did not differ between subjects with renal artery lesions and EH. By contrast, cortical R2* levels were elevated for severe ARAS (21.6 ±9.4 /sec) as compared with either EH (17.8±2.3 /sec, p<.01) or moderate ARAS (15.7± 2.1 /sec, p<.01). Changes in medullary R2* after furosemide administration tended to be blunted in severe ARAS as compared to unaffected (contralateral) kidneys. These results demonstrate that severe vascular occlusion overwhelms the capacity of the kidney to adapt to reduced blood flow, manifest as overt cortical hypoxia as measured by BOLD MRI. The level of cortical hypoxia is out of proportion to medulla and may provide a marker to identify irreversible parenchymal injury. PMID:22042812

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2011-01-01

    Estimating moment-to-moment changes in blood oxygenation level dependent (BOLD) activation levels from functional magnetic resonance imaging (fMRI) data has applications for learned regulation of regional activation, brain state monitoring, and brain-machine interfaces. In each of these contexts, accurate estimation of the BOLD signal in as little time as possible is desired. This is a challenging problem due to the low signal-to-noise ratio of fMRI data. Previous methods for real-time fMRI analysis have either sacrificed the ability to compute moment-to-moment activation changes by averaging several acquisitions into a single activation estimate or have sacrificed accuracy by failing to account for prominent sources of noise in the fMRI signal. Here we present a new method for computing the amount of activation present in a single fMRI acquisition that separates moment-to-moment changes in the fMRI signal intensity attributable to neural sources from those due to noise, resulting in a feedback signal more reflective of neural activation. This method computes an incremental general linear model fit to the fMRI time series, which is used to calculate the expected signal intensity at each new acquisition. The difference between the measured intensity and the expected intensity is scaled by the variance of the estimator in order to transform this residual difference into a statistic. Both synthetic and real data were used to validate this method and compare it to the only other published real-time fMRI method. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Anatomical, BOLD, blood-flow MRI of non-human primate (baboon) retina

    PubMed Central

    Zhang, Yi; Wey, Hsiao-Ying; Nateras, Oscar San Emeterio; Peng, Qi; De La Garza, Bryan H.; Duong, Timothy Q

    2011-01-01

    The goal of this study was to demonstrate high-resolution anatomical, BOLD (blood-oxygenation-level-dependent), and blood-flow (BF) MRI on large non-human primate (NHP) retinas using a 3-Tesla clinical scanner as a first step toward translation. Baboon was chosen because of its evolutionary similarity to human. Anesthetized preparation, free of eye-movement artifacts, was used to evaluate clinical scanner hardware feasibility. Anatomical MRI (0.1×0.2×2.0 mm) before contrast-agent injection detected three alternating bright-dark-bright layers. The hyperintense inner strip nearest to the vitreous was enhanced by an intravascular contrast agent, likely included the ganglion and bipolar cell layer and the embedded retinal vessels. The hypointense middle strip showed no contrast enhancement, likely included the avascular outer unclear layer and photoreceptor segments. The hyperintense outer strip showed contrast enhancement, likely corresponded to the choroid vascular layer. In the posterior retina, the total thickness including the choroid was 617±101µm (±SD, n=7). BOLD fMRI (0.3×0.6×2.0 mm) of oxygen inhalation relative to air increased 6.5±1.4%. Basal BF (2×2×2mm) was 83±30mL/100g/min (air), and hypercapnia increased BF by 25±9% (P<0.05). This study demonstrates multimodal MRI to image anatomy, physiology and function on large NHP retinas using a clinical scanner, offering encouraging data to explore human applications. PMID:21360746

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

    PubMed Central

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

    2015-01-01

    The mechanisms of neurovascular coupling underlying generation of BOLD fMRI signals remain incompletely understood. It has been proposed that release of vasoactive substances by astrocytes couples neuronal activity to changes in cerebrovascular blood flow. However, the role of astrocytes in fMRI responses remains controversial. Astrocytes communicate via release of ATP, and here we tested the hypothesis that purinergic signaling plays a role in the mechanisms underlying fMRI. An established fMRI paradigm was used to trigger BOLD responses in the forepaw region of the somatosensory cortex (SSFP) of an anesthetized rat. Forepaw stimulation induced release of ATP in the SSFP region. To interfere with purinergic signaling by promoting rapid breakdown of the vesicular and/or released ATP, a lentiviral vector was used to express a potent ectonucleotidase, transmembrane prostatic acid phosphatase (TMPAP), in the SSFP region. TMPAP expression had no effect on resting cerebral blood flow, cerebrovascular reactivity, and neuronal responses to sensory stimulation. However, TMPAP catalytic activity markedly reduced the magnitude of BOLD fMRI responses triggered in the SSFP region by forepaw stimulation. Facilitated ATP breakdown could result in accumulation of adenosine. However, blockade of A1 receptors had no effect on BOLD responses and did not reverse the effect of TMPAP. These results suggest that purinergic signaling plays a significant role in generation of BOLD fMRI signals. We hypothesize that astrocytes activated during periods of enhanced neuronal activity release ATP, which propagates astrocytic activation, stimulates release of vasoactive substances and dilation of cerebral vasculature. PMID:25834053

  17. Whole-brain three-dimensional T2-weighted BOLD functional magnetic resonance imaging at 7 Tesla.

    PubMed

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

    2014-12-01

    A new acquisition scheme for T2-weighted spin-echo BOLD fMRI is introduced. It uses a T2-preparation module to induce blood-oxygenation-level-dependent (BOLD) contrast, followed by a single-shot three-dimensional (3D) fast gradient-echo readout with short echo time (TE). It differs from most spin-echo BOLD sequences in that BOLD contrast is generated before the readout, which eliminates the "dead time" due to long TE required for T2 contrast, and substantially improves acquisition efficiency. This approach, termed "3D T2prep-GRE," was implemented at 7 Tesla (T) with a typical spatial (2.5 × 2.5 × 2.5 mm(3) ) and temporal (TR = 2.3 s) resolution for functional MRI (fMRI) and whole-brain coverage (55 slices), and compared with the widely used 2D spin-echo EPI sequence. In fMRI experiments of simultaneous visual/motor activities, 3D T2prep-GRE showed minimal distortion and little signal dropout across the whole brain. Its lower power deposition allowed greater spatial coverage (55 versus 17 slices with identical TR, resolution and power level), temporal SNR (60% higher) and CNR (35% higher) efficiency than 2D spin-echo EPI. It also showed smaller T2* contamination. This approach is expected to be useful for ultra-high field fMRI, especially for regions near air cavities. The concept of using T2-preparation to generate BOLD contrast can be combined with many other sequences at any field strength. © 2013 Wiley Periodicals, Inc.

  18. Quantification of venous blood signal contribution to BOLD functional activation in the auditory cortex at 3 T.

    PubMed

    Casciaro, Sergio; Bianco, Roberto; Distante, Alessandro

    2008-11-01

    Most modern techniques for functional magnetic resonance imaging (fMRI) rely on blood-oxygen-level-dependent (BOLD) contrast as the basic principle for detecting neuronal activation. However, the measured BOLD effect depends on a transfer function related to neurophysiological changes accompanying electrical neural activation. The spatial accuracy and extension of the region of interest are determined by vascular effect, which introduces incertitude on real neuronal activation maps. Our efforts have been directed towards the development of a new methodology that is capable of combining morphological, vascular and functional information; obtaining new insight regarding foci of activation; and distinguishing the nature of activation on a pixel-by-pixel basis. Six healthy volunteers were studied in a parametric auditory functional experiment at 3 T; activation maps were overlaid on a high-resolution brain venography obtained through a novel technique. The BOLD signal intensities of vascular and nonvascular activated voxels were analyzed and compared: it was shown that nonvascular active voxels have lower values for signal peak (P<10(-7)) and area (P<10(-8)) with respect to vascular voxels. The analysis showed how venous blood influenced the measured BOLD signals, supplying a technique to filter possible venous artifacts that potentially can lead to misinterpretation of fMRI results. This methodology, although validated in the auditory cortex activation, maintains a general applicability to any cortical fMRI study, as the basic concepts on which it relies on are not limited to this cortical region. The results obtained in this study can represent the basis for new methodologies and tools that are capable of adding further characterization to the BOLD signal properties.

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

    PubMed

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

    2015-04-01

    The mechanisms of neurovascular coupling underlying generation of BOLD fMRI signals remain incompletely understood. It has been proposed that release of vasoactive substances by astrocytes couples neuronal activity to changes in cerebrovascular blood flow. However, the role of astrocytes in fMRI responses remains controversial. Astrocytes communicate via release of ATP, and here we tested the hypothesis that purinergic signaling plays a role in the mechanisms underlying fMRI. An established fMRI paradigm was used to trigger BOLD responses in the forepaw region of the somatosensory cortex (SSFP) of an anesthetized rat. Forepaw stimulation induced release of ATP in the SSFP region. To interfere with purinergic signaling by promoting rapid breakdown of the vesicular and/or released ATP, a lentiviral vector was used to express a potent ectonucleotidase, transmembrane prostatic acid phosphatase (TMPAP), in the SSFP region. TMPAP expression had no effect on resting cerebral blood flow, cerebrovascular reactivity, and neuronal responses to sensory stimulation. However, TMPAP catalytic activity markedly reduced the magnitude of BOLD fMRI responses triggered in the SSFP region by forepaw stimulation. Facilitated ATP breakdown could result in accumulation of adenosine. However, blockade of A1 receptors had no effect on BOLD responses and did not reverse the effect of TMPAP. These results suggest that purinergic signaling plays a significant role in generation of BOLD fMRI signals. We hypothesize that astrocytes activated during periods of enhanced neuronal activity release ATP, which propagates astrocytic activation, stimulates release of vasoactive substances and dilation of cerebral vasculature. Copyright © 2015 the authors 0270-6474/15/355284-09$15.00/0.

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

    PubMed Central

    Ibinson, JW; Vogt, KM

    2013-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-12-01

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

  3. Back pain in seniors: the Back pain Outcomes using Longitudinal Data (BOLD) cohort baseline data

    PubMed Central

    2014-01-01

    Background Back pain represents a substantial burden globally, ranking first in a recent assessment among causes of years lived with disability. Though back pain is widely studied among working age adults, there are gaps with respect to basic descriptive epidemiology among seniors, especially in the United States. Our goal was to describe how pain, function and health-related quality of life vary by demographic and geographic factors among seniors presenting to primary care providers with new episodes of care for back pain. Methods We examined baseline data from the Back pain Outcomes using Longitudinal Data (BOLD) registry, the largest inception cohort to date of seniors presenting to a primary care provider for back pain. The sample included 5,239 patients ≥ 65 years old with a new primary care visit for back pain at three integrated health systems (Northern California Kaiser-Permanente, Henry Ford Health System [Detroit], and Harvard Vanguard Medical Associates [Boston]). We examined differences in patient characteristics across healthcare sites and associations of patient sociodemographic and clinical characteristics with baseline patient-reported measures of pain, function, and health-related quality of life. Results Patients differed across sites in demographic and other characteristics. The Detroit site had more African-American patients (50%) compared with the other sites (7-8%). The Boston site had more college graduates (68%) compared with Detroit (20%). Female sex, lower educational status, African-American race, and older age were associated with worse functional disability as measured by the Roland-Morris Disability Questionnaire. Except for age, these factors were also associated with worse pain. Conclusions Baseline pain and functional impairment varied substantially with a number of factors in the BOLD cohort. Healthcare site was an important factor. After controlling for healthcare site, lower education, female sex, African-American race

  4. Quantitative analysis of the postcontractile blood-oxygenation-level-dependent (BOLD) effect in skeletal muscle

    PubMed Central

    Towse, Theodore F.; Slade, Jill M.; Ambrose, Jeffrey A.; DeLano, Mark C.

    2011-01-01

    Previous studies show that transient increases in both blood flow and magnetic resonance image signal intensity (SI) occur in human muscle after brief, single contractions, and that the SI increases are threefold larger in physically active compared with sedentary subjects. This study examined the relationship between these transient changes by measuring anterior tibial artery flow (Doppler ultrasound), anterior muscle SI (3T, one-shot echo-planar images, TR/TE = 1,000/35), and muscle blood volume and hemoglobin saturation [near-infrared spectroscopy (NIRS)] in the same subjects after 1-s-duration maximum isometric ankle dorsiflexion contractions. Arterial flow increased to a peak 5.9 ± 0.7-fold above rest (SE, n = 11, range 2.6–10.2) within 7 s and muscle SI increased to a peak 2.7 ± 0.6% (range 0.0–6.0%) above rest within 12 s after the contractions. The peak postcontractile SI change was significantly correlated with both peak postcontractile flow (r = 0.61, n = 11) and with subject activity level (r = 0.63, n = 10) estimated from 7-day accelerometer recordings. In a subset of 7 subjects in which NIRS data acquisition was successful, the peak magnitude of the postcontractile SI change agreed well with SI calculated from the NIRS blood volume and saturation changes (r = 0.80, slope = 1.02, intercept = 0.16), confirming the blood-oxygenation-level-dependent (BOLD) mechanism underlying the SI change. The magnitudes of postcontractile changes in blood saturation and SI were reproduced by a simple one-compartment muscle vascular model that incorporated the observed pattern of postcontractile flow, and which assumed muscle O2 consumption peaks within 2 s after a brief contraction. The results show that muscle postcontractile BOLD SI changes depend critically on the balance between O2 delivery and O2 consumption, both of which can be altered by chronic physical activity. PMID:21330621

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  8. Personality in the cockroach Diploptera punctata: Evidence for stability across developmental stages despite age effects on boldness.

    PubMed

    Stanley, Christina R; Mettke-Hofmann, Claudia; Preziosi, Richard F

    2017-01-01

    Despite a recent surge in the popularity of animal personality studies and their wide-ranging associations with various aspects of behavioural ecology, our understanding of the development of personality over ontogeny remains poorly understood. Stability over time is a central tenet of personality; ecological pressures experienced by an individual at different life stages may, however, vary considerably, which may have a significant effect on behavioural traits. Invertebrates often go through numerous discrete developmental stages and therefore provide a useful model for such research. Here we test for both differential consistency and age effects upon behavioural traits in the gregarious cockroach Diploptera punctata by testing the same behavioural traits in both juveniles and adults. In our sample, we find consistency in boldness, exploration and sociality within adults whilst only boldness was consistent in juveniles. Both boldness and exploration measures, representative of risk-taking behaviour, show significant consistency across discrete juvenile and adult stages. Age effects are, however, apparent in our data; juveniles are significantly bolder than adults, most likely due to differences in the ecological requirements of these life stages. Size also affects risk-taking behaviour since smaller adults are both bolder and more highly explorative. Whilst a behavioural syndrome linking boldness and exploration is evident in nymphs, this disappears by the adult stage, where links between other behavioural traits become apparent. Our results therefore indicate that differential consistency in personality can be maintained across life stages despite age effects on its magnitude, with links between some personality traits changing over ontogeny, demonstrating plasticity in behavioural syndromes.

  9. Personality in the cockroach Diploptera punctata: Evidence for stability across developmental stages despite age effects on boldness

    PubMed Central

    Mettke-Hofmann, Claudia; Preziosi, Richard F.

    2017-01-01

    Despite a recent surge in the popularity of animal personality studies and their wide-ranging associations with various aspects of behavioural ecology, our understanding of the development of personality over ontogeny remains poorly understood. Stability over time is a central tenet of personality; ecological pressures experienced by an individual at different life stages may, however, vary considerably, which may have a significant effect on behavioural traits. Invertebrates often go through numerous discrete developmental stages and therefore provide a useful model for such research. Here we test for both differential consistency and age effects upon behavioural traits in the gregarious cockroach Diploptera punctata by testing the same behavioural traits in both juveniles and adults. In our sample, we find consistency in boldness, exploration and sociality within adults whilst only boldness was consistent in juveniles. Both boldness and exploration measures, representative of risk-taking behaviour, show significant consistency across discrete juvenile and adult stages. Age effects are, however, apparent in our data; juveniles are significantly bolder than adults, most likely due to differences in the ecological requirements of these life stages. Size also affects risk-taking behaviour since smaller adults are both bolder and more highly explorative. Whilst a behavioural syndrome linking boldness and exploration is evident in nymphs, this disappears by the adult stage, where links between other behavioural traits become apparent. Our results therefore indicate that differential consistency in personality can be maintained across life stages despite age effects on its magnitude, with links between some personality traits changing over ontogeny, demonstrating plasticity in behavioural syndromes. PMID:28489864

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

    PubMed

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

    2014-04-01

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

  11. Measurement of oxygen extraction fraction (OEF): An optimized BOLD signal model for use with hypercapnic and hyperoxic calibration.

    PubMed

    Merola, Alberto; Murphy, Kevin; Stone, Alan J; Germuska, Michael A; Griffeth, Valerie E M; Blockley, Nicholas P; Buxton, Richard B; Wise, Richard G

    2016-04-01

    Several techniques have been proposed to estimate relative changes in cerebral metabolic rate of oxygen consumption (CMRO2) by exploiting combined BOLD fMRI and cerebral blood flow data in conjunction with hypercapnic or hyperoxic respiratory challenges. More recently, methods based on respiratory challenges that include both hypercapnia and hyperoxia have been developed to assess absolute CMRO2, an important parameter for understanding brain energetics. In this paper, we empirically optimize a previously presented "original calibration model" relating BOLD and blood flow signals specifically for the estimation of oxygen extraction fraction (OEF) and absolute CMRO2. To do so, we have created a set of synthetic BOLD signals using a detailed BOLD signal model to reproduce experiments incorporating hypercapnic and hyperoxic respiratory challenges at 3T. A wide range of physiological conditions was simulated by varying input parameter values (baseline cerebral blood volume (CBV0), baseline cerebral blood flow (CBF0), baseline oxygen extraction fraction (OEF0) and hematocrit (Hct)). From the optimization of the calibration model for estimation of OEF and practical considerations of hypercapnic and hyperoxic respiratory challenges, a new "simplified calibration model" is established which reduces the complexity of the original calibration model by substituting the standard parameters α and β with a single parameter θ. The optimal value of θ is determined (θ=0.06) across a range of experimental respiratory challenges. The simplified calibration model gives estimates of OEF0 and absolute CMRO2 closer to the true values used to simulate the experimental data compared to those estimated using the original model incorporating literature values of α and β. Finally, an error propagation analysis demonstrates the susceptibility of the original and simplified calibration models to measurement errors and potential violations in the underlying assumptions of isometabolism

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

    PubMed

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

    2012-03-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-09-15

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

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

    PubMed Central

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

    2011-01-01

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

  16. Blood oxygen level-dependent (BOLD) MRI: A novel technique for the assessment of myocardial ischemia as identified by nuclear imaging SPECT.

    PubMed

    Egred, M; Waiter, G D; Redpath, T W; Semple, S K I; Al-Mohammad, A; Walton, S

    2007-12-01

    The different levels of deoxyhemoglobin in the ischemic myocardium, induced by stressors such as dipyridamole, can be detected by blood oxygen level-dependent (BOLD) MRI and may be used to diagnose myocardial ischemia. The aim of this study was to assess the signal change in the myocardium on BOLD MRI as well as wall thickening between rest and dipyridamole stress images in ischemic and non-ischemic myocardium as identified on SPECT imaging. Twelve patients with stress-induced myocardial ischemia on SPECT underwent rest and dipyridamole stress MRI using a double breath-hold, T2()-weighted, ECG-gated sequence to produce BOLD contrast images as well as cine-MRI for wall thickening assessment in 10 of the 12 patients. Signal change on BOLD MRI and wall thickening were compared between rest and stress images in ischemic and non-ischemic myocardial segments as identified on SPECT. In each patient, two MRI slices containing 16 segments per slice were analysed. In total, there were 384 segments for BOLD analysis and 320 for wall thickening. For BOLD signal 137 segments correlated to segments with reversible ischemia on SPECT and 247 to normal segments, while for wall thickening 112 segments correlated to segments with reversible ischemia and 208 to normal segments. The average BOLD MRI signal intensity change was -13.8 (+/-16.3)% in the ischemic segments compared to -10.3 (+/-14.7)% in the non-ischemic segments (p=0.05). The average wall thickening was 6.4 (+/-3.4) mm in the ischemic segments compared to 8.7 (+/-3.8) mm in the non-ischemic segments (p<0.0001). Stress-induced ischemic myocardium has a different signal change and wall thickening than non-ischemic myocardium and may be differentiated on BOLD MRI. Larger studies are needed to define a threshold for detection and to determine the sensitivity and specificity of this technique.

  17. BOLD signal effects of transcranial alternating current stimulation (tACS) in the alpha range: A concurrent tACS-fMRI study.

    PubMed

    Vosskuhl, Johannes; Huster, René J; Herrmann, Christoph S

    2016-10-15

    Many studies have proven transcranial alternating current stimulation (tACS) to manipulate brain activity. Until now it is not known, however, how these manipulations in brain activity are represented in brain metabolism or how spatially specific these changes are. Alpha-tACS has been shown to enhance the amplitude of the individual alpha frequency (IAF) and a negative correlation between alpha amplitude and occipital BOLD signal was reported in numerous EEG/fMRI experiments. Thus, alpha-tACS was chosen to test the effects of tACS on the BOLD signal. A reduction thereof was expected during alpha-tACS which shows the spatial extent of tACS effects beyond modeling studies. Three groups of subjects were measured in an MRI scanner, receiving tACS at either their IAF (N=11), 1Hz (control; N=12) or sham (i.e., no stimulation - a second control; N=11) while responding to a visual vigilance task. Stimulation was administered in an interleaved pattern of tACS-on runs and tACS-free baseline periods. The BOLD signal was analyzed in response to tACS-onset during resting state and in response to seldom target stimuli. Alpha-tACS at 1.0mA reduced the task-related BOLD response to visual targets in the occipital cortex as compared to tACS-free baseline periods. The deactivation was strongest in an area where the BOLD signal was shown to correlate negatively with alpha amplitude. A direct effect of tACS on resting state BOLD signal levels could not be shown. Our findings suggest that tACS-related changes in BOLD activity occur only as a modulation of an existing BOLD response.

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

    PubMed Central

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

    2009-01-01

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

  19. Complexity of spontaneous BOLD activity in default mode network is correlated with cognitive function in normal male elderly: a multiscale entropy analysis.

    PubMed

    Yang, Albert C; Huang, Chu-Chung; Yeh, Heng-Liang; Liu, Mu-En; Hong, Chen-Jee; Tu, Pei-Chi; Chen, Jin-Fan; Huang, Norden E; Peng, Chung-Kang; Lin, Ching-Po; Tsai, Shih-Jen

    2013-02-01

    The nonlinear properties of spontaneous fluctuations in blood oxygen level-dependent (BOLD) signals remain unexplored. We test the hypothesis that complexity of BOLD activity is reduced with aging and is correlated with cognitive performance in the elderly. A total of 99 normal older and 56 younger male subjects were included. Cognitive function was assessed using Cognitive Abilities Screening Instrument and Wechsler Digit Span Task. We employed a complexity measure, multiscale entropy (MSE) analysis, and investigated appropriate parameters for MSE calculation from relatively short BOLD signals. We then compared the complexity of BOLD signals between the younger and older groups, and examined the correlation between cognitive test scores and complexity of BOLD signals in various brain regions. Compared with the younger group, older subjects had the most significant reductions in MSE of BOLD signals in posterior cingulate gyrus and hippocampal cortex. For older subjects, MSE of BOLD signals from default mode network areas, including hippocampal cortex, cingulate cortex, superior and middle frontal gyrus, and middle temporal gyrus, were found to be positively correlated with major cognitive functions, such as attention, orientation, short-term memory, mental manipulation, and language. MSE from subcortical regions, such as amygdala and putamen, were found to be positively correlated with abstract thinking and list-generating fluency, respectively. Our findings confirmed the hypothesis that complexity of BOLD activity was correlated with aging and cognitive performance based on MSE analysis, and may provide insights on how dynamics of spontaneous brain activity relates to aging and cognitive function in specific brain regions. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  1. Changes in BOLD and ADC weighted imaging in acute hypoxia during sea-level and altitude adapted states.

    PubMed

    Rostrup, Egill; Larsson, Henrik B W; Born, Alfred P; Knudsen, Gitte M; Paulson, Olaf B

    2005-12-01

    Acute normobaric hypoxia as well as longstanding hypobaric hypoxia induce pronounced physiological changes and may eventually lead to impairment of cerebral function. The aim of the present study is to investigate the effect of hypoxia on the cerebral activation response as well as to explore possible structural changes as measured by diffusion weighted imaging. Eleven healthy sea-level residents were studied after 5 weeks of adaptation to high altitude conditions at Chacaltaya, Bolivia (5260 m). The subjects were studied immediately after return to sea-level in hypoxic and normoxic conditions, and the examinations repeated 6 months later after re-adaptation to sea-level conditions. The BOLD response, measured at 1.5 T, was severely reduced during acute hypoxia both in the altitude and sea-level adapted states (50% reduction during an average S(a)O(2) of 75%). On average, the BOLD response magnitude was 23% lower in altitude than sea-level adaptation in the normoxic condition, but in the hypoxic condition, no significant differences were found. A small but statistically significant decrease in the apparent diffusion coefficient (ADC) was seen in some brain regions during acute hypoxia, whereas ADC was slightly elevated in high altitude as compared to sea-level adaptation. It is concluded that hypoxia significantly diminishes the BOLD response, and the mechanisms underlying this finding are discussed. Furthermore, altitude adaptation may influence both the magnitude of the activation-related response, as well as micro-structural features.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2005-05-01

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

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

    PubMed

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

    2016-12-01

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

  5. Consecutive TMS-fMRI reveals an inverse relationship in BOLD signal between object and scene processing.

    PubMed

    Mullin, Caitlin R; Steeves, Jennifer K E

    2013-12-04

    The human visual system is capable of recognizing an infinite number of scenes containing an abundance of rich visual information. There are several cortical regions associated with the representation of a scene, including those specialized for object processing (the lateral occipital area [LO]) and for the spatial layout of scenes (the parahippocampal place area). Although behavioral studies have demonstrated that these image categories (scenes and objects) exert an influence on each other such that scene context can facilitate object identification or that scene categorization can be impaired by the presence of a salient object, little is known about the apparent cortical interactions involved in building the conscious representation of a complete scene. It has been shown that transcranial magnetic stimulation (TMS) to the left LO disrupts object categorization but facilitates scene categorization. Here, we show that this effect is also reflected by changes in the BOLD signal such that TMS to the left LO decreases BOLD signal at the stimulation site (LO) while viewing objects and increases BOLD signal in the left PPA when viewing scenes. This suggests that these regions, although likely not on a strict hierarchy of bottom-up coding, share functional communication likely in the form of inhibitory connections.

  6. Increased BOLD Variability in the Parietal Cortex and Enhanced Parieto-Occipital Connectivity during Tactile Perception in Congenitally Blind Individuals

    PubMed Central

    Leo, Andrea; Bernardi, Giulio; Handjaras, Giacomo; Bonino, Daniela; Ricciardi, Emiliano; Pietrini, Pietro

    2012-01-01

    Previous studies in early blind individuals posited a possible role of parieto-occipital connections in conveying nonvisual information to the visual occipital cortex. As a consequence of blindness, parietal areas would thus become able to integrate a greater amount of multimodal information than in sighted individuals. To verify this hypothesis, we compared fMRI-measured BOLD signal temporal variability, an index of efficiency in functional information integration, in congenitally blind and sighted individuals during tactile spatial discrimination and motion perception tasks. In both tasks, the BOLD variability analysis revealed many cortical regions with a significantly greater variability in the blind as compared to sighted individuals, with an overlapping cluster located in the left inferior parietal/anterior intraparietal cortex. A functional connectivity analysis using this region as seed showed stronger correlations in both tasks with occipital areas in the blind as compared to sighted individuals. As BOLD variability reflects neural integration and processing efficiency, these cross-modal plastic changes in the parietal cortex, even if described in a limited sample, reinforce the hypothesis that this region may play an important role in processing nonvisual information in blind subjects and act as a hub in the cortico-cortical pathway from somatosensory cortex to the reorganized occipital areas. PMID:22792493

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

    PubMed

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

    2016-01-01

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

  8. Amplitude of Sensorimotor Mu Rhythm Is Correlated with BOLD from Multiple Brain Regions: A Simultaneous EEG-fMRI Study

    PubMed Central

    Yin, Siyang; Liu, Yuelu; Ding, Mingzhou

    2016-01-01

    The mu rhythm is a field oscillation in the ∼10Hz range over the sensorimotor cortex. For decades, the suppression of mu (event-related desynchronization) has been used to index movement planning, execution, and imagery. Recent work reports that non-motor processes, such as spatial attention and movement observation, also desynchronize mu, raising the possibility that the mu rhythm is associated with the activity of multiple brain regions and systems. In this study, we tested this hypothesis by recording simultaneous resting-state EEG-fMRI from healthy subjects. Independent component analysis (ICA) was applied to extract the mu components. The amplitude (power) fluctuations of mu were estimated as a time series using a moving-window approach, which, after convolving with a canonical hemodynamic response function (HRF), was correlated with blood-oxygen-level-dependent (BOLD) signals from the entire brain. Two main results were found. First, mu power was negatively correlated with BOLD from areas of the sensorimotor network, the attention control network, the putative mirror neuron system, and the network thought to support theory of mind. Second, mu power was positively correlated with BOLD from areas of the salience network, including anterior cingulate cortex and anterior insula. These results are consistent with the hypothesis that sensorimotor mu rhythm is associated with multiple brain regions and systems. They also suggest that caution should be exercised when attempting to interpret mu modulation in terms of a single brain network. PMID:27499736

  9. High estrogen and chronic haloperidol lead to greater amphetamine-induced BOLD activation in awake, amphetamine-sensitized female rats.

    PubMed

    Madularu, Dan; Kulkarni, Praveen; Yee, Jason R; Kenkel, William M; Shams, Waqqas M; Ferris, Craig F; Brake, Wayne G

    2016-06-01

    The ovarian hormone estrogen has been implicated in schizophrenia symptomatology. Low levels of estrogen are associated with an increase in symptom severity, while exogenous estrogen increases the efficacy of antipsychotic medication, pointing at a possible interaction between estrogen and the dopaminergic system. The aim of this study is to further investigate this interaction in an animal model of some aspects of schizophrenia using awake functional magnetic resonance imaging. Animals receiving 17β-estradiol and haloperidol were scanned and BOLD activity was assessed in response to amphetamine. High 17β-estradiol replacement and chronic haloperidol treatment showed increased BOLD activity in regions of interest and neural networks associated with schizophrenia (hippocampal formations, habenula, amygdala, hypothalamus etc.), compared with low, or no 17β-estradiol. These data show that chronic haloperidol treatment has a sensitizing effect, possibly on the dopaminergic system, and this effect is dependent on hormonal status, with high 17β-estradiol showing the greatest BOLD increase. Furthermore, these experiments further support the use of imaging techniques in studying schizophrenia, as modeled in the rat, but can be extended to addiction and other disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Increased BOLD variability in the parietal cortex and enhanced parieto-occipital connectivity during tactile perception in congenitally blind individuals.

    PubMed

    Leo, Andrea; Bernardi, Giulio; Handjaras, Giacomo; Bonino, Daniela; Ricciardi, Emiliano; Pietrini, Pietro

    2012-01-01

    Previous studies in early blind individuals posited a possible role of parieto-occipital connections in conveying nonvisual information to the visual occipital cortex. As a consequence of blindness, parietal areas would thus become able to integrate a greater amount of multimodal information than in sighted individuals. To verify this hypothesis, we compared fMRI-measured BOLD signal temporal variability, an index of efficiency in functional information integration, in congenitally blind and sighted individuals during tactile spatial discrimination and motion perception tasks. In both tasks, the BOLD variability analysis revealed many cortical regions with a significantly greater variability in the blind as compared to sighted individuals, with an overlapping cluster located in the left inferior parietal/anterior intraparietal cortex. A functional connectivity analysis using this region as seed showed stronger correlations in both tasks with occipital areas in the blind as compared to sighted individuals. As BOLD variability reflects neural integration and processing efficiency, these cross-modal plastic changes in the parietal cortex, even if described in a limited sample, reinforce the hypothesis that this region may play an important role in processing nonvisual information in blind subjects and act as a hub in the cortico-cortical pathway from somatosensory cortex to the reorganized occipital areas.

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

    PubMed

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

    2014-12-01

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

  12. Indication of BOLD-specific venous flow-volume changes from precisely controlled hyperoxic vs. hypercapnic calibration.

    PubMed

    Mark, Clarisse I; Pike, G Bruce

    2012-04-01

    Deriving cerebral metabolic rate of oxygen consumption (CMRO(2)) from blood oxygenation level-dependent (BOLD) signals involves a flow-volume parameter (α), reflecting total cerebral blood volume changes, and a calibration constant (M). Traditionally, the former is assumed a fixed value and the latter is measured under alterations in fixed inspired fractional concentrations of carbon dioxide. We recently reported on reductions in M-variability via precise control of end-tidal pressures of both hypercapnic (HC) and hyperoxic (HO) gases. In light of these findings, our aim was to apply the improved calibration alternatives to neuronal activation, making use of their distinct vasoactive natures to evaluate the α-value. Nine healthy volunteers were imaged at 3 T while simultaneously measuring BOLD and arterial spin-labeling signals during controlled, graded, HC, and HO, followed by visual (VC) and sensorimotor cortices (SMC) activation. On the basis of low M- and CMRO(2)-variability, the comparison of these calibration alternatives accurately highlighted a reduced venous flow-volume relationship (α=0.16±0.02, with α(VC)=0.12±0.04, and α(SMC)=0.20±0.02), as appropriate for BOLD modeling.

  13. Amplitude of Sensorimotor Mu Rhythm Is Correlated with BOLD from Multiple Brain Regions: A Simultaneous EEG-fMRI Study.

    PubMed

    Yin, Siyang; Liu, Yuelu; Ding, Mingzhou

    2016-01-01

    The mu rhythm is a field oscillation in the ∼10Hz range over the sensorimotor cortex. For decades, the suppression of mu (event-related desynchronization) has been used to index movement planning, execution, and imagery. Recent work reports that non-motor processes, such as spatial attention and movement observation, also desynchronize mu, raising the possibility that the mu rhythm is associated with the activity of multiple brain regions and systems. In this study, we tested this hypothesis by recording simultaneous resting-state EEG-fMRI from healthy subjects. Independent component analysis (ICA) was applied to extract the mu components. The amplitude (power) fluctuations of mu were estimated as a time series using a moving-window approach, which, after convolving with a canonical hemodynamic response function (HRF), was correlated with blood-oxygen-level-dependent (BOLD) signals from the entire brain. Two main results were found. First, mu power was negatively correlated with BOLD from areas of the sensorimotor network, the attention control network, the putative mirror neuron system, and the network thought to support theory of mind. Second, mu power was positively correlated with BOLD from areas of the salience network, including anterior cingulate cortex and anterior insula. These results are consistent with the hypothesis that sensorimotor mu rhythm is associated with multiple brain regions and systems. They also suggest that caution should be exercised when attempting to interpret mu modulation in terms of a single brain network.

  14. Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli.

    PubMed

    Wang, Rong; Wu, Lingjie; Tang, Zuohua; Sun, Xinghuai; Feng, Xiaoyuan; Tang, Weijun; Qian, Wen; Wang, Jie; Jin, Lixin; Zhong, Yufeng; Xiao, Zebin

    2017-04-15

    Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p < 0.05). In conclusion, the bilateral visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices.

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

    PubMed

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

    2013-10-01

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

  16. ESIP: Boldly going towards ESIP 2.0 and your phone ...

    EPA Pesticide Factsheets

    The Gulf of Maine Council’s EcoSystem Indicator Partnership (ESIP) was formed in 2006 to evaluate changes in the health of the Gulf of Maine ecosystems through the use of indicators. ESIP’s initial approach to indicator development focused on seven ecosystem themes, which were based on priority issues identified by scientists, decision-makers and other stakeholders. To date, ESIP has made indicator data available online through its Indicator Reporting Tool and published fact sheets on six of its indicator themes: aquaculture, aquatic habitats, climate change, coastal development, contaminants, and eutrophication. Indicator data and information on ESIP’s final theme – fisheries – will be available in 2016. The ESIP community is now looking to the future and is poised to begin the next phase (ESIP 2.0). As part of a bold and innovative new approach, ESIP 2.0 will focus on indicators to track ecosystem services; the benefits that people and coastal communities obtain from the ecosystem. The current state of science on ecosystem services is growing rapidly and will be summarized. ESIP is participating in conversations with other organizations and agencies to determine the best approach to incorporate indicators of ecosystem goods and services along with traditional, environmental indicators. Together with ongoing work that relates watershed drivers and environmental impacts, the Gulf of Maine community will help lead the effort towards better incorporatio

  17. ESIP: Boldly going towards ESIP 2.0 and your phone ...

    EPA Pesticide Factsheets

    The Gulf of Maine Council’s EcoSystem Indicator Partnership (ESIP) was formed in 2006 to evaluate changes in the health of the Gulf of Maine ecosystems through the use of indicators. ESIP’s initial approach to indicator development focused on seven ecosystem themes, which were based on priority issues identified by scientists, decision-makers and other stakeholders. To date, ESIP has made indicator data available online through its Indicator Reporting Tool and published fact sheets on six of its indicator themes: aquaculture, aquatic habitats, climate change, coastal development, contaminants, and eutrophication. Indicator data and information on ESIP’s final theme – fisheries – will be available in 2016. The ESIP community is now looking to the future and is poised to begin the next phase (ESIP 2.0). As part of a bold and innovative new approach, ESIP 2.0 will focus on indicators to track ecosystem services; the benefits that people and coastal communities obtain from the ecosystem. The current state of science on ecosystem services is growing rapidly and will be summarized. ESIP is participating in conversations with other organizations and agencies to determine the best approach to incorporate indicators of ecosystem goods and services along with traditional, environmental indicators. Together with ongoing work that relates watershed drivers and environmental impacts, the Gulf of Maine community will help lead the effort towards better incorporatio

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

    PubMed Central

    Tosetti, Michela; Morrone, Maria Concetta

    2015-01-01

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

  19. Progression to deep sleep is characterized by changes to BOLD dynamics in sensory cortices

    PubMed Central

    Davis, Ben; Tagliazucchi, Enzo; Jovicich, Jorge; Laufs, Helmut; Hasson, Uri

    2016-01-01

    Sleep has been shown to subtly disrupt the spatial organization of functional connectivity networks in the brain, but in a way that largely preserves the connectivity within sensory cortices. Here we evaluated the hypothesis that sleep does impact sensory cortices, but through alteration of activity dynamics. We therefore examined the impact of sleep on hemodynamics using a method for quantifying non-random, high frequency signatures of the blood-oxygen-level dependent (BOLD) signal (amplitude variance asymmetry; AVA). We found that sleep was associated with the elimination of these dynamics in a manner that is restricted to auditory, motor and visual cortices. This elimination was concurrent with increased variance of activity in these regions. Functional connectivity between regions showing AVA during wakefulness maintained a relatively consistent hierarchical structure during wakefulness and N1 and N2 sleep, despite a gradual reduction of connectivity strength as sleep progressed. Thus, sleep is related to elimination of high frequency non-random activity signatures in sensory cortices that are robust during wakefulness. The elimination of these AVA signatures conjointly with preservation of the structure of functional connectivity patterns may be linked to the need to suppress sensory inputs during sleep while still maintaining the capacity to react quickly to complex multimodal inputs. PMID:26724779

  20. Distinct patterns of viewpoint-dependent BOLD activity during common-object recognition and mental rotation.

    PubMed

    Wilson, Kevin D; Farah, Martha J

    2006-01-01

    A fundamental but unanswered question about the human visual system concerns the way in which misoriented objects are recognized. One hypothesis maintains that representations of incoming stimuli are transformed via parietally based spatial normalization mechanisms (eg mental rotation) to match view-specific representations in long-term memory. Using fMRI, we tested this hypothesis by directly comparing patterns of brain activity evoked during classic mental rotation and misoriented object recognition involving everyday objects. BOLD activity increased systematically with stimulus rotation within the ventral visual stream during object recognition and within the dorsal visual stream during mental rotation. More specifically, viewpoint-dependent activity was significantly greater in the right superior parietal lobule during mental rotation than during object recognition. In contrast, viewpoint-dependent activity was significantly greater in the right fusiform gyrus during object recognition than during mental rotation. In addition to these differences in viewpoint-dependent activity, object recognition and mental rotation produced distinct patterns of brain activity, independent of stimulus rotation: object recognition resulted in greater overall activity within ventral stream visual areas and mental rotation resulted in greater overall activity within dorsal stream visual areas. The present results are inconsistent with the hypothesis that misoriented object recognition is mediated by structures within the parietal lobe that are known to be involved in mental rotation.

  1. Exploiting Magnetic Resonance Angiography Imaging Improves Model Estimation of BOLD Signal

    PubMed Central

    Hu, Zhenghui; Liu, Cong; Shi, Pengcheng; Liu, Huafeng

    2012-01-01

    The change of BOLD signal relies heavily upon the resting blood volume fraction () associated with regional vasculature. However, existing hemodynamic data assimilation studies pretermit such concern. They simply assign the value in a physiologically plausible range to get over ill-conditioning of the assimilation problem and fail to explore actual . Such performance might lead to unreliable model estimation. In this work, we present the first exploration of the influence of on fMRI data assimilation, where actual within a given cortical area was calibrated by an MR angiography experiment and then was augmented into the assimilation scheme. We have investigated the impact of on single-region data assimilation and multi-region data assimilation (dynamic cause modeling, DCM) in a classical flashing checkerboard experiment. Results show that the employment of an assumed in fMRI data assimilation is only suitable for fMRI signal reconstruction and activation detection grounded on this signal, and not suitable for estimation of unobserved states and effective connectivity study. We thereby argue that introducing physically realistic in the assimilation process may provide more reliable estimation of physiological information, which contributes to a better understanding of the underlying hemodynamic processes. Such an effort is valuable and should be well appreciated. PMID:22384043

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

    PubMed

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

    2006-09-01

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

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

    PubMed Central

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

    2011-01-01

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

  4. Progression to deep sleep is characterized by changes to BOLD dynamics in sensory cortices.

    PubMed

    Davis, Ben; Tagliazucchi, Enzo; Jovicich, Jorge; Laufs, Helmut; Hasson, Uri

    2016-04-15

    Sleep has been shown to subtly disrupt the spatial organization of functional connectivity networks in the brain, but in a way that largely preserves the connectivity within sensory cortices. Here we evaluated the hypothesis that sleep does impact sensory cortices, but through alteration of activity dynamics. We therefore examined the impact of sleep on hemodynamics using a method for quantifying non-random, high frequency signatures of the blood-oxygen-level dependent (BOLD) signal (amplitude variance asymmetry; AVA). We found that sleep was associated with the elimination of these dynamics in a manner that is restricted to auditory, motor and visual cortices. This elimination was concurrent with increased variance of activity in these regions. Functional connectivity between regions showing AVA during wakefulness maintained a relatively consistent hierarchical structure during wakefulness and N1 and N2 sleep, despite a gradual reduction of connectivity strength as sleep progressed. Thus, sleep is related to elimination of high frequency non-random activity signatures in sensory cortices that are robust during wakefulness. The elimination of these AVA signatures conjointly with preservation of the structure of functional connectivity patterns may be linked to the need to suppress sensory inputs during sleep while still maintaining the capacity to react quickly to complex multimodal inputs.

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

    PubMed

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

    2013-08-01

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

  6. The impact of COPD on health status: findings from the BOLD study.

    PubMed

    Janson, Christer; Marks, Guy; Buist, Sonia; Gnatiuc, Louisa; Gislason, Thorarinn; McBurnie, Mary Ann; Nielsen, Rune; Studnicka, Michael; Toelle, Brett; Benediktsdottir, Bryndis; Burney, Peter

    2013-12-01

    The aim of this study was to describe the impact of chronic obstructive pulmonary disease (COPD) on health status in the Burden of Obstructive Lung Disease (BOLD) populations. We conducted a cross-sectional, general population-based survey in 11 985 subjects from 17 countries. We measured spirometric lung function and assessed health status using the Short Form 12 questionnaire. The physical and mental health component scores were calculated. Subjects with COPD (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70, n = 2269) had lower physical component scores (44±10 versus 48±10 units, p<0.0001) and mental health component scores (51±10 versus 52±10 units, p = 0.005) than subjects without COPD. The effect of reported heart disease, hypertension and diabetes on physical health component scores (-3 to -4 units) was considerably less than the effect of COPD Global Initiative for Chronic Obstructive Lung Disease grade 3 (-8 units) or 4 (-11 units). Dyspnoea was the most important determinant of a low physical and mental health component scores. In addition, lower forced expiratory volume in 1 s, chronic cough, chronic phlegm and the presence of comorbidities were all associated with a lower physical health component score. COPD is associated with poorer health status but the effect is stronger on the physical than the mental aspects of health status. Severe COPD has a greater negative impact on health status than self-reported cardiovascular disease and diabetes.

  7. BOLD data representing activation and connectivity for rare no-go versus frequent go cues.

    PubMed

    Meffert, Harma; Hwang, Soonjo; Nolan, Zachary T; Chen, Gang; Blair, James R

    2016-06-01

    The neural circuitry underlying response control is often studied using go/no-go tasks, in which participants are required to respond as fast as possible to go cues and withhold from responding to no-go stimuli. In the current task, response control was studied using a fully counterbalanced design in which blocks with a low frequency of no-go cues (75% go, 25% no-go) were alternated with blocks with a low frequency of go cues (25% go, 75% no-go); see also "Segregating attention from response control when performing a motor inhibition task: Segregating attention from response control" [1]. We applied a whole brain corrected, paired t-test to the data assessing for regions differentially activated by low frequency no-go cues relative to high frequency go cues. In addition, we conducted a generalized psychophysiological interaction analysis on the data using a right inferior frontal gyrus seed region. This region was identified through the BOLD response t-test and was chosen because right inferior gyrus is highly implicated in response inhibition.

  8. Case-finding options for COPD: Results from the BOLD Study

    PubMed Central

    Jithoo, Anamika; Enright, Paul; Burney, Peter; Buist, A Sonia; Bateman, Eric D; Tan, Wan C; Studnicka, Michael; Mejza, Filip; Gillespie, Suzanne; Vollmer, William M

    2012-01-01

    Aim To compare strategies for COPD case-finding using data from the Burden of Obstructive Lung Disease (BOLD) study. Methods Population-based samples of adults aged ≥40 years (n= 9390) from 14 countries completed a questionnaire and spirometry. We compared the screening efficiency of different staged algorithms that used questionnaire data and/or PEF to identify persons at risk for COPD and hence needing confirmatory spirometry. Separate algorithms were fitted for moderate/severe COPD and for severe COPD. We estimated the cost of each algorithm in 1000 people. Results For moderate/severe COPD, use of questionnaire data alone permitted high sensitivity (97%), but required confirmatory spirometry on 80% of participants. Use of PEF only required confirmatory spirometry in only 19-22% of subjects with 83-84% sensitivity. For severe COPD, use of PEF achieved 91-93% sensitivity, requiring confirmatory spirometry in <9% of participants. Cost analysis suggested that a staged screening algorithm using only PEF initially, followed by confirmatory spirometry as needed, was the most cost-effective case finding strategy. Conclusion Our results support the use of PEF as a simple, cost-effective initial screening tool for conducting COPD case-finding in adults ≥40 years. These findings should be validated in real-world settings such as the primary care environment. PMID:22743668

  9. The impact of COPD on health status: findings from the BOLD study

    PubMed Central

    Janson, Christer; Marks, Guy; Buist, Sonia; Gnatiuc, Louisa; Gislason, Thorarinn; McBurnie, Mary Ann; Nielsen, Rune; Studnicka, Michael; Toelle, Brett; Benediktsdottir, Bryndis; Burney, Peter

    2013-01-01

    The aim of this study was to describe the impact of chronic obstructive pulmonary disease (COPD) on health status in the Burden of Obstructive Lung Disease (BOLD) populations. We conducted a cross-sectional, general population-based survey in 11 985 subjects from 17 countries. We measured spirometric lung function and assessed health status using the Short Form 12 questionnaire. The physical and mental health component scores were calculated. Subjects with COPD (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70, n = 2269) had lower physical component scores (44±10 versus 48±10 units, p<0.0001) and mental health component scores (51±10 versus 52±10 units, p = 0.005) than subjects without COPD. The effect of reported heart disease, hypertension and diabetes on physical health component scores (-3 to -4 units) was considerably less than the effect of COPD Global Initiative for Chronic Obstructive Lung Disease grade 3 (-8 units) or 4 (-11 units). Dyspnoea was the most important determinant of a low physical and mental health component scores. In addition, lower forced expiratory volume in 1 s, chronic cough, chronic phlegm and the presence of comorbidities were all associated with a lower physical health component score. COPD is associated with poorer health status but the effect is stronger on the physical than the mental aspects of health status. Severe COPD has a greater negative impact on health status than self-reported cardiovascular disease and diabetes. PMID:23722617

  10. The 5 R's: an emerging bold standard for conducting relevant research in a changing world.

    PubMed

    Peek, C J; Glasgow, Russell E; Stange, Kurt C; Klesges, Lisa M; Purcell, E Peyton; Kessler, Rodger S

    2014-01-01

    Research often fails to find its way into practice or policy in a timely way, if at all. Given the current pressure and pace of health care change, many authors have recommended different approaches to make health care research more relevant and rapid. An emerging standard for research, the "5 R's" is a synthesis of recommendations for care delivery research that (1) is relevant to stakeholders; (2) is rapid and recursive in application; (3) redefines rigor; (4) reports on resources required; and (5) is replicable. Relevance flows from substantive ongoing participation by stakeholders. Rapidity and recursiveness occur through accelerated design and peer reviews followed by short learning/implementation cycles through which questions and answers evolve over time. Rigor is the disciplined conduct of shared learning within the specific changing situations in diverse settings. Resource reporting includes costs of interventions. Replicability involves designing for the factors that may affect subsequent implementation of an intervention or program in different contexts. These R's of the research process are mutually reinforcing and can be supported by training that fosters collaborative and reciprocal relationships among researchers, implementers, and other stakeholders. In sum, a standard is emerging for research that is both rigorous and relevant. Consistent and bold application will increase the value, timeliness, and applicability of the research enterprise. © 2014 Annals of Family Medicine, Inc.

  11. Reliable and efficient approach of BOLD signal with dual Kalman filtering.

    PubMed

    Liu, Cong; Hu, Zhenghui

    2012-01-01

    By introducing the conflicting effects of dynamic changes in blood flow, volume, and blood oxygenation, Balloon model provides a biomechanical compelling interpretation of the BOLD signal. In order to obtain optimal estimates for both the states and parameters involved in this model, a joint filtering (estimate) method has been widely used. However, it is flawed in several aspects (i) Correlation or interaction between the states and parameters is incorporated despite its nonexistence in biophysical reality. (ii) A joint representation for states and parameters necessarily means the large dimension of state space and will in turn lead to huge numerical cost in implementation. Given this knowledge, a dual filtering approach is proposed and demonstrated in this paper as a highly competent alternative, which can not only provide more reliable estimates, but also in a more efficient way. The two approaches in our discussion will be based on unscented Kalman filter, which has become the algorithm of choice in numerous nonlinear estimation and machine learning applications.

  12. A call to action: bold ideas from the Minnesota Women's Heart Summit.

    PubMed

    Ali, Nora; Lindquist, Ruth; Boucher, Jackie L; Witt, Dawn; Ambroz, Teresa; Konety, Suma H; Luepker, Russell; Windenburg, Denise; Hayes, Sharonne N

    2012-05-01

    Minnesota has the lowest overall coronary heart disease mortality rate in the United States. Yet disparities between men and women persist with regard to prevention, detection, and treatment. This has led to a gender gap not only in terms of care but also in survival rates. In an effort to better understand and close the gender gap, the Minneapolis Heart Institute, the Minneapolis Heart Institute Foundation, the University of Minnesota, and Mayo Clinic hosted a multidisciplinary Women's Heart Summit in April 2010. The goals of the summit were to stimulate dialogue and devise strategies to eliminate untimely deaths of women from heart disease. Summit participants were asked to contribute suggestions--called "Bold Ideas"--to address sex-based differences in the prevention, detection, and treatment of heart disease. Ideas were categorized according to three themes: educational programming, modifications to the health care system, and government involvement and funding. From these, several solutions emerged: 1) Involve obstetric/gynecologic physicians in providing heart-health education; 2) involve mid-level providers (midwives and other advanced practice women's health care providers) and other health professionals in women's heart health education, and 3) maximize the use of social media and online newsfeeds to raise awareness of heart disease in women. This article summarizes the discussion of the main ideas submitted by summit participants.

  13. To boldly climb: behavioural and cognitive differences in migrating European glass eels.

    PubMed

    Podgorniak, T; Blanchet, S; De Oliveira, E; Daverat, F; Pierron, F

    2016-01-01

    European eel (Anguilla anguilla) is a catadromous fish species that received substantial attention as its population has markedly declined in the last three decades. The possible causes of this decline include habitat fragmentation factors such as dams and weirs. In some cases, these obstacles are equipped with fish friendly passage devices that may select young eels according to their climbing behaviour. We tested how individual climbing tendency was related to the event of fishway passage experienced in the field and classified fish climbing profiles as climbing 'leaders', 'followers', 'finishers' and 'no climbers'. Moreover, we analysed the brain transcription level of genes related to neurogenesis and synaptic plasticity and compared it to climbing profiles. We found that fish from the upstream segments of an impounded river had a higher climbing propensity. Their behaviour was also more repeatable throughout the whole test than the obstacle-naive fish from the downstream segment. Moreover, we found that boldly climbing 'leaders' had lower levels of transcription of synapse-related genes than the climbing 'followers'. These differences could be related to coping styles of fish, where proactive 'leaders' express a routine and risky behaviour, whereas reactive fish need an environmental assessment before exploratory behaviour. Our study showed that differences in climbing propensity exist in glass eels separated by water obstacles. Moreover, eels could adopt climbing different strategies according to the way they deal with environmental stress and to the cognitive abilities they possess.

  14. To boldly climb: behavioural and cognitive differences in migrating European glass eels

    PubMed Central

    Podgorniak, T.; Blanchet, S.; De Oliveira, E.; Daverat, F.; Pierron, F.

    2016-01-01

    European eel (Anguilla anguilla) is a catadromous fish species that received substantial attention as its population has markedly declined in the last three decades. The possible causes of this decline include habitat fragmentation factors such as dams and weirs. In some cases, these obstacles are equipped with fish friendly passage devices that may select young eels according to their climbing behaviour. We tested how individual climbing tendency was related to the event of fishway passage experienced in the field and classified fish climbing profiles as climbing ‘leaders’, ‘followers’, ‘finishers’ and ‘no climbers’. Moreover, we analysed the brain transcription level of genes related to neurogenesis and synaptic plasticity and compared it to climbing profiles. We found that fish from the upstream segments of an impounded river had a higher climbing propensity. Their behaviour was also more repeatable throughout the whole test than the obstacle-naive fish from the downstream segment. Moreover, we found that boldly climbing ‘leaders’ had lower levels of transcription of synapse-related genes than the climbing ‘followers’. These differences could be related to coping styles of fish, where proactive ‘leaders’ express a routine and risky behaviour, whereas reactive fish need an environmental assessment before exploratory behaviour. Our study showed that differences in climbing propensity exist in glass eels separated by water obstacles. Moreover, eels could adopt climbing different strategies according to the way they deal with environmental stress and to the cognitive abilities they possess. PMID:26909192

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2008-02-15

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

  18. Reliability comparison of spontaneous brain activities between BOLD and CBF contrasts in eyes-open and eyes-closed resting states.

    PubMed

    Zou, Qihong; Miao, Xinyuan; Liu, Dapeng; Wang, Danny J J; Zhuo, Yan; Gao, Jia-Hong

    2015-11-01

    Blood oxygenation level dependent (BOLD) and arterial spin labeling (ASL) are two predominant resting-state fMRI techniques in mapping spontaneous brain activities. At single voxel level, cerebral blood flow (CBF) measured by ASL and amplitude of low frequency fluctuations (ALFF) of BOLD have been recognized as useful indices to characterize brain function in health and disease. However, no study has directly compared the test-retest reliability between BOLD and CBF contrasts on the same group of subjects at single voxel level. Moreover, both eyes-open and eyes-closed conditions have been employed as resting states, but it is still not clear which state is more reliable. Here we collected BOLD and ASL data during eyes-open and eyes-closed states across three scanning visits on twenty-two healthy young subjects. CBF-mean, BOLD- and CBF-ALFF were computed to characterize corresponding brain activities at single voxel level. Seed-based functional connectivity (FC) with the posterior cingulate cortex (PCC) was further calculated for both BOLD and CBF data. Intra-class correlation was used as the index of long-term reliability between visits 1 and 2 (two months apart) and short-term reliability between visits 2 and 3 (on the same day). Both short- and long-term reliabilities for CBF-mean and BOLD-ALFF were high, but were lower for CBF-ALFF, BOLD- and CBF-FC in both eyes-open and eyes-closed states. Direct comparisons showed that brain regions with the highest reliability of CBF-mean were mainly in the gray matter. The reliability of CBF-ALFF and BOLD-FC was lower than that of BOLD-ALFF, and the reliability of CBF-FC was lower than those of both CBF-ALFF and BOLD-FC. Furthermore, we observed that reliabilities of the eyes-open state were higher than those of the eyes-closed state for both imaging contrasts, though the effect size was small. Voxel-wise comparisons demonstrated that the long-term reliability of BOLD-ALFF was significantly higher with eyes open in the

  19. Can personality predict individual differences in brook trout spatial learning ability?

    PubMed

    White, S L; Wagner, T; Gowan, C; Braithwaite, V A

    2017-08-01

    While differences in individual personality are common in animal populations, understanding the ecological significance of variation has not yet been resolved. Evidence suggests that personality may influence learning and memory; a finding that could improve our understanding of the evolutionary processes that produce and maintain intraspecific behavioural heterogeneity. Here, we tested whether boldness, the most studied personality trait in fish, could predict learning ability in brook trout. After quantifying boldness, fish were trained to find a hidden food patch in a maze environment. Stable landmark cues were provided to indicate the location of food and, at the conclusion of training, cues were rearranged to test for learning. There was a negative relationship between boldness and learning as shy fish were increasingly more successful at navigating the maze and locating food during training trials compared to bold fish. In the altered testing environment, only shy fish continued using cues to search for food. Overall, the learning rate of bold fish was found to be lower than that of shy fish for several metrics suggesting that personality could have widespread effects on behaviour. Because learning can increase plasticity to environmental change, these results have significant implications for fish conservation. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Shy birds play it safe: personality in captivity predicts risk responsiveness during reproduction in the wild.

    PubMed

    Cole, Ella F; Quinn, John L

    2014-05-01

    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. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  1. Shy birds play it safe: personality in captivity predicts risk responsiveness during reproduction in the wild

    PubMed Central

    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

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

    PubMed

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

    2008-08-01

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

  3. Fractal analysis of spontaneous fluctuations of the BOLD signal in the human brain networks.

    PubMed

    Li, Yi-Chia; Huang, Yun-An

    2014-05-01

    To investigate what extent brain regions are continuously interacting during resting-state, independent component analyses (ICA) was applied to analyze resting-state functional MRI (RS-fMRI) data. According to the analyzed results, it was surprisingly found that low frequency fluctuations (LFFs), which belong to the 1/f signal (a signal with power spectrum whose power spectral density is inversely proportional to the frequency), have been classified into groups using ICA; furthermore, the spatial distributions of these groups within the brain were found to resemble the spatial distributions of different networks, which manifests that the signal characteristics of RS LFFs are distinct across networks. In our work, we applied the 1/f model in the fractal analyses to further investigate this distinction. Twenty healthy participants got involved in this study. They were scanned to acquire the RS-fMRI data. The acquired data were first processed with ICA to obtain the networks of the resting brain. Afterward, the blood-oxygenation level dependent (BOLD) signals of these networks were processed with the fractal analyses for obtaining the fractal parameter α. α was found to significantly vary across networks, which reveals that the fractal characteristic of LFFs differs across networks. According to prior literatures, this difference could be brought by the discrepancy of hemodynamic response amplitude (HRA) between networks. Hence, in our work, we also performed the computational simulation to discover the relationship between α and HRA. Based on the simulation results, HRA is highly linear-correlated with the fractal characteristics of LFFs which is revealed by α. Our results support that the origin of RS-fMRI signals contains arterial fluctuations. Hence, in addition to the commonly used method such as synchrony analysis and power spectral analysis, another approach, the fractal analysis, is suggested for acquiring the information of hemodynamic responses by means

  4. To Boldly Go: America's Next Era in Space. The Universe Now and Beyond

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Dr. France Cordova, NASA's Chief Scientist opened this, the third session in the NASA Administrator's Seminar Series, by asking the following question: 'What would be a bold and aspiring agenda for America's next era in space?' It aimed at answering the following questions: What do we know about the universe? How do we know it? (Dr. Cordova also mentioned that the first seminar was about the definition of cellular life and how to recognize it, and featured as speakers, Dr. Lynn Margoles and Dr. Leslie Orgle.) Administrator Daniel S. Goldin was introduced; he welcomed the attendees, and remarked that NASA personnel have a critical need to explain to Congress and the public why a space program is important. Congress and the public pay for the space programs. Therefore the programs' importance cannot remain in the sole domain of scientists. The first speaker, Dr. Vera Ruben of the Department of Terrestrial Magnetism at the Carnegie Institute of Washington, was introduced as an art historian expert in cosmology and an observational astronomer. Dr. Ruben brought up a number of questions regarding the substance, location, and origin of dark matter, radiation, galaxies, and the lumpy structure of galaxies in space, as well as the age and density of our universe. The next speaker was Dr. Bohdan Paczynski, a theoretical astrophysicist from Princeton University's Department of Astrophysical Sciences. The final speaker, Dr. Linda Schale is a cosmologist from the University of Texas at Austin. She was said to be a 'paleontologist of the human mind' who tries 'to understand mechanisms people use to understand the world'. The concluding discussion centered on why NASA scientists don t communicate better with people who are not highly educated. This is a big concern because to continue its work, NASA needs to communicate the importance of its goals to the average person. Additional information is included in the original extended abstract.

  5. To Boldly Go: America's Next Era in Space. The Universe Now and Beyond

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Dr. France Cordova, NASA's Chief Scientist opened this, the third session in the NASA Administrator's Seminar Series, by asking the following question: 'What would be a bold and aspiring agenda for America's next era in space?' It aimed at answering the following questions: What do we know about the universe? How do we know it? (Dr. Cordova also mentioned that the first seminar was about the definition of cellular life and how to recognize it, and featured as speakers, Dr. Lynn Margoles and Dr. Leslie Orgle.) Administrator Daniel S. Goldin was introduced; he welcomed the attendees, and remarked that NASA personnel have a critical need to explain to Congress and the public why a space program is important. Congress and the public pay for the space programs. Therefore the programs' importance cannot remain in the sole domain of scientists. The first speaker, Dr. Vera Ruben of the Department of Terrestrial Magnetism at the Carnegie Institute of Washington, was introduced as an art historian expert in cosmology and an observational astronomer. Dr. Ruben brought up a number of questions regarding the substance, location, and origin of dark matter, radiation, galaxies, and the lumpy structure of galaxies in space, as well as the age and density of our universe. The next speaker was Dr. Bohdan Paczynski, a theoretical astrophysicist from Princeton University's Department of Astrophysical Sciences. The final speaker, Dr. Linda Schale is a cosmologist from the University of Texas at Austin. She was said to be a 'paleontologist of the human mind' who tries 'to understand mechanisms people use to understand the world'. The concluding discussion centered on why NASA scientists don t communicate better with people who are not highly educated. This is a big concern because to continue its work, NASA needs to communicate the importance of its goals to the average person. Additional information is included in the original extended abstract.

  6. Airflow Obstruction and Use of Solid Fuels for Cooking or Heating: BOLD Results.

    PubMed

    Amaral, André F S; Patel, Jaymini; Kato, Bernet S; Obaseki, Daniel O; Lawin, Hervé; Tan, Wan C; Juvekar, Sanjay K; Harrabi, Imed; Studnicka, Michael; Wouters, Emiel F M; Loh, Li-Cher; Bateman, Eric D; Mortimer, Kevin; Buist, A Sonia; Burney, Peter G J

    2017-09-12

    Evidence supporting the association of COPD or airflow obstruction with use of solid fuels is conflicting and inconsistent. To assess the association of airflow obstruction with self-reported use of solid fuels for cooking or heating. We analysed 18,554 adults from the BOLD study, who had provided acceptable post-bronchodilator spirometry measurements and information on use of solid fuels. The association of airflow obstruction with use of solid fuels for cooking or heating was assessed by sex, within each site, using regression analysis. Estimates were stratified by national income and meta-analysed. We carried out similar analyses for spirometric restriction, chronic cough and chronic phlegm. We found no association between airflow obstruction and use of solid fuels for cooking or heating (ORmen=1.20, 95%CI 0.94-1.53; ORwomen=0.88, 95%CI 0.67-1.15). This was true for low/middle and high income sites. Among never smokers there was also no evidence of an association of airflow obstruction with use of solid fuels (ORmen=1.00, 95%CI 0.57-1.76; ORwomen=1.00, 95%CI 0.76-1.32). Overall, we found no association of spirometric restriction, chronic cough or chronic phlegm with the use of solid fuels. However, we found that chronic phlegm was more likely to be reported among female never smokers and those who had been exposed for ≥20 years. Airflow obstruction assessed from post-bronchodilator spirometry was not associated with use of solid fuels for cooking or heating.

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

    PubMed

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

    2016-09-01

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

  8. Chronic Airflow Obstruction in a Black African Population: Results of BOLD Study, Ile-Ife, Nigeria.

    PubMed

    Obaseki, Daniel O; Erhabor, Gregory E; Gnatiuc, Louisa; Adewole, Olufemi O; Buist, Sonia A; Burney, Peter G

    2016-01-01

    Global estimates suggest that Chronic Obstructive Pulmonary Disease (COPD) is emerging as a leading cause of death in developing countries but there are few spirometry-based general population data on its prevalence and risk factors in sub-Saharan Africa. We used the Burden of Obstructive Lung Disease (BOLD) protocol to select a representative sample of adults aged 40 years and above in Ile-Ife, Nigeria. All the participants underwent spirometry and provided information on smoking history, biomass and occupational exposures as well as diagnosed respiratory diseases and symptoms. Chronic Airflow Obstruction (CAO) was defined as the ratio of post-bronchodilator (BD) one second Forced Expiratory Volume (FEV1) to Forced Vital Capacity (FVC) below the lower limit of normal (LLN) of the population distribution for FEV1/FVC. The overall prevalence of obstruction (post-BD FEV1/FVC < LLN) was 7.7% (2.7% above LLN) using Global Lung Function Initiative (GLI) equations. It was associated with few respiratory symptoms; 0.3% reported a previous doctor-diagnosed chronic bronchitis, emphysema or COPD. Independent predictors included a lack of education (OR 2.5, 95% CI: 1.0, 6.4) and a diagnosis of either TB (OR 23.4, 95% CI: 2.0, 278.6) or asthma (OR 35.4, 95%CI: 4.9, 255.8). There was no association with the use of firewood or coal for cooking or heating. The vast majority of this population (89%) are never smokers. We conclude that the prevalence of CAO is low in Ile-Ife, Nigeria and unrelated to biomass exposure. The key independent predictors are poor education, and previous diagnosis of tuberculosis or asthma.

  9. Graph network analysis of immediate motor-learning induced changes in resting state BOLD.

    PubMed

    Sami, S; Miall, R C

    2013-01-01

    Recent studies have demonstrated that following learning tasks, changes in the resting state activity of the brain shape regional connections in functionally specific circuits. Here we expand on these findings by comparing changes induced in the resting state immediately following four motor tasks. Two groups of participants performed a visuo-motor joystick task with one group adapting to a transformed relationship between joystick and cursor. Two other groups were trained in either explicit or implicit procedural sequence learning. Resting state BOLD data were collected immediately before and after the tasks. We then used graph theory-based approaches that include statistical measures of functional integration and segregation to characterize changes in biologically plausible brain connectivity networks within each group. Our results demonstrate that motor learning reorganizes resting brain networks with an increase in local information transfer, as indicated by local efficiency measures that affect the brain's small world network architecture. This was particularly apparent when comparing two distinct forms of explicit motor learning: procedural learning and the joystick learning task. Both groups showed notable increases in local efficiency. However, a change in local efficiency in the inferior frontal and cerebellar regions also distinguishes between the two learning tasks. Additional graph analytic measures on the "non-learning" visuo-motor performance task revealed reversed topological patterns in comparison with the three learning tasks. These findings underscore the utility of graph-based network analysis as a novel means to compare both regional and global changes in functional brain connectivity in the resting state following motor learning tasks.

  10. Altitude and COPD prevalence: analysis of the PREPOCOL-PLATINO-BOLD-EPI-SCAN study.

    PubMed

    Horner, Andreas; Soriano, Joan B; Puhan, Milo A; Studnicka, Michael; Kaiser, Bernhard; Vanfleteren, Lowie E G W; Gnatiuc, Louisa; Burney, Peter; Miravitlles, Marc; García-Rio, Francisco; Ancochea, Julio; Menezes, Ana M; Perez-Padilla, Rogelio; Montes de Oca, Maria; Torres-Duque, Carlos A; Caballero, Andres; González-García, Mauricio; Buist, Sonia; Flamm, Maria; Lamprecht, Bernd

    2017-08-23

    COPD prevalence is highly variable and geographical altitude has been linked to it, yet with conflicting results. We aimed to investigate this association, considering well known risk factors. A pooled analysis of individual data from the PREPOCOL-PLATINO-BOLD-EPI-SCAN studies was used to disentangle the population effect of geographical altitude on COPD prevalence. Post-bronchodilator FEV1/FVC below the lower limit of normal defined airflow limitation consistent with COPD. High altitude was defined as >1500 m above sea level. Undiagnosed COPD was considered when participants had airflow limitation but did not report a prior diagnosis of COPD. Among 30,874 participants aged 56.1 ± 11.3 years from 44 sites worldwide, 55.8% were women, 49.6% never-smokers, and 12.9% (3978 subjects) were residing above 1500 m. COPD prevalence was significantly lower in participants living at high altitude with a prevalence of 8.5% compared to 9.9%, respectively (p < 0.005). However, known risk factors were significantly less frequent at high altitude. Hence, in the adjusted multivariate analysis, altitude itself had no significant influence on COPD prevalence. Living at high altitude, however, was associated with a significantly increased risk of undiagnosed COPD. Furthermore, subjects with airflow limitation living at high altitude reported significantly less respiratory symptoms compared to subjects residing at lower altitude. Living at high altitude is not associated with a difference in COPD prevalence after accounting for individual risk factors. However, high altitude itself was associated with an increased risk of undiagnosed COPD.

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

    PubMed

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

    2013-09-01

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

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

    PubMed Central

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

    2013-01-01

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

  13. Context Matters: Multiple Novelty Tests Reveal Different Aspects of Shyness-Boldness in Farmed American Mink (Neovison vison)

    PubMed Central

    Noer, Christina Lehmkuhl; Needham, Esther Kjær; Wiese, Ann-Sophie; Balsby, Thorsten Johannes Skovbjerg; Dabelsteen, Torben

    2015-01-01

    Animal personality research is receiving increasing interest from related fields, such as evolutionary personality psychology. By merging the conceptual understanding of personality, the contributions to both fields of research may be enhanced. In this study, we investigate animal personality based on the definition of personality traits as underlying dispositional factors, which are not directly measurable, but which predispose individuals to react through different behavioural patterns. We investigated the shyness-boldness continuum reflected in the consistency of inter-individual variation in behavioural responses towards novelty in 47 farmed American mink (Neovison vison), which were raised in identical housing conditions. Different stages of approach behaviour towards novelty, and how these related within and across contexts, were explored. Our experimental design contained four tests: two novel object tests (non-social contexts) and two novel animated stimuli tests (social contexts). Our results showed consistency in shyness measures across multiple tests, indicating the existence of personality in farmed American mink. It was found that consistency in shyness measures differs across non-social and social contexts, as well as across the various stages in the approach towards novel objects, revealing that different aspects of shyness exist in the farmed American mink. To our knowledge this is the first study to reveal aspects of the shyness-boldness continuum in the American mink. Since the mink were raised in identical housing conditions, inherited factors may have been important in shaping the consistent inter-individual variation. Body weight and sex had no effect on the personality of the mink. Altogether, our results suggest that the shyness-boldness continuum cannot be explained by a simple underlying dispositional factor, but instead encompasses a broader term of hesitating behaviour that might comprise several different personality traits. PMID

  14. Context Matters: Multiple Novelty Tests Reveal Different Aspects of Shyness-Boldness in Farmed American Mink (Neovison vison).

    PubMed

    Noer, Christina Lehmkuhl; Needham, Esther Kjær; Wiese, Ann-Sophie; Balsby, Thorsten Johannes Skovbjerg; Dabelsteen, Torben

    2015-01-01

    Animal personality research is receiving increasing interest from related fields, such as evolutionary personality psychology. By merging the conceptual understanding of personality, the contributions to both fields of research may be enhanced. In this study, we investigate animal personality based on the definition of personality traits as underlying dispositional factors, which are not directly measurable, but which predispose individuals to react through different behavioural patterns. We investigated the shyness-boldness continuum reflected in the consistency of inter-individual variation in behavioural responses towards novelty in 47 farmed American mink (Neovison vison), which were raised in identical housing conditions. Different stages of approach behaviour towards novelty, and how these related within and across contexts, were explored. Our experimental design contained four tests: two novel object tests (non-social contexts) and two novel animated stimuli tests (social contexts). Our results showed consistency in shyness measures across multiple tests, indicating the existence of personality in farmed American mink. It was found that consistency in shyness measures differs across non-social and social contexts, as well as across the various stages in the approach towards novel objects, revealing that different aspects of shyness exist in the farmed American mink. To our knowledge this is the first study to reveal aspects of the shyness-boldness continuum in the American mink. Since the mink were raised in identical housing conditions, inherited factors may have been important in shaping the consistent inter-individual variation. Body weight and sex had no effect on the personality of the mink. Altogether, our results suggest that the shyness-boldness continuum cannot be explained by a simple underlying dispositional factor, but instead encompasses a broader term of hesitating behaviour that might comprise several different personality traits.

  15. Psychotic symptoms influence the development of anterior cingulate BOLD variability in 22q11.2 deletion syndrome.

    PubMed

    Zöller, Daniela; Padula, Maria Carmela; Sandini, Corrado; Schneider, Maude; Scariati, Elisa; Van De Ville, Dimitri; Schaer, Marie; Eliez, Stephan

    2017-08-10

    Chromosome 22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental disorder associated with a broad phenotype of clinical, cognitive and psychiatric features. Due to the very high prevalence of schizophrenia (30-40%), the investigation of psychotic symptoms in the syndrome is promising to reveal biomarkers for the development of psychosis, also in the general population. Since schizophrenia is seen as a disorder of the dynamic interactions between brain networks, we here investigated brain dynamics, assessed by the variability of blood oxygenation level dependent (BOLD) signals, in patients with psychotic symptoms. We included 28 patients with 22q11DS presenting higher positive psychotic symptoms, 29 patients with lower positive psychotic symptoms and 69 healthy controls between 10 and 30years old. To overcome limitations of mass-univariate approaches, we employed multivariate analysis, namely partial least squares correlation, combined with proper statistical testing, to analyze resting-state BOLD signal variability and its age-relationship in patients with positive psychotic symptoms. Our results revealed a missing positive age-relationship in the dorsal anterior cingulate cortex (dACC) in patients with higher positive psychotic symptoms, leading to globally lower variability in the dACC in those patients. Patients without positive psychotic symptoms and healthy controls had the same developmental trajectory in this region. Alterations of brain structure and function in the ACC have been previously reported in 22q11DS and linked to psychotic symptoms. The present results support the implication of this region in the development of psychotic symptoms and suggest aberrant BOLD signal variability development as a potential biomarker for psychosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. BOLD-based Techniques for Quantifying Brain Hemodynamic and Metabolic Properties – Theoretical Models and Experimental Approaches

    PubMed Central

    Yablonskiy, Dmitriy A.; Sukstanskii, Alexander L.; He, Xiang

    2012-01-01

    Quantitative evaluation of brain hemodynamics and metabolism, particularly the relationship between brain function and oxygen utilization, is important for understanding normal human brain operation as well as pathophysiology of neurological disorders. It can also be of great importance for evaluation of hypoxia within tumors of the brain and other organs. A fundamental discovery by Ogawa and co-workers of the BOLD (Blood Oxygenation Level Dependent) contrast opened a possibility to use this effect to study brain hemodynamic and metabolic properties by means of MRI measurements. Such measurements require developing theoretical models connecting MRI signal to brain structure and functioning and designing experimental techniques allowing MR measurements of salient features of theoretical models. In our review we discuss several such theoretical models and experimental methods for quantification brain hemodynamic and metabolic properties. Our review aims mostly at methods for measuring oxygen extraction fraction, OEF, based on measuring blood oxygenation level. Combining measurement of OEF with measurement of CBF allows evaluation of oxygen consumption, CMRO2. We first consider in detail magnetic properties of blood – magnetic susceptibility, MR relaxation and theoretical models of intravascular contribution to MR signal under different experimental conditions. Then, we describe a “through-space” effect – the influence of inhomogeneous magnetic fields, created in the extravascular space by intravascular deoxygenated blood, on the MR signal formation. Further we describe several experimental techniques taking advantage of these theoretical models. Some of these techniques - MR susceptometry, and T2-based quantification of oxygen OEF – utilize intravascular MR signal. Another technique – qBOLD – evaluates OEF by making use of through-space effects. In this review we targeted both scientists just entering the MR field and more experienced MR researchers

  17. Towards prognostic biomarkers from BOLD fluctuations to differentiate a first epileptic seizure from new-onset epilepsy.

    PubMed

    Gupta, Lalit; Janssens, Rick; Vlooswijk, Mariëlle C G; Rouhl, Rob P W; de Louw, Anton; Aldenkamp, Albert P; Ulman, Shrutin; Besseling, René M H; Hofman, Paul A M; van Kranen-Mastenbroek, Vivianne H; Hilkman, Danny M; Jansen, Jacobus F A; Backes, Walter H

    2017-03-01

    The diagnosis of epilepsy cannot be reliably made prior to a patient's second seizure in most cases. Therefore, adequate diagnostic tools are needed to differentiate subjects with a first seizure from those with a seizure preceding the onset of epilepsy. The objective was to explore spontaneous blood oxygen level-dependent (BOLD) fluctuations in subjects with a first-ever seizure and patients with new-onset epilepsy (NOE), and to find characteristic biomarkers for seizure recurrence after the first seizure. We examined 17 first-seizure subjects, 19 patients with new-onset epilepsy (NOE), and 18 healthy controls. All subjects underwent clinical investigation and received electroencephalography and resting-state functional magnetic resonance imaging (MRI). The BOLD time series were analyzed in terms of regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFFs). We found significantly stronger amplitudes (higher fALFFs) in patients with NOE relative to first-seizure subjects and healthy controls. The frequency range of 73-198 mHz (slow-3 subband) appeared most useful for discriminating patients with NOE from first-seizure subjects. The ReHo measure did not show any significant differences. The fALFF appears to be a noninvasive measure that characterizes spontaneous BOLD fluctuations and shows stronger amplitudes in the slow-3 subband of patients with NOE relative first-seizure subjects and healthy controls. A larger study population with follow-up is required to determine whether fALFF holds promise as a potential biomarker for identifying subjects at increased risk to develop epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  18. BOLD signal in insula is differentially related to cardiac function during compassion meditation in experts vs. novices.

    PubMed

    Lutz, Antoine; Greischar, Lawrence L; Perlman, David M; Davidson, Richard J

    2009-09-01

    The brain and the cardiovascular system influence each other during the processing of emotion. The study of the interactions of these systems during emotion regulation has been limited in human functional neuroimaging, despite its potential importance for physical health. We have previously reported that mental expertise in cultivation of compassion alters the activation of circuits linked with empathy and theory of mind in response to emotional stimuli. Guided by the finding that heart rate increases more during blocks of compassion meditation than neutral states, especially for experts, we examined the interaction between state (compassion vs. neutral) and group (novice, expert) on the relation between heart rate and BOLD signal during presentation of emotional sounds presented during each state. Our findings revealed that BOLD signal in the right middle insula showed a significant association with heart rate (HR) across state and group. This association was stronger in the left middle/posterior insula when experts were compared to novices. The positive coupling of HR and BOLD was higher within the compassion state than within the neutral state in the dorsal anterior cingulate cortex for both groups, underlining the role of this region in the modulation of bodily arousal states. This state effect was stronger for experts than novices in somatosensory cortices and the right inferior parietal lobule (group by state interaction). These data confirm that compassion enhances the emotional and somatosensory brain representations of others' emotions, and that this effect is modulated by expertise. Future studies are needed to further investigate the impact of compassion training on these circuits.

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

    PubMed

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

    2013-01-01

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

  20. Streamlining the use of BOLD specimen data to record species distributions: a case study with ten Nearctic species of Microgastrinae (Hymenoptera: Braconidae)

    PubMed Central

    Penev, Lyubomir; Ratnasingham, Sujeevan; Smith, M. Alex; Sones, Jayme; Telfer, Angela; deWaard, Jeremy R.; Hebert, Paul D. N.

    2014-01-01

    Abstract The Barcode of Life Data Systems (BOLD) is designed to support the generation and application of DNA barcode data, but it also provides a unique source of data with potential for many research uses. This paper explores the streamlining of BOLD specimen data to record species distributions – and its fast publication using the Biodiversity Data Journal (BDJ), and its authoring platform, the Pensoft Writing Tool (PWT). We selected a sample of 630 specimens and 10 species of a highly diverse group of parasitoid wasps (Hymenoptera: Braconidae, Microgastrinae) from the Nearctic region and used the information in BOLD to uncover a significant number of new records (of locality, provinces, territories and states). By converting specimen information (such as locality, collection date, collector, voucher depository) from the BOLD platform to the Excel template provided by the PWT, it is possible to quickly upload and generate long lists of "Material Examined" for papers discussing taxonomy, ecology and/or new distribution records of species. For the vast majority of publications including DNA barcodes, the generation and publication of ancillary data associated with the barcoded material is seldom highlighted and often disregarded, and the analysis of those data sets to uncover new distribution patterns of species has rarely been explored, even though many BOLD records represent new and/or significant discoveries. The introduction of journals specializing in – and streamlining – the release of these datasets, such as the BDJ, should facilitate thorough analysis of these records, as shown in this paper. PMID:25473326

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

    PubMed

    Fellner, Marie-Christin; Volberg, Gregor; Wimber, Maria; Goldhacker, Markus; Greenlee, Mark W; Hanslmayr, Simon

    2016-01-01

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

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

    PubMed Central

    Volberg, Gregor; Goldhacker, Markus; Hanslmayr, Simon

    2016-01-01

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

  3. Neural Mechanisms of Age-Related Slowing: The ΔCBF/ΔCMRO2 Ratio Mediates Age-Differences in BOLD Signal and Human Performance

    PubMed Central

    Hutchison, Joanna L.; Lu, Hanzhang; Rypma, Bart

    2013-01-01

    The precise mechanisms that give rise to the blood-oxygen-level-dependent (BOLD) activation differences that accompany age-related cognitive slowing remain fundamentally unknown. We sought to isolate the origin of age-related BOLD changes by comparing blood-flow and oxygen-metabolic constituents of the BOLD response using dual-echo arterial spin labeling during visual stimulation and CO2 ingestion. We hypothesized, and our results confirmed, that age-related changes in the ratio of fractional cerebral blood flow to fractional cerebral metabolic rate of oxygen consumption (ΔCBF/ΔCMRO2) lead to the BOLD changes that are observed in older adults. ΔCBF/ΔCMRO2 was also significantly related to performance, suggesting that age-related cognitive slowing results from neural cell assemblies that operate less efficiently, requiring greater oxygen metabolism that is not matched by blood-flow changes relative to younger adults. Age-related changes in ΔCBF/ΔCMRO2 are sufficient to explain variations in BOLD responding and performance cited throughout the literature, assuming no bias based on physiological baseline CMRO2. PMID:22879349

  4. Fractal Analysis of Brain Blood Oxygenation Level Dependent (BOLD) Signals from Children with Mild Traumatic Brain Injury (mTBI)

    PubMed Central

    Dona, Olga; DeMatteo, Carol; Connolly, John F.

    2017-01-01

    Background 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. Methods 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. Results and Conclusions 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

  5. SU-D-207A-03: Potential Role of BOLD MRI in Discrimination of Aggressive Tumor Habitat in Prostate Cancer

    SciTech Connect

    Ford, J; Lopez, C; Tschudi, Y; Breto, A; Padgett, K; Pollack, A; Stoyanova, R

    2016-06-15

    Purpose: To determine whether blood oxygenation level dependent (BOLD) MRI signal measured in prostate cancer patients, in addition to quantitative diffusion and perfusion parameters from multiparametric (mp)MRI exams, can help discriminate aggressive and/or radioresistant lesions. Methods: Several ongoing clinical trials in our institution require mpMRI exam to determine eligibility (presence of identifiable tumor lesion on mpMRI) and prostate volumes for dose escalation. Upon consent, patients undergo fiducial markers placement and a T2*-weighted imaging at the time of CT sim to facilitate the fusion. In a retrospective analysis eleven clinical trial patients were identified who had undergone mpMRI on GE 3T magnet, followed by T2*-weighted imaging (time-period mean±SD = 48±20 days) using a consistent protocol (gradient echo, TR/TE=30/11.8ms, flip angle=12, matrix=256×256×75, voxel size=1.25×1.25×2.5mm). ROIs for prostate tumor lesions were automatically determined using ADC threshold ≤1200 µm2/s. Although the MR protocol was not intended for BOLD analysis, we utilized the T2*-weighted signal normalized to that in nearby muscle; likewise, T2-weighted lesion signal was normalized to muscle, following rigid registration of the T2 to T2* images. The ratio of these normalized signals, T2*/T2, is a measure of BOLD effect in the prostate tumors. Perfusion parameters (Ktrans, ve, kep) were also calculated. Results: T2*/T2 (mean±SE) was found to be substantially lower for Gleason score (GS) 8&9 (0.82±0.04) compared to GS 7 (1.08±0.07). A k-means cluster analysis of T2*/T2 versus kep = Ktrans/ve revealed two distinct clusters, one with higher T2*/T2 and lower kep, containing only GS 7 lesions, and another with lower T2*/T2 and higher kep, associated with tumor aggressiveness. This latter cluster contained all GS 8&9 lesions, as well as some GS 7. Conclusion: BOLD MRI, in addition to ADC and kep, may play a role (perhaps orthogonal to Gleason score) in

  6. Fractal Analysis of Brain Blood Oxygenation Level Dependent (BOLD) Signals from Children with Mild Traumatic Brain Injury (mTBI).

    PubMed

    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

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

    PubMed

    An, Dongmei; Dubeau, François; Gotman, Jean

    2015-03-01

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

  8. Formative research and development of innovative tools for "Better Outcomes in Labour Difficulty" (BOLD): study protocol.

    PubMed

    Bohren, Meghan A; Oladapo, Olufemi T; Tunçalp, Özge; Wendland, Melanie; Vogel, Joshua P; Tikkanen, Mari; Fawole, Bukola; Mugerwa, Kidza; Souza, João Paulo; Bahl, Rajiv; Gülmezoglu, A Metin

    2015-05-26

    Most complications during labour and childbirth could be averted with timely interventions by skilled healthcare providers. Yet, the quality and outcomes of childbirth care remains suboptimal in many health facilities in low-resource settings. To accelerate the reduction of childbirth-related maternal, fetal and newborn mortality and morbidity, the World Health Organization has initiated the "Better Outcomes in Labour Difficulty" (BOLD) project to address weaknesses in labour care processes and better connect health systems and communities. The project seeks to develop a "Simplified, Effective, Labour Monitoring-to-Action" tool (SELMA) to assist healthcare providers to monitor labour and take decisive actions more efficiently; and by developing an innovative set of service prototypes and/or tools termed "Passport to Safer Birth", designed with communities and healthcare providers, to promote access to quality care for women during childbirth. This protocol describes the formative research activities to support the development of these tools. We will employ qualitative research and service design methodologies in eight health facilities and their catchment communities in Nigeria and Uganda. In the health facilities, focus group discussions (FGD) and in-depth interviews (IDI) will be conducted among different cadres of healthcare providers and facility administrators. In the communities, FGDs and IDIs will be conducted among women who have delivered in a health facility. We will use service design methods to explore women's journey to access and receive childbirth care in order to innovate and design services around the needs and expectations of women, within the context of the health system. This formative research will serve several roles. First, it will provide an in-depth understanding of healthcare providers and health system issues to be accounted for in the final design and implementation of SELMA. Second, it will help to identify key moments ("touch points

  9. Multi-echo EPI of human fear conditioning reveals improved BOLD detection in ventromedial prefrontal cortex.

    PubMed

    Fernandez, Brice; Leuchs, Laura; Sämann, Philipp G; Czisch, Michael; Spoormaker, Victor I

    2017-08-01

    Standard T2(*) weighted functional magnetic resonance imaging (fMRI) performed with echo-planar imaging (EPI) suffers from signal loss in the ventromedial prefrontal cortex (vmPFC) due to macroscopic field inhomogeneity. However, this region is of special interest to affective neuroscience and psychiatry. The Multi-echo EPI (MEPI) approach has several advantages over EPI but its performance against EPI in the vmPFC has not yet been examined in a study with sufficient statistical power using a task specifically eliciting activity in this region. We used a fear conditioning task with MEPI to compare the performance of MEPI and EPI in vmPFC and control regions in 32 healthy young subjects. We analyzed activity associated with short (12ms), standard (29ms) and long (46ms) echo times, and a voxel-wise combination of these three echo times. Behavioral data revealed successful differentiation of the conditioned versus safety stimulus; activity in the vmPFC was shown by the contrast "safety stimulus > conditioned stimulus" as in previous research and proved significantly stronger with the combined MEPI than standard single-echo EPI. Then, we aimed to demonstrate that the additional cluster extent (ventral extension) detected in the vmPFC with MEPI reflects activation in a relevant cluster (i.e., not just non-neuronal noise). To do this, we used resting state data from the same subjects to show that the time-course of this region was both connected to bilateral amygdala and the default mode network. Overall, we demonstrate that MEPI (by means of the weighted sum combination approach) outperforms standard EPI in vmPFC; MEPI performs always at least as good as the best echo time for a given brain region but provides all necessary echo times for an optimal BOLD sensitivity for the whole brain. This is relevant for affective neuroscience and psychiatry given the critical role of the vmPFC in emotion regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The value of blood oxygenation level-dependent (BOLD) MR imaging in differentiation of renal solid mass and grading of renal cell carcinoma (RCC): analysis based on the largest cross-sectional area versus the entire whole tumour.

    PubMed

    Wu, Guang-Yu; Suo, Shi-Teng; Lu, Qing; Zhang, Jin; Zhu, Wan-Qiu; Xu, Jian-Rong

    2015-01-01

    To study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade. Ninety-five patients with 139 renal masses (93 malignant and 46 benign) who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*largest) and from the whole tumour (R2*whole). Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis. The intra-observer agreement was very good for R2*largest and R2*whole (all > 0.8). The inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79) was good and was significantly improved compared with the R2*largest (0.61, 95% confidence interval: 0.52~0.68), as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*whole (AUC=0.79/0.78[observer1/observer2]) and R2*largest (AUC=0.75[observer1]) was good and significantly higher (p=0.01 for R2*largest[observer2] vs R2*whole[observer2], p<0.01 for R2*whole[observer1] vs R2*largest[observer2]) than R2*largest for observer 2 (AUC=0.64). For the grading of clear-cell RCC, both R2*whole and R2*largest were good (all > 0.7) and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1]). BOLD MRI could provide a feasible parameter

  11. Collegiality and careerism trump critical questions and bold new ideas: a student's perspective and solution. The structure of scientific funding limits bold new ideas.

    PubMed

    Nicholson, Joshua M

    2012-06-01

    Funding agencies (and journals) seem to be discriminating against ideas that are contrary to the mainstream, leading to leading to the preferential funding of predictable and safe research over radically new ideas. To remedy this problem a restructuring of the scientific funding system is needed, e.g. by utilizing laymen--together with scientists--to evaluate grant proposals. Copyright © 2012 WILEY Periodicals, Inc.

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2007-06-01

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

  14. Boldness in a deep sea hermit crab to simulated tactile predator attacks is unaffected by ocean acidification

    NASA Astrophysics Data System (ADS)

    Kim, Tae Won; Barry, James P.

    2016-09-01

    Despite rapidly growing interest in the effects of ocean acidification on marine animals, the ability of deep-sea animals to acclimate or adapt to reduced pH conditions has received little attention. Deep-sea species are generally thought to be less tolerant of environmental variation than shallow-living species because they inhabit relatively stable conditions for nearly all environmental parameters. To explore whether deep-sea hermit crabs ( Pagurus tanneri) can acclimate to ocean acidification over several weeks, we compared behavioral "boldness," measured as time taken to re-emerge from shells after a simulated predatory attack by a toy octopus, under ambient (pH ˜7.6) and expected future (pH ˜7.1) conditions. The boldness measure for crab behavioral responses did not differ between different pH treatments, suggesting that future deep-sea acidification would not influence anti-predatory behavior. However, we did not examine the effects of olfactory cues released by predators that may affect hermit crab behavior and could be influenced by changes in the ocean carbonate system driven by increasing CO2 levels.

  15. A behavioral view on chimpanzee personality: exploration tendency, persistence, boldness, and tool-orientation measured with group experiments.

    PubMed

    Massen, Jorg J M; Antonides, Alexandra; Arnold, Anne-Marie K; Bionda, Thomas; Koski, Sonja E

    2013-09-01

    Human and nonhuman animals show personality: temporal and contextual consistency in behavior patterns that vary among individuals. In contrast to most other species, personality of chimpanzees, Pan troglodytes, has mainly been studied with non-behavioral methods. We examined boldness, exploration tendency, persistence and tool-orientation in 29 captive chimpanzees using repeated experiments conducted in an ecologically valid social setting. High temporal repeatability and contextual consistency in all these traits indicated they reflected personality. In addition, Principal Component Analysis revealed two independent syndromes, labeled exploration-persistence and boldness. We found no sex or rank differences in the trait scores, but the scores declined with age. Nonetheless, there was considerable inter-individual variation within age-classes, suggesting that behavior was not merely determined by age but also by dispositional effects. In conclusion, our study complements earlier rating studies and adds new traits to the chimpanzee personality, thereby supporting the existence of multiple personality traits among chimpanzees. We stress the importance of ecologically valid behavioral research to assess multiple personality traits and their association, as it allows inclusion of ape studies in the comparison of personality structures across species studied behaviorally, and furthers our attempts to unravel the causes and consequences of animal personality.

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2016-01-01

    The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these “task-negative” BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process. PMID:25385710

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

    PubMed Central

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

    2015-01-01

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

  20. Individual variation in behavioural plasticity: direct and indirect effects of boldness, exploration and sociability on habituation to predators in lizards

    PubMed Central

    Rodríguez-Prieto, Iñaki; Martín, José; Fernández-Juricic, Esteban

    2011-01-01

    Little is known about the factors causing variation in behavioural plasticity and the interplay between personality and plasticity. Habituation to predators is a special case of behavioural plasticity. We investigated the direct and indirect effects of boldness, exploration and sociability traits on the habituation ability of Iberian wall lizards, considering exposure and sex effects. Individual boldness was consistent across several non-habituation contexts, but it did not significantly affect habituation. Exploration had a strong direct effect on habituation, with more exploratory individuals being able to habituate faster than less exploratory ones, probably because of their ability to assess risk better. Individual variation in habituation was also affected by sociability, but this was an indirect effect mediated by exposure to the predator. Less social individuals avoided refuges with conspecific cues, increasing exposure to the predator and eventually habituation. Finally, the direct effects of sex (females habituated faster than males) were opposite to its indirect effects through exposure. We conclude that risk assessment, instead of the proactivity–reactivity gradient usually considered in the literature, can affect behavioural plasticity through complex interactions between direct and indirect effects, including exploratory behaviour, degree of exposure to the predator and sex, which represent novel mechanisms generating inter-individual variation in plasticity. PMID:20685703

  1. Oxygenation in cervical cancer and normal uterine cervix assessed using blood oxygenation level-dependent (BOLD) MRI at 3T.

    PubMed

    Hallac, Rami R; Ding, Yao; Yuan, Qing; McColl, Roderick W; Lea, Jayanthi; Sims, Robert D; Weatherall, Paul T; Mason, Ralph P

    2012-12-01

    Hypoxia is reported to be a biomarker for poor prognosis in cervical cancer. However, a practical noninvasive method is needed for the routine clinical evaluation of tumor hypoxia. This study examined the potential use of blood oxygenation level-dependent (BOLD) contrast MRI as a noninvasive technique to assess tumor vascular oxygenation at 3T. Following Institutional Review Board-approved informed consent and in compliance with the Health Insurance Portability and Accountability Act, successful results were achieved in nine patients with locally advanced cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA] and three normal volunteers. In the first four patients, dynamic T₂*-weighted MRI was performed in the transaxial plane using a multi-shot echo planar imaging sequence whilst patients breathed room air followed by oxygen (15 dm³/min). Later, a multi-echo gradient echo examination was added to provide quantitative R₂* measurements. The baseline T₂*-weighted signal intensity was quite stable, but increased to various extents in tumors on initiation of oxygen breathing. The signal in normal uterus increased significantly, whereas that in the iliacus muscle did not change. R₂* responded significantly in healthy uterus, cervix and eight cervical tumors. This preliminary study demonstrates that BOLD MRI of cervical cancer at 3T is feasible. However, more patients must be evaluated and followed clinically before any prognostic value can be determined. Copyright © 2012 John Wiley & Sons, Ltd.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Mikkelsen, Kaare B; Lund, Torben E

    2013-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  5. The fMRI BOLD response to unisensory and m