Blood Oxygenation Level-dependent Signal Changes Research Articles

Oxygen-induced frequency shifts in hyperoxia: a significant component of BOLD signal.

In comparison to the well-documented significance of intravascular deoxyhemoglobin (deoxyHgb), the effects of dissolved oxygen on the blood-oxygen-level-dependent (BOLD) signal have not been widely reported. Based on the fact that the prolonged inspiration of high oxygen fraction gas can result in up to a sixfold increase of the baseline tissue oxygenation, the current study focused on the influence of dissolved oxygen on the BOLD signal during hyperoxia. As results, our in vitro study revealed that the r1 and r2 (relaxivities) of the oxygen-treated serum were 0.22 mM(-1) · s(-1) and 0.19 mM(-1) · s(-1) , respectively. In an in vivo experiment, hyperoxic respiration induced negative BOLD contrast (i.e. signal decrease) in 18-42% of measured brain regions, voxels with accompanying significant decreases in both the T(*)2 (-12.1% to -19.4%) and T1 (-5.8% to -3.3%) relaxation times. In contrast, the T(*)2 relaxation time significantly increased (11.2% to 14.0%) for the voxels displaying positive BOLD contrast (in 41-50% of the measured brain), which reflected a hyperoxygenation-induced reduction in tissue deoxyHgb concentration. These data imply that hyperoxia-driven BOLD signal changes are primarily determined by the counteracting effects of extravascular oxygen and intravascular deoxyHgb. Oxygen-induced magnetic susceptibility was further demonstrated by the study of 1 min hypoxia, which induced BOLD signal changes opposite to those under hyperoxia. Vasoconstriction was more common in voxels with negative BOLD contrast than in voxels with positive contrast (% change of blood volume, -9.8% to -12.8% versus 2.0% to 2.2%), which further suggests that negative BOLD contrast is mainly evoked by an increase in extravascular oxygen concentration. Conclusively, frequency shifts, which are induced by the accumulation of oxygen molecules and associated magnetic field inhomogeneity, are a significant source of the negative BOLD contrast during hyperoxia.

Spotlight on the April 29 Issue

The RESTORE trial investigated the effects of stopping natalizumab treatment in patients with MS. MRI disease activity recurred starting at 12 weeks while relapses were reported as early as 4 weeks. Results suggest that planned natalizumab interruption is unlikely to be a useful strategy to reduce natalizumab risks. See p. 1491; Editorial, p. 1484 Simultaneous EEG-fMRI recordings were performed in 13 children with myoclonic astatic epilepsy. Individual generalized spike and wave discharges associated with blood oxygenation level–dependent signal changes were analyzed in every patient. The results demonstrated that somatosensory cortex, putamen, and …

Dual echo vessel-encoded ASL for simultaneous BOLD and CBF reactivity assessment in patients with ischemic cerebrovascular disease.

Blood oxygenation level-dependent (BOLD)-weighted and vessel-encoded arterial spin labeling (VE-ASL) MRI provide complementary information and can be used in sequence to gauge hemodynamic contributions to cerebrovascular reactivity. Here, cerebrovascular reactivity is assessed using dual echo VE-ASL MRI to understand how VE labeling preparations influence BOLD and ASL contrast in flow-limited and healthy perfusion territories. Patients (n = 12; age = 55 +/- 14 years; 6F/6M) presenting with ischemic steno-occlusive cerebrovascular disease underwent 3.0T angiographic imaging, T1 -weighted structural, and planning-free dual echo hypercarbic hyperoxic (i.e., carbogen) VE-ASL MRI. Vasculopathy extent, timecourses, and cerebrovascular reactivity (signal change and Z-statistic) for different VE-ASL images were contrasted across flow territories and Bonferroni-corrected P-values reported. BOLD cerebrovascular reactivity (i.e., long-TE VE-ASL) Z-statistics were similarly sensitive to asymmetric disease (P ≤ 0.002) regardless of labeling scenario. Cerebral blood flow reactivity correlated significantly with BOLD reactivity (Z-statistic). However, BOLD signal changes did not differ significantly between labeling scenarios (P > 0.003) or across territories (P > 0.002), indicating BOLD signal changes in response to carbogen offer low sensitivity to lateralizing disease. Dual echo VE-ASL can provide simultaneous cerebral blood flow and qualitative BOLD contrast consistent with lateralizing disease severity in patients with asymmetric steno-occlusive disease. The methodological strengths and limitations of composite BOLD and VE-ASL measurements in the clinic are discussed.

Assessment of myocardial reactivity to controlled hypercapnia with free-breathing T2-prepared cardiac blood oxygen level-dependent MR imaging.

To examine whether controlled and tolerable levels of hypercapnia may be an alternative to adenosine, a routinely used coronary vasodilator, in healthy human subjects and animals. Human studies were approved by the institutional review board and were HIPAA compliant. Eighteen subjects had end-tidal partial pressure of carbon dioxide (PetCO2) increased by 10 mm Hg, and myocardial perfusion was monitored with myocardial blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. Animal studies were approved by the institutional animal care and use committee. Anesthetized canines with (n = 7) and without (n = 7) induced stenosis of the left anterior descending artery (LAD) underwent vasodilator challenges with hypercapnia and adenosine. LAD coronary blood flow velocity and free-breathing myocardial BOLD MR responses were measured at each intervention. Appropriate statistical tests were performed to evaluate measured quantitative changes in all parameters of interest in response to changes in partial pressure of carbon dioxide. Changes in myocardial BOLD MR signal were equivalent to reported changes with adenosine (11.2% ± 10.6 [hypercapnia, 10 mm Hg] vs 12% ± 12.3 [adenosine]; P = .75). In intact canines, there was a sigmoidal relationship between BOLD MR response and PetCO2 with most of the response occurring over a 10 mm Hg span. BOLD MR (17% ± 14 [hypercapnia] vs 14% ± 24 [adenosine]; P = .80) and coronary blood flow velocity (21% ± 16 [hypercapnia] vs 26% ± 27 [adenosine]; P > .99) responses were similar to that of adenosine infusion. BOLD MR signal changes in canines with LAD stenosis during hypercapnia and adenosine infusion were not different (1% ± 4 [hypercapnia] vs 6% ± 4 [adenosine]; P = .12). Free-breathing T2-prepared myocardial BOLD MR imaging showed that hypercapnia of 10 mm Hg may provide a cardiac hyperemic stimulus similar to adenosine.

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

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

Hemodynamic Response Function (HRF) in Epilepsy Patients with Hippocampal Sclerosis and Focal Cortical Dysplasia

Simultaneous recording of electroencephalography and functional magnetic resonance imaging (EEG-fMRI) has recently been applied for mapping the hemodynamic changes related to epileptic activity. The aim of this study is to compare the hemodynamic response function (HRF) to epileptic spikes in patients with focal cortical dysplasia (FCD) and those with hippocampal sclerosis (HS). In EEG-fMRI studies, the HRF represents the temporal evolution of blood oxygenation level-dependent signal changes. Several studies demonstrated that amplitude and latency of the HRF are variable in patients with epilepsy. However, the consistency of HRF parameters with underlying brain pathology is unknown. In this study, we examined 14 patients with FCD and 12 with unilateral HS selected from our EEG-fMRI database and compared the amplitude and latency of the HRF peak. We analyzed (1) HRFs in peak activation clusters, (2) HRFs in peak deactivation clusters, and (3) the maximum absolute responses within the EEG spike field, activation or deactivation. We found that the HRF peak amplitude in deactivation clusters was larger in the HS group than in the FCD when the deactivation occurred in default mode network (DMN) regions. This result suggests that spikes in patients with HS affect the DMN more strongly than those with FCD. However, if we focus on the maximum absolute t-value in the spike field, there is no significant difference between the two groups. The current study indicates that it is not necessary to use different HRF models for EEG-fMRI studies in patients with FCD and HS.

EEG-fMRI in myoclonic astatic epilepsy (Doose syndrome)

To identify neuronal networks underlying generalized spike and wave discharges (GSW) in myoclonic astatic epilepsy (MAE). Simultaneous EEG-fMRI recordings were performed in 13 children with MAE. Individual GSW-associated blood oxygenation level-dependent (BOLD) signal changes were analyzed in every patient. A group analysis was performed to determine common syndrome-specific hemodynamic changes across all patients. GSW were recorded in 11 patients, all showing GSW-associated BOLD signal changes. Activation was detected in the thalamus (all patients), premotor cortex (6 patients), and putamen (6 patients). Deactivation was found in the default mode areas (7 patients). The group analysis confirmed activations in the thalamus, premotor cortex, putamen, and cerebellum and deactivations in the default mode network. In addition to the thalamocortical network, which is commonly found in idiopathic generalized epilepsies, GSW in patients with MAE are characterized by BOLD signal changes in brain structures associated with motor function. The results are in line with animal studies demonstrating that somatosensory cortex, putamen, and cerebellum are involved in the generation of myoclonic seizures. The involvement of these structures might predispose to the typical seizure semiology of myoclonic jerks observed in MAE.

Distinct fine‐scale fMRI activation patterns of contra‐ and ipsilateral somatosensory areas 3b and 1 in humans

Inter-areal and ipsilateral cortical responses to tactile stimulation have not been well described in human S1 cortex. By taking advantage of the high signal-to-noise ratio at 7 T, we quantified blood oxygenation level dependent (BOLD) response patterns and time courses to tactile stimuli on individual distal finger pads at a fine spatial scale, and examined whether there are inter-areal (area 3b versus area 1) and interhemispheric response differences to unilateral tactile stimulation in healthy human subjects. We found that 2-Hz tactile stimulation of individual fingertips evoked detectable BOLD signal changes in both contralateral and ipsilateral area 3b and area 1. Contralateral digit activations were organized in an orderly somatotopic manner, and BOLD responses in area 3b were more digit selective than those in area 1. However, the area of cortex that was responsive to stimulation of a single digit (stimulus-response field) was similar across areas. In the ipsilateral hemisphere, response magnitudes in both areas 3b and 1 were significantly weaker than those of the contralateral hemisphere. Digit activations exhibited no clear somatotopic organizational pattern in either area 3b or area 1, yet digit selectivity was retained in area 1 but not in area 3b. The observation of distinct digit-selective responses of contralateral area 3b versus area 1 supports a higher order function of contralateral area 1 in spatial integration. In contrast, ipsilateral cortices may play a less discriminative role in the perception of unilateral tactile sensation in humans.

Gait-related brain activity in people with Parkinson disease with freezing of gait.

Approximately 50% of people with Parkinson disease experience freezing of gait, described as a transient inability to produce effective stepping. Complex gait tasks such as turning typically elicit freezing more commonly than simple gait tasks, such as forward walking. Despite the frequency of this debilitating and dangerous symptom, the brain mechanisms underlying freezing remain unclear. Gait imagery during functional magnetic resonance imaging permits investigation of brain activity associated with locomotion. We used this approach to better understand neural function during gait-like tasks in people with Parkinson disease who experience freezing- “FoG+” and people who do not experience freezing- ”FoG−“. Nine FoG+ and nine FoG− imagined complex gait tasks (turning, backward walking), simple gait tasks (forward walking), and quiet standing during measurements of blood oxygen level dependent (BOLD) signal. Changes in BOLD signal (i.e. beta weights) during imagined walking and imagined standing were analyzed across FoG+ and FoG− groups in locomotor brain regions including supplementary motor area, globus pallidus, putamen, mesencephalic locomotor region, and cerebellar locomotor region. Beta weights in locomotor regions did not differ for complex tasks compared to simple tasks in either group. Across imagined gait tasks, FoG+ demonstrated significantly lower beta weights in the right globus pallidus with respect to FoG−. FoG+ also showed trends toward lower beta weights in other right-hemisphere locomotor regions (supplementary motor area, mesencephalic locomotor region). Finally, during imagined stand, FoG+ exhibited lower beta weights in the cerebellar locomotor region with respect to FoG−. These data support previous results suggesting FoG+ exhibit dysfunction in a number of cortical and subcortical regions, possibly with asymmetric dysfunction towards the right hemisphere.

Modafinil augments brain activation associated with reward anticipation in the nucleus accumbens

The nucleus accumbens (NAc) works as a key brain structure of the reward system, in which reward-related neural activity is well correlated with dopamine release from mesolimbic dopaminergic neurons. Since modafinil can modulate dopaminergic transmission through re-uptake inhibition of dopamine, we investigated whether modafinil affects the reward-related brain activity in the NAc in healthy subjects. Twenty healthy participants underwent two series of functional magnetic resonance imaging while performing monetary incentive delay task in which they were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money, under modafinil or placebo condition. Blood oxygenation-level dependent (BOLD) activation signals during gain and loss anticipations were analyzed in the NAc as an a priori region of interest as well as the whole brain. Modafinil significantly changed subjective feelings toward positive ones. The activation of BOLD signals was observed during gain anticipation under the placebo and modafinil conditions in the left and bilateral NAc, respectively. The modafinil condition showed significantly higher BOLD signal change at the highest gain (+¥500) cue compared to the placebo condition. The present study showed that modafinil affects reward processing in the NAc in healthy subjects through enhancing more positive anticipation, and it may provide a basis for the use of this drug for treating anhedonia observed in psychiatric disorders.

Spatial correlation of hemodynamic changes related to interictal epileptic discharges with electric and magnetic source imaging

Blood oxygenation level-dependent (BOLD) signal changes at the time of interictal epileptic discharges (IEDs) identify their associated vascular/hemodynamic responses. BOLD activations and deactivations can be found within the epileptogenic zone but also at a distance. Source imaging identifies electric (ESI) and magnetic (MSI) sources of IEDs, with the advantage of a higher temporal resolution. Therefore, the objective of our study was to evaluate the spatial concordance between ESI/MSI and BOLD responses for similar IEDs. Twenty-one patients with similar IEDs in simultaneous electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) and in simultaneous EEG/magnetoencephalogram (MEG) recordings were studied. IEDs in EEG/fMRI acquisition were analyzed in an event-related paradigm within a general linear model (GLM). ESI/MSI of averaged IEDs was performed using the Maximum Entropy on the Mean. We assessed the spatial concordance between ESI/MSI and clusters of BOLD activations/deactivations with surface-based metrics. ESI/MSI were concordant with one BOLD cluster for 20/21 patients (concordance with activation: 14/21 patients, deactivation: 6/21 patients, no concordance: 1/21 patients; concordance with MSI only: 3/21, ESI only: 2/21). These BOLD clusters exhibited in 19/20 cases the most significant voxel. BOLD clusters that were spatially concordant with ESI/MSI were concordant with IEDs from invasive recordings in 8/11 patients (activations: 5/8, deactivations: 3/8). As the results of BOLD, ESI and MSI are often concordant, they reinforce our confidence in all of them. ESI and MSI confirm the most significant BOLD cluster within BOLD maps, emphasizing the importance of these clusters for the definition of the epileptic focus.

A conceptual model for CO2-induced redistribution of cerebral blood flow with experimental confirmation using BOLD MRI

Cerebrovascular reactivity (CVR) is the change in cerebral blood flow (CBF) in response to a change in a vasoactive stimulus. Paradoxical reductions in CBF in response to vasodilatory stimulation (‘steal’) are associated with vascular pathology. However, a pathophysiological interpretation of ‘steal’ requires a comprehensive conceptual model linking pathology and changes in blood flow. Herein, we extend a simple model explaining steal published in the late 1960s by incorporating concepts of CBF regulation from more recent studies to generate a comprehensive dynamic model. The main elements of the model are: (a) the relationship between changes in CBF and the arterial partial pressure of carbon dioxide (PaCO2) in healthy vascular regions is sigmoidal; (b) vascular regions vasodilate to compensate for decreased perfusion pressure, leading to (c) an encroachment on vasodilatory reserve and, reduced CVR; (d) a vasodilatory stimulus may increase CBF capacity above the flow capacity of major cerebral blood vessels; and (e) this limitation induces competitive intra-cerebral redistribution of flow from territories with low vasodilatory reserve to those with high reserve. We used CVR measurements generated by applying precise, computer-controlled changes in PaCO2 as the vasoactive stimulus, and measured blood oxygen level dependent (BOLD) MRI signals as high resolution surrogates of CBF to test predictions derived from this model. Subjects were 16 healthy adults and 16 patients with known cerebral steno-occlusive diseases. We observed regional sigmoidal PaCO2–BOLD response curves with a range of slopes; graded changes in PaCO2 resulted in redistributions of BOLD signal consistent with the known underlying vascular pathology and predictions of the model. We conclude that this model can be applied to provide a hemodynamic interpretation to BOLD signal changes in response to hypercapnia, and thereby aid in relating CVR maps to pathophysiological conditions.

Abstract W P368: Longitudinal Change in fMRI Blood Oxygen Level Dependent Signal in Cerebral Amyloid Angiopathy

Introduction: Previous cross-sectional studies show that cerebral amyloid angiopathy (CAA) is associated with reduced blood oxygen level dependent (BOLD) signal change in response to a visual task, and that this reduction is due to impaired vascular reactivity. However, there are no data on the rate at which the BOLD signal changes over time in CAA. We hypothesized that fMRI activation would decline in CAA, representing progressively impaired vasoreactivity, and this decline would be associated with increased white matter hyperintensity (WMH) volume. Methods: fMRI BOLD amplitude was measured in response to a visual task (alternating checkerboard pattern) at study entry and 1-year follow-up for 18 patients with probable CAA by Boston criteria, and 15 healthy controls. fMRI data were matched to a canonical BOLD signal using a general linear model resulting in z-statistic images with a significance threshold of p<0.05 using FSL. The amplitude of the BOLD signal percent change from baseline was measured in the 200 most active voxels in the primary visual cortex. WMH were identified on fluid attenuated inversion recovery (FLAIR) images and the volume was measured using Quantomo software (Cybertrials Inc, Canada). Results: BOLD amplitude was lower at follow-up than baseline in CAA, but the difference was not significant (mean change -0.14±0.55, p=0.30). Mean BOLD amplitude was similar at baseline and follow-up in controls (mean change 0.20±0.49, p=0.14). The difference in rate of change over time between CAA and controls was borderline significant (p=0.04). fMRI was lower at follow-up than baseline in 11/18 CAA compared to 4/15 controls (p=0.08). In CAA patients, WMH increased over time (median 1.44 mL interquartile range -0.22 to 9.70mL, p=0.01). However, BOLD amplitude change and WMH change were not related (r=-0.01, p=0.96). Discussion: Although we did not see significant fMRI BOLD signal reduction from baseline to 1 year in CAA, we did see a difference in change over time between CAA and controls, consistent with our hypothesis that impaired vasoreactivity is a feature of CAA. Studies with larger numbers of patients, or longer duration of follow-up, are needed to more precisely determine the rate of change over time in reduction of fMRI BOLD amplitude in CAA.

Blood oxygenation level dependent, blood volume, and blood flow responses to carbogen and hypoxic hypoxia in 9L rat gliomas as measured by MRI

PurposeTo study vascular responsiveness to hypoxia and hypercarbia together with vessel size index (VSI) in a 9L rat glioma (n = 11) using multimodal MRI.Materials and MethodsVSI was determined using T2 and MRI following AMI‐227 contrast agent. Blood oxygenation level dependent (BOLD) signal response was determined using T2 EPI MRI, blood volume changes using AMI‐227 and blood flow by means of continuous arterial spin labeling.ResultsVSI in the cortex, tumor rim, and core of 2.2 ± 1.0, 18.2 ± 5.4, and 23.9 ± 14.7 μm, respectively, showing a larger average vessel size in glioma than in the brain parenchyma. BOLD and blood volume signal changes to hypoxia and hypercapnia were much more profound in the tumor rim than the core. Hypoxia led to rim BOLD signal change that was larger in amplitude and it attained the low value much faster than either core or brain cortex. The vasculature in the rim appears more responsive to respiratory challenges in terms of volume adaptation than the core. Blood flow values within the gliomas were much lower than in the contralateral brain. Neither hypercarbia nor hypoxia had an effect on the tumor blood flow.ConclusionVascular responses of 9L gliomas to respiratory challenge, in particular hypoxia, are heterogeneous between the core and rim zones, potentially offering a means to classify and separate intratumor tissues with differing hemodynamic characteristics. J. Magn. Reson. Imaging 2014;39:110–119. © 2013 Wiley Periodicals, Inc.

Advantages and Disadvantages of Resting State Functional Connectivity Magnetic Resonance Imaging for Clinical Applications

Functional Magnetic Resonance Imaging (fMRI) is a powerful non-invasive technique for imaging BOLD (Blood Oxygenation Level Dependent) signal changes that is due to changes in brain hemodynamics responses associated to local neuronal activity to identify activated brain regions [1,2]. This technique allows researchers in laboratory environment to investigate the BOLD signals to determine the activated brain reigns for different stimuli or the processing of various cognitive tasks [3,4]. Furthermore, fMRI can be used in clinical applications to determine the brain abnormalities in population of subjects with neurological disease. Our knowledge about brain functions comes from task-state studies in the presence of external stimuli that the neural activity and subject responses are measured for analysis. However, the brain is very active in resting-state without any stimuli. Recent findings that have been proven very valuable in the clinical area of fMRI applications, involves investigation of brain fluctuations at resting condition and their results demonstrate that spontaneous modulation of the BOLD does not produce randomly. Spontaneous modulations in BOLD signal are structured in spatial patterns that make correlated networks between various brain regions. The analysis of brain fluctuations in BOLD signal usually involves spatial patterns of correlated activity across regions of interests that are known as resting state connectivity networks. After data acquisition and preprocessing [5], there are two important data analysis techniques for studying the resting state functional connectivity: seed-based correlations approaches that are based on calculating the correlation between extracted regions of interests to identify spatial pattern of spontaneous activity and ICA (Independent Component Analyses)-based approaches that use all brain voxels activity to separate brain functional networks that are correlated with spontaneous component of BOLD signal (to account for non-neural noise with considering maximally independent spontaneous BOLD fluctuations) [4,6-8]. Functional connectivity approaches are divided into resting state and task state studies [4,9,10].

Epilepsy and phenylketonuria: a case description and EEG-fMRI findings

Phenylketonuria (PKU) is characterized by phenylalanine accumulation due to phenylalanine hydroxylase deficiency. Up to 50% of PKU patients experience seizures. We evaluated an adult PKU patient who suffered from absences and primarily generalized tonicclonic seizures, associated with generalized spikeand-wave discharges (GSWs) on EEG. An analysis of blood oxygenation level-dependent (BOLD) signal changes during interictal epileptiform discharges showed early activation of the left perirolandic cortex followed by a BOLD signal decrease within cortical regions belonging to the default mode network and left frontoparietal cortex. Moreover, deactivation of the head of the right caudate nucleus and the left thalamus was observed. The fMRI pattern observed in our patient during GSWs is similar but not identical to that observed in idiopathic generalized epilepsy, suggesting different neurophysiological mechanisms. This is the first description of BOLD-fMRI patterns in a PKU patient with epilepsy. Similar studies in more patients might help to uncover the pathophysiology of seizures in this disease.

Neural mechanisms of high‐risk decisions‐to‐drink in alcohol‐dependent women

A hallmark of alcohol dependence (AD) is continually drinking despite the risk of negative consequences. Currently, it is not known if the pattern of disordered activation in AD is more compatible with an over-sensitive reward system, a deficit in control systems or a combination of both to produce the high risk-taking behavior observed in alcohol dependents (ADs). Here, alcohol cues were used in an ecological decisions-to-drink task that involved high- and low-risk scenarios where the chance of serious negative imagined consequences was varied. Non-alcohol cues were included as control stimuli. Functional magnetic resonance imaging (fMRI) was used to measure blood oxygen level-dependent (BOLD) signal change in 15 alcohol-dependent and 16 control women. This design allowed us to address two major questions concerning AD: first, is there a specific pattern of disordered activation that drives the heightened endorsement of high-risk decisions-to-drink in ADs? And, second, is that pattern specific to decisions-to-drink or does it generalize to other appetitive and/or neutral cues? The results showed that, during high-risk decisions-to-drink, alcohol-dependent women activated reward circuits, cognitive control circuits and regions of the default-mode network (DMN), while control women deactivated approach circuits and showed enhanced activation in regions of the DMN. Group differences were found only for decisions-to-drink, suggesting that they are specific to alcohol cues. Simultaneous activation of reward networks, cognitive control networks and the DMN in alcohol-dependent women suggests that over-endorsement of high-risk drinking decisions by alcohol-dependent women may be due to a problem with switching between different neural networks.

Apnea-Induced Cortical BOLD-fMRI and Peripheral Sympathoneural Firing Response Patterns of Awake Healthy Humans

End-expiratory breath-holds (BH) and Mueller manoeuvres (MM) elicit large increases in muscle sympathetic nerve activity (MSNA). In 16 healthy humans (9♀, 35±4 years) we used functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast to determine the cortical network associated with such sympathoexcitation. We hypothesized that increases in MSNA evoked by these simulated apneas are accompanied by BOLD contrast changes in the insular cortex, thalamus and limbic cortex. A series of 150 whole-brain images were collected during 3 randomly performed 16-second end-expiratory BHs and MMs (-30 mmHg). The identical protocol was repeated separately with MSNA recorded from the fibular nerve. The time course of the sympathoexcitatory response to both breathing tasks were correlated with whole-brain BOLD signal changes. Brain sites demonstrating both positive (activation) and negative (deactivation) correlations with the MSNA time course were identified. Sympathetic burst incidence increased (p<0.001) from 29±6 (rest) to 49±6 (BH) and 47±6 bursts/100 heartbeats (MM). Increased neural activity (Z-scores) was identified in the right posterior and anterior insular cortices (3.74, 3.64), dorsal anterior cingulate (3.42), fastigial and dentate cerebellar nuclei (3.02, 3.34). Signal intensity decreased in the left posterior insula (3.28) and ventral anterior cingulate (3.01). Apnea both activates and inhibits elements of a cortical network involved in the generation of sympathetic outflow. These findings identify a neuroanatomical substrate to guide future investigations into central mechanisms contributing to disorders characterized by elevated basal MSNA and exaggerated sympathetic responses to simulated apneas such as sleep apnea and heart failure.

A Functional Magnetic Resonance Imaging Study of Working Memory in Youth after Sports-Related Concussion: Is It Still Working?

Abstract In children, the importance of detecting deficits after mild traumatic brain injury (mTBI) or concussion has grown with the increasing popularity of leisure physical activities and contact sports. Whereas most postconcussive symptoms (PCS) are similar for children and adults, the breadth of consequences to children remains largely unknown. To investigate the effect of mTBI on brain function, we compared working memory performance and related brain activity using blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 15 concussed youths and 15 healthy age-matched control subjects. Neuropsychological tests, self-perceived PCS, and levels of anxiety and depression were also assessed. Our results showed that, behaviorally, concussed youths had significantly worse performances on the working memory tasks, as well as on the Rey figure delayed recall and verbal fluency. fMRI results revealed that, compared to healthy children, concussed youths had significantly reduced task-related activity in bilateral dorsolateral prefrontal cortex, left premotor cortex, supplementary motor area, and left superior parietal lobule during performance of verbal and nonverbal working memory tasks. Additionally, concussed youths also showed less activation than healthy controls in the dorsal anterior cingulate cortex, left thalamus, and left caudate nucleus during the nonverbal task. Regression analysis indicated that BOLD signal changes in bilateral dorsolateral prefrontal cortex were significantly correlated with performance such that greater activities in these regions, relative to the control condition, were associated with greater accuracy. Our findings confirmed functional alterations in brain activity after concussion in youths, a result similar to that observed in adults. However, significant differences were noted. In particular, the observation of reduced working memory accuracy suggests that youths may be unable to engage compensatory strategies to maintain cognitive performance after mTBI. This has significant implications for safe return to daily activities, including competitive sport.

The Two Sides of Pain Communication: Effects of Pain Expressiveness on Vicarious Brain Responses Revealed in Chronic Back Pain Patients

The dominant socioaffective model of empathy has emphasized the overlap between brain mechanisms involved in the encoding and the decoding of internal states. The role of dispositional empathy has been extensively studied in this research, but several other individual factors fundamental to communication processes have been largely ignored. We studied the effects of dispositional expressiveness in chronic back pain patients to determine if the decoding of communicative and noncommunicative information signaling pain in others would be enhanced in individuals displaying a spontaneous propensity to consistently express more pain during a behavioral-observational naturalistic standardized lifting task performed on 2 separate occasions. Blood oxygenation level–dependent signal change was measured in response to pictures showing facial pain expressions and hands/feet in pain-evoking situations in chronic back pain patients and healthy controls. Vicarious brain responses to others’ pain were comparable between groups. However, more expressive patients rated others’ pain higher and showed stronger vicarious pain responses in the right ventral part of the inferior frontal gyrus, the right insula, and the midbrain. Activity in the right insula correlated positively with both the patients' expressiveness (encoding) and the intensity of the pain perceived in the images (decoding), suggesting that this structure linked the dispositional expressiveness with vicarious pain perception. Importantly, these effects were independent from dispositional empathy and were found with both communicative (facial expression) and noncommunicative (hand and foot) cues. These results suggest that dispositional expressiveness is a self-related factor that facilitates vicarious pain processing and might reflect individual tendencies to rely on social coping strategies. PerspectiveThis article shows that pain expressivity in chronic pain patients increased the vicarious brain responses and the sensibility to others' pain. These results may help provide empirical support for better defining models of pain communication in chronic pain patients.