Blood Oxygenation Level Dependent fMRI Data Research Articles

Heartbeat-evoked neural response abnormalities in generalized anxiety disorder during peripheral adrenergic stimulation.

Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of cardiovascular signaling differentially affects the heartbeat-evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.5 and 2.0 micrograms, μg) were administered in a randomized, double-blinded and placebo-controlled fashion to dynamically perturb the cardiovascular system while recording the associated EEG-fMRI responses. During the 0.5 μg isoproterenol infusion, the GAD group (n = 24) exhibited significantly larger changes in HEP amplitude in an opposite direction than the healthy comparison (HC) group (n = 24). In addition, the GAD group showed significantly larger absolute HEP amplitudes than theHC groupduring saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP amplitude were identified during the 2.0 μg isoproterenol infusion. Using analyzable blood oxygenation level-dependent fMRI data from participants with concurrent EEG-fMRI data (21 GAD and 21 HC), we found that the aforementioned HEP effects were uncorrelated with fMRI signals in the insula, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, amygdala, and somatosensory cortex, brain regions implicated in cardiac signal processing in prior fMRI studies. These findings provide additional evidence of dysfunctional cardiac interoception in GAD and identify neural processes at the electrophysiological level that may be independent from blood oxygen level-dependent responses during peripheral adrenergic stimulation.

Direct machine learning reconstruction of respiratory variation waveforms from resting state fMRI data in a pediatric population

In many functional magnetic resonance imaging (fMRI) studies, respiratory signals are unavailable or do not have acceptable quality due to issues with subject compliance, equipment failure or signal error. In large databases, such as the Human Connectome Projects, over half of the respiratory recordings may be unusable. As a result, the direct removal of low frequency respiratory variations from the blood oxygen level-dependent (BOLD) signal time series is not possible. This study proposes a deep learning-based method for reconstruction of respiratory variation (RV) waveforms directly from BOLD fMRI data in pediatric participants (aged 5 to 21 years old), and does not require any respiratory measurement device. To do this, the Lifespan Human Connectome Project in Development (HCP-D) dataset, which includes respiratory measurements, was used to both train a convolutional neural network (CNN) and evaluate its performance. Results show that a CNN can capture informative features from the BOLD signal time course and reconstruct accurate RV timeseries, especially when the subject has a prominent respiratory event. This work advances the use of direct estimation of physiological parameters from fMRI, which will eventually lead to reduced complexity and decrease the burden on participants because they may not be required to wear a respiratory bellows.

Altered Neurovascular Coupling for Multidisciplinary Intensive Rehabilitation in Parkinson's Disease.

Effective rehabilitation in Parkinson's disease (PD) is related to brain reorganization with restoration of cortico-subcortical networks and compensation of frontoparietal networks; however, further neural rehabilitation evidence from a multidimensional perspective is needed. To investigate how multidisciplinary intensive rehabilitation treatment affects neurovascular coupling, 31 PD patients (20 female) before and after treatment and 30 healthy controls (17 female) underwent blood oxygenation level-dependent functional magnetic resonance imaging and arterial spin labeling scans. Cerebral blood flow (CBF) was used to measure perfusion, and fractional amplitude of low-frequency fluctuation (fALFF) was used to measure neural activity. The global CBF-fALFF correlation and regional CBF/fALFF ratio were calculated as neurovascular coupling. Dynamic causal modeling (DCM) was used to evaluate treatment-related alterations in the strength and directionality of information flow. Treatment reduced CBF-fALFF correlations. The altered CBF/fALFF exhibited increases in the left angular gyrus and the right inferior parietal gyrus and decreases in the bilateral thalamus and the right superior frontal gyrus. The CBF/fALFF alteration in right superior frontal gyrus showed correlations with motor improvement. Further, DCM indicated increases in connectivity from the superior frontal gyrus and decreases from the thalamus to the inferior parietal gyrus. The benefits of rehabilitation were reflected in the dual mechanism, with restoration of executive control occurring in the initial phase of motor learning and compensation of information integration occurring in the latter phase. These findings may yield multimodal insights into the role of rehabilitation in disease modification and identify the dorsolateral superior frontal gyrus as a potential target for noninvasive neuromodulation in PD.SIGNIFICANCE STATEMENT Although rehabilitation has been proposed as a promising supplemental treatment for PD as it results in brain reorganization, restoring cortico-subcortical networks and eliciting compensatory activation of frontoparietal networks, further multimodal evidence of the neural mechanisms underlying rehabilitation is needed. We measured the ratio of perfusion and neural activity derived from arterial spin labeling and blood oxygenation level-dependent fMRI data and found that benefits of rehabilitation seem to be related to the dual mechanism, restoring executive control in the initial phase of motor learning and compensating for information integration in the latter phase. We also identified the dorsolateral superior frontal gyrus as a potential target for noninvasive neuromodulation in PD patients.

A Novel Finding in Cerebral Blood Flow in Patients with Sickle Cell Disease Using Bold Functional MRI

Background: Sickle cell disease (SCD) is an inherited blood disorder which is associated with acute and chronic pain, as well as other vascular complications such as arterial steno-occlusion, stroke, and silent cerebral infarction. Alterations of cerebral blood flow have been found to be associated with different painful stages in SCD, thus cerebral blood flow might be correlated with the disease severity determined by varied pain conditions in SCD. Blood oxygen level dependent (BOLD) imaging is a blood-related contrast technology in functional magnetic resonance imaging (fMRI). We have previously demonstrated the feasibility of using low frequency oscillation (LFO) in BOLD fMRI to track the hemodynamic features of the blood flow with maximum cross-correlation coefficient (MCCC) and the Delay Time (i.e., blood arrival time at different brain regions) (Tong et al., JCBFM. 2017). Positive MCCC value was found between the LFO BOLD signals extracted from the global mean (GMean, averaged signal across the whole brain) and the superior sagittal sinus (SSS) in our previous findings (Tong et al., JCBFM. 2018). In this study, we aim to use LFO BOLD signals to explore the cerebral hemodynamic features with MCCCs and their associations with hematological and disease severity related outcomes in patients with SCD. Methods: Ten subjects with SCD aged 14-43 years old (5 HbSS, 3 HbSC, 1 HbSB+, 1 HbB0) and 10 age- and sex-matched controls from a publicly available dataset Human Connectome Project (HCP) (Essen et al., Neuroimage, 2013) were included for data analysis. T1-weighted and resting-state BOLD fMRI (repetition time (TR)=1.05 sec) were collected using a 3T SIEMENS (Prisma) scanner. A BOLD fMRI dataset with TR of 0.72 sec from healthy subjects was used as control. All the BOLD fMRI data were preprocessed using FSL to correct the motion artifact. The SSS region was identified in the T1-weighted image using FSL. The corresponding SSS mask was then applied in the BOLD fMRI image to extract the BOLD fMRI signals in the SSS region. The GMean BOLD signal was averaged across the whole brain. BOLD fMRI Signals were demeaned and band-pass filtered (0.01-0.1 Hz) to acquire the LFO signals. Cross-correlation between the SSS-LFO signal and GMean-LFO signal was performed to calculate the MCCC and their corresponding Delay Time. Correlations between the MCCCs of the two LFO signals (from SSS and GMean) and each hematological index were further performed. Results: Consistent with the healthy control in our previous findings, half of the patients (3 HbSC, 1 HbSB+, and 1 HbSS) presented positive MCCC values. However, interestingly, negative MCCC values were found from another half of the patients (4 HbSS and 1 HbB0, Figure 1, p < 0.05 for all subjects). Notably, all patients with HbSC presented positive MCCC values that are similar to controls whereas 4 out 5 patients with HbSS (80%) were found to have negative MCCC values. More importantly, higher percentages of HbS and lower total Hgb (HbS(%): r=-0.73, p=0.03; Hgb(GM/dL): r=0.69, p=0.03) were found to be significantly associated with the negative MCCC values. Conclusions: We found a never-before-seen negative MCCC signature between the BOLD fMRI signals in the SSS and the GMean in a subset of patients with SCD compared with healthy controls. This might indicate a significant change in cerebral blood flow in a subset of patients with SS disease compared with SC and controls. Importantly, we further observed that this never-before-seen negative MCCC signature is highly associated with the percentage of the HbS and total Hgb that are known to be correlated with disease severity. This might be due to the microvascular shunting (Juttukonda et al., JCBFM, 2019) that exists in patients who have high percentage of HbS. This study is the first to associate BOLD fMRI derived hemodynamic metrics with disease severity related outcomes in SCD. This never-before-seen anti-correlation MCCC signature may have tremendous promise as a novel biomarker for SCD severity and differentiate pain characteristics in different sickle cell phenotypes, and further investigation in larger number of subjects is needed to understand variations between SCD phenotypes and its relationship to clinical outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A line through the brain: implementation of human line-scanning at 7T for ultra-high spatiotemporal resolution fMRI

Functional magnetic resonance imaging (fMRI) is a widely used tool in neuroscience to detect neurally evoked responses, e.g. the blood oxygenation level-dependent (BOLD) signal. Typically, BOLD fMRI has millimeter spatial resolution and temporal resolution of one to few seconds. To study the sub-millimeter structures and activity of the cortical gray matter, the field needs an fMRI method with high spatial and temporal resolution. Line-scanning fMRI achieves very high spatial resolution and high sampling rate, at the cost of a sacrifice in volume coverage. Here, we present a human line-scanning implementation on a 7T MRI system. First, we investigate the quality of the saturation pulses that suppress MR signal outside the line. Second, we established the best coil combination for reconstruction. Finally, we applied the line-scanning method in the occipital lobe during a visual stimulation task, showing BOLD responses along cortical depth, every 250 µm with a 200 ms repetition time (TR). We found a good correspondence of t-statistics values with 2D gradient-echo echo planar imaging (GE-EPI) BOLD fMRI data with the same temporal resolution and voxel volume (R = 0.6 ± 0.2). In summary, we demonstrate the feasibility of line-scanning in humans and this opens line-scanning fMRI for applications in cognitive and clinical neuroscience.

Coordinated Human Brainstem and Spinal Cord Networks during the Expectation of Pain Have Elements Unique from Resting-State Effects

Functional magnetic resonance imaging (fMRI) research on the human brainstem (BS) and spinal cord (SC) has identified extensive BS/SC resting-state networks (RSNs) by showing spontaneous coordinated blood oxygenation-level dependent (BOLD) signal fluctuations in the absence of a stimulus. Studies have shown that these networks can be influenced by participants’ level of arousal or attention (e.g., watching a video), and linked network function to autonomic homeostatic regulation. Here we explore how the cognitive state of expecting pain can influence connectivity in these networks. Data from two studies (a predictable pain stimulus study, and a resting-state study) were compared to show the effects of expecting pain on BS/SC networks, and how networks differed from networks associated with the resting-state. In each study, BOLD fMRI data were obtained from the cervical SC and brainstem in healthy participants at 3 tesla using a T2-weighted single-shot fast spin-echo imaging method. Functional connectivity was investigated within the entire 3D volume by means of structural equation modeling (SEM) and analyses of covariance (ANCOVA). Results showed extensive connectivity within/across BS and SC regions during the expectation of pain, and ANCOVA analyses showed that connectivity in specific components of these networks varied with individual pain sensitivity. Comparing these results to RSN fluctuations revealed commonalities in coordination between BS and SC regions, and specific BS–BS connectivity fluctuations unique to the expectation of pain. Based on the regions involved, these results provide evidence of brainstem regulation specific to the expectation of pain.

Voxelwise optimization of hemodynamic lags to improve regional CVR estimates in breath-hold fMRI.

Cerebrovascular Reactivity (CVR), the responsiveness of blood vessels to a vasodilatory stimulus, is an important indicator of cerebrovascular health. Assessing CVR with fMRI, we can measure the change in the Blood Oxygen Level Dependent (BOLD) response induced by a change in CO2 pressure (%BOLD/mmHg). However, there exists a temporal offset between the recorded CO2 pressure and the local BOLD response, due to both measurement and physiological delays. If this offset is not corrected for, voxel-wise CVR values will not be accurate. In this paper, we propose a framework for mapping hemodynamic lag in breath-hold fMRI data. As breath-hold tasks drive task-correlated head motion artifacts in BOLD fMRI data, our framework for lag estimation fits a model that includes polynomial terms and head motion parameters, as well as a shifted variant of the CO2 regressor (±9 s in 0.3 s increments), and the hemodynamic lag at each voxel is the shift producing the maximum total model R2 within physiological constraints. This approach is evaluated in 8 subjects with multi-echo fMRI data, resulting in robust maps of hemodynamic delay that show consistent regional variation across subjects, and improved contrast-to-noise compared to methods where motion regression is ignored or performed earlier in preprocessing.Clinical Relevance- We map hemodynamic lag using breathhold fMRI, providing insight into vascular transit times and improving the regional accuracy of cerebrovascular reactivity measurements.

Blood Oxygen Level–Dependent Response Changes in the Ipsilateral Primary Somatosensory Cortex and Thalamus of Patients With Moyamoya Disease During Median Nerve Electrical Stimulation

The objective of this study was to investigate the changes in the blood oxygen level-dependent (BOLD) response in the ipsilateral primary somatosensory cortex (SI) and thalamus of patients with moyamoya disease (MMD) during sensory stimulation. Sixty-four MMD patients, and 15 healthy volunteers were enrolled. Thirty-three MMD patients exhibited paroxysmal numbness or hypoesthesia in the unilateral limbs. Fifteen patients with acroparesthesia underwent unilateral encephaloduroarteriosynangiosis (EDAS). All volunteers underwent BOLD functional magnetic resonance imaging (BOLD-fMRI) under median nerve electrical stimulation (MNES). Blood oxygen level-dependent fMRI data were processed to obtain time-signal intensity curves in the activation areas of the bilateral SI and thalamus. Processed dynamic susceptibility contrast-enhanced magnetic resonance imaging data were used to measure the time to peak of the BOLD response in the regions of interest, including the bilateral SI, thalamus, and cerebellum. Changes in the time-signal intensity curve-related hemodynamic parameters in the ipsilateral SI and thalamus were examined between healthy controls, nonacroparesthesia patients, and asymptomatic and symptomatic sides of unilateral acroparesthesia patients during MNES. Changes in these parameters in MMD patients before and after EDAS were examined. Compared with healthy volunteers, 3 groups of MMD patients exhibited an increased peak of the positive BOLD response in the ipsilateral thalamus during MNES (0.65 ± 0.24 vs 0.79 ± 0.35, 0.94 ± 0.57, and 0.89 ± 0.50; P = 0.0335). The positive response peak in the ipsilateral SI markedly increased in MMD patients with acroparesthesia during MNES on the asymptomatic side (0.56 ± 0.37 vs 0.38 ± 0.27, P = 0.0243). The time to peak negative response in the ipsilateral SI was prolonged during MNES on the symptomatic side after EDAS (12.14 ± 8.90 seconds vs 18.86 ± 9.20 seconds, P = 0.0201). During sensory stimulation treatment, BOLD response changes occurred in the ipsilateral SI and thalamus of MMD patients. These changes enabled the contralateral hemisphere of the brain to better deal with sensory stimuli.

Comparing Coordinated Networks Across the Brainstem and Spinal Cord in the Resting State and Altered Cognitive State.

Resting-state (RS) functional magnetic resonance imaging (fMRI) has been used to investigate networks of activity within the brain, as well as the brainstem (BS) and spinal cord (SC). While previous research has shown coordinated resting state networks (RSNs) in the BS/SC, their function is still unclear. The aim of this study was to investigate the function of RSNs across these regions, by examining how these networks change when participants are experiencing different cognitive states (RS, listening to an audio presentation, or watching a video). RS blood oxygenation-level dependent fMRI data were obtained from the human cervical SC and BS in 20 healthy participants (14 women, 6 men), at 3 tesla, with T2-weighted single-shot fast spin-echo imaging. Functional connectivity was investigated within the entire three-dimensional region by means of temporal correlations between anatomical regions and by structural equation modeling (SEM). Both correlational analyses and SEM showed extensive connectivity within and across BS and SC regions, and 37% to 40% of significant connections were consistent across study conditions. However, significant differences in connectivity between specific regions of the BS and SC were also identified which depended on the study conditions. The results indicate that connectivity across the RS SC/BS is influenced by a person's cognitive/emotional state. The known anatomical functions of the regions involved support the conclusion that this RS network may play a role in the integration of homeostatic autonomic functions.

Amygdala and prefrontal cortex activity varies with individual differences in the emotional response to psychosocial stress.

Stress elicits a variety of psychophysiological responses that show large interindividual variability. Determining the neural mechanisms that mediate individual differences in the emotional response to stress would provide new insight that would have important implications for understanding stress-related disorders. Therefore, the present study examined individual differences in the relationship between brain activity and the emotional response to stress. In the largest stress study to date, 239 participants completed the Montreal Imaging Stress Task (MIST) while heart rate, skin conductance response (SCR), cortisol, self-reported stress, and blood oxygen level dependent (BOLD) functional MRI (fMRI) signal responses were measured. The relationship between differential responses (heart rate, SCR, cortisol, and self-reported stress) and differential BOLD fMRI data was analyzed. Dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and amygdala activity varied with the behavioral response (i.e., SCR and self-reported stress). These results suggest the PFC and amygdala support processes that are important for the expression and regulation of the emotional response to stress, and that stress-related PFC and amygdala activity underlie interindividual variability in peripheral physiologic measures of the stress response. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Investigation of Resting-State BOLD Networks in the Human Brainstem and Spinal Cord

Resting-state functional magnetic resonance imaging (rs-fMRI) has been used to investigate networks within the cortex and has also provided some insight into the networks present in the brainstem (BS) and spinal cord (SC). The purpose of this study was to investigate resting-state blood oxygenation-level dependent (BOLD) fluctuations in the BS/SC and to identify resting-state networks (RSNs) across these regions. Resting-state BOLD fMRI data were obtained from the entire BS and cervical SC in 16 healthy participants, at 3 T, with T2-weighted single-shot fast spin-echo imaging. Data were spatially normalized and processed to remove physiological noise. Cluster-cluster functional connectivity was investigated across the entire 3D region by means of temporal correlations, and structural equation modeling (SEM) was used to investigate RSNs. Extensive connectivity was observed within and across BS and SC regions, with connections spanning up to 120 mm, although shorter connections were more prevalent. SEM results revealed extensive brainstem-cord connectivity that included specific anatomical regions within the brainstem. The results indicate the presence of a complex resting-state network which is highly interconnected in the spinal cord. Known anatomical connections between cortical and BS regions support the conclusion that the observed resting-state BOLD fluctuations in the BS/SC may be related to autonomic regulation. Future studies are required to further investigate these resting-state BOLD networks.

Awake Mouse Imaging: From Two-Photon Microscopy to Blood Oxygen Level–Dependent Functional Magnetic Resonance Imaging

BackgroundFunctional magnetic resonance imaging (fMRI) in awake behaving mice is well positioned to bridge the detailed cellular-level view of brain activity, which has become available owing to recent advances in microscopic optical imaging and genetics, to the macroscopic scale of human noninvasive observables. However, though microscopic (e.g., two-photon imaging) studies in behaving mice have become a reality in many laboratories, awake mouse fMRI remains a challenge. Owing to variability in behavior among animals, performing all types of measurements within the same subject is highly desirable and can lead to higher scientific rigor. MethodsWe demonstrated blood oxygenation level–dependent fMRI in awake mice implanted with long-term cranial windows that allowed optical access for microscopic imaging modalities and optogenetic stimulation. We started with two-photon imaging of single-vessel diameter changes (n = 1). Next, we implemented intrinsic optical imaging of blood oxygenation and flow combined with laser speckle imaging of blood flow obtaining a mesoscopic picture of the hemodynamic response (n = 16). Then we obtained corresponding blood oxygenation level–dependent fMRI data (n = 5). All measurements could be performed in the same mice in response to identical sensory and optogenetic stimuli. ResultsThe cranial window did not deteriorate the quality of fMRI and allowed alternation between imaging modalities in each subject. ConclusionsThis report provides a proof of feasibility for multiscale imaging approaches in awake mice. In the future, this protocol could be extended to include complex cognitive behaviors translatable to humans, such as sensory discrimination or attention.

High-resolution human brain functional χ mapping reveals focal and bidirectional BOLD responses

A blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) study produces a four-dimensional (4D) complex-valued data set. Conventional magnitude-based brain functional mapping is an indirect measure of brain activity due to a dataflow in a cascade of MRI transformations (e.g., a dipole convolution). The MRI transformations also impose a MRI parameter dependence to BOLD fMRI data (e.g. the dependence on B0 and TE). By solving an inverse MRI problem, we may reconstruct a brain magnetic susceptibility source distribution (denoted by χ) from a brain MR image, thereby achieving a more direct representation of the vascular origin than the MRI data representation. For a complex-valued BOLD fMRI dataset, we can extract net BOLD phase responses (δP) through a complex division, and then reconstruct BOLD susceptibility responses (δχ) therefrom. In this paper, we compare the functional maps depicted in different dataspaces (magnitude image, δP image, δχ source) based on numeric characterizations of activation blobs by pattern analysis. Through an experimental demonstration with high-field (7 T) and high-resolution (0.5 mm in-plane) finger-tapping experiment, we show that the δχ-depicted functional map reveals task-evoked bidirectional BOLD δχ responses at the motor cortex region. The positive and negative activations are spatially separated and balanced, indicating conservation of concurrent excitations and inhibitions. We also observe that the source-depicted activation spots are more compact than the image-depicted spots, which is attributed to the dipole effect removal by inverse MRI.

Functional magnetic resonance imaging in chronic ischaemic stroke.

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

Amygdala on the Lookout.

results present an explanatory challenge: why would the amygdala be hypoactive in paranoid individuals who exhibit heightened threat perception and elevated physiological arousal? To explain this paradoxical finding, some investigators hypothesized that reduced frontal control over the amygdala due to dysconnectivity of frontolimbic circuitry could lead to hypervigilanceand misattribution of fear to incoming signals (3). AnotherpossibilityisthatmethodologicallimitationsofBOLD fMRI have obstructed a more accurate quantification of amygdala activity. In this issue of the Journal, a new study conducted by Pinkham and colleagues (5) offers a methodological explanation for discrepant findings concerning aberrant amygdala activity in paranoid schizophrenia. The authors definitively demonstrate higher baseline amygdala activity in paranoid compared with nonparanoid patients with schizophrenia, by employing arterial spin labeling perfusion MRI. Arterial spin labeling allows for a noninvasive and quantitative measurement of regional cerebral blood flow (CBF) by using magneticallylabeledarterialbloodwaterasanendogenoustracer (asopposedtoexogenousradioactivetracersusedinpositron emission tomography) (6). There are both important methodological and conceptual advances here worthy of note. In addition to arterial spin labeling, the authors acquired BOLD fMRI data while participants rated photographs of faces for trustworthiness. By measuring resting state regional CBF and task-related BOLD activity in the same participants, the authors were able to examine group differences in baseline amygdala activity alongside differences in task-related fluctuations of amygdalaactivity.Suchcomparisonsareparticularlyrelevant to schizophrenia, as prior evidence of amygdala hypoactivation relied on BOLD contrasts blind to potential group differences in baseline activity. Indeed, Pinkham and colleagues found that acutely paranoid patients exhibited higher resting CBF in the bilateral amygdala compared with nonparanoid patients and healthy comparison subjects, who did not differ from each other. On the other hand, the BOLD fMRI task analysis revealed a general trend of amygdala hypoactivation in paranoid compared with nonparanoid participants. Thus, observed taskrelated amygdala hypoactivity likely reflects higher baseline amygdala activity that mitigates the stimulus-driven signal change detected by the BOLD contrast. Additional wholebrain group comparisons found greater CBF in the internal capsule, the corpus callosum, and portions of the inferior temporal and fusiform gyri in paranoid compared with nonparanoid patients. Overall, these results suggest that paranoia

Simultaneous fMRI–PET of the opioidergic pain system in human brain

MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI–PET brain imaging to dissect neurochemically distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI–PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET data were acquired with an opioid radioligand, [11C]diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI–PET imaging study, we show co-localized responses in thalamus and striatum related to pain processing, while modality specific brain networks were also found. Co-localized fMRI and PET signal changes in the thalamus were positively correlated suggesting that pain-induced changes in opioid neurotransmission contribute a significant component of the fMRI signal change in this region. Simultaneous fMRI–PET provides unique opportunities allowing us to relate specific neurochemical events to functional hemodynamic activation and to investigate the impacts of neurotransmission on neurovascular coupling of the human brain in vivo.

All that glitters is not BOLD: inconsistencies in functional MRI

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.

Multivariate Classification of Blood Oxygen Level-Dependent fMRI Data with Diagnostic Intention: A Clinical Perspective

There has been a recent upsurge of reports about applications of pattern-recognition techniques from the field of machine learning to functional MR imaging data as a diagnostic tool for systemic brain disease or psychiatric disorders. Entities studied include depression, schizophrenia, attention deficit hyperactivity disorder, and neurodegenerative disorders like Alzheimer dementia. We review these recent studies which-despite the optimism from some articles-predominantly constitute explorative efforts at the proof-of-concept level. There is some evidence that, in particular, support vector machines seem to be promising. However, the field is still far from real clinical application, and much work has to be done regarding data preprocessing, model optimization, and validation. Reporting standards are proposed to facilitate future meta-analyses or systematic reviews.

Abnormal functional connectivity of amygdala in late-onset depression was associated with cognitive deficits.

BackgroundMajor depressive disorder (MDD) is associated with decreased function of cortico-limbic circuits, which play important roles in the pathogenesis of MDD. Abnormal functional connectivity (FC) with the amygdala, which is involved in cortico-limbic circuits, has also been observed in MDD. However, little is known about connectivity alterations in late-onset depression (LOD) or whether disrupted connectivity is correlated with cognitive impairment in LOD.Methods and ResultsA total of twenty-two LOD patients and twenty-two matched healthy controls (HC) underwent neuropsychological tests and resting state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and FC with bilateral amygdala seeds were used to analyze blood oxygen level-dependent fMRI data between two groups. Compared with HC, LOD patients showed decreased ReHo in the right middle frontal gyrus and left superior frontal gyrus. In the LOD group, the left amygdala had decreased FC with the right middle frontal gyrus and the left superior frontal gyrus in the amygdala positive network, and it had increased FC with the right post-central gyrus in the amygdala negative network. However, significantly reduced FC with the right amygdala was observed in the right middle occipital gyrus in the amygdala negative network. Further correlative analyses revealed that decreased FC between the amygdala and the right middle occipital gyrus was negatively correlated with the verbal fluency test (VFT, r = −0.485, P = 0.022) and the digit span test (DST, r = −0.561, P = 0.007).ConclusionsOur findings of reduced activity of the prefrontal gyrus and abnormal FC with the bilateral amygdala may be key markers of cognitive dysfunction in LOD patients.

Correlated slow fluctuations in respiration, EEG, and BOLD fMRI

Low-frequency temporal fluctuations of physiological signals (<0.1 Hz), such as the respiration and cardiac pulse rate, occur naturally during rest and have been shown to be correlated with blood-oxygenation-level-dependent (BOLD) signal fluctuation. Such physiological signal modulations have been considered as sources of noise and their effects on BOLD signal are commonly removed in functional magnetic resonance imaging (fMRI) studies. However, possible neural correlates of the physiological fluctuations have not been considered nor examined in detail. In the present study we investigated this possibility by simultaneously acquiring electroencephalogram (EEG) with BOLD fMRI data, respiratory and cardiac waveforms in healthy human subjects at eyes-closed and eyes-open resting. We quantified the concurrent changes of the EEG power in the alpha frequency band, the respiration volume, and the cardiac pulse rate, then assessed the temporal correlations between alpha EEG power and physiological signal fluctuations. In addition, time-shifted time courses of alpha EEG power or physiological data were included as regressors to examine their correlations with the whole-brain BOLD fMRI signals. We observed a significant correlation between alpha EEG global field power and respiration, particularly at eyes-closed resting condition. Similar spatial patterns were observed between the correlation maps of BOLD with alpha EEG power and respiration, with negative correlations coinciding in the visual cortex, superior/middle temporal gyrus, inferior frontal gyrus, and inferior parietal lobule and positive correlations in the thalamus and caudate. Regressing out the physiological variations in the BOLD signal resulted in reduced correlation between BOLD and alpha EEG power. These results suggest a mutual link of neuronal origin between alpha EEG power, respiration, and BOLD signals.