Blood Oxygen Level-dependent Activity Research Articles

Abnormal visual cortex activity using functional magnetic resonance imaging in treatment resistant photophobia in Friedreich Ataxia

PurposeFriedreich ataxia (FDRA) is a debilitating neurodegenerative disease that can have ophthalmological manifestations including visual dysfunction, nystagmus, and optic atrophy. However, severe photophobia has not been reported nor evaluated with functional magnetic resonance imaging (fMRI). MethodsA 64-year-old white female with a 37-year history of FDRA presented to the eye clinic with worsening photophobia of 3 years. To measure her visual cortex activation and subjective responses during episodes of photophobia, she underwent event-related fMRI with light stimuli. In comparison, the same protocol was conducted in an individual with photophobia but without FDRA. After the fMRI, both patients were treated with 35 units of BoNT-A applied to the forehead. ResultsAnalysis of visual cortex activity in response to light stimulus in the FDRA patient showed no correlation between blood oxygen level dependent (BOLD) activation and light stimuli in the first (r = −0.100, p = 0.235), and a weak negative correlation in the second half of the fMRI scan (r = −0.236 p = 0.004). In notable contrast, significant positive correlations were noted between visual cortex activity and the light stimulus (1st half: r = 0.742, p < 0.001, vs. 2nd half: r = 0.614, p < 0.001) in the comparator. Six weeks later, no improvement in photophobia was noted in either patient. Conclusion and importanceOur study highlights photophobia as one potential ocular manifestation of FDRA and suggests that one underlying contributor may be a decoupled cortical neurovascular response to light. Our study provides novel information that may guide physiologic understanding and future treatments in this disease.

Prefrontal cortex engagement during an fMRI task of emotion regulation as a potential predictor of treatment response in borderline personality disorder.

Borderline personality disorder (BPD) is a severe mental illness, with high rates of co-morbid depression and suicidality. Despite the importance of optimizing treatment in BPD, little is known about how neural processes relate to individual treatment response. This study examines how baseline regional brain blood oxygen level dependent (BOLD) activation during a functional magnetic resonance imaging (fMRI) task of emotion regulation is related to treatment response following a six-month randomized clinical trial of Dialectical Behavior Therapy (DBT) or Selective Serotonin Reuptake Inhibitor (SSRI) treatment. Unmedicated females with BPD (N = 37), with recent suicidal behavior or self-injury, underwent an fMRI task in which negative personal memories were presented and they were asked to distance (i.e., downregulate their emotional response) or immerse (i.e., experience emotions freely). Patients were then randomized to DBT (N = 16) or SSRI (N = 21) treatment, with baseline and post-treatment depression and BPD severity assessed. BOLD activity in prefrontal cortex, anterior cingulate, and insula was associated with distancing. Baseline BOLD during distancing in dorsolateral, ventrolateral, and orbital prefrontal cortex (dlPFC, vlPFC, OFC) differentially predicted depression response across treatment groups, with higher activity predicting better response in the SSRI group, and lower activity predicting better response in the DBT group. All female samples. Findings indicate that greater prefrontal engagement during emotion regulation may predict more antidepressant benefit from SSRIs, whereas lower engagement may predict better response to DBT. These results suggest different mechanisms of action for SSRI and DBT treatment, and this may allow fMRI to guide individualized treatment selection.

Association between neurovascular coupling and neural signals in the resting state as revealed by a combined fMRI and magnetoencephalography study in humans.

The blood oxygenation level-dependent (BOLD) activation reflects hemodynamic events mediated by neurovascular coupling. During task performance, the BOLD hemodynamic response in a relevant area is mainly driven by the high levels of synaptic activity (reflected in local field potentials, LFPs) but, in contrast, during a task-free, resting state, the contribution to BOLD of such neural events is small, as expected by the comparatively (to the task state) low level of neural events. Concomitant recording of BOLD and LFP at rest in animal experiments has estimated the neural contribution to BOLD to ∼10%. Such experiments have not been performed in humans. As an approximation, we recorded (in the same subject, n = 57 healthy participants) at a task-free, resting state the BOLD signal and, in a different session, the magnetoencephalographic (MEG) signal, which reflects purely neural (synaptic) events. We then calculated the turnover of these signals by computing the successive moment-to-moment difference in the BOLD and MEG time series and retaining the median of the absolute value of the differenced series (BOLD and TMEG, respectively). The correlation between normalized turnovers of BOLD (TBOLD) and turnovers of MEG (TMEG) was r = 0.336 (r2 = 0.113; P = 0.011). These results estimate that 11.3% of the variance in TBOLD can be explained by the variance in TMEG. This estimate is close to the aforementioned estimate obtained by direct recordings in animal experiments. NEW & NOTEWORTHY Here, we report on a weak positive association between turnovers of blood oxygenation level-dependent (TBOLD) and magnetoencephalographic (TMEG) signals in 57 healthy human subjects in a resting, task-free state. More specifically, we found that the purely neural TMEG accounted for 11.1% of the TBOLD, a percentage remarkably close to that found between resting-state local field potentials (LFPs) and BOLD recorded concurrently in animal experiments.

Impact of analytic decisions on test–retest reliability of individual and group estimates in functional magnetic resonance imaging: A multiverse analysis using the monetary incentive delay task

Abstract Empirical studies reporting low test–retest reliability of individual blood oxygen-level dependent (BOLD) signal estimates in functional magnetic resonance imaging (fMRI) data have resurrected interest among cognitive neuroscientists in methods that may improve reliability in fMRI. Over the last decade, several individual studies have reported that modeling decisions, such as smoothing, motion correction, and contrast selection, may improve estimates of test–retest reliability of BOLD signal estimates. However, it remains an empirical question whether certain analytic decisions consistently improve individual- and group-level reliability estimates in an fMRI task across multiple large, independent samples. This study used three independent samples (Ns: 60, 81, 119) that collected the same task (Monetary Incentive Delay task) across two runs and two sessions to evaluate the effects of analytic decisions on the individual (intraclass correlation coefficient [ICC(3,1)]) and group (Jaccard/Spearman rho) reliability estimates of BOLD activity of task fMRI data. The analytic decisions in this study vary across four categories: smoothing kernel (five options), motion correction (four options), task parameterizing (three options), and task contrasts (four options), totaling 240 different pipeline permutations. Across all 240 pipelines, the median ICC estimates are consistently low, with a maximum median ICC estimate of .43 – .55 across the 3 samples. The analytic decisions with the greatest impact on the median ICC and group similarity estimates are the Implicit Baseline contrast, Cue Model parameterization, and a larger smoothing kernel. Using an Implicit Baseline in a contrast condition meaningfully increased group similarity and ICC estimates as compared with using the Neutral cue. This effect was largest for the Cue Model parameterization; however, improvements in reliability came at the cost of interpretability. This study illustrates that estimates of reliability in the MID task are consistently low and variable at small samples, and a higher test–retest reliability may not always improve interpretability of the estimated BOLD signal.

Нейровизуализационный подход для выявления биомаркеров рабочей памяти у больных с хронической ишемией мозга

Verbal working memory (VWM) is a fundamental function responsible for temporary storage and short-term handling of verbal information. The study was aimed to determine the working memory biomarker associated with imaging of the source of infra-slow electrical activity in patients with chronic cerebral ischemia (CCI). A total of 50 patients with CCI took part in the study: 16 males and 34 females aged 50–85 years. VWM was evaluated by the Luria test. The subjects were divided into two groups matched by age with the VWM below and above the average level for the studied sample. The infra-slow, below 0.1 Hz, electrical activity, otherwise known as the DC potentials (DCPs) of the brain, was recorded with five monopolar leads: frontal, central, occipital, right and left temporal. The resting state fMRI was used to analyze brain regions with the activated BOLD (blood-oxygen-level-dependent) signal that were associated with the brain regions responsible for VWM and the DCP generation sources recorded with the non-polarizable electrodes. The differences in BOLD signal activation and infra-slow activity amplitude were found in two VWM groups. These resting-state neural networks, VWM and the neural network responsible for DCP generation, overlapped in frontal regions. There were significant differences in DCP recorded with the frontal lead in two VWM groups (р = 0.00004). In patients with CCI, infra-slow activity, recorded with the frontal lead that is generated by the neural network fragment representing an intersection of the VWM network and the part of the brain responsible for DCP generation in the frontal region, is a VWM biomarker.

Effects of chronic naltrexone treatment on relapse-related behavior and neural responses to fentanyl in awake nonhuman primates.

Naltrexone, an opioid antagonist that blocks the reinforcing properties of opioid agonists, is often prescribed to preclude relapse to opioid use disorder (OUD) following detoxification. However, few laboratory studies have directly investigated the ability of naltrexone to alter relapse-inducing effects of opioid agonists, including their priming strength in reinstatement studies and their impact in brain regions known to be involved in drug-induced reinforcement in MRI studies. Here we directly address this issue by investigating the effects of continuous exposure to naltrexone on 1) fentanyl-induced reinstatement of drug-seeking behavior, 2) fentanyl-induced patterns of blood oxygenation level dependent (BOLD) activation in the nucleus accumbens (NAcc), and 3) fentanyl-induced changes in NAcc functional connectivity (FC) in awake non-human primates that are engaged in ongoing opioid self-administration studies. We found that naltrexone antagonizes the priming strength of fentanyl as shown by a rightward shift in its reinstatement dose-effect curve and that naltrexone surmountably antagonizes the BOLD response induced by fentanyl. However, while naltrexone also countered fentanyl's effects on NAcc FC, the effects were not surmounted by a higher dose of fentanyl. Together, these data suggest that, in contrast to naltrexone's modulation of fentanyl's effects on behavior and BOLD responses, their interactive effects on FC between multiple brain regions do not reflect their receptor-mediated activity. Additionally, we demonstrated opposing effects in the absence and presence of naltrexone on NAcc FC at baseline (i.e., in the absence of any fentanyl prime) suggesting that naltrexone alters FC at baseline, even though naltrexone appears behaviorally silent in the absence of an agonist prime. Together these data provide additional insight into ways in which naltrexone interacts with opioid agonists, both behaviorally and in the brain. Further understanding the effects of opioid agonists on patterns of FC could help elucidate our understanding of the neural processes that contribute to the initiation of and relapse to opioid-seeking behavior in OUD.

Self-Regulation of the Posterior-Frontal Brain Activity with Real-Time fMRI Neurofeedback to Influence Perceptual Discrimination.

The Global Neuronal Workspace (GNW) hypothesis states that the visual percept is available to conscious awareness only if recurrent long-distance interactions among distributed brain regions activate neural circuitry extending from the posterior areas to prefrontal regions above a certain excitation threshold. To directly test this hypothesis, we trained 14 human participants to increase blood oxygenation level-dependent (BOLD) signals with real-time functional magnetic resonance imaging (rtfMRI)-based neurofeedback simultaneously in four specific regions of the occipital, temporal, insular and prefrontal parts of the brain. Specifically, we hypothesized that the up-regulation of the mean BOLD activity in the posterior-frontal brain regions lowers the perceptual threshold for visual stimuli, while down-regulation raises the threshold. Our results showed that participants could perform up-regulation (Wilcoxon test, session 1: p = 0.022; session 4: p = 0.041) of the posterior-frontal brain activity, but not down-regulation. Furthermore, the up-regulation training led to a significant reduction in the visual perceptual threshold, but no substantial change in perceptual threshold was observed after the down-regulation training. These findings show that the up-regulation of the posterior-frontal regions improves the perceptual discrimination of the stimuli. However, further questions as to whether the posterior-frontal regions can be down-regulated at all, and whether down-regulation raises the perceptual threshold, remain unanswered.

Functional magnetic resonance imaging of the lumbosacral cord during a lower extremity motor task

Abstract Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) can be used to map neuronal function in the cervical cord, yet conclusive evidence supporting its applicability in the lumbosacral cord is still lacking. This study aimed to (i) demonstrate the feasibility of BOLD fMRI for indirectly mapping neural activity in the lumbosacral cord during a unilateral lower extremity motor task and (ii) investigate the impact of echo time (TE) on the BOLD effect size. Twelve healthy volunteers underwent BOLD fMRI using four reduced field-of-view single-shot gradient-echo echo planar imaging sequences, all with the same geometry but different TE values ranging from 20 to 42 ms. Each sequence was employed to acquire a single 6-min rest run and two 10-min task runs, which included alternating 15-s blocks of rest and unilateral ankle dorsi- and plantar flexion. We detected lateralized task-related BOLD activity at neurological levels L3-S2, centered at the ipsilateral (right) ventral spinal cord but also extending into the ipsilateral dorsal spinal cord. This pattern of activation is consistent with our current understanding of spinal cord organization, wherein lower motor neurons are located in the ventral gray matter horn, while interneurons neurons of the proprioceptive pathway, activated during the movement, are located in the dorsal horns and the intermediate gray matter. At the subject level, BOLD activity showed considerable variability but was lateralized in all participants. The highest BOLD effect size within the ipsilateral ventral spinal cord, as well as the highest split-half reliability, was observed at a TE of 42 ms. Sequences with a shorter TE (20 and 28 ms) also detected activity in the medioventral part of the spinal cord, likely representing large vein effects. In summary, our results demonstrate the feasibility of detecting task-related BOLD activity in the lumbosacral cord induced by voluntary lower limb movements. BOLD fMRI in the lumbosacral cord has significant implications for assessing motor function and its alterations in disease or after spinal cord injury.

Impact of analytic decisions on test-retest reliability of individual and group estimates in functional magnetic resonance imaging: a multiverse analysis using the monetary incentive delay task.

Empirical studies reporting low test-retest reliability of individual blood oxygen-level dependent (BOLD) signal estimates in functional magnetic resonance imaging (fMRI) data have resurrected interest among cognitive neuroscientists in methods that may improve reliability in fMRI. Over the last decade, several individual studies have reported that modeling decisions, such as smoothing, motion correction and contrast selection, may improve estimates of test-retest reliability of BOLD signal estimates. However, it remains an empirical question whether certain analytic decisions consistently improve individual and group level reliability estimates in an fMRI task across multiple large, independent samples. This study used three independent samples (Ns: 60, 81, 119) that collected the same task (Monetary Incentive Delay task) across two runs and two sessions to evaluate the effects of analytic decisions on the individual (intraclass correlation coefficient [ICC(3,1)]) and group (Jaccard/Spearman rho) reliability estimates of BOLD activity of task fMRI data. The analytic decisions in this study vary across four categories: smoothing kernel (five options), motion correction (four options), task parameterizing (three options) and task contrasts (four options), totaling 240 different pipeline permutations. Across all 240 pipelines, the median ICC estimates are consistently low, with a maximum median ICC estimate of .43 - .55 across the three samples. The analytic decisions with the greatest impact on the median ICC and group similarity estimates are the Implicit Baseline contrast, Cue Model parameterization and a larger smoothing kernel. Using an Implicit Baseline in a contrast condition meaningfully increased group similarity and ICC estimates as compared to using the Neutral cue. This effect was largest for the Cue Model parameterization; however, improvements in reliability came at the cost of interpretability. This study illustrates that estimates of reliability in the MID task are consistently low and variable at small samples, and a higher test-retest reliability may not always improve interpretability of the estimated BOLD signal.

Task-Dependent Brain Activity in Generalized Anxiety Disorder Determined By Bayesian Spatio-Temporal Single Case Model

Introduction: Data obtained from functional magnetic resonance imaging (fMRI) have a complex structure. Considering the special features of this type of data in analyses is of particular importance. Previous studies on generalized anxiety disorder (GAD) as a prevalent mental disorder using functional neuroimaging have had conflicting results. In this study, we apply a Bayesian spatiotemporal model to this type of data which considers both spatial and temporal dependence among regions which is one of the most essential features to consider. Methods: In this single-subject study, we analyze data from a patient with GAD and a healthy participant. Both participants are 24-year-old women who are assigned an emotion reactivity task (matching neutral and negative facial expressions) inside a scanner. The spatial Bayesian variable selection method is used to detect blood oxygen level-dependent activation in fMRI data. Results: Activation areas in neutral and negative facial expressions are provided for both participants by posterior probability map. The results of our study show a greater level of activity in the GAD participant in comparison to the healthy participant in responding to the negative matching task. Conclusion: the GAD patient showed more neural activity in response to negative facial expressions than the healthy participant in brain regions related to emotional response in the areas of the frontal Pole, middle frontal gyrus, insular cortex, and frontal orbital cortex. Moreover, the inferior frontal gyrus in the patient with GAD showed more reaction to negative emotional stimuli.

Thermal stimulus task fMRI in the cervical spinal cord at 7 Tesla.

Although functional magnetic resonance imaging (fMRI) is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0 . Increasing field strength enables higher spatial resolution and improved sensitivity to blood oxygenation level-dependent (BOLD) signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D echo-planar imaging (EPI) protocols, which differ in sensitivity to spatial and temporal B0 inhomogeneity. The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. All protocols used 3 mm slice thickness. For each protocol, the BOLD response to 13 10-s noxious thermal stimuli applied to the right thumb was acquired in a 10-min fMRI run. Image quality, temporal signal to noise ratio (SNR), and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment. PRACTITIONER POINTS: First stimulus task fMRI results in the spinal cord at 7 T. Single-shot 0.75 mm 2D EPI produced the highest mean z-statistic. Multi-shot 0.60 mm 2D EPI provided the best-localized activation and least distortion.

Controlled noninvasive modulation of deep brain regions in humans

Transcranial focused ultrasound provides noninvasive and reversible approaches for precise and personalized manipulations of brain circuits, with the potential to transform our understanding of brain function and treatments of brain dysfunction. However, effective applications in humans have been limited by the human head, which attenuates and distorts ultrasound severely and unpredictably. This has led to uncertain ultrasound intensities delivered into the brain. Here, we address this lingering barrier using a direct measurement approach that can be repeatedly applied to the human brain. The approach uses an ultrasonic scan of the head to measure and compensate for the attenuation of the ultrasound by all obstacles within the ultrasound path. No other imaging modality is required and the method is parameter-free and personalized to each subject. The approach accurately restores operators’ intended intensities inside ex-vivo human skulls. Moreover, the approach is critical for effective modulation of deep brain regions in humans. When applied, the approach modulates fMRI Blood Oxygen Level Dependent (BOLD) activity in disease-relevant deep brain regions. This tool unlocks the potential of emerging approaches based on low-intensity ultrasound for controlled manipulations of neural circuits in humans.

Neurochemistry and functional connectivity in the brain of people with Charles Bonnet syndrome.

Charles Bonnet syndrome (CBS) is a condition in which people with vision loss experience complex visual hallucinations. These complex visual hallucinations may be caused by increased excitability in the visual cortex that are present in some people with vision loss but not others. We aimed to evaluate the association between γ-aminobutyric acid (GABA) in the visual cortex and CBS. We also tested the relationship among visually evoked responses, functional connectivity, and CBS. This is a prospective, case-controlled, cross-sectional observational study. We applied 3-Tesla magnetic resonance spectroscopy, as well as task-based and resting state (RS) connectivity functional magnetic resonance imaging in six participants with CBS and six controls without CBS. GABA+ was measured in the early visual cortex (EVC) and in the lateral occipital cortex (LOC). Participants also completed visual acuity and cognitive tests, and the North-East Visual Hallucinations Interview. The two groups were well-matched for age, gender, visual acuity and cognitive scores. There was no difference in GABA+ levels between groups in the visual cortex. Most participants showed the expected blood oxygenation level dependent (BOLD) activation to images of objects and the phase-scrambled control. Using a fixed effects analysis, we found that BOLD activation was greater in participants with CBS compared to controls. Analysis of RS connectivity with LOC and EVC showed little difference between groups. A fixed effects analysis showed a correlation between the extent of functional connectivity with LOC and hallucination strength. Overall, our results provide no strong evidence for an association between GABAergic inhibition in the visual cortex and CBS. We only found subtle differences in visual function and connectivity between groups. These findings suggest that the neurochemistry and visual connectivity for people with Charles Bonnet hallucinations are comparable to a sight loss population. Differences between groups may emerge when investigating subtle and transient changes that occur at the time of visual hallucinations.

Amygdala-related electrical fingerprint is modulated with neurofeedback training and correlates with deep-brain activation: proof-of-concept in borderline personality disorder.

The modulation of brain circuits of emotion is a promising pathway to treat borderline personality disorder (BPD). Precise and scalable approaches have yet to be established. Two studies investigating the amygdala-related electrical fingerprint (Amyg-EFP) in BPD are presented: one study addressing the deep-brain correlates of Amyg-EFP, and a second study investigating neurofeedback (NF) as a means to improve brain self-regulation. Study 1 combined electroencephalography (EEG) and simultaneous functional magnetic resonance imaging to investigate the replicability of Amyg-EFP-related brain activation found in the reference dataset (N = 24 healthy subjects, 8 female; re-analysis of published data) in the replication dataset (N = 16 female individuals with BPD). In the replication dataset, we additionally explored how the Amyg-EFP would map to neural circuits defined by the research domain criteria. Study 2 investigated a 10-session Amyg-EFP NF training in parallel to a 12-weeks residential dialectical behavior therapy (DBT) program. Fifteen patients with BPD completed the training, N = 15 matched patients served as DBT-only controls. Study 1 replicated previous findings and showed significant amygdala blood oxygenation level dependent activation in a whole-brain regression analysis with the Amyg-EFP. Neurocircuitry activation (negative affect, salience, and cognitive control) was correlated with the Amyg-EFP signal. Study 2 showed Amyg-EFP modulation with NF training, but patients received reversed feedback for technical reasons, which limited interpretation of results. Recorded via scalp EEG, the Amyg-EFP picks up brain activation of high relevance for emotion. Administering Amyg-EFP NF in addition to standardized BPD treatment was shown to be feasible. Clinical utility remains to be investigated.

Poster Session I: Binocular facilitation of the BOLD response to melanopsin stimulation in the suprachiasmatic nucleus.

In a recent analysis of archival data, Spitschan and Cajochen (2019) identify what appears to be substantial binocular facilitation of melatonin suppression due to melanopic light stimulation. This putative effect likely originates in the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) which project directly to the suprachiasmatic nucleus (SCN) of the hypothalamus. We asked whether we could measure a direct physiological correlate of this binocular facilitation using a binocular, MRI-compatible, 10-primary spectral stimulation device. We present preliminary findings from a functional magnetic resonance imaging (fMRI) study designed to explore the blood oxygen level dependent (BOLD) response to monocular and binocular melanopic light stimulation. The study used a 30 s on/off design with three 'ocularity' conditions (binocular-low, monocular-high, binocular-high) and two classes of targeted photoreceptors (melanopsin and LMS cones). Throughout each scan, subjects (N=18) also responded to brief, cone-directed sinusoidal modulations of varying intensity. We report that binocular vs. monocular melanopsin stimulation induced significant BOLD activation in SCN but that this effect was not seen for cone-directed stimulation. This is consistent with the binocular facilitation effect described by Spitschan and Cajochen (2019) and provides the first direct evidence of melanopsin-driven activation and binocular facilitation in human subcortical nuclei.

Neural correlates of deceased-related attention during acute grief in suicide-related bereavement

BackgroundIndividuals who have lost a loved one to suicide demonstrate an attentional bias to deceased-related stimuli during early grief. Regulating attention toward reminders of the deceased during acute bereavement may be linked to grief trajectory and pathological grief development. Despite the potential prognostic importance, little is known about underlying neural circuitry correlates of deceased-related grief processing. The current study examines neural substrates of deceased-related attentional processing during acute grief in individuals bereaved by suicide. MethodsThirty-seven participants grieving the loss of a first-degree relative or partner to suicide in the prior six months, underwent functional magnetic resonance imaging (fMRI) while performing an emotional Stroop task using words related to the deceased and a living attachment figure, in order to examine neural correlates of deceased-specific attentional processing. Clinical interviews were conducted at baseline. ResultsDeceased-related attentional bias was associated with blood oxygen level-dependent (BOLD) activation in a brain network, including dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), orbitofrontal cortex (OFC), and insula. Greater activation of a bilateral prefrontal cluster during deceased-specific attention was negatively correlated with self-reported grief avoidance behaviors. LimitationsLack of non-suicide grief control and small sample size. ConclusionsThese data, if confirmed, indicate a neural network specific to deceased-related attention, and that cognitive control regions within this network appear to be related to grief avoidance behaviors during acute bereavement.

Persistent post-COVID headache is associated with suppression of scale-free functional brain dynamics in non-hospitalized individuals.

Post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long-term effects of COVID-19 and post-COVID headache on brain function remain poorly understood, particularly among non-hospitalized individuals. This study focused on the power-law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post-COVID syndrome, with greatest reductions among those with persistent headache. Resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID-19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu-like symptoms but tested negative for COVID-19. Individuals were assessed an average of 4-5 months after COVID testing, in a cross-sectional, observational study design. No significant differences in H values were found between non-headache COVID-19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non-headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity. These findings provide new insights into the neurophysiological mechanisms that underlie persistent post-COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition.

Is the Brainstem Activation Different Between Healthy Young Male and Female Volunteers at Initiation of Voiding? A High Definition 7-Tesla Magnetic Resonance Imaging Study.

Assessing brainstem function in humans through typical neuroimaging modalities has been challenging. Our objective was to evaluate brain and brainstem activation patterns during initiation of voiding in healthy males and females utilizing a 7 Tesla magnetic resonance imaging (MRI) scanner and a noninvasive brain-bladder functional MRI (fMRI) protocol. Twenty healthy adult volunteers (10 males and 10 females) with no history of urinary symptoms were recruited. Each volunteer underwent a clinic uroflow and postvoid residual assessment and was asked to consume water prior to entering the scanner. Anatomical and diffusion tensor images were obtained first, followed by a blood oxygenation level dependent (BOLD) resting-state fMRI (rs-fMRI) during the empty bladder. Subjects indicated when they felt the urge to void, and a full bladder rs-fMRI was obtained. Once completed, the subjects began 5 voiding cycles, where the first 7.5 seconds of each voiding cycle was identified as "initiation of voiding." BOLD activation maps were generated, and regions of interests with a t-value greater than 2.1 were deemed statistically significant. We present 5 distinct regions within the periaqueductal gray (PAG) and pontine micturition center (PMC) with statistically significant activation associated with an initiation of voiding in both men and women, 3 within the PAG and 2 within the PMC. Several additional areas in the brain also demonstrated activation as well. When comparing males to females, there was an overall lower BOLD activation seen in females throughout all regions, with the exception of the caudate lobe. Our study effectively defines regions within the PAG and PMC involved in initiation of voiding in healthy volunteers. To our knowledge, this is the first study investigating differences between male and female brainstem activation utilizing an ultra-high definition 7T MRI.

Relation ofresting brain signal variability to cognitive andsocioemotional measures inan adult lifespan sample.

Temporal variability of the fMRI-derived blood-oxygen-level-dependent (BOLD) signal during cognitive tasks shows important associations with individual differences in age and performance. Less is known about relations between spontaneous BOLD variability measured at rest and relatively stable cognitive measures, such as IQ or socioemotional function. Here, we examined associations among resting BOLD variability, cognitive/socioemotional scores from the NIH Toolbox and optimal time of day for alertness (chronotype) in a sample of 157 adults from 20 to 86 years of age. To investigate individual differences in these associations independently of age, we regressed age out from both behavioral and BOLD variability scores. We hypothesized that greater BOLD variability would be related to higher fluid cognition scores, more positive scores on socioemotional scales and a morningness chronotype. Consistent with this idea, we found positive correlations between resting BOLD variability, positive socioemotional scores (e.g. self-efficacy) and morning chronotype, as well as negative correlations between variability and negative emotional scores (e.g. loneliness). Unexpectedly, we found negative correlations between BOLD variability and fluid cognition. These results suggest that greater resting brain signal variability facilitates optimal socioemotional function and characterizes those with morning-type circadian rhythms, but individuals with greater fluid cognition may be more likely to show less temporal variability in spontaneous measures of BOLD activity.

Segmented spin-echo echo-planar imaging improves whole-brain BOLD functional MRI in awake pigeon brains.

Functional magnetic resonance imaging (fMRI) in awake small animals such as pigeons or songbirds opens a new window into the neural fundaments of cognitive behavior. However, high-field fMRI in the avian brain is challenging due to strong local magnetic field inhomogeneities caused by air cavities in the skull. A spoiled gradient-echo fMRI sequence has already been used to map the auditory network in songbirds, but due to susceptibility artifacts only 50% of the whole brain could be recorded. Since whole-brain fMRI coverage is vital to reveal whole-brain networks, an MRI sequence that is less susceptible to these artifacts was required. This was recently achieved in various bird species by using a rapid acquisition with relaxation enhancement (RARE) sequence. Weak blood oxygen level-dependent (BOLD) sensitivity, low temporal resolution, and heat caused by the long train of RF refocusing pulses are the main limits of RARE fMRI at high magnetic fields. To go beyond some of these limitations, we here describe the implementation of a two-segmented spin-echo echo-planar imaging (SE-EPI). The proposed sequence covers the whole brain of awake pigeons. The sequence was applied to investigate the auditory network in awake pigeons and assessed the relative merits of this method in comparison with the single-shot RARE sequence. At the same imaging resolution but with a volume acquisition of 3 s versus 4 s for RARE, the two-segmented SE-EPI provided twice the strength of BOLD activity compared with the single-shot RARE sequence, while the image signal-to-noise ratio (SNR) and in particular the temporal SNR were very similar for the two sequences. In addition, the activation patterns in two-segmented SE-EPI data are more symmetric and larger than single-shot RARE results. Two-segmented SE-EPI represents a valid alternative to the RARE sequence in avian fMRI research since it yields more than twice the BOLD sensitivity per unit of time with much less energy deposition and better temporal resolution, particularly for event-related experiments.