Blood Oxygenation Level-dependent Signal Changes Research Articles

Increased Recruitment of Domain-General Neural Networks in Language Processing Following Intensive Language-Action Therapy: fMRI Evidence From People With Chronic Aphasia.

PurposeThis study aimed to provide novel insights into the neural correlates of language improvement following intensive language-action therapy (ILAT; also known as constraint-induced aphasia therapy).MethodSixteen people with chronic aphasia underwent clinical aphasia assessment (Aachen Aphasia Test [AAT]), as well as functional magnetic resonance imaging (fMRI), both administered before (T1) and after ILAT (T2). The fMRI task included passive reading of single written words, with hashmark strings as visual baseline.ResultsBehavioral results indicated significant improvements of AAT scores across therapy, and fMRI results showed T2−T1 blood oxygenation-level-dependent (BOLD) signal change in the left precuneus to be modulated by the degree of AAT score increase. Subsequent region-of-interest analysis of this precuneus cluster confirmed a positive correlation of T2−T1 BOLD signal change and improvement on the clinical aphasia test. Similarly, the entire default mode network revealed a positive correlation between T2−T1 BOLD signal change and clinical language improvement.ConclusionThese results are consistent with a more efficient recruitment of domain-general neural networks in language processing, including those involved in attentional control, following aphasia therapy with ILAT.

0073 Left Anterior Cingulate Hyperarousal During Sleep Anxiety-Inducing Emotional Tasks Performance in Patients with Insomnia Disorder

Abstract Introduction Patients with insomnia frequently experience sleep/insomnia-related anxiety; this anxiety has been associated with hyperarousal. We investigated the underlying brain function changes in patients with insomnia during emotional task performance that induced sleep/insomnia-related anxiety. Methods Functional magnetic resonance imaging (fMRI) was performed during emotional task performance in healthy individuals and patients with insomnia who met the diagnostic criteria of insomnia disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and had chronic insomnia for more than 6 months. The participants underwent fMRI scanning during three types of emotional task performance—insomnia-anxiety task, reading sentences that cause insomnia-related anxiety; general-anxiety task, reading sentences that cause anxiety for everyone; and neutral task, reading neutral sentences that do not cause emotional anxiety. The images obtained from fMRI and blood oxygen level-dependent (BOLD) signal changes were compared between patients with insomnia and healthy controls. Interim analysis was performed with the data of 13 patients with insomnia and 9 controls. Results The brain activity in the left anterior cingulate was higher during insomnia-anxiety task performance than that during general-anxiety task performance in the insomnia group (voxel-wise uncorrected p < 0.05; cluster size, 100). In the insomnia group, the brain activity during insomnia-anxiety task performance was not lower in any brain area than that during general-anxiety task performance. Conclusion We show that patients with chronic insomnia experience sleep anxiety related with hyperarousal in the left anterior cingulate area. Additional subject recruitment and re-analysis are needed to confirm the findings of this interim analysis. Support This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03032431).

Developmental patterns of CBF and BOLD responses to visual stimulus

To investigate the developmental changes of cerebral blood flow (CBF) and hemodynamic responses to changing neural activity, we used the arterial spin label (ASL) technique to measure resting CBF and simultaneous CBF / blood-oxygen-level dependent (BOLD) signal changes during visual stimulation in 97 typically developing children and young adults (age 13.35 [6.02, 25.25] (median [min, max]) years old at the first time point). The longitudinal study protocol included three MRIs (2.7 ± 0.06 obtained), one year apart, for each participant. Mixed-effect linear and non-linear statistical models were used to analyze age effects on CBF and BOLD signals. Resting CBF decreased exponentially with age (p = 0.0001) throughout the brain, and developmental trajectories differed across brain lobes. The absolute CBF increase in visual cortex during stimulation was constant over the age range, but the fractional CBF change increased with age (p = 0.0001) and the fractional BOLD signal increased with age (p = 0.0001) correspondingly. These findings suggest that the apparent neural hemodynamic coupling in visual cortex does not change after age six years, but age-related BOLD signal changes continue through adolescence primarily due to the changes with age in resting CBF.

Imaging brain function with simultaneous BOLD and viscoelasticity contrast: fMRI/fMRE

Magnetic resonance elastography (MRE) is emerging as a new tool for studying viscoelastic changes in the brain resulting from functional processes. Here, we demonstrate a novel time series method to generate robust functional magnetic resonance elastography (fMRE) activation maps in response to a visual task with a flashing checkerboard stimulus. Using a single-shot spin-echo (SS-SE) pulse sequence, the underlying raw images inherently contain blood-oxygen-level dependent (BOLD) contrast, allowing simultaneous generation of functional magnetic resonance imaging (fMRI) activation maps from the magnitude and functional magnetic resonance elastography (fMRE) maps from the phase. This allows an accurate comparison of the spatially localized stiffness (fMRE) and BOLD (fMRI) changes within a single scan, eliminating confounds inherent in separately acquired scans. Results indicate that tissue stiffness within the visual cortex increases 6–11% with visual stimuli, whereas the BOLD signal change was 1–2%. Furthermore, the fMRE and fMRI activation maps have strong spatial overlap within the visual cortex, providing convincing evidence that fMRE is possible in the brain. However, the fMRE temporal SNR (tSNRfMRE) maps are heterogeneous across the brain. Using a dictionary matching approach to characterize the time series, the viscoelastic changes are consistent with a viscoelastic response function (VRF) time constant of 12.1 ​s ± 3.0 ​s for a first-order exponential decay, or a shape parameter of 8.1 ​s ± 1.4 ​s for a gamma-variate.

Cortical laminar resting-state signal fluctuations scale with the hypercapnic blood oxygenation level-dependent response.

Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level‐dependent (BOLD) response. This is achieved by scaling, using information from a perfusion‐sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath‐hold task. In this work, we seek for a validation of the use of the resting‐state fluctuation amplitude () as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth‐dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. from the primary motor cortex was, thus, compared to the amplitude of hypercapnia‐induced signal changes () and with the factor of the Davis model on a laminar level. High linear correlations were observed for and () and somewhat reduced for and (). Laminar profiles of ‐normalized BOLD signal changes yielded good agreement with corresponding VASO profiles. Overall, this suggests that contains strong vascular components and is also modulated by baseline quantities contained in the factor. We conclude that may replace the scaling factor for normalizing the laminar BOLD response.

Short- and long-term reproducibility of BOLD signal change induced by breath-holding at 1.5 and 3 T.

Cerebrovascular reactivity (CVR) can give insight into the cerebrovascular function. CVR can be estimated by measuring a blood-oxygen-level-dependent (BOLD) response combined with breath-holding (BH). The reproducibility of this technique has been addressed and existing studies have focused on short-term reproducibility using a 3 T magnetic resonance imaging (MRI) system. However, little is known about the long-term reproducibility of this procedure and the corresponding reproducibility using a 1.5 T MRI system. Here, we systematically examined the short- and long-term reproducibility of BOLD responses to BH across field strengths. Nine subjects participated in three MRI sessions separated by 30 minutes (sessions 1 and 2: short term) and 68-92 days (sessions 1 and 3, long term) at both 1.5 and 3 T MRI. Our findings revealed that significant differences between field strengths were detected in the activated gray matter volume and BOLD signal change (both P < 0.001), with smaller magnitudes at 1.5 T. However, activation patterns were reproducible, independent of the time interval, brain region or field strength. All interscan coefficient of variation values were below the 33% fiducial limit, and the intraclass correlation coefficient values were above 0.4, which is usually considered the acceptability limit in functional studies. These findings suggest that the response of BOLD signal to BH for assessing CVR is reproducible over time at 1.5 and 3 T. This technique can be considered a tool for monitoring longitudinal changes in patients with cerebrovascular diseases, and its use should be encouraged for clinical 1.5 T MRI systems.

A randomized, placebo-controlled, phase 1 study to evaluate the effects of TAK-063 on ketamine-induced changes in fMRI BOLD signal in healthy subjects

RationalePhosphodiesterase 10A inhibitor TAK-063 has shown effects that suggest efficacy in schizophrenia treatment.ObjectiveThis randomized, double-blind, placebo-controlled, incomplete-crossover study investigated effects of single oral administration of TAK-063 on ketamine-induced changes in blood oxygen level-dependent (BOLD) signal in healthy males.MethodsHealthy men aged 18 to 45 years with normal magnetic resonance imaging (MRI) scans and electroencephalogram measurements at screening were eligible. Each subject was randomized to one of nine treatment schedules: all subjects received placebo and two of three doses of TAK-063 followed by ketamine. The primary endpoint was ketamine-induced brain activity in select regions of the brain during resting state. Secondary endpoints included pharmacokinetic parameters of TAK-063, proportion of subjects with treatment-emergent adverse events (AEs), and percentage of subjects meeting criteria for abnormal safety laboratory tests and vital sign measurements.ResultsThe study comprised 27 subjects. Prior to ketamine infusion, TAK-063 exerted region-specific effects on resting state functional MRI (fMRI) BOLD signal. After ketamine administration, TAK-063 reduced the Cohen’s effect size for resting-state fMRI BOLD signal in key brain regions examined, and exerted similar effects on BOLD signal during the working memory task across all doses. TAK-063 was safe and well tolerated.ConclusionsOur results are consistent with non-clinical studies of ketamine and TAK-063 and clinical studies of ketamine and risperidone. It is unknown whether these data are predictive of potential antipsychotic efficacy, and further analyses are required.

Spatial task-related brain activity and its association with preferred and fast pace gait speed in older adults

Task-related brain activity is associated with preferred pace gait speed in older adults. Whether similar regional brain activity relates to fast pace gait speed has yet to be determined, but may provide insight into neural substrate important for walking under various conditions. This study measured regional blood-oxygen-level dependent (BOLD) changes using functional magnetic resonance imaging (fMRI) in response to a spatial Simon/Stroop task in community-dwelling older adults (N = 20, 63–80y). Preferred pace, fast pace, and dual-task gait speeds (picking up objects at preferred pace; fast walking over obstacles) were measured across a 7-meter course. Time to complete a fast pace 400 m walk test was also recorded. Partial correlations were used for all analyses after adjusting for age. Accuracy on incongruent trials of the spatial task was positively correlated with all fast walking conditions (all p < 0.01), but not preferred pace walking conditions. BOLD signal change in the left middle frontal gyrus during the spatial task was associated with preferred pace gait speed (r = 0.51, p = 0.02) and fast walking over obstacles (r = 0.53, p = 0.01). Interestingly, BOLD signal change in the bilateral precuneus was associated with fast pace gait speed (r = 0.58, p < 0.01), fast walking over obstacles (r = 0.48, p = 0.03), and 400 m walk time (r=−0.49, p = 0.02). These results find preferred and fast pace gait speed are associated with different regional task-related brain activity, with activation in the precuneus related with greater performance during fast pace walking.

EEG-correlated fMRI of human alpha (de-)synchronization

ObjectivesWe investigated blood oxygenation level-dependent (BOLD) brain activity changes in wakefulness and light sleep and in relation to those associated with the posterior alpha rhythm, the most prominent feature of the clinical EEG. Studies have reported different sets of brain regions changing their oxygen consumption with waxing and waning alpha oscillations. Here, we hypothesize that these dissimilar activity patterns reflect different wakefulness-dependent brain states. MethodsWe recorded BOLD signal changes and electroencephalography (EEG) simultaneously in 149 subjects at rest. Based on American Academy of Sleep Medicine criteria, we selected subjects exhibiting wakefulness or light sleep (N1). We identified brain regions in which BOLD signal changes correlated with (i) clinical sleep stages, (ii) alpha band power and (iii) a multispectral EEG index, respectively. ResultsDuring light sleep, we found increased BOLD activity in parieto-occipital regions. In wakefulness compared to light sleep, we revealed BOLD signal increases in the thalamus. The multispectral EEG-index revealed hippocampal activity changes in light sleep not reported before. ConclusionChanges in alpha oscillations reflect different brain states associated with different levels of wakefulness and thalamic activity. We can link the previously described parieto-occipital pattern to drowsiness. Additionally, in that stage, we identify hippocampal activity fluctuations. SignificanceThalamic activity varies with early changes of wakefulness, which is important to consider in resting state experiments. The EEG-indexed activation of the hippocampus during light sleep suggests that memory encoding might already take place during this early stage of sleep.

Extraction of the cardiac waveform from simultaneous multislice fMRI data using slice sorted averaging and a deep learning reconstruction filter

Cardiac signal contamination has long confounded the analysis of blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Cardiac pulsation results in significant BOLD signal changes, especially in and around blood vessels. Until the advent of simultaneous multislice echo-planar imaging (EPI) acquisition, the time resolution of whole brain EPI was insufficient to avoid cardiac aliasing (and acquisitions with repetition times (TRs) under 400–500 ms are still uncommon). As a result, direct detection and removal of the cardiac signal with spectral filters is generally not possible. Modelling methods have been developed to mitigate cardiac contamination, and recently developed techniques permit the visualization of cardiac signal propagation through the brain in undersampled data (e.g., TRs > 1s), which is useful in its own right for finding blood vessels. However, both of these techniques require data from which to estimate cardiac phase, which is generally not available for the data in many large databases of existing imaging data, and even now is not routinely recorded in many fMRI experiments.Here we present a method to estimate the cardiac waveform directly from a multislice fMRI dataset, without additional physiological measurements, such as plethysmograms. The pervasive spatial extent and temporal structure of the cardiac contamination signal across the brain offers an opportunity to exploit the nature of multislice imaging to extract this signal from the fMRI data itself. While any particular slice is recorded at the TR of the imaging experiment, slices are recorded much more quickly – typically from 10 to 20 Hz - sufficiently fast to fully sample the cardiac signal. Using the fairly permissive assumptions that the cardiac signal is a) pseudoperiodic b) somewhat coherent within any given slice, and c) is similarly shaped throughout the brain, we can extract a good estimate of the cardiac phase as a function of time from fMRI data alone. If we make further assumptions about the shape and consistency of cardiac waveforms, we can develop a deep learning filter to greatly improve our estimate of the cardiac waveform.

Simultaneous fMRI-EEG-DTI recording of MMN in patients with schizophrenia.

Functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), and diffusion tensor imaging (DTI) recording have complementary spatiotemporal resolution limitations but can be powerful methods when used together to enable both functional and anatomical modeling, with each neuroimaging procedure used to maximum advantage. We recorded EEGs during event-related fMRI followed by DTI in 15 healthy volunteers and 12 patients with schizophrenia using an omission mismatch negativity (MMN) paradigm. Blood oxygenation level-dependent (BOLD) signal changes were calculated in a region of interest (ROI) analysis, and fractional anisotropy (FA) in the white matter fibers related to each area was compared between groups using tract-specific analysis. Patients with schizophrenia had reduced BOLD activity in the left middle temporal gyrus, and BOLD activity in the right insula and right parahippocampal gyrus significantly correlated with positive symptoms on the Positive and Negative Syndrome Scale (PANSS) and hostility subscores. BOLD activation of Heschl’s gyri also correlated with the limbic system, including the insula. FA values in the left anterior cingulate cortex (ACC) significantly correlated with changes in the BOLD signal in the right superior temporal gyrus (STG), and FA values in the right ACC significantly correlated with PANSS scores. This is the first study to examine MMN using simultaneous fMRI, EEG, and DTI recording in patients with schizophrenia to investigate the potential implications of abnormalities in the ACC and limbic system, including the insula and parahippocampal gyrus, as well as the STG. Structural changes in the ACC during schizophrenia may represent part of the neural basis for the observed MMN deficits. The deficits seen in the feedback/feedforward connections between the prefrontal cortex and STG modulated by the ACC and insula may specifically contribute to impaired MMN generation and clinical manifestations.

Cerebral Autoregulation Evidenced by Synchronized Low Frequency Oscillations in Blood Pressure and Resting-State fMRI.

Resting-state functional magnetic resonance imaging (rs-fMRI) is a widely used technique for mapping the brain’s functional architecture, so delineating the main sources of variance comprising the signal is crucial. Low frequency oscillations (LFO) that are not of neural origin, but which are driven by mechanisms related to cerebral autoregulation (CA), are present in the blood-oxygenation-level-dependent (BOLD) signal within the rs-fMRI frequency band. In this study we use a MR compatible device (Caretaker, Biopac) to obtain a non-invasive estimate of beat-to-beat mean arterial pressure (MAP) fluctuations concurrently with rs-fMRI at 3T. Healthy adult subjects (n = 9; 5 male) completed two 20-min rs-fMRI scans. MAP fluctuations were decomposed into different frequency scales using a discrete wavelet transform, and oscillations at approximately 0.1 Hz show a high degree of spatially structured correlations with matched frequency fMRI fluctuations. On average across subjects, MAP fluctuations at this scale of the wavelet decomposition explain ∼2.2% of matched frequency fMRI signal variance. Additionally, a simultaneous multi-slice multi-echo acquisition was used to collect 10-min rs-fMRI at three echo times at 7T in a separate group of healthy adults (n = 5; 5 male). Multiple echo times were used to estimate the R2∗ decay at every time point, and MAP was shown to strongly correlate with this signal, which suggests a purely BOLD (i.e., blood flow related) origin. This study demonstrates that there is a significant component of the BOLD signal that has a systemic physiological origin, and highlights the fact that not all localized BOLD signal changes necessarily reflect blood flow supporting local neural activity. Instead, these data show that a proportion of BOLD signal fluctuations in rs-fMRI are due to localized control of blood flow that is independent of local neural activity, most likely reflecting more general systemic autoregulatory processes. Thus, fMRI is a promising tool for studying flow changes associated with cerebral autoregulation with high spatial resolution.

Advanced visual network and cerebellar hyperresponsiveness to trigeminal nociception in migraine with aura

BackgroundDespite the growing body of advanced studies investigating the neuronal correlates of pain processing in patients with migraine without aura (MwoA), only few similar studies have been conducted in patients with migraine with aura (MwA). Therefore, we aimed to explore the functional brain response to trigeminal noxious heat stimulation in patients with MwA.MethodsSeventeen patients with MwA and 15 age- and sex-matched healthy controls (HC) underwent whole-brain blood oxygen level–dependent (BOLD) fMRI during trigeminal noxious heat stimulation. To examine the specificity of any observed differences between patients with MwA and HC, the functional response of neural pathways to trigeminal noxious heat stimulation in patients with MwA was compared with 18 patients with MwoA. Secondary analyses investigated the correlations between BOLD signal changes and clinical parameters of migraine severity.ResultsWe observed a robust cortical and subcortical pattern of BOLD response to trigeminal noxious heat stimulation across all participants. Patients with MwA showed a significantly increased activity in higher cortical areas known to be part of a distributed network involved in advanced visual processing, including lingual gyrus, inferior parietal lobule, inferior frontal gyrus and medial frontal gyrus. Moreover, a significantly greater cerebellar activation was observed in patients with MwA when compared with both patients with MwA and HC. Interestingly, no correlations were found between migraine severity parameters and magnitude of BOLD response in patients with MwA.ConclusionOur findings, characterized by abnormal visual pathway response to trigeminal noxious heat stimulation, support the role of a functional integration between visual and trigeminal pain networks in the pathophysiological mechanisms underlying migraine with aura. Moreover, they expand the concept of “neurolimbic-pain network” as a model of MwoA including both limbic dysfunction and cortical dys-excitability. Indeed, we suggest a model of “neurolimbic-visual-pain network” in MwA patients, characterized by dysfunctional correlations between pain-modulating circuits not only with the cortical limbic areas but with advanced visual areas as well. Furthermore, the abnormal cerebellar response to trigeminal noxious heat stimulation may suggest a dysfunctional cerebellar inhibitory control on thalamic sensory gating, impinging on the advanced visual processing cortical areas in patients with MwA.

Effects of Hemodynamic Response Function Selection on Rat fMRI Statistical Analyses.

The selection of the appropriate hemodynamic response function (HRF) for signal modeling in functional magnetic resonance imaging (fMRI) is important. Although the use of the boxcar-shaped hemodynamic response function (BHRF) and canonical hemodynamic response (CHRF) has gained increasing popularity in rodent fMRI studies, whether the selected HRF affects the results of rodent fMRI has not been fully elucidated. Here we investigated the signal change and t-statistic sensitivities of BHRF, CHRF, and impulse response function (IRF). The effect of HRF selection on different tasks was analyzed by using data collected from two groups of rats receiving either 3 mA whisker pad or 3 mA forepaw electrical stimulations (n = 10 for each group). Under whisker pad stimulation with large blood-oxygen-level dependent (BOLD) signal change (4.31 ± 0.42%), BHRF significantly underestimated signal changes (P < 0.001) and t-statistics (P < 0.001) compared with CHRF or IRF. CHRF and IRF did not provide significantly different t-statistics (P > 0.05). Under forepaw stimulation with small BOLD signal change (1.71 ± 0.34%), different HRFs provided insignificantly different t-statistics (P > 0.05). Therefore, the selected HRF can influence data analysis in rodent fMRI experiments with large BOLD responses but not in those with small BOLD responses.

Regional Cerebral Activation Accompanies Sympathoexcitation in Women With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is associated with increased sympathetic nervous system activation, but the cerebral pathways involved are unclear. To compare cerebral [blood oxygen level-dependent (BOLD) functional MRI], pressor [blood pressure (BP), heart rate (HR], and muscle sympathetic nerve activity (MSNA) responses to isometric forearm contraction (IFC) in women with PCOS and matched control subjects. Case-control study. Referral center. Patients with PCOS (n = 20; mean ± SD data: age, 29.8 ± 4.8 years; body mass index (BMI), 26.1 ± 4.9 kg/ m2) and 20 age- and BMI-matched control subjects (age, 29.7 ± 5.0 years; BMI, 26.1 ± 4.8 kg/ m2). BP, HR, catecholamine, and MSNA responses to 30% IFC. BOLD signal change was modeled for BP response to 30% IFC. Although HR and BP increased to a similar extent in both groups after IFC, MSNA burst frequency increased by 68% in the PCOS group compared with 11.9% in control subjects (n = 7 in both groups; P = 0.002). Brain activation indexed by the BOLD signal in response to IFC was significantly greater in the PCOS group (n = 15) compared with controls (n = 15) in the right orbitofrontal cortex (P < 0.0001). Adjustment for insulin sensitivity, but not hyperandrogenism, abolished these between-group differences. Our study confirms enhanced sympathoexcitation in women with PCOS and demonstrates increased regional brain activation in response to IFC. The right orbitofrontal cortex BOLD signal change in women with PCOS is associated with insulin sensitivity. Additional studies are warranted to clarify whether this may offer a novel target for cardiovascular risk reduction.

Signal Changes in Hippocampal Subfields during Controlled Breathing Patterns by Using Functional MRI

The purpose of this study was to investigate the functional properties of each hippocampal subfield and determine its association with decreased working memory due to abnormal breathing. Eleven healthy volunteers participated in this study and performed a breathing task in magnetic resonance imaging (MRI). To quantify the effects of various breathing patterns on the hippocampus, we segmented its subfields and then applied them to the functional MRI (fMRI) data to measure the signal change according to the respiration pattern. The results indicated that mouth breathing (mouth inhalation and exhalation) had the biggest effect on signal change. Of all subfields studied, the hippocampal head showed the greatest change. These findings imply that mouth breathing can significantly induce blood oxygenation level-dependent (BOLD) signal change in the hippocampus; especially, the hippocampal head is the most susceptible to breathing alterations, suggesting that it could be strongly associated with poor working memory in habitual mouth-breathers.

Decreased regional brain activity in response to sleep‐related sounds after cognitive behavioral therapy for psychophysiological insomnia

Patients with psychophysiological insomnia (PI) experience hyperarousal, especially as a reaction to sound stimuli. In the current study, we explored brain activity changes in response to sleep-related sounds (SS) in patients with insomnia after cognitive behavioral therapy for insomnia (CBT-I). In 14 drug-free PI patients, regional brain activity in response to SS, and to white noise sound (NS) as neutral stimuli, was investigated before and after individual CBT-I using functional magnetic resonance imaging. Blood oxygen level-dependent (BOLD) signals to SS and NS were compared before and after CBT-I. In addition, the association between clinical improvement after CBT-I and changes in brain activity in response to SS and NS was analyzed. Compared with baseline, regional brain activity in response to SS after CBT-I decreased in the left middle temporal and left middle occipital gyrus. In regression analysis, a reduction in the Dysfunctional Beliefs and Attitudes about Sleep (DBAS) Scale score after CBT-I was associated with decrease in brain activity in response to SS in both thalami. However, brain activity in response to NS showed no BOLD signal changes and no association with DBAS change. Cortical hyperactivity, which may cause hyperarousal in PI, was found to decrease after CBT-I. CBT-I targeting changes in beliefs and attitudes about sleep may induce its therapeutic effects by reducing thalamic brain activity in response to sleep-related stimuli.

Reliability of supraspinal correlates to lower urinary tract stimulation in healthy participants – A fMRI study

Previous functional neuroimaging studies provided evidence for a specific supraspinal network involved in lower urinary tract (LUT) control. However, data on the reliability of blood oxygenation level-dependent (BOLD) signal changes during LUT task-related functional magnetic resonance imaging (fMRI) across separate measurements are lacking. Proof of the latter is crucial to evaluate whether fMRI can be used to assess supraspinal responses to LUT treatments.Therefore, we prospectively assessed task-specific supraspinal responses from 20 healthy participants undergoing two fMRI measurements (test-retest) within 5–8 weeks. The fMRI measurements, conducted in a 3T magnetic resonance (MR) scanner, comprised a block design of repetitive bladder filling and drainage using an automated MR-compatible and MR-synchronized infusion-drainage device. Following transurethral catheterization and bladder pre-filling with body warm saline until participants perceived a persistent desire to void (START condition), fMRI was recorded during repetitive blocks (each 15 s) of INFUSION and WITHDRAWAL of 100 mL body warm saline into respectively from the bladder. BOLD signal changes were calculated for INFUSION minus START. In addition to whole brain analysis, we assessed BOLD signal changes within multiple ‘a priori’ region of interest (ROI), i.e. brain areas known to be involved in the LUT control from previous literature. To evaluate reliability of the fMRI results between visits, we applied different types of analyses: coefficient of variation (CV), intraclass correlation coefficient (ICC), Sørensen-Dice index, Bland-Altman method, and block-wise BOLD signal comparison.All participants completed the study without adverse events. The desire to void was rated significantly higher for INFUSION compared to START or WITHDRAWAL at both measurements without any effect of visit. At whole brain level, significant (p < 0.05, cluster corrected, k ≥ 41 voxels) BOLD signal changes were found for the contrast INFUSION compared to START in several brain areas. Overlap of activation maps from both measurements were observed in the orbitofrontal cortex, insula, ventrolateral prefrontal cortex (VLPFC), and inferior parietal lobe. The two highest ICCs, based on a ROI's mean beta weight, were 0.55 (right insular cortex) and 0.47 (VLPFC). Spatial congruency (Sørensen-Dice index) of all voxels within each ROI between measurements was highest in the insular cortex (left 0.55, right 0.44). In addition, the mean beta weight of the right insula and right VLPFC demonstrated the lowest CV and narrowest Bland and Altman 95% limits of agreement.In conclusion, the right insula and right VLPFC were revealed as the two most reliable task-specific ROIs using our automated, MR-synchronized protocol. Achieving high reliability using a viscero-sensory/interoceptive task such as repetitive bladder filling remains challenging and further endeavour is highly warranted to better understand which factors influence fMRI outcomes and finally to assess LUT treatment effects on the supraspinal level.

Initial evidence for hypothalamic gliosis in children with obesity by quantitative T2 MRI and implications for blood oxygen‐level dependent response to glucose ingestion

In adults, hypothalamic gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion. Children with obesity (N=11) had longer T2 relaxation times, consistent with gliosis, in the mediobasal hypothalamus (MBH) compared to controls (N=9; P=0.004). Moreover, there was a highly significant group*region interaction (P=0.002), demonstrating that signs of gliosis were specific to MBH and not to reference regions. Longer T2 relaxation times correlated with measures of higher adiposity, including visceral fat percentage (P=0.01). Mean glucose-induced hypothalamic blood oxygen-level dependent signal change did not differ between groups (P=0.11). However, mean left MBH T2 relaxation time negatively correlated with glucose-induced hypothalamic signal change (P<0.05). Imaging signs of hypothalamic gliosis were present in children with obesity and positively associated with more severe adiposity. Children with the strongest evidence for gliosis showed the least activation after glucose ingestion. These initial findings suggest that the hypothalamus is both structurally and functionally affected in childhood obesity.

Posterior cingulate cortex/precuneus blood oxygen-level dependent signal changes during the repetition of an attention task in meditators and nonmeditators.

Among several cognitive advantages, meditation is thought to enhance practitioners' capacity for sustained attention. In the present study, we explored this question by testing meditation practitioners (meditators) and nonpractitioners (nonmeditators) on a task that requires sustained attention, the Stroop Word-Color Task (SWCT), while using functional MRI. Participants were all right-handed and included 23 regular meditators as well as 17 nonmeditators. Participants viewed color words (i.e. 'red,' 'blue,' or 'green') presented one at a time on the screen that were written in either the same color (congruent condition) or a different color (incongruent condition) and were asked to indicate the color of the print. Participants also viewed noncolor words written in unrelated colors (neutral condition). Both groups completed the same two acquisition runs. Although both meditators and nonmeditators gave faster responses on run 2 than run 1 for both the neutral and incongruent trials, nonmeditators showed decreased activation and meditators showed increased activation in precuneus/posterior cingulate cortex. These regions were previously shown to be activated in the SWCT and belong to default mode network as well as to cognitive control network. Attention to repetitive stimuli during two equal runs of SWCT is mediated by the precuneus/posterior cingulate cortex, and mental training through meditation may influence the activity of these regions during such tasks.