Blood Oxygen Level-dependent Signal Research Articles

Reversal of neurovascular decoupling and cognitive impairment in patients with end-stage renal disease during a hemodialysis session: Evidence from a comprehensive fMRI analysis.

Neurovascular (NV) decoupling is a potential neuropathologic mechanism of cognitive impairment in patients with end-stage renal disease (ESRD). Hemodialysis improves cognitive impairment at 24 h post-dialysis, which suggests a potential neuroprotective effect of hemodialysis treatment on the brain. We investigated the effects of hemodialysis treatment on the reversal of NV decoupling associated with cognitive improvement. A total of 39 patients with ESRD and 39 healthy controls were enrolled. All patients were imaged twice during a dialysis session: before hemodialysis (T1pre-dialysis ) and at 24 h after dialysis (T2post-dialysis ). The healthy controls were imaged once. NV coupling was characterized based on correlation coefficients between four types of blood oxygen level-dependent signals and cerebral blood flow (CBF). A battery of neuropsychological and blood tests was performed before the imaging. Patients with ESRD showed improvements in memory and executive function at T2post-dialysis compared with that at T1pre-dialysis . At both T1pre-dialysis and T2post-dialysis , patients with ESRD had lower amplitude of low-frequency fluctuation (ALFF)-CBF coupling than healthy controls. Additionally, patients with ESRD had higher ALFF-CBF coupling at T2post-dialysis than at T1pre-dialysis . Higher memory scores, higher hemoglobin level, lower total plasma homocysteine level, lower systolic blood pressure variance, and lower ultrafiltration volume were associated with higher ALFF-CBF coupling in patients with ESRD after a hemodialysis session. These findings indicate that partial correction of anemia and hyperhomocysteinemia, stable systolic blood pressure, and fluid restriction may be closely linked to the reversal of NV decoupling and improvement in cognition in patients with ESRD.

The many layers of BOLD. The effect of hypercapnic and hyperoxic stimuli on macro- and micro-vascular compartments quantified by CVR, M, and CBV across cortical depth

Ultra-high field functional magnetic resonance imaging (fMRI) offers the spatial resolution to measure neuronal activity at the scale of cortical layers. However, cortical depth dependent vascularization differences, such as a higher prevalence of macro-vascular compartments near the pial surface, have a confounding effect on depth-resolved blood-oxygen-level dependent (BOLD) fMRI signals. In the current study, we use hypercapnic and hyperoxic breathing conditions to quantify the influence of all venous vascular and micro-vascular compartments on laminar BOLD fMRI, as measured with gradient-echo (GE) and spin-echo (SE) scan sequences, respectively. We find that all venous vascular and micro-vascular compartments are capable of comparable theoretical maximum signal intensities, as represented by the M-value parameter. However, the capacity for vessel dilation, as reflected by the cerebrovascular reactivity (CVR), is approximately two and a half times larger for all venous vascular compartments combined compared to the micro-vasculature at superficial layers. Finally, there is roughly a 35% difference in estimates of CBV changes between all venous vascular and micro-vascular compartments, although this relative difference was approximately uniform across cortical depth. Thus, our results suggest that fMRI BOLD signal differences across cortical depth are likely caused by differences in dilation properties between macro- and micro-vascular compartments.

Improved laminar specificity and sensitivity by combining SE and GE BOLD signals

The most widely used gradient-echo (GE) blood oxygenation level-dependent (BOLD) contrast has high sensitivity, but low specificity due to draining vein contributions, while spin-echo (SE) BOLD approach at ultra-high magnetic fields is highly specific to neural active sites but has lower sensitivity. To obtain high specificity and sensitivity, we propose to utilize a vessel-size-sensitive filter to the GE-BOLD signal, which suppresses macrovascular contributions and to combine selectively retained microvascular GE-BOLD signals with the SE-BOLD signals. To investigate our proposed idea, fMRI with 0.8 mm isotropic resolution was performed on the primary motor and sensory cortices in humans at 7 T by implementing spin- and gradient-echo (SAGE) echo planar imaging (EPI) acquisition. Microvascular-passed sigmoidal filters were designed based upon the vessel-size-sensitive ΔR2*/ΔR2 value for retaining GE-BOLD signals originating from venous vessels with ≤ 45 μm and ≤ 65 μm diameter. Unlike GE-BOLD fMRI, the laminar profile of SAGE-BOLD fMRI with the vessel-size-sensitive filter peaked at ∼ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity over GE-BOLD fMRI. Also, the functional sensitivity of SAGE BOLD at middle layers (0.75–1.5 mm) was improved by ∼ 80% to ∼100% when compared with SE BOLD. In summary, we showed that combined GE- and SE-BOLD fMRI with the vessel-size-sensitive filter indeed yielded improved laminar specificity and sensitivity and is therefore an excellent tool for high spatial resolution ultra-high filed (UHF)-fMRI studies for resolving mesoscopic functional units.

Modelling the depth-dependent VASO and BOLD responses in human primary visual cortex.

Functional magnetic resonance imaging (fMRI) using a blood-oxygenation-level-dependent (BOLD) contrast is a common method for studying human brain function noninvasively. Gradient-echo (GRE) BOLD is highly sensitive to the blood oxygenation change in blood vessels; however, the spatial signal specificity can be degraded due to signal leakage from activated lower layers to superficial layers in depth-dependent (also called laminar or layer-specific) fMRI. Alternatively, physiological variables such as cerebral blood volume using the VAscular-Space-Occupancy (VASO) contrast have shown higher spatial specificity compared to BOLD. To better understand the physiological mechanisms such as blood volume and oxygenation changes and to interpret the measured depth-dependent responses, models are needed which reflect vascular properties at this scale. For this purpose, we extended and modified the "cortical vascular model" previously developed to predict layer-specific BOLD signal changes in human primary visual cortex to also predict a layer-specific VASO response. To evaluate the model, we compared the predictions with experimental results of simultaneous VASO and BOLD measurements in a group of healthy participants. Fitting the model to our experimental data provided an estimate of CBV change in different vascular compartments upon neural activity. We found that stimulus-evoked CBV change mainly occurs in small arterioles, capillaries, and intracortical arteries and that the contribution from venules and ICVs is smaller. Our results confirm that VASO is less susceptible to large vessel effects compared to BOLD, as blood volume changes in intracortical arteries did not substantially affect the resulting depth-dependent VASO profiles, whereas depth-dependent BOLD profiles showed a bias towards signal contributions from intracortical veins.

Multi-echo investigations of positive and negative CBF and concomitant BOLD changes

Unlike the positive blood oxygenation level-dependent (BOLD) response (PBR), commonly taken as an indication of an ‘activated’ brain region, the physiological origin of negative BOLD signal changes (i.e. a negative BOLD response, NBR), also referred to as ‘deactivation’ is still being debated. In this work, an attempt was made to gain a better understanding of the underlying mechanism by obtaining a comprehensive measure of the contributing cerebral blood flow (CBF) and its relationship to the NBR in the human visual cortex, in comparison to a simultaneously induced PBR in surrounding visual regions. To overcome the low signal-to-noise ratio (SNR) of CBF measurements, a newly developed multi-echo version of a center-out echo planar-imaging (EPI) readout was employed with pseudo-continuous arterial spin labeling (pCASL). It achieved very short echo and inter-echo times and facilitated a simultaneous detection of functional CBF and BOLD changes at 3 T with improved sensitivity. Evaluations of the absolute and relative changes of CBF and the effective transverse relaxation rate, R2*, the coupling ratios, and their dependence on CBF at rest, CBFrest, indicated differences between activated and deactivated regions. Analysis of the shape of the respective functional responses also revealed faster negative responses with more pronounced post-stimulus transients. Resulting differences in the flow-metabolism coupling ratios were further examined for potential distinctions in the underlying neuronal contributions.

Assessment of cerebrovascular function in patients with sickle cell disease using transfer function analysis.

In patients with sickle cell disease (SCD), the delivery of oxygen to the brain is compromised by anemia, abnormal rheology, and steno‐occlusive vascular disease. Successful compensation depends on an increase in oxygen supply such as that provided by an increase in cerebral blood flow (CBF). We used magnetic resonance imaging to provide a high‐resolution assessment of the ability of SCD patients to respond to a vasoactive stimulus in middle, anterior, and posterior cerebral artery territories for both white and gray matter. Cerebrovascular reactivity (CVR) was measured as the blood oxygen level dependent signal (a surrogate for CBF) response to an increase in the end tidal partial pressure of CO2 (PETCO2). The dynamic aspect of the response was measured as the time constant of the first order response kinetics (tau). To confirm and support these findings we used an alternative examination of the response, transfer function analysis (TFA), to measure the responsiveness (gain), the speed of response (phase), and the consistency of the response over time (coherence). We tested 34 patients with SCD and compared the results to those of 24 healthy controls participants. The results from a three‐way ANOVA showed that patients with SCD have reduced CVR (p < 0.001) and lower coherence (p < 0.001) in gray matter and white matter and reduced gain in gray matter only (p < 0.001). In terms of the speed of the response to CO2, tau (p < 0.001) and TFA phase (p < 0.001) were increased in SCD patients compared to healthy control subjects. These findings show that the cerebrovascular responsiveness to CO2 in patients with SCD is both decreased and slowed compared to healthy controls.

Concordance of functional MRI memory task and resting-state functional MRI connectivity used in surgical planning for pediatric temporal lobe epilepsy.

Assessing memory is often critical in surgical evaluation, although difficult to assess in young children and in patients with variable task abilities. While obtaining interpretable data from task-based functional MRI (fMRI) measures is common in compliant and awake patients, it is not known whether functional connectivity MRI (fcMRI) data show equivalent results. If this were the case, it would have substantial clinical and research generalizability. To evaluate this possibility, the authors evaluated the concordance between fMRI and fcMRI data collected in a presurgical epilepsy cohort. Task-based fMRI data for autobiographical memory tasks and resting-state fcMRI data were collected in patients with epilepsy evaluated at Seattle Children's Hospital between 2010 and 2017. To assess memory-related activation and laterality, signal change in task-based measures was computed as a percentage of the average blood oxygen level-dependent signal over the defined regions of interest. An fcMRI data analysis was performed using 1000 Functional Connectomes Project scripts based on Analysis of Functional NeuroImages and FSL (Functional Magnetic Resonance Imaging of the Brain Software Library) software packages. Lateralization indices (LIs) were estimated for activation and connectivity measures. The concordance between these two measures was evaluated using correlation and regression analysis. In this epilepsy cohort studied, the authors observed concordance between fMRI activation and fcMRI connectivity, with an LI regression coefficient of 0.470 (R2 = 0.221, p = 0.00076). Previously published studies have demonstrated fMRI and fcMRI overlap between measures of vision, attention, and language. In the authors' clinical sample, task-based measures of memory and analogous resting-state mapping were similarly linked in pattern and strength. These results support the use of fcMRI methods as a proxy for task-based memory performance in presurgical patients, perhaps including those who are more limited in their behavioral compliance. Future investigations to extend these results will be helpful to explore how the magnitudes of effect are associated with neuropsychological performance and postsurgical behavioral changes.

A Meta-Analysis of fMRI Studies of Youth Cannabis Use: Alterations in Executive Control, Social Cognition/Emotion Processing, and Reward Processing in Cannabis Using Youth.

Background: Adolescent cannabis use (CU) is associated with adverse health outcomes and may be increasing in response to changing cannabis laws. Recent imaging studies have identified differences in brain activity between adult CU and controls that are more prominent in early onset users. Whether these differences are present in adolescent CU and relate to age/developmental stage, sex, or cannabis exposure is unknown. Methods: A systematic review and subsequent effect-size seed-based d mapping (SDM) meta-analysis were conducted to examine differences in blood-oxygen-level-dependent (BOLD) response during fMRI studies between CU and non-using typically developing (TD) youth. Supplemental analyses investigated differences in BOLD signal in CU and TD youth as a function of sex, psychiatric comorbidity, and the dose and severity of cannabis exposure. Results: From 1371 citations, 45 fMRI studies were identified for inclusion in the SDM meta-analysis. These studies compared BOLD response contrasts in 1216 CU and 1486 non-using TD participants. In primary meta-analyses stratified by cognitive paradigms, CU (compared to TD) youth showed greater activation in the rostral medial prefrontal cortex (rmPFC) and decreased activation in the dorsal mPFC (dmPFC) and dorsal anterior cingulate cortex (dACC) during executive control and social cognition/emotion processing, respectively. In meta-regression analyses and subgroup meta-analyses, sex, cannabis use disorder (CUD) severity, and psychiatric comorbidity were correlated with brain activation differences between CU and TD youth in mPFC and insular cortical regions. Activation differences in the caudate, thalamus, insula, dmPFC/dACC, and precentral and postcentral gyri varied as a function of the length of abstinence. Conclusions: Using an SDM meta-analytic approach, this report identified differences in neuronal response between CU and TD youth during executive control, emotion processing, and reward processing in cortical and subcortical brain regions that varied as a function of sex, CUD severity, psychiatric comorbidity, and length of abstinence. Whether aberrant brain function in CU youth is attributable to common predispositional factors, cannabis-induced neuroadaptive changes, or both warrants further investigation.

Cerebral blood flow predicts multiple demand network activity and fluid intelligence across the adult lifespan

The preservation of cognitive function in old age is a public health priority. Cerebral hypoperfusion is a hallmark of dementia but its impact on maintaining cognitive ability across the lifespan is less clear. We investigated the relationship between baseline cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) response during a fluid reasoning task in a population-based adult lifespan cohort. As age differences in CBF could lead to non-neuronal contributions to the BOLD signal, we introduced commonality analysis to neuroimaging to dissociate performance-related CBF effects from the physiological confounding effects of CBF on the BOLD response. Accounting for CBF, we confirmed that performance- and age-related differences in BOLD responses in the multiple-demand network were implicated in fluid reasoning. Age differences in CBF explained not only performance-related BOLD responses but also performance-independent BOLD responses. Our results suggest that CBF is important for maintaining cognitive function, while its non-neuronal contributions to BOLD signals reflect an age-related confound. Maintaining perfusion into old age may serve to support brain function and preserve cognitive performance.

Separating neuronal activity and systemic low-frequency oscillation related BOLD responses at nodes of the default mode network during resting-state fMRI with multiband excitation echo-planar imaging

Functional magnetic resonance imaging (fMRI) evaluates brain activity using blood oxygenation level-dependent (BOLD) contrast. Resting-state fMRI (rsfMRI) examines spontaneous brain function using BOLD in the absence of a task, and the default mode network (DMN) has been identified from that. The DMN is a set of nodes within the brain that appear to be active and in communication when the subject is in an awake resting state. In addition to signal changes related to neural activity, it is thought that the BOLD signal may be affected by systemic low-frequency oscillations (SysLFOs) that are non-neuronal in source and likely propagate throughout the brain to arrive at different regions at different times. However, it may be difficult to distinguish between the response due to neuronal activity and the arrival of a SysLFO in specific regions. Conventional single-shot EPI (Conv) acquisition requires a longish repetition time, but faster image acquisition has recently become possible with multiband excitation EPI (MB). In this study, we evaluated the time-lag between nodes of the DMN using both Conv and MB protocols to determine whether it is possible to distinguish between neuronal activity and SysLFO related responses during rsfMRI. While the Conv protocol data suggested that SysLFOs substantially influence the apparent time-lag of neuronal activity, the MB protocol data implied that the effects of SysLFOs and neuronal activity on the BOLD response may be separated. Using a higher time-resolution acquisition for rsfMRI might help to distinguish neuronal activity induced changes to the BOLD response from those induced by non-neuronal sources.

Decreased BOLD signals elicited by 40-Hz auditory stimulation of the right primary auditory cortex in bipolar disorder: An fMRI study.

BackgroundA number studies have been conducted on abnormalities in the cortical circuitry of gamma oscillations, including deficit in auditory steady-state response (ASSR) to gamma-frequency (≧ 30-Hz) stimulation, in patients with bipolar disorder (BD). In the current study, we investigated neural responses during click stimulation by blood oxygen level-dependent (BOLD) signals. We focused on Broadman 41 and 42, the main sources of ASSR.Materials and methodsWe acquired BOLD responses elicited by click trains of 80-, 40-, 30- and 20-Hz frequencies from 25 patients with BD to 27 healthy controls (HC) with normal hearing between 22 and 59 years of age assessed via a standard general linear-model-based analysis. We extracted contrast values by identifying the primary auditory cortex and Brodmann areas 41 and 42 as regions of interest (ROI)s.ResultsBD group showed significantly decreased ASSR-BOLD signals in response to 40-Hz stimuli compared to the HC group in the right Brodmann areas 41 and 42. We found significant negative correlations between the BOLD change in the right Brodmann areas 41 and 42 and Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) scores, also the BOLD change in the right Brodmann areas 41 and 42 and the Positive and Negative Syndrome Scale (PANSS)-Negative scores.ConclusionThe observed decrease in BOLD signal patterns in the right primary auditory cortex during 40-Hz ASSR may be a potential biomarker option for bipolar disorder.

Recognition and Processing of Visual Information after Neuronavigated Transcranial Magnetic Stimulation Session

Background: Transcranial magnetic stimulation (TMS) is a method of noninvasive and painless stimulation of the nervous system, which is based on Faraday’s law of electromagnetic induction. Over the past twenty years, the TMS technique has been deployed as a tool for the diagnosis and therapy of neurodegenerative diseases, as well as in the treatment of mental disorders (e.g., depression). Methods: We tested the inhibitory effects of repetitive TMS (rTMS) on reaction times to militarily relevant visual stimuli amidst distractors and on accompanying blood oxygenation level dependent (BOLD) signal functional magnetic resonance imaging (fMRI) in 20 healthy people. rTMS was applied over the visual cortices, V1, on both hemispheres with the inhibitory theta burst paradigm with the intensity of 70% of the active motor threshold fMRI in 20 healthy people. Results: Analysis of the reaction time to visual stimuli after using TMS to the V1 visual cortex revealed an increase in the number of incorrect recognitions, and the reaction time was from 843 to 910 ms. In the subgroup of participants (n = 15), after the stimulation, there were significant reductions of BOLD signal in blood flow within V1 cortices. Conclusions: The studies of reaction times after the rTMS revealed the inhibitory effect of rTMS on the reaction times and recognition performance of significant (military) objects in the visual field.

Vascular and neuronal effects of general anesthesia on the brain: An fMRI study.

A number of functional magnetic resonance imaging (fMRI) studies rely on application of anesthetic agents during scanning that can modulate and complicate interpretation of the measured hemodynamic blood oxygenation level-dependent (BOLD) response. The purpose of the present study was to investigate the effect of general anesthesia on two main components of BOLD signal including neuronal activity and vascular response. Breath-holding (BH) fMRI was conducted in wakefulness and under anesthesia states in 9 patients with drug-resistant epilepsy who needed to get scanned under anesthesia during laser interstitial thermal therapy. BOLD and BOLD cerebrovascular reactivity (BOLD-CVR) maps were compared using t-test between two states to assess the effect of anesthesia on neuronal activity and vascular factors (p<.05). Overall, our findings revealed an increase in BOLD-CVR and decrease in BOLD response under anesthesia in several brain regions. The results proposed that the modulatory mechanism of anesthetics on neuronal and vascular components of BOLD signal may work in different ways. This experiment for the first human study showed that anesthesia may play an important role in dissociation between neuronal and vascular responses contributed to hemodynamic BOLD signal using BH fMRI imaging that may assist the implication of general anesthesia and interpretation of outcomes in clinical setting.

Investigating form and content of emotional and non-emotional laughing.

As cold actions (i.e. actions devoid of an emotional content), also emotions are expressed with different vitality forms. For example, when an individual experiences a positive emotion, such as laughing as expression of happiness, this emotion can be conveyed to others by different intensities of face expressions and body postures. In the present study, we investigated whether the observation of emotions, expressed with different vitality forms, activates the same neural structures as those involved in cold action vitality forms processing. To this purpose, we carried out a functional magnetic resonance imaging study in which participants were tested in 2 conditions: emotional and non-emotional laughing both conveying different vitality forms. There are 3 main results. First, the observation of emotional and non-emotional laughing conveying different vitality forms activates the insula. Second, the observation of emotional laughing activates a series of subcortical structures known to be related to emotions. Furthermore, a region of interest analysis carried out in these structures reveals a significant modulation of the blood-oxygen-leveldependent (BOLD) signal during the processing of different vitality forms exclusively in the right amygdala, right anterior thalamus/hypothalamus, and periaqueductal gray. Third, in a subsequent electromyography study, we found a correlation between the zygomatic muscles activity and BOLD signal in the right amygdala only.

Anterior Insula Activation During Cardiac Interoception Relates to Depressive Symptom Severity in HIV-Positive and HIV-Negative Postmenopausal Women.

ABSTRACTObjectiveThis study aimed to determine whether subclinical symptoms of depression in postmenopausal women are associated with blood oxygen level–dependent (BOLD) activity within the anterior insula during cardiac interoceptive awareness and whether this association differs for persons living with the human immunodeficiency virus (PWH).MethodTwenty-three postmenopausal (mean [standard deviation] age = 56.5 [4.8] years) and 27 HIV-negative women (mean [standard deviation] age = 56.4 [8.0]) underwent functional magnetic resonance imaging while performing a heartbeat detection task. BOLD activation within the bilateral anterior insula based on the contrast of a heartbeat detection condition with and without a distracting tone was entered along with age, HIV status, and psychological stress into two multivariate regression models with self-reported depressive symptom severity as the outcome.ResultsDepressive symptoms did not vary by HIV status, nor was there a main effect or interaction for PWH on insula BOLD activation. Depressive symptoms were positively associated with psychological stress for the left (β = 0.310, t(49) = 2.352, p = .023) and right brain models (β = 0.296, t(49) = 2.265, p = .028) as well as the magnitude of BOLD activation in the left insula (β = 0.290, t(49) = 2.218, p = .032) and right insula (β = 0.318, t(49) = 2.453, p = .018), respectively. Exploratory analyses revealed that greater magnitude of BOLD activation attributed to exteroceptive noise (tone) was also correlated with self-reported distrust and preoccupation with interoceptive sensations.ConclusionsResults support an active interference model for interoceptive awareness wherein greater BOLD signal in the anterior insula in the presence of distracting exteroceptive stimuli may reflect greater prediction error, a feature of depression.

A Dynamic Approach to Depression Treatment Prediction

Major depressive disorder is often treated clinically as a single disorder, but it represents a highly heterogeneous phenomenon ( 1 Malhi G.S. Mann J.J. Depression. Lancet. 2018; 392: 2299-2312 Abstract Full Text Full Text PDF PubMed Scopus (954) Google Scholar ). Symptom profiles can differ greatly between individuals, and episodes may last for weeks, months, or even years. Treatment response is also highly variable and currently unpredictable. Unpacking the neural basis of depression’s heterogeneity might one day allow for individualized treatment. Resting-state connectivity offers a method for characterizing human brain networks. The method relies on correlated fluctuations of intrinsic brain activity when individuals are at rest without any particular task to perform and is commonly measured via blood oxygen level–dependent signal during functional magnetic resonance imaging. These correlations between sets of regions reveal resting-state networks connecting anatomically and functionally related areas. Resting-state networks are relatively stable within individuals and consistent across groups ( 2 Gratton C. Laumann T.O. Nielsen A.N. Greene D.J. Gordon E.M. Gilmore A.W. et al. Functional brain networks are dominated by stable group and individual factors, not cognitive or daily variation. Neuron. 2018; 98: 439-452.e5 Abstract Full Text Full Text PDF PubMed Scopus (338) Google Scholar ). As a result, resting-state functional magnetic resonance imaging has rapidly gained popularity for relating human brain networks to both normal function and pathological dysfunction. SEE CORRESPONDING ARTICLE ON PAGE 533 SEE CORRESPONDING ARTICLE ON PAGE 533 SEE CORRESPONDING ARTICLE ON PAGE 533 Dynamic Resting-State Network Biomarkers of Antidepressant Treatment ResponseBiological PsychiatryVol. 92Issue 7PreviewDelivery of effective antidepressant treatment has been hampered by a lack of objective tools for predicting or monitoring treatment response. This study aimed to address this gap by testing novel dynamic resting-state functional network markers of antidepressant response. Full-Text PDF

Genome-wide association study of the human brain functional connectome reveals strong vascular component underlying global network efficiency

Complex brain networks play a central role in integrating activity across the human brain, and such networks can be identified in the absence of any external stimulus. We performed 10 genome-wide association studies of resting state network measures of intrinsic brain activity in up to 36,150 participants of European ancestry in the UK Biobank. We found that the heritability of global network efficiency was largely explained by blood oxygen level-dependent (BOLD) resting state fluctuation amplitudes (RSFA), which are thought to reflect the vascular component of the BOLD signal. RSFA itself had a significant genetic component and we identified 24 genomic loci associated with RSFA, 157 genes whose predicted expression correlated with it, and 3 proteins in the dorsolateral prefrontal cortex and 4 in plasma. We observed correlations with cardiovascular traits, and single-cell RNA specificity analyses revealed enrichment of vascular related cells. Our analyses also revealed a potential role of lipid transport, store-operated calcium channel activity, and inositol 1,4,5-trisphosphate binding in resting-state BOLD fluctuations. We conclude that that the heritability of global network efficiency is largely explained by the vascular component of the BOLD response as ascertained by RSFA, which itself has a significant genetic component.

Sickle cell cerebrovascular reactivity to a CO2 stimulus: Too little, too slow.

Background: Despite increased cerebral blood flow (CBF), cerebral infarcts occur in patients with sickle cell disease (SCD). This suggests increased CBF does not meet metabolic demand possibly due to compromised cerebral vasodilatory response. Hypothesis: In adult SCD patients, cerebrovascular reactivity (CVR) and speed of vasodilatory response (tau) to a standardized vasodilatory stimulus, are reduced compared to normal subjects. Methods: Functional brain imaging performed as part of routine care in adult SCD patients without known large vessel cerebral vasculopathy was reviewed retrospectively. CVR was calculated as the change in CBF measured as the blood-oxygenation-level-dependent (BOLD)-magnetic resonance imaging signal, in response to a standard vasoactive stimulus of carbon dioxide (CO2). The tau corresponding to the best fit between the convolved end-tidal partial pressures of CO2 and BOLD signal was defined as the speed of vascular response. CVR and tau were normalized using a previously generated atlas of 42 healthy controls. Results: Fifteen patients were included. CVR was reduced in grey and white matter (mean Z-score for CVR −0.5 [−1.8 to 0.3] and −0.6 [−2.3 to 0.7], respectively). Tau Z-scores were lengthened in grey and white matter (+0.9 [−0.5 to 3.3] and +0.8 [−0.7 to 2.7], respectively). Hematocrit was the only significant independent predictor of CVR on multivariable regression. Conclusion: Both measures of cerebrovascular health (CVR and tau) in SCD patients were attenuated compared to normal controls. These findings show that CVR represents a promising tool to assess disease state, stroke risk, and therapeutic efficacy of treatments in SCD and merits further investigation.

Cortical depth profiles of auditory and visual 7T functional MRI responses in human superior temporal areas.

Invasive neurophysiological studies in nonhuman primates have shown different laminar activation profiles to auditory vs. visual stimuli in auditory cortices and adjacent polymodal areas. Means to examine the underlying feedforward vs. feedback type influences noninvasively have been limited in humans. Here, using 1-mm isotropic resolution 3D echo-planar imaging at 7 T, we studied the intracortical depth profiles of functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signals to brief auditory (noise bursts) and visual (checkerboard) stimuli. BOLD percent-signal-changes were estimated at 11 equally spaced intracortical depths, within regions-of-interest encompassing auditory (Heschl's gyrus, Heschl's sulcus, planum temporale, and posterior superior temporal gyrus) and polymodal (middle and posterior superior temporal sulcus) areas. Effects of differing BOLD signal strengths for auditory and visual stimuli were controlled via normalization and statistical modeling. The BOLD depth profile shapes, modeled with quadratic regression, were significantly different for auditory vs. visual stimuli in auditory cortices, but not in polymodal areas. The different depth profiles could reflect sensory-specific feedforward versus cross-sensory feedback influences, previously shown in laminar recordings in nonhuman primates. The results suggest that intracortical BOLD profiles can help distinguish between feedforward and feedback type influences in the human brain. Further experimental studies are still needed to clarify how underlying signal strength influences BOLD depth profiles under different stimulus conditions.

Neural substrates of saccadic adaptation: Plastic changes versus error processing and forward versus backward learning

Previous behavioral, clinical, and neuroimaging studies suggest that the neural substrates of adaptation of saccadic eye movements involve, beyond the central role of the cerebellum, several, still incompletely determined, cortical areas. Furthermore, no neuroimaging study has yet tackled the differences between saccade lengthening (“forward adaptation”) and shortening (“backward adaptation”) and neither between their two main components, i.e. error processing and oculomotor changes. The present fMRI study was designed to fill these gaps. Blood-oxygen-level-dependent (BOLD) signal and eye movements of 24 healthy volunteers were acquired while performing reactive saccades under 4 conditions repeated in short blocks of 16 trials: systematic target jump during the saccade and in the saccade direction (forward: FW) or in the opposite direction (backward: BW), randomly directed FW or BW target jump during the saccade (random: RND) and no intra-saccadic target jump (stationary: STA). BOLD signals were analyzed both through general linear model (GLM) approaches applied at the whole-brain level and through sensitive Multi-Variate Pattern Analyses (MVPA) applied to 34 regions of interest (ROIs) identified from independent 'Saccade Localizer’ functional data. Oculomotor data were consistent with successful induction of forward and backward adaptation in FW and BW blocks, respectively. The different analyses of voxel activation patterns (MVPAs) disclosed the involvement of 1) a set of ROIs specifically related to adaptation in the right occipital cortex, right and left MT/MST, right FEF and right pallidum; 2) several ROIs specifically involved in error signal processing in the left occipital cortex, left PEF, left precuneus, Medial Cingulate cortex (MCC), left inferior and right superior cerebellum; 3) ROIs specific to the direction of adaptation in the occipital cortex and MT/MST (left and right hemispheres for FW and BW, respectively) and in the pallidum of the right hemisphere (FW). The involvement of the left PEF and of the (left and right) occipital cortex were further supported and qualified by the whole brain GLM analysis: clusters of increased activity were found in PEF for the RND versus STA contrast (related to error processing) and in the left (right) occipital cortex for the FW (BW) versus STA contrasts [related to the FW (BW) direction of error and/or adaptation]. The present study both adds complementary data to the growing literature supporting a role of the cerebral cortex in saccadic adaptation through feedback and feedforward relationships with the cerebellum and provides the basis for improving conceptual frameworks of oculomotor plasticity and of its link with spatial cognition.