Effect of motion, cortical orientation and spatial resolution on quantitative imaging of cortical R2* and magnetic susceptibility at 0.3 mm in-plane resolution at 7 T.

MR images of the effective relaxation rate R2* and magnetic susceptibility χ derived from multi-echo T2*-weighted (T2*w) MRI can provide insight into iron and myelin distributions in the brain, with the potential of providing biomarkers for neurological disorders. Quantification of R2* and χ at submillimeter resolution in the cortex in vivo has been difficult because of challenges such as head motion, limited signal to noise ratio, long scan time, and motion related magnetic field fluctuations. This work aimed to improve the robustness for quantifying intracortical R2* and χ and analyze the effects from motion, spatial resolution, and cortical orientation. T2*w data was acquired with a spatial resolution of 0.3 × 0.3 × 0.4 mm3 at 7 T and downsampled to various lower resolutions. A combined correction for motion and B0 changes was deployed using volumetric navigators. Such correction improved the T2*w image quality rated by experienced image readers and test-retest reliability of R2* and χ quantification with reduced median inter-scan differences up to 10 s-1 and 5 ppb, respectively. R2* and χ near the line of Gennari, a cortical layer high in iron and myelin, were as much as 10 s-1 and 10 ppb higher than the region at adjacent cortical depth. In addition, a significant effect due to the cortical orientation relative to the static field (B0) was observed in χ with a peak-to-peak amplitude of about 17 ppb. In retrospectively downsampled data, the capability to distinguish different cortical depth regions based on R2* or χ contrast remained up to isotropic 0.5 mm resolution. This study highlights the unique characteristics of R2* and χ along the cortical depth at submillimeter resolution and the need for motion and B0 corrections for their robust quantification in vivo.

Cerebrovascular activity is a major factor in the cerebrospinal fluid flow dynamics.

Cerebrospinal fluid (CSF) provides physical protection to the central nervous system as well as an essential homeostatic environment for the normal functioning of neurons. Additionally, it has been proposed that the pulsatile movement of CSF may assist in glymphatic clearance of brain metabolic waste products implicated in neurodegeneration. In awake humans, CSF flow dynamics are thought to be driven primarily by cerebral blood volume fluctuations resulting from a number of mechanisms, including a passive vascular response to blood pressure variations associated with cardiac and respiratory cycles. Recent research has shown that mechanisms that rely on the action of vascular smooth muscle cells ("cerebrovascular activity") such as neuronal activity, changes in intravascular CO2, and autonomic activation from the brainstem, may lead to CSF pulsations as well. Nevertheless, the relative contribution of these mechanisms to CSF flow remains unclear. To investigate this further, we developed an MRI approach capable of disentangling and quantifying CSF flow components of different time scales associated with these mechanisms. This approach was evaluated on human control subjects (n = 12) performing intermittent voluntary deep inspirations, by determining peak flow velocities and displaced volumes between these mechanisms in the fourth ventricle. We found that peak flow velocities were similar between the different mechanisms, while displaced volumes per cycle were about a magnitude larger for deep inspirations. CSF flow velocity peaked at around 10.4 s (range 7.1-14.8 s, n = 12) following deep inspiration, consistent with known cerebrovascular activation delays for this autonomic challenge. These findings point to an important role of cerebrovascular activity in the genesis of CSF pulsations. Other regulatory triggers for cerebral blood flow such as autonomic arousal and orthostatic challenges may create major CSF pulsatile movement as well. Future quantitative comparison of these and possibly additional types of CSF pulsations with the proposed approach may help clarify the conditions that affect CSF flow dynamics.

Autonomic arousals contribute to brain fluid pulsations during sleep.

During sleep, slow waves of neuro-electrical activity engulf the human brain and aid in the consolidation of memories. Recent research suggests that these slow waves may also promote brain health by facilitating the removal of metabolic waste, possibly by orchestrating the pulsatile flow of cerebrospinal fluid (CSF) through local neural control over vascular tone. To investigate the role of slow waves in the generation of CSF pulsations, we analyzed functional MRI data obtained across the full sleep-wake cycle and during a waking respiratory task. This revealed a novel generating mechanism that relies on the autonomic regulation of cerebral vascular tone without requiring slow electrocortical activity or even sleep. Therefore, the role of CSF pulsations in brain waste clearance may, in part, depend on proper autoregulatory control of cerebral blood flow.

Multiple sclerosis cortical lesion detection with deep learning at ultra-high-field MRI.

Manually segmenting multiple sclerosis (MS) cortical lesions (CLs) is extremely time consuming, and past studies have shown only moderate inter-rater reliability. To accelerate this task, we developed a deep-learning-based framework (CLAIMS: Cortical Lesion AI-Based Assessment in Multiple Sclerosis) for the automated detection and classification of MS CLs with 7 T MRI. Two 7 T datasets, acquired at different sites, were considered. The first consisted of 60 scans that include 0.5 mm isotropic MP2RAGE acquired four times (MP2RAGE×4), 0.7 mm MP2RAGE, 0.5 mm T2 *-weighted GRE, and 0.5 mm T2 *-weighted EPI. The second dataset consisted of 20 scans including only 0.75 × 0.75 × 0.9 mm3 MP2RAGE. CLAIMS was first evaluated using sixfold cross-validation with single and multi-contrast 0.5 mm MRI input. Second, the performance of the model was tested on 0.7 mm MP2RAGE images after training with either 0.5 mm MP2RAGE×4, 0.7 mm MP2RAGE, or alternating the two. Third, its generalizability was evaluated on the second external dataset and compared with a state-of-the-art technique based on partial volume estimation and topological constraints (MSLAST). CLAIMS trained only with MP2RAGE×4 achieved results comparable to those of the multi-contrast model, reaching a CL true positive rate of 74% with a false positive rate of 30%. Detection rate was excellent for leukocortical and subpial lesions (83%, and 70%, respectively), whereas it reached 53% for intracortical lesions. The correlation between disability measures and CL count was similar for manual and CLAIMS lesion counts. Applying a domain-scanner adaptation approach and testing CLAIMS on the second dataset, the performance was superior to MSLAST when considering a minimum lesion volume of 6 µL (lesion-wise detection rate of 71% versus 48%). The proposed framework outperforms previous state-of-the-art methods for automated CL detection across scanners and protocols. In the future, CLAIMS may be useful to support clinical decisions at 7 T MRI, especially in the field of diagnosis and differential diagnosis of MS patients.

Cortical lesion hotspots and association of subpial lesions with disability in multiple sclerosis.

BACKGROUND: Dramatic improvements in visualization of cortical (especially subpial) multiple sclerosis (MS) lesions allow assessment of impact on clinical course. OBJECTIVE: Characterize cortical lesions by 7 tesla (T) T2*-/T1-weighted magnetic resonance imaging (MRI); determine relationship with other MS pathology and contribution to disability. METHODS: Sixty-four adults with MS (45 relapsing-remitting/19 progressive) underwent 3 T brain/spine MRI, 7 T brain MRI, and clinical testing. RESULTS: Cortical lesions were found in 94% (progressive: median 56/range 2-203; relapsing-remitting: 15/0-168; p = 0.004). Lesion distribution across 50 cortical regions was nonuniform (p = 0.006), with highest lesion burden in supplementary motor cortex and highest prevalence in superior frontal gyrus. Leukocortical and white matter lesion volumes were strongly correlated (r = 0.58, p < 0.0001), while subpial and white matter lesion volumes were moderately correlated (r = 0.30, p = 0.002). Leukocortical (p = 0.02) but not subpial lesions (p = 0.40) were correlated with paramagnetic rim lesions; both were correlated with spinal cord lesions (p = 0.01). Cortical lesion volumes (total and subtypes) were correlated with expanded disability status scale, 25-foot timed walk, nine-hole peg test, and symbol digit modality test scores. CONCLUSION: Cortical lesions are highly prevalent and are associated with disability and progressive disease. Subpial lesion burden is not strongly correlated with white matter lesions, suggesting differences in inflammation and repair mechanisms.

FMRI based on transition-band balanced SSFP in comparison with EPI on a high-performance 0.55 T scanner.

PURPOSE: Low-field (<1 tesla) MRI scanners allow more widespread diagnostic use for a range of cardiac, musculoskeletal, and neurological applications. However, the feasibility of performing robust fMRI at low field has yet to be fully demonstrated. To address this gap, we investigated task-based fMRI using a highly sensitive transition-band balanced steady-state free precession approach and standard EPI on a 0.55 tesla scanner equipped with modern high-performance gradient coils and a receive array. METHODS: TR and flip-angle of transition-band steady-state free precession were optimized for 0.55 tesla by simulations. Static shimming was employed to compensate for concomitant field effects. Visual task-based fMRI data were acquired from 8 healthy volunteers. For comparison, standard EPI data were also acquired with TE = T2∗ . Retrospective image-based correction for physiological effects (RETROICOR) was used to quantify physiological noise effects. RESULTS: Activation was robustly detected using both methods in a 4-min scan time. Transition-band steady-state free precession was found to be sensitive to interference from subtle spatial and temporal (field drift, respiration) variations in the magnetic field, counteracting potential advantages of the reduced magnetic susceptibility effects compared to its utilization at high field. These adverse effects could be partially remedied with static shimming and postprocessing approaches. Standard EPI proved more robust against the sources of interference. CONCLUSION: BOLD contrast is sufficiently large at 0.55 tesla for robust detection of brain activation and may be employed to broaden the spectrum of applications of low-field MRI. Standard EPI outperforms transition-band steady-state free precession in terms of signal stability.

B0-field dependence of MRI T1 relaxation in human brain.

Tissue longitudinal relaxation characterized by recovery time T1 or rate R1 is a fundamental MRI contrast mechanism that is increasingly being used to study the brain's myelination patterns in both health and disease. Nevertheless, the quantitative relationship between T1 and myelination, and its dependence on B0 field strength, is still not well known. It has been theorized that in much of brain tissue, T1 field-dependence is driven by that of macromolecular protons (MP) through a mechanism called magnetization transfer (MT). Despite the explanatory power of this theory and substantial support from in-vitro experiments at low fields (<3 â€‹T), in-vivo evidence across clinically relevant field strengths is lacking. In this study, T1-weighted MRI was acquired in a group of eight healthy volunteers at four clinically relevant field strengths (0.55, 1.5, 3 and 7 â€‹T) using the same pulse sequence at a single site, and jointly analyzed based on the two-pool model of MT. MP fraction and free-water pool T1 were obtained in several brain structures at 3 and 7 â€‹T, which allowed distinguishing between contributions from macromolecular content and iron to tissue T1. Based on this, the T1 of MP in white matter, indirectly determined by assuming a field independent T1 of free water, was shown to increase approximately linearly with B0. This study advances our understanding of the T1 contrast mechanism and its relation to brain myelin content across the wide range of currently available MRI strengths, and it has the potential to inform design of T1 mapping methods for improved reproducibility in the human brain.

Reducing motion sensitivity in 3D high-resolution T2*-weighted MRI by navigator-based motion and nonlinear magnetic field correction.

T2*-weighted gradient echo (GRE) MRI at high field is uniquely sensitive to the magnetic properties of tissue and allows the study of brain and vascular anatomy at high spatial resolution. However, it is also sensitive to B0 field changes induced by head motion and physiological processes such as the respiratory cycle. Conventional motion correction techniques do not take these field changes into account, and consequently do not fully recover image quality in T2*-weighted MRI. Here, a novel approach was developed to address this by monitoring the B0 field with a volumetric EPI phase navigator. The navigator was acquired at a shorter echo time than that of the (higher resolution) T2*-weighted GRE imaging data and accelerated with parallel imaging for high temporal resolution. At 4 â€‹mm isotropic spatial resolution and 0.54 â€‹s temporal resolution, the accuracy for estimation of rotation and translation was better than 0.2° and 0.1 â€‹mm, respectively. The 10% and 90% percentiles of B0 measurement error using the navigator were -1.8 and 1.5 Hz  at 7 T, respectively. A fast retrospective reconstruction algorithm correcting for both motion and nonlinear B0 changes was also developed. The navigator and reconstruction algorithm were evaluated in correcting motion-corrupted high-resolution T2*-weighted GRE MRI on healthy human subjects at 7 â€‹T. Excellent image quality was demonstrated with the proposed correction method.

Eight-channel parallel transmit-receive system for 7 T MRI with optically controlled and monitored on-coil current-mode RF amplifiers.

PURPOSE: To demonstrate a practical implementation of an eight-channel parallel-transmit system for brain imaging at 7 T based on on-coil amplifier technology. METHODS: An eight-channel parallel transmit-receive system was built with optimized on-coil switch-mode current RF power amplifiers. The amplifiers were optically controlled from an eight-channel interface that was connected to a 7 T MRI scanner. The interface also optically received a down-converted version of the coil current sensed in each amplifier for monitoring and feedback adjustments. RESULTS: Each on-coil amplifier delivered more than 100 W peak power and provided enough amplifier decoupling (<-15 dB) for the implemented eight-channel array configuration. Phantom and human images were acquired to demonstrate practical operation of this new technology in a 7 T MRI scanner. CONCLUSION: Further development and improvement of previously demonstrated on-coil technology led to successful implementation of an eight-channel parallel-transmit system able to deliver strong B1 fields for typical brain imaging applications. This is an important step forward toward implementation of on-coil RF amplification for high-field MRI.

Impulse response timing differences in BOLD and CBV weighted fMRI.

Recent advances in BOLD fMRI scan techniques have substantially improved spatial and temporal resolution, currently reaching to sub-millimeter and sub-second levels respectively. Unfortunately, there remain physiological barriers that prevent achieving this resolution in practice. BOLD contrast relies on the hemodynamic response to neuronal activity, whose associated cerebral blood oxygenation (CBO) changes may spread over several millimeters and last several seconds. Recent reports have suggested that significant improvements may be possible with cerebral blood volume (CBV)-weighted fMRI, which highlights the CBV changes rather than the BOLD changes associated with the hemodynamic response. Nevertheless, quantitative comparisons between CBV and BOLD are sparse, in particular regarding their temporal characteristics in human brain. To address this, we studied a cohort of subjects that received injection of ferumoxytol, an intravascular iron-oxide based contrast agent that introduces strong CBV contrast. An event-related visual stimulus paradigm was used to compare the impulse response (IR) for CBV and BOLD contrast, obtained with and without ferumoxytol, respectively. Experiments performed at 7 T (n = 5) at 1.2-1.5 mm spatial and 1 s temporal resolution showed that the onset time and time-to-peak of the CBV IR averaged 0.8 and 3.5 s respectively, both 0.6 s shorter than the BOLD IR. While significant, these improvements are relatively small and not expected to lead to practical advantages for the extraction of temporal information about neural activity. Nonlinearities in the observed IR were also compared and found to be similar between the CBV and BOLD, indicating that these are likely not caused by a 'ceiling' effect in the CBO response, but rather support a previously proposed model of vascular compliance, in which changes in vascular tone elicited by a preceding stimulus affect the IR.

Contribution of systemic vascular effects to fMRI activity in white matter.

To investigate a potential contribution of systemic physiology to recently reported BOLD fMRI signals in white matter, we compared photo-plethysmography (PPG) and whole-brain fMRI signals recorded simultaneously during long resting-state scans from an overnight sleep study. We found that intermittent drops in the amplitude of the PPG signal exhibited strong and widespread correlations with the fMRI signal, both in white matter (WM) and in gray matter (GM). The WM signal pattern resembled that seen in previous resting-state fMRI studies and closely tracked the location of medullary veins. Its temporal cross-correlation with the PPG amplitude was bipolar, with an early negative value. In GM, the correlation was consistently positive. Consistent with previous studies comparing physiological signals with fMRI, these findings point to a systemic vascular contribution to WM fMRI signals. The PPG drops are interpreted as systemic vasoconstrictive events, possibly related to intermittent increases in sympathetic tone related to fluctuations in arousal state. The counter-intuitive polarity of the WM signal is explained by long blood transit times in the medullary vasculature of WM, which cause blood oxygenation loss and a substantial timing mismatch between blood volume and blood oxygenation effects. A similar mechanism may explain previous findings of negative WM signals around large draining veins during both task- and resting-state fMRI.

Effect of head motion on MRI B0 field distribution.

PURPOSE: To identify and characterize the sources of B0 field changes due to head motion, to reduce motion sensitivity in human brain MRI. METHODS: B0 fields were measured in 5 healthy human volunteers at various head poses. After measurement of the total field, the field originating from the subject was calculated by subtracting the external field generated by the magnet and shims. A subject-specific susceptibility model was created to quantify the contribution of the head and torso. The spatial complexity of the field changes was analyzed using spherical harmonic expansion. RESULTS: Minor head pose changes can cause substantial and spatially complex field changes in the brain. For rotations and translations of approximately 5 º and 5 mm, respectively, at 7 T, the field change that is associated with the subject's magnetization generates a standard deviation (SD) of about 10 Hz over the brain. The stationary torso contributes to this subject-associated field change significantly with a SD of about 5 Hz. The subject-associated change leads to image-corrupting phase errors in multi-shot T 2 * -weighted acquisitions. CONCLUSION: The B0 field changes arising from head motion are problematic for multishot T 2 * -weighted imaging. Characterization of the underlying sources provides new insights into mitigation strategies, which may benefit from individualized predictive field models in addition to real-time field monitoring and correction strategies.

Optically controlled on-coil amplifier with RF monitoring feedback.

PURPOSE: To develop a new optically controlled on-coil amplifier that facilitates safe use of multi-channel radiofrequency (RF) transmission in MRI by real-time monitoring of signal phase and amplitude. METHODS: Monitoring was carried out with a 4-channel prototype system by sensing, down sampling, digitizing, and optically transmitting the RF transmit signal to a remote PC to control the amplifiers. Performance was evaluated with benchtop and 7 T MRI experiments. RESULTS: Monitored amplitude and phase were stable across repetitions and had standard deviations of 0.061 µT and 0.0073 rad, respectively. The feedback system allowed inter-channel phase and B1 amplitude to be adjusted within two iterations. MRI experiments demonstrated the feasibility of this approach to perform safe and accurate multi-channel RF transmission and monitoring at high field. CONCLUSION: We demonstrated a 4-channel transceiver system based on optically controlled on-coil amplifiers with RF signal monitoring and feedback control. The approach allows the safe and precise control of RF transmission fields, required to achieve uniform excitation at high field. Magn Reson Med 79:2833-2841, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Synthesized tissue-equivalent dielectric phantoms using salt and polyvinylpyrrolidone solutions.

PURPOSE: To explore the use of polyvinylpyrrolidone (PVP) for simulated materials with tissue-equivalent dielectric properties. METHODS: PVP and salt were used to control, respectively, relative permittivity and electrical conductivity in a collection of 63 samples with a range of solute concentrations. Their dielectric properties were measured with a commercial probe and fitted to a 3D polynomial in order to establish an empirical recipe. The material's thermal properties and MR spectra were measured. RESULTS: The empirical polynomial recipe (available at https://www.amri.ninds.nih.gov/cgi-bin/phantomrecipe) provides the PVP and salt concentrations required for dielectric materials with permittivity and electrical conductivity values between approximately 45 and 78, and 0.1 to 2 siemens per meter, respectively, from 50 MHz to 4.5 GHz. The second- (solute concentrations) and seventh- (frequency) order polynomial recipe provided less than 2.5% relative error between the measured and target properties. PVP side peaks in the spectra were minor and unaffected by temperature changes. CONCLUSION: PVP-based phantoms are easy to prepare and nontoxic, and their semitransparency makes air bubbles easy to identify. The polymer can be used to create simulated material with a range of dielectric properties, negligible spectral side peaks, and long T2 relaxation time, which are favorable in many MR applications. Magn Reson Med 80:413-419, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Optically controlled switch-mode current-source amplifiers for on-coil implementation in high-field parallel transmission.

PURPOSE: We tested the feasibility of implementing parallel transmission (pTX) for high-field MRI using a radiofrequency (RF) amplifier design to be located on or in the immediate vicinity of an RF transmit coil. METHOD: We designed a current-source switch-mode amplifier based on miniaturized, nonmagnetic electronics. Optical RF carrier and envelope signals to control the amplifier were derived, through a custom-built interface, from the RF source accessible in the scanner control. Amplifier performance was tested by benchtop measurements as well as with imaging at 7T (300 MHz) and 11.7 T (500 MHz). The ability to perform pTX was evaluated by measuring interchannel coupling and phase adjustment in a two-channel setup. RESULTS: The amplifier delivered in excess of 44 W RF power and caused minimal interference with MRI. The interface derived accurate optical control signals with carrier frequencies ranging from 64 to 750 MHz. Decoupling better than 14 dB was obtained between two coil loops separated by only 1 cm. Application to MRI was demonstrated by acquiring artifact-free images at 7 T and 11.7 T. CONCLUSION: We propose an optically controlled miniaturized RF amplifier for on-coil implementation at high fields that should facilitate implementation of high-density pTX arrays. Magn Reson Med 76:340-349, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

A torque balance measurement of anisotropy of the magnetic susceptibility in white matter.

PURPOSE: Recent MRI studies have suggested that the magnetic susceptibility of white matter (WM) in the human brain is anisotropic, providing a new contrast mechanism for the visualization of fiber bundles and allowing the extraction of cellular compartment-specific information. This study provides an independent confirmation and quantification of this anisotropy. METHODS: Anisotropic magnetic susceptibility results in a torque exerted on WM when placed in a uniform magnetic field, tending to align the WM fibers with the field. To quantify the effect, excised spinal cord samples were placed in a torque balance inside the magnet of a 7 T MRI system and the magnetic torque was measured as function of orientation. RESULTS: All tissue samples (n = 5) showed orienting effects, confirming the presence of anisotropic susceptibility. Analysis of the magnetic torque resulted in reproducible values for the WM volume anisotropy that ranged from 13.6 to 19.2 ppb. CONCLUSION: The independently determined anisotropy values confirm estimates inferred from MRI experiments and validate the use of anisotropy to extract novel information about brain fiber structure and myelination.

A 7T spine array based on electric dipole transmitters.

PURPOSE: The goal of this study was to explore the feasibility of using an array of electric dipole antennas for RF transmission in spine MRI at high fields. METHOD: A two-channel transmit array based on an electric dipole design was quantitatively optimized for 7T spine imaging and integrated with a receive array combining eight loop coils. Using B1+ mapping, the transmit efficiency of the dipole array was compared with a design using quadrature loop pairs. The radiofrequency energy deposition for each array was measured using a home-built dielectric phantom and MR thermometry. The performance of the proposed array was qualitatively demonstrated in human studies. RESULTS: The results indicate dramatically improved transmit efficiency for the dipole design compared with the loop excitation. A gain of up to 76% was achieved within the spinal region. CONCLUSION: For imaging of the spine, electric dipole-based transmitters provide an attractive alternative to the traditional loop-based design. Easy integration with existing receive array technology facilitates practical use at high fields.

Neuroelectrical decomposition of spontaneous brain activity measured with functional magnetic resonance imaging.

Spontaneous activity in the human brain occurs in complex spatiotemporal patterns that may reflect functionally specialized neural networks. Here, we propose a subspace analysis method to elucidate large-scale networks by the joint analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data. The new approach is based on the notion that the neuroelectrical activity underlying the fMRI signal may have EEG spectral features that report on regional neuronal dynamics and interregional interactions. Applying this approach to resting healthy adults, we indeed found characteristic spectral signatures in the EEG correlates of spontaneous fMRI signals at individual brain regions as well as the temporal synchronization among widely distributed regions. These spectral signatures not only allowed us to parcel the brain into clusters that resembled the brain's established functional subdivision, but also offered important clues for disentangling the involvement of individual regions in fMRI network activity.

Early anti-correlated BOLD signal changes of physiologic origin.

Negative BOLD signals that are synchronous with resting state fluctuations have been observed in large vessels in the cortical sulci and surrounding the ventricles. In this study, we investigated the origin of these negative BOLD signals by applying a Cued Deep Breathing (CDB) task to create transient hypocapnia and a resultant global fMRI signal decrease. We hypothesized that a global stimulus would amplify the effect in large vessels and that using a global negative (vasoconstrictive) stimulus would test whether these voxels exhibit either inherently negative or simply anti-correlated BOLD responses. Significantly anti-correlated, but positive, BOLD signal changes during respiratory challenges were identified in voxels primarily located near edges of brain spaces containing CSF. These positive BOLD responses occurred earlier than the negative CDB response across most of gray matter voxels. These findings confirm earlier suggestions that in some brain regions, local, fractional changes in CSF volume may overwhelm BOLD-related signal changes, leading to signal anti-correlation. We show that regions with CDB anti-correlated signals coincide with most, but not all, of the regions with negative BOLD signal changes observed during a visual and motor stimulus task. Thus, the addition of a physiological challenge to fMRI experiments can help identify which negative BOLD signals are passive physiological anti-correlations and which may have a putative neuronal origin.

Reproducible, data-driven characterization of sleep based on brain dynamics and transitions from whole-night fMRI.

Understanding the function of sleep requires studying the dynamics of brain activity across whole-night sleep and their transitions. However, current gold standard polysomnography (PSG) has limited spatial resolution to track brain activity. Additionally, previous fMRI studies were too short to capture full sleep stages and their cycling. To study whole-brain dynamics and transitions across whole-night sleep, we used an unsupervised learning approach, the Hidden Markov model (HMM), on two-night, 16-hour fMRI recordings of 12 non-sleep-deprived participants who reached all PSG-based sleep stages. This method identified 21 recurring brain states and their transition probabilities, beyond PSG-defined sleep stages. The HMM trained on one night accurately predicted the other, demonstrating unprecedented reproducibility. We also found functionally relevant subdivisions within rapid eye movement (REM) and within non-REM 2 stages. This study provides new insights into brain dynamics and transitions during sleep, aiding our understanding of sleep disorders that impact sleep transitions.