Fast 3D fMRI acquisition with high spatial resolutions over a reduced FOV.

PURPOSE: To develop and demonstrate a fast 3D fMRI acquisition technique with high spatial resolution over a reduced FOV, named k-t 3D reduced FOV imaging (3D-rFOVI). METHODS: Based on 3D gradient-echo EPI, k-t 3D-rFOVI used a 2D RF pulse to reduce the FOV in the in-plane phase-encoding direction, boosting spatial resolution without increasing echo train length. For image acceleration, full sampling was applied in the central k-space region along the through-slab direction (kz) for all time frames, while randomized undersampling was used in outer kz regions at different time frames. Images were acquired at 3T and reconstructed using a method based on partial separability. fMRI detection sensitivity of k-t 3D-rFOVI was quantitively analyzed with simulation data. Human visual fMRI experiments were performed to evaluate k-t 3D-rFOVI and compare it with a commercial multiband EPI sequence. RESULTS: The simulation data showed that k-t 3D-rFOVI can detect 100% of fMRI activations with an acceleration factor (R) of 2 and ˜80% with R = 6. In the human fMRI data acquired with 1.5-mm spatial resolution and 800-ms volume TR (TRvol), k-t 3D-rFOVI with R = 4 detected 46% more activated voxels in the visual cortex than the multiband EPI. Additional fMRI experiments showed that k-t 3D-rFOVI can achieve TRvol of 480 ms with R = 6, while reliably detecting visual activation. CONCLUSIONS: k-t 3D-rFOVI can simultaneously achieve a high spatial resolution (1.5-mm isotropically) and short TRvol (480-ms) at 3T. It offers a robust acquisition technique for fast fMRI studies over a focused brain volume.

Human NREM Sleep Promotes Brain-Wide Vasomotor and Respiratory Pulsations.

The physiological underpinnings of the necessity of sleep remain uncertain. Recent evidence suggests that sleep increases the convection of cerebrospinal fluid (CSF) and promotes the export of interstitial solutes, thus providing a framework to explain why all vertebrate species require sleep. Cardiovascular, respiratory and vasomotor brain pulsations have each been shown to drive CSF flow along perivascular spaces, yet it is unknown how such pulsations may change during sleep in humans. To investigate these pulsation phenomena in relation to sleep, we simultaneously recorded fast fMRI, magnetic resonance encephalography (MREG), and electroencephalography (EEG) signals in a group of healthy volunteers. We quantified sleep-related changes in the signal frequency distributions by spectral entropy analysis and calculated the strength of the physiological (vasomotor, respiratory, and cardiac) brain pulsations by power sum analysis in 15 subjects (age 26.5 ± 4.2 years, 6 females). Finally, we identified spatial similarities between EEG slow oscillation (0.2-2 Hz) power and MREG pulsations. Compared with wakefulness, nonrapid eye movement (NREM) sleep was characterized by reduced spectral entropy and increased brain pulsation intensity. These effects were most pronounced in posterior brain areas for very low-frequency (≤0.1 Hz) vasomotor pulsations but were also evident brain-wide for respiratory pulsations, and to a lesser extent for cardiac brain pulsations. There was increased EEG slow oscillation power in brain regions spatially overlapping with those showing sleep-related MREG pulsation changes. We suggest that reduced spectral entropy and enhanced pulsation intensity are characteristic of NREM sleep. With our findings of increased power of slow oscillation, the present results support the proposition that sleep promotes fluid transport in human brain.SIGNIFICANCE STATEMENT We report that the spectral power of physiological brain pulsation mechanisms driven by vasomotor, respiration, and cardiac rhythms in human brain increase during sleep, extending previous observations of their association with glymphatic brain clearance during sleep in rodents. The magnitudes of increased pulsations follow the rank order of vasomotor greater than respiratory greater than cardiac pulsations, with correspondingly declining spatial extents. Spectral entropy, previously known as vigilance and as an anesthesia metric, decreased during NREM sleep compared with the awake state in very low and respiratory frequencies, indicating reduced signal complexity. An EEG slow oscillation power increase occurring in the early sleep phase (NREM 1-2) spatially overlapped with pulsation changes, indicating reciprocal mechanisms between those measures.

Investigating mechanisms of fast BOLD responses: The effects of stimulus intensity and of spatial heterogeneity of hemodynamics.

Recent studies have demonstrated that fast fMRI can track neural activity well above the temporal limit predicted by the canonical hemodynamic response model. While these findings are promising, the biophysical mechanisms underlying these fast fMRI phenomena remain underexplored. In this study, we discuss two aspects of the hemodynamic response, complementary to several existing hypotheses, that can accommodate faster fMRI dynamics beyond those predicted by the canonical model. First, we demonstrate, using both visual and somatosensory paradigms, that the timing and shape of hemodynamic response functions (HRFs) vary across graded levels of stimulus intensity-with lower-intensity stimulation eliciting faster and narrower HRFs. Second, we show that as the spatial resolution of fMRI increases, voxel-wise HRFs begin to deviate from the canonical model, with a considerable portion of voxels exhibiting faster temporal dynamics than predicted by the canonical HRF. Collectively, both stimulus/task intensity and image resolution can affect the sensitivity of fMRI to fast brain activity, which may partly explain recent observations of fast fMRI signals. It is further noteworthy that, while the present investigations focus on fast neural responses, our findings suggest that a revised hemodynamic model may benefit the many fMRI studies using paradigms with wide ranges of contrast levels (e.g., resting or naturalistic conditions) or with modern, high-resolution MR acquisitions.

Spectral analysis of physiological brain pulsations affecting the BOLD signal.

Physiological pulsations have been shown to affect the global blood oxygen level dependent (BOLD) signal in human brain. While these pulsations have previously been regarded as noise, recent studies show their potential as biomarkers of brain pathology. We used the extended 5 Hz spectral range of magnetic resonance encephalography (MREG) data to investigate spatial and frequency distributions of physiological BOLD signal sources. Amplitude spectra of the global image signals revealed cardiorespiratory envelope modulation (CREM) peaks, in addition to the previously known very low frequency (VLF) and cardiorespiratory pulsations. We then proceeded to extend the amplitude of low frequency fluctuations (ALFF) method to each of these pulsations. The respiratory pulsations were spatially dominating over most brain structures. The VLF pulsations overcame the respiratory pulsations in frontal and parietal gray matter, whereas cardiac and CREM pulsations had this effect in central cerebrospinal fluid (CSF) spaces and major blood vessels. A quasi-periodic pattern (QPP) analysis showed that the CREM pulsations propagated as waves, with a spatiotemporal pattern differing from that of respiratory pulsations, indicating them to be distinct intracranial physiological phenomenon. In conclusion, the respiration has a dominant effect on the global BOLD signal and directly modulates cardiovascular brain pulsations.

Model-based physiological noise removal in fast fMRI.

Recent improvements in the speed and sensitivity of fMRI acquisition techniques suggest that fast fMRI can be used to detect and precisely localize sub-second neural dynamics. This enhanced temporal resolution has enormous potential for neuroscientists. However, physiological noise poses a major challenge for the analysis of fast fMRI data. Physiological noise scales with sensitivity, and its autocorrelation structure is altered in rapidly sampled data, suggesting that new approaches are needed for physiological noise removal in fast fMRI. Existing strategies either rely on external physiological recordings, which can be noisy or difficult to collect, or employ data-driven approaches which make assumptions that may not hold true in fast fMRI. We created a statistical model of harmonic regression with autoregressive noise (HRAN) to estimate and remove cardiac and respiratory noise from the fMRI signal directly. This technique exploits the fact that cardiac and respiratory noise signals are fully sampled (rather than aliasing) when imaging at fast rates, allowing us to track and model physiology over time without requiring external physiological measurements. We then created a joint model of neural hemodynamics, and physiological and autocorrelated noise to more accurately remove noise. We first verified that HRAN accurately estimates cardiac and respiratory dynamics and that our model demonstrates goodness-of-fit in fast fMRI data. In task-driven data, we then demonstrated that HRAN is able to remove physiological noise while leaving the neural signal intact, thereby increasing detection of task-driven voxels. Finally, we established that in both simulations and fast fMRI data HRAN is able to improve statistical inferences as compared with gold-standard physiological noise removal techniques. In conclusion, we created a tool that harnesses the novel information in fast fMRI to remove physiological noise, enabling broader use of the technology to study human brain function.

Time-domain principal component reconstruction (tPCR): A more efficient and stable iterative reconstruction framework for non-Cartesian functional MRI.

PURPOSE: To improve the reconstruction efficiency (i.e., computational load) and stability of iterative reconstruction for non-Cartesian fMRI when using high undersampling rates and/or in the presence of strong off-resonance effects. THEORY AND METHODS: The magnetic resonance encephalography (MREG) sequence with 3D non-Cartesian trajectory and 0.1s repetition time (TR) was applied to acquire fMRI datasets. Different from a conventional time-point-by-time-point sequential reconstruction (SR), the proposed time-domain principal component reconstruction (tPCR) performs three steps: (1) decomposing the k-t-space fMRI datasets into time-domain principal component space using singular value decomposition, (2) reconstructing each principal component with redistributed computation power according to their weights, and (3) combining the reconstructed principal components back to image-t-space. The comparison of reconstruction accuracy was performed by simulation experiments and then verified in real fMRI data. RESULTS: The simulation experiments showed that the proposed tPCR was able to significantly reduce reconstruction errors, and subsequent functional activation errors, relative to SR at identical computational cost. Alternatively, at fixed reconstruction accuracy, computation time was greatly reduced. The improved performance was particularly obvious for L1-norm nonlinear reconstructions relative to L2-norm linear reconstructions and robust to different regularization strength, undersampling rates, and off-resonance effects intensity. By examining activation maps, tPCR was also found to give similar improvements in real fMRI experiments. CONCLUSION: The proposed proof-of-concept tPCR framework could improve (1) the reconstruction efficiency of iterative reconstruction, and (2) the reconstruction stability especially for nonlinear reconstructions. As a practical consideration, the improved reconstruction speed promotes the application of highly undersampled non-Cartesian fast fMRI.

Improved autoregressive model for correction of noise serial correlation in fast fMRI.

PURPOSE: In rapidly acquired functional MRI (fast fMRI) data, the noise serial correlations (SC) can produce problematically overestimated T-statistics which lead to invalid statistical inferences. This study aims to evaluate and improve the accuracy of high-order autoregressive model (AR(p), where p is the model order) based prewhitening method in the SC correction. METHODS: Fast fMRI images were acquired at rest (null data) using a multiband simultaneous multi-slice echo planar imaging pulse sequence with repetition time (TR) = 300 and 500 ms. The SC effect in the fast fMRI data was corrected using the prewhitening method based on two AR(p) models: (1) the conventional model (fixed AR(p)) which preselects a constant p for all the image voxels; (2) an improved model (ARAICc ) that employs the corrected Akaike information criterion voxel-wise to automatically select the model orders for each voxel. To evaluate accuracy of SC correction, false positive characteristics were measured by assuming the presence of block and event-related tasks in the null data without image smoothing. The performance of prewhitening was also examined in smoothed images by adding pseudo task fMRI signals into the null data and comparing the detected to simulated activations (ground truth). RESULTS: The measured false positive characteristics agreed well with the theoretical curve when using the ARAICc , and the activation maps in the smoothed data matched the ground truth. The ARAICc showed improved performance than the fixed AR(p) method. CONCLUSION: The ARAICc can effectively remove noise SC, and accurate statistical analysis results can be obtained with the ARAICc correction in fast fMRI.

Enhanced subject-specific resting-state network detection and extraction with fast fMRI.

Resting-state networks have become an important tool for the study of brain function. An ultra-fast imaging technique that allows to measure brain function, called Magnetic Resonance Encephalography (MREG), achieves an order of magnitude higher temporal resolution than standard echo-planar imaging (EPI). This new sequence helps to correct physiological artifacts and improves the sensitivity of the fMRI analysis. In this study, EPI is compared with MREG in terms of capability to extract resting-state networks. Healthy controls underwent two consecutive resting-state scans, one with EPI and the other with MREG. Subject-level independent component analyses (ICA) were performed separately for each of the two datasets. Using Stanford FIND atlas parcels as network templates, the presence of ICA maps corresponding to each network was quantified in each subject. The number of detected individual networks was significantly higher in the MREG data set than for EPI. Moreover, using short time segments of MREG data, such as 50 seconds, one can still detect and track consistent networks. Fast fMRI thus results in an increased capability to extract distinct functional regions at the individual subject level for the same scan times, and also allow the extraction of consistent networks within shorter time intervals than when using EPI, which is notably relevant for the analysis of dynamic functional connectivity fluctuations. Hum Brain Mapp 38:817-830, 2017. © 2016 Wiley Periodicals, Inc.

Effect of temporal resolution and serial autocorrelations in event-related functional MRI.

PURPOSE: To assess the impact of colored noise on statistics in event-related functional MRI (fMRI) (visual stimulation using checkerboards) acquired by simultaneous multislice imaging enabling repetition times (TRs) between 2.64 to 0.26 s. METHODS: T-values within the visual cortex obtained with analysis tools that assume a first-order autoregressive plus white noise process (AR(1)+w) with a fixed AR coefficient versus higher-order AR models with spatially varying AR coefficients were compared. In addition, dependency of T-values on correction of physiological noise (respiration, heart rate) was evaluated. RESULTS: Optimal statistical power was obtained for a TR of 0.33 s, but T-values as obtained by AR(1)+w models were strongly dependent on the predefined AR coefficients in fMRI with short TRs which required higher-order AR models to achieve stable statistics. Direct estimation of AR coefficients revealed the highest values within the default mode network while physiological noise had little influence on statistics in cortical structures. CONCLUSION: Colored noise in event-related fMRI obtained at short TRs originates mainly from neural sources and calls for more sophisticated correction of serial autocorrelations which cannot be achieved with standard methods relying on AR(1)+w models with globally fixed AR coefficients. Magn Reson Med 76:1805-1813, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Fast fMRI provides high statistical power in the analysis of epileptic networks.

EEG-fMRI is a unique method to combine the high temporal resolution of EEG with the high spatial resolution of MRI to study generators of intrinsic brain signals such as sleep grapho-elements or epileptic spikes. While the standard EPI sequence in fMRI experiments has a temporal resolution of around 2.5-3s a newly established fast fMRI sequence called MREG (Magnetic-Resonance-Encephalography) provides a temporal resolution of around 100ms. This technical novelty promises to improve statistics, facilitate correction of physiological artifacts and improve the understanding of epileptic networks in fMRI. The present study compares simultaneous EEG-EPI and EEG-MREG analyzing epileptic spikes to determine the yield of fast MRI in the analysis of intrinsic brain signals. Patients with frequent interictal spikes (>3/20min) underwent EEG-MREG and EEG-EPI (3T, 20min each, voxel size 3×3×3mm, EPI TR=2.61s, MREG TR=0.1s). Timings of the spikes were used in an event-related analysis to generate activation maps of t-statistics. (FMRISTAT, |t|>3.5, cluster size: 7 voxels, p<0.05 corrected). For both sequences, the amplitude and location of significant BOLD activations were compared with the spike topography. 13 patients were recorded and 33 different spike types could be analyzed. Peak T-values were significantly higher in MREG than in EPI (p<0.0001). Positive BOLD effects correlating with the spike topography were found in 8/29 spike types using the EPI and in 22/33 spikes types using the MREG sequence. Negative BOLD responses in the default mode network could be observed in 3/29 spike types with the EPI and in 19/33 with the MREG sequence. With the latter method, BOLD changes were observed even when few spikes occurred during the investigation. Simultaneous EEG-MREG thus is possible with good EEG quality and shows higher sensitivity in regard to the localization of spike-related BOLD responses than EEG-EPI. The development of new methods of analysis for this sequence such as modeling of physiological noise, temporal analysis of the BOLD signal and defining appropriate thresholds is required to fully profit from its high temporal resolution.

The temporal specificity of BOLD fMRI is systematically related to anatomical and vascular features of the human brain.

The ability to detect fast responses with functional MRI depends on the speed of hemodynamic responses to neural activity, because hemodynamic responses act as a temporal low-pass filter smoothing out rapid changes. However, hemodynamic responses (their shape and timing) are highly variable across the brain and across stimuli. This heterogeneity of responses implies that the temporal specificity of fMRI signals, or the ability of fMRI to preserve fast information, should also vary substantially across the cortex. In this work we investigated how local differences in hemodynamic response timing impact the temporal specificity of fMRI. We conducted our research using ultra-high field (7T) fMRI at high spatiotemporal resolution, using the primary visual cortex (V1) as a model area for investigation. We used visual stimuli oscillating at slow and fast frequencies to probe the temporal specificity of individual voxels. As expected, we identified substantial variability in temporal specificity, with some voxels preserving their responses to fast neural activity more effectively than others. We investigated which voxels had the highest temporal specificity and related those to anatomical and vascular features of V1. We found that low temporal specificity is only weakly explained by the presence of large veins or cerebral cortical depth. Notably, however, temporal specificity depended strongly on a voxel's position along the anterior-posterior anatomical axis of V1, with voxels within the calcarine sulcus being capable of preserving close to 25% of their amplitude as the frequency of stimulation increased from 0.05-Hz to 0.20-Hz, and voxels nearest to the occipital pole preserving less than 18%. These results indicate that detection biases in high-resolution fMRI will depend on the anatomical and vascular features of the area being imaged, and that these biases will differ depending on the timing of the underlying neuronal activity. Importantly, this spatial heterogeneity of temporal specificity suggests that it could be exploited to achieve higher specificity in some locations, and that tailored data analysis strategies may help improve the detection and interpretation of fast fMRI responses.

Increased interictal synchronicity of respiratory related brain pulsations in epilepsy.

Respiratory brain pulsations have recently been shown to drive electrophysiological brain activity in patients with epilepsy. Furthermore, functional neuroimaging indicates that respiratory brain pulsations have increased variability and amplitude in patients with epilepsy compared to healthy individuals. To determine whether the respiratory drive is altered in epilepsy, we compared respiratory brain pulsation synchronicity between healthy controls and patients. Whole brain fast functional magnetic resonance imaging was performed on 40 medicated patients with focal epilepsy, 20 drug-naïve patients and 102 healthy controls. Cerebrospinal fluid associated respiratory pulsations were used to generate individual whole brain respiratory synchronization maps, which were compared between groups. Finally, we analyzed the seizure frequency effect and diagnostic accuracy of the respiratory synchronization defect in epilepsy. Respiratory brain pulsations related to the verified fourth ventricle pulsations were significantly more synchronous in patients in frontal, periventricular and mid-temporal regions, while the seizure frequency correlated positively with synchronicity. The respiratory brain synchronicity had a good diagnostic accuracy (ROCAUC = 0.75) in discriminating controls from medicated patients. The elevated respiratory brain synchronicity in focal epilepsy suggests altered physiological effect of cerebrospinal fluid pulsations possibly linked to regional brain water dynamics involved with interictal brain physiology.

Cardiovascular Pulsatility Increases in Visual Cortex Before Blood Oxygen Level Dependent Response During Stimulus.

The physiological pulsations that drive tissue fluid homeostasis are not well characterized during brain activation. Therefore, we used fast magnetic resonance encephalography (MREG) fMRI to measure full band (0-5 Hz) blood oxygen level-dependent (BOLDFB) signals during a dynamic visual task in 23 subjects. This revealed brain activity in the very low frequency (BOLDVLF) as well as in cardiac and respiratory bands. The cardiovascular hemodynamic envelope (CHe) signal correlated significantly with the visual BOLDVLF response, considered as an independent signal source in the V1-V2 visual cortices. The CHe preceded the canonical BOLDVLF response by an average of 1.3 (± 2.2) s. Physiologically, the observed CHe signal could mark increased regional cardiovascular pulsatility following vasodilation.

Statistical power or more precise insights into neuro-temporal dynamics? Assessing the benefits of rapid temporal sampling in fMRI.

Functional magnetic resonance imaging (fMRI), a non-invasive and widely used human neuroimaging method, is most known for its spatial precision. However, there is a growing interest in its temporal sensitivity. This is despite the temporal blurring of neuronal events by the blood oxygen level dependent (BOLD) signal, the peak of which lags neuronal firing by 4-6 seconds. Given this, the goal of this review is to answer a seemingly simple question - "What are the benefits of increased temporal sampling for fMRI?". To answer this, we have combined fMRI data collected at multiple temporal scales, from 323 to 1000 milliseconds, with a review of both historical and contemporary temporal literature. After a brief discussion of technological developments that have rekindled interest in temporal research, we next consider the potential statistical and methodological benefits. Most importantly, we explore how fast fMRI can uncover previously unobserved neuro-temporal dynamics - effects that are entirely missed when sampling at conventional 1 to 2 second rates. With the intrinsic link between space and time in fMRI, this temporal renaissance also delivers improvements in spatial precision. Far from producing only statistical gains, the array of benefits suggest that the continued temporal work is worth the effort.

Imaging faster neural dynamics with fast fMRI: A need for updated models of the hemodynamic response.

Fast fMRI enables the detection of neural dynamics over timescales of hundreds of milliseconds, suggesting it may provide a new avenue for studying subsecond neural processes in the human brain. The magnitudes of these fast fMRI dynamics are far greater than predicted by canonical models of the hemodynamic response. Several studies have established nonlinear properties of the hemodynamic response that have significant implications for fast fMRI. We first review nonlinear properties of the hemodynamic response function that may underlie fast fMRI signals. We then illustrate the breakdown of canonical hemodynamic response models in the context of fast neural dynamics. We will then argue that the canonical hemodynamic response function is not likely to reflect the BOLD response to neuronal activity driven by sparse or naturalistic stimuli or perhaps to spontaneous neuronal fluctuations in the resting state. These properties suggest that fast fMRI is capable of tracking surprisingly fast neuronal dynamics, and we discuss the neuroscientific questions that could be addressed using this approach.

Respiratory-related brain pulsations are increased in epilepsy-a two-centre functional MRI study.

Resting-state functional MRI has shown potential for detecting changes in cerebral blood oxygen level-dependent signal in patients with epilepsy, even in the absence of epileptiform activity. Furthermore, it has been suggested that coefficient of variation mapping of fast functional MRI signal may provide a powerful tool for the identification of intrinsic brain pulsations in neurological diseases such as dementia, stroke and epilepsy. In this study, we used fast functional MRI sequence (magnetic resonance encephalography) to acquire ten whole-brain images per second. We used the functional MRI data to compare physiological brain pulsations between healthy controls (n = 102) and patients with epilepsy (n = 33) and furthermore to drug-naive seizure patients (n = 9). Analyses were performed by calculating coefficient of variation and spectral power in full band and filtered sub-bands. Brain pulsations in the respiratory-related frequency sub-band (0.11-0.51 Hz) were significantly (P < 0.05) increased in patients with epilepsy, with an increase in both signal variance and power. At the individual level, over 80% of medicated and drug-naive seizure patients exhibited areas of abnormal brain signal power that correlated well with the known clinical diagnosis, while none of the controls showed signs of abnormality with the same threshold. The differences were most apparent in the basal brain structures, respiratory centres of brain stem, midbrain and temporal lobes. Notably, full-band, very low frequency (0.01-0.1 Hz) and cardiovascular (0.8-1.76 Hz) brain pulses showed no differences between groups. This study extends and confirms our previous results of abnormal fast functional MRI signal variance in epilepsy patients. Only respiratory-related brain pulsations were clearly increased with no changes in either physiological cardiorespiratory rates or head motion between the subjects. The regional alterations in brain pulsations suggest that mechanisms driving the cerebrospinal fluid homeostasis may be altered in epilepsy. Magnetic resonance encephalography has both increased sensitivity and high specificity for detecting the increased brain pulsations, particularly in times when other tools for locating epileptogenic areas remain inconclusive.

Lag Analysis of Fast fMRI Reveals Delayed Information Flow Between the Default Mode and Other Networks in Narcolepsy.

Narcolepsy is a chronic neurological disease characterized by dysfunction of the hypocretin system in brain causing disruption in the wake-promoting system. In addition to sleep attacks and cataplexy, patients with narcolepsy commonly report cognitive symptoms while objective deficits in sustained attention and executive function have been observed. Prior resting-state functional magnetic resonance imaging (fMRI) studies in narcolepsy have reported decreased inter/intranetwork connectivity regarding the default mode network (DMN). Recently developed fast fMRI data acquisition allows more precise detection of brain signal propagation with a novel dynamic lag analysis. In this study, we used fast fMRI data to analyze dynamics of inter resting-state network (RSN) information signaling between narcolepsy type 1 patients (NT1, n = 23) and age- and sex-matched healthy controls (HC, n = 23). We investigated dynamic connectivity properties between positive and negative peaks and, furthermore, their anticorrelative (pos-neg) counterparts. The lag distributions were significantly (P < 0.005, familywise error rate corrected) altered in 24 RSN pairs in NT1. The DMN was involved in 83% of the altered RSN pairs. We conclude that narcolepsy type 1 is characterized with delayed and monotonic inter-RSN information flow especially involving anticorrelations, which are known to be characteristic behavior of the DMN regarding neurocognition.

Spectral entropy indicates electrophysiological and hemodynamic changes in drug-resistant epilepsy - A multimodal MREG study.

OBJECTIVE: Epilepsy causes measurable irregularity over a range of brain signal frequencies, as well as autonomic nervous system functions that modulate heart and respiratory rate variability. Imaging dynamic neuronal signals utilizing simultaneously acquired ultra-fast 10 Hz magnetic resonance encephalography (MREG), direct current electroencephalography (DC-EEG), and near-infrared spectroscopy (NIRS) can provide a more comprehensive picture of human brain function. Spectral entropy (SE) is a nonlinear method to summarize signal power irregularity over measured frequencies. SE was used as a joint measure to study whether spectral signal irregularity over a range of brain signal frequencies based on synchronous multimodal brain signals could provide new insights in the neural underpinnings of epileptiform activity. METHODS: Ten patients with focal drug-resistant epilepsy (DRE) and ten healthy controls (HC) were scanned with 10 Hz MREG sequence in combination with EEG, NIRS (measuring oxygenated, deoxygenated, and total hemoglobin: HbO, Hb, and HbT, respectively), and cardiorespiratory signals. After pre-processing, voxelwise SEMREG was estimated from MREG data. Different neurophysiological and physiological subfrequency band signals were further estimated from MREG, DC-EEG, and NIRS: fullband (0-5 Hz, FB), near FB (0.08-5 Hz, NFB), brain pulsations in very-low (0.009-0.08 Hz, VLFP), respiratory (0.12-0.4 Hz, RFP), and cardiac (0.7-1.6 Hz, CFP) frequency bands. Global dynamic fluctuations in MREG and NIRS were analyzed in windows of 2 min with 50% overlap. RESULTS: Right thalamus, cingulate gyrus, inferior frontal gyrus, and frontal pole showed significantly higher SEMREG in DRE patients compared to HC. In DRE patients, SE of cortical Hb was significantly reduced in FB (p = .045), NFB (p = .017), and CFP (p = .038), while both HbO and HbT were significantly reduced in RFP (p = .038, p = .045, respectively). Dynamic SE of HbT was reduced in DRE patients in RFP during minutes 2 to 6. Fitting to the frontal MREG and NIRS results, DRE patients showed a significant increase in SEEEG in FB in fronto-central and parieto-occipital regions, in VLFP in parieto-central region, accompanied with a significant decrease in RFP in frontal pole and parietal and occipital (O2, Oz) regions. CONCLUSION: This is the first study to show altered spectral entropy from synchronous MREG, EEG, and NIRS in DRE patients. Higher SEMREG in DRE patients in anterior cingulate gyrus together with SEEEG and SENIRS results in 0.12-0.4 Hz can be linked to altered parasympathetic function and respiratory pulsations in the brain. Higher SEMREG in thalamus in DRE patients is connected to disturbances in anatomical and functional connections in epilepsy. Findings suggest that spectral irregularity of both electrophysiological and hemodynamic signals are altered in specific way depending on the physiological frequency range.

Marker-based ballistocardiographic artifact correction improves spike identification in EEG-fMRI of focal epilepsy patients.

OBJECTIVES: Ballistocardiographic (BCG) artifacts resemble interictal epileptic discharges (IEDs) and can lead to incorrect IED identification in EEG-fMRI. This study investigates IEDs marked in EEGs corrected using information from a moiré phase tracking (MPT) marker. METHODS: EEG-fMRI from 18 patients was processed with conventional methods for BCG removal, while 9 patients used a MPT marker. IEDs were marked first without ECG information. In a second review, suspicious IEDs synchronous with the BCG were discarded. After each review, an event-related fMRI analysis was performed on the marked IEDs. RESULTS: No difference was found in the proportion of suspicious IEDs in the 2 patient groups. However, the distribution of IED timings was significantly related to the cardiac cycle in 11 of 18 patients recorded without MPT marker, but only 2 of 9 patients with marker. In patients recorded without marker, failing to discard suspicious IEDs led to more inaccurate fMRI maps and more distant activations. CONCLUSIONS: BCG artifact correction based on MPT recordings allowed a more straightforward identification of IEDs that did not require ECG information in the large majority of patients. SIGNIFICANCE: Marker-based ballistocardiographic artifact correction greatly facilitates the study of the generators of interictal discharges with EEG-fMRI.

Negative BOLD in default-mode structures measured with EEG-MREG is larger in temporal than extra-temporal epileptic spikes.

INTRODUCTION: EEG-fMRI detects BOLD changes associated with epileptic interictal discharges (IED) and can identify epileptogenic networks in epilepsy patients. Besides positive BOLD changes, negative BOLD changes have sometimes been observed in the default-mode network, particularly using group analysis. A new fast fMRI sequence called MREG (Magnetic Resonance Encephalography) shows increased sensitivity to detect IED-related BOLD changes compared to the conventional EPI sequence, including frequent occurrence of negative BOLD responses in the DMN. The present study quantifies the concordance between the DMN and negative BOLD related to IEDs of temporal and extra-temporal origin. METHODS: Focal epilepsy patients underwent simultaneous EEG-MREG. Areas of overlap were calculated between DMN regions, defined as precuneus, posterior cingulate, bilateral inferior parietal and mesial prefrontal cortices according to a standardized atlas, and significant negative BOLD changes revealed by an event-related analysis based on the timings of IED seen on EEG. Correlation between IED number/lobe of origin and the overlap were calculated. RESULTS: 15 patients were analyzed, some showing IED over more than one location resulting in 30 different IED types. The average overlap between negative BOLD and DMN was significantly larger in temporal (23.7 ± 19.6 cm(3)) than extra-temporal IEDs (7.4 ± 5.1 cm(3), p = 0.008). There was no significant correlation between the number of IEDs and the overlap between DMN structures and negative BOLD areas. DISCUSSION: MREG results in an increased sensitivity to detect negative BOLD responses related to focal IED in single patients, with responses often occurring in DMN regions. In patients with high overlap with the DMN, this suggests that epileptic IEDs may be associated with a brief decrease in attention and cognitive ability. Interestingly this observation was not dependent on the frequency of IED but more common in IED of temporal origin.