Introduction:Brain physiological pulsations drive glymphatic clearance of neurotoxins from the brain. Neurodegenerative proteinopathies, including Parkinson's disease (PD), have altered glymphatic function. This study compares brain physiological pulsations important for glymphatic clearance in PD and healthy controls (HC). Methods:PD (N = 13) and HC (N = 20) participants were evaluated using magnetic resonance encephalography (MREG), an ultrafast, 3D spherical stack-of-spirals dynamic neuroimaging technique, to assess spectral power and optical flow in cardiovascular, respiratory, and low-frequency vasomotor bands as indirect proxies for glymphatic clearance. Group differences were analyzed with two-sample t-tests, controlling for age and sex. Results:PD participants demonstrated significantly reduced power in the cardiovascular frequency band and reduced optical flow magnitude in the low-frequency vasomotor band in regions important for visual and cognitive processing and sensorimotor function. Conclusion:PD is associated with alterations in physiological pulsations important for glymphatic flow. Glymphatic clearance may represent a potential therapeutic target for neurodegenerative diseases.
Introduction: To leverage high-frequency oscillations (HFOs) as a biomarker with significant potential, this study compared a large set of detectors on a unified dataset, aiming to evaluate their clinical applicability under realistic conditions. Methods: Eleven automatic detectors were applied to a retrospective dataset of intracranial and scalp EEGs from 27 consecutive pediatric patients. Inter-detector agreement was assessed using Spearman Rho, and the area under the curve (AUC) for seizure onset zone (SOZ) prediction served as a consistent reference standard to enable reliable comparisons across recording modalities. Analyses were conducted separately for HFO and Spike-HFO detections. Results: The average age of our cohort was 12.4 years (SD 4.0; range 5-18). AUC values in scalp EEG ranged from 0.61 to 0.67 for HFOs and from 0.53 to 0.63 for Spike-HFO. AUC values in intracranial EEG ranged from 0.48 to 0.66 for HFOs and 0.54 to 0.69 in Spike-HFO. Although only three of the 11 detectors were specifically developed or adapted for scalp EEG, the detectors generally achieved higher AUC values and stronger agreement in scalp EEG. Conclusions: We present the first study comparing intracranial and scalp detectors by testing them beyond the modalities for which they were originally designed. Although the clinical utility of detections was comparable across EEG modalities, it remained lower than reported in original studies assessing the diagnostic value of HFOs. Caution is warranted when applying a publicly available detector to a new dataset, and detector robustness remains a critical issue. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by the German Research Foundation [grant number 530582215]; and the Canadian Institute for Health Research [grant number 480576]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Conjoint Health Research Ethics Board of the University of Calgary gave ethical approval for this work (REB20-0938). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Since the EEG data files include sensitive patient information and therefore belong to the Alberta Childrens Hospital, uploading them to a public repository could compromise individual privacy. All other data produced in the present study are available upon reasonable request to the authors (submitted to ORCID 0000-0002-8598-4357).
The discovery of the glymphatic system and meningeal lymphatic vessels revolutionized the understanding of brain waste clearance. These findings challenged the long-held notion of central nervous system (CNS) immune privilege and provided insights into how the brain maintains homeostasis despite lacking conventional lymphatic drainage. However, the impact of pathological conditions, particularly CNS cancers, on the glymphatic system and vice versa remains underexplored. Glioblastoma (GBM) is the most common and aggressive primary adult CNS cancer. Its presence results in glymphatic dysfunction with significant clinical implications. Recent studies suggest that the glymphatic system interacts with GBM to influence immunity, drug delivery, fluid regulation, and tumor progression, stressing its significant role in GBM biology and potentially treatment response. This review highlights the evidence for glymphatic dysfunction in GBM and its consequences. Furthermore, we discuss the potential to harness the power of the glymphatic system to improve patient outcomes in this terrible disease.
BACKGROUND:The glymphatic system facilitates efficient waste clearance in the brain through the movement of cerebrospinal fluid (CSF) along perivascular spaces. Animal studies have demonstrated that glymphatic efficiency declines with age, but evidence for such decline in humans is limited. We hypothesized that reduced glymphatic efficiency in older adults may be related to age-related worsening of sleep quality, potentially contributing to cognitive impairment. METHODS:20 participants aged ≥60 years provided multi-dimensional cognitive measures, overnight polysomnography, and Magnetic Resonance Encephalography (MREG) performed the morning following the PSG. MREG is a single-shot, three-dimensional (3D) sequence employing a spherical stack-of-spirals trajectory that undersamples 3D k-space, enabling whole-brain data acquisition every 100 milliseconds to non-invasively and dynamically assess brain physiological pulsations. Spectral power and optical flow analyses quantified physiological pulsations within cardiovascular (CvB; 0.52-1.6 Hz), respiratory (RFB; 0.11-0.44 Hz), and low-frequency (LFB; 0.008-0.1 Hz) bands. These measures were correlated with cognitive test scores and sleep parameters assessed by overnight polysomnography. RESULTS:Significant associations emerged between physiological pulsations, sleep, and cognitive measures. Cardiovascular pulsation strength correlated with non-rapid eye movement (NREM) stage 3 (N3) sleep percentage (peak voxel in right frontal pole; r = 0.72, p < 0.001) and language domain performance (left calcarine gyrus; r = 0.56, p = 0.01). Respiratory pulsations correlated strongly with sleep onset latency (right inferior temporal gyrus; r = 0.75, p < 0.001). Additionally, low-frequency pulsations were associated with sleep onset latency (right precentral gyrus; r = 0.67, p = 0.002). These findings suggest that glymphatic efficiency, as reflected by brain pulsations, is closely linked to sleep quality and cognitive performance in older adults, particularly involving cortical and subcortical structures relevant to cognitive and sleep regulatory functions. CONCLUSION:This study uniquely demonstrates that brain physiological pulsations measured non-invasively with MREG are significantly associated with sleep architecture and cognitive performance in older adults. These findings underscore the potential of MREG to assess glymphatic function and provide important insights into the mechanisms linking sleep disturbances, cognitive decline, and aging. The identified correlations between pulsations and specific brain regions highlight potential pathways through which impaired glymphatic function could contribute to cognitive decline in older adults, suggesting promising avenues for future clinical and research applications.
We must reconcile the needs of the internal world and the demands of the external world to make decisions relevant to homeostasis, well-being, and flexible behavior. Engagement with the internal (eg interoceptive) world is linked to medial brain systems, whereas the extrapersonal space (eg exteroceptive) is associated with lateral brain systems. Using Human Connectome Project data, we found three association tracts connecting the action-related frontal lobe with perception-related posterior lobes. A lateral dorsal tract and a medial dorsal tract interact independently with a ventral tract at frontal and posterior hubs. The two frontal and the two posterior hubs are interconnected, forming a meta-loop that integrates lateral and medial brain systems. The four anatomical hubs correspond to the common nodes of the intrinsic cognitive brain networks such as the default mode network. These functional networks depend on the integration of both realms. Thus, the positioning of functional cognitive networks can be understood as the intersection of long anatomical association tracts. The strength of structural connectivity within lateral and medial brain systems correlates with performance on behavioral tests assessing theory of mind. The meta-loop provides an anatomical framework to associate neurological and psychiatric symptoms with functional and structural changes.
The Blood-Brain Barrier is the gatekeeper of the CNS. It effectively shields the brain from blood-borne harm but simultaneously represents a significant challenge for treating neurological diseases. Altering its permeability enables increasing the local drug concentration and thereby improving the therapeutic effect. Although permeability increase is achieved by raised tissue temperature, the determination of the thermal dosage suffers from imprecise thermometry during hyperthermia application. Knowledge of the thermal dosage is crucial for improving hyperthermia related interventions of the CNS. Here we show an approach to determine the thermal threshold for localized Blood-Brain Barrier disruption estimated by MR thermometry. Methods: Using an IR laser ({\lambda} = 1470nm) we showed that highly localized Blood-Brain Barrier opening can be achieved with mild to moderate hyperthermia. Non-invasive MR thermometry has been used to determine the temperature at the heating site. Blood-Brain Barrier opening has been monitored by DCE-MRI in vivo and post mortem via Evan's Blue extravasation. Results: The Blood-Brain Barrier permeability can be altered locally with minimal thermal dosages. Thus mild hyperthermia represents a promising approach to making the brain accessible for therapeutic interventions.
OBJECTIVE:To use intracranial electroencephalography (EEG) to characterize functional magnetic resonance imaging (fMRI) activation maps associated with high-frequency oscillations (HFOs) (80-250 Hz) and examine their proximity to HFO- and seizure-generating tissue. METHODS:Forty-five patients implanted with intracranial depth electrodes underwent a simultaneous EEG-fMRI study at 3 T. HFOs were detected algorithmically from cleaned EEG and visually confirmed by an experienced electroencephalographer. HFOs that co-occurred with interictal epileptiform discharges (IEDs) were subsequently identified. fMRI activation maps associated with HFOs were generated that occurred either independently of IEDs or within ±200 ms of an IED. For all significant analyses, the Maximum, Second Maximum, and Closest activation clusters were identified, and distances were measured to both the electrodes where the HFOs were observed and the electrodes involved in seizure onset. RESULTS:We identified 108 distinct groups of HFOs from 45 patients. We found that HFOs with IEDs produced fMRI clusters that were closer to the local field potentials of the corresponding HFOs observed within the EEG than HFOs without IEDs. In addition to the fMRI clusters being closer to the location of the EEG correlate, HFOs with IEDs generated Maximum clusters with greater z-scores and larger volumes than HFOs without IEDs. We also observed that HFOs with IEDs resulted in more discrete activation maps. SIGNIFICANCE:Intracranial EEG-fMRI can be used to probe the hemodynamic response to HFOs. The hemodynamic response associated with HFOs that co-occur with IEDs better identifies known epileptic tissue than HFOs that occur independently.
Theranostic platforms, combining diagnostic and therapeutic approaches within one system, have garnered interest in augmenting invasive surgical, chemical, and ionizing interventions.Magnetic particle imaging (MPI) offers a quite recent alternative to established radiation-based diagnostic modalities with its versatile tracer material (superparamagnetic iron oxide nanoparticles, SPION).It also offers a bimodal theranostic framework that can combine tomographic imaging with therapeutic techniques using the very same SPION.Methods: We show the interleaved combination of MPI-based imaging, therapy (highly localized magnetic fluid hyperthermia (MFH)) and therapy safety control (MPI-based thermometry) within one theranostic platform in all three spatial dimensions using a commercial MPI system and a custom-made heating insert.The heating characteristics as well as theranostic applications of the platform were demonstrated by various phantom experiments using commercial SPION.Results: We have shown the feasibility of an MPI-MFH-based theranostic platform by demonstrating high spatial control of the therapeutic target, adequate MPI-based thermometry, and successful in situ interleaved MPI-MFH application.Conclusions: MPI-MFH-based theranostic platforms serve as valuable tools that enable the synergistic integration of diagnostic and therapeutic approaches.The transition into in vivo studies will be essential to further validate their potential, and it holds promising prospects for future advancements.
Various subjective and objective methods have been proposed to identify which interictal epileptiform discharge (IED)-related EEG-functional MRI (fMRI) results are more likely to delineate seizure-generating tissue in patients with drug-resistant focal epilepsy for the purposes of surgical planning. In this intracranial EEG-fMRI study, we evaluated the utility of these methods to localize clinically relevant regions preoperatively and compared the extent of resection of these areas to postoperative outcome.Seventy patients admitted for intracranial video-EEG monitoring were recruited for a simultaneous intracranial EEG-fMRI study. For all analyses of blood oxygen level-dependent responses associated with IEDs, an experienced epileptologist identified the most clinically relevant brain activation cluster using available clinical information. The maximum cluster (the cluster with the highest z-score) was also identified for all analyses and assigned to one of three confidence levels (low, medium or high) based on the difference of the peak z-scores between the maximum and second maximum cluster (the cluster with the second highest peak z-value). The distance was measured and compared between the peak voxel of the aforementioned clusters and the electrode contacts where the interictal discharge and seizure onset were recorded. In patients who subsequently underwent epilepsy surgery, the spatial concordance between the aforementioned clusters and the area of resection was determined and compared to postoperative outcome.We evaluated 106 different IEDs in 70 patients. Both subjective (identification of the clinically relevant cluster) and objective (maximum cluster much more significant than the second maximum cluster) methods of culling non-localizing EEG-fMRI activation maps increased the spatial concordance between these clusters and the corresponding IED or seizure onset zone contacts. However, only the objective methods of identifying medium and high confidence maps resulted in a significant association between resection of the peak voxel of the maximum cluster and postoperative outcome. Resection of this area was associated with good postoperative outcomes but was not sufficient for seizure freedom. On the other hand, we found that failure to resect the medium and high confidence maximum clusters was associated with a poor post-surgical outcome (negative predictive value = 1.0, sensitivity = 1.0).Methods to identify higher confidence EEG-fMRI results are needed to localize areas necessary for good postoperative outcomes. However, resection of the peak voxel within higher confidence maximum clusters is not sufficient for good outcomes. Conversely, failure to resect the peak voxel in these clusters is associated with a poor post-surgical outcome. Wilson et al. evaluate the utility of intracranial EEG-fMRI as a tool to help predict outcomes in epilepsy surgery. Removal of the brain area where peak activation (as revealed by fMRI) is associated with brief seizure discharges is necessary, but not sufficient, for good post-surgical outcomes.
Electrical neurostimulation is currently used to manage epilepsy, but the most effective approach for minimizing seizure occurrence is uncertain. While functional MRI (fMRI) can reveal which brain areas are affected by stimulation, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. In this study, we utilized the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy (mTLE) to systematically examine the brain-wide responses to electrical stimulation using fMRI. We compared fMRI responses of saline-injected controls and epileptic mice during stimulation in the septal hippocampus (HC) at 10 Hz and demonstrated the effects of different stimulation amplitudes (80–230 μA) and frequencies (1–100 Hz) in epileptic mice. Motivated by recent studies exploring 1 Hz stimulation to prevent epileptic seizures, we furthermore investigated the effect of prolonged 1 Hz stimulation with fMRI. Compared to sham controls, epileptic mice showed less propagation to the contralateral HC, but significantly stronger responses in the ipsilateral HC and a wider spread to the entorhinal cortex and septal region. Varying the stimulation amplitude had little effect on the resulting activation patterns, whereas the stimulation frequency represented the key parameter and determined whether the induced activation remained local or spread from the hippocampal formation into cortical areas. Prolonged stimulation of epileptic mice at 1 Hz caused a slight reduction in local excitability. In this way, our study contributes to a better understanding of these stimulation paradigms.
OBJECTIVE:Temporal lobe epilepsy (TLE) has a high probability of becoming drug resistant and is frequently considered for surgical intervention. However, 30% of TLE cases have nonlesional magnetic resonance imaging (MRI) scans, which is associated with worse surgical outcomes. Characterizing interactions between temporal and extratemporal structures in these patients may help understand these poor outcomes. Simultaneous intracranial electroencephalography-functional MRI (iEEG-fMRI) can measure the hemodynamic changes associated with interictal epileptiform discharges (IEDs) recorded directly from the brain. This study was designed to characterize the whole brain patterns of IED-associated fMRI activation recorded exclusively from the mesial temporal lobes of patients with nonlesional TLE. METHODS:Eighteen patients with nonlesional TLE undergoing iEEG monitoring with mesial temporal IEDs underwent simultaneous iEEG-fMRI at 3 T. IEDs were marked, and statistically significant clusters of fMRI activation were identified. The locations of IED-associated fMRI activation for each patient were determined, and patients were grouped based on the location and pattern of fMRI activation. RESULTS:Two patterns of IED-associated fMRI activation emerged: primarily localized (n = 7), where activation was primarily located within the ipsilateral temporal lobe, and primarily diffuse (n = 11), where widespread bilateral extratemporal activation was detected. The primarily diffuse group reported significantly fewer focal to bilateral tonic-clonic seizures and had better postsurgical outcomes. SIGNIFICANCE:Simultaneous iEEG-fMRI can measure the hemodynamic changes associated with focal IEDs not visible on scalp EEG, such as those arising from the mesial temporal lobe. Significant fMRI activation associated with these IEDs was observed in all patients. Two distinct patterns of IED-associated activation were seen: primarily localized to the ipsilateral temporal lobe and more widespread, bilateral activation. Patients with widespread IED associated-activation had fewer focal to bilateral tonic-clonic seizures and better postsurgical outcome, which may suggest a neuroprotective mechanism limiting the spread of ictal events.
Hintergrund Unterschiede in Integrität der grauen und weißen Substanz bei asymmetrischem Hörverlust (AHL) und normalem Hören (NH) wurde mit Hilfe von strukturellem MRI und Diffusions-Tensor-Imaging (DTI) untersucht.
Purpose To explore the differences in gray and white matter integrity between patients with asymmetric hearing loss (AHL) and normal-hearing controls (NH) using structural MRI and diffusion tensor imaging (DTI).
Background Electrical neurostimulation is a potentially effective therapy in epilepsy but the optimal approach is not yet clear. The parameter space is wide and the effects of different stimulations are not immediately obvious. Functional MRI (fMRI) can reveal which brain areas are affected by stimulation and help understand the induced effects. However, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. Preclinical stimulation-fMRI studies can provide predictive value and help identify optimal neurostimulation parameters. Objective To systematically investigate the brain-wide responses to hippocampal electrical stimulations in a mouse model of mesial temporal lobe epilepsy (mTLE) using fMRI. Methods We applied electrical stimulation in the intrahippocampal kainate mouse model of mTLE and assessed the effect of different stimulation amplitudes (80-230 µA) and frequencies (1-100 Hz). In addition, the effect of prolonged 1 Hz stimulation was explored. Saline-injected mice served as controls. Results Varying the stimulation amplitudes had little effect on the resulting activation patterns. Low frequency stimulation led to a local response at the stimulation site only, whereas high frequency resulted in a spread of activation from the hippocampal formation into cortical and frontal areas. Prolonged low frequency stimulation reduced excitability. Conclusions While the amplitude parameter offers little opportunity to vary the outcome, the frequency represented the key parameter and determined whether the induced activation remained local or spread across the brain. This is in line with the few DBS-fMRI results obtained in epilepsy patients demonstrating the translational value of fMRI.
Functional connectivity (FC) of resting-state fMRI (rs-fMRI) is a popular method for characterizing brain connectivity. rs-fMRI indirectly measures neuronal fluctuations through blood-oxygenation-level dependent (BOLD) signal and is susceptible to various physiological noise which lead to spurious correlations. We investigated the relationship between rs-fMRI FC and band-limited power (BLP) coupling measured using intracranial EEG (icEEG). Both static and dynamic connectivity analyses revealed a relationship between BOLD FC and icEEG BLP coupling across multiple frequency bands. However, this relationship depends on distance and electrode type. BOLD FC is distinct in fluctuations and spatial variability, suggesting non-neural signal sources in rs-fMRI connectivity.
The potential of using features derived from resting-state fMRI time series to localize epileptic brain areas was studied. Static and dynamic correlations between local spike rates measured with intracranial EEG and regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and functional connectivity (FC), respectively, were analyzed based on data collected from 13 subjects with refractory epilepsy. While static measures of ReHo and ALFF were not statistically correlated with spike rates measured during long-term monitoring, static correlation with FC was apparent. However, in dynamic analysis, temporal variations in instantaneous spike rates were associated with synchronous fluctuations of both ALFF and FC.
Simultaneous EEG-fMRI is a growing and promising field, as it has great potential to further our understanding of the spatiotemporal dynamics of brain function in health and disease. In particular, there is much interest in understanding the fMRI correlates of brain activity in the gamma band ( > 30 Hz), as these frequencies are thought to be associated with cognitive processes involving perception, attention, and memory, as well as with disorders such as schizophrenia and autism. However, progress in this area has been limited due to issues such as MR-induced artifacts in EEG recordings, which seem to be more problematic for gamma frequencies. This paper presents a noise removal method for the gamma band of EEG that is based on the Holo-Hilbert spectral analysis (HHSA), but with a new implementation strategy. HHSA uses a nested empirical mode decomposition (EMD) to identify amplitude and frequency modulations (AM and FM, respectively) by averaging over frequencies with high and significant powers. Our method examines gamma band by applying two layers of EMD to the FM and AM components, removing components with very low power based on the power-instantaneous frequency spectrum, and subsequently reconstructs the denoised gamma-band signal from the remaining components. Simulations demonstrate that our proposed method efficiently reduces artifacts while preserving the original gamma signal which is especially critical for simultaneous EEG/fMRI studies.
Aphasia, the impairment to understand or produce language, is a frequent disorder after stroke with devastating effects. Conventional speech and language therapy include each formal intervention for improving language and communication abilities. In the chronic stage after stroke, it is effective compared with no treatment, but its effect size is small. We present a new language training approach for the rehabilitation of patients with aphasia based on a brain-computer interface system. The approach exploits its capacity to provide feedback time-locked to a brain state. Thus, it implements the idea that reinforcing an appropriate language processing strategy may induce beneficial brain plasticity. In our approach, patients perform a simple auditory target word detection task whilst their EEG was recorded. The constant decoding of these signals by machine learning models generates an individual and immediate brain-state-dependent feedback. It indicates to patients how well they accomplish the task during a training session, even if they are unable to speak. Results obtained from a proof-of-concept study with 10 stroke patients with mild to severe chronic aphasia (age range: 38-76 years) are remarkable. First, we found that the high-intensity training (30 h, 4 days per week) was feasible, despite a high-word presentation speed and unfavourable stroke-induced EEG signal characteristics. Second, the training induced a sustained recovery of aphasia, which generalized to multiple language aspects beyond the trained task. Specifically, all tested language assessments (Aachen Aphasia Test, Snodgrass & Vanderwart, Communicative Activity Log) showed significant medium to large improvements between pre- and post-training, with a standardized mean difference of 0.63 obtained for the Aachen Aphasia Test, and five patients categorized as non-aphasic at post-training assessment. Third, our data show that these language improvements were accompanied neither by significant changes in attention skills nor non-linguistic skills. Investigating possible modes of action of this brain-computer interface-based language training, neuroimaging data (EEG and resting-state functional MRI) indicates a training-induced faster word processing, a strengthened language network and a rebalancing between the language- and default mode networks.
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.
PurposeSpin‐echo (SE) functional MRI (fMRI) can be highly advantageous compared to gradient‐echo (GE) fMRI with respect to magnetic field‐inhomogeneity artifacts. However, at 3T, the majority of blood oxygenation level‐dependent (BOLD) fMRI experiments are performed using ‐weighted GE sequences because of their superior sensitivity compared to SE‐fMRI. The presented SE implementation of a highly accelerated GE pulse sequence therefore aims to improve the sensitivity of SE‐fMRI while profiting from a reduction of susceptibility‐induced signal dropout.MethodsSpin‐echo MR encephalography (SE‐MREG) is compared with the more conventionally used spin‐echo echo‐planar imaging (SE‐EPI) and spin‐echo simultaneous multislice (SE‐SMS) at 3T in terms of capability to detect neuronal activations and resting‐state functional connectivity. For activation analysis, healthy subjects underwent consecutive SE‐MREG (pulse repetition time [TR] = 0.25 seconds), SE‐SMS (TR = 1.3 seconds), and SE‐EPI (TR = 4.4 seconds) scans in pseudorandomized order applied to a visual block design paradigm for generation of t‐statistics maps. For the investigation of functional connectivity, additional resting‐state data were acquired for 5 minutes and a seed‐based correlation analysis using Stanford’s FIND (Functional Imaging in Neuropsychiatric Disorders) atlas was performed.ResultsThe increased sampling rate of SE‐MREG relative to SE‐SMS and SE‐EPI improves the sensitivity to detect BOLD activation by 33% and 54%, respectively, and increases the capability to extract resting‐state networks. Compared with a brain region that is not affected by magnetic field inhomogeneities, SE‐MREG shows 2.5 times higher relative signal strength than GE‐MREG in mesial temporal structures.ConclusionSE‐MREG offers a viable possibility for whole‐brain fMRI with consideration of brain regions that are affected by strong susceptibility‐induced magnetic field gradients.