Functional MRI Signal Research Articles

Compensatory functional connectome changes in a rat model of traumatic brain injury.

Penetrating cortical impact injuries alter neuronal communication beyond the injury epicentre, across regions involved in affective, sensorimotor and cognitive processing. Understanding how traumatic brain injury reorganizes local and brain wide nodal interactions may provide valuable quantitative parameters for monitoring pathological progression and recovery. To this end, we investigated spontaneous fluctuations in the functional MRI signal obtained at 11.1 T in rats sustaining controlled cortical impact and imaged at 2- and 30-days post-injury. Graph theory-based calculations were applied to weighted undirected matrices constructed from 12 879 pairwise correlations between functional MRI signals from 162 regions. Our data indicate that on Days 2 and 30 post-controlled cortical impact there is a significant increase in connectivity strength in nodes located in contralesional cortical, thalamic and basal forebrain areas. Rats imaged on Day 2 post-injury had significantly greater network modularity than controls, with influential nodes (with high eigenvector centrality) contained within the contralesional module and participating less in cross-modular interactions. By Day 30, modularity and cross-modular interactions recover, although a cluster of nodes with low strength and low eigenvector centrality remain in the ipsilateral cortex. Our results suggest that changes in node strength, modularity, eigenvector centrality and participation coefficient track early and late traumatic brain injury effects on brain functional connectivity. We propose that the observed compensatory functional connectivity reorganization in response to controlled cortical impact may be unfavourable to brain wide communication in the early post-injury period.

Novel Composite Gold-Aluminum Electrode with Application to Neural Recording and Stimulation in Ultrahigh Field Magnetic Resonance Imaging Scanners.

Traditional electrodes used for neural recording and stimulation generate large regions of signal void (no functional MRI signal) when used in ultrahigh field (UHF) MRI scanners. This is a significant disadvantage when simultaneous neural recording/stimulation and fMRI signal acquisition is desired, for example in understanding the functional mechanisms of deep brain stimulation (DBS). In this work, a novel gold-aluminum microwire neural electrode is presented which overcomes this disadvantage. The gold-aluminum design greatly reduces the magnetic susceptibility difference between the electrode and brain tissue leading to significantly reduced regions of signal void. Gold-aluminum microwire samples are imaged at ultrahigh field 16.4 Tesla and compared with gold-only and aluminum-only microwire samples. First, B0 field mapping was used to quantify field distortions at 16.4T and compared with analytical computations in an agarose phantom. The gold-aluminum microwire samples generated substantially less field distortion and signal loss in comparison with gold-only and aluminum-only samples at 16.4T using gradient echo imaging and echo planar imaging sequences. Next, the proposed gold-aluminum electrode was used to successfully record local field potential signals from a rat cortex. The newly proposed gold-aluminum microwire electrode exhibits reduced field distortions and signal loss at 16.4T, a finding which translates to MRI scanners of lower magnetic field strengths as well. The design can be easily reproduced for widespread study of DBS using MRI in animal models. Additionally, the use of non-reactive gold and aluminum materials presents an avenue for translation to human implant applications in the future.

Analysis of functional MRI signal complexity based on permutation fuzzy entropy in bipolar disorder.

Bipolar disorder is a manifestation of an emotional disease and is associated with emotional and cognitive dysfunction. The entropy-based method has been widely used to study the complexity of resting-state functional MRI (rs-fMRI) signals in mental diseases; however, alterations in the brain rs-fMRI signal complexities in bipolar disorder patients remain unclear, and previously used entropy methods are sensitive to noise. Here, we performed a work using permutation fuzzy entropy (PFEN), which has better performance than previously used methods, to analyze the brain complexity of bipolar disorder patients. Based on PFEN research, we obtained brain entropy maps of 49 bipolar disorder patients and 49 normal control, extracted the regions of interest to analyze the complexity of abnormal brain regions and further analyzed the correlation between the PFEN values of abnormal brain regions and the clinical measurement scores. Compared with the values in the normal control group, we found that significantly increased PFEN values mainly appeared in the middle temporal gyrus, angular gyrus, superior occipital gyrus and medial superior frontal gyrus, and the decreased PFEN values were found in the inferior temporal gyrus in bipolar disorder patients. In addition, the PFEN values of the angular gyrus was significantly negatively correlated with clinical scores. These findings improve our understanding of the pathophysiology of bipolar disorder patients.

Altered Complexity of Spontaneous Brain Activity in Schizophrenia and Bipolar Disorder Patients.

Schizophrenia (SC) and bipolar disorder (BP) share elements of symptoms and the underlying neural mechanisms for both remain unclear. Recently, the complexity of spontaneous functional MRI (fMRI) signals in brain activity has been investigated in SC and BP using multiscale sample entropy (MSE) with inconsistent results. To perform MSE analysis across five time scales to assess differences in resting-state fMRI signal complexity in SC, BP, and normal controls (NC). Retrospective. Fifty SC, 49 BP, and 49 NC. A 3 T, T2* weighted echo planar imaging (EPI) sequence. The mean MSEs of all gray matter (GM) and of 12 regions of interest (ROIs) were extracted using masks across the five scales. The regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) in these ROIs were also determined and the relationship between the three measures was investigated. The correlations between cognitive assessment scores and MSE values were also explored. Bonferroni correction, One-way ANOVA, Spearman rank correlation coefficient (r), Gaussian random field (GRF) correction. There were decreased GM MSE values in the patient groups (F=9.629, P < 0.05). SC and BP patients demonstrated lower complexity than NCs in the calcarine fissure, precuneus, inferior occipital gyrus, lingual gyrus and cerebellum, and higher complexity in the median cingulate, thalamus, hippocampus, middle temporal gyrus and middle frontal gyrus. There were significant differences between SC and BP patients in the precuneus (F=4.890, P < 0.05) and inferior occipital gyrus (F=5.820, P < 0.05). Calcarine fissure, cingulate, temporal gyrus, occipital gyrus, hippocampus, precuneus, frontal gyrus, and lingual gyrus MSE values were significantly correlated with both ReHo (r > 0.282, P < 0.05) and ALFF (r > 0.278, P < 0.05). Furthermore, median temporal MSE (r=-0.321, P < 0.05) on scale 3 and (r=-0.307, P < 0.05) on scale 4 and median cingulate MSE (r=-0.337, P < 0.05) on scale 5 was significantly negatively correlated with cognitive assessment scores. These data highlight different patterns of brain signal intensity complexity in SC and BP. 1 TECHNICAL EFFICACY: Stage 1.

Combining anatomical and functional networks for neuropathology identification: A case study on autism spectrum disorder.

While the prevalence of Autism Spectrum Disorder (ASD) is increasing, research continues in an effort to identify common etiological and pathophysiological bases. In this regard, modern machine learning and network science pave the way for a better understanding of the neuropathology and the development of diagnosis aid systems. The present work addresses the classification of neurotypical and ASD subjects by combining knowledge about both the structure and the functional activity of the brain. In particular, we model the brain structure as a graph, and the resting-state functional MRI (rs-fMRI) signals as values that live on the nodes of that graph. We then borrow tools from the emerging field of Graph Signal Processing (GSP) to build features related to the frequency content of these signals. In order to make these features highly discriminative, we apply an extension of the Fukunaga-Koontz transform. Finally, we use these new markers to train a decision tree, an interpretable classification scheme, which results in a final diagnosis aid model. Interestingly, the resulting decision tree outperforms state-of-the-art methods on the publicly available Autism Brain Imaging Data Exchange (ABIDE) collection. Moreover, the analysis of the predictive markers reveals the influence of the frontal and temporal lobes in the diagnosis of the disorder, which is in line with previous findings in the literature of neuroscience. Our results indicate that exploiting jointly structural and functional information of the brain can reveal important information about the complexity of the neuropathology.

Intrinsic, dynamic and effective connectivity among large-scale brain networks modulated by oxytocin

The neuropeptide oxytocin is a key modulator of social-emotional behavior and its intranasal administration can influence the functional connectivity of brain networks involved in the control of attention, emotion and reward reported in humans. However, no studies have systematically investigated the effects of oxytocin on dynamic or directional aspects of functional connectivity. The present study employed a novel computational framework to investigate these latter aspects in 15 oxytocin-sensitive regions using data from randomized placebo-controlled between-subject resting state functional MRI studies incorporating 200 healthy subjects. In order to characterize the temporal dynamics, the ‘temporal state’ was defined as a temporal segment of the whole functional MRI signal which exhibited a similar functional interaction pattern among brain regions of interest. Results showed that while no significant effects of oxytocin were found on brain temporal state related characteristics (including temporal state switching frequency, probability of transitions between neighboring states, and averaged dwell time on each state) oxytocin extensively (n = 54 links) modulated effective connectivity among the 15 regions. The effects of oxytocin were primarily characterized by increased effective connectivity both between and within emotion, reward, salience, attention and social cognition processing networks and their interactions with the default mode network. Top-down control over emotional processing regions such as the amygdala was particularly affected. Oxytocin also increased effective homotopic interhemispheric connectivity in almost all these regions. Additionally, the effects of oxytocin on effective connectivity were sex-dependent, being more extensive in males. Overall, these findings suggest that modulatory effects of oxytocin on both within- and between-network interactions may underlie its functional influence on social-emotional behaviors, although in a sex-dependent manner. These findings may be of particular relevance to potential therapeutic use of oxytocin in psychiatric disorders associated with social dysfunction, such as autism spectrum disorder and schizophrenia, where directionality of treatment effects on causal interactions between networks may be of key importance .

Improved Task-based Functional MRI Language Mapping in Patients with Brain Tumors through Marchenko-Pastur Principal Component Analysis Denoising

Background Functional MRI improves preoperative planning in patients with brain tumors, but task-correlated signal intensity changes are only 2%-3% above baseline. This makes accurate functional mapping challenging. Marchenko-Pastur principal component analysis (MP-PCA) provides a novel strategy to separate functional MRI signal from noise without requiring user input or prior data representation. Purpose To determine whether MP-PCA denoising improves activation magnitude for task-based functional MRI language mapping in patients with brain tumors. Materials and Methods In this Health Insurance Portability and Accountability Act-compliant study, MP-PCA performance was first evaluated by using simulated functional MRI data with a known ground truth. Right-handed, left-language-dominant patients with brain tumors who successfully performed verb generation, sentence completion, and finger tapping functional MRI tasks were retrospectively identified between January 2017 and August 2018. On the group level, for each task, histograms of z scores for original and MP-PCA denoised data were extracted from relevant regions and contralateral homologs were seeded by a neuroradiologist blinded to functional MRI findings. Z scores were compared with paired two-sided t tests, and distributions were compared with effect size measurements and the Kolmogorov-Smirnov test. The number of voxels with a z score greater than 3 was used to measure task sensitivity relative to task duration. Results Twenty-three patients (mean age ± standard deviation, 43 years ± 18; 13 women) were evaluated. MP-PCA denoising led to a higher median z score of task-based functional MRI voxel activation in left hemisphere cortical regions for verb generation (from 3.8 ± 1.0 to 4.5 ± 1.4; P < .001), sentence completion (from 3.7 ± 1.0 to 4.3 ± 1.4; P < .001), and finger tapping (from 6.9 ± 2.4 to 7.9 ± 2.9; P < .001). Median z scores did not improve in contralateral homolog regions for verb generation (from -2.7 ± 0.54 to -2.5 ± 0.40; P = .90), sentence completion (from -2.3 ± 0.21 to -2.4 ± 0.37; P = .39), or finger tapping (from -2.3 ± 1.20 to -2.7 ± 1.40; P = .07). Individual functional MRI task durations could be truncated by at least 40% after MP-PCA without degradation of clinically relevant correlations between functional cortex and functional MRI tasks. Conclusion Denoising with Marchenko-Pastur principal component analysis led to higher task correlations in relevant cortical regions during functional MRI language mapping in patients with brain tumors. © RSNA, 2020 Online supplemental material is available for this article.

Reconstruction of respiratory variation signals from fMRI data

Functional MRI signals can be heavily influenced by systemic physiological processes in addition to local neural activity. For example, widespread hemodynamic fluctuations across the brain have been found to correlate with natural, low-frequency variations in the depth and rate of breathing over time. Acquiring peripheral measures of respiration during fMRI scanning not only allows for modeling such effects in fMRI analysis, but also provides valuable information for interrogating brain-body physiology. However, physiological recordings are frequently unavailable or have insufficient quality. Here, we propose a computational technique for reconstructing continuous low-frequency respiration volume (RV) fluctuations from fMRI data alone. We evaluate the performance of this approach across different fMRI preprocessing strategies. Further, we demonstrate that the predicted RV signals can account for similar patterns of temporal variation in resting-state fMRI data compared to measured RV fluctuations. These findings indicate that fluctuations in respiration volume can be extracted from fMRI alone, in the common scenario of missing or corrupted respiration recordings. The results have implications for enriching a large volume of existing fMRI datasets through retrospective addition of respiratory variations information.

Largest scale dissociation of brain activity at propofol-induced loss of consciousness.

The brain is a functional unit made up of multilevel connected elements showing a pattern of synchronized activity that varies in different states. The wake-sleep cycle is a major variation of brain functional condition that is ultimately regulated by subcortical arousal- and sleep-promoting cell groups. We analyzed the evolution of functional MRI (fMRI) signal in the whole cortex and in a deep region including most sleep- and wake-regulating subcortical nuclei at loss of consciousness induced by the hypnotic agent propofol. Optimal data were obtained in 21 of the 30 healthy participants examined. A dynamic analysis of fMRI time courses on a time-scale of seconds was conducted to characterize consciousness transition, and functional connectivity maps were generated to detail the anatomy of structures showing different dynamics. Inside the magnet, loss of consciousness was marked by the participants ceasing to move their hands. We observed activity synchronization after loss of consciousness within both the cerebral cortex and subcortical structures. However, the evolution of fMRI signal was dissociated, showing a transient reduction of global cortico-subcortical coupling that was restored during the unconscious state. An exception to cortico-subcortical decoupling was a brain network related to self-awareness (i.e. the default mode network) that remained connected to subcortical brain structures. Propofol-induced unconsciousness is thus characterized by an initial, transitory dissociated synchronization at the largest scale of brain activity. Such cortico-subcortical decoupling and subsequent recoupling may allow the brain to detach from waking activity and reorganize into a functionally distinct state.

FMRI hemodynamic response function (HRF) as a novel marker of brain function: applications for understanding obsessive-compulsive disorder pathology and treatment response.

The hemodynamic response function (HRF) represents the transfer function linking neural activity with the functional MRI (fMRI) signal, modeling neurovascular coupling. Since HRF is influenced by non-neural factors, to date it has largely been considered as a confound or has been ignored in many analyses. However, underlying biophysics suggests that the HRF may contain meaningful correlates of neural activity, which might be unavailable through conventional fMRI metrics. Here, we estimated the HRF by performing deconvolution on resting-state fMRI data from a longitudinal sample of 25 healthy controls scanned twice and 44 adults with obsessive-compulsive disorder (OCD) before and after 4-weeks of intensive cognitive-behavioral therapy (CBT). HRF response height, time-to-peak and full-width at half-maximum (FWHM) in OCD were abnormal before treatment and normalized after treatment in regions including the caudate. Pre-treatment HRF predicted treatment outcome (OCD symptom reduction) with 86.4% accuracy, using machine learning. Pre-treatment HRF response height in the caudate head and time-to-peak in the caudate tail were top-predictors of treatment response. Time-to-peak in the caudate tail, a region not typically identified in OCD studies using conventional fMRI activation or connectivity measures, may carry novel importance. Additionally, pre-treatmentresponse height in caudate head predicted post-treatment OCD severity (R = -0.48, P = 0.001), and was associated with treatment-related OCD severity changes (R = -0.44, P = 0.0028), underscoring its relevance. With HRF being a reliable marker sensitive to brain function, OCD pathology, and intervention-related changes, these results could guide future studies towards novel discoveries not possible through conventional fMRI approaches like standard BOLD activation or connectivity.

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.

Transcriptional and imaging-genetic association of cortical interneurons, brain function, and schizophrenia risk

Inhibitory interneurons orchestrate information flow across the cortex and are implicated in psychiatric illness. Although interneuron classes have unique functional properties and spatial distributions, the influence of interneuron subtypes on brain function, cortical specialization, and illness risk remains elusive. Here, we demonstrate stereotyped negative correlation of somatostatin and parvalbumin transcripts within human and non-human primates. Cortical distributions of somatostatin and parvalbumin cell gene markers are strongly coupled to regional differences in functional MRI variability. In the general population (n = 9,713), parvalbumin-linked genes account for an enriched proportion of heritable variance in in-vivo functional MRI signal amplitude. Single-marker and polygenic cell deconvolution establish that this relationship is spatially dependent, following the topography of parvalbumin expression in post-mortem brain tissue. Finally, schizophrenia genetic risk is enriched among interneuron-linked genes and predicts cortical signal amplitude in parvalbumin-biased regions. These data indicate that the molecular-genetic basis of brain function is shaped by interneuron-related transcripts and may capture individual differences in schizophrenia risk.

Temporal lobe epilepsy alters spatio-temporal dynamics of the hippocampal functional network.

Mesial temporal lobe epilepsy (TLE) is characterized by transient abnormal electrical activity originating in the hippocampus. The objective of this study was to characterize dynamic spatio-temporal fluctuations in hippocampal network connectivity in mTLE using functional connectivity (FC) mapping in 41 unilateral mTLE patients (28 right, 13 left) and 56 healthy control participants using 3T MRI. Dynamic FC was computed across the scan using sliding 60-s windows. This was compared to static FC computed using the whole 10-min functional MRI scan, and to the variance in the hippocampal functional MRI signal. Four states of healthy hippocampal dynamic FC were identified and compared to TLE patients. TLE patients fluctuated between these four states, but the hippocampus ipsilateral to the seizure focus spent more time in a state distinguished by lower prefrontal and parietal FC than the dominant healthy state. Increased time spent in this state was associated with increased impairment in static FC and increased variance in the hippocampal functional MRI signal. Overall, this work provides evidence that increases in variance in signal fluctuations occurring at the seizure focus in the hippocampus in patients with mTLE may contribute to disruptions in healthy FC network dynamics within an fMRI scan that contribute to decreases in static hippocampal FC. These alterations result in decreased hippocampal connectivity to bilateral prefrontal and parietal regions in TLE which may be related to behavior and cognitive impairments in these patients. Therefore, characterization of an individual patient's hippocampal dynamics at different time scales may provide more specific spatio-temporal profiles of network impairment that may be related to hippocampal dysfunction in TLE.

Origins of the Resting-State Functional MRI Signal: Potential Limitations of the "Neurocentric" Model.

Resting-state functional connectivity (rsFC) is emerging as a research tool for systems and clinical neuroscience. The mechanism underlying resting-state functional MRI (rsfMRI) signal, however, remains incompletely understood. A widely held assumption is that the spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal reflect ongoing neuronal processes (herein called “neurocentric” model). In support of this model, evidence from human and animal studies collectively reveals that the spatial synchrony of spontaneously occurring electrophysiological signal recapitulates BOLD rsFC networks. Two recent experiments from independent labs designed to specifically examine neuronal origins of rsFC, however, suggest that spontaneously occurring neuronal events, as assessed by multiunit activity or local field potential (LFP), although statistically significant, explain only a small portion (∼10%) of variance in resting-state BOLD fluctuations. These two studies, although each with its own limitations, suggest that the spontaneous fluctuations in rsfMRI, may have complex cellular origins, and the “neurocentric” model may not apply to all brain regions.

Multiscale Dynamics of Spontaneous Brain Activity Is Associated With Walking Speed in Older Adults.

In older adults, compromised white matter tract integrity within the brain has been linked to impairments in mobility. We contend that poorer integrity disrupts mobility by altering the processing of sensorimotor and cognitive and attentional resources in neural networks. The richness of information processing in a given network can be quantified by calculating the complexity of resting-state functional MRI time series. We hypothesized that (i) older adults with lower brain complexity, specifically within sensorimotor, executive, and attention networks, would exhibit slower walking speed and greater dual-task costs (ie, dual-task cost) and (ii) such complexity would mediate the effect of white matter integrity on these metrics of mobility. Fifty-three older adults completed a walking assessment and a neuroimaging protocol. Brain complexity was quantified by calculating the multiscale entropy of the resting-state functional MRI signal within seven previously defined functional networks. The white matter integrity across structures of the corpus callosum was quantified using fractional anisotropy. Participants with lower resting-state complexity within the sensorimotor, executive, and attention networks walked more slowly under single- and dual-task (ie, walking while performing a serial-subtraction task) conditions (β > 0.28, p ≤ .01) and had a greater dual-task cost (β < -0.28, p < .04). Complexity in these networks mediated the influence of the corpus callosum genu on both single- (indirect effects > 0.15, 95% confidence intervals = 0.02-0.32) and dual-task walking speeds (indirect effects > 0.13, 95% confidence intervals = 0.02-0.33). These results suggest that the multiscale dynamics of resting-state brain activity correlate with mobility and mediate the effect of the microstructural integrity in the corpus callosum genu on walking speed in older adults.

Impaired interactions among white-matter functional networks in antipsychotic-naive first-episode schizophrenia.

Schizophrenia has been conceptualized as a disorder arising from structurally pathological alterations to white‐matter fibers in the brain. However, few studies have focused on white‐matter functional changes in schizophrenia. Considering that converging evidence suggests that white‐matter resting state functional MRI (rsfMRI) signals can effectively depict neuronal activity and psychopathological status, this study examined white‐matter network‐level interactions in antipsychotic‐naive first‐episode schizophrenia (FES) to facilitate the interpretation of the psychiatric pathological mechanisms in schizophrenia. We recruited 42 FES patients (FESs) and 38 healthy controls (HCs), all of whom underwent rsfMRI. We identified 11 white‐matter functional networks, which could be further classified into deep, middle, and superficial layers of networks. We then examined network‐level interactions among these 11 white‐matter functional networks using coefficient Granger causality analysis. We employed group comparisons on the influences among 11 networks using network‐based statistic. Excitatory influences from the middle superior corona radiate network to the superficial orbitofrontal and deep networks were disrupted in FESs compared with HCs. Additionally, an extra failure of suppression within superficial networks (including the frontoparietal network, temporofrontal network, and the orbitofrontal network) was observed in FESs. We additionally recruited an independent cohort (13 FESs and 13 HCs) from another center to examine the replicability of our findings across centers. Similar replication results further verified the white‐matter functional network interaction model of schizophrenia. The novel findings of impaired interactions among white‐matter functional networks in schizophrenia indicate that the pathophysiology of schizophrenia may also lie in white‐matter functional abnormalities.

Brain activity during traditional textbook and audiovisual-3D learning.

IntroductionAudiovisual educational tools have increasingly been used during the past years to complement and compete with traditional textbooks. However, little is known as to how the brain processes didactic information presented in different formats. We directly assessed brain activity during learning using both traditional textbook and audiovisual‐3D material.MethodsA homogeneous sample of 30 young adults with active study habits was assessed. Educational material on the subject of Cardiology was adapted to be presented during the acquisition of functional MRI.ResultsWhen tested after image acquisition, participants obtained similar examination scores for both formats. Evoked brain activity was robust during both traditional textbook and audiovisual‐3D lessons, but a greater number of brain systems were implicated in the processing of audiovisual‐3D information, consistent with its multisource sensory nature. However, learning was not associated with group mean brain activations, but was instead predicted by distinct functional MRI signal changes in the frontal lobes and showed distinct cognitive correlates. In the audiovisual‐3D version, examination scores were positively correlated with late‐evoked prefrontal cortex activity and working memory, and negatively correlated with language‐related frontal areas and verbal memory. As for the traditional textbook version, the fewer results obtained suggested the opposite pattern, with examination scores negatively correlating with prefrontal cortex activity evoked during the lesson.ConclusionsOverall, the results indicate that a similar level of knowledge may be achieved via different cognitive strategies. In our experiment, audiovisual learning appeared to benefit from prefrontal executive resources (as opposed to memorizing verbal information) more than traditional textbook learning.

Environmental Barriers Disrupt Grid-like Representations in Humans during Navigation

Environmental barriers fundamentally shape our behavior and conceptualization of space [1-5]. Evidence from rodents suggests that, in contrast to an open-field environment, where grid cells exhibit firing patterns with a 6-fold rotational symmetry [5, 6], barriers within the field abolish the 6-fold symmetry and fragment the grid firing fields into compartmentalized repeating "submaps" [5]. These results suggest that barriers may exert their influence on the cognitive map through organization of the metric representation of space provided by entorhinal neurons. We directly tested this hypothesis in humans, combining functional MRI with a virtual navigation paradigm in which we manipulated the local barrier structure. When participants performed a fixed-route foraging task in an open field, the functional MRI signal in rightentorhinal cortex exhibited a 6-fold periodic modulation by movement direction associated with conjunctive grid cell firing [7]. However, when environments were compartmentalized by barriers, the grid-like 6-fold spatial metric was abolished. Instead, a 4-fold modulation of the entorhinal signal was observed, consistent with a vectorized organization of spatial metrics predicted by rodent models of navigation [5]. Collectively, these results provide mechanistic insight into why barriers compartmentalize our cognitive map, indicating that boundaries exert a powerful influence on the way environments are represented in human entorhinal cortex. Given that our daily environments are rarely wide open and are often segmented by barriers (e.g., the buildings of our home city), our findings have implications for applying models of cognitive mapping based on grid-like metrics [8] to naturalistic circumstances.

Functional MRI and resting state connectivity in white matter - a mini-review

Functional MRI (fMRI) signals are robustly detectable in white matter (WM) but they have been largely ignored in the fMRI literature. Their nature, interpretation, and relevance as potential indicators of brain function remain under explored and even controversial. Blood oxygenation level dependent (BOLD) contrast has for over 25 years been exploited for detecting localized neural activity in the cortex using fMRI. While BOLD signals have been reliably detected in grey matter (GM) in a very large number of studies, such signals have rarely been reported from WM. However, it is clear from our own and other studies that although BOLD effects are weaker in WM, using appropriate detection and analysis methods they are robustly detectable both in response to stimuli and in a resting state. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both GM and WM, and their relative low frequency (0.01–0.1 Hz) signal powers are comparable. They also vary with baseline neural activity e.g. as induced by different levels of anesthesia, and alter in response to a stimulus. In previous work we reported that BOLD signals in WM in a resting state exhibit anisotropic temporal correlations with neighboring voxels. On the basis of these findings, we derived functional correlation tensors that quantify the correlational anisotropy in WM BOLD signals. We found that, along many WM tracts, the directional preferences of these functional correlation tensors in a resting state are grossly consistent with those revealed by diffusion tensors, and that external stimuli tend to enhance visualization of specific and relevant fiber pathways. These findings support the proposition that variations in WM BOLD signals represent tract-specific responses to neural activity. We have more recently shown that sensory stimulations induce explicit BOLD responses along parts of the projection fiber pathways, and that task-related BOLD changes in WM occur synchronously with the temporal pattern of stimuli. WM tracts also show a transient signal response following short stimuli analogous to but different from the hemodynamic response function (HRF) characteristic of GM. Thus there is converging and compelling evidence that WM exhibits both resting state fluctuations and stimulus-evoked BOLD signals very similar (albeit weaker) to those in GM. A number of studies from other laboratories have also reported reliable observations of WM activations. Detection of BOLD signals in WM has been enhanced by using specialized tasks or modified data analysis methods. In this mini-review we report summaries of some of our recent studies that provide evidence that BOLD signals in WM are related to brain functional activity and deserve greater attention by the neuroimaging community.

Reduced Network Dynamics on Functional MRI Signals Cognitive Impairment in Multiple Sclerosis.

Background Previous studies have demonstrated extensive functional network disturbances in patients with multiple sclerosis (MS), showing a less efficient brain network. Recent studies indicate that the dynamic properties of the brain network show a strong correlation with cognitive function. Purpose To investigate network dynamics on functional MRI in cognitively impaired patients with MS. Materials and Methods In secondary analysis of prospectively acquired data, with imaging performed between 2008 and 2012, differences in regional functional network dynamics (ie, eigenvector centrality dynamics) between cognitively impaired and cognitively preserved participants with MS were investigated. Functional network dynamics were computed on images from functional MRI (3 T) by using a sliding-window approach. Cognitively impaired and preserved groups were compared by using a clusterwise permutation-based method. Results The study included 96 healthy control subjects and 332 participants with MS (including 226 women and 106 men; median age, 48.1 years ± 11.0). Among the 332 participants with MS, 87 were cognitively impaired and 180 had preserved cognitive function; mildly impaired patients (n = 65) were excluded. The cognitively impaired group included a higher proportion of men compared with the cognitively preserved group (35 of 87 [40%] vs 48 of 180 [27%], respectively; P = .02) and had a higher mean age (51.1 years vs 46.3 years, respectively; P < .01). The clusterwise permutation-based comparison at P less than .05 showed reduced centrality dynamics in default-mode, frontoparietal, and visual network regions on functional MRI in cognitively impaired participants versus cognitively preserved participants. A subsequent correlation and hierarchical clustering analysis revealed that the default-mode and visual networks normally demonstrate negatively correlated fluctuations in functional importance (r = -0.23 in healthy control subjects), with an almost complete loss of this negative correlation in cognitively impaired participants compared with cognitively preserved participants (r = -0.04 vs r = -0.14; corrected P = .02). Conclusion As shown on functional MRI, cognitively impaired patients with multiple sclerosis not only demonstrate reduced dynamics in default-mode, frontoparietal, and visual networks, but also show a loss of interplay between default-mode and visual networks. © RSNA, 2019 Online supplemental material is available for this article. See also the article by Eijlers et al and the editorial by Zivadinov and Dwyer in this issue.