Atlasing white matter and grey matter joint contributions to resting-state networks in the human brain

Over the past two decades, the study of resting-state functional magnetic resonance imaging (fMRI) has revealed the existence of multiple brain areas displaying synchronous functional blood oxygen level-dependent signals (BOLD) - resting-state networks (RSNs). The variation in functional connectivity between the different areas of a resting-state network or between multiple networks, have been extensively studied and linked to cognitive states and pathologies. However, the white matter connections supporting each network remain only partially described. In this work, we developed a data-driven method to systematically map the white and grey matter contributing to resting-state networks. Using the Human Connectome Project, we generated an atlas of 30 resting-state networks, each with two maps: white matter and grey matter. By integrating structural and functional neuroimaging data, this method builds an atlas that unlocks the joint anatomical exploration of white and grey matter to resting-state networks. The method also allows highlighting the overlap between networks, which revealed that most (89%) of the brain's white matter is shared amongst multiple networks, with 16% shared by at least 7 resting-state networks. These overlaps, especially the existence of regions shared by numerous networks, suggest that white matter lesions in these areas might strongly impact the correlations and the communication within resting-state networks. We provide an open-source software to explore the joint contribution of white and grey matter to RSNs and facilitate the study of the impact of white matter damage on RSNs.

Improved Activation and Hemodynamic Response Function of Olfactory fMRI Using Simultaneous Multislice with Reduced TR Acquisition

Objectives. The respiration could decrease the time synchronization between odor stimulation and data acquisition, consequently deteriorating the functional activation and hemodynamic response function (HRF) in olfactory functional magnetic resonance imaging (fMRI) with a conventional repetition time (TR). In this study, we aimed to investigate whether simultaneous multislice (SMS) technology with reduced TR could improve the blood oxygen level-dependent (BOLD) activation and optimize HRF modeling in olfactory fMRI. Methods. Sixteen young healthy subjects with normal olfaction underwent olfactory fMRI on a 3T MRI scanner using a 64 channel head coil. FMRI data were acquired using SMS acceleration at three different TRs: 3000 ms, 1000 ms, and 500 ms. Both metrics of BOLD activation (activated voxels, mean, and maximum t -scores) and the HRF modeling (response height and time to peak) were calculated in the bilateral amygdalae, hippocampi, and insulae. Results. The 500 ms and 1000 ms TRs both significantly improved the number of activated voxels, mean, and maximum t -score in the amygdalae and insulae, compared with a 3000 ms TR (all P < 0.05 ). But the increase of these metrics in the hippocampi did not reach a statistical significance (all P > 0.05 ). No significant difference in any BOLD activation metrics between TR 500 ms and 1000 ms was observed in all regions of interest (ROIs) (all P > 0.05 ). The HRF curves showed that higher response height and shorter time to peak in all ROIs were obtained at 500 ms and 1000 ms TRs compared to 3000 ms TR. TR 500 ms had a more significant effect on response height than TR 1000 ms in the amygdalae ( P = 0.017 ), and there was no significant difference in time to peak between TR 500 ms and 1000 ms in all ROIs (all P > 0.05 ). Conclusions. The fast image acquisition technique of SMS with reduced TR could significantly improve the functional activation and HRF curve in olfactory fMRI.

The influence of non-neural factors on BOLD signal magnitude

To what extent is the size of the blood-oxygen-level-dependent (BOLD) response influenced by factors other than neural activity? In a re-analysis of three neuroimaging datasets, we find large systematic inhomogeneities in the BOLD response magnitude in primary visual cortex (V1): stimulus-evoked BOLD responses, expressed in units of percent signal change, are up to 50% larger along the representation of the horizontal meridian than the vertical meridian. To assess whether this surprising effect can be interpreted as differences in local neural activity, we quantified several factors that potentially contribute to the size of the BOLD response. We find strong relationships between BOLD response magnitude and cortical thickness, cortical curvature, and the presence of large veins. These relationships are consistently found across subjects and suggest that variation in BOLD response magnitudes across cortical locations reflects, in part, differences in anatomy and vascularization. To compensate for these factors, we implement a regression-based correction method and show that after correction, BOLD responses become more homogeneous across V1. The correction reduces the horizontal/vertical difference by about half, indicating that some of the difference is likely not due to neural activity differences. Additionally, we find that while the cerebral sinuses overlap with the vertical meridian representation in V1, they do not explain the observed horizontal/vertical difference. We conclude that interpretation of variation in BOLD response magnitude across cortical locations should consider the influence of the potential confounding factors of cortical thickness, curvature, and vascularization.

Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Neurotoxin Therapy for Treatment of Focal Spasticity

Background: Botulinum NeuroToxin-A (BoNT-A) relieves muscle spasticity and increases range of motion necessary for stroke rehabilitation. Determining the effects of BoNT-A therapy on brain neuroplasticity could help physicians customize its use and predict its outcome.Objective: The purpose of this study was to investigate the effects of Botulinum Toxin-A therapy for treatment of focal spasticity on brain activation and functional connectivity.Design: We used functional Magnetic Resonance Imaging (fMRI) to track changes in blood oxygen-level dependent (BOLD) activation and functional connectivity associated with BoNT-A therapy in nine chronic stroke participants, and eight age-matched controls. Scans were acquired before BoNT-A injections (W0) and 6 weeks after the injections (W6). The task fMRI scan consisted of a block design of alternating mass finger flexion and extension. The voxel-level changes in BOLD activation, and pairwise changes in functional connectivity were analyzed for BoNT-A treatment (stroke W0 vs. W6).Results: BoNT-A injection therapy resulted in significant increases in brain activation in the contralesional premotor cortex, cingulate gyrus, thalamus, superior cerebellum, and in the ipsilesional sensory integration area. Lastly, cerebellar connectivity correlated with the Fugl-Meyer assessment of motor impairment before injection, while premotor connectivity correlated with the Fugl-Meyer score after injection.Conclusion: BoNT-A therapy for treatment of focal spasticity resulted in increased brain activation in areas associated with motor control, and cerebellar connectivity correlated with motor impairment before injection. These results suggest that neuroplastic effects might take place in response to improvements in focal spasticity.

High-resolution relaxometry-based calibrated fMRI in murine brain: Metabolic differences between awake and anesthetized states

Functional magnetic resonance imaging (fMRI) techniques using the blood-oxygen level-dependent (BOLD) signal have shown great potential as clinical biomarkers of disease. Thus, using these techniques in preclinical rodent models is an urgent need. Calibrated fMRI is a promising technique that can provide high-resolution mapping of cerebral oxygen metabolism (CMRO2). However, calibrated fMRI is difficult to use in rodent models for several reasons: rodents are anesthetized, stimulation-induced changes are small, and gas challenges induce noisy CMRO2 predictions. We used, in mice, a relaxometry-based calibrated fMRI method which uses cerebral blood flow (CBF) and the BOLD-sensitive magnetic relaxation component, R2′, the same parameter derived in the deoxyhemoglobin-dilution model of calibrated fMRI. This method does not use any gas challenges, which we tested on mice in both awake and anesthetized states. As anesthesia induces a whole-brain change, our protocol allowed us to overcome the former limitations of rodent studies using calibrated fMRI. We revealed 1.5-2 times higher CMRO2, dependent upon brain region, in the awake state versus the anesthetized state. Our results agree with alternative measurements of whole-brain CMRO2 in the same mice and previous human anesthesia studies. The use of calibrated fMRI in rodents has much potential for preclinical fMRI.

Prior Methamphetamine Use Disorder History Does Not Impair Interoceptive Processing of Soft Touch in HIV Infection

Introduction: Interoception, defined as the sense of the internal state of one’s body, helps motivate goal-directed behavior. Prior work has shown that methamphetamine (METH) use disorder is associated with altered interoception, and that this may contribute to risky behavior. As people with HIV (PWH) may also experience disrupted bodily sensations (e.g., neuropathy), an important question is whether PWH with a history of METH use disorder might exhibit greater impairment of interoceptive processing. Methods: Eighty-three participants stratified by HIV infection and a past history of methamphetamine use disorder experienced a soft touch paradigm that included slow brush strokes on the left forearm and palm during blood-oxygen level-dependent functional MRI acquisition. To assess differences in interoception and reward, voxelwise analyses were constrained to the insula, a hub for the evaluation of interoceptive cues, and the striatum, which is engaged in reward processing. Results: Overall, individuals with a history of METH use disorder had an attenuated neural response to pleasant touch in both the insula and striatum. Longer abstinence was associated with greater neural response to touch in the insula, suggesting some improvement in responsivity. However, only PWH with no METH use disorder history had lower brain activation in the insula relative to non-using seronegative controls. Conclusions: Our findings suggest that while METH use disorder history and HIV infection independently disrupt the neural processes associated with interoception, PWH with METH use disorder histories do not show significant differences relative to non-using seronegative controls. These findings suggest that the effects of HIV infection and past methamphetamine use might not be additive with respect to interoceptive processing impairment.

Resting-state functional MRI signal fluctuation amplitudes are correlated with brain amyloid-β deposition in patients with mild cognitive impairment

Mounting evidence suggests that amyloid-β (Aβ) and vascular etiologies are intertwined in the pathogenesis of Alzheimer’s disease (AD). Blood-oxygen-level-dependent (BOLD) signals, measured by resting-state functional MRI (rs-fMRI), are associated with neuronal activity and cerebrovascular hemodynamics. Nevertheless, it is unclear if BOLD fluctuations are associated with Aβ deposition in individuals at high risk of AD. Thirty-three patients with amnestic mild cognitive impairment underwent rs-fMRI and AV45 PET. The AV45 standardized uptake value ratio (AV45-SUVR) was calculated using cerebral white matter as reference, to assess Aβ deposition. The whole-brain normalized amplitudes of low-frequency fluctuations (sALFF) of local BOLD signals were calculated in the frequency band of 0.01–0.08 Hz. Stepwise increasing physiological/vascular signal regressions on the rs-fMRI data examined whether sALFF-AV45 correlations were driven by vascular hemodynamics, neuronal activities, or both. We found that sALFF and AV45-SUVR were negatively correlated in regions of default-mode and visual networks (precuneus, angular, lingual and fusiform gyri). Regions with higher sALFF had less Aβ accumulation. Correlated cluster sizes in MNI space ( r ≈ −0.47) were reduced from 3018 mm3 to 1072 mm3 with stronger cardiovascular regression. These preliminary findings imply that local brain blood fluctuations due to vascular hemodynamics or neuronal activity can affect Aβ homeostasis.

Aesthetic appraisals of literary style and emotional intensity in narrative engagement are neurally dissociable

Humans are deeply affected by stories, yet it is unclear how. In this study, we explored two aspects of aesthetic experiences during narrative engagement - literariness and narrative fluctuations in appraised emotional intensity. Independent ratings of literariness and emotional intensity of two literary stories were used to predict blood-oxygen-level-dependent signal changes in 52 listeners from an existing fMRI dataset. Literariness was associated with increased activation in brain areas linked to semantic integration (left angular gyrus, supramarginal gyrus, and precuneus), and decreased activation in bilateral middle temporal cortices, associated with semantic representations and word memory. Emotional intensity correlated with decreased activation in a bilateral frontoparietal network that is often associated with controlled attention. Our results confirm a neural dissociation in processing literary form and emotional content in stories and generate new questions about the function of and interaction between attention, social cognition, and semantic systems during literary engagement and aesthetic experiences.

Decreased Resting-State Functional Complexity in Elderly with Subjective Cognitive Decline

Individuals with subjective cognitive decline (SCD) are at high risk of developing preclinical or clinical state of Alzheimer’s disease (AD). Resting state functional magnetic resonance imaging, which can indirectly reflect neuron activities by measuring the blood-oxygen-level-dependent (BOLD) signals, is promising in the early detection of SCD. This study aimed to explore whether the nonlinear complexity of BOLD signals can describe the subtle differences between SCD and normal aging, and uncover the underlying neuropsychological implications of these differences. In particular, we introduce amplitude-aware permutation entropy (AAPE) as the novel measure of brain entropy to characterize the complexity in BOLD signals in each brain region of the Brainnetome atlas. Our results demonstrate that AAPE can reflect the subtle differences between both groups, and the SCD group presented significantly decreased complexities in subregions of the superior temporal gyrus, the inferior parietal lobule, the postcentral gyrus, and the insular gyrus. Moreover, the results further reveal that lower complexity in SCD may correspond to poorer cognitive performance or even subtle cognitive impairment. Our findings demonstrated the effectiveness and sensitiveness of the novel brain entropy measured by AAPE, which may serve as the potential neuroimaging marker for exploring the subtle changes in SCD.