Blood Oxygen Level-dependent Signal Research Articles

Explainable Multimodal Graph Isomorphism Network for Interpreting Sex Differences in Adolescent Neurodevelopment

Background: A fundamental grasp of the variability observed in healthy individuals holds paramount importance in the investigation of neuropsychiatric conditions characterized by sex-related phenotypic distinctions. Functional magnetic resonance imaging (fMRI) serves as a meaningful tool for discerning these differences. Among deep learning models, graph neural networks (GNNs) are particularly well-suited for analyzing brain networks derived from fMRI blood oxygen level-dependent (BOLD) signals, enabling the effective exploration of sex differences during adolescence. Method: In the present study, we introduce a multi-modal graph isomorphism network (MGIN) designed to elucidate sex-based disparities using fMRI task-related data. Our approach amalgamates brain networks obtained from multiple scans of the same individual, thereby enhancing predictive capabilities and feature identification. The MGIN model adeptly pinpoints crucial subnetworks both within and between multi-task fMRI datasets. Moreover, it offers interpretability through the utilization of GNNExplainer, which identifies pivotal sub-network graph structures contributing significantly to sex group classification. Results: Our findings indicate that the MGIN model outperforms competing models in terms of classification accuracy, underscoring the benefits of combining two fMRI paradigms. Additionally, our model discerns the most significant sex-related functional networks, encompassing the default mode network (DMN), visual (VIS) network, cognitive (CNG) network, frontal (FRNT) network, salience (SAL) network, subcortical (SUB) network, and sensorimotor (SM) network associated with hand and mouth movements. Remarkably, the MGIN model achieves superior sex classification accuracy when juxtaposed with other state-of-the-art algorithms, yielding a noteworthy 81.67% improvement in classification accuracy. Conclusion: Our model’s superiority emanates from its capacity to consolidate data from multiple scans of subjects within a proven interpretable framework. Beyond its classification prowess, our model guides our comprehension of neurodevelopment during adolescence by identifying critical subnetworks of functional connectivity.

Neuroplasticity of visual brain network induced by hypoxia.

The effects of hypoxia on brain function remain largely unknown. This study aimed to clarify this issue by visual-stimulated functional magnetic resonance imaging design. Twenty-three college students with a 30-d high-altitude exposure were tested before, 1week and 3months after returning to sea level. Brain functional magnetic resonance imaging and retinal electroretinogram were acquired. One week after returning to sea level, decreased blood oxygenation level dependent in the right lingual gyrus accompanied with increased blood oxygenation level dependent in the frontal cortex and insular cortex, and decreased amplitude of electroretinogram a-wave in right eye; moreover, the bilateral lingual gyri showed increased functional connectivity within the dorsal visual stream pathway, and the blood oxygenation level dependent signals in the right lingual gyrus showed positive correlation with right retinal electroretinogram a-wave. Three months after returning to sea level, the blood oxygenation level dependent signals recovered to normal level, while intensively increased blood oxygenation level dependent signals in a broad of brain regions and decreased retinal electroretinogram were also existed. In conclusion, hypoxic exposure has long-term effects on visual cortex, and the impaired retinal electroretinogram may contribute to it. The increased functional connectivity of dorsal stream may compensate for the decreased function of retinal photoreceptor cells to maintain normal visual function.

Denoising of the gradient artifact present in simultaneous studies of muscle blood oxygen level dependent (BOLD) signal and electromyography (EMG)

The MR-induced gradient artifact affects EMG recordings during simultaneous muscle BOLD/EMG acquisitions. However, no dedicated hardware can remove the gradient artifact easily, and alternative methods are expensive and time-consuming. This study aimed to develop three denoising methods requiring different processing levels and MR-compatible hardware.At two time points, surface EMG was recorded from the lower leg of 6 participants (50:50 sex ratio, age = 26.24.6 yrs., height = 173.59.2 cm, weight = 71.511.4 kg) using a plantar flexion-based block design consisting of 30s of rest followed by 30s of flexion for 5 min, under three conditions: inside the MRI bore, with and without a BOLD sequence (3 T, BOLD sequence, GRE EPI, 10 slices, 6464 matrix, 2 mm thickness, and TE/TR/flip = 35/3000 ms/70), and outside the MRI environment. Simultaneous BOLD/EMG recordings were denoised using average artifact subtraction with three methods of artifact template creation, each having varying timing and hardware requirements. Method M1 builds the artifact template by recording the scanner triggers coming from the MRI; M2 creates the artifact template with a constant artifact period computed as TR/[number of slices]; M3 estimates the artifact template by looking at the periodicity of the gradient artifact located in the EMG recordings. Following postprocessing, SNR analysis was performed, comparing rest-to-flexion periods, to assess the efficacy of denoising methods and to compare differences between conditions.Linear mixed-effects models showed no significant differences in the mean SNR between denoising methods (p = 0.656). Furthermore, EMG SNR measurements were significantly affected by the magnetic environment (p < 0.05) but not by muscle fatigue over time (p = 0.975).EMG recordings contaminated with gradient artifacts during simultaneous BOLD/EMG can be efficiently denoised using all proposed methods, with two methods requiring no extra hardware. With minimal post-processing, EMG can easily be performed during muscle BOLD MRI studies.

P157 Neurocognitive insights: functional magnetic resonance imaging of spatial working memory and sustained attention in people with systemic lupus erythematous

Abstract Background/Aims Cognitive impairment (CI) is common in people with systemic lupus erythematosus (pwSLE). Treatment options are limited and the effects upon the brain is unclear. Differences in brain structure seen in SLE do not always associate with CI, however significant associations have been found with functional magnetic resonance imaging (fMRI). Using fMRI, this study aims to further explore potential compensatory brain mechanisms used in SLE that help with cognitive function. Methods Participants were recruited into one of two groups;pwSLE (meeting EULAR/ACR criteria) or healthy controls(HC). Demographic, clinical and psychiatric data and patient reported outcome measures were collected.Cognitive function was assessed using the ACR Neuropsychological Battery. Brain scans included two structural and two fMRI scans done during stage 1 and 2 of a cognitive task. Stage 1 of the task had an encoding, retention and working memory (WM) component. Stage 2 of the task examined long-term memory. Differences between task performances were examined using t-tests. The fMRI data was modelled using SPM12 to look for differences in blood-oxygen-level-dependent (BOLD) brain responses between the study groups during the different stages/components of the task. Results To-date 37 pwSLE and 10 HCs have been recruited. The median ages were 36 (HC) and 40 (pwSLE) years. From the pwSLE group the average disease duration was 15 years, the average SLEDAI-2K score was 5 and percentages of those on antimalarials, corticosteroids, and immunosuppressants and biologics were 66%, 32%, and 54%, respectively. There were no differences on task performance between the two groups. Greater BOLD responses were seen in the HC compared to the pwSLE group during stage 1 encoding and WM phases as well as during stage 2 (long-term memory). pwSLE had less attenuated BOLD signals during the stage 1 retention phase compared to HCs (Table 1). Conclusion We found altered brain responses to our cognitive task between pwSLE and HCs. Predominantly the HC group had greater BOLD responses in cognitive regions during the task compared to the pwSLE group. However, we did not find any difference between the two groups in regards to cognitive performance. This study is still ongoing and additional results are expected. Disclosure M. Barraclough: None. M. McCowen: None. S. McKie: None. A. Kafkas: None. B. Parker: None. J. Diaz-Martinez: None. A. Knight: None. K. Bingham: None. M. Li: None. J. Su: None. M. Kakvan: None. C. Munoz Grajales: None. M. Tartaglia: None. L. Ruttan: None. J. Wither: None. D. Bonilla: None. N. Anderson: None. D. Montaldi: None. R. Elliott: None. P. Katz: None. D. Beaton: None. R. Green: None. I. Bruce: None. Z. Touma: None.

Exercise-induced calf muscle hyperemia quantified with dynamic blood oxygen level-dependent (BOLD) imaging

Muscle hyperemia in exercise is usually the combined result of increased cardiac output and local muscle vasodilation, with the latter reflecting muscle's capacity for increased blood perfusion to support exercise. In this study, we aim to quantify muscle's vasodilation capability with dynamic BOLD imaging. A deoxyhemoglobin-kinetics model is proposed to analyze dynamic BOLD signals acquired during exercise recovery, deriving a hyperemia index (HI) for a muscle group of interest. We demonstrated the method's validity with calf muscles of healthy subjects who performed plantar flexion for muscle stimulation. In a test with exercise load incrementally increasing from 0 to 16 lbs., gastrocnemius HI showed considerable variance among the 4 subjects, but with a consistent trend, i.e. low at light load (e.g. 0–6 lbs) and linearly increasing at heavy load. The high variability among different subjects was confirmed with the other 10 subjects who exercised with a same moderate load of 8 lbs., with coefficient of variance among subjects' medial gastrocnemius 87.8%, lateral gastrocnemius 111.8% and soleus 132.3%. These findings align with the fact that intensive exercise induces high muscle hyperemia, but a comparison among different subjects is hard to make, presumably due to the subjects' different rate of oxygen utilization. For the same 10 subjects who exercised with load of 8 lbs., we also performed dynamic contrast enhanced (DCE) MRI to measure muscle perfusion (F). With a moderate correlation of 0.654, HI and F displayed three distinctive responses of calf muscles: soleus of all the subjects were in the cluster of low F and low HI, and gastrocnemius of most subjects had high F and either low or high HI. This finding suggests that parameter F encapsulates blood flow through vessels of all sizes, but BOLD-derived HI focuses on capillary flow and therefore is a more specific indicator of muscle vasodilation. In conclusion, the proposed hyperemia index has the potential of quantitatively assessing muscle vasodilation induced with exercise.

Dynamic Functional Hyperconnectivity After Psilocybin Intake Is Primarily Associated With Oceanic Boundlessness

BackgroundPsilocybin is a widely studied psychedelic substance that leads to the psychedelic state, a specific altered state of consciousness. To date, the relationship between the psychedelic state’s neurobiological and experiential patterns remains undercharacterized because they are often analyzed separately. We investigated the relationship between neurobiological and experiential patterns after psilocybin by focusing on the link between dynamic cerebral connectivity and retrospective questionnaire assessment. MethodsHealthy participants were randomized to receive either psilocybin (n = 22) or placebo (n = 27) and scanned for 6 minutes in an eyes-open resting state during the peak subjective drug effect (102 minutes posttreatment) in ultrahigh field 7T magnetic resonance imaging. The 5-Dimensional Altered States of Consciousness Rating Scale was administered 360 minutes after drug intake. ResultsUnder psilocybin, there were alterations across all dimensions of the 5-Dimensional Altered States of Consciousness Rating Scale and widespread increases in averaged brain functional connectivity. Time-varying functional connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low blood oxygen level–dependent signal amplitude, suggesting heightened cortical arousal. In terms of neuroexperiential links, canonical correlation analysis showed higher transition probabilities to the hyperconnected pattern with feelings of oceanic boundlessness and secondly with visionary restructuralization. ConclusionsPsilocybin generates profound alterations at both the brain and the experiential levels. We suggest that the brain’s tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. These findings illuminate the intricate interplay between brain dynamics and subjective experience under psilocybin, thereby providing insights into the neurophysiology and neuroexperiential qualities of the psychedelic state.

Effect of blood oxygen-level-dependent signal data trimming on functional connectivity metrics

In the big data era, with a lack of comparable functional neuroimaging data, researchers try to combine heterogeneous data of different lengths, trimming those to the same number of timepoints (NTPs). However, the effects of trimming blood-oxygen-level dependent (BOLD) signal data on functional connectivity (FC) are still poorly understood.Resting-state functional magnetic resonance imaging data from thirty healthy subjects were pre-processed for five different NTPs, from which FC matrices were computed. These BOLD signal correlation matrices were binarized for several thresholds, excluding weak correlations. Graph metrics were computed to study FC differences between different NTPs. The study included node degree analysis for each brain region and assessment of small-worldness coefficients (σ and ω), whereas in small-world networks, characteristic values are σ > 1 and ω≈ 0, indicating a balance between high clustering coefficients and short characteristic path lengths.A tendency of decreasing global network degrees for higher NTPs was observed, translating the loss of stronger correlations with longer BOLD signals. Trimming such data affects brain regions differently, probably due to brain network dynamics. Regarding small-worldness, we observed that σ was greater than 1 for all the different NTPs, showing an increasing trend for higher NTPs (median value: σBRAIN= 3.05). In addition, ω consistently remained greater than 0 for all NTPs, gradually approaching 0 as the NTPs increased (median value ωBRAIN= 0.20). As such, the results suggest a tendency for an increase of small-world properties for increasing NTPs. Nonetheless, the overall properties of brain networks almost remain constant. In conclusion, trimming BOLD signal data leads to small differences in FC.

Stochastic brain dynamics exhibits differential regional distribution and maturation-related changes

Functional magnetic resonance imaging (fMRI) is a powerful non-invasive method for studying brain function by analyzing blood oxygenation level-dependent (BOLD) signals. These signals arise from intricate interplays of deterministic and stochastic biological elements. Quantifying the stochastic part is challenging due to its reliance on assumptions about the deterministic segment. We present a methodological framework to estimate intrinsic stochastic brain dynamics in fMRI data without assuming deterministic dynamics. Our approach utilizes Approximate Entropy and its behavior in noisy series to identify and characterize dynamical noise in unobservable fMRI dynamics. Applied to extensive fMRI datasets (645 Cam-CAN, 1086 Human Connectome Project subjects), we explore lifelong maturation of intrinsic brain noise. Findings indicate 10% to 60% of fMRI signal power is due to intrinsic stochastic brain elements, varying by age. These components demonstrate a physiological role of neural noise which shows a distinct distributions across brain regions and increase linearly during maturation.

Insomnia disorder characterized by probabilistic metastable substates using blood-oxygenation-level-dependent (BOLD) phase signals.

From a clinical point of view, how to force a transition from insomnia brain state to healthy brain state by external driven stimulation is of great interest. This needs to define brain state of insomnia disorder as metastable substates. The current study was to identify recurrent substates of insomnia disorder in terms of probability of occurrence, lifetime, and alternation profiles by using leading eigenvector dynamics analysis (LEiDA) method. We enrolled 32 patients with insomnia disorder and 30 healthy subjects. We firstly obtained the BOLD phase coherence matrix from Hilbert transform of BOLD signals and then extracted all the leading eigenvectors from the BOLD phase coherence matrix for all subjects across all time points. Lastly, we clustered the leading eigenvectors using a k-means clustering algorithm to find the probabilistic metastable substates (PMS) and calculate the probability of occurrence and associated lifetime for substates. The resulting 3 clusters were optimal for brain state of insomnia disorder and healthy brain state, respectively. The occurred probabilities of the PMS were significantly different between the patients with insomnia disorder and healthy subjects, with 0.51 versus 0.44 for PMS-1 (p < 0.001), 0.25 versus 0.27 for PMS-2 (p = 0.051), and 0.24 versus 0.29 for PMS-3 (p < 0.001), as well as the lifetime (in TR) of 36.65 versus 33.15 for PMS-1 (p = 0.068), 14.36 versus 15.43 for PMS-2 (p = 0.117), and 14.80 versus 16.34 for PMS-3 (p = 0.042). The values of the diagonal of the transition matrix were much higher than the probabilities of switching states, indicating the metastable nature of substates. The resulted probabilistic metastable substates hint the characteristic brain dynamics of insomnia disorder. The results may lay a foundation to help determine how to force a transition from insomnia brain state to healthy brain state by external driven stimulation.

Aberrant thalamocortical connectivity and shifts between the resting state and task state in patients with schizophrenia.

Prominent pathological hypotheses for schizophrenia include auditory processing deficits and dysconnectivity within cerebral networks. However, most neuroimaging studies have focused on impairments in either resting-state or task-related functional connectivity in patients with schizophrenia. The aims of our study were to examine (1) blood oxygen level-dependent (BOLD) signals during auditory steady-state response (ASSR) tasks, (2) functional connectivity during the resting-state and ASSR tasks and (3) state shifts between the resting-state and ASSR tasks in patients with schizophrenia. To reduce the functional consequences of scanner noise, we employed resting-state and sparse sampling auditory fMRI paradigms in 25 schizophrenia patients and 25 healthy controls. Auditory stimuli were binaural click trains at frequencies of 20, 30, 40 and 80 Hz. Based on the detected ASSR-evoked BOLD signals, we examined the functional connectivity between the thalamus and bilateral auditory cortex during both the resting state and ASSR task state, as well as their alterations. The schizophrenia group exhibited significantly diminished BOLD signals in the bilateral auditory cortex and thalamus during the 80 Hz ASSR task (corrected p < 0.05). We observed a significant inverse relationship between the resting state and ASSR task state in altered functional connectivity within the thalamo-auditory network in schizophrenia patients. Specifically, our findings demonstrated stronger functional connectivity in the resting state (p < 0.004) and reduced functional connectivity during the ASSR task (p = 0.048), which was mediated by abnormal state shifts, within the schizophrenia group. These results highlight the presence of abnormal thalamocortical connectivity associated with deficits in the shift between resting and task states in patients with schizophrenia.

Quantification of mediation effects of white matter functional characteristics on cognitive decline in aging.

Cognitive decline with aging involves multifactorial processes, including changes in brain structure and function. This study focuses on the role of white matter functional characteristics, as reflected in blood oxygenation level-dependent signals, in age-related cognitive deterioration. Building on previous research confirming the reproducibility and age-dependence of blood oxygenation level-dependent signals acquired via functional magnetic resonance imaging, we here employ mediation analysis to test if aging affects cognition through white matter blood oxygenation level-dependent signal changes, impacting various cognitive domains and specific white matter regions. We used independent component analysis of resting-state blood oxygenation level-dependent signals to segment white matter into coherent hubs, offering a data-driven view of white matter's functional architecture. Through correlation analysis, we constructed a graph network and derived metrics to quantitatively assess regional functional properties based on resting-state blood oxygenation level-dependent fluctuations. Our analysis identified significant mediators in the age-cognition relationship, indicating that aging differentially influences cognitive functions by altering the functional characteristics of distinct white matter regions. These findings enhance our understanding of the neurobiological basis of cognitive aging, highlighting the critical role of white matter in maintaining cognitive integrity and proposing new approaches to assess interventions targeting cognitive decline in older populations.

Towards clinical translation of 7 Tesla MRI in the human brain

Clinical translation of 7 tesla (T) MRI of the brain promises high image quality and potentially improved clinical diagnosis for patients compared to current standard lower field-strength MRI at 1.5 and 3T.Here we describe how physics principles underlying ultra-high field (UHF) strength MRI affect 7T image quality, and how these can be exploited to translate 7T brain imaging into clinical practice. UHF MRI profits from higher inherent signal-to-noise ratio (SNR) and a resultant increase in achievable spatial resolution or acceleration factors; increase in sensitivity to magnetic susceptibility differences and a higher amplitude of the Blood Oxygen Level Dependent (BOLD) signal; increase in longitudinal relaxation time; and increased frequency dispersion and spectral resolution in MR spectroscopy.Examples are presented of different brain pathologies, which are better illustrated on 7T compared to lower field strength by applying sequences and imaging techniques that exploit these intrinsic strengths of 7T MRI. This includes imaging of various vascular pathologies, epilepsy and brain tumours.

A preliminary study of dynamic neurochemical changes in the dorsolateral prefrontal cortex during working memory.

Working memory (WM) is one of the fundamental cognitive functions associated with the dorsolateral prefrontal cortex (DLPFC). However, the neurochemical mechanisms of WM, including the dynamic changes in neurometabolites such as glutamate and GABA in the DLPFC, remain unclear. Here, we investigated WM-related glutamate and GABA changes, alongside hemodynamic responses in the DLPFC, using a combination of functional magnetic resonance spectroscopy (fMRS) and functional magnetic resonance imaging (fMRI). During a WM task, we measured Glx (glutamate + glutamine) and GABA levels using GABA editing MEscher-GArwood Point REsolved Spectroscopy (MEGA-PRESS) sequence and blood-oxygen-level-dependent (BOLD) signal changes. In the DLPFC, we observed elevated Glx levels and increased BOLD signal changes during a 2-back task. Specifically, the Glx levels in the DLPFC were significantly higher during the 2-back task compared with fixation, although this difference was not significant when compared with a 0-back task. However, Glx levels during the 0-back task were higher than during fixation. Furthermore, there was a positive correlation between Glx levels in the DLPFC during the 2-back task and the corresponding BOLD signal changes. Notably, higher Glx increases were associated with increased DLPFC activation and lower WM task performance in individuals. No notable changes in DLPFC GABA levels were observed during WM processing. These findings suggest that the modulation of glutamatergic activity in the DLPFC may play a crucial role in both working memory processing and its associated performance outcomes.

Neuropathological characteristics of abnormal white matter functional signaling in adolescents with major depression.

Major depression disorder (MDD) constitutes a significant mental health concern. Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults, with a corresponding increased risk of suicide. In studying brain dysfunction associated with MDD in adole-scents, research on brain white matter (WM) is sparse. Some researchers even mistakenly regard the signals generated by the WM as noise points. In fact, studies have shown that WM exhibits similar blood oxygen level-dependent signal fluctuations. The alterations in WM signals and their relationship with disease severity in adolescents with MDD remain unclear. To explore potential abnormalities in WM functional signals in adolescents with MDD. This study involved 48 adolescent patients with MDD and 31 healthy controls (HC). All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview (MINI) suicide inventory. In addition, a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects' image data. The DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity, followed by a two-sample t-test between the MDD and HC groups. Independent component analysis (ICA) was also used to evaluate the WM functional signal. Pearson's correlation was performed to assess the relationship between statistical test results and clinical scales. Compared to HC, individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body, left posterior limb of the internal capsule, right superior corona radiata, and bilateral posterior corona radiata [P < 0.001, family-wise error (FWE) voxel correction]. The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata, and decreased in the left superior longitudinal fasciculus (P < 0.001, FWE voxel correction). The ICA results of WM overlapped with those of regional homo-geneity. The fALFF of WM signal in the left posterior limb of the internal capsule was negatively correlated with the MINI suicide scale (P = 0.026, r = -0.32), and the right posterior corona radiata was also negatively correlated with the MINI suicide scale (P = 0.047, r = -0.288). Adolescents with MDD involves changes in WM functional signals, and these differences in brain regions may increase the risk of suicide.

Brain activation during processing of mouth actions in patients with disorders of consciousness.

In the past 2 decades, several attempts have been made to promote a correct diagnosis and possible restorative interventions in patients suffering from disorders of consciousness. Sensory stimulation has been proved to be useful in sustaining the level of arousal/awareness and to improve behavioural responsiveness with a significant effect on oro-motor functions. Recently, action observation has been proposed as a stimulation strategy in patients with disorders of consciousness, based on neurophysiological evidence that the motor cortex can be activated not only during action execution but also when actions are merely observed in the absence of motor output, or during listening to action sounds and speech. This mechanism is provided by the activity of mirror neurons. In the present study, a group of patients with disorders of consciousness (11 males, 4 females; median age: 55 years; age range: 19-74 years) underwent task-based functional MRI in which they had, in one condition, to observe and listen to the sound of mouth actions, and in another condition, to listen to verbs with motor or abstract content. In order to verify the presence of residual activation of the mirror neuron system, the brain activations of patients were compared with that of a group of healthy individuals (seven males, eight females; median age: 33.4 years; age range: 24-65 years) performing the same tasks. The results show that brain activations were lower in patients with disorders of consciousness compared with controls, except for primary auditory areas. During the audiovisual task, 5 out of 15 patients with disorders of consciousness showed only residual activation of low-level visual and auditory areas. Activation of high-level parieto-premotor areas was present in six patients. During the listening task, three patients showed only low-level activations, and six patients activated also high-level areas. Interestingly, in both tasks, one patient with a clinical diagnosis of vegetative state showed activations of high-level areas. Region of interest analysis on blood oxygen level dependent signal change in temporal, parietal and premotor cortex revealed a significant linear relation with the level of clinical functioning, assessed with coma recovery scale-revised. We propose a classification of the patient's response based on the presence of low-level and high-level activations, combined with the patient's functional level. These findings support the use of action observation and listening as possible stimulation strategies in patients with disorders of consciousness and highlight the relevance of combined methods based on functional assessment and brain imaging to provide more detailed neuroanatomical specificity about residual activated areas at both cortical and subcortical levels.

Thermal stimulus task fMRI in the cervical spinal cord at 7 Tesla.

Although functional magnetic resonance imaging (fMRI) is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0 . Increasing field strength enables higher spatial resolution and improved sensitivity to blood oxygenation level-dependent (BOLD) signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D echo-planar imaging (EPI) protocols, which differ in sensitivity to spatial and temporal B0 inhomogeneity. The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. All protocols used 3 mm slice thickness. For each protocol, the BOLD response to 13 10-s noxious thermal stimuli applied to the right thumb was acquired in a 10-min fMRI run. Image quality, temporal signal to noise ratio (SNR), and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment. PRACTITIONER POINTS: First stimulus task fMRI results in the spinal cord at 7 T. Single-shot 0.75 mm 2D EPI produced the highest mean z-statistic. Multi-shot 0.60 mm 2D EPI provided the best-localized activation and least distortion.

Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease.

Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2 = 0.32, p = 0.0006) and APA amplitude (R2 = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

High-definition tDCS over primary motor cortex modulates brain signal variability and functional connectivity in episodic migraine

ObjectiveThis study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal variability and functional connectivity in the trigeminal pain pathway, and their association with changes in migraine attacks. MethodsTwenty-five episodic migraine patients were randomized for ten daily sessions of active or sham M1 HD-tDCS. Resting-state blood-oxygenation-level-dependent (BOLD) signal variability and seed-based functional connectivity were assessed pre- and post-treatment. A mediation analysis was performed to test whether BOLD signal variability mediates the relationship between treatment group and moderate-to-severe headache days. ResultsThe active M1 HD-tDCS group showed reduced BOLD variability in the spinal trigeminal nucleus (SpV) and thalamus, but increased variability in the rostral anterior cingulate cortex (rACC) compared to the sham group. Connectivity decreased between medial pulvinar-temporal pole, medial dorsal-precuneus, and the ventral posterior medial nucleus-SpV, but increased between the rACC-amygdala, and the periaqueductal gray-parahippocampal gyrus. Changes in medial pulvinar variability mediated the reduction in moderate-to-severe headache days at one-month post-treatment. ConclusionsM1 HD-tDCS alters BOLD signal variability and connectivity in the trigeminal somatosensory and modulatory pain system, potentially alleviating migraine headache attacks. SignificanceM1 HD-tDCS realigns brain signal variability and connectivity in migraineurs closer to healthy control levels.

Exploring timescale-specific functional brain networks and their associations with aging and cognitive performance in a healthy cohort without dementia

IntroductionFunctional brain networks (FBNs) coordinate brain functions and are studied in fMRI using blood-oxygen-level-dependent (BOLD) signal correlations. Previous research links FBN changes to aging and cognitive decline, but various physiological factors influnce BOLD signals. Few studies have investigated the intrinsic components of the BOLD signal in different timescales using signal decomposition. This study aimed to explore differences between intrinsic FBNs and traditional BOLD-FBN, examining their associations with age and cognitive performance in a healthy cohort without dementia. Materials and methodsA total of 396 healthy participants without dementia (men = 157; women = 239; age range = 20–85 years) were enrolled in this study. The BOLD signal was decomposed into several intrinsic signals with different timescales using ensemble empirical mode decomposition, and FBNs were constructed based on both the BOLD and intrinsic signals. Subsequently, network features—global efficiency and local efficiency values—were estimated to determine their relationship with age and cognitive performance. ResultsThe findings revealed that the global efficiency of traditional BOLD-FBN correlated significantly with age, with specific intrinsic FBNs contributing to these correlations. Moreover, local efficiency analysis demonstrated that intrinsic FBNs were more meaningful than traditional BOLD-FBN in identifying brain regions related to age and cognitive performance. ConclusionsThese results underscore the importance of exploring timescales of BOLD signals when constructing FBN and highlight the relevance of specific intrinsic FBNs to aging and cognitive performance. Consequently, this decomposition-based FBN-building approach may offer valuable insights for future fMRI studies.

A Cross-Sectional and Longitudinal Integrated Study on Brain Functional Changes in a Neuropathic Pain Rat Model.

Human and animal imaging studies demonstrated that chronic pain profoundly alters the structure and the functionality of several brain regions and even causes mental dysfunctions such as depression and anxiety disorders. In this article, we conducted a multimodal study cross-sectionally and longitudinally, to evaluate how neuropathic pain affects the brain. Using the spared nerve injury (SNI) model which promotes long-lasting mechanical allodynia, results showed that neuropathic pain deeply modified the intrinsic organization of the brain functional network 2 weeks after injury. There are significant changes in the activity of the left thalamus (Th_L) and left olfactory bulb (OB_L) brain regions after SNI, as evidenced by both the blood oxygen level-dependent (BOLD) signal and c-Fos expression. Importantly, these changes were closely related to mechanical pain behavior of rats. However, it is worth noting that after morphine administration for analgesia, only the increased activity in the TH region is reversed, while the decreased activity in the OB region becomes more prominent. Functional connectivity (FC) and c-Fos correlation analysis further showed these two regions of interest (ROIs) exhibit different FC patterns with other brain regions. Our study comprehensively revealed the adaptive changes of brain neural networks induced by nerve injury in both cross-sectional and longitudinal dimensions and emphasized the abnormal activity and FC of Th_L and OB_L in the pathological condition. It provides reliable assistance in exploring the intricate mechanisms of diseases.