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•We found that there are non-hemodynamic components in intrinsic optical imaging data.•We found that the non-hemodynamic components result in insufficient substruction of hemodynamic noise from wide-field fluorescent imaging data.•We developed a linear regression method that can calculate the non-hemodynamic components and lead to more precise hemodynamic subtraction.•We demonstrate that the new method works on data from various experiments. Accurate interpretation of in vivo wide-field fluorescent imaging (WFFI) data requires precise separation of raw fluorescence signals into neural and hemodynamic components. The classical Beer-Lambert law-based approach, which uses concurrent 530-nm illumination to estimate relative changes in cerebral blood volume (CBV), fails to account for the scattering and reflection of 530-nm photons from non-neuronal components leading to biased estimates of CBV changes and subsequent misrepresentation of neural activity. This study introduces a novel linear regression approach designed to overcome this limitation. This correction provides a more reliable representation of CBV changes and neural activity in fluorescence data. Our method is validated across multiple datasets, demonstrating its superiority over the classical approach.

Spinal cord stimulation (SCS) therapy is an established treatment for chronic neuropathic pain, but methodological limitations have prohibited detailed investigation of activation patterns it produces in the SC. Functional ultrasound imaging (fUS) is an emerging technology that monitors local hemodynamic changes in the brain with high sensitivity and spatiotemporal resolution that are tightly coupled to neural functional activity. In this study, fUS was used to investigate neuromodulation patterns produced by clinical SCS paradigms in an ovine model that enabled testing with implanted clinical hardware. Activation of local superficial dorsal horn (SDH) regions during SCS therapy was evaluated using fUS to detect hemodynamic changes in spinal blood volume (∆SBV). Standard SCS leads were percutaneously implanted midline overlying the dura of the exposed cord (T12-L1) to enable stimulation and recording evoked compound action potentials (eCAPs). Hemodynamic activation patterns were mapped across two vertebral segments at amplitudes between 100-200% eCAP threshold for conventional tonic, multiphase, burst, high frequency and multi-frequency SCS paradigms. SCS stimulation resulted in significant activation of the SDH in differing patterns across two vertebral segments. The magnitude and volume of ∆SBV increased at higher amplitudes and was typically maximal in the SDH regions underlying the active electrodes. Therapy mode significantly influenced total area and depth of ∆SBV. Multiphase therapy produced the largest area of ∆SBV followed by multi-frequency and other SCS modes. Multiphase therapy also produced the greatest depth of ∆SBV followed by multi-frequency and burst therapies. This work demonstrates that fUS can effectively measure SCS neural response patterns in the pain processing laminae of a large animal model implanted with a clinical SCS system. Hemodynamic responses in the SC varied significantly across SCS therapy modes, with multiphase stimulation providing a greater area of coverage and depth of response versus other common stimulation types.

This chapter contains sections titled: Introduction The Venous Influence on the Functional Specificity of Bold fMRI Functional SWI (fSWI) Susceptibility‐Induced Phase Changes Removal of the Vein Contribution in fMRI Using Phase Information References

Simultaneous electroencephalography–functional MRI (EEG‐fMRI) is a unique and noninvasive method for epilepsy presurgical evaluation. When selecting voxels by null‐hypothesis tests, the conventional analysis may overestimate fMRI response amplitudes related to interictal epileptic discharges (IEDs), especially when IEDs are rare. We aimed to estimate fMRI response amplitudes represented by blood oxygen level dependent (BOLD) percentage changes related to IEDs using a hierarchical model. It involves the local and distributed hemodynamic response homogeneity to regularize estimations. Bayesian inference was applied to fit the model. Eighty‐two epilepsy patients who underwent EEG‐fMRI and subsequent surgery were included in this study. A conventional voxel‐wise general linear model was compared to the hierarchical model on estimated fMRI response amplitudes and on the concordance between the highest response cluster and the surgical cavity. The voxel‐wise model overestimated fMRI responses compared to the hierarchical model, evidenced by a practically and statistically significant difference between the estimated BOLD percentage changes. Only the hierarchical model differentiated brief and long‐lasting IEDs with significantly different BOLD percentage changes. Overall, the hierarchical model outperformed the voxel‐wise model on presurgical evaluation, measured by higher prediction performance. When compared with a previous study, the hierarchical model showed higher performance metric values, but the same or lower sensitivity. Our results demonstrated the capability of the hierarchical model of providing more physiologically reasonable and more accurate estimations of fMRI response amplitudes induced by IEDs. To enhance the sensitivity of EEG‐fMRI for presurgical evaluation, it may be necessary to incorporate more appropriate spatial priors and bespoke decision strategies.

Introduction While the clinical efficacy of deep brain stimulation (DBS) the treatment of motor‐related symptoms is well established, the mechanism of action of the resulting cognitive and behavioral effects has been elusive. Methods By combining functional magnetic resonance imaging (fMRI) and DBS, we investigated the pattern of blood‐oxygenation‐level‐dependent (BOLD) signal changes induced by stimulating the nucleus accumbens in a large animal model. Results We found that diffused BOLD activation across multiple functional networks, including the prefrontal, limbic, and thalamic regions during the stimulation, resulted in a significant change in inter‐regional functional connectivity. More importantly, the magnitude of the modulation was closely related to the strength of the inter‐regional resting‐state functional connectivity. Conclusions Nucleus accumbens stimulation affects the functional activity in networks that underlie cognition and behavior. Our study provides an insight into the nature of the functional connectivity, which mediates activation effect via brain networks. Deep brain stimulation on nucleus accumbens of eight healthy swine evoked blood‐oxygenated‐level‐dependent (BOLD) activation in multiple cortical and subcortical brain regions.

(1) Background: The vitamin D level in blood is one of the markers of the functional reserves of the human body and can contribute to more successful adaptation in the Arctic. (2) Methods: The study involved 38 participants in the project “Arctic Floating University—2021”. The determination of vitamin D content was carried out at the beginning of the expedition. A dynamic study was carried out for 20 days in the morning and in the evening. The functional state parameters of the participants were assessed using psychophysiological and questionnaire methods. Statistical methods: Mann–Whitney U-test and correlation analysis. (3) Results: It was found that at the beginning of the expedition, the functional state of participants with more severe vitamin D deficiency is characterized by a shorter average duration of RR intervals (p = 0.050) and reduced SDNN values (p = 0.015). The higher the content of vitamin D, the greater increase in speed (r = 0.510), the higher the increase in projective performance (r = 0.485), and the smaller the increase in projective stress (r = −0.334). Significant relationships between the subjective characteristics of functional states and the vitamin D of participants have not been established. (4) Conclusion: With an increase in the severity of vitamin D deficiency in the blood, the adaptive capabilities of participants decrease during an expedition to the Arctic.

Worldwide, ethanol abuse causes thousands of fatal accidents annually as well as innumerable social dysfunctions and severe medical disorders. Yet, few studies have used the blood oxygenation level dependent functional magnetic resonance imaging method (BOLD fMRI) to map how alcohol alters brain functions, as fMRI relies on neurovascular coupling, which may change due to the vasoactive properties of alcohol. We monitored the hemodynamic response function (HRF) with a high temporal resolution. In both motor cortices and the visual cortex, alcohol prolonged the time course of the HRF, indicating an overall slow-down of neurovascular coupling rather than an isolated reduction in neuronal activity. However, in the supplementary motor area, alcohol-induced changes to the HRF suggest a reduced neuronal activation. This may explain why initiating and coordinating complex movements, including speech production, are often impaired earlier than executing basic motor patterns. Furthermore, the present study revealed a potential pitfall associated with the statistical interpretation of pharmacological fMRI studies based on the general linear model: if the functional form of the HRF is changed between the conditions data may be erroneously interpreted as increased or decreased neuronal activation. Thus, our study not only presents an additional key to how alcohol affects the network of brain functions but also implies that potential changes to neurovascular coupling have to be taken into account when interpreting BOLD fMRI. Therefore, measuring individual drug-induced HRF changes is recommended for pharmacological fMRI.

Cognitive behavioural therapy (CBT) is a successful treatment of obsessive compulsive disorder (OCD). It is known to induce changes in cerebral metabolism; however, the dynamics of these changes and their relation to clinical change remain largely unknown, precluding the identification of individualized response biomarkers. In order to study the dynamics of treatment response, we performed systematic clinical and functional magnetic resonance imaging (fMRI) evaluation of 35 OCD patients immediately before a 3-month course of CBT, halfway through and at its end, as well as 6 months after. To sensitize fMRI probing, we used an original exposure task using neutral, generic and personalized obsession-inducing images. As expected, CBT produced a significant improvement in OCD. This improvement was continuous over the course of the therapy; therefore, outcome could be predicted by response at mid-therapy (r 2 = 0.67, p < 0.001). Haemodynamic response to the task was located in the anterior cingulate and orbitofrontal cortices and was stronger during exposure to personalized obsession-inducing images. In addition, both the anxiety ratings and the haemodynamic response to the obsession-inducing images in the anterior cingulate and the left but not the right orbitofrontal clusters decreased with symptom improvement. Interestingly, haemodynamic activity continued to decrease after stabilization of clinical symptoms. Using an innovative and highly sensitive exposure paradigm in fMRI, we showed that clinical and haemodynamic phenotypes have similar time courses during CBT. Our results, which suggest that the initial CBT sessions are crucial, prompt us to investigate the anatomo-functional modifications underlying the very first weeks of the therapy.

Background/Objectives: Early detection of increased vascular stiffness in young populations may facilitate the development of more effective strategies for the primary prevention of arterial hypertension and other age-related cardiovascular diseases. To examine gender differences in orthostatic increases in vascular stiffness during the head-up tilt test (HUTT), standardized by hydrostatic column height. Materials and Methods: A total of 133 healthy adults aged 18–20 years (93 females and 40 males) were evaluated. Blood pressure and pulse wave velocity at the brachial–ankle artery site (baPWV) were measured using an ABI system 100 PWV multichannel sphygmomanometer. Orthostatic changes in arterial stiffness were assessed during a head-up tilt test (HUTT) using the Luanda protocol, which standardizes hydrostatic column height. The functional reserve coefficient (FRC) of orthostatic circulatory regulation was introduced as a measure of adaptive capacity: FRC = ΔbaPWV/baPWVb. This coefficient accounts for both structural (baPWVb) and functional (ΔbaPWV = baPWVt − baPWVb) components influencing cardiovascular system adaptation, which exhibit multidirectional changes with age. Results: Baseline baPWV (baPWVb) values in the horizontal position showed no significant differences between genders and were within normal age ranges. However, baPWV values in the upright HUTT position (baPWVt) were significantly higher in men (p = 0.0007). Dynamic biomarkers of vascular reserve, including ΔbaPWV and FRC, were also significantly elevated in men (p = 0.0009 and p = 0.0064, respectively). Conclusions: While baseline baPWVb values were comparable between genders, dynamic biomarkers of vascular reserve, such as ΔbaPWV and FRC, were significantly higher in men. Prospective studies are needed to establish optimal reference values for these dynamic biomarkers, enabling the assessment of individual trends in vascular aging and evaluating the effects of treatment, lifestyle modifications, and other preventive measures on vascular health.

Non-invasive Brain-Computer Interfaces (BCI) have demonstrated great promise for neuroprosthetics and assistive devices. Here we aim to investigate methods to combine Electroencephalography (EEG) and functional Near-Infrared Spectroscopy (fNIRS) in an asynchronous Sensory Motor rhythm (SMR)-based BCI. We attempted to classify 4 different executed movements, namely, Right-Arm-Left-Arm-Right-Hand-Left-Hand tasks. Previous studies demonstrated the benefit of EEG-fNIRS combination. However, since normally fNIRS hemodynamic response shows a long delay, we investigated new features, involving slope indicators, in order to immediately detect changes in the signals. Moreover, Common Spatial Patterns (CSPs) have been applied to both EEG and fNIRS signals. 15 healthy subjects took part in the experiments and since 25 trials per class were available, CSPs have been regularized with information from the entire population of participants and optimized using genetic algorithms. The different features have been compared in terms of performance and the dynamic accuracy over trials shows that the introduced methods diminish the fNIRS delay in the detection of changes.