Blood Oxygenation Level-dependent Signal Changes Research Articles

Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.

Multi-modal Magnetic Resonance Imaging to Assess Cerebrovascular Function in Atrial Fibrillation Patients

Atrial fibrillation (AF) is associated with an increased risk of cognitive decline, dementia, and stroke. Low cerebral blood flow (CBF) and low cerebrovascular carbon dioxide reactivity (CVRCO2) are associated with poor brain health outcomes. In the current study we employed magnetic resonance imaging (MRI) to quantify resting CBF and CVRCO2 in patients with AF and age-matched normal sinus rhythm (NSR) controls. We hypothesised that both resting CBF and CVRCO2 would be lower in patients with AF. Patients with AF (n=11, 65±14 years, 2 women) and NSR (n=12, 63±9 years, 7 women) underwent arterial spin labelling (ASL) at rest, and blood oxygen level-dependent (BOLD) MRI during a single-step increase in partial pressure of carbon dioxide (measured by end-tidal carbon dioxide (PETCO2)) induced by changing the fraction of inspired CO2 to 5% (21% O2, balance N2). Region of interest time courses were extracted with grey matter, middle cerebral artery, and posterior cerebral artery territory masks. CVRCO2 was defined as the percentage change (%Δ) in BOLD signal vs %Δ in PETCO2. Baseline CBF was not different between NSR and AF in grey matter (62±17 vs. 58±10 ml/min/100g, respectively; p=0.226), middle cerebral artery (59±16 vs. 56±14 ml/min/100g; p=0.361) and posterior cerebral artery (61±17 vs 53±15 ml/min/100g; p=0.138) territories. BOLD-derived CVRC02 was not different between NSR and AF groups in grey matter (0.11±0.04 vs. 0.12±0.03 %ΔBOLD/%ΔmmHg, respectively; p=0.372), middle cerebral artery (0.09±0.04 vs. 0.10±0.03 %ΔBOLD/%ΔmmHg; p=0.405) and posterior cerebral artery (0.13±0.04 vs. 0.14±0.05 %ΔBOLD/%ΔmmHg; p=0.367) territories. Collectively, these pilot data suggest that MRI-derived cerebrovascular CO2 responsiveness is not different in patients with AF and age-matched NSR controls that have similar resting CBF. Further investigations are required to extend these preliminary findings to a larger cohort to fully elucidate the effects of AF on cerebrovascular function. Support provided by the Royal Society of New Zealand Te Apārangi Marsden Fund (19-UOA-170). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

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.

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.

Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity.

Impaired cerebrovascular reactivity (CVR) has been correlated with recurrent ischemic stroke. However, for clinical purposes, most CVR techniques are rather complex, time-consuming, and lack validation for quantitative measurements. The recent adaptation of a standardized hypercapnic stimulus in combination with a blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging signal as a surrogate for cerebral blood flow offers a potential universally comparable CVR assessment. We investigated the association between impaired BOLD-CVR and risk for recurrent ischemic events. We conducted a retrospective analysis of patients with symptomatic cerebrovascular large vessel disease who had undergone a prospective hypercapnic-challenged BOLD-CVR protocol at a single tertiary stroke referral center between June 2014 and April 2020. These patients were followed up for recurrent acute ischemic events for up to 3 years. BOLD-CVR (%BOLD signal change per mm Hg CO2) was calculated on a voxel-by-voxel basis. Impaired BOLD-CVR of the affected (ipsilateral to the vascular pathology) hemisphere was defined as an average BOLD-CVR, falling 2 SD below the mean BOLD-CVR of the right hemisphere in a healthy age-matched reference cohort (n=20). Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate. Of 130 eligible patients, 28 experienced recurrent strokes (median, 85 days, interquartile range, 5-166 days). Risk factors associated with an increased recurrent stroke rate included impaired BOLD-CVR, a history of atrial fibrillation, and heart insufficiency. After adjusting for sex, age group, and atrial fibrillation, impaired BOLD-CVR exhibited a hazard ratio of 10.73 (95% CI, 4.14-27.81; P<0.001) for recurrent ischemic stroke. Among patients with symptomatic cerebrovascular large vessel disease, those exhibiting impaired BOLD-CVR in the affected hemisphere had a 10.7-fold higher risk of recurrent ischemic stroke events compared with individuals with nonimpaired BOLD-CVR.

Baseline cerebrovascular reactivity predicts longitudinal enlarged perivascular space burden in the basal ganglia among cognitively normal older adults

AbstractBackgroundIncreasing evidence suggests that enlarged perivascular spaces (ePVS) on magnetic resonance images (MRIs) are associated with cognitive dysfunction in aging. However, the etiology of ePVS remains unknown. Here we tested the possibility that cerebrovascular dysfunction, as assessed by an MRI measure of cerebrovascular reactivity (CVR), may contribute to ePVS development.Method79 cognitively normal, older adults (46 women, age range 60‐84) were recruited to undergo baseline MRI scanning and follow‐up scanning approximately 2.5 years later. Of the 79 participants scanned at baseline, 50 returned for follow‐up. Participants were scanned on a 3T Siemens Prisma scanner with a 64‐channel head coil. All scanning methods were identical across time points and included collection of T1‐weighted, T2‐weighted FLAIR, and quantitative susceptibility mapping (QSM) images. Cerebrovascular dysfunction was assessed using CVR, a measure of the ability of cerebrovasculature to dilate in response to vasoactive stimuli. Participants underwent blocked administration of breathing either room air or hypercapnic gas, while blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) was performed. CVR values were computed for baseline scans in specific regions by dividing change in BOLD signal by change in end‐tidal CO2. Baseline and follow‐up ePVS counts were performed by a single rater who was blinded to participant demographics. ePVS were individually and manually counted using STRIVE criteria in a representative, axial slice of the basal ganglia (BGePVS) and centrum semiovale (CSePVS).ResultBGePVS and CSePVS significantly increased during the follow‐up period. Mixed effects models indicated that baseline basal ganglia CVR values significantly predicted increased BGePVS counts after controlling for age, sex, education, and time point (p = &lt;0.001). Furthermore, this effect was present bilaterally: Baseline CVR in the left hemisphere predicted increased BGePVS in the left hemisphere (p = &lt;0.001) and baseline CVR in the right hemisphere predicted increased BGePVS in the right hemisphere (p = &lt;0.001). Conversely, there was no longitudinal relationship between baseline CVR and increased CSePVS (p = 0.449).ConclusionThese results demonstrate that low baseline CVR is a risk factor for later development of ePVS. Localization of these findings to the basal ganglia suggests that it is particularly vulnerable to cerebrovascular dysfunction.

Vascular contribution to the relationship between cerebrovascular reactivity and cognition

AbstractBackgroundBrain vascular health is closely related to cognitive performance, and cerebrovascular reactivity (CVR), an indicator of cerebral blood flow (CBF) compensatory capacity in response to vasoactive stimuli, may help elucidate this relationship. Arterial spin labeling (ASL) and blood‐oxygen‐level‐dependent (BOLD) are two representative methods for measuring CVR, although BOLD is a complex combination of CBF, cerebral volume, and cerebral metabolic rate of oxygen. This study aimed to investigate the relationship between cognition and two different CVR methods.MethodSeventy‐nine subjects (age: 68.7±7.2 years) enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core underwent MRI, including both dynamic pseudo‐continuous ASL (PCASL) under a hypercapnic respiratory challenge and multi‐TI PCASL for resting CBF and ATT mapping. The dynamic PCASL with a longer TE (20ms) provided simultaneous acquisition of ASL and BOLD. CVR was obtained by calculating CBF or BOLD signal changes during a hypercapnic period. Voxel‐wise multiple linear regression analyses were performed to examine the relationship between CVR and mild cognitive impairment (MCI), adjusting for age, sex, glycemic status, APOE e4 allele, hypertensive status, and years of education. False positive cluster thresholding was applied for each modality. Additional statistical analyses were conducted to investigate differences in baseline CBF and ATT between cognitively healthy and MCI groups within the voxel clusters that showed significantly different CVR values.ResultIn the BOLD‐based CVR analysis, two voxel clusters in the white matter (WM) of superior temporal and parietal lobes showed lower CVR in the MCI group compared to the cognitively healthy group (Figure 1). Additionally, reduced CBF and prolonged ATT were observed within the clusters (Figure 2 and 3).ConclusionSubjects with MCI exhibited lower BOLD‐based CVR in WM, while no association was found between ASL‐based CVR and MCI. BOLD‐based CVR may be a more sensitive measure than ASL‐based CVR in association with cognition, particularly in WM where optimization of ASL acquisition is challenging. The impaired CVR in the MCI group may be due to cerebrovascular impairments, such as reduced CBF and prolonged ATT.

Current State of Functional MRI in the Presurgical Planning of Brain Tumors.

Surgical resection of brain tumors is challenging because of the delicate balance between maximizing tumor removal and preserving vital brain functions. Functional MRI (fMRI) offers noninvasive preoperative mapping of widely distributed brain areas and is increasingly used in presurgical functional mapping. However, its impact on survival and functional outcomes is still not well-supported by evidence. Task-based fMRI (tb-fMRI) maps blood oxygen level-dependent (BOLD) signal changes during specific tasks, while resting-state fMRI (rs-fMRI) examines spontaneous brain activity. rs-fMRI may be useful for patients who cannot perform tasks, but its reliability is affected by tumor-induced changes, challenges in data processing, and noise. Validation studies comparing fMRI with direct cortical stimulation (DCS) show variable concordance, particularly for cognitive functions such as language; however, concordance for tb-fMRI is generally greater than that for rs-fMRI. Preoperative fMRI, in combination with MRI tractography and intraoperative DCS, may result in improved survival and extent of resection and reduced functional deficits. fMRI has the potential to guide surgical planning and help identify targets for intraoperative mapping, but there is currently limited prospective evidence of its impact on patient outcomes. This review describes the current state of fMRI for preoperative assessment in patients undergoing brain tumor resection. Keywords: MR-Functional Imaging, CNS, Brain/Brain Stem, Anatomy, Oncology, Functional MRI, Functional Anatomy, Task-based, Resting State, Surgical Planning, Brain Tumor © RSNA, 2023.

Whole-brain, gray, and white matter time-locked functional signal changes with simple tasks and model-free analysis

Recent studies have revealed the production of time-locked blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signals throughout the entire brain in response to tasks, challenging the existence of sparse and localized brain functions and highlighting the pervasiveness of potential false negative fMRI findings. "Whole-brain" actually refers to gray matter, the only tissue traditionally studied with fMRI. However, several reports have demonstrated reliable detection of BOLD signals in white matter, which have previously been largely ignored. Using simple tasks and analyses, we demonstrate BOLD signal changes across the whole brain, in both white and gray matters, in similar manner to previous reports of whole brain studies. We investigated whether white matter displays time-locked BOLD signals across multiple structural pathways in response to a stimulus in a similar manner to the cortex. We find that both white and gray matter show time-locked activations across the whole brain, with a majority of both tissue types showing statistically significant signal changes for all task stimuli investigated. We observed a wide range of signal responses to tasks, with different regions showing different BOLD signal changes to the same task. Moreover, we find that each region may display different BOLD responses to different stimuli. Overall, we present compelling evidence that, just like all gray matter, essentially all white matter in the brain shows time-locked BOLD signal changes in response to multiple stimuli, challenging the idea of sparse functional localization and the prevailing wisdom of treating white matter BOLD signals as artifacts to be removed.

GABA and Glutamate in hMT+ Link to Individual Differences in Residual Visual Function After Occipital Stroke.

Damage to the primary visual cortex following an occipital stroke causes loss of conscious vision in the contralateral hemifield. Yet, some patients retain the ability to detect moving visual stimuli within their blind field. The present study asked whether such individual differences in blind field perception following loss of primary visual cortex could be explained by the concentration of neurotransmitters γ-aminobutyric acid (GABA) and glutamate or activity of the visual motion processing, human middle temporal complex (hMT+). We used magnetic resonance imaging in 19 patients with chronic occipital stroke to measure the concentration of neurotransmitters GABA and glutamate (proton magnetic resonance spectroscopy) and functional activity in hMT+ (functional magnetic resonance imaging). We also tested each participant on a 2-interval forced choice detection task using high-contrast, moving Gabor patches. We then measured and assessed the strength of relationships between participants' residual vision in their blind field and in vivo neurotransmitter concentrations, as well as visually evoked functional magnetic resonance imaging activity in their hMT+. Levels of GABA and glutamate were also measured in a sensorimotor region, which served as a control. Magnetic resonance spectroscopy-derived GABA and glutamate concentrations in hMT+ (but not sensorimotor cortex) strongly predicted blind-field visual detection abilities. Performance was inversely related to levels of both inhibitory and excitatory neurotransmitters in hMT+ but, surprisingly, did not correlate with visually evoked blood oxygenation level-dependent signal change in this motion-sensitive region. Levels of GABA and glutamate in hMT+ appear to provide superior information about motion detection capabilities inside perimetrically defined blind fields compared to blood oxygenation level-dependent signal changes-in essence, serving as biomarkers for the quality of residual visual processing in the blind-field. Whether they also reflect a potential for successful rehabilitation of visual function remains to be determined.

A mechanistic computational framework to investigate the hemodynamic fingerprint of the blood oxygenation level-dependent signal.

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is one of the most used imaging techniques to map brain activity or to obtain clinical information about human cortical vasculature, in both healthy and disease conditions. Nevertheless, BOLD fMRI is an indirect measurement of brain functioning triggered by neurovascular coupling. The origin of the BOLD signal is quite complex, and the signal formation thus depends, among other factors, on the topology of the cortical vasculature and the associated hemodynamic changes. To understand the hemodynamic evolution of the BOLD signal response in humans, it is beneficial to have a computational framework available that virtually resembles the human cortical vasculature, and simulates hemodynamic changes and corresponding MRI signal changes via interactions of intrinsic biophysical and magnetic properties of the tissues. To this end, we have developed a mechanistic computational framework that simulates the hemodynamic fingerprint of the BOLD signal based on a statistically defined, three-dimensional, vascular model that approaches the human cortical vascular architecture. The microvasculature is approximated through a Voronoi tessellation method and the macrovasculature is adapted from two-photon microscopy mice data. Using this computational framework, we simulated hemodynamic changes-cerebral blood flow, cerebral blood volume, and blood oxygen saturation-induced by virtual arterial dilation. Then we computed local magnetic field disturbances generated by the vascular topology and the corresponding blood oxygen saturation changes. This mechanistic computational framework also considers the intrinsic biophysical and magnetic properties of nearby tissue, such as water diffusion and relaxation properties, resulting in a dynamic BOLD signal response. The proposed mechanistic computational framework provides an integrated biophysical model that can offer better insights regarding the spatial and temporal properties of the BOLD signal changes.

Potential biomarker of brain response to opioid antagonism in adolescents with eating disorders: a pilot study.

Eating Disorders (ED) affect up to 5% of youth and are associated with reward system alterations and compulsive behaviors. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and/or purging. The presumed mechanism of action is blockade of reward activation; however, not all patients respond, and the optimal dose is unknown. Developing a tool to detect objective drug response in the brain will facilitate drug development and therapeutic optimization. This pilot study evaluated neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED. Youth aged 13-21 with binge/purge ED completed functional magnetic resonance imaging (fMRI) pre- and post-oral naltrexone. fMRI detected blood oxygenation-level dependent (BOLD) signal at rest and during two reward probes (monetary incentive delay, MID, and passive food view, PFV) in predefined regions of interest associated with reward and inhibitory control. Effect sizes for Δ%BOLD (post-naltrexone vs. baseline) were estimated using linear mixed effects modeling. In 12 youth (16-21 years, 92% female), BOLD signal changes were detected following naltrexone in the nucleus accumbens during PFV (Δ%BOLD -0.08 ± 0.03; Cohen's d -1.06, p = 0.048) and anterior cingulate cortex during MID (Δ%BOLD 0.06 ± 0.03; Cohen's d 1.25, p = 0.086). fMRI detected acute reward pathway modulation in this small sample of adolescents with binge/purge ED. If validated in future, larger trials, task-based Δ%BOLD detected by fMRI may serve as a pharmacodynamic biomarker of opioid antagonism to facilitate the development of novel therapeutics targeting the reward pathway, enable quantitative pharmacology trials, and inform drug dosing. https://clinicaltrials.gov/ct2/show/NCT04935931, NCT#04935931.

Left or right ear? A neuroimaging study using combined taVNS/fMRI to understand the interaction between ear stimulation target and lesion location in chronic stroke

BackgroundImplanted vagus nerve stimulation (VNS) and transcutaneous auricular VNS (taVNS) have been primarily administered clinically to the unilateral-left vagus nerve. This left-only convention has proved clinically beneficial in brain disorders. However, in stroke survivors, the presence of a lesion in the brain may complicate VNS-mediated signaling, and it is important to understand the laterality effects of VNS in stroke survivors to optimize the intervention. ObjectiveTo understand whether taVNS delivered to different ear targets relative to the lesion (ipsilesional vs contralesional vs bilateral vs sham) impacts blood oxygenation level dependent (BOLD) signal propagation in stroke survivors. MethodsWe enrolled 20 adults with a prior history of stroke. Each participant underwent a single visit, during which taVNS was delivered concurrently during functional magnetic resonance imaging (fMRI) acquisition. Each participant received three discrete active stimulation conditions (ipsilesional, contralesional, bilateral) and one sham condition in a randomized order. Stimulation-related BOLD signal changes in the active conditions were compared to sham conditions to understand the interaction taVNS and laterality effects. ResultsAll active taVNS conditions deactivated the contralesional default mode network related regions compared to sham, however only ipsilesional taVNS enhanced the activations in the ipsilesional visuomotor and secondary visual cortex. Furthermore, we reveal an interaction in task activations between taVNS and cortical visuomotor areas, where ipsilesional taVNS significantly increased ipsilesional visuomotor activity and decreased contralesional visuomotor activity compared to sham. ConclusionLaterality of taVNS relative to the lesion is a critical factor in optimizing taVNS in a stroke population, with ipsilesional stimulation providing largest direct brain activation and should be explored further when designing taVNS studies in neurorehabilitation.

1534-P: Nasal-Insulin–Induced Change of Functional MRI Signal at the Level of Hypothalamic Nuclei in the Patients with Type 2 Diabetes Mellitus

Insulin resistance in the hypothalamus is related to both increased appetite and systemic metabolic deterioration and may be an essential cause of metabolic diseases. In human studies, hypothalamic activity after intranasal insulin administration (INIA) has been measured by functional MRI (fMRI). However, to date, the resolution of fMRI has not been high enough to assess which neuronal nuclei in the hypothalamus are responsible for insulin. The purpose of this study was to investigate whether we can assess hypothalamic reaction after INIA at the nuclear level using high-resolution fMRI and if so, to examine its association with clinical parameters. Here, we studied 20 men with type 2 diabetes (T2DM) and 20 non-obese men without diabetes (CON). All subjects underwent fMRI with INIA (160 IU human insulin). The average of the cleaned blood oxygenation level-dependent (BOLD) signal from -15 min to 0 min was used as the baseline value in each subject. The signal change compared to the baseline value was calculated at every 5 min after INIA. The mean ages of subjects were both around 50 years and HbA1c levels were 6.88±1.13% in T2DM and 5.24±0.25% in CON (p&amp;lt;0.001). There were significant differences in the BOLD signal changes after INIA in the posterior nucleus (PH) at 5 min and posterior lateral hypothalamic area (LHAp) at 5 and 10 min between T2DM and CON. In other hypothalamic nuclei, there were no significant differences between T2DM and CON in the rate of change of the BOLD signal up to 30 min after INIA. Multiple regression analysis revealed that fasting plasma glucose (FPG) was a significant independent variable for activity change of the PH at 5 min and LHAp at 5 and 10 min, while BMI and HOMA-IR were not. In summary, we successfully detected nasal-insulin-induced change of fMRI signal at the level of hypothalamic nuclei. We found the differences in neural activity in the PH and LHAp early after INIA between those with and without diabetes, which were associated with FPG. Disclosure M.Kiya: None. Y.Tamura: None. H.Kaga: None. N.Ito: None. T.Tajima: None. H.Naito: None. M.Sato: None. S.Kadowaki: None. S.Kakehi: None. H.Watada: Research Support; Boehringer Ingelheim Japan, Inc., Mitsubishi Tanabe Pharma Corporation, LifeScan Diabetes Institute, Eli Lilly Japan K.K., Sun Pharmaceutical Industries Ltd., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Merck Sharp &amp; Dohme Corp., Sanwa Kagaku Kenkyusho, Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Novo Nordisk, Abbott Japan Co., Ltd., Astellas Pharma Inc., Merck Sharp &amp; Dohme Corp., Kissei Pharmaceutical Co., Ltd., AstraZeneca, Ono Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Eli Lilly Japan K.K. Funding Japan Society for the Promotion of Science (21H03380, 22K17835); Ministry of Education, Culture, Sports, Science and Technology of Japan; Suzuken Memorial Foundation

Examining temporal features of BOLD-based cerebrovascular reactivity in clinical populations.

Conventional cerebrovascular reactivity (CVR) estimation has demonstrated that many brain diseases and/or conditions are associated with altered CVR. Despite the clinical potential of CVR, characterization of temporal features of a CVR challenge remains uncommon. This work is motivated by the need to develop CVR parameters that characterize individual temporal features of a CVR challenge. Data were collected from 54 adults and recruited based on these criteria: (1) Alzheimer's disease diagnosis or subcortical Vascular Cognitive Impairment, (2) sleep apnea, and (3) subjective cognitive impairment concerns. We investigated signal changes in blood oxygenation level dependent (BOLD) contrast images with respect to hypercapnic and normocapnic CVR transition periods during a gas manipulation paradigm. We developed a model-free, non-parametric CVR metric after considering a range of responses through simulations to characterize BOLD signal changes that occur when transitioning from normocapnia to hypercapnia. The non-parametric CVR measure was used to examine regional differences across the insula, hippocampus, thalamus, and centrum semiovale. We also examined the BOLD signal transition from hypercapnia back to normocapnia. We found a linear association between isolated temporal features of successive CO2 challenges. Our study concluded that the transition rate from hypercapnia to normocapnia was significantly associated with the second CVR response across all regions of interest (p < 0.001), and this association was highest in the hippocampus (R2 = 0.57, p < 0.0125). This study demonstrates that it is feasible to examine individual responses associated with normocapnic and hypercapnic transition periods of a BOLD-based CVR experiment. Studying these features can provide insight on between-subject differences in CVR.

MP03-15 THE INFLUENCE OF STROKE LATERALITY ON FUNCTIONAL BRAIN ACTIVITY DURING MICTURITION: A URODYNAMIC-FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY

You have accessJournal of UrologyCME1 Apr 2023MP03-15 THE INFLUENCE OF STROKE LATERALITY ON FUNCTIONAL BRAIN ACTIVITY DURING MICTURITION: A URODYNAMIC-FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY Aidin Abedi, Veronica Stefania Montero Arcila, Luis Alejandro Morales Ojeda, Rita Jen, Priya Kohli, Nhi Ha, Sarah Ponce, David Chapman, David Ginsberg, Kay Jann, and Evgeniy Kreydin Aidin AbediAidin Abedi More articles by this author , Veronica Stefania Montero ArcilaVeronica Stefania Montero Arcila More articles by this author , Luis Alejandro Morales OjedaLuis Alejandro Morales Ojeda More articles by this author , Rita JenRita Jen More articles by this author , Priya KohliPriya Kohli More articles by this author , Nhi HaNhi Ha More articles by this author , Sarah PonceSarah Ponce More articles by this author , David ChapmanDavid Chapman More articles by this author , David GinsbergDavid Ginsberg More articles by this author , Kay JannKay Jann More articles by this author , and Evgeniy KreydinEvgeniy Kreydin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Hemispheric differences in brain function account for the differential effects of stroke laterality on various domains of cognition, sensory-motor function, and decision making. Similarly, the size and location of stroke determine the type and severity of bladder dysfunction in patients with neurogenic lower urinary tract dysfunction (NLUTD). However, the changes in functional brain activity in relation to the side of stroke are yet to be understood. This study aimed to determine the differential patterns of micturition-related neural activity in right- vs. left-sided strokes. METHODS: Patients with a history of chronic (>1yr) ischemic or hemorrhagic strokes and NLUTD were enrolled. Patients underwent urodynamic assessment while micturition-related brain activity was simultaneously assessed using functional magnetic resonance imaging with the blood-oxygen-level-dependent (BOLD) technique. Statistical parametric mapping (SPM) was used to assess the changes in BOLD signal during a 10-second period of maximum urgency. The signal intensity was compared between left- versus right-sided strokes, with age, gender, and time since stroke as covariates. Statistically significant clusters were identified using a p value of <0.001 and cluster size of >25 voxels. RESULTS: A total of 23 patients (16 men, 69.57%; mean age 53.61±9.82) were enrolled, of whom 16 (69.57%) suffered from right-sided strokes. Analysis of the BOLD signal changes during the period of maximum urgency yielded increased intensity in patients with left-sided strokes in eight areas spanning the anterior cingulate (Brodmann area 32), inferior frontal gyrus, middle frontal gyrus, and limbic area (cingulate gyrus) on the left hemisphere; frontal sub-gyral area on the right; and superior frontal gyrus (Brodmann area 8) bilaterally. Two clusters located in the left cerebellar anterior lobe and right limbic lobe (posterior cingulate) showed decreased BOLD signal in left-sided strokes compared to right-sided counterparts. CONCLUSIONS: This study demonstrated the differences in micturition-related brain activity between left- and right-sided strokes and identified ten areas of differential activity. Patients with right-sided strokes demonstrated markedly diminished brain activity in several brain regions that are known to play a role in LUT control. Consistent with the inherent functional differences across the brain hemispheres, stroke laterality is correlated with the changes in brain activation during micturition. Source of Funding: Urology Care Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e29 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aidin Abedi More articles by this author Veronica Stefania Montero Arcila More articles by this author Luis Alejandro Morales Ojeda More articles by this author Rita Jen More articles by this author Priya Kohli More articles by this author Nhi Ha More articles by this author Sarah Ponce More articles by this author David Chapman More articles by this author David Ginsberg More articles by this author Kay Jann More articles by this author Evgeniy Kreydin More articles by this author Expand All Advertisement PDF downloadLoading ...

Spectral peak areas do not vary according to spectral averaging scheme used in functional MRS experiments at 3 T with interleaved visual stimulation

Abstract Brain response to visual stimulation can be probed quantitatively using functional magnetic resonance spectroscopy (fMRS), which relies on the blood oxygenation level dependent (BOLD) contrast mechanism. BOLD effect in fMRS is associated with changes in the areas, widths, and heights of the MR spectra. This study investigated the effect of spectral averaging scheme (NEX value) on BOLD changes in the spectra. Using a visual stimulus at 8 Hz in single and interleaved stimulation paradigms, the BOLD effects in spectra acquired from the occipital brain region of three healthy volunteers (mean age ± SD = 32.7 ± 3.5 years) were compared for two fMRS data sets acquired with two NEX values (“2” and “8”) available on a 3 T MR scanner. BOLD signal changes were estimated as percentage changes in spectral areas, heights, and widths of six cerebral metabolites and water using the SAGE software package (version 7). There was a general trend of lower BOLD effects with NEX = 8 in both stimulation paradigms. In the single stimulation paradigm, NEX = 8 was associated with significantly lower N-acetyl aspartate (NAA) spectral height (p = 0.03), creatine (p = 0.04) and choline (p = 0.02) spectral widths, and NAA (p = 0.03), water (p &lt; 0.01), and glutamate (p = 0.02) spectral areas. In the interleaved stimulation paradigm, NEX = 8 was associated with significantly lower glutamate spectral height (p = 0.02), water (p = 0.03), and glutamine (p = 0.03) spectral widths, but there was no significant difference in all spectral areas between the two NEX values. Even though the two NEX values offered some differences in observable BOLD effects, their spectral areas were not significantly different in the interleaved visual stimulation experiments.

Ultra-high-field pharmacological functional MRI of dopamine D1 receptor-related interventions in anesthetized rats.

The dopamine D1 receptor (D1R) is associated with schizophrenia, Parkinson's disease, and attention deficit hyperactivity disorder. Although the receptor is considered a therapeutic target for these diseases, its neurophysiological function has not been fully elucidated. Pharmacological functional MRI (phfMRI) has been used to evaluate regional brain hemodynamic changes induced by neurovascular coupling resulting from pharmacological interventions, thus phfMRI studies can be used to help understand the neurophysiological function of specific receptors. Herein, the blood oxygenation level-dependent (BOLD) signal changes associated with D1R action in anesthetized rats was investigated by using a preclinical ultra-high-field 11.7-T MRI scanner. PhfMRI was performed before and after administration of the D1-like receptor agonist (SKF82958), antagonist (SCH39166), or physiological saline subcutaneously. Compared to saline, the D1-agonist induced a BOLD signal increase in the striatum, thalamus, prefrontal cortex, and cerebellum. At the same time, the D1-antagonist reduced the BOLD signal in the striatum, thalamus, and cerebellum by evaluating temporal profiles. PhfMRI detected D1R-related BOLD signal changes in the brain regions associated with high expression of D1R. We also measured the early expression of c-fos at the mRNA level to evaluate the effects of SKF82958 and isoflurane anesthesia on neuronal activity. Regardless of the presence of isoflurane anesthesia, c-fos expression level was increased in the region where positive BOLD responses were observed with administration of SKF82958. These findings demonstrated that phfMRI could be used to identify the effects of direct D1 blockade on physiological brain functions and also for neurophysiological assessment of dopamine receptor functions in living animals.

Increased pain unpleasantness and pain-related fMRI activation in the periaqueductal gray in Alzheimer's disease.

Pain continues to be underrecognized and undertreated in people with Alzheimer's disease (AD). The periaqueductal gray (PAG) is essential to pain processing and modulation yet is damaged by AD. While evidence exists of altered neural processing of pain in AD, there has not been a focused investigation of the PAG during pain in people with AD. To investigate the role of the PAG in sensory and affective pain processing for people living with AD. Participants from a larger study completed pain psychophysics assessments and then a perceptually-matched heat pain task (warmth, mild, and moderate pain) during a functional MRI scan. In this cross-sectional study, we examined blood oxygenation level-dependent (BOLD) responses in the PAG and other pain-related regions in participants with AD (n = 18) and cognitively intact older adults (age- and sex-matched, n = 18). Associations of BOLD percent signal change and psychophysics were also examined. There were significant main effects of AD status on the temperature needed to reach each perception of warmth or pain, where people with AD reached higher temperatures. Furthermore, participants with AD rated mild and moderate pain as more unpleasant than controls. PAG BOLD activation was greater in AD relative to controls during warmth and mild pain percepts. No significant differences were found for moderate pain or in other regions of interest. Greater PAG activation during mild pain was associated with higher affective/unpleasantness ratings of mild pain in participants with AD but not in controls. Results suggest a role for the PAG in altered pain responses in people with AD. The PAG is the primary source of endogenous opioid pain inhibition in the neuroaxis, thus, altered PAG function in AD suggests possible changes in descending pain inhibitory circuits. People with AD may have a greater risk of suffering from pain compared to cognitively intact older adults.