Neurovascular Coupling Research Articles

Neurovascular coupling: a review of spontaneous neocortical dynamics linking neuronal activity to hemodynamics and what we have learned from the rodent brain.

The brain is a complex neural network whose functional dynamics offer valuable insights into behavioral performance and health. Advances in fMRI have provided a unique window into studying human brain networks, providing us with a powerful tool for clinical research. Yet many questions about the underlying correlates between spontaneous fMRI and neural activity remain poorly understood, limiting the impact of this research. Cross-species studies have proven essential in deepening our understanding of how neuronal activity is coupled to increases in local cerebral blood flow, changes in blood oxygenation, and the measured fMRI signal. In this article, we review some fundamental mechanisms implicated in neurovascular coupling. We then examine neurovascular coupling within the context of spontaneous cortical functional networks and their dynamics, summarizing key findings from mechanistic studies in rodents. In doing so we highlight the nuances of the neurovascular coupling which ultimately influences the interpretation of derived hemodynamic functional networks, their dynamics, and the neural underpinnings they represent.

Control of neurovascular coupling by ATP-sensitive potassium channels.

Regional blood flow within the brain is tightly coupled to regional neuronal activity, a process known as neurovascular coupling (NVC). In this study, we demonstrate the striking role of SUR2- and Kir6.1-dependent ATP-sensitive potassium (KATP) channels in control of NVC in the sensory cortex of conscious mice, in response to mechanical stimuli. We demonstrate that either globally increased (pinacidil-activated) or decreased (glibenclamide-inhibited) KATP activity markedly disrupts NVC; pinacidil-activation is capable of completely abolishing stimulus-evoked cortical hemodynamic responses, while glibenclamide slows and reduces the response. The response is similarly slowed and reduced in SUR2 KO animals, while animals expressing gain-of-function (GOF) mutations in Kir6.1, which underlie Cantú syndrome, exhibit baseline reduction of NVC as well as increased sensitivity to pinacidil. In revealing the dramatic effects of either increasing or decreasing SUR2/Kir6.1-dependent KATP activity on NVC, whether pharmacologically or genetically induced, the study has important implications both for monogenic KATP channel diseases and for more common brain pathologies.

Resting state BOLD-perfusion coupling patterns using multiband multi-echo pseudo-continuous arterial spin label imaging

The alteration of neurovascular coupling (NVC), where acute localized blood flow increases following neural activity, plays a key role in several neurovascular processes including aging and neurodegeneration. While not equivalent to NVC, the coupling between simultaneously measured cerebral blood flow (CBF) with arterial spin labeling (ASL) and blood oxygenation dependent (BOLD) signals, can also be affected. Moreover, the acquisition of BOLD data allows the assessment of resting state (RS) fMRI metrics. In this study a multiband, multi-echo (MBME) pseudo-continuous ASL (pCASL) sequence was used to collect simultaneous BOLD and ASL data in a group of healthy control subjects, and the patterns of BOLD-CBF coupling were evaluated. Coupling was also correlated with the BOLD RS measures. The variability, reproducibility, and reliability of the metrics were also computed in a multi-session subgroup. Areas of higher coupling were observed in the visual, motor, parietal, and frontal cortices and corresponded to major brain networks. Areas of significant correlation between coupling and BOLD RS measures corresponded to areas of heightened coupling. Higher variability and lower reliability were found for coupling metrics compared to BOLD RS metrics. These results indicate BOLD-CBF coupling metrics may be useful for studying neurovascular physiology.

MiRNAs, piRNAs, and lncRNAs: A Triad of Non-Coding RNAs Regulating The Neurovascular Unit in Diabetic Retinopathy And Their Therapeutic Potentials.

Diabetic Retinopathy (DR), a leading complication of diabetes mellitus, has long been considered as a microvascular disease of the retina. However, recent evidence suggests that DR is a neurovascular disease, characterized by the degeneration of retinal neural tissue and microvascular abnormalities encompassing ischemia, neovascularization, and blood-retinal barrier breakdown, ultimately leading to blindness. The intricate relationship between the retina and vascular cells constitutes a neurovascular unit, a multi-cellular framework of retinal neurons, glial cells, immune cells, and vascular cells, which facilitates neurovascular coupling, linking neuronal activity to blood flow. These interconnections between the neurovascular components get compromised due to hyperglycemia and are further associated with the progression of DR early on in the disease. As a result, therapeutic approaches are needed to avert the advancement of DR by acting at its initial stage to delay or prevent the pathogenesis. Non-coding RNAs (ncRNAs) such as microRNAs, piwi-interacting RNAs, and long non-coding RNAs regulate various cellular components in the neurovascular unit. These ncRNAs are key regulators of neurodegeneration, apoptosis, inflammation, and oxidative stress in DR. In this review, research related to alterations in the expression of ncRNAs and, correspondingly, their effect on the disintegration of the neurovascular coupling will be discussed briefly to understand the potential of ncRNAs as therapeutic targets for treating this debilitating disease.

Characterizing astrocyte-mediated neurovascular coupling by combining optogenetics and biophysical modeling.

Vasoactive signaling from astrocytes is an important contributor to the neurovascular coupling (NVC), which aims at providing energy to neurons during brain activation by increasing blood perfusion in the surrounding vasculature. Pharmacological manipulations have been previously combined with experimental techniques (e.g., transgenic mice, uncaging, and multiphoton microscopy) and stimulation paradigms to isolate in vivo individual pathways of the astrocyte-mediated NVC. Unfortunately, these pathways are highly nonlinear and non-additive. To separate these pathways in a unified framework, we combine a comprehensive biophysical model of vasoactive signaling from astrocytes with a unique optogenetic stimulation method that selectively induces astrocytic Ca2+ signaling in a large population of astrocytes. We also use a sensitivity analysis and an optimization technique to estimate key model parameters. Optogenetically-induced Ca2+ signals in astrocytes cause a cerebral blood flow (CBF) response with two major components. Component-1 was rapid and smaller (ΔCBF∼13%, 18 seconds), while component-2 was slowest and highest (ΔCBF ∼18%, 45 seconds). The proposed biophysical model was adequate in reproducing component-2, which was validated with a pharmacological manipulation. Model's predictions were not in contradiction with previous studies. Finally, we discussed scenarios accounting for the existence of component-1, which once validated might be included in our model.

Periodontitis Increases Gingival, Serum and Hippocampus β-Amyloid Expressions but Reduces Neurovascular Coupling in Basilar Artery of Rats.

Neurodegenerative diseases are characterized by early increased beta-amyloid (Aβ) and decreased cerebrovascular reactivity. We investigated Aβ in gingiva, serum or hippocampus and neurovascular reactivity in basilar artery (BA) of periodontitis rats, to test the impact of Aβ on BA vasoreactivity exvivo. Periodontitis was induced in 32 rats using silk-ligation. Rats were sacrificed at weeks 0, 1, 2 and 4. Gingival TNF-α, IL-1β and Aβ were quantified via immunoblotting. Alveolar bone destruction was examined by micro-computed tomography. Serum and hippocampus Aβ values were measured by enzyme-linked immunosorbent assay and fluorescence staining, respectively. Vasoreactivity was measured by myography on isolated BA. From Week 1, gingival TNF-α and IL-1β and bone destruction increased. Gingiva, serum and hippocampus Aβ values increased from Week 2. Nicotine-induced BA relaxation declined from Week 2, while acetylcholine-induced relaxation decreased by Week 4. Bone loss correlated with Aβ and nicotine-induced relaxation. Correlations were observed between Aβs in tissues, between two induced BA relaxations and between Aβ expressions and the induced relaxations. Exvivo, Aβ reduced nicotine- and isoproterenol-induced relaxations but not electrical stimulated relaxation. Periodontitis may increase Aβ expressions and reduce BA neurovascular reactivity, with Aβ contributing to this abnormal neurovascular coupling.

Unveiling the Interplay: Neurovascular Coupling, Astrocytes and G Protein-Coupled Receptors in Alzheimer’s Disease

Unveiling the Interplay: Neurovascular Coupling, Astrocytes and G Protein-Coupled Receptors in Alzheimer’s Disease

Unlocking the potential of photobiomodulation therapy for brain neurovascular coupling: The biological effects and medical applications.

Photobiomodulation (PBM) therapy stands as an innovative neurostimulation modality that has demonstrated both efficacy and safety in improving brain function. This therapy exerts multifaceted influences on neurons, blood vessels, and their intricate interplay known as neurovascular coupling (NVC). Growing evidence indicates that NVC may present a promising target for PBM intervention. However, the detailed mechanisms underlying its therapeutic benefits remain to be fully understood. This review aims to elucidate the potential metabolic pathways and signaling cascades involved in the modulatory effects of PBM, while also exploring the extensive repertoire of PBM applications in neurologic and psychiatric conditions. The prospects of PBM within the realm of NVC investigation are intensively considered, providing deeper insights into the powerful capabilities of PBM therapy and its potential to revolutionize neurostimulation treatments.

Contralateral Neurovascular Coupling in Patients with Ischemic Stroke After Endovascular Thrombectomy.

Neurovascular coupling (NVC) refers to the process of aligning cerebral blood flow with neuronal metabolic demand. This study explores the potential of contralateral NVC-linking neural electrical activity on the stroke side with cerebral blood flow velocity (CBFV) on the contralesional side-as a marker of physiological function of the brain. Our aim was to examine the association between contralateral NVC and neurological outcomes in patients with ischemic stroke following endovascular thrombectomy. We concurrently recorded the CBFVs of the middle cerebral arteries and electroencephalographic (EEG) signals of patients after endovascular thrombectomy. We employed phase-amplitude cross-frequency coupling to quantify the contralateral coupling between EEG activity on the stroke side and CBFV on the contralesional side. Key neurological outcomes were measured, including changes in National Institute of Health Stroke Scale (NIHSS) scores, infarct volume progression over 7days, and modified Rankin Scale scores at 90days. A total of 52 study participants were enrolled in our study (mean age 61.5 ± 10.4years; 90.4% male; median preprocedural NIHSS score 14 [interquartile range 10-17]). We successfully computed contralateral NVC in 48 study participants. A significant association emerged between contralateral coupling and improvements in NIHSS scores over 7days (theta band, P = 0.030) and in infarct volume progression (delta band, P = 0.001; theta band, P = 0.013). Stronger contralateral NVC in the delta and theta bands correlated with better outcomes at 90days (adjusted odds ratio for delta 7.53 [95% confidence interval 1.13-50.30], P = 0.037; adjusted odds ratio for theta 6.36 [95% confidence interval 1.09-37.01], P = 0.039). A better contralateral coupling between stroke-side EEG and contralesional CBFV is associated with favorable neurological outcomes, suggesting that contralateral NVC analysis may aid in assessing brain function after recanalization. Replication with a deeper understanding of the mechanisms is needed before clinical translation.

Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health.

Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of SARS-CoV-2 infection, affecting approximately 10% to over 30% of those infected. It presents a significant clinical challenge, notably due to pronounced neurocognitive symptoms such as brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing to a central role of cerebromicrovascular dysfunction. This review investigates key pathophysiological mechanisms contributing to cerebrovascular dysfunction in long COVID and their impacts on brain health. We discuss how endothelial tropism of SARS-CoV-2 and direct vascular infection trigger endothelial dysfunction, impaired neurovascular coupling, and blood-brain barrier disruption, resulting in compromised cerebral perfusion. Furthermore, the infection appears to induce mitochondrial dysfunction, enhancing oxidative stress and inflammation within cerebral endothelial cells. Autoantibody formation following infection also potentially exacerbates neurovascular injury, contributing to chronic vascular inflammation and ongoing blood-brain barrier compromise. These factors collectively contribute to the emergence of white matter hyperintensities, promote amyloid pathology, and may accelerate neurodegenerative processes, including Alzheimer's disease. This review also emphasizes the critical role of advanced imaging techniques in assessing cerebromicrovascular health and the need for targeted interventions to address these cerebrovascular complications. A deeper understanding of the cerebrovascular mechanisms of long COVID is essential to advance targeted treatments and mitigate its long-term neurocognitive consequences.

Combining InVivo Two-Photon and Laser Speckle Microscopy With the ExVivo Capillary-Parenchymal Arteriole Preparation as a Novel Approach to Study Neurovascular Coupling.

Cerebral blood flow (CBF) decline is increasingly recognized as an area of importance for targeting neurodegenerative disorders, yet full understanding of the mechanisms that underlie CBF changes are lacking. Animal models are crucial for expanding our knowledge as methods for studying global CBF and neurovascular coupling in humans are limited and require expensive specialized scanners. Use of appropriate animal models can increase our understanding of cerebrovascular function, so we have combined chronic cranial windows with invivo two-photon and laser speckle microscopy and exvivo capillary-parenchymal arteriole (CaPA) preparations. Chronic cranial windows allow for longitudinal direct observation of the cerebral microvasculature and surrounding parenchyma while the CaPA preparation can assess capillary and arteriole function in isolation of the neuronal tissue. Here, we found that extra-dural cranial windows and related imaging protocols do not affect vascular function in the CaPA preparation. Cortical vessels from animals that have undergone imaging can therefore be taken to discover physiological alterations in the cerebral vasculature that contribute to any observed invivo changes. This approach will enhance neurodegenerative research with the benefit of limiting animal usage.

Cardiorespiratory dynamics in the brain: Review on the significance of cardiovascular and respiratory correlates in functional MRI signal.

Cardiorespiratory signals have long been treated as "noise" in functional magnetic resonance imaging (fMRI) research, with the goal of minimizing their impact to isolate neural activity. However, there is a growing recognition that these signals, once seen as confounding variables, provide valuable insights into brain function and overall health. This shift reflects the dynamic interaction between the cardiovascular, respiratory, and neural systems, which together support brain activity. In this review, we explore the role of cardiorespiratory dynamics-such as heart rate variability (HRV), respiratory sinus arrhythmia (RSA), and changes in blood flow, oxygenation, and carbon dioxide levels-embedded within fMRI signals. These physiological signals reflect critical aspects of neurovascular coupling and are influenced by factors such as physiological stress, breathing patterns, and age-related changes. We also discuss the complexities of distinguishing these signals from neuronal activity in fMRI data, given their significant contribution to signal variability and interactions with cerebrospinal fluid (CSF). Recognizing the influence of these cardiorespiratory dynamics is crucial for improving the interpretation of fMRI data, shedding light on heart-brain and respiratory-brain connections, and enhancing our understanding of circulation, oxygen delivery, and waste elimination within the brain.

Comparative analysis of intraoperative thermal and optical imaging for identification of the human primary sensory cortex.

The precise identification and preservation of functional brain areas during neurosurgery are crucial for optimizing surgical outcomes and minimizing postoperative deficits. Intraoperative imaging plays a vital role in this context, offering insights that guide surgeons in protecting critical cortical regions. We aim to evaluate and compare the efficacy of intraoperative thermal imaging (ITI) and intraoperative optical imaging (IOI) in detecting the primary somatosensory cortex, providing a detailed assessment of their potential integration into surgical practice. Data from nine patients undergoing tumor resection in the region of the somatosensory cortex were analyzed. Both IOI and ITI were employed simultaneously, with a specific focus on the areas identified as the primary somatosensory cortex (S1 region). The methodologies included a combination of imaging techniques during distinct phases of rest and stimulation, confirmed by electrophysiological monitoring of somatosensory evoked potentials to verify the functional areas identified by both imaging methods. The data were analyzed using a Fourier-based analytical framework to distinguish physiological signals from background noise. Both ITI and IOI successfully generated reliable activity maps following median nerve stimulation. IOI showed greater consistency across various clinical scenarios, including those involving cortical tumors. Quantitative analysis revealed that IOI could more effectively differentiate genuine neuronal activity from artifacts compared with ITI, which was occasionally prone to false positives in the presence of cortical abnormalities. ITI and IOI produce comparable functional maps with moderate agreement in Cohen's kappa values. Their distinct physiological mechanisms suggest complementary use in specific clinical scenarios, such as cortical tumors or impaired neurovascular coupling. IOI excels in spatial resolution and mapping reliability, whereas ITI provides additional insights into metabolic changes and tissue properties, especially in pathological areas. Combined, these modalities could enhance the understanding and analysis of functional and pathological processes in complex neurosurgical cases.

Altered neurovascular coupling and structure-function coupling in Moyamoya disease affect postoperative collateral formation

Chronic ischemia in moyamoya disease (MMD) impaired white matter microstructure and neural functional network. However, the coupling between cerebral blood flow (CBF) and functional connectivity and the association between structural and functional network are largely unknown. 38 MMD patients and 20 sex/age-matched healthy controls (HC) were included for T1-weighted imaging, arterial spin labeling imaging, resting-state functional MRI and diffusion tensor imaging. All patients had preoperative and postoperative digital subtraction angiography. Upon constructing the structural connectivity (SC) and functional connectivity (FC) networks, the SC-FC coupling was calculated. After obtaining the graph theoretical parameters, neurovascular coupling represented the spatial correlation between node degree centrality (DC) of functional networks and CBF. The CBF-DC coupling and SC-FC coupling were compared between MMD and HC groups. We further analyzed the correlation between coupling indexes and cognitive scores, as well as postoperative collateral formation. Compared with HC, CBF-DC coupling was decreased in MMD (p = 0.021), especially in the parietal lobe (p = 0.047). SC-FC coupling in MMD decreased in frontal, occipital, and subcortical regions. Cognitive scores were correlated with the CBF-DC coupling in frontal lobes (r = 0.394, p = 0.029) and SC-FC coupling (r = 0.397, p = 0.027). The CBF-DC coupling of patients with good postoperative collateral formation was higher (p = 0.041). Overall, neurovascular decoupling and structure-functional decoupling at the cortical level may be the underlying neuropathological mechanisms of MMD.

Neurovascular unit impairment in iron deficiency anemia.

Iron is one of the crucial elements for CNS development and function and its deficiency (ID) is the most common worldwide nutrient deficit in the world. Iron deficiency anemia (IDA) in pregnant women and infants is a worldwide health problem due to its high prevalence and its irreversible long-lasting effects on brain development. Even with iron supplementation, IDA during pregnancy and/or breastfeeding can result in irreversible cognitive, motor, and behavioral impairments. The neurovascular unit (NVU) plays an important role in iron transport within the CNS as well as in the blood brain-barrier (BBB) formation and maturation, vasculogenesis/angiogenesis, neurovascular coupling and metabolic waste clearance. In animal models of IDA, significant changes have been observed at the capillary level, including alterations in iron transport, vasculogenesis, astrocyte endfeet, and pericytes. Despite these findings, the role of the NVU in IDA remains poorly understood. This review summarizes the potential effects of ID/IDA on brain development, myelination and neuronal function and discusses the role of NVU cells in iron metabolism, BBB, vasculogenesis/angiogenesis, neurovascular coupling and metabolic waste clearance. Furthermore, it emphasizes the need to view the NVU as a whole and as a potential target for ID/IDA. However, it remains unclear to what extent NVU alterations contribute to neuronal dysfunction, myelination abnormalities, and synaptic disturbances described in IDA.

Cortical hemodynamics of electrographic status epilepticus in the critically ill.

The pathophysiological mechanisms of status epilepticus (SE) underlying potential brain injury remain largely unclear. This study aims to employ functional near-infrared spectroscopy (fNIRS) combined with video-electroencephalography (vEEG) to monitor brain hemodynamics continuously and non-invasively in critically ill adult patients experiencing electrographic SE. Our primary focus is to investigate neurovascular coupling and cerebrovascular changes associated with seizures, particularly during recurring and/or prolonged episodes. Eleven critically ill adult patients underwent simultaneous vEEG-fNIRS with large cortical coverage. Data from seven patients with identified electrographic SE were analyzed. The timing of recorded seizures was marked using standardized critical care EEG terminology. A general linear model was employed to extract the hemodynamic response to seizures from the fNIRS recordings. Linear mixed-effects models were utilized to correlate hemodynamic responses with seizure characteristics. A total of >200 h of monitoring and >1000 seizures were recorded. In most patients, an increase in oxyhemoglobin (HbO) and a decrease in deoxyhemoglobin (HbR) were observed during shorter-duration seizures. Although a similar response could also be seen initially for longer-duration seizures, this hemodynamic change was often followed by a progressive decline in HbO concentration and an increase in HbR. At the systemic level, no significant difference in peripheral oxygenation occurred during seizures, and only small changes in mean arterial blood pressure and heart rate occurred in four and two patients, respectively. We demonstrate the feasibility of using multichannel vEEG-fNIRS to measure the hemodynamic changes associated with electrographic seizures in critically ill adult patients. Our findings suggest that disrupted neurovascular coupling is more prevalent during prolonged seizures compared to recurrent short-duration seizures. This research provides valuable insights into the dynamic interplay between neuronal activity and hemodynamics during critical care seizures.

Brain glucose metabolism: Role of nitric oxide.

One possible reason for failure in achieving optimal glycemic control in patients with type 2 diabetes (T2D) is that less attention has been paid to the brain, a fundamental player in glucose homeostasis, that consumes about 25% of total glucose utilization. In addition, animal and human studies indicate that nitric oxide (NO) is a critical player in glucose metabolism. NO synthesis from L-arginine is lower in patients with T2D, and endothelial NO synthase (eNOS)-derived NO bioavailability is lower in T2D. NO in the nervous system plays a role in neurovascular coupling (NVC) and the hypothalamic control of glucose sensing and energy homeostasis, influencing glucose utilization. This review explores NO's role in the brain's glucose metabolism. Literature indicates that glucose metabolism is different between neurons and astrocytes. Unlike neurons, astrocytes have a higher rate of glycolysis and a greater ability for lactate production. Astrocytes produce a greater amount of NO than neurons. NO inhibits mitochondrial respiration in both neurons and astrocytes and decreases intracellular ATP. NO-induced inhibition of mitochondrial respiration in neurons is not accompanied by compensatory glycolysis because phosphofructokinase 2.3 (PFK2.3), the most potent activator of PFK1 and thus glycolysis, is subjected to ubiquitylation and proteasomal degradation by cadherin-1 (Cdh1)-activated anaphase-promoting complex/cyclosome (APC/C), which leads to a low glycolytic rate in neurons. In astrocytes, NO inhibits mitochondrial respiration, but astrocytes display compensatory glycolysis by activating the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway.

COVID-19 Exacerbates Neurovascular Uncoupling and Contributes to Endothelial Dysfunction in Patients with Mild Cognitive Impairment.

Mild cognitive impairment (MCI) affects nearly 20% of older adults worldwide, with no targetable interventions for prevention. COVID-19 adversely affects cognition, with >70% of older adults with Long COVID presenting with cognitive complaints. Neurovascular coupling (NVC), an essential mechanism of cognitive function, declines with aging and is further attenuated in neurocognitive disorders. The effect of COVID-19 on NVC responses has yet to be addressed in older adults who are vulnerable to dementia progression. Participants with MCI and a history of COVID-19 (COV+, N = 31) and MCI participants with no history of infection (COV- N = 11) participated in this cross-sectional study to determine if COVID-19 affects cerebrocortical NVC responses and vascular function. Functional near-infrared spectroscopy was used to measure cerebrocortical NVC responses, and endothelial function was assessed via insonation of the brachial artery during a flow-mediated dilation protocol. NVC responses were elicited by the working memory n-back paradigm. NVC in the left dorsolateral prefrontal cortex and endothelial function was decreased in the COV+ group compared to the COV- group. These data provide mechanistic insight into how COVID-19 may exacerbate long-term cognitive sequela seen in older adults, highlighting the urgent need for further research and clinical trials to explore novel therapeutic interventions aimed at preserving/restoring NVC.

Global Impact of Aging on the Hemodynamic Response Function in the Gray Matter of Human Cerebral Cortex.

In functional magnetic resonance imaging, the hemodynamic response function (HRF) is a stereotypical response to local changes in cerebral hemodynamics and oxygen metabolism due to briefly (< 4 s) evoked neural activity. Accordingly, the HRF is often used as an impulse response with the assumption of linearity in data analysis. In cognitive aging studies, it has been very common to interpret differences in brain activation as age-related changes in neural activity. Contrary to this assumption, however, evidence has accrued that normal aging may also significantly affect the vasculature, thereby affecting cerebral hemodynamics and metabolism, confounding interpretation of fMRI cognitive aging studies. In this study, use was made of a multisensory task to evoke the HRF in ~87% of cerebral cortex in cognitively intact adults with ages ranging from 22 to 75 years. This widespread activation enabled us to investigate age trends in the spatial distributions of HRF characteristics within the majority of cortical gray matter, which we termed as global age trends. The task evoked both positive and negative HRFs, which were characterized using model-free parameters in native-space coordinates. We found significant global age trends in the distributions of HRF parameters in terms of both amplitudes (e.g., peak amplitude and contrast-to-noise ratio) and temporal dynamics (e.g., full-width-at-half-maximum). Our findings offer insight into how age-dependent changes affect neurovascular coupling and show promise for use of HRF parameters as non-invasive indicators for age-related pathology.

Evaluation of Neurovascular Coupling in Early-Onset and Late-Onset Epilepsy of Unknown Etiology.

Previous studies have shown neurovascular coupling (NVC) dysfunction in epilepsy, suggesting its role in the pathological mechanisms. However, it remains unclear whether NVC abnormalities exist in epilepsy of unknown etiology (EU). To integrate multiparametric MRI to assess NVC and its relationship with cognition in early-onset and late-onset EU patients. Prospective. Ninety-six EU patients (46 early-onset, M/F = 20/26; 50 late-onset, M/F = 29/21) and 60 healthy controls (HCs, M/F = 25/35). 3.0 T, resting-state gradient echo-planar imaging, pseudo-continuous arterial spin labeling (pc-ASL), and T1-weighted brain volume sequence. Functional MRI data were analyzed to assess intrinsic brain activity including amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS), while pc-ASL provided cerebral blood flow (CBF) measurements. Coupling correlation coefficients and ratios of CBF to neural activity were calculated to evaluate global and regional NVC. Two-sample t-test, Analysis of Variance, Kruskal-Wallis test, Chi-square test, Analysis of Covariance, family-wise error/Bonferroni correction, partial correlation analyses. Statistical significance was defined as P < 0.05. Whole-brain analysis revealed increased ALFF values in both patient groups' left precentral and postcentral gyri. Both patient groups had lower global NVC coefficients than HCs, with reduced CBF-ALFF (0.28 vs. 0.30), CBF-fALFF (0.43 vs. 0.45), and CBF-ReHo (0.40 vs. 0.41) in early-onset patients, and lower CBF-fALFF (0.38 vs. 0.45) and CBF-ReHo (0.32 vs. 0.41) in late-onset patients. Regional analysis showed significantly decreased CBF/ALFF ratios in the left precentral and postcentral gyri (T = 3.85 to 5.33). Reduced global NVC in early-onset patients was significantly associated with poorer executive function (r = 0.323), while global coupling in late-onset patients was negatively correlated with disease duration (r = -0.348 to -0.426). This study showed abnormal global and regional NVC in both early-onset and late-onset EU patients, emphasizing the potential role of NVC in the pathophysiological mechanisms of EU. 1 TECHNICAL EFFICACY: Stage 1.