Study protocol for a pilot clinical trial to understand neural mechanisms of response to a psychological treatment for pain and anxiety in pediatric functional abdominal pain disorders (FAPD).

BACKGROUND: Functional abdominal pain disorders (FAPD) are the most common chronic pain conditions of childhood and are made worse by co-occurring anxiety. Our research team found that the Aim to Decrease Pain and Anxiety Treatment (ADAPT), a six-session coping skills program using cognitive behavioral therapy strategies, was effective in improving pain-related symptoms and anxiety symptoms compared to standard care. In follow-up, this current randomized clinical trial (RCT) aims to test potential neural mechanisms underlying the effect of ADAPT. Specifically, this two-arm RCT will explore changes in amygdalar functional connectivity (primary outcome) following the ADAPT protocol during the water loading symptom provocation task (WL-SPT). Secondary (e.g., changes in regional cerebral blood flow via pulsed arterial spin labeling MRI) and exploratory (e.g., the association between the changes in functional connectivity and clinical symptoms) outcomes will also be investigated. METHODS: We will include patients ages 11 to 16 years presenting to outpatient pediatric gastroenterology care at a midwestern children's hospital with a diagnosis of FAPD plus evidence of clinical anxiety based on a validated screening tool (the Generalized Anxiety Disorder-7 [GAD-7] measure). Eligible participants will undergo baseline neuroimaging involving the WL-SPT, and assessment of self-reported pain, anxiety, and additional symptoms, prior to being randomized to a six-week remotely delivered ADAPT program plus standard medical care or standard medical care alone (waitlist). Thereafter, subjects will complete a post assessment neuroimaging visit similar in nature to their first visit. CONCLUSIONS: This small scale RCT aims to increase understanding of potential neural mechanisms of response to ADAPT. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT03518216.

Association of Blood Pressure With Brain White Matter Microstructural Integrity Assessed With MRI Diffusion Tensor Imaging in Healthy Young Adults.

BACKGROUND: High blood pressure (BP) in middle-aged and older adults is associated with a brain white matter (WM) microstructural abnormality. However, little evidence is available in healthy young adults. We investigated the associations between high BP and WM microstructural integrity in young adults. METHODS: This study included 1015 healthy young adults (542 women, 22-37 years) from the Human Connectome Project. Brachial systolic and diastolic BP were measured using a semiautomatic or manual sphygmomanometer. Diffusion-weighted magnetic resonance imaging was acquired to obtain diffusion tensor imaging metrics of free water (FW) content, FW-corrected WM fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity. Using whole-brain voxel-wise linear regression models and ANCOVA, we examined associations of BP and hypertension stage with diffusion tensor imaging metrics after adjusting for age, sex, education, body mass index, smoking status, alcohol consumption history, and differences in the b value used for diffusion magnetic resonance imaging. RESULTS: Systolic and diastolic BP of the sample (mean±SD) were 122.8±13.0 and 76.0±9.9 mm Hg, respectively. Associations of BP with diffusion tensor imaging metrics revealed regional heterogeneity for FW-corrected fractional anisotropy. High BP and high hypertension stage were associated with higher FW and lower FW-corrected axial diffusivity, FW-corrected radial diffusivity, and FW-corrected mean diffusivity. Moreover, associations of high diastolic BP and hypertension stage with high FW were found only in men not in women. CONCLUSIONS: High BP in young adults is associated with altered brain WM microstructural integrity, suggesting that high BP may have damaging effects on brain WM microstructural integrity in early adulthood, particularly in men.

Causalized convergent cross-mapping and its approximate equivalence with directed information in causality analysis.

Convergent cross-mapping (CCM) has attracted increased attention recently due to its capability to detect causality in nonseparable systems under deterministic settings, which may not be covered by the traditional Granger causality. From an information-theoretic perspective, causality is often characterized as the directed information (DI) flowing from one side to the other. As information is essentially nondeterministic, a natural question is: does CCM measure DI flow? Here, we first causalize CCM so that it aligns with the presumption in causality analysis-the future values of one process cannot influence the past of the other, and then establish and validate the approximate equivalence of causalized CCM (cCCM) and DI under Gaussian variables through both theoretical derivations and fMRI-based brain network causality analysis. Our simulation result indicates that, in general, cCCM tends to be more robust than DI in causality detection. The underlying argument is that DI relies heavily on probability estimation, which is sensitive to data size as well as digitization procedures; cCCM, on the other hand, gets around this problem through geometric cross-mapping between the manifolds involved. Overall, our analysis demonstrates that cross-mapping provides an alternative way to evaluate DI and is potentially an effective technique for identifying both linear and nonlinear causal coupling in brain neural networks and other settings, either random or deterministic, or both.

Ascending aortic impedance in young endurance athletes: a time-resolved phase-contrast MRI study.

Ventricular-vascular coupling in endurance athletes remains incompletely understood. The purpose of this study was to determine the ascending aortic impedance in endurance athletes and explore its associations with traditional cardiovascular measurements. In 15 young male endurance runners and 19 young healthy men, time-resolved (CINE) two-dimensional (2-D) phase-contrast MRI quantified the ascending aortic flow while the pressure waveform was simultaneously collected via a generalized transfer function. The aortic impedance modulus and phase were calculated in the frequency domain while characteristic impedance (ZcF) was calculated by averaging moduli between the 4th and 8th heart rate (HR) harmonics. Stroke volume (SV), left ventricular (LV) morphometry, double product, aortic compliance, and total peripheral resistance (TPR) were also measured. Endurance athletes had higher SV, slower HR, greater LV end-diastolic volume and mass, and lower double product than sedentary participants (all P < 0.05). ZcF was significantly lower in athletes than in sedentary participants (73.3 ± 19.2 vs. 93.4 ± 19.0 dyn·s/cm5, P = 0.005). Furthermore, ZcF was negatively correlated with SV (r = -0.691) and aortic compliance (r = -0.601) but was positively correlated with double product (r = 0.445) and TPR (r = 0.458; all P < 0.05). Multivariate analysis revealed that ZcF was the strongest predictor of SV followed by TPR and HR (adjusted R2 = 0.788, P < 0.001). Therefore, our findings collectively suggest that LV afterload quantified by aortic ZcF is significantly lower in endurance athletes than in sedentary adults. The lower pulsatile LV afterload may contribute to greater SV in endurance athletes.NEW & NOTEWORTHY This is the first study to investigate aortic impedance with the noninvasive, simultaneous recordings of aortic pressure using SphygmoCor XCEL and flow using phase-contrast MRI. We found that the characteristic impedance (Zc) is significantly lower in endurance athletes than sedentary adults, is the strongest predictor of stroke volume (SV), and is inversely associated with aortic compliance. These findings suggest that aortic impedance is a key determinant of the ventricular-vascular coupling adapted to long-term training in endurance athletes.

Novel inductively coupled ear-bars (ICEs) to enhance restored fMRI signal from susceptibility compensation in rats.

Functional magnetic resonance imaging faces inherent challenges when applied to deep-brain areas in rodents, e.g. entorhinal cortex, due to the signal loss near the ear cavities induced by susceptibility artifacts and reduced sensitivity induced by the long distance from the surface array coil. Given the pivotal roles of deep brain regions in various diseases, optimized imaging techniques are needed. To mitigate susceptibility-induced signal losses, we introduced baby cream into the middle ear. To enhance the detection sensitivity of deep brain regions, we implemented inductively coupled ear-bars, resulting in approximately a 2-fold increase in sensitivity in entorhinal cortex. Notably, the inductively coupled ear-bar can be seamlessly integrated as an add-on device, without necessitating modifications to the scanner interface. To underscore the versatility of inductively coupled ear-bars, we conducted echo-planner imaging-based task functional magnetic resonance imaging in rats modeling Alzheimer's disease. As a proof of concept, we also demonstrated resting-state-functional magnetic resonance imaging connectivity maps originating from the left entorhinal cortex-a central hub for memory and navigation networks-to amygdala hippocampal area, Insular Cortex, Prelimbic Systems, Cingulate Cortex, Secondary Visual Cortex, and Motor Cortex. This work demonstrates an optimized procedure for acquiring large-scale networks emanating from a previously challenging seed region by conventional magnetic resonance imaging detectors, thereby facilitating improved observation of functional magnetic resonance imaging outcomes.

Recruitment methods and yield rates for a multisite clinical trial exploring risk reduction for Alzheimer's disease (rrAD).

INTRODUCTION: The risk reduction for Alzheimer's disease (rrAD) trial was a multisite clinical trial to assess exercise and intensive vascular pharmacological treatment on cognitive function in community-dwelling older adults at increased risk for Alzheimer's disease. METHODS: Eligibility, consent, and randomization rates across different referral sources were compared. Informal interviews conducted with each site's project team were conducted upon study completion. RESULTS: Initially, 3290 individuals were screened, of whom 28% were eligible to consent, 805 consented to participate (87.2% of those eligible), and 513 (36.3% of those consented) were randomized. Emails sent from study site listservs/databases yielded the highest amount (20.9%) of screened individuals. Professional referrals from physicians yielded the greatest percentage of consented individuals (57.1%). Referrals from non-professional contacts (ie, friends, family; 75%) and mail/phone contact from a site (73.8%) had the highest yield of randomization. DISCUSSION: Professional referrals or email from listservs/registries were most effective for enrolling participants. The greatest yield of eligible/randomized participants came from non-professional and mail/phone contacts. Future trials should consider special efforts targeting these recruitment approaches. Highlights: Clinical trial recruitment is commonly cited as a significant barrier to advancing our understanding of cognitive health interventions.The most cited referral source was email, followed by interviews/editorials on the radio, television, local newspapers, newsletters, or magazine articles.The referral method that brought in the largest number of contacts was email but did not result in the greatest yield of consents or eligible participants.The sources that yielded the greatest likelihood of consent were professional referrals (ie, physician), social media, and mail/phone contact from study site.The greatest yield of eligible/randomized participants came from non-professional contacts and mail/phone contact from a site.Findings suggest that sites may need to focus on more selective referral sources, such as using contact mailing and phone lists, rather than more widely viewed recruitment sources, such as social media or TV/radio advertisements.

Ultra-Low-Cost Disposable Hand-Held Clinical-Scale Propane Gas Hyperpolarizer for Pulmonary Magnetic Resonance Imaging Sensing.

Hyperpolarized magnetic resonance imaging (MRI) contrast agents are revolutionizing the field of biomedical imaging. Hyperpolarized Xe-129 was recently FDA approved as an inhalable MRI contrast agent for functional lung imaging sensing. Despite success in research settings, modern Xe-129 hyperpolarizers are expensive (up to $1M), large, and complex to site and operate. Moreover, Xe-129 sensing requires specialized MRI hardware that is not commonly available on clinical MRI scanners. Here, we demonstrate that proton-hyperpolarized propane gas can be produced on demand using a disposable, hand-held, clinical-scale hyperpolarizer via parahydrogen-induced polarization, which relies on parahydrogen as a source of hyperpolarization. The device consists of a heterogeneous catalytic reactor connected to a gas mixture storage can containing pressurized hyperpolarization precursors: propylene and parahydrogen (10 bar total pressure). Once the built-in flow valve of the storage can is actuated, the precursors are ejected from the can into a reactor, and a stream of hyperpolarized propane gas is ejected from the reactor. Robust operation of the device is demonstrated for producing proton sensing polarization of 1.2% in a wide range of operational pressures and gas flow rates. We demonstrate that the propylene/parahydrogen gas mixture can retain potency for days in the storage can with a monoexponential decay time constant of 6.0 ± 0.5 days, which is limited by the lifetime of the parahydrogen singlet spin state in the storage container. The utility of the produced sensing agent is demonstrated for phantom imaging on a 3 T clinical MRI scanner located 100 miles from the agent/device preparation site and also for ventilation imaging of excised pig lungs using a 0.35 T clinical MRI scanner. The cost of the device components is less than $35, which we envision can be reduced to less than $5 for mass-scale production. The hyperpolarizer device can be reused, recycled, or disposed.

Auditory rhythm discrimination in adults who stutter: An fMRI study.

Rhythm perception deficits have been linked to neurodevelopmental disorders affecting speech and language. Children who stutter have shown poorer rhythm discrimination and attenuated functional connectivity in rhythm-related brain areas, which may negatively impact timing control required for speech. It is unclear whether adults who stutter (AWS), who are likely to have acquired compensatory adaptations in response to rhythm processing/timing deficits, are similarly affected. We compared rhythm discrimination in AWS and controls (total n = 36) during fMRI in two matched conditions: simple rhythms that consistently reinforced a periodic beat, and complex rhythms that did not (requiring greater reliance on internal timing). Consistent with an internal beat deficit hypothesis, behavioral results showed poorer complex rhythm discrimination for AWS than controls. In AWS, greater stuttering severity was associated with poorer rhythm discrimination. AWS showed increased activity within beat-based timing regions and increased functional connectivity between putamen and cerebellum (supporting interval-based timing) for simple rhythms.

Hippocampus shape characterization with 3D Zernike transformation in clinical Alzheimer's disease progression.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia among older adults. Mild cognitive impairment (MCI) is considered a transitional phase between healthy cognitive aging and dementia. Progressive brain volume reduction/atrophy, particularly of the hippocampus, is associated with the transition from normal to MCI, and then to AD. We aimed to develop methods to characterize the shape of hippocampus and explore its potential as an imaging marker to monitor clinical AD progression. We implemented a 3D Zernike transformation to characterize the shape changes of hippocampus in 428 older subjects with high-quality T1 -weighted volumetric brain scans from the Alzheimer's Disease Neuroimaging Initiative data set (151 normal, 258 MCI, and 19 AD). Over 2 years, 15 cognitively normal subjects converted to MCI, and 42 subjects with MCI converted to AD. We found a significant correlation between hippocampal volume changes and Zernike shape metrics. Before a clinical diagnosis of AD, the shapes of the left and right hippocampi changed slowly. After AD diagnosis, both volume and shape changed rapidly but were uncorrelated to each other. During the transition from a clinical diagnosis of MCI to AD, the shape of the left and right hippocampi changed in a correlated manner but became uncorrelated after AD diagnosis. Finally, the pace of hippocampus shape change was associated with its shape and the subject's age and disease condition. In conclusion, the hippocampus shape features characterized with 3D Zernike transformation, in complement to volume measures, may serve as a novel imaging marker to monitor clinical AD progression.

Microstructural organization of the corpus callosum in young endurance athletes: A global tractography study.

Introduction: Aerobic exercise training has been shown to improve microstructural organization of the corpus callosum (CC); however, evidence of this topographic effect is limited. Purpose: To compare the CC microstructural organization between endurance athletes and sedentary adults using a white-matter fiber tractography approach. Materials and methods: Diffusion tensor imaging (DTI) and T1-weighted structural data were collected from 15 male young endurance athletes and 16 age- and sex-matched sedentary adults. DTI data were analyzed with a global probabilistic tractography method based on neighborhood anatomical information. Fractional anisotropy (FA) and mean, radial (RD), and axial diffusivities were measured in the eight CC tracts: rostrum, genu, splenium, and body's prefrontal, premotor, central, parietal, and temporal tracts. Cortical thickness of the CC tract endpoints and the CC tract length and volume were also measured. Physical activity level was assessed by metabolic equivalents (METs). Results: The athlete group had an average VO2max of 69.5 ± 3.1 ml/kg/min, which is above 90%ile according to the American College of Sports Medicine guideline. Compared with the sedentary group, the athlete group had higher FA in the CC body's premotor and parietal tracts and the CC splenium. These tracts showed lower RD in the athlete compared with sedentary group. The voxelwise analysis confirmed that the athlete group had higher FA in the CC and other white matter regions than the sedentary group, including the corona radiata, internal capsule, and superior longitudinal fasciculus. Cortical thickness of the CC tract endpoints and the CC tract lengths and volumes were similar between the two groups. Physical activity levels were positively correlated with FA in the CC body's parietal (r = 0.486, p = 0.006) and temporal (r = 0.425, p = 0.017) tracts and the CC splenium (r = 0.408, p = 0.023). Conclusion: Young endurance athletes have higher microstructural organization of the CC tracts connected the sensorimotor and visual cortices than the age- and sex-matched sedentary adults.

Brain white matter hyperintensity lesion characterization in 3D T2 fluid-attenuated inversion recovery magnetic resonance images: Shape, texture, and their correlations with potential growth.

Analyses of age-related white matter hyperintensity (WMH) lesions manifested in T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance images (MRI) have been mostly on understanding the size and location of the WMH lesions and rarely on the morphological characterization of the lesions. This work extends our prior analyses of the morphological characteristics and texture of WMH from 2D to 3D based on 3D T2 FLAIR images. 3D Zernike transformation was used to characterize WMH shape; a fuzzy logic method was used to characterize the lesion texture. We then clustered 3D WMH lesions into groups based on their 3D shape and texture features. A potential growth index (PGI) to assess dynamic changes in WMH lesions was developed based on the image texture features of the WMH lesion penumbra. WMH lesions with various sizes were segmented from brain images of 32 cognitively normal older adults. The WMH lesions were divided into two groups based on their size. Analyses of Variance (ANOVAs) showed significant differences in PGI among WMH shape clusters (P = 1.57 × 10-3 for small lesions; P = 3.14 × 10-2 for large lesions). Significant differences in PGI were also found among WMH texture group clusters (P = 1.79 × 10-6). In conclusion, we presented a novel approach to characterize the morphology of 3D WMH lesions and explored the potential to assess the dynamic morphological changes of WMH lesions using PGI.

Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults.

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the "Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts" (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression techniques for older adults from a large multi-site clinical trial of exercise and intensive pharmacological vascular risk factor reduction. The Risk Reduction for Alzheimer's Disease (rrAD) trial included hypertensive older adults (60-84 years old) at elevated risk of developing Alzheimer's Disease (AD). We compared the performance of censoring, censoring combined with global signal regression, non-aggressive and aggressive ICA-AROMA, as well as the Spatially Organized Component Klassifikator (SOCK) on the rs-fMRI baseline scans from 434 rrAD subjects. All techniques were rated based on network reproducibility, network identifiability, edge activity, spatial smoothness, and loss of temporal degrees of freedom (tDOF). We found that non-aggressive ICA-AROMA did not perform as well as the other four techniques, which performed table with marginal differences, demonstrating the validity of these techniques. Considering reproducibility as the most important factor for longitudinal studies, given low false-positive rates and a better preserved, more cohesive temporal structure, currently aggressive ICA-AROMA is likely the most suitable noise regression technique for rs-fMRI studies of older adults.

Functional connectivity of cortical resting-state networks is differentially affected by rest conditions.

Optimal conditions for resting-state functional magnetic resonance imaging (rs-fMRI) are still highly debated. Here, we comprehensively assessed the effects of various rest conditions on all cortical resting-state networks (RSNs) defined by an established atlas. Twenty-two healthy college students (22 ± 4 years old, 12 females) were scanned on a GE 3T MRI scanner. Rs-fMRI datasets were collected under four different conditions for each subject: (1) eyes open in dim light (Eyes-Open), (2) eyes closed and awake (Eyes-Closed), (3) eyes closed while remembering four numbers through the scan session (Eyes-Closed-Number) and (4) asked to watch a movie (Movie). We completed a thorough examination of the 17 functional RSNs defined by Yeo and colleagues. Importantly, the movie led to changes in global connectivity and should be avoided as a rest condition. Conversely, there were no significant connectivity differences between conditions within the frontoparietal control and limbic networks and the following subnetworks as defined by Yeo et al.: default-B, dorsal-attention-B and salience/ventral-attention-B. These were not even significant when compared to the highly stimulative Movie condition. A significant difference was not found between Eyes-Closed and Eyes-Closed-Number conditions in whole-brain, within-network and between-network comparisons. When considering other rest conditions, however, we observed connectivity changes in some subnetworks, including those of the default-mode network. Overall, we found conditions with more external stimulation led to more changes in functional connectivity during rs-fMRI. In conclusion, the comprehensive results of our study can aid in choosing rest conditions for the study of overall and specific functional networks.

Brain information processing capacity modeling.

Neurophysiological measurements suggest that human information processing is evinced by neuronal activity. However, the quantitative relationship between the activity of a brain region and its information processing capacity remains unclear. We introduce and validate a mathematical model of the information processing capacity of a brain region in terms of neuronal activity, input storage capacity, and the arrival rate of afferent information. We applied the model to fMRI data obtained from a flanker paradigm in young and old subjects. Our analysis showed that-for a given cognitive task and subject-higher information processing capacity leads to lower neuronal activity and faster responses. Crucially, processing capacity-as estimated from fMRI data-predicted task and age-related differences in reaction times, speaking to the model's predictive validity. This model offers a framework for modelling of brain dynamics in terms of information processing capacity, and may be exploited for studies of predictive coding and Bayes-optimal decision-making.

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

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

Developmental Factors That Predict Head Movement During Resting-State Functional Magnetic Resonance Imaging in 3-7-Year-Old Stuttering and Non-stuttering Children.

Early childhood marks a period of dynamic neurocognitive development. Preschool-age coincides with the onset of many childhood disorders and is a developmental period that is frequently studied to determine markers of neurodevelopmental disorders. Magnetic resonance imaging (MRI) is often used to explore typical brain development and the neural bases of neurodevelopmental disorders. However, acquiring high-quality MRI data in young children is challenging. The enclosed space and loud sounds can trigger unease and cause excessive head movement. A better understanding of potential factors that predict successful MRI acquisition would increase chances of collecting useable data in children with and without neurodevelopmental disorders. We investigated whether age, sex, stuttering status, and childhood temperament as measured using the Child Behavioral Questionnaire, could predict movement extent during resting-state functional MRI (rs-fMRI) in 76 children aged 3-7 years, including 42 children who stutter (CWS). We found that age, sex, and temperament factors could predict motion during rs-fMRI scans. The CWS were not found to differ significantly from controls in temperament or head movement during scanning. Sex and age were significant predictors of movement. However, age was no longer a significant predictor when temperament, specifically effortful control, was considered. Controlling for age, boys with higher effortful control scores moved less during rs-fMRI procedures. Additionally, boys who showed higher negative affectivity showed a trend for greater movement. Considering temperament factors in addition to age and sex may help predict the success of acquiring useable rs-fMRI (and likely general brain MRI) data in young children in MR neuroimaging.

Alzheimer's Disease Progressively Reduces Visual Functional Network Connectivity.

BACKGROUND: Postmortem studies of brains with Alzheimer's disease (AD) not only find amyloid-beta (Aß) and neurofibrillary tangles (NFT) in the visual cortex, but also reveal temporally sequential changes in AD pathology from higher-order association areas to lower-order areas and then primary visual area (V1) with disease progression. OBJECTIVE: This study investigated the effect of AD severity on visual functional network. METHODS: Eight severe AD (SAD) patients, 11 mild/moderate AD (MAD), and 26 healthy senior (HS) controls undertook a resting-state fMRI (rs-fMRI) and a task fMRI of viewing face photos. A resting-state visual functional connectivity (FC) network and a face-evoked visual-processing network were identified for each group. RESULTS: For the HS, the identified group-mean face-evoked visual-processing network in the ventral pathway started from V1 and ended within the fusiform gyrus. In contrast, the resting-state visual FC network was mainly confined within the visual cortex. AD disrupted these two functional networks in a similar severity dependent manner: the more severe the cognitive impairment, the greater reduction in network connectivity. For the face-evoked visual-processing network, MAD disrupted and reduced activation mainly in the higher-order visual association areas, with SAD further disrupting and reducing activation in the lower-order areas. CONCLUSION: These findings provide a functional corollary to the canonical view of the temporally sequential advancement of AD pathology through visual cortical areas. The association of the disruption of functional networks, especially the face-evoked visual-processing network, with AD severity suggests a potential predictor or biomarker of AD progression.

Hippocampal and rostral anterior cingulate blood flow is associated with affective symptoms in chronic traumatic brain injury.

OBJECTIVE: The purpose of this study was to assess cerebral blood flow (CBF) and its association with self-reported symptoms in chronic traumatic brain injury (TBI). PARTICIPANTS: Sixteen participants with mild to severe TBI and persistent self-reported neurological symptoms, 6 to 72 months post-injury were included. For comparison, 16 age- and gender-matched healthy normal control participants were also included. MAIN MEASURES: Regional CBF and brain volume were assessed using pseudo-continuous Arterial Spin Labeling (PCASL) and T1-weighted data respectively. Cognitive function and self-reported symptoms were assessed in TBI participants using the national institutes of health (NIH) Toolbox Cognition Battery and Patient-Reported Outcome Measurement Information System respectively. Associations between CBF and cognitive function, symptoms were assessed. RESULTS: Global CBF and regional brain volumes were similar between groups, but region of interest (ROI) analysis revealed lower CBF bilaterally in the thalamus, hippocampus, left caudate, and left amygdala in the TBI group. Voxel-wise analysis revealed that CBF in the hippocampus, parahippocampus, rostral anterior cingulate, inferior frontal gyrus, and other temporal regions were negatively associated with self-reported anger, anxiety, and depression symptoms. Furthermore, region of interest (ROI) analysis revealed that hippocampal and rostral anterior cingulate CBF were negatively associated with symptoms of fatigue, anxiety, depression, and sleep issues. CONCLUSION: Regional CBF deficit was observed in the group with chronic TBI compared to the normal control (NC) group despite similar volume of cerebral structures. The observed negative correlation between regional CBF and affective symptoms suggests that CBF-targeted intervention may potentially improve affective symptoms and quality of life after TBI, which needs to be assessed in future studies.

Brain blood and cerebrospinal fluid flow dynamics during rhythmic handgrip exercise in young healthy men and women.

KEY POINTS: The cerebral fluid response to exercise, including the arterial and venous cerebral blood flow (CBF) and cerebrospinal fluid (CSF), currently remains unknown. We used time-resolved phase-contrast magnetic resonance imaging to assess changes in CBF and CSF flow dynamics during moderate-intensity rhythmic handgrip (RHG) exercise in young healthy men and women. Our data demonstrated that RHG increases the cerebral arterial inflow and venous outflow while decreasing the pulsatile CSF flow during RHG. Furthermore, changes in blood stroke volume at the measured arteries, veins, and sinuses and CSF stroke volume at the cerebral aqueduct were positively correlated with each other during RHG. Male and female participants exhibited distinct blood pressure responses to RHG, but their cerebral fluid responses were similar. These results collectively suggest that RHG influences both CBF and CSF flow dynamics in a way that is consistent with the Monro-Kellie hypothesis to maintain intracranial volume-pressure homeostasis in young healthy adults. ABSTRACT: Cerebral blood flow (CBF) increases during exercise, but its impact on cerebrospinal fluid (CSF) flow remains unknown. This study investigated CBF and CSF flow dynamics during moderate-intensity rhythmic handgrip (RHG) exercise in young healthy men and women. Twenty-six participants (12 women) underwent the RHG and resting control conditions in random order. Participants performed 3 sets of RHG, during which cine phase-contrast magnetic resonance imaging (PC-MRI) was performed to measure blood stroke volume (SV) and flow rate in the internal carotid (ICA) and vertebral (VA) arteries, the internal jugular vein (IJV), the superior sagittal (SSS) and straight sinuses (SRS), and CSF SV and flow rate in the cerebral aqueduct of Sylvius. Blood pressure, end-tidal CO2 (EtCO2 ), heart rate (HR), and respiratory rate were simultaneously measured during cine PC-MRI scans. Compared with control conditions, RHG showed significant elevations of HR, mean arterial pressure, and respiratory rate with a mild reduction of EtCO2 (all P < 0.05). RHG decreased blood SV in the measured arteries, veins, and sinuses and CSF SV in the aqueduct (all P < 0.05). Conversely, RHG increased blood flow in the ICA, VA, and IJV (all P < 0.05). At the aqueduct, RHG decreased the absolute CSF flow rate (P = 0.0307), which was calculated as a sum of the caudal and cranial CSF flow rates. Change in the ICA SV was positively correlated with changes in the IJV, SSS, SRS, and aqueductal SV during RHG (all P < 0.05). These findings demonstrate a close coupling between the CBF and CSF flow dynamics during RHG in young healthy adults.