The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
Infancy is marked by rapid neural and emotional development. The relation between brain function and emotion in infancy, however, is not well understood. Methods for measuring brain function predominantly rely on the BOLD signal; however, interpretation of the BOLD signal in infancy is challenging because the neuronal-hemodynamic relation is immature. Regional cerebral blood flow (rCBF) provides a context for the infant BOLD signal and can yield insight into the developmental maturity of brain regions that may support affective behaviors. This study aims to elucidate the relations among rCBF, age, and emotion in infancy. One hundred and seven mothers reported their infants' (infant age M ± SD = 6.14 ± 0.51 months) temperament. A subsample of infants completed MRI scans, 38 of whom produced usable perfusion MRI during natural sleep to quantify rCBF. Mother-infant dyads completed the repeated Still-Face Paradigm, from which infant affect reactivity and recovery to stress were quantified. We tested associations of infant age at scan, temperament factor scores, and observed affect reactivity and recovery with voxel-wise rCBF. Infant age was positively associated with CBF in nearly all voxels, with peaks located in sensory cortices and the ventral prefrontal cortex, supporting the formulation that rCBF is an indicator of tissue maturity. Temperamental Negative Affect and recovery of positive affect following a stressor were positively associated with rCBF in several cortical and subcortical limbic regions, including the orbitofrontal cortex and inferior frontal gyrus. This finding yields insight into the nature of affective neurodevelopment during infancy. Specifically, infants with relatively increased prefrontal cortex maturity may evidence a disposition toward greater negative affect and negative reactivity in their daily lives yet show better recovery of positive affect following a social stressor.
© 2019 John Wiley & Sons Ltd.
BACKGROUND - Vascular risk factors promote cerebral small vessel disease and neuropathological changes, particularly in white matter where large-caliber axons are located. How Alzheimer's disease pathology influences the brain's vulnerability in this regard is not well understood.
OBJECTIVE - Systemic vascular risk was assessed in relation to cerebrospinal fluid concentrations of neurofilament light, a biomarker of large-caliber axonal injury, evaluating for interactions by clinical and protein markers of Alzheimer's disease.
METHODS - Among Alzheimer's Disease Neuroimaging Initiative participants with normal cognition (n = 117), mild cognitive impairment (n = 190), and Alzheimer's disease (n = 95), linear regression related vascular risk (as measured by the modified Framingham Stroke Risk Profile) to neurofilament light, adjusting for age, sex, education, and cognitive diagnosis. Interactions were assessed by cognitive diagnosis, and by cerebrospinal fluid markers of Aβ42, hyperphosphorylated tau, and total tau.
RESULTS - Vascular risk and neurofilament light were not related in the main effect model (p = 0.08). However, interactions emerged for total tau (p = 0.01) and hyperphosphorylated tau (p = 0.002) reflecting vascular risk becoming more associated with cerebrospinal fluid neurofilament light in the context of greater concentrations of tau biomarkers. An interaction also emerged for the Alzheimer's disease biomarker profiles (p = 0.046) where in comparison to the referent 'normal' biomarker group, individuals with abnormal levels of both Aβ42 and total tau showed stronger associations between vascular risk and neurofilament light.
CONCLUSION - Older adults may be more vulnerable to axonal injury in response to higher vascular risk burdens in the context of concomitant Alzheimer's disease pathology.
Functional MRI (fMRI) signals are robustly detectable in white matter (WM) but they have been largely ignored in the fMRI literature. Their nature, interpretation, and relevance as potential indicators of brain function remain under explored and even controversial. Blood oxygenation level dependent (BOLD) contrast has for over 25 years been exploited for detecting localized neural activity in the cortex using fMRI. While BOLD signals have been reliably detected in grey matter (GM) in a very large number of studies, such signals have rarely been reported from WM. However, it is clear from our own and other studies that although BOLD effects are weaker in WM, using appropriate detection and analysis methods they are robustly detectable both in response to stimuli and in a resting state. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both GM and WM, and their relative low frequency (0.01-0.1 Hz) signal powers are comparable. They also vary with baseline neural activity e.g. as induced by different levels of anesthesia, and alter in response to a stimulus. In previous work we reported that BOLD signals in WM in a resting state exhibit anisotropic temporal correlations with neighboring voxels. On the basis of these findings, we derived functional correlation tensors that quantify the correlational anisotropy in WM BOLD signals. We found that, along many WM tracts, the directional preferences of these functional correlation tensors in a resting state are grossly consistent with those revealed by diffusion tensors, and that external stimuli tend to enhance visualization of specific and relevant fiber pathways. These findings support the proposition that variations in WM BOLD signals represent tract-specific responses to neural activity. We have more recently shown that sensory stimulations induce explicit BOLD responses along parts of the projection fiber pathways, and that task-related BOLD changes in WM occur synchronously with the temporal pattern of stimuli. WM tracts also show a transient signal response following short stimuli analogous to but different from the hemodynamic response function (HRF) characteristic of GM. Thus there is converging and compelling evidence that WM exhibits both resting state fluctuations and stimulus-evoked BOLD signals very similar (albeit weaker) to those in GM. A number of studies from other laboratories have also reported reliable observations of WM activations. Detection of BOLD signals in WM has been enhanced by using specialized tasks or modified data analysis methods. In this mini-review we report summaries of some of our recent studies that provide evidence that BOLD signals in WM are related to brain functional activity and deserve greater attention by the neuroimaging community.
Copyright © 2019 Elsevier Inc. All rights reserved.
Translation of many non-invasive hemodynamic MRI methods to cerebrovascular disease patients has been hampered by well-known artifacts associated with delayed blood arrival times and reduced microvascular compliance. Using machine learning and support vector machine (SVM) algorithms, we investigated whether arrival time-related artifacts in these methods could be exploited as novel contrast sources to discriminate angiographically confirmed stenotic flow territories. Intracranial steno-occlusive moyamoya patients ( = 53; age = 45 ± 14.2 years; sex = 43 F) underwent (i) catheter angiography, (ii) anatomical MRI, (iii) cerebral blood flow (CBF)-weighted arterial spin labeling, and (iv) cerebrovascular reactivity (CVR)-weighted hypercapnic blood-oxygenation-level-dependent MRI. Mean, standard deviation (std), and 99th percentile of CBF, CVR, CVR, and CVR were calculated in major anterior and posterior flow territories perfused by vessels with vs. without stenosis (≥70%) confirmed by catheter angiography. These and demographic variables were input into SVMs to evaluate discriminatory capacity for stenotic flow territories using k-fold cross-validation and receiver-operating-characteristic-area-under-the-curve to quantify variable combination relevance. Anterior circulation CBF-std, attributable to heterogeneous endovascular signal and prolonged arterial transit times, was the best performing single variable and CVR-mean and CBF-std, both reflective of delayed vascular compliance, were a high-performing two-variable combination (specificity = 0.67; sensitivity = 0.75). Findings highlight the relevance of hemodynamic imaging and machine learning for identifying cerebrovascular impairment.
Accurate estimates of the BOLD hemodynamic response function (HRF) are crucial for the interpretation and analysis of event-related functional MRI data. To date, however, there have been no comprehensive measurements of the HRF in white matter (WM) despite increasing evidence that BOLD signals in WM change after a stimulus. We performed an event-related cognitive task (Stroop color-word interference) to measure the HRF in selected human WM pathways. The task was chosen in order to produce robust, distributed centers of activity throughout the cortex. To measure the HRF in WM, fiber tracts were reconstructed between each pair of activated cortical areas. We observed clear task-specific HRFs with reduced magnitudes, delayed onsets and prolonged initial dips in WM tracts compared with activated grey matter, thus calling for significant changes to current standard models for accurately characterizing the HRFs in WM and for modifications of standard methods of analysis of functional imaging data.
Parkinson's disease (PD) is characterized by dysfunction in frontal cortical and striatal networks that regulate action control. We investigated the pharmacological effect of dopamine agonist replacement therapy on frontal cortical activity and motor inhibition. Using Arterial Spin Labeling MRI, we examined 26 PD patients in the off- and on-dopamine agonist medication states to assess the effect of dopamine agonists on frontal cortical regional cerebral blood flow. Motor inhibition was measured by the Simon task in both medication states. We applied the dual process activation suppression model to dissociate fast response impulses from motor inhibition of incorrect responses. General linear regression model analyses determined the medication effect on regional cerebral blood flow and motor inhibition, and the relationship between regional cerebral blood flow and motor inhibitory proficiency. We show that dopamine agonist administration increases frontal cerebral blood flow, particularly in the pre-supplementary motor area (pre-SMA) and the dorsolateral prefrontal cortex (DLPFC). Higher regional blood flow in the pre-SMA, DLPFC and motor cortex was associated with better inhibitory control, suggesting that treatments which improve frontal cortical activity could ameliorate motor inhibition deficiency in PD patients.
Copyright © 2019 Elsevier Ltd. All rights reserved.