Medial temporal lobe gray matter microstructure in preclinical Alzheimer's disease.

INTRODUCTION: Typical MRI measures of neurodegeneration have limited sensitivity in early disease stages. Diffusion MRI (dMRI) microstructural measures may allow for detection in preclinical stages. METHODS: Participants had dMRI and either beta-amyloid PET or plasma biomarkers of Alzheimer's pathology within 18 months of MRI. Microstructure was measured in portions of the medial temporal lobe (MTL) with high neurofibrillary tangle (NFT) burden based on a previously developed post mortem 3D-map. Regressions examined relationships between microstructure and markers of Alzheimer's pathology in preclinical disease and then across disease stages. RESULTS: There was higher isometric volume fraction in amyloid-positive compared to amyloid-negative cognitively unimpaired individuals in high tangle MTL regions. Similarly, plasma biomarkers and 18F-flortaucipir were associated with microstructural changes in preclinical disease. Additional microstructural effects were seen across disease stages. DISCUSSION: Combining a post mortem atlas of NFT pathology with microstructural measures allows for detection of neurodegeneration in preclinical Alzheimer's disease. Highlights Typical markers of neurodegeneration are not sensitive in preclinical Alzheimer's. dMRI measured microstructure in regions with high NFT. Microstructural changes occur in medial temporal regions in preclinical disease. Microstructural changes occur in other typical Alzheimer's regions in later stages. Combining post mortem pathology atlases with in vivo MRI is a powerful framework.

Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications.

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

Spatiotemporal cerebral blood flow dynamics underlies emergence of the limbic-sensorimotor-association cortical gradient in human infancy.

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin labeled MRI, we found the emergence of the cortical hierarchy revealed by highest-resolution infant CBF maps available to date. Infant CBF across cortical regions increased in a biphasic pattern with initial rapid and sequentially slower rate, with break-point ages increasing along the limbic-sensorimotor-association cortical gradient. Increases in CBF in sensorimotor cortices were associated with enhanced language and motor skills, and frontoparietal association cortices for cognitive skills. The study discovered emergence of the hierarchical limbic-sensorimotor-association cortical gradient in infancy, and offers standardized reference of infant brain CBF and insight into the physiological basis of cortical specialization and real-world infant developmental functioning.

In vivo B 1 + enhancement of calf MRI at 7 T via optimized flexible metasurfaces.

PURPOSE: Ultrahigh field (≥7 T) MRI is at the cutting edge of medical imaging, enabling enhanced spatial and spectral resolution as well as enhanced susceptibility contrast. However, transmit ( B 1 + $$ {\mathrm{B}}_1^{+} $$ ) field inhomogeneity due to standing wave effects caused by the shortened RF wavelengths at 7 T is still a challenge to overcome. Novel hardware methods such as dielectric pads have been shown to improve the B 1 + $$ {\mathrm{B}}_1^{+} $$ field inhomogeneity but are currently limited in their corrective effect by the range of high-permittivity materials available and have a fixed shelf life. In this work, an optimized metasurface design is presented that demonstrates in vivo enhancement of the B 1 + $$ {\mathrm{B}}_1^{+} $$ field. METHODS: A prototype metasurface was optimized by an empirical capacitor sweep and by varying the period size. Phantom temperature experiments were performed to evaluate potential metasurface heating effects during scanning. Lastly, in vivo gradient echo images and B 1 + $$ {\mathrm{B}}_1^{+} $$ maps were acquired on five healthy subjects on a 7 T system. Dielectric pads were also used as a comparison throughout the work as a standard comparison. RESULTS: The metasurfaces presented here enhanced the average relative SNR of the gradient echo images by a factor of 2.26 compared to the dielectric pads factor of 1.61. Average B 1 + $$ {\mathrm{B}}_1^{+} $$ values reflected a similar enhancement of 27.6% with the metasurfaces present versus 8.9% with the dielectric pads. CONCLUSION: The results demonstrate that metasurfaces provide superior performance to dielectric padding as shown by B 1 + $$ {\mathrm{B}}_1^{+} $$ maps reflecting their direct effects and resulting enhancements in image SNR at 7 T.

The influence of hand posture on tactile processing: Evidence from a 7T functional magnetic resonance imaging study.

Although behavioral evidence has shown that postural changes influence the ability to localize or detect tactile stimuli, little is known regarding the brain areas that modulate these effects. This 7T functional magnetic resonance imaging (fMRI) study explores the effects of touch of the hand as a function of hand location (right or left side of the body) and hand configuration (open or closed). We predicted that changes in hand configuration would be represented in contralateral primary somatosensory cortex (S1) and the anterior intraparietal area (aIPS), whereas change in position of the hand would be associated with alterations in activation in the superior parietal lobule. Multivoxel pattern analysis and a region of interest approach partially supported our predictions. Decoding accuracy for hand location was above chance level in superior parietal lobule (SPL) and in the anterior intraparietal (aIPS) area; above chance classification of hand configuration was observed in SPL and S1. This evidence confirmed the role of the parietal cortex in postural effects on touch and the possible role of S1 in coding the body form representation of the hand.

Automated Quality Evaluation Index for Arterial Spin Labeling Derived Cerebral Blood Flow Maps.

BACKGROUND: Arterial spin labeling (ASL) derived cerebral blood flow (CBF) maps are prone to artifacts and noise that can degrade image quality. PURPOSE: To develop an automated and objective quality evaluation index (QEI) for ASL CBF maps. STUDY TYPE: Retrospective. POPULATION: Data from N = 221 adults, including patients with Alzheimer's disease (AD), Parkinson's disease, and traumatic brain injury. FIELD STRENGTH/SEQUENCE: Pulsed or pseudocontinuous ASL acquired at 3 T using non-background suppressed 2D gradient-echo echoplanar imaging or background suppressed 3D spiral spin-echo readouts. ASSESSMENT: The QEI was developed using N = 101 2D CBF maps rated as unacceptable, poor, average, or excellent by two neuroradiologists and validated by 1) leave-one-out cross validation, 2) assessing if CBF reproducibility in N = 53 cognitively normal adults correlates inversely with QEI, 3) if iterative discarding of low QEI data improves the Cohen's d effect size for CBF differences between preclinical AD (N = 27) and controls (N = 53), 4) comparing the QEI with manual ratings for N = 50 3D CBF maps, and 5) comparing the QEI with another automated quality metric. STATISTICAL TESTS: Inter-rater reliability and manual vs. automated QEI were quantified using Pearson's correlation. P < 0.05 was considered significant. RESULTS: The correlation between QEI and manual ratings (R = 0.83, CI: 0.76-0.88) was similar (P = 0.56) to inter-rater correlation (R = 0.81, CI: 0.73-0.87) for the 2D data. CBF reproducibility correlated negatively (R = -0.74, CI: -0.84 to -0.59) with QEI. The effect size comparing patients and controls improved (R = 0.72, CI: 0.59-0.82) as low QEI data was discarded iteratively. The correlation between QEI and manual ratings (R = 0.86, CI: 0.77-0.92) of 3D ASL was similar (P = 0.09) to inter-rater correlation (R = 0.78, CI: 0.64-0.87). The QEI correlated (R = 0.87, CI: 0.77-0.92) significantly better with manual ratings than did an existing approach (R = 0.54, CI: 0.30-0.72). DATA CONCLUSION: Automated QEI performed similarly to manual ratings and can provide scalable ASL quality control. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Sleep-stage-dependent alterations in cerebral oxygen metabolism quantified by magnetic resonance.

A key function of sleep is to provide a regular period of reduced brain metabolism, which is critical for maintenance of healthy brain function. The purpose of this work was to quantify the sleep-stage-dependent changes in brain energetics in terms of cerebral metabolic rate of oxygen (CMRO2 ) as a function of sleep stage using quantitative magnetic resonance imaging (MRI) with concurrent electroencephalography (EEG) during sleep in the scanner. Twenty-two young and older subjects with regular sleep hygiene and Pittsburgh Sleep Quality Index (PSQI) in the normal range were recruited for the study. Cerebral blood flow (CBF) and venous oxygen saturation (SvO2 ) were obtained simultaneously at 3 Tesla field strength and 2.7-s temporal resolution during an 80-min time series using OxFlow, an in-house developed imaging sequence. The method yields whole-brain CMRO2 in absolute physiologic units via Fick's Principle. Nineteen subjects yielded evaluable data free of subject motion artifacts. Among these subjects, 10 achieved slow-wave (N3) sleep, 16 achieved N2 sleep, and 19 achieved N1 sleep while undergoing the MRI protocol during scanning. Mean CMRO2 was 98 ± 7(µmol min-1 )/100 g awake, declining progressively toward deepest sleep stage: 94 ± 10.8 (N1), 91 ± 11.4 (N2), and 76 ± 9.0 µmol min-1 /100 g (N3), with each level differing significantly from the wake state. The technology described is able to quantify cerebral oxygen metabolism in absolute physiologic units along with non-REM sleep stage, indicating brain oxygen consumption to be closely associated with depth of sleep, with deeper sleep stages exhibiting progressively lower CMRO2 levels.

Impact of white matter hyperintensities on structural connectivity and cognition in cognitively intact ADNI participants.

We used indirect brain mapping with virtual lesion tractography to test the hypothesis that the extent of white matter tract disconnection due to white matter hyperintensities (WMH) is associated with corresponding tract-specific cognitive performance decrements. To estimate tract disconnection, WMH masks were extracted from FLAIR MRI data of 481 cognitively intact participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) and used as regions of avoidance for fiber tracking in diffusion MRI data from 50 healthy young participants from the Human Connectome Project. Estimated tract disconnection in the right inferior fronto-occipital fasciculus, right frontal aslant tract, and right superior longitudinal fasciculus mediated the effects of WMH volume on executive function. Estimated tract disconnection in the left uncinate fasciculus mediated the effects of WMH volume on memory and in the right frontal aslant tract on language. In a subset of ADNI control participants with amyloid data, positive status increased the probability of periventricular WMH and moderated the relationship between WMH burden and tract disconnection in executive function performance.

Leveraging Multi-echo EPI to Enhance BOLD Sensitivity in Task-based Olfactory fMRI.

Functional magnetic resonance imaging (fMRI) using blood-oxygenation-level-dependent (BOLD) contrast relies on gradient echo echo-planar imaging (GE-EPI) to quantify dynamic susceptibility changes associated with the hemodynamic response to neural activity. However, acquiring BOLD fMRI in human olfactory regions is particularly challenging due to their proximity to the sinuses where large susceptibility gradients induce magnetic field distortions. BOLD fMRI of the human olfactory system is further complicated by respiratory artifacts that are highly correlated with event onsets in olfactory tasks. Multi-Echo EPI (ME-EPI) acquires gradient echo data at multiple echo times (TEs) during a single acquisition and can leverage signal evolution over the multiple echo times to enhance BOLD sensitivity and reduce artifactual signal contributions. In the current study, we developed a ME-EPI acquisition protocol for olfactory task-based fMRI and demonstrated significant improvement in BOLD signal sensitivity over conventional single-echo EPI (1E-EPI). The observed improvement arose from both an increase in BOLD signal changes through a T 2 * -weighted echo combination and a reduction in non-BOLD artifacts through the application of the Multi-Echo Independent Components Analysis (ME-ICA) denoising method. This study represents one of the first direct comparisons between 1E-EPI and ME-EPI in high-susceptibility regions and provides compelling evidence in favor of using ME-EPI for future task-based fMRI studies.

Sleep deprivation attenuates neural responses to outcomes from risky decision-making.

Sleep loss impacts a broad range of brain and cognitive functions. However, how sleep deprivation affects risky decision-making remains inconclusive. This study used functional MRI to examine the impact of one night of total sleep deprivation (TSD) on risky decision-making behavior and the underlying brain responses in healthy adults. In this study, we analyzed data from N = 56 participants in a strictly controlled 5-day and 4-night in-laboratory study using a modified Balloon Analogue Risk Task. Participants completed two scan sessions in counter-balanced order, including one scan during rested wakefulness (RW) and another scan after one night of TSD. Results showed no differences in participants' risk-taking propensity and risk-induced activation between RW and TSD. However, participants showed significantly reduced neural activity in the anterior cingulate cortex and bilateral insula for loss outcomes, and in bilateral putamen for win outcomes during TSD compared with RW. Moreover, risk-induced activation in the insula negatively correlated with participants' risk-taking propensity during RW, while no such correlations were observed after TSD. These findings suggest that sleep loss may impact risky decision-making by attenuating neural responses to decision outcomes and impairing brain-behavior associations.

Mapping the Relationship of White Matter Lesions to Depression in Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated neurological disorder, and up to 50% of patients experience depression. We investigated how white matter network disruption is related to depression in MS. METHODS: Using electronic health records, 380 participants with MS were identified. Depressed individuals (MS+Depression group; n = 232) included persons who had an ICD-10 depression diagnosis, had a prescription for antidepressant medication, or screened positive via Patient Health Questionnaire (PHQ)-2 or PHQ-9. Age- and sex-matched nondepressed individuals with MS (MS-Depression group; n = 148) included persons who had no prior depression diagnosis, had no psychiatric medication prescriptions, and were asymptomatic on PHQ-2 or PHQ-9. Research-quality 3T structural magnetic resonance imaging was obtained as part of routine care. We first evaluated whether lesions were preferentially located within the depression network compared with other brain regions. Next, we examined if MS+Depression patients had greater lesion burden and if this was driven by lesions in the depression network. Primary outcome measures were the burden of lesions (e.g., impacted fascicles) within a network and across the brain. RESULTS: MS lesions preferentially affected fascicles within versus outside the depression network (ß = 0.09, 95% CI = 0.08 to 0.10, p < .001). MS+Depression patients had more lesion burden (ß = 0.06, 95% CI = 0.01 to 0.10, p = .015); this was driven by lesions within the depression network (ß = 0.02, 95% CI = 0.003 to 0.040, p = .020). CONCLUSIONS: We demonstrated that lesion location and burden may contribute to depression comorbidity in MS. MS lesions disproportionately impacted fascicles in the depression network. MS+Depression patients had more disease than MS-Depression patients, which was driven by disease within the depression network. Future studies relating lesion location to personalized depression interventions are warranted.

Early-stage mapping of macromolecular content in APPNL-F mouse model of Alzheimer's disease using nuclear Overhauser effect MRI.

Non-invasive methods of detecting early-stage Alzheimer's disease (AD) can provide valuable insight into disease pathology, improving the diagnosis and treatment of AD. Nuclear Overhauser enhancement (NOE) MRI is a technique that provides image contrast sensitive to lipid and protein content in the brain. These macromolecules have been shown to be altered in Alzheimer's pathology, with early disruptions in cell membrane integrity and signaling pathways leading to the buildup of amyloid-beta plaques and neurofibrillary tangles. We used template-based analyzes of NOE MRI data and the characteristic Z-spectrum, with parameters optimized for increase specificity to NOE, to detect changes in lipids and proteins in an AD mouse model that recapitulates features of human AD. We find changes in NOE contrast in the hippocampus, hypothalamus, entorhinal cortex, and fimbria, with these changes likely attributed to disruptions in the phospholipid bilayer of cell membranes in both gray and white matter regions. This study suggests that NOE MRI may be a useful tool for monitoring early-stage changes in lipid-mediated metabolism in AD and other disorders with high spatial resolution.

Microvascular reperfusion during endovascular therapy: the balance of supply and demand.

BACKGROUND: Endovascular therapy (EVT) has revolutionized the treatment of acute stroke, but large vessel recanalization does not always result in tissue-level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during EVT. We aimed to leverage diffuse correlation spectroscopy (DCS), a novel transcranial optical imaging technique, to assess the relationship between microvascular CBF and post-EVT outcomes. METHODS: Frontal lobe CBF was monitored by DCS in 40 patients undergoing EVT. Baseline CBF deficit was calculated as the percentage of CBF impairment on pre-EVT CT perfusion. Microvascular reperfusion was calculated as the percentage increase in DCS-derived CBF that occurred with recanalization. The adequacy of reperfusion was defined by persistent CBF deficit, calculated as: baseline CBF deficit - microvascular reperfusion. A good functional outcome was defined as 90-day modified Rankin Scale score ≤2. RESULTS: Thirty-six of 40 patients achieved successful recanalization, in whom microvascular reperfusion in itself was not associated with infarct volume or functional outcome. However, patients with good functional outcomes had a smaller persistent CBF deficit (median 1% (IQR -11%-16%)) than patients with poor outcomes (median 28% (IQR 2-50%)) (p=0.02). Smaller persistent CBF deficit was also associated with smaller infarct volume (p=0.004). Multivariate models confirmed that persistent CBF deficit was independently associated with infarct volume and functional outcome. CONCLUSIONS: CBF augmentation alone does not predict post-EVT outcomes, but when microvascular reperfusion closely matches the baseline CBF deficit, patients experience favorable clinical and radiographic outcomes. By recognizing inadequate reperfusion, bedside CBF monitoring may provide opportunities to personalize post-EVT care aimed at CBF optimization.

Aging and Alzheimer's disease have dissociable effects on local and regional medial temporal lobe connectivity.

Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer's disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer's disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging. However, the extent to which Alzheimer's and aging-related pathological processes relate to functional disruption of the medial temporal lobe-dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity alterations in the medial temporal lobe and its immediate functional neighbourhood-the Anterior-Temporal and Posterior-Medial brain networks-in normal agers, individuals with preclinical Alzheimer's disease and patients with Mild Cognitive Impairment or mild dementia due to Alzheimer's disease. In the Anterior-Temporal network and in the perirhinal cortex, in particular, we observed an inverted 'U-shaped' relationship between functional connectivity and Alzheimer's stage. According to our results, the preclinical phase of Alzheimer's disease is characterized by increased functional connectivity between the perirhinal cortex and other regions of the medial temporal lobe, as well as between the anterior medial temporal lobe and its one-hop neighbours in the Anterior-Temporal system. This effect is no longer present in symptomatic Alzheimer's disease. Instead, patients with symptomatic Alzheimer's disease displayed reduced hippocampal connectivity within the medial temporal lobe as well as hypoconnectivity within the Posterior-Medial system. For normal aging, our results led to three main conclusions: (i) intra-network connectivity of both the Anterior-Temporal and Posterior-Medial networks declines with age; (ii) the anterior and posterior segments of the medial temporal lobe become increasingly decoupled from each other with advancing age; and (iii) the posterior subregions of the medial temporal lobe, especially the parahippocampal cortex, are more vulnerable to age-associated loss of function than their anterior counterparts. Together, the current results highlight evolving medial temporal lobe dysfunction in Alzheimer's disease and indicate different neurobiological mechanisms of the medial temporal lobe network disruption in aging versus Alzheimer's disease.

Disconnectome associated with progressive white matter hyperintensities in aging: a virtual lesion study.

Objective: White matter hyperintensities (WMH) are commonly seen on T2-weighted magnetic resonance imaging (MRI) in older adults and are associated with an increased risk of cognitive decline and dementia. This study aims to estimate changes in the structural connectome due to age-related WMH by using a virtual lesion approach. Methods: High-quality diffusion-weighted imaging data of 30 healthy subjects were obtained from the Human Connectome Project (HCP) database. Diffusion tractography using q-space diffeomorphic reconstruction (QSDR) and whole brain fiber tracking with 107 seed points was conducted using diffusion spectrum imaging studio and the brainnetome atlas was used to parcellate a total of 246 cortical and subcortical nodes. Previously published WMH frequency maps across age ranges (50's, 60's, 70's, and 80's) were used to generate virtual lesion masks for each decade at three lesion frequency thresholds, and these virtual lesion masks were applied as regions of avoidance (ROA) in fiber tracking to estimate connectivity changes. Connections showing significant differences in fiber density with and without ROA were identified using paired tests with False Discovery Rate (FDR) correction. Results: Disconnections appeared first from the striatum to middle frontal gyrus (MFG) in the 50's, then from the thalamus to MFG in the 60's and extending to the superior frontal gyrus in the 70's, and ultimately including much more widespread cortical and hippocampal nodes in the 80's. Conclusion: Changes in the structural disconnectome due to age-related WMH can be estimated using the virtual lesion approach. The observed disconnections may contribute to the cognitive and sensorimotor deficits seen in aging.

Antidepressant effects of acute sleep deprivation are reduced in highly controlled environments.

BACKGROUND: Numerous studies summarized in a recent meta-analysis have shown sleep deprivation rapidly improves depressive symptoms in approximately 50 % of individuals with major depressive disorder (MDD), however those studies were typically conducted in clinical settings. Here we investigated the effects of sleep deprivation utilizing a highly controlled experimental approach. METHODS: 36 antidepressant-free individuals with MDD and 10 healthy controls (HC) completed a 5 day/4-night protocol consisting of adaptation, baseline, total sleep deprivation (TSD), and recovery phases. Light was kept consistently dim (≤50 lx), meals were regulated, and activity was restricted. In-the-moment mood was assessed using a modified Hamilton Rating Scale for Depression (HRSD) at screening and each morning following the experimental nights. RESULTS: Day of study had a significant effect on mood in both groups. Post-hoc analyses revealed that significant effects were attributed to mood improvement in the MDD group following study initiation prior to beginning TSD, and in the HC group following recovery sleep, but were not due to mood improvement in the MDD group during TSD. No further improvement in mood occurred during 36 h of TSD. LIMITATIONS: Strict eligibility requirements may limit generalizability. The requirement to be medication free may have biased toward a less severely depressed sample. CONCLUSIONS: Results revealed that individuals with moderate MDD can experience a significant reduction in depressive symptoms upon entering a highly controlled laboratory environment. Environmental effects on mood can be substantial and need to be considered.

Mapping the relationship of white matter lesions to depression in multiple sclerosis.

Importance: Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects nearly one million people in the United States. Up to 50% of patients with MS experience depression. Objective: To investigate how white matter network disruption is related to depression in MS. Design: Retrospective case-control study of participants who received research-quality 3-tesla neuroimaging as part of MS clinical care from 2010-2018. Analyses were performed from May 1 to September 30, 2022. Setting: Single-center academic medical specialty MS clinic. Participants: Participants with MS were identified via the electronic health record (EHR). All participants were diagnosed by an MS specialist and completed research-quality MRI at 3T. After excluding participants with poor image quality, 783 were included. Inclusion in the depression group (MS+Depression) required either: 1) ICD-10 depression diagnosis (F32-F34.*); 2) prescription of antidepressant medication; or 3) screening positive via Patient Health Questionnaire-2 (PHQ-2) or -9 (PHQ-9). Age- and sex-matched nondepressed comparators (MS-Depression) included persons with no depression diagnosis, no psychiatric medications, and were asymptomatic on PHQ-2/9. Exposure: Depression diagnosis. Main Outcomes and Measures: We first evaluated if lesions were preferentially located within the depression network compared to other brain regions. Next, we examined if MS+Depression patients had greater lesion burden, and if this was driven by lesions specifically in the depression network. Outcome measures were the burden of lesions (e.g., impacted fascicles) within a network and across the brain. Secondary measures included between-diagnosis lesion burden, stratified by brain network. Linear mixed-effects models were employed. Results: Three hundred-eighty participants met inclusion criteria, (232 MS+Depression: age[SD]=49[12], %females=86; 148 MS-Depression: age[SD]=47[13], %females=79). MS lesions preferentially affected fascicles within versus outside the depression network (ß=0.09, 95% CI=0.08-0.10, P<0.001). MS+Depression had more white matter lesion burden (ß=0.06, 95% CI=0.01-0.10, P=0.015); this was driven by lesions within the depression network (ß=0.02, 95% CI 0.003-0.040, P=0.020). Conclusions and Relevance: We provide new evidence supporting a relationship between white matter lesions and depression in MS. MS lesions disproportionately impacted fascicles in the depression network. MS+Depression had more disease than MS-Depression, which was driven by disease within the depression network. Future studies relating lesion location to personalized depression interventions are warranted.

B 1 + $$ {\mathrm{B}}_1

PURPOSE: Nuclear Overhauser effect magnetization transfer ratio (NOEMTR ) is a technique used to investigate brain lipids and macromolecules in greater detail than other techniques and benefits from increased contrast at 7 T. However, this contrast can become degraded because of B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities present at ultra-high field strengths. High-permittivity dielectric pads (DP) have been used to correct for these inhomogeneities via displacement currents generating secondary magnetic fields. The purpose of this work is to demonstrate that dielectric pads can be used to mitigate B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities and improve NOEMTR contrast in the temporal lobes at 7 T. METHODS: Partial 3D NOEMTR contrast images and whole brain B 1 + $$ {\mathrm{B}}_1^{+} $$ field maps were acquired on a 7 T MRI across six healthy subjects. Calcium titanate DP, having a relative permittivity of 110, was placed next to the subject's head near the temporal lobes. Pad corrected NOEMTR images had a separate postprocessing linear correction applied. RESULTS: DP provided supplemental B 1 + $$ {\mathrm{B}}_1^{+} $$ to the temporal lobes while also reducing the B 1 + $$ {\mathrm{B}}_1^{+} $$ magnitude across the posterior and superior regions of the brain. This resulted in a statistically significant increase in NOEMTR contrast in substructures of the temporal lobes both with and without linear correction. The padding also produced a convergence in NOEMTR contrast toward approximately equal mean values. CONCLUSION: NOEMTR images showed significant improvement in temporal lobe contrast when DP were used, which resulted from an increase in B 1 + $$ {\mathrm{B}}_1^{+} $$ homogeneity across the entire brain slab. DP-derived improvements in NOEMTR are expected to increase the robustness of the brain substructural measures both in healthy and pathological conditions.

Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation.

Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala-cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala-ACC connectivity.

Young versus older subject diffusion magnetic resonance imaging data for virtual white matter lesion tractography.

White matter hyperintensity (WMH) lesions on T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and changes in adjacent normal-appearing white matter can disrupt computerized tract reconstruction and result in inaccurate measures of structural brain connectivity. The virtual lesion approach provides an alternative strategy for estimating structural connectivity changes due to WMH. To assess the impact of using young versus older subject diffusion MRI data for virtual lesion tractography, we leveraged recently available diffusion MRI data from the Human Connectome Project (HCP) Lifespan database. Neuroimaging data from 50 healthy young (39.2 ± 1.6 years) and 46 healthy older (74.2 ± 2.5 years) subjects were obtained from the publicly available HCP-Aging database. Three WMH masks with low, moderate, and high lesion burdens were extracted from the WMH lesion frequency map of locally acquired FLAIR MRI data. Deterministic tractography was conducted to extract streamlines in 21 WM bundles with and without the WMH masks as regions of avoidance in both young and older cohorts. For intact tractography without virtual lesion masks, 7 out of 21 WM pathways showed a significantly lower number of streamlines in older subjects compared to young subjects. A decrease in streamline count with higher native lesion burden was found in corpus callosum, corticostriatal tract, and fornix pathways. Comparable percentages of affected streamlines were obtained in young and older groups with virtual lesion tractography using the three WMH lesion masks of increasing severity. We conclude that using normative diffusion MRI data from young subjects for virtual lesion tractography of WMH is, in most cases, preferable to using age-matched normative data.