Objective:With aging, people with HIV (PWH) have diminishing postural stability that increases liability for falls. Factors and neuromechanisms contributing to instability are incompletely known. Brain white matter abnormalities seen as hyperintense (WMH) signals have been considered to underlie instability in normal aging and PWH. We questioned whether sway-WMH relations endured after accounting for potentially relevant demographic, physiological, and HIV-related variables.Design:Mixed cross-sectional/longitudinal data were acquired over 15 years in 141 PWH and 102 age-range matched controls, 25-80 years old.Methods:Multimodal structural MRI data were quantified for seven total and regional WMH volumes. Static posturography acquired with a force platform measured sway path length separately with eyes closed and eyes open. Statistical analyses used multiple regression with mixed modeling to test contributions from non-MRI and nonpath data on sway path-WMH relations.Results:In simple correlations, longer sway paths were associated with larger WMH volumes in PWH and controls. When demographic, physiological, and HIV-related variables were entered into multiple regressions, the sway-WMH relations under both vision conditions in the controls were attenuated when accounting for age and two-point pedal discrimination. Although the sway-WMH relations in PWH were influenced by age, 2-point pedal discrimination, and years with HIV infection, the sway-WMH relations endured for five of the seven regions in the eyes-open condition.Conclusion:The constellation of age-related increasing instability while standing, degradation of brain white matter integrity, and peripheral pedal neuropathy is indicative of advancing fraility and liability for falls as people age with HIV infection.

Recent advances in generative models have paved the way for enhanced generation of natural and medical images, including synthetic brain MRIs. However, the mainstay of current AI research focuses on optimizing synthetic MRIs with respect to visual quality (such as signal-to-noise ratio) while lacking insights into their relevance to neuroscience. To generate high-quality T1-weighted MRIs relevant for neuroscience discovery, we present a two-stage Diffusion Probabilistic Model (called BrainSynth) to synthesize high-resolution MRIs conditionally-dependent on metadata (such as age and sex). We then propose a novel procedure to assess the quality of BrainSynth according to how well its synthetic MRIs capture macrostructural properties of brain regions and how accurately they encode the effects of age and sex. Results indicate that more than half of the brain regions in our synthetic MRIs are anatomically plausible, i.e., the effect size between real and synthetic MRIs is small relative to biological factors such as age and sex. Moreover, the anatomical plausibility varies across cortical regions according to their geometric complexity. As is, the MRIs generated by BrainSynth significantly improve the training of a predictive model to identify accelerated aging effects in an independent study. These results indicate that our model accurately capture the brain's anatomical information and thus could enrich the data of underrepresented samples in a study. The code of BrainSynth will be released as part of the MONAI project at https://github.com/Project-MONAI/GenerativeModels.

The thalamus, with its reciprocal connections to and from cortical, subcortical, and cerebellar regions, is a central active participant in multiple functional brain networks. Structural MRI studies measuring the entire thalamus without respect to its regional or nuclear divisions report volume shrinkage in diseases including HIV infection, alcohol use disorder (AUD), and their comorbidity (HIV+AUD). Here, we examined relations between thalamic subregions (anterior, ventral, medial, and posterior) and neuropsychological functions (attention/working memory, executive functioning, episodic memory, and motor skills). Volumes of thalamic subregions were derived from automatic segmentations of standard T1 weighted MRIs of 65 individuals with HIV, 189 with AUD, 80 with HIV+AUD comorbidity, and 141 healthy controls (CTRL). Total thalamic volume was smaller and cognitive and motor composite scores were lower in the three diagnostic groups relative to the CTRL group. The AUD and HIV+AUD groups had significantly smaller thalamic subregional volumes than the CTRL group. The HIV+AUD group had smaller anterior thalamic volume than the HIV-only group and smaller ventral thalamic volume than the AUD-only group. In the HIV+AUD group, memory scores correlated with anterior thalamic volumes, attention/working memory scores correlated with posterior and medial thalamic volumes, and motor skill scores correlated with posterior thalamic volumes. Exploratory analyses focused on the HIV+AUD group indicated that within the posterior thalamic region, the pulvinar and medial geniculate nuclei were related to attention/working memory scores, and the pulvinar was related to motor skills scores. This study is novel in locating volume deficits in specific thalamic subregions, in addition to the thalamus as a whole, in HIV, AUD, and their comorbidity and in identifying functional ramifications of these deficits. Taken together, this study highlights the relevance of thalamic subregional volume deficits to dissociable cognitive and motor processes.

Grip strength is considered one of the simplest and reliable indices of general health. Although motor ability and strength are commonly affected in people with alcohol use disorder (AUD), factors predictive of grip strength decline in AUD have not been investigated. Here, we employed a data-driven analysis predicting grip strength from measurements in 53 controls and 110 AUD participants, 53 of whom were comorbid with HIV infection. Controls and AUD were matched on sex, age, and body mass index. Measurements included commonly available metrics of brain structure, neuropsychological functioning, behavioural status, haematological and health status, and demographics. Based on 5-fold stratified cross-validation, a machine learning approach predicted grip strength separately for each cohort. The strongest (top 10%) predictors of grip were then tested against grip strength with correlational analysis. Leading grip strength predictors for both cohorts were cerebellar volume and mean corpuscular haemoglobin concentration. Predictors specific to controls were Backwards Digit Span, precentral gyrus volume, diastolic blood pressure, and mean platelet volume, which together significantly predicted grip strength ( R 2  = 0.255, p  = 0.001). Unique predictors for AUD were comorbidity for HIV infection, social functioning, insular volume, and platelet count, which together significantly predicted grip strength ( R 2  = 0.162, p  = 0.002). These cohort-specific predictors were doubly dissociated. Salient predictors of grip strength differed by diagnosis with only modest overlap. The constellation of cohort-specific predictive measurements of compromised grip strength provides insight into brain, behavioural, and physiological factors that may signal subtly affected yet treatable processes of physical decline and frailty.

This work implements a method for measuring cerebral kinetics of glucose metabolism using 1 H magnetic resonance spectroscopy (MRS) in rats using a small-animal 7T MRI system. The method has been demonstrated to be readily applied to nonhuman primates and human subjects using clinical MRI systems. The extension to small animals requires intravenous administration of small quantities of 13C-labeled glucose, and adaptation of data analysis procedures to data acquired at high magnetic field strength. We demonstrate robust quantification of 13 C enrichment within the glutamate at the C4 position. This methodology will facilitate future translational research involving preclinical models of human disease.

Objective: The prevalence of mild to moderate cognitive impairment, including episodic memory deficits, in people living with HIV (PLWH) remains high despite the life-extending success of antiretroviral pharmacotherapy. With PLWH now reaching near-normal life expectancy, questions concerning a potential synergy between age- and HIV disease-related effects, including degradation in fronto-limbic circuits, neural systems also compromised in Parkinson’s disease (PD), have emerged. Participants and Methods: This cross-sectional study examined the similarities and differences in component processes of verbal episodic memory and their neural correlates in 42 PLWH, 41 individuals with PD, and 37 controls (CTRL) (all participants aged 45-79 years). Learning over five trials, short-delay (SD) and long-delay, (LD), free-recall (FR) and cued-recall (CR) indices were assessed using the California Verbal Learning Test-2. Retention scores for FR and CR were derived adjusting for Trial 5 performance. All memory scores were age- and education-corrected based on the control group and reported as Z-scores. Regional brain volumes were calculated using 3T MRI data and the SRI24 atlas to delineate frontal (precentral, superior, orbital, middle, inferior, supplemental motor, and medial) and limbic (hippocampus, thalamus) regions. Brain volumes were age- and head-sized corrected based on 238 controls (19-86 years old). Results: Compared with the CTRL group, the HIV and PD groups were impaired on learning across trials and on SD and LD free- and cued-recall, with no group difference between the HIV and PD groups on any score. All three groups benefited similarly from cues compared with free-recall. The HIV and PD groups did not differ from CTRL on retention scores. Regarding brain volumes, the HIV group had smaller middle frontal volumes than the PD or CTRL groups and smaller thalamic volumes than the PD group. Correlational analyses (Bonferroni correction for 8 comparisons, p<.01) indicated that fewer total number of words recalled on Trial 5, learning over Trials 1-5, total words recalled on SD-CR, LD-FR, and LD-CR were associated with smaller orbitofrontal volume in the HIV but not the PD group; the correlations between orbitofrontal volume and memory scores were significantly different between the HIV and PD groups. In PD, but not HIV, lower retention scores on SD-FR and LD-CR correlated to smaller hippocampal volume. Conclusions: Impairment in learning and cued recall performance indicate that both encoding and retrieval processes are affected in PLWH and PD. Neural correlates of verbal memory differed between groups, with orbitofrontal volume associated with learning and recall in PLWH, whereas hippocampal volume was associated with retention scores in PD. Together, these results suggest that different nodes within the fronto-limbic mnemonic circuitry underlie the mutual verbal episodic memory deficits observed in older PLWH and PD. Support: AA023165, AA005965, AA107347, AA010723, NS07097, MH113406, and the Michael J. Fox Foundation for Parkinson’s Research

Minor artifacts introduced during image acquisition are often negligible to the human eye, such as a confined field of view resulting in MRI missing the top of the head. This cropping artifact, however, can cause suboptimal processing of the MRI resulting in data omission or decreasing the power of subsequent analyses. We propose to avoid data or quality loss by restoring these missing regions of the head via variational autoencoders (VAE), a deep generative model that has been previously applied to high resolution image reconstruction. Based on diffusion weighted images (DWI) acquired by the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), we evaluate the accuracy of inpainting the top of the head by common autoencoder models (U-Net, VQVAE, and VAE-GAN) and a custom model proposed herein called U-VQVAE. Our results show that U-VQVAE not only achieved the highest accuracy, but also resulted in MRI processing producing lower fractional anisotropy (FA) in the supplementary motor area than FA derived from the original MRIs. Lower FA implies that inpainting reduces noise in processing DWI and thus increases the quality of the generated results. The code is available at https://github.com/RdoubleA/DWI-inpainting.

The Blood-Oxygen-Level-Dependent (BOLD) signal of resting-state fMRI (rs-fMRI) records the temporal dynamics of intrinsic functional networks in the brain. However, existing deep learning methods applied to rs-fMRI either neglect the functional dependency between different brain regions in a network or discard the information in the temporal dynamics of brain activity. To overcome those shortcomings, we propose to formulate functional connectivity networks within the context of spatio-temporal graphs. We train a spatio-temporal graph convolutional network (ST-GCN) on short sub-sequences of the BOLD time series to model the non-stationary nature of functional connectivity. Simultaneously, the model learns the importance of graph edges within ST-GCN to gain insight into the functional connectivities contributing to the prediction. In analyzing the rs-fMRI of the Human Connectome Project (HCP, N=1,091) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA, N=773), ST-GCN is significantly more accurate than common approaches in predicting gender and age based on BOLD signals. Furthermore, the brain regions and functional connections significantly contributing to the predictions of our model are important markers according to the neuroscience literature.

Development of the human brain continues throughout adolescence and into young adulthood and is characterized by declining cortical gray matter. Initiation of heavy drinking alcohol, which commonly occurs during neurodevelopment years, can potentially alter normal brain trajectories. This analysis questioned the effect of initiating heavy drinking on developmental trajectories of supratentorial cortex and the cerebellum.

Healthy aging is accompanied by compromise in brain white matter fiber integrity that is more pronounced in anterior than posterior and in superior than inferior fiber systems. To study the functional ramifications of degraded and intact structural connectivity in aging we used behavioral testing of interhemispheric function in combination with diffusion tensor imaging (DTI). Here, we focused on callosal fibers structurally connecting the two cerebral hemispheres and pontine fibers connecting the two cerebral hemispheres with the cerebellum. Quantitative analysis used our novel DTI-based fiber tract-driven topographical mapping to measure structure-function relations at specific locations within fiber tracts. In healthy older adults, we found callosal fiber compromise that was most pronounced in anterior genu regions. In young adults, faster interhemispheric visuomotor transfer time was correlated with greater fiber integrity in the genu. By contrast, faster interhemispheric visuomotor transfer time was best predicted by greater fiber integrity in medial callosal body regions in older adults. Although pons fiber integrity did not differ between young and older adults, greater integrity of anterior pontine fibers branching into the right cerebellar cortex were related to faster bilateral than unilateral visuomotor processing speed in older adults only, supporting a role for the pons in interhemispheric facilitation.

In alcohol-dependent patients, alcohol-associated cues elicit brain activations in mesocorticolimbic networks related to the rewarding properties of the drug and were previously found to be associated with relapse behaviour. Functional magnetic resonance imaging (fMRI) was used to assess cue-reactivity during the presentation of alcohol-related pictures in 73 recently detoxified alcohol-dependent patients before and after randomized double-blind treatment with naltrexone, acamprosate or placebo. Using Cox-regression we examined the effect of fMRI cue-reactivity and treatment on the time to the first severe relapse. In early abstinence, the activated network consisted of the ventral striatum, cingulate gyrus and prefrontal areas. After 2 weeks of treatment with naltrexone, acamprosate or placebo cue-elicited brain activity in the striatum and the thalamus was decreased in comparison with the first medication-free fMRI session. With increasing fMRI, cue-reactivity at the first fMRI session relapse risk was reduced in the Naltrexone compared with the Acamprosate group for the ventral striatum. Notably, remaining cue-induced brain activation in the ventral striatum during the second fMRI session was negatively associated with the time to first severe relapse. fMRI cue-reactivity can be used as a prognostic factor for relapse in alcohol-dependent patients. Alcohol-dependent patients with high fMRI cue-reactivity might especially benefit from Naltrexone treatment. [This work was supported by the DFG (He 2597/4-1&4-2; Sm 80/1-1) and the BMBF (01EB0110&01EB0410 km).]

slice through the heart acquired with dynamic spCSI after injection of hyperpolarized [1-C]-lactate. The images were averaged over 4 time points (10 to 25 s). Fig. 1: (a) Time courses of Lac, Pyr, and Bic from a 15-mm slice through a rat heart in vivo after injection of 2.8 mL hyperpolarized [1-C]pyruvate (BGL = 137mg/dL). (b) Same as (a), but after injection of 2.8 mL hyperpolarized [1-C]-lactate (BGL = 146 mg/dL). Hyperpolarized [1-C]-Lactate as a Tool for the In Vivo Investigation of Cardiac Metabolism