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Background Prenatal alcohol exposure has been linked to impairment in cerebellar structure and function, including eyeblink conditioning. The deep cerebellar nuclei, which play a critical role in cerebellar-mediated learning, receive extensive inputs from brain stem and cerebellar cortex and provide the point of origin for most of the output fibers to other regions of the brain. We used in vivo 1H magnetic resonance spectroscopy ( MRS) to examine effects of prenatal alcohol exposure on neurochemistry in this important cerebellar region. Methods MRS data from the deep cerebellar nuclei were acquired from 37 children with heavy prenatal alcohol exposure and 17 non- or minimally exposed controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa. Results Increased maternal alcohol consumption around time of conception was associated with lower N-Acetylaspartate ( NAA) levels in the deep nuclei ( r = −0.33, p < 0.05). Higher levels of alcohol consumption during pregnancy were related to lower levels of the choline-containing metabolites ( r = −0.37, p < 0.01), glycerophosphocholine plus phosphocholine (Cho). Alcohol consumption levels both at conception ( r = 0.35, p < 0.01) and during pregnancy ( r = 0.38, p < 0.01) were related to higher levels of glutamate plus glutamine (Glx). All these effects continued to be significant after controlling for potential confounders. Conclusions The lower NAA levels seen in relation to prenatal alcohol exposure may reflect impaired neuronal integrity in the deep cerebellar nuclei. Our finding of lower Cho points to disrupted Cho metabolism of membrane phospholipids, reflecting altered neuropil development with potentially reduced content of dendrites and synapses. The alcohol-related alterations in Glx may suggest a disruption of the glutamate-glutamine cycling involved in glutamatergic excitatory neurotransmission. [ABSTRACT FROM AUTHOR]

Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to ?9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization. [ABSTRACT FROM AUTHOR]

Metabolic imaging of the human brain by in-vivo magnetic resonance spectroscopic imaging (MRSI) can non-invasively probe neurochemistry in healthy and disease conditions. MRSI at ultra-high field (≥ 7 T) provides increased sensitivity for fast high-resolution metabolic imaging, but comes with technical challenges due to non-uniform B0 field. Here, we show that an integrated RF-receive/B0-shim (AC/DC) array coil can be used to mitigate 7 T B0 inhomogeneity, which improves spectral quality and metabolite quantification over a whole-brain slab. Our results from simulations, phantoms, healthy and brain tumor human subjects indicate improvements of global B0 homogeneity by 55%, narrower spectral linewidth by 29%, higher signal-to-noise ratio by 31%, more precise metabolite quantification by 22%, and an increase by 21% of the brain volume that can be reliably analyzed. AC/DC shimming provide the highest correlation (R2 = 0.98, P = 0.001) with ground-truth values for metabolite concentration. Clinical translation of AC/DC and MRSI is demonstrated in a patient with mutant-IDH1 glioma where it enables imaging of D-2-hydroxyglutarate oncometabolite with a 2.8-fold increase in contrast-to-noise ratio at higher resolution and more brain coverage compared to previous 7 T studies. Hence, AC/DC technology may help ultra-high field MRSI become more feasible to take advantage of higher signal/contrast-to-noise in clinical applications. [ABSTRACT FROM AUTHOR]

People living with HIV are at three times greater risk for depressive symptoms. Inflammation is a notable predictor of depression, and people with HIV exhibit chronic inflammation despite antiretroviral therapy. We hypothesised that inflammatory biomarkers may mediate the association between HIV status and depressive symptoms. Participants (N = 60, 53% girls, median [interquartile range (IQR)] age 15.5 [15.0, 16.0] years, 70% living with HIV, of whom 90.5% were virally-suppressed) completed the nine-item Patient Health Questionnaire (PHQ-9). We measured choline and myo-inositol in basal ganglia, midfrontal gray matter, and peritrigonal white matter using magnetic resonance spectroscopy, and 16 inflammatory proteins in blood serum using ELISA and Luminex™ multiplex immunoassays. Using structural equation mediation modelling, we calculated standardised indirect effect estimates with 95% confidence intervals. Median [IQR] total PHQ-9 score was 3 [0, 7]. HIV status was significantly associated with total PHQ-9 score (B = 3.32, p = 0.022). Participants with HIV showed a higher choline-to-creatine ratio in the basal ganglia than those without HIV (β = 0.86, pFDR = 0.035). In blood serum, participants with HIV showed higher monocyte chemoattractant protein-1 (MCP-1, β = 0.59, pFDR = 0.040), higher chitinase-3 like-1 (YKL-40, β = 0.73, pFDR = 0.032), and lower interleukin-1beta (IL-1β, β = -0.67, pFDR = 0.047) than those without HIV. There were no significant associations of any biomarkers with total PHQ-9 score. None of the indirect effects were significant, mediating <13.1% of the association. Findings remained consistent when accounting for age, gender, and time between neuroimaging and PHQ-9 administration. Using a robust analytical approach in a community-based sample, we have shown that participants living with HIV reported greater depressive symptoms than those without HIV, but we did not find that neuroimaging and blood biomarkers of inflammation significantly mediated this association. Further studies with participants experiencing severe depression may help to elucidate the links between HIV, inflammation, and depression. [ABSTRACT FROM AUTHOR]

Lissencephaly (LIS) is a rare neurodevelopmental disorder with severe symptoms caused by abnormal neuronal migration during cortical development. It is caused by both genetic and non-genetic factors. Despite frequent studies about the cortex, comprehensive elucidation of structural abnormalities and their effects on the white matter is limited. The main objective of this study is to analyze abnormal neuronal migration pathways and white matter fiber organization in LIS1-associated LIS using diffusion MRI (dMRI) tractography. For this purpose, slabs of brain specimens with LIS (n = 3) and age and sex-matched controls (n = 4) were scanned with 3T dMRI. Our high-resolution ex vivo dMRI successfully identified common abnormalities across the samples. The results revealed an abnormal increase in radially oriented subcortical fibers likely associated with radial migration pathways and u-fibers and a decrease in association fibers in all LIS specimens. [ABSTRACT FROM AUTHOR]

Background: Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection. Methods: 75 CHER participants in follow-up care at FAMCRU (Family Centre for Research with Ubuntu), as well as 66 age-matched controls, received magnetic resonance imaging (MRI) on a 3 T Siemens Allegra at ages 5, 7 and/or 9 years. MR images were processed, and cortical surfaces reconstructed using the FreeSurfer longitudinal processing stream. Vertex-wise linear mixed effects (LME) analyses were performed across the whole brain to compare the means and linear rates of change of cortical thickness and gyrification from 5 to 9 years between CPHIV and controls, as well as to examine effects of ART interruption. Results: Children without HIV demonstrated generalized cortical thinning from 5 to 9 years, with the rate of thinning varying by region, as well as regional age-related gyrification increases. Overall, the means and developmental trajectories of cortical thickness and gyrification were similar in CPHIV. However, at an uncorrected p < 0.005, 6 regions were identified where the cortex of CPHIV was thicker than in uninfected children, namely bilateral insula, left supramarginal, lateral orbitofrontal and superior temporal, and right medial superior frontal regions. Planned ART interruption did not affect development of cortical morphometry. Conclusions: Although our results suggest that normal development of cortical morphometry between the ages of 5 and 9 years is preserved in CPHIV who started ART early, these findings require further confirmation with longitudinal follow-up through the vulnerable adolescent period. [ABSTRACT FROM AUTHOR]

Similar cortical morphometry trajectories from 5 to 9 years in children with perinatal HIV who started treatment before age 2 years and uninfected controls. Correction to: Similar cortical morphometry trajectories from 5 to 9 years in children with perinatal HIV who started treatment before age 2 years and uninfected controls The original article can be found online at https://doi.org/10.1186/s12868-023-00783-7. [Extracted from the article]

Background: Traumatic axonal injury (TAI) may be reversible, yet there are currently no clinical imaging tools to detect axonal recovery in patients with traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to characterize serial changes in fractional anisotropy (FA) within TAI lesions of the corpus callosum (CC). We hypothesized that recovery of FA within a TAI lesion correlates with better functional outcome.Methods: Patients who underwent both an acute DTI scan (≤day 7) and a subacute DTI scan (day 14 to inpatient rehabilitation discharge) at a single institution were retrospectively analyzed. TAI lesions were manually traced on the acute diffusion-weighted images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured within the TAI lesions at each time point. FA recovery was defined by a longitudinal increase in CC FA that exceeded the coefficient of variation for FA based on values from healthy controls. Acute FA, ADC, AD, and RD were compared in lesions with and without FA recovery, and correlations were tested between lesional FA recovery and functional recovery, as determined by disability rating scale score at discharge from inpatient rehabilitation.Results: Eleven TAI lesions were identified in 7 patients. DTI detected FA recovery within 2 of 11 TAI lesions. Acute FA, ADC, AD, and RD did not differ between lesions with and without FA recovery. Lesional FA recovery did not correlate with disability rating scale scores.Conclusions: In this retrospective longitudinal study, we provide initial evidence that FA can recover within TAI lesions. However, FA recovery did not correlate with improved functional outcomes. Prospective histopathological and clinical studies are needed to further elucidate whether lesional FA recovery indicates axonal healing and has prognostic significance. [ABSTRACT FROM AUTHOR]

Background and Purpose: Alexander disease (AxD) is a neurodegenerative disorder caused by heterozygous Glial Fibrillary Acidic Protein mutation. The characteristic structural findings of AxD, such as leukodystrophic features, are well known, while association fibers of AxD remain uninvestigated. The aim of this study was to explore global and subcortical fibers in four brains with AxD using ex vivo diffusion tractography METHODS: High-angular-resolution diffusion magnetic resonance imaging (HARDI) tractography and diffusion-tensor imaging (DTI) tractography were used to evaluate long and short association fibers and compared to histological findings in brain specimens obtained from four donors with AxD and two donors without neurological disorders RESULTS: AxD brains showed impairment of long association fibers, except for the arcuate fasciculus and cingulum bundle, and abnormal trajectories of the inferior longitudinal and fronto-occipital fasciculi on HARDI tractography and loss of multidirectionality in subcortical fibers on DTI tractography. In histological studies, AxD brains showed diffuse low density on Klüver-Barrera and neurofilament staining and sporadic Rosenthal fibers on hematoxylin and eosin staining CONCLUSIONS: This study describes the spatial distribution of degenerations of short and long association fibers in AxD brains using combined tractography and pathological findings. [ABSTRACT FROM AUTHOR]

Children with perinatally acquired HIV (CPHIV) have poor cognitive outcomes despite early combination antiretroviral therapy (cART). While CPHIV‐related brain alterations can be investigated separately using proton magnetic resonance spectroscopy (1H‐MRS), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and functional MRI (fMRI), a set of multimodal MRI measures characteristic of children on cART has not been previously identified. We used the embedded feature selection of a logistic elastic‐net (EN) regularization to select neuroimaging measures that distinguish CPHIV from controls and measured their classification performance via the area under the receiver operating characteristic curve (AUC) using repeated cross validation. We also wished to establish whether combining MRI modalities improved the models. In single modality analysis, sMRI volumes performed best followed by DTI, whereas individual EN models on spectroscopic, gyrification, and cortical thickness measures showed no class discrimination capability. Adding DTI and 1H‐MRS in basal measures to sMRI volumes produced the highest classification performance validation accuracy=85%AUC=0.80. The best multimodal MRI set consisted of 22 DTI and sMRI volume features, which included reduced volumes of the bilateral globus pallidus and amygdala, as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the right corticospinal tract in cART‐treated CPHIV. Consistent with previous studies of CPHIV, select subcortical volumes obtained from sMRI provide reasonable discrimination between CPHIV and controls. This may give insight into neuroimaging measures that are relevant in understanding the effects of HIV on the brain, thereby providing a starting point for evaluating their link with cognitive performance in CPHIV. [ABSTRACT FROM AUTHOR]

The neural circuits that support human cognition are a topic of enduring interest. Yet, there are limited tools available to map brain circuits in the human and nonhuman primate brain. We harnessed high-resolution diffusion MR tractography, anatomic, and transcriptomic data from individuals of either sex to investigate the evolution and development of frontal cortex circuitry. We applied machine learning to RNA sequencing data to find corresponding ages between humans and macaques and to compare the development of circuits across species. We transcriptionally defined neural circuits by testing for associations between gene expression and white matter maturation. We then considered transcriptional and structural growth to test whether frontal cortex circuit maturation is unusually extended in humans relative to other species. We also considered gene expression and high-resolution diffusion MR tractography of adult brains to test for cross-species variation in frontal cortex circuits. We found that frontal cortex circuitry development is extended in primates, and concomitant with an expansion in corticocortical pathways compared with mice in adulthood. Importantly, we found that these parameters varied relatively little across humans and studied primates. These data identify a surprising collection of conserved features in frontal cortex circuits across humans and Old World monkeys. Our work demonstrates that integrating transcriptional and structural data across temporal dimensions is a robust approach to trace the evolution of brain pathways in primates. [ABSTRACT FROM AUTHOR]

Perivascular spaces (PVS) are compartments surrounding cerebral blood vessels that become visible on MRI when enlarged. Enlarged PVS (EPVS) are commonly seen in patients with cerebral small vessel disease (CSVD) and have been suggested to reflect dysfunctional perivascular clearance of soluble waste products from the brain. In this study, we investigated histopathological correlates of EPVS and how they relate to vascular amyloid-β (Aβ) in cerebral amyloid angiopathy (CAA), a form of CSVD that commonly co-exists with Alzheimer's disease (AD) pathology. We used ex vivo MRI, semi-automatic segmentation and validated deep-learning-based models to quantify EPVS and associated histopathological abnormalities. Severity of MRI-visible PVS during life was significantly associated with severity of MRI-visible PVS on ex vivo MRI in formalin fixed intact hemispheres and corresponded with PVS enlargement on histopathology in the same areas. EPVS were located mainly around the white matter portion of perforating cortical arterioles and their burden was associated with CAA severity in the overlying cortex. Furthermore, we observed markedly reduced smooth muscle cells and increased vascular Aβ accumulation, extending into the WM, in individually affected vessels with an EPVS. Overall, these findings are consistent with the notion that EPVS reflect impaired outward flow along arterioles and have implications for our understanding of perivascular clearance mechanisms, which play an important role in the pathophysiology of CAA and AD. [ABSTRACT FROM AUTHOR]

Abstract: There is increasing evidence regarding the importance of the hypothalamus for understanding sex differences in relation to neurological, psychiatric, endocrine and sleep disorders. Although different in histology, physiology, connections and function, multiple hypothalamic nuclei subserve non-voluntary functions and are nodal points for the purpose of maintaining homeostasis of the organism. Thus, given the critical importance of hypothalamic nuclei and their key multiple roles in regulating basic functions, it is important to develop the ability to conduct in vivo human studies of anatomic structure, volume, connectivity, and function of hypothalamic regions represented at the level of its nuclei. The goals of the present study were to develop a novel method of semi-automated volumetric parcellation for the human hypothalamus that could be used to investigate clinical conditions using MRI and to demonstrate its applicability. The proposed new method subdivides the hypothalamus into five parcels based on visible anatomic landmarks associated with specific nuclear groupings and was confirmed using two ex vivo hypothalami that were imaged in a 7 T (7T) scanner and processed histologically. Imaging results were compared with histology from the same brain. Further, the method was applied to 44 healthy adults (26 men; 18 women, comparable on age, handedness, ethnicity, SES) to derive normative volumes and assess sex differences in hypothalamic regions using 1.5 T MRI. Men compared to women had a significantly larger total hypothalamus, relative to cerebrum size, similar for both hemispheres, a difference that was primarily driven by the tuberal region, with the sex effect size being largest in the superior tuberal region and, to a lesser extent, inferior tuberal region. Given the critical role of hypothalamic nuclei in multiple chronic diseases and the importance of sex differences, we argue that the use of the novel methodology presented here will allow for critical investigations of these disorders and further delineation of potential treatments, particularly sex-specific approaches to gene and drug discoveries that involve hypothalamic nuclei. [Copyright &y& Elsevier]

Introduction: Many children living with HIV (CLWH) display impaired cognition. Although early combination antiretroviral therapy (ART) produces improved cognitive outcomes, more long‐term outcome data are needed. After concluding the Children with HIV Early antiRetroviral (CHER) trial in 2011, we investigated cognitive performance, at seven and nine years of age. Participants had been randomized to deferred ART (ART‐Def; n = 22); immediate time‐limited ART for 40 weeks (ART‐40W; n = 30) and immediate time‐limited ART for 96 weeks (ART‐96W; n = 18). We also recruited HIV‐exposed uninfected (CHEU; n = 28) and HIV‐unexposed (CHU; n = 35) children. Methods: Data were collected between May 2012 and December 2017. Mixed‐model repeated‐measures ANOVAs assessed differences over time between CLWH (ART‐40W, ART‐96W and ART‐Def) and CHIV‐ CHEU and CHU between ART‐Early (ART‐40W and ART‐96W), ART‐Def, CHEU and CHU; and between ART‐40W, ART‐96W, ART‐Def, CHEU and CHU. Results: All comparisons found significant effects of Time for most outcome variables (better scores at nine than at seven years; ps < 0.05). The first ANOVAs found that for (a) motor dexterity, CLWH performed worse than CHIV‐ at seven years (p < 0.001) but improved to equivalence at nine years, (b) visual‐spatial processing and problem solving, only CLWH (p < 0.04) showed significant performance improvement over time and (c) working memory and executive function, CLWH performed worse than CHIV‐ at both seven and nine years (p = 0.03 and 0.04). The second ANOVAs found that for (a) working memory, CHU performed better than ART‐Early and CHEU (p < 0.01 and <0.04), and (b) motor dexterity, ART‐Def performed worse than ART‐Early, CHEU and CHU at seven years (p = 0.02, <0.001 and <0.001 respectively) but improved to equivalence at nine years (ps > 0.17). Similarly, for motor dexterity, ART‐Def performed worse than ART‐96W, CHEU and CHU at seven years (p < 0.04, <0.001 and <0.001) but improved to equivalence at nine years (ps > 0.20). Conclusions: Although neurocognitive developmental trajectories for treatment groups and controls were largely similar (i.e. performance improvements from 7 to 9), all ART‐treated children, regardless of treatment arm, remain at risk for cognitive deficits over early school ages. Although the nature of these deficits may change as cognitive development proceeds, there are potential negative consequences for these children's future learning, reasoning and adaptive functioning. [ABSTRACT FROM AUTHOR]

Small subclinical hyperintense lesions are frequently encountered on brain diffusion-weighted imaging (DWI) scans of patients with cerebral amyloid angiopathy (CAA). Interpretation of these DWI+ lesions, however, has been limited by absence of histopathological examination. We aimed to determine whether DWI+ lesions represent acute microinfarcts on histopathology in brains with advanced CAA, using a combined in vivo MRI—ex vivo MRI—histopathology approach. We first investigated the histopathology of a punctate cortical DWI+ lesion observed on clinical in vivo MRI 7 days prior to death in a CAA case. Subsequently, we assessed the use of ex vivo DWI to identify similar punctate cortical lesions post-mortem. Intact formalin-fixed hemispheres of 12 consecutive cases with CAA and three non-CAA controls were subjected to high-resolution 3 T ex vivo DWI and T2 imaging. Small cortical lesions were classified as either DWI+/T2+ or DWI−/T2+. A representative subset of lesions from three CAA cases was selected for detailed histopathological examination. The DWI+ lesion observed on in vivo MRI could be matched to an area with evidence of recent ischemia on histopathology. Ex vivo MRI of the intact hemispheres revealed a total of 130 DWI+/T2+ lesions in 10/12 CAA cases, but none in controls (p = 0.022). DWI+/T2+ lesions examined histopathologically proved to be acute microinfarcts (classification accuracy 100%), characterized by presence of eosinophilic neurons on hematoxylin and eosin and absence of reactive astrocytes on glial fibrillary acidic protein-stained sections. In conclusion, we suggest that small DWI+ lesions in CAA represent acute microinfarcts. Furthermore, our findings support the use of ex vivo DWI as a method to detect acute microinfarcts post-mortem, which may benefit future histopathological investigations on the etiology of microinfarcts. [ABSTRACT FROM AUTHOR]

Abstract An adiabatic MEscher-GArwood (MEGA)-editing scheme, using asymmetric hyperbolic secant editing pulses, was developed and implemented in a B 1 +-insensitive, 1D-semiLASER (Localization by Adiabatic SElective Refocusing) MR spectroscopic imaging (MRSI) sequence for the non-invasive mapping of γ-aminobutyric acid (GABA) over a whole brain slice. Our approach exploits the advantages of edited-MRSI at 7T while tackling challenges that arise with ultra-high-field-scans. Spatial-spectral encoding, using density-weighted, concentric circle echo planar trajectory readout, enabled substantial MRSI acceleration and an improved point-spread-function, thereby reducing extracranial lipid signals. Subject motion and scanner instabilities were corrected in real-time using volumetric navigators optimized for 7T, in combination with selective reacquisition of corrupted data to ensure robust subtraction-based MEGA-editing. Simulations and phantom measurements of the adiabatic MEGA-editing scheme demonstrated stable editing efficiency even in the presence of ±0.15 ppm editing frequency offsets and B 1 + variations of up to ±30% (as typically encountered in vivo at 7T), in contrast to conventional Gaussian editing pulses. Volunteer measurements were performed with and without global inversion recovery (IR) to study regional GABA levels and their underlying, co-edited, macromolecular (MM) signals at 2.99 ppm. High-quality in vivo spectra allowed mapping of pure GABA and MM-contaminated GABA+ (GABA + MM) along with Glx (Glu + Gln), with high-resolution (eff. voxel size: 1.4 cm3) and whole-slice coverage in 24 min scan time. Metabolic ratio maps of GABA/tNAA, GABA+/tNAA, and Glx/tNAA were correlated linearly with the gray matter fraction of each voxel. A 2.15-fold increase in gray matter to white matter contrast was observed for GABA when enabling IR, which we attribute to the higher abundance of macromolecules at 2.99 ppm in the white matter than in the gray matter. In conclusion, adiabatic MEGA-editing with 1D-semiLASER selection is as a promising approach for edited-MRSI at 7T. Our sequence capitalizes on the benefits of ultra-high-field MRSI while successfully mitigating the challenges related to B 0 /B 1 + inhomogeneities, prolonged scan times, and motion/scanner instability artifacts. Robust and accurate 2D mapping has been shown for the neurotransmitters GABA and Glx. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Even with the increased roll out of combination antiretroviral therapy (cART), paediatric HIV infection is associated with neurodevelopmental delays and neurocognitive deficits that may be accompanied by alterations in brain structure. Few neuroimaging studies have been done in children initiating ART before 2 years of age, and even fewer in children within the critical stage of brain development between 5 and 11 years. We hypothesized that early ART would limit HIV-related brain morphometric deficits at age 7. Study participants were 7-year old HIV-infected (HIV+) children from the Children with HIV Early Antiretroviral Therapy (CHER) trial whose viral loads were supressed at a young age, and age-matched uninfected controls. We used structural magnetic resonance imaging (MRI) and FreeSurfer (http://www.freesurfer.net/) software to investigate effects of HIV and age at ART initiation on cortical thickness, gyrification and regional brain volumes. HIV+ children showed reduced gyrification compared to controls in bilateral medial parietal regions, as well as reduced volumes of the right putamen, left hippocampus, and global white and gray matter and thicker cortex in small lateral occipital region. Earlier ART initiation was associated with lower gyrification and thicker cortex in medial frontal regions. Although early ART appears to preserve cortical thickness and volumes of certain brain structures, HIV infection is nevertheless associated with reduced gyrification in the parietal cortex, and lower putamen and hippocampus volumes. Our results indicate that in early childhood gyrification is more sensitive than cortical thickness to timing of ART initiation. Future work will clarify the implications of these morphometric effects for neuropsychological function. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) studies have shown that prenatal exposure to methamphetamine is associated with alterations in white matter microstructure, but to date no tractography studies have been performed in neonates. The striato-thalamo-orbitofrontal circuit and its associated limbic-striatal areas, the primary circuit responsible for reinforcement, has been postulated to be dysfunctional in drug addiction. This study investigated potential white matter changes in the striatal-orbitofrontal circuit in neonates with prenatal methamphetamine exposure. Mothers were recruited antenatally and interviewed regarding methamphetamine use during pregnancy, and DTI sequences were acquired in the first postnatal month. Target regions of interest were manually delineated, white matter bundles connecting pairs of targets were determined using probabilistic tractography in AFNI-FATCAT, and fractional anisotropy (FA) and diffusion measures were determined in white matter connections. Regression analysis showed that increasing methamphetamine exposure was associated with reduced FA in several connections between the striatum and midbrain, orbitofrontal cortex, and associated limbic structures, following adjustment for potential confounding variables. Our results are consistent with previous findings in older children and extend them to show that these changes are already evident in neonates. The observed alterations are likely to play a role in the deficits in attention and inhibitory control frequently seen in children with prenatal methamphetamine exposure. [ABSTRACT FROM AUTHOR]

Though social influence is a critical factor in the initiation and maintenance of marijuana use, the neural correlates of influence in those who use marijuana are unknown. In this study, marijuana-using young adults (MJ; n = 20) and controls (CON; n = 23) performed a decision-making task in which they made a perceptual choice after viewing the choices of unknown peers via photographs, while they underwent functional magnetic resonance imaging scans. The MJ and CON groups did not show differences in the overall number of choices that agreed with versus opposed group influence, but only the MJ group showed reaction time slowing when deciding against group choices. Longer reaction times were associated with greater activation of frontal regions. The MJ goup, compared to CON, showed significantly greater activation in the caudate when presented with peer information. Across groups, caudate activation was associated with self-reported susceptibility to influence. These findings indicate that young adults who use MJ may exhibit increased effort when confronted with opposing peer influence, as well as exhibit greater responsivity of the caudate to social information. These results not only better define the neural basis of social decisions, but also suggest that marijuana use is associated with exaggerated neural activity during decision making that involves social information. [ABSTRACT FROM AUTHOR]

Abstract: The full potential of magnetic resonance spectroscopic imaging (MRSI) is often limited by localization artifacts, motion-related artifacts, scanner instabilities, and long measurement times. Localized adiabatic selective refocusing (LASER) provides accurate B1-insensitive spatial excitation even at high magnetic fields. Spiral encoding accelerates MRSI acquisition, and thus, enables 3D-coverage without compromising spatial resolution. Real-time position- and shim/frequency-tracking using MR navigators correct motion- and scanner instability-related artifacts. Each of these three advanced MRI techniques provides superior MRSI data compared to commonly used methods. In this work, we integrated in a single pulse sequence these three promising approaches. Real-time correction of motion, shim, and frequency-drifts using volumetric dual-contrast echo planar imaging-based navigators were implemented in an MRSI sequence that uses low-power gradient modulated short-echo time LASER localization and time efficient spiral readouts, in order to provide fast and robust 3D-MRSI in the human brain at 3T. The proposed sequence was demonstrated to be insensitive to motion- and scanner drift-related degradations of MRSI data in both phantoms and volunteers. Motion and scanner drift artifacts were eliminated and excellent spectral quality was recovered in the presence of strong movement. Our results confirm the expected benefits of combining a spiral 3D-LASER-MRSI sequence with real-time correction. The new sequence provides accurate, fast, and robust 3D metabolic imaging of the human brain at 3T. This will further facilitate the use of 3D-MRSI for neuroscience and clinical applications. [Copyright &y& Elsevier]

We present a technique for automatically assigning a neuroanatomical label to each voxel in an MRI volume based on probabilistic information automatically estimated from a manually labeled training set. In contrast to existing segmentation procedures that only label a small number of tissue classes, the current method assigns one of 37 labels to each voxel, including left and right caudate, putamen, pallidum, thalamus, lateral ventricles, hippocampus, and amygdala. The classification technique employs a registration procedure that is robust to anatomical variability, including the ventricular enlargement typically associated with neurological diseases and aging. The technique is shown to be comparable in accuracy to manual labeling, and of sufficient sensitivity to robustly detect changes in the volume of noncortical structures that presage the onset of probable Alzheimer''s disease. [Copyright &y& Elsevier]

• Analysis of longitudinal trajectories of brain metabolite levels offer increased power to detect group differences and confirmed elevated GPC+PCh levels in PHIV children from 5-11 years in gray and white matter. • Age-related increases demonstrated in GPC+PCh in gray matter-containing regions. • Despite finding elevated GPC+PCh across regions and regionally elevated mI in children with PHIV, the trajectories of most metabolites were not different from those of HIV negative controls. • Age-related increases in BG NAA levels were lower in PHIV children than uninfected controls. • The CRM latent factor output shows that concentrations of metabolites within a region are associated more than across regions, apart from the concentration of GPC+PCh which is strongly associated across the three brain regions that were investigated. Treatment guidelines recommend that children with perinatal HIV infection (PHIV) initiate antiretroviral therapy (ART) early in life and remain on it lifelong. As part of a longitudinal study examining the long-term consequences of PHIV and early ART on the developing brain, 89 PHIV children and a control group of 85 HIV uninfected children (HIV-) received neuroimaging at ages 5, 7, 9 and 11 years, including single voxel magnetic resonance spectroscopy (MRS) in three brain regions, namely the basal ganglia (BG), midfrontal gray matter (MFGM) and peritrigonal white matter (PWM). We analysed age-related changes in absolute metabolite concentrations using a multivariate approach traditionally applied to ecological data, the Correlated Response Model (CRM) and compared these to results obtained from a multilevel mixed effect modelling (MMEM) approach. Both approaches produce similar outcomes in relation to HIV status and age effects on longitudinal trajectories. Both methods found similar age-related increases in both PHIV and HIV- children in almost all metabolites across regions. We found significantly elevated GPC+PCh across regions (95% CI=[0.033; 0.105] in BG; 95% CI=[0.021; 0.099] in PWM; 95% CI=[0.059; 0.137] in MFGM) and elevated mI in MFGM (95% CI=[0.131; 0.407]) among children living with PHIV compared to HIV- children; additionally the CRM model also indicated elevated mI in BG (95% CI=[0.008; 0.248]). These findings suggest persistent inflammation across the brain in young children living with HIV despite early ART initiation. [ABSTRACT FROM AUTHOR]

Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison 'single-shot' datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with functional MRI quality reductions. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects from motion estimates. Subsequently, we demonstrate that utilizing a band-stop filter improves post-processing fMRI data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package. • Respiratory perturbations of the main field inflate fMRI head motion estimates. • Breathing-related head motion artifacts compromise functional connectivity quality. • Notch filtering motion estimates (respiratory frequency band) improves data quality. • Motion estimate filtering can be achieved in real-time with FIRMM software. [ABSTRACT FROM AUTHOR]

The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method was proposed to evaluate glymphatic system (GS) function. However, few studies have validated its reliability and reproducibility. Fifty participants' DTI data from the MarkVCID consortium were included in this study. Two pipelines by using DSI studio and FSL software were developed for data processing and ALPS index calculation. The ALPS index was obtained by the average of bilateral ALPS index and was used for testing the cross-vendor, inter-rater and test-retest reliability by using R studio software. The ALPS index demonstrated favorable inter-scanner reproducibility (ICC=0.77 to 0.95, P< 0.001), inter-rater reliability (ICC=0.96 to 1, P< 0.001) and test-retest repeatability (ICC=0.89 to 0.95, P< 0.001), offering a potential biomarker for in vivo evaluation of GS function.

The human brain undergoes substantial developmental changes in the first five years of life. Particularly in the white matter, myelination of axons occurs near birth and continues at a rapid pace during the first 2 to 3 years. Diffusion MRI (dMRI) has revolutionized our understanding of developmental trajectories in white matter. However, the mm-resolution of in vivo techniques bears significant limitation in revealing the microstructure of the developing brain. Polarization sensitive optical coherence tomography (PSOCT) is a three-dimensional (3D) optical imaging technique that uses polarized light interferometry to target myelinated fiber tracts with micrometer resolution. Previous studies have shown that PSOCT contributes significantly to the elucidation of myelin content and quantification of fiber orientation in adult human brains. In this study, we utilized the PSOCT technique to study developing brains during the first 5 years of life in combination with ex vivo dMRI. The results showed that the optical properties of PSOCT quantitatively reveal the myelination process in young children. The imaging contrast of the optic axis orientation is a sensitive measure of fiber orientations in largely unmyelinated brains as young as 3-months-old. The micrometer resolution of PSOCT provides substantially enriched information about complex fiber networks and complements submillimeter dMRI. This new optical tool offers great potential to reveal the white matter structures in normal neurodevelopment and developmental disorders in unprecedented detail.