Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-naïve HIV-infected individuals.

Our study aimed to investigate the short-term effect of combination antiretroviral therapy (cART) on cognitive performance and functional and structural connectivity and their relationship to plasma levels of antiretroviral (ARV) drugs. Seventeen ARV treatment-naïve HIV-infected individuals (baseline mean CD4 cell count, 479 ± 48 cells/mm3) were age matched with 17 HIV-uninfected individuals. All subjects underwent a detailed neurocognitive and functional assessment and magnetic resonance imaging. HIV-infected subjects were scanned before starting cART and 12 weeks after initiation of treatment. Uninfected subjects were assessed once at baseline. Functional connectivity (FC) was assessed within the default mode network while structural connectivity was assessed by voxel-wise analysis using tract-based spatial statistics (TBSS) and probabilistic tractography within the DMN. Tenofovir and emtricitabine blood concentration were measured at week 12 of cART. Prior to cART, HIV-infected individuals had significantly lower cognitive performance than control subjects as measured by the total Z-score from the neuropsychological tests assessing six cognitive domains (p = 0.020). After 12 weeks of cART treatment, there remained only a weak cognitive difference between HIV-infected and HIV-uninfected subjects (p = 0.057). Mean FC was lower in HIV-infected individuals compared with those uninfected (p = 0.008), but FC differences became non-significant after treatment (p = 0.197). There were no differences in DTI metrics between HIV-infected and HIV-uninfected individuals using the TBSS approach and limited evidence of decreased structural connectivity within the DMN in HIV-infected individuals. Tenofovir and emtricitabine plasma concentrations did not correlate with either cognitive performance or imaging metrics.ConclusionsTwelve weeks of cART improves cognitive performance and functional connectivity in ARV treatment-naïve HIV-infected individuals with relatively preserved immune function. Longer periods of observation are necessary to assess whether this effect is maintained

Image analysis and statistical inference in neuroimaging with R

R is a language and environment for statistical computing and graphics. It can be considered an alternative implementation of the S language developed in the 1970s and 1980s for data analysis and graphics (Becker and Chambers, 1984; Becker et al., 1988). The R language is part of the GNU project and offers versions that compile and run on almost every major operating system currently available. We highlight several R packages built specifically for the analysis of neuroimaging data in the context of functional MRI, diffusion tensor imaging, and dynamic contrast-enhanced MRI. We review their methodology and give an overview of their capabilities for neuroimaging. In addition we summarize some of the current activities in the area of neuroimaging software development in R

Decreased functional connectivity with aging and disease duration in schizophrenia

Objective: Progressive brain changes late in the disease course of schizophrenia may be detected with functional connectivity. This study compared functional connectivity between patients with schizophrenia late in the disease course with matched healthy controls. Method: Subjects included 18 patients with schizophrenia with minimum 15 years disease duration and 28 matched healthy controls from the MIND Clinical Imaging Consortium database. The functional magnetic resonance imaging paradigm was the auditory oddball task. We used independent components analysis to identify temporally cohesive but spatially distributed neural networks. We selected the executive control and default mode networks for additional analysis. The temporal course of each spatial component was then regressed with a model of the hemodynamic time course based on the experimental paradigm to measure functional connectivity. The beta weights from this regression were used for additional group level analysis. Results: The anterior default mode network had a main effect by group (patients with schizophrenia and healthy controls) and an interaction with group and aging. As the patient group aged, they had less negative modulation of the anterior default mode network. The patient group also had significantly less positive modulation of the executive control network. Conclusions: These results show evidence of changes in functional connectivity in the anterior default mode network late in the disease course of schizophrenia. The decreased functional connectivity may be attributable to the progressive disease course of schizophrenia

Combination of Resting State fMRI, DTI, and sMRI Data to Discriminate Schizophrenia by N-way MCCA + jICA

Multimodal brain imaging data have shown increasing utility in answering both scientifically interesting and clinically relevant questions. Each brain imaging technique provides a different view of brain function or structure, while multimodal fusion capitalizes on the strength of each and may uncover hidden relationships that can merge findings from separate neuroimaging studies. However, most current approaches have focused on pair-wise fusion and there is still relatively little work on N-way data fusion and examination of the relationships among multiple data types. We recently developed an approach called “mCCA + jICA” as a novel multi-way fusion method which is able to investigate the disease risk factors that are either shared or distinct across multiple modalities as well as the full correspondence across modalities. In this paper, we applied this model to combine resting state fMRI (amplitude of low-frequency fluctuation, ALFF), gray matter (GM) density, and DTI (fractional anisotropy, FA) data, in order to elucidate the abnormalities underlying schizophrenia patients (SZs, n = 35) relative to healthy controls (HCs, n = 28). Both modality-common and modality-unique abnormal regions were identified in SZs, which were then used for successful classification for seven modality-combinations, showing the potential for a broad applicability of the mCCA + jICA model and its results. In addition, a pair of GM-DTI components showed significant correlation with the positive symptom subscale of Positive and Negative Syndrome Scale (PANSS), suggesting that GM density changes in default model network along with white-matter disruption in anterior thalamic radiation are associated with increased positive PANSS. Findings suggest the DTI anisotropy changes in frontal lobe may relate to the corresponding functional/structural changes in prefrontal cortex and superior temporal gyrus that are thought to play a role in the clinical expression of SZ

Imaging the kidney using magnetic resonance techniques: structure to function

Purpose of review Magnetic resonance imaging (MRI) offers the possibility to non-invasively assess both the structure and function of the kidney in a single MR scan session. This review summarises recent advancements in functional renal MRI techniques, with a particular focus on their clinical relevance. Recent findings A number of MRI techniques have been developed that provide non-invasive measures of relevance to the pathophysiology of kidney disease. Diffusion-weighted imaging (DWI) has been used in chronic kidney disease (CKD) and renal transplantation, and appears promising as a measure of renal impairment and fibrosis. Longitudinal relaxation time (T1) mapping has been utilised in cardiac MRI to measure fibrosis and oedema; recent work suggests its potential for assessment of the kidney. Blood oxygen level dependent (BOLD) MRI to measure renal oxygenation has been extensively studied, but a number of other factors affect results making it hard to draw definite conclusions as to its utility as an independent measure. Phase contrast and arterial spin labelling (ASL) can measure renal artery blood flow and renal perfusion respectively without exogenous contrast, in contrast to dynamic contrast enhanced (DCE) studies. Current data on clinical use of such functional renal MR measures is largely restricted to cross-sectional studies. Summary Renal MRI has seen significant recent interest and advances. Current evidence demonstrates its potential, and next steps include wider evaluation of its clinical application

LOCUS: A Novel Decomposition Method for Brain Network Connectivity Matrices using Low-rank Structure with Uniform Sparsity

Network-oriented research has been increasingly popular in many scientific areas. In neuroscience research, imaging-based network connectivity measures have become the key for understanding brain organizations, potentially serving as individual neural fingerprints. There are major challenges in analyzing connectivity matrices including the high dimensionality of brain networks, unknown latent sources underlying the observed connectivity, and the large number of brain connections leading to spurious findings. In this paper, we propose a novel blind source separation method with low-rank structure and uniform sparsity (LOCUS) as a fully data-driven decomposition method for network measures. Compared with the existing method that vectorizes connectivity matrices ignoring brain network topology, LOCUS achieves more efficient and accurate source separation for connectivity matrices using low-rank structure. We propose a novel angle-based uniform sparsity regularization that demonstrates better performance than the existing sparsity controls for low-rank tensor methods. We propose a highly efficient iterative Node-Rotation algorithm that exploits the block multi-convexity of the objective function to solve the non-convex optimization problem for learning LOCUS. We illustrate the advantage of LOCUS through extensive simulation studies. Application of LOCUS to Philadelphia Neurodevelopmental Cohort neuroimaging study reveals biologically insightful connectivity traits which are not found using the existing method

Multimodal Fusion With Reference: Searching for Joint Neuromarkers of Working Memory Deficits in Schizophrenia

Multimodal fusion is an effective approach to take advantage of cross-information among multiple imaging data to better understand brain diseases. However, most current fusion approaches are blind, without adopting any prior information. To date, there is increasing interest to uncover the neurocognitive mapping of specific behavioral measurement on enriched brain imaging data; hence, a supervised, goal-directed model that enables a priori information as a reference to guide multimodal data fusion is in need and a natural option. Here we proposed a fusion with reference model, called “multi-site canonical correlation analysis with reference plus joint independent component analysis” (MCCAR+jICA), which can precisely identify co-varying multimodal imaging patterns closely related to reference information, such as cognitive scores. In a 3-way fusion simulation, the proposed method was compared with its alternatives on estimation accuracy of both target component decomposition and modality linkage detection. MCCAR+jICA outperforms others with higher precision. In human imaging data, working memory performance was utilized as a reference to investigate the covarying functional and structural brain patterns among 3 modalities and how they are impaired in schizophrenia. Two independent cohorts (294 and 83 subjects respectively) were used. Interestingly, similar brain maps were identified between the two cohorts, with substantial overlap in the executive control networks in fMRI, salience network in sMRI, and major white matter tracts in dMRI. These regions have been linked with working memory deficits in schizophrenia in multiple reports, while MCCAR+jICA further verified them in a repeatable, joint manner, demonstrating the potential of such results to identify potential neuromarkers for mental disorders

Magnetic Resonance Imaging in Huntington's Disease.

Magnetic resonance imaging (MRI) is a noninvasive technique used routinely to image the body in both clinical and research settings. Through the manipulation of radio waves and static field gradients, MRI uses the principle of nuclear magnetic resonance to produce images with high spatial resolution, appropriate for the investigation of brain structure and function