The success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion-driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three-dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications.

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Diffusion tensor imaging: Concepts and applications

Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge.

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Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water

Objectives To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death.

Design Systematic review and meta-analysis.

Data sources PubMed from 1966 to 23 November 2009.

Study selection Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death.

Data extraction Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome.

Data synthesis 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested.

Conclusion White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

https://www.bmj.com/content/bmj/341/bmj.c3666.full.pdf

The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis

https://cyberleninka.org/article/n/551463.pdf

Towards a neural basis of auditory sentence processing.

Resting fMRI studies have identified intrinsic spinal cord activity, which forms organised motor (ventral) and sensory (dorsal) resting-state networks. However, to facilitate the use of spinal fMRI in, for example, clinical studies, it is crucial to first assess the reliability of the method, particularly given the unique anatomical, physiological, and methodological challenges associated with acquiring the data. Here we demonstrate a novel implementation for acquiring BOLD-sensitive resting-state spinal fMRI, which was used to characterise functional connectivity relationships in the cervical cord and assess their test-retest reliability in 23 young healthy volunteers. Resting-state networks were estimated in two ways: (1) by extracting the mean timeseries from anatomically constrained seed masks and estimating voxelwise connectivity maps and (2) by calculating seed-to-seed correlations between extracted mean timeseries. Seed regions corresponded to the four grey matter horns (ventral/dorsal and left/right) of C5-C8 segmental levels. Test-retest reliability was assessed using the intraclass correlation coefficient (ICC) in the following ways: for each voxel in the cervical spine; each voxel within an activated cluster; the mean signal as a summary estimate within an activated cluster; and correlation strength in the seed-to-seed analysis. Spatial overlap of clusters derived from voxelwise analysis between sessions was examined using Dice coefficients. Following voxelwise analysis, we observed distinct unilateral dorsal and ventral organisation of cervical spinal resting-state networks that was largely confined in the rostro-caudal extent to each spinal segmental level, with more sparse connections observed between segments (Bonferroni corrected p < 0.003, threshold-free cluster enhancement with 5000 permutations). Additionally, strongest correlations were observed between within-segment ipsilateral dorso-ventral connections, followed by within-segment dorso-dorsal and ventro-ventral connections. Test-retest reliability of these networks was mixed. Reliability was poor when assessed on a voxelwise level, with more promising indications of reliability when examining the average signal within clusters. Reliability of correlation strength between seeds was highly variable, with highest reliability achieved in ipsilateral dorso-ventral and dorso-dorsal/ventro-ventral connectivity. However, the spatial overlap of networks between sessions was excellent. We demonstrate that while test-retest reliability of cervical spinal resting-state networks is mixed, their spatial extent is similar across sessions, suggesting that these networks are characterised by a consistent spatial representation over time.

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A novel implementation of spinal fMRI demonstrates segmental organisation of functionally connected networks in the cervical spinal cord: A test-retest reliability study

The neurobiological effects of clozapine are under characterised. We examined the effects clozapine treatment on subcortical volume and cortical thickness and investigated whether macrostructural changes were linked to alterations in glutamate or N-acetylaspartate (NAA). Data were acquired in 24 patients with treatment-resistant schizophrenia before and 12 weeks after switching to clozapine. During clozapine treatment we observed reductions in caudate and putamen volume, lateral ventricle enlargement (P < 0.001), and reductions in thickness of the left inferior temporal cortex, left caudal middle frontal cortex, and the right temporal pole. Reductions in right caudate volume were associated with local reductions in NAA (P = 0.002). None of the morphometric changes were associated with changes in glutamate levels. These results indicate that clozapine treatment is associated with subcortical volume loss and cortical thinning and that at least some of these effects are linked to changes in neuronal or metabolic integrity. 

https://www.nature.com/articles/s41537-022-00230-2.pdf

Subcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia

Looping Star is a near-silent, multi-echo, 3D functional magnetic resonance imaging (fMRI) technique. It reduces acoustic noise by at least 25dBA, with respect to gradient-recalled echo echo-planar imaging (GRE-EPI)-based fMRI. Looping Star has successfully demonstrated sensitivity to the cerebral blood-oxygen-level-dependent (BOLD) response during block design paradigms but has not been applied to event-related auditory perception tasks. Demonstrating Looping Star's sensitivity to such tasks could (a) provide new insights into auditory processing studies, (b) minimise the need for invasive ear protection, and (c) facilitate the translation of numerous fMRI studies to investigations in sound-averse patients. We aimed to demonstrate, for the first time, that multi-echo Looping Star has sufficient sensitivity to the BOLD response, compared to that of GRE-EPI, during a well-established event-related auditory discrimination paradigm: the "oddball" task. We also present the first quantitative evaluation of Looping Star's test-retest reliability using the intra-class correlation coefficient. Twelve participants were scanned using single-echo GRE-EPI and multi-echo Looping Star fMRI in two sessions. Random-effects analyses were performed, evaluating the overall response to tones and differential tone recognition, and intermodality analyses were computed. We found that multi-echo Looping Star exhibited consistent sensitivity to auditory stimulation relative to GRE-EPI. However, Looping Star demonstrated lower test-retest reliability in comparison with GRE-EPI. This could reflect differences in functional sensitivity between the techniques, though further study is necessary with additional cognitive paradigms as varying cognitive strategies between sessions may arise from elimination of acoustic scanner noise.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/hbm.25407

Revealing the mechanisms behind novel auditory stimuli discrimination: An evaluation of silent functional MRI using looping star.

/pdf/altered-medial-temporal-activation-related-to-local-2dfwfr29q7.pdf

David J. Lythgoe

Papers

A novel implementation of spinal fMRI demonstrates segmental organisation of functionally connected networks in the cervical spinal cord: A test-retest reliability study

Subcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia

Revealing the mechanisms behind novel auditory stimuli discrimination: An evaluation of silent functional MRI using looping star.

Altered medial temporal activation related to local glutamate levels in subjects prodromal signs of psychosis

200 – Brain glutamate and grey matter volume in the early phase of psychosis