From Brownian motion to virtual biopsy: a historical perspective from 40 years of diffusion MRI.

Diffusion MRI was introduced in 1985, showing how the diffusive motion of molecules, especially water, could be spatially encoded with MRI to produce images revealing the underlying structure of biologic tissues at a microscopic scale. Diffusion is one of several Intravoxel Incoherent Motions (IVIM) accessible to MRI together with blood microcirculation. Diffusion imaging first revolutionized the management of acute cerebral ischemia by allowing diagnosis at an acute stage when therapies can still work, saving the outcomes of many patients. Since then, the field of diffusion imaging has expanded to the whole body, with broad applications in both clinical and research settings, providing insights into tissue integrity, structural and functional abnormalities from the hindered diffusive movement of water molecules in tissues. Diffusion imaging is particularly used to manage many neurologic disorders and in oncology for detecting and classifying cancer lesions, as well as monitoring treatment response at an early stage. The second major impact of diffusion imaging concerns the wiring of the brain (Diffusion Tensor Imaging, DTI), allowing to obtain from the anisotropic movement of water molecules in the brain white-matter images in 3 dimensions of the brain connections making up the Connectome. DTI has opened up new avenues of clinical diagnosis and research to investigate brain diseases, neurogenesis and aging, with a rapidly extending field of application in psychiatry, revealing how mental illnesses could be seen as Connectome spacetime disorders. Adding that water diffusion is closely associated to neuronal activity, as shown from diffusion fMRI, one may consider that diffusion MRI is ideally suited to investigate both brain structure and function. This article retraces the early days and milestones of diffusion MRI which spawned over 40 years, showing how diffusion MRI emerged and expanded in the research and clinical fields, up to become a pillar of modern clinical imaging.

In Humans, Insulo-striate Structural Connectivity is Largely Biased Toward Either Striosome-like or Matrix-like Striatal Compartments.

The insula is an integral component of sensory, motor, limbic, and executive functions, and insular dysfunction is associated with numerous human neuropsychiatric disorders. Insular efferents project widely, but insulo-striate projections are especially numerous. The targets of these insulo-striate projections are organized into tissue compartments, the striosome and matrix. These striatal compartments have distinct embryologic origins, afferent and efferent connectivity, dopamine pharmacology, and susceptibility to injury. Striosome and matrix appear to occupy separate sets of cortico-striato-thalamo-cortical loops, so a bias in insulo-striate projections toward one compartment may also embed an insular subregion in distinct regulatory and functional networks. Compartment-specific mapping of insulo-striate structural connectivity is sparse; the insular subregions are largely unmapped for compartment-specific projections. In 100 healthy adults, diffusion tractography was utilized to map and quantify structural connectivity between 19 structurally-defined insular subregions and each striatal compartment. Insulo-striate streamlines that reached striosome-like and matrix-like voxels were concentrated in distinct insular zones (striosome: rostro- and caudoventral; matrix: caudodorsal) and followed different paths to reach the striatum. Though tractography was generated independently in each hemisphere, the spatial distribution and relative bias of striosome-like and matrix-like streamlines were highly similar in the left and right insula. 16 insular subregions were significantly biased toward 1 compartment: 7 toward striosome-like voxels and 9 toward matrix-like voxels. Striosome-favoring bundles had significantly higher streamline density, especially from rostroventral insular subregions. The biases in insulo-striate structural connectivity that were identified mirrored the compartment-specific biases identified in prior studies that utilized injected tract tracers, cytoarchitecture, or functional MRI. Segregating insulo-striate structural connectivity through either striosome or matrix may be an anatomic substrate for functional specialization among the insular subregions.

Dynamic functional connectivity in verbal cognitive control and word reading.

Cognitive control processes enable the suppression of automatic behaviors and the initiation of appropriate responses. The Stroop color naming task serves as a benchmark paradigm for understanding the neurobiological model of verbal cognitive control. Previous research indicates a predominant engagement of the prefrontal and premotor cortex during the Stroop task compared to reading. We aim to further this understanding by creating a dynamic atlas of task-preferential modulations of functional connectivity through white matter. Patients undertook word-reading and Stroop tasks during intracranial EEG recording. We quantified task-related high-gamma amplitude modulations at 547 nonepileptic electrode sites, and a mixed model analysis identified regions and timeframes where these amplitudes differed between tasks. We then visualized white matter pathways with task-preferential functional connectivity enhancements at given moments. Word reading, compared to the Stroop task, exhibited enhanced functional connectivity in inter- and intra-hemispheric white matter pathways from the left occipital-temporal region 350-600 ms before response, including the posterior callosal fibers as well as the left vertical occipital, inferior longitudinal, inferior fronto-occipital, and arcuate fasciculi. The Stroop task showed enhanced functional connectivity in the pathways from the left middle-frontal pre-central gyri, involving the left frontal u-fibers and anterior callosal fibers. Automatic word reading largely utilizes the left occipital-temporal cortices and associated white matter tracts. Verbal cognitive control predominantly involves the left middle frontal and precentral gyri and its connected pathways. Our dynamic tractography atlases may serve as a novel resource providing insights into the unique neural dynamics and pathways of automatic reading and verbal cognitive control.

Lateral thinking: Neurodegeneration of the cortical cholinergic system in Alzheimer's disease.

INTRODUCTION: Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression. METHODS: 187 participants were included in this study who were either healthy controls (HC; n = 50) or had early mild cognitive impairment (EMCI; n = 50), late MCI (LMCI; n = 37), or AD (n = 50). NBM volume was calculated using voxel-based morphometry and mean diffusivity (MD) of the lateral and medial NBM tracts were extracted using probabilistic tractography. Between group differences in NBM volume and tract MD were compared using linear mixed models controlling for age, sex, and either total intracranial volume or MD of a control mask, respectively. Associations between NBM volume and tract MD with executive function, memory, language, and visuospatial function were also analysed. RESULTS: NBM volume was smallest in AD followed by LMCI (p < 0.0001), with no difference between EMCI and HC. AD had highest MD for both tracts compared to all other groups (p < 0.01). Both MCI groups had higher lateral tract MD compared to HC (p < 0.05). Medial tract MD was higher in LMCI (p = 0.008), but not EMCI (p = 0.09) compared to HC. Higher lateral tract MD was associated with executive function (p = 0.001) and language (p = 0.02). DISCUSSION: Integrity of the lateral NBM tract is most sensitive to the earliest stages of AD and should be considered an important therapeutic target for early detection and intervention.

Involvement of the cerebellum in structural connectivity enhancement in episodic migraine.

BACKGROUND: The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls. METHODS: To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM. RESULTS: We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine. CONCLUSIONS: A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.

A diffusion tensor imaging white matter atlas of the domestic canine brain.

There is increasing reliance on magnetic resonance imaging (MRI) techniques in both research and clinical settings. However, few standardized methods exist to permit comparative studies of brain pathology and function. To help facilitate these studies, we have created a detailed, MRI-based white matter atlas of the canine brain using diffusion tensor imaging. This technique, which relies on the movement properties of water, permits the creation of a three-dimensional diffusivity map of white matter brain regions that can be used to predict major axonal tracts. To generate an atlas of white matter tracts, thirty neurologically and clinically normal dogs underwent MRI imaging under anesthesia. High-resolution, three-dimensional T1-weighted sequences were collected and averaged to create a population average template. Diffusion-weighted imaging sequences were collected and used to generate diffusivity maps, which were then registered to the T1-weighted template. Using these diffusivity maps, individual white matter tracts-including association, projection, commissural, brainstem, olfactory, and cerebellar tracts-were identified with reference to previous canine brain atlas sources. To enable the use of this atlas, we created downloadable overlay files for each white matter tract identified using manual segmentation software. In addition, using diffusion tensor imaging tractography, we created tract files to delineate major projection pathways. This comprehensive white matter atlas serves as a standard reference to aid in the interpretation of quantitative changes in brain structure and function in clinical and research settings.

Sex differences in patterns of white matter neuroplasticity after balance training in young adults.

Introduction: In past work we demonstrated different patterns of white matter (WM) plasticity in females versus males associated with learning a lab-based unilateral motor skill. However, this work was completed in neurologically intact older adults. The current manuscript sought to replicate and expand upon these WM findings in two ways: (1) we investigated biological sex differences in neurologically intact young adults, and (2) participants learned a dynamic full-body balance task. Methods: 24 participants (14 female, 10 male) participated in the balance training intervention, and 28 were matched controls (16 female, 12 male). Correlational tractography was used to analyze changes in WM from pre- to post-training. Results: Both females and males demonstrated skill acquisition, yet there were significant differences in measures of WM between females and males. These data support a growing body of evidence suggesting that females exhibit increased WM neuroplasticity changes relative to males despite comparable changes in motor behavior (e.g., balance). Discussion: The biological sex differences reported here may represent an important factor to consider in both basic research (e.g., collapsing across females and males) as well as future clinical studies of neuroplasticity associated with motor function (e.g., tailored rehabilitation approaches).

Diffusion tensor imaging and gray matter volumetry to evaluate cerebral remodeling processes after a pure motor stroke: a longitudinal study.

BACKGROUND AND OBJECTIVES: Clinical factors are not sufficient to fix a prognosis of recovery after stroke. Pyramidal tract or alternate motor fiber (aMF: reticulo-, rubrospinal pathways and transcallosal fibers) integrity and remodeling processes assessable by diffusion tensor MRI (DTI) and voxel-based morphometry (VBM) may be of interest. The primary objective was to study longitudinal cortical brain changes using VBM and longitudinal corticospinal tract changes using DTI during the first 4 months after lacunar cerebral infarction. The second objective was to determine which changes were correlated to clinical improvement. METHODS: Twenty-one patients with deep brain ischemic infarct with pure motor deficit (NIHSS score ≥ 2) were recruited at Purpan Hospital and included. Motor deficit was measured [Nine peg hole test (NPHT), dynamometer (DYN), Hand-Tapping Test (HTT)], and a 3T MRI scan (VBM and DTI) was performed during the acute and subacute phases. RESULTS: White matter changes: corticospinal fractional anisotropy (FACST) was significantly reduced at follow-up (approximately 4 months) on the lesion side. FAr (FA ratio in affected/unaffected hemispheres) in the corona radiata was correlated to the motor performance at the NPHT, DYN, and HTT at follow-up. The presence of aMFs was not associated with the extent of recovery. Grey matter changes: VBM showed significant increased cortical thickness in the ipsilesional premotor cortex at follow-up. VBM changes in the anterior cingulum positively correlated with improvement in motor measures between baseline and follow-up. DISCUSSION: To our knowledge, this study is original because is a longitudinal study combining VBM and DTI during the first 4 months after stroke in a series of patients selected on pure motor deficit. Our data would suggest that good recovery relies on spared CST fibers, probably from the premotor cortex, rather than on the aMF in this group with mild motor deficit. The present study suggests that VBM and FACST could provide reliable biomarkers of post-stroke atrophy, reorganization, plasticity and recovery. GOV IDENTIFIER: NCT01862172, registered May 24, 2013.

Phonological, orthographic and morphological skills are related to structural properties of ventral and motor white matter pathways in skilled and impaired readers.

Using diffusion tensor imaging (DTI), we assessed the extent to which fractional anisotropy values in the dorsal (i.e., arcuate fasciculus; AF) versus ventral (i.e., inferior fronto-occipital fasciculus; IFOF) distinction of structural white matter pathways associated with selected reading processes, could be replicated in skilled adult readers (N = 17) and extended to adults with reading impairments (N = 13). In addition to the AF and IFOF, motor-based tracts (i.e., posterior limb of the internal capsule (PLIC) and the frontal aslant tract (FAT)) were isolated to explore their role in reading performance. Several interesting relationships with reading performance emerged. First, orthographic awareness was related to the left IFOF in skilled readers, whereas orthographic awareness was related to left PLIC for impaired readers. Morphological awareness was related to left FAT for skilled readers, whereas morphological awareness was related to right AF, right IFOF and left PLIC for impaired readers. Overall, these findings support the notion that adult reading performance (both skilled and impaired) is related to the structural properties of the ventral white matter pathways. More consideration should be paid to motor pathways, particularly the PLIC, and their role in compensatory reading strategies in individuals with reading impairments.

Three-dimensional virtual reality-assisted surgical planning for neuronavigated sacrectomy of a chordoma: a technical note.

PURPOSE: Sacral chordomas are slow growing but locally aggressive tumours with a high rate of local recurrence if not completely removed. Surgical resection with negative margins represents the most important survival predictor but it can be challenging to accomplish. Thanks to improvements in intraoperative imaging and surgical techniques, en bloc resection through a partial sacral resection with wide surgical margins has become feasible but it comes with a significant morbidity rate. In this technical note we detail the virtual reality-assisted surgical planning used during resection. METHODS: A 70-year-old patient underwent en bloc resection of the tumor by an antero-posterior two-stage surgery approach. Pre-operatively, based on MR- and CT-imaging, virtual objects were designed, representing the tumour, the surrounding bone and the neurovascular structures. This 3D-model was used to plan the well delimited partial sacral resection and the posterior surgical approach. Intraoperatively the instruments were registered, allowing for a real-time visualization of the tumor, of the neurovascular structures, and for an optimal margin control resection. RESULTS: Postoperatively the patient was intact in the lower extremities, without any deficit up to S1 roots. An intentional middle-low sacral amputation of S2-S5 roots was necessary to have a wide resection with free margins. At follow-up, the patient did not present any lower extremities motor deficit with an improvement of sensory function on S1 dermatome. CONCLUSION: Three-dimensional virtual reality-assisted surgical planning for neuronavigated sacrectomy in chordoma is useful, feasible and safe. This technology can increase surgeon's chances to perform a larger margin-free resection decreasing the risk of neurovascular damage.

Subcortical Aphasia: An Update.

PURPOSE OF REVIEW: This review aims to rediscuss the leading theories concerning the role of basal ganglia and the thalamus in the genesis of aphasic symptoms in the absence of gross anatomical lesions in cortical language areas as assessed by conventional neuroimaging studies. RECENT FINDINGS: New concepts in language processing and modern neuroimaging techniques have enabled some progress in resolving the impasse between the current dominant theories: (a) direct and specific linguistic processing and (b) subcortical structures as processing relays in domain-general functions. Of particular interest are studies of connectivity based on functional magnetic resonance imaging (MRI) and tractography that highlight the impact of white matter pathway lesions on aphasia development and recovery. Connectivity studies have put into evidence the central role of the arcuate fasciculus (AF), inferior frontal occipital fasciculus (IFOF), and uncinate fasciculus (UF) in the genesis of aphasia. Regarding the thalamus, its involvement in lexical-semantic processing through modulation of the frontal cortex is becoming increasingly apparent.

Bounding tractogram redundancy.

Introduction: In tractography, redundancy poses a significant challenge, often resulting in tractograms that include anatomically implausible streamlines or those that fail to represent the brain's white matter architecture accurately. Current filtering methods aim to refine tractograms by addressing these issues, but they lack a unified measure of redundancy and can be computationally demanding. Methods: We propose a novel framework to quantify tractogram redundancy based on filtering tractogram subsets without endorsing a specific filtering algorithm. Our approach defines redundancy based on the anatomical plausibility and diffusion signal representation of streamlines, establishing both lower and upper bounds for the number of false-positive streamlines and the tractogram redundancy. Results: We applied this framework to tractograms from the Human Connectome Project, using geometrical plausibility and statistical methods informed by the streamlined attributes and ensemble consensus. Our results establish bounds for the tractogram redundancy and the false-discovery rate of the tractograms. Conclusion: This study advances the understanding of tractogram redundancy and supports the refinement of tractography methods. Future research will focus on further validating the proposed framework and exploring tractogram compression possibilities.

Validation of Tenths Stereotactic Coordinates Method Using Probabilistic Tractography of the Ansa Lenticularis in Parkinson's Disease Patients.

OBJECTIVE: To evaluate the accuracy of stereotactic coordinates to target the ansa lenticularis (AL) using 2 surgical planning methods, the conventional millimeter method (MM) and the normalized Tenths method (TM), assessed through individualized probabilistic tractography. METHODS: Stereotactic targeting of the AL was assessed in 2 groups: 16 patients with Parkinson's disease and 16 healthy controls from Group 1, and 39 Parkinson's disease patients from Group 2. Structural and diffusion magnetic resonance imaging probabilistic tractography identified the AL based on the Schaltenbrand-Wahren Atlas. The MM defined stereotactic coordinates in millimeters, while the TM refined the planning by dividing the intercommissural line (AC-PC) distance into 10 equal parts, normalizing the "X," "Y," and "Z" coordinates for each patient. We subsequently compared the percentage of structural connectivity (%conn) of the AL with predefined regions of interest (ROIs), including the frontopontine-corticothalamic tracts, globus pallidus internus-ventral oral anterior, and ventral oral posterior, and quantified the streamlines in 142 brain hemispheres using the MM and TM coordinates. RESULTS: Despite anatomical variations in intercommissural (AC-PC) line lengths between both groups (22.5 ± 2.09 mm and 24.4 ± 2.56 mm, respectively; P = 0.002), as well as differences in magnetic resonance imaging acquisition parameters, we found that the TM significantly enhanced streamline identification and %conn compared to the MM. These enhancements were noted across ROIs: frontopontine-corticothalamic and globus pallidus internus-ventral oral anterior in both hemispheres, and globus pallidus internus-ventral oral posterior in the left (P < 0.001) and right hemispheres (P = 0.03). CONCLUSIONS: TM surpasses MM in identifying the structural connectivity between the AL and predefined ROIs, underscoring the advantages of coordinate normalization. However, variations in AC-PC line lengths and Euclidean distances between methods could lead to inaccuracies in the coordinate settings, potentially affecting the precision of structural connectivity and the efficacy of therapeutic outcomes.

On the role of the arcuate fasciculus in word production and repetition: a reply to Van den Hoven et al. (2024).

Van den Hoven et al. contested my interpretation of Wernicke regarding the role of the arcuate fasciculus (AF) in word production. Here, I clarify and defend my interpretation. They also questioned the assumption of AF subtracts in my modern account, stating that subtracts are difficult to distinguish anatomically due to overlapping terminations. Here, I make clear that overlap in terminations was actually part of my account, in which differentially damaged subtracts explained patients' differential naming and repetition performance as well as types of repetition performance.

Connectomic insights into the impact of 1p/19q co-deletion in dominant hemisphere insular glioma patients.

Objectives: This study aimed to elucidate the influences of 1p/19q co-deletion on structural connectivity alterations in patients with dominant hemisphere insular diffuse gliomas. Methods: We incorporated 32 cases of left insular gliomas and 20 healthy controls for this study. Using diffusion MRI, we applied correlational tractography, differential tractography, and graph theoretical analysis to explore the potential connectivity associated with 1p/19q co-deletion. Results: The study revealed that the quantitative anisotropy (QA) of key deep medial fiber tracts, including the anterior thalamic radiation, superior thalamic radiation, fornix, and cingulum, had significant negative associations with 1p/19q co-deletion (FDR = 4.72 × 10-5). These tracts are crucial in maintaining the integrity of brain networks. Differential analysis further supported these findings (FWER-corrected p < 0.05). The 1p/19q non-co-deletion group exhibited significantly higher clustering coefficients (FDR-corrected p < 0.05) and reduced betweenness centrality (FDR-corrected p < 0.05) in regions around the tumor compared to HC group. Graph theoretical analysis indicated that non-co-deletion patients had increased local clustering and decreased betweenness centrality in peritumoral brain regions compared to co-deletion patients and healthy controls (FDR-corrected p < 0.05). Additionally, despite not being significant through correction, patients with 1p/19q co-deletion exhibited lower trends in weighted average clustering coefficient, transitivity, small worldness, and global efficiency, while showing higher tendencies in weighted path length compared to patients without the co-deletion. Conclusion: The findings of this study underline the significant role of 1p/19q co-deletion in altering structural connectivity in insular glioma patients. These alterations in brain networks could have profound implications for the neural functionality in patients with dominant hemisphere insular gliomas.

Atlas-guided brain projection tracts: From regions of interest to tractography 3D rendering.

The use of diffusion tensor imaging (DTI) has seen significant development over the last two decades, in particular with the development of the tractography of association tracts for preoperative planning of surgery. However, projection tracts are difficult to differentiate from one another and tractography studies have failed to reconstruct these ascending/descending pathways from/to the spinal cord. The present study proposes an atlas of regions of interest (ROIs) designed specifically for projection tracts tractography. Forty-nine healthy subjects were included in this prospective study. Brain DTI was acquired using the same 3 T MRI scanner, with 32 diffusion directions. Distortions were corrected using the FSL software package. ROIs were drawn using the anterior commissure (AC)-posterior commissure (PC) line on the following landmarks: the pyramid for the corticospinal tract, the medio-caudal part of the red nucleus for the rubrospinal tract, the pontine reticular nucleus for corticoreticular tract, the superior and inferior cerebellar peduncles for, respectively, the anterior and posterior spinocerebellar tract, the gracilis and cuneatus nucleus for the dorsal columns, and the ventro-posterolateral nucleus for the spinothalamic tract. Fiber tracking was performed using a deterministic algorithm using DSI Studio software. ROI coordinates, according to AC-PC line, were given for each tract. Tractography was obtained for each tract, allowing tridimensional rendering and comparison of tracking metrics between tracts. The present study reports the accurate design of specific ROIs for tractography of each projection tract. This could be a useful tool in order to differentiate projection tracts at the spinal cord level.

Evaluation of microstructural brain changes in post-coronavirus disease 2019 (COVID-19) patients with neurological symptoms: a cross-sectional study.

Background: Changes in both the vascular system and brain tissues can occur after a prior episode of coronavirus disease 2019 (COVID-19), detectable through modifications in diffusion parameters using magnetic resonance imaging (MRI) techniques. These changes in diffusion parameters may be particularly prominent in highly organized structures such as the corpus callosum (CC), including its major components, which have not been adequately studied following COVID-19 infection. Therefore, the study aimed to evaluate microstructural changes in whole-brain (WB) diffusion, with a specific focus on the CC. Methods: A total of 101 probands (age range from 18 to 69 years) participated in this retrospective study, consisting of 55 volunteers and 46 post-COVID-19 patients experiencing neurological symptoms. The participants were recruited from April 2022 to September 2023 at the Institute for Clinical and Experimental Medicine in Prague, Czech Republic. All participants underwent MRI examinations on a 3T MR scanner with a diffusion protocol, complemented by additional MRI techniques. Two volunteers and five patients were excluded from the study due to motion artefacts, severe hypoperfusion or the presence of lesions. Participants were selected by a neurologist based on clinical examination and a serological test for COVID-19 antibodies. They were then divided into three groups: a control group of healthy volunteers (n=28), an asymptomatic group (n=25) with a history of infection but no symptoms, and a symptomatic group (n=41) with a history of COVID-19 and neurological symptoms. Symptomatic patients did not exhibit neurological symptoms before contracting COVID-19. Diffusion data underwent eddy current and susceptibility distortion corrections, and fiber tracking was performed using default parameters in DSI studio. Subsequently, various diffusion metrics, were computed within the reconstructed tracts of the WB and CC. To assess the impact of COVID-19 and its associated symptoms on diffusion indices within the white matter of the WB and CC regions, while considering age, we employed a statistical analysis using a linear mixed-effects model within the R framework. Results: Statistical analysis revealed a significant difference in mean diffusivity (MD) between the symptomatic and control groups in the forceps minor (P=0.001) and CC body (P=0.003). In addition to changes in diffusion, alterations in brain perfusion were observed in two post-COVID-19 patients who experienced a severe course. Furthermore, hyperintense lesions were identified in subcortical and deep white matter areas in the vast majority of symptomatic patients. Conclusions: The main finding of our study was that post-COVID-19 patients exhibit increased MD in the forceps minor and body of the CC. This finding suggests a potential association between microstructural brain changes in post-COVID-19 patients and reported neurological symptoms, with significant implications for research and clinical applications.

Current Auditory Hallucinations Are Not Associated With Specific White Matter Diffusion Alterations in Schizophrenia.

Background and Hypothesis: Studies have linked auditory hallucinations (AH) in schizophrenia spectrum disorders (SCZ) to altered cerebral white matter microstructure within the language and auditory processing circuitry (LAPC). However, the specificity to the LAPC remains unclear. Here, we investigated the relationship between AH and DTI among patients with SCZ using diffusion tensor imaging (DTI). Study Design: We included patients with SCZ with (AH+; n = 59) and without (AH-; n = 81) current AH, and 140 age- and sex-matched controls. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were extracted from 39 fiber tracts. We used principal component analysis (PCA) to identify general factors of variation across fiber tracts and DTI metrics. Regression models adjusted for sex, age, and age2 were used to compare tract-wise DTI metrics and PCA factors between AH+, AH-, and healthy controls and to assess associations with clinical characteristics. Study Results: Widespread differences relative to controls were observed for MD and RD in patients without current AH. Only limited differences in 2 fiber tracts were observed between AH+ and controls. Unimodal PCA factors based on MD, RD, and AD, as well as multimodal PCA factors, differed significantly relative to controls for AH-, but not AH+. We did not find any significant associations between PCA factors and clinical characteristics. Conclusions: Contrary to previous studies, DTI metrics differed mainly in patients without current AH compared to controls, indicating a widespread neuroanatomical distribution. This challenges the notion that altered DTI metrics within the LAPC is a specific feature underlying AH.

Progressive remodeling of structural networks following surgery for operculo-insular epilepsy.

Introduction: Operculo-insular epilepsy (OIE) is a rare condition amenable to surgery in well-selected cases. Despite the high rate of neurological complications associated with OIE surgery, most postoperative deficits recover fully and rapidly. We provide insights into this peculiar pattern of functional recovery by investigating the longitudinal reorganization of structural networks after surgery for OIE in 10 patients. Methods: Structural T1 and diffusion-weighted MRIs were performed before surgery (t0) and at 6 months (t1) and 12 months (t2) postoperatively. These images were processed with an original, comprehensive structural connectivity pipeline. Using our method, we performed comparisons between the t0 and t1 timepoints and between the t1 and t2 timepoints to characterize the progressive structural remodeling. Results: We found a widespread pattern of postoperative changes primarily in the surgical hemisphere, most of which consisted of reductions in connectivity strength (CS) and regional graph theoretic measures (rGTM) that reflect local connectivity. We also observed increases in CS and rGTMs predominantly in regions located near the resection cavity and in the contralateral healthy hemisphere. Finally, most structural changes arose in the first six months following surgery (i.e., between t0 and t1). Discussion: To our knowledge, this study provides the first description of postoperative structural connectivity changes following surgery for OIE. The ipsilateral reductions in connectivity unveiled by our analysis may result from the reversal of seizure-related structural alterations following postoperative seizure control. Moreover, the strengthening of connections in peri-resection areas and in the contralateral hemisphere may be compatible with compensatory structural plasticity, a process that could contribute to the recovery of functions seen following operculo-insular resections for focal epilepsy.

Main Paths of Brain Fibers in Diffusion Images Mixed with a Noise to Improve Performance of Tractography Algorithm-Evaluation in Phantom.

Background: Some voxels may alter the tractography results due to unintentional alteration of noises and other unwanted factors. Objective: This study aimed to investigate the effect of local phase features on tractography results providing data are mixed by a Gaussian or random distribution noise. Material and Methods: In this simulation study, a mask was firstly designed based on the local phase features to decrease false-negative and -positive tractography results. The local phase features are calculated according to the local structures of images, which can be zero-dimensional, meaning just one point (equivalent to noise in tractography algorithm), a line (equivalent to a simple fiber), or an edge (equivalent to structures more complex than a simple fiber). A digital phantom evaluated the feasibility current model with the maximum complexities of configurations in fibers, including crossing fibers. In this paper, the diffusion images were mixed separately by a Gaussian or random distribution noise in 2 forms a zero-mean noise and a noise with a mean of data. Results: The local mask eliminates the pixels of unfitted values with the main structures of images, due to noise or other interferer factors. Conclusion: The local phase features of diffusion images are an innovative solution to determine principal diffusion directions.