Tract Integrity Research Articles

Increased fiber density of the fornix in patients with chronic tinnitus revealed by diffusion-weighted MRI.

Up to 45% of the elderly population suffer from chronic tinnitus - the phantom perception of sound that is often perceived as ringing, whistling, or hissing "in the ear" without external stimulation. Previous research investigated white matter changes in tinnitus patients using diffusion-weighted magnetic resonance imaging (DWI) to assess measures such as fractional anisotropy (a measure of microstructural integrity of fiber tracts) or mean diffusivity (a measure for general water diffusion). However, findings overlap only minimally and are sometimes even contradictory. We here present the first study encompassing higher diffusion data that allow to focus on changes in tissue microstructure, such as number of axons (fiber density) and macroscopic alterations, including axon diameter, and a combination of both. In order to deal with the crossing-fibers problem, we applied a fixel-based analysis using a constrained spherical deconvolution signal modeling approach. We investigated differences between tinnitus patients and control participants as well as how cognitive abilities and tinnitus distress are related to changes in white matter morphology in chronic tinnitus. For that aim, 20 tinnitus patients and 20 control participants, matched in age, sex and whether they had hearing loss or not, underwent DWI, audiometric and cognitive assessments, and filled in questionnaires targeting anxiety and depression. Our results showed increased fiber density in the fornix in tinnitus patients compared to control participants. The observed changes might, reflect compensatory structural alterations related to the processing of negative emotions or maladaptive changes related to the reinforced learning of the chronic tinnitus sensation. Due to the low sample size, the study should be seen as a pilot study that motivates further research to investigate underlying white matter morphology alterations in tinnitus.

White Matter Tract Integrity Is Reduced in Depression and in Individuals With Genetic Liability to Depression

BackgroundWhile major depression has been linked to changes in white matter architecture, it remains unclear whether risk factors for depression are directly associated with these alterations. We reexamined white matter fiber tracts in individuals with depressive symptoms and investigated the connection between genetic and environmental risk for depression and structural changes in the brain. MethodsWe included 19,183 participants from the UK Biobank imaging cohort, with depression status and adverse life experience based on questionnaire data and genetic liability for depression quantified by polygenic scores. The integrity of 27 white matter tracts was assessed using mean fractional anisotropy derived from diffusion magnetic resonance imaging. ResultsWhite matter integrity was reduced, particularly in thalamic and intracortical fiber tracts, in individuals with depressive symptoms, independent of current symptom status. In a group of healthy individuals without depression, increasing genetic risk and increasing environmental risk were associated with reduced integrity in relevant fiber tracts, particularly in thalamic radiations. This association was stronger than expected based on statistical dependencies between samples, as confirmed by subsequent in silico simulations and permutation tests. ConclusionsWhite matter alterations in thalamic and association tracts are associated with depressive symptoms and genetic risk for depression in unaffected individuals, suggesting an intermediate phenotype at the brain level.

Association between altered white matter networks and post operative ventricle volume in shunt-treated pediatric hydrocephalus

ObjectiveThe objective of this study was to use probabilistic tractography in combination with white matter microstructure metrics to characterize differences in white matter networks between shunt-treated pediatric hydrocephalus patients relative to healthy controls. We were also able to explore the relationship between these white matter networks and postoperative ventricle volume. MethodsNetwork-based statistics was used in combination with whole-brain probabilistic tractography to determine dysregulated white matter networks in a sample of patients with pediatric hydrocephalus (n = 8), relative to controls (n = 36). Metrics such as streamline count (SC), as well as the mean of the fractional anisotropy along a tract, axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were assessed. In networks that were found to be significantly different for patients with hydrocephalus, tracts were evaluated to assess their relationship with postoperative lateral ventricle volume. ResultsPatients with pediatric hydrocephalus had various networks that were either upregulated or downregulated relative to controls across all white matter measures. Predominately, network dysregulation occurred in tracts involving structures located outside of the frontal lobe. Furthermore tracts with values suggesting decreased white matter integrity were not only found between subcortical structures, but also cortical structures. While there were various tracts with white matter metrics that were initially predicted by lateral ventricle volume, only two tracts remained significant following multiple comparisons. ConclusionsThis cross-sectional study in pediatric patients with hydrocephalus and healthy controls demonstrated using whole-brain probabilistic tractography that there are various networks with dysregulated white matter integrity in hydrocephalus patients relative to controls. These dysregulated networks have tracts connecting structures throughout the brain, and the regions were predominately located centrally and posteriorly. Postoperative ventricle volume did not predict the white matter integrity of many tracts. Future studies with larger sample sizes are needed to further understand these results.

Insights and improvements in correspondence between axonal volume fraction measured with diffusion-weighted MRI and electron microscopy.

Biophysical diffusion-weighted imaging (DWI) models are increasingly used in neuroscience to estimate the axonal water fraction ( ), which in turn is key for noninvasive estimation of the axonal volume fraction ( ). These models require thorough validation by comparison with a reference method, for example, electron microscopy (EM). While EM studies often neglect the unmyelinated axons and solely report the fraction of myelinated axons, in DWI both myelinated and unmyelinated axons contribute to the DWI signal. However, DWI models often include simplifications, for example, the neglect of differences in the compartmental relaxation times or fixed diffusivities, which in turn might affect the estimation of . We investigate whether linear calibration parameters (scaling and offset) can improve the comparability between EM- and DWI-based metrics of . To this end, we (a) used six DWI models based on the so-called standard model of white matter (WM), including two models with fixed compartmental diffusivities (e.g., neurite orientation dispersion and density imaging, NODDI) and four models that fitted the compartmental diffusivities (e.g., white matter tract integrity, WMTI), and (b) used a multimodal data set including ex vivo diffusion DWI and EM data in mice with a broad dynamic range of fibre volume metrics. We demonstrated that the offset is associated with the volume fraction of unmyelinated axons and the scaling factor is associated with different compartmental and can substantially enhance the comparability between EM- and DWI-based metrics of . We found that DWI models that fitted compartmental diffusivities provided the most accurate estimates of the EM-based . Finally, we introduced a more efficient hybrid calibration approach, where only the offset is estimated but the scaling is fixed to a theoretically predicted value. Using this approach, a similar one-to-one correspondence to EM was achieved for WMTI. The method presented can pave the way for use of validated DWI-based models in clinical research and neuroscience.

Different cutoff value of motor evoked potentials for the postoperative outcome in the ossification of the posterior longitudinal ligament surgery in the cervical and thoracic spine

BACKGROUND CONTEXTTranscranial muscle motor evoked potentials (Tc-mMEPs), a key component of intraoperative neurophysiologic monitoring (IONM), effectively reflect the changes in corticospinal tract integrity and are closely related to the occurrence of the postoperative motor deficit (PMD). Most institutions have applied a specified (fixed) alarm criterion for the heterogeneous groups in terms of etiologies or lesion location. However, given the high risk of PMD in ossification of the posterior longitudinal ligament (OPLL) surgery, it is essential to determine a tailored cutoff value for IONM. PURPOSEWe aimed to establish the intraoperative cutoff value of Tc-mMEPs reduction for predicting PMD in OPLL according to lesion levels. DESIGNRetrospective analysis using a review of electrical medical records. PATIENT SAMPLEIn this study, we included 126 patients diagnosed with OPLL, who underwent surgery and IONM. OUTCOME MEASURESThe occurrence of PMD immediately and 1 year after operation, as well as the decrement of intraoperative Tc-mMEPs amplitude. METHODSWe analyzed OPLL surgery outcomes using Tc-mMEPs monitoring. Limbs with acceptable baseline Tc-mMEPs in the tibialis anterior or abductor hallucis were included in the final set. PMD was defined as a ≥1 decrease in Medical Research Council score in the legs, and it was evaluated immediately and 1year after operation. The reduction ratios of Tc-mMEPs amplitude compared with baseline value were calculated at the two time points: the maximal decrement during surgery and at the end of surgery. Receiver operating characteristic curve analysis was used to determine the cutoff value of Tc-mMEPs amplitude decrement for predicting PMDs. RESULTSIn total, 203 limbs from 102 patients with cervical OPLL and 42 limbs from 24 patients with thoracic OPLL were included. PMD developed more frequently in thoracic lesions than in cervical lesions (immediate, 9.52% vs 2.46%; 1 year, 4.76% vs 0.99%). The Tc-mMEPs amplitude cutoff point at the end of surgery for PMD (both immediate and 1-year) was a decrease of 93% in cervical and 50% in thoracic OPLL surgeries. Similarly, the Tc-mMEPs amplitude cutoff point at the maximal decrement during surgery for PMD (both immediate and 1 year) was a reduction of 97% in cervical and 85% in thoracic OPLL surgeries. CONCLUSIONSThe thoracic lesion exhibited a lower cutoff value than the cervical lesion for both immediate and long-term persistent PMD in OPLL surgery (Tc-mMEPs at the end of surgery measuring 93% vs 50%; and Tc-mMEPs at the maximal decrement measuring 97% vs 85% for cervical and thoracic lesions, respectively). To enhance the reliability of monitoring, considering the application of tailored alarm criteria for Tc-mMEPs changes based on lesion location in OPLL could be beneficial.

Relationship between disproportionately enlarged subarachnoid-space hydrocephalus and white matter tract integrity in normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case–control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0–12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity.

Higher baseline cerebrospinal fluid platelet‐derived growth factor receptor‐β levels are associated with slower reductions in longitudinal cerebral blood flow among cognitively unimpaired individuals

AbstractBackgroundCerebrospinal fluid (CSF) platelet‐derived growth factor receptor‐β (PDGFR‐β) is an emerging biomarker hypothesized to reflect pericyte damage. CSF PDGFR‐β levels are increased in Alzheimer’s disease (AD), but it is unknown if pericyte injury contributes to cerebrovascular changes common in AD. We examined if PDGFR‐β relates to changes in cerebral blood flow (CBF) and white matter injury in older adults.MethodVanderbilt Memory and Aging Project participants (n = 152, baseline age 73±7 years, 43% mild cognitive impairment [MCI]) underwent baseline lumbar puncture and serial brain MRI over a 7‐year (5.5±2.3) follow‐up period. CSF PDGFR‐β concentrated was measured by immunoassay. MRI included pseudo‐continuous arterial spin‐labeling to quantify CBF, T2‐FLAIR to quantify white matter hyperintensities (WMHs), and diffusion tensor imaging (DTI) to quantify white matter microstructural integrity. Ordinary least squares regression and linear mixed‐effects models related baseline CSF PDGFR‐β to baseline and longitudinal whole brain and regional CBF, WMH, and DTI metrics, adjusting for baseline demographic variables, modified Framingham Stroke Risk Profile, cognitive status, apolipoprotein‐ε4 status, and regional tissue volume. Longitudinal models adjusted for follow‐up time. Follow‐up models tested a CSF PDGFR‐β x cognitive status interaction.ResultIn main models, higher CSF PDGFR‐β levels were cross‐sectionally associated with lower mean diffusivity (indicating better microstructural integrity) in white matter tracts in the frontal, temporal, parietal, and occipital lobes (p‐values<0.03) but were unrelated to WMHs (p‐values>0.18). Models investigating associations with longitudinal white matter variables were null (p‐values>0.35). CSF PDGFR‐β cross‐sectionally interacted with diagnosis on temporal lobe CBF, such that higher CSF PDGFR‐β related to higher CBF in MCI participants (p = 0.01). In longitudinal models, baseline CSF PDGFR‐β interacted with cognitive status on whole brain and occipital lobe CBF (p‐values<0.04). Stratified models showed higher baseline CSF PDGFR‐β related slower reductions in longitudinal CBF in whole brain (p = 0.02), frontal (p = 0.04), temporal (p = 0.02), parietal (p = 0.01), and occipital lobes (p = 0.008) in cognitively unimpaired participants only.ConclusionAmong older adults, higher CSF PDGFR‐β levels are associated with better white matter integrity at study entry and predict slower reductions in longitudinal CBF among cognitively unimpaired individuals. Results suggest that higher PDGFR‐β levels may reflect subclinical vascular remodeling that provides protection to future cerebrovascular compromise.

Hearing impairment is associated with cognitive decline, brain atrophy and tau pathology

AbstractBackgroundThe association between hearing impairment and Alzheimer’s disease (AD) and the mechanisms involved remain unclear.MethodsSurvival analyses were performed in 66,577 participants from the UK Biobank to investigate whether hearing impairment is associated with an increased risk of AD. The association of hearing status with cognitive function, brain structure and CSF proteins were explored in cross‐sectional, longitudinal, and mediation analyses across the UK Biobank (n = 165,550), Chinese Alzheimer’s Biomarker and Lifestyle (CABLE, n = 867), and Alzheimer’s Disease Neuroimaging Initiative (ADNI, n = 802).ResultsHearing impairment was associated with an increased risk of AD over 11 years of follow‐up (HR 1.80, 95%CI 1.50‐2.15). Poor hearing status was associated with worse cognitive function in cross‐sectional and longitudinal studies. Moreover, hearing impairment was significantly related to lower volume of the temporal cortex, hippocampus, amygdala, inferior parietal lobe, precuneus and orbitofrontal cortex, to lower integrity of white matter tracts, and to a higher level of CSF tau protein. Mediation analyses showed that brain structure and CSF tau partly mediated the association between hearing impairment and cognitive decline.ConclusionHearing impairment is a risk factor for AD, and is associated with brain structure, tau pathology, and cognitive decline.

Developing Topics.

Apathy, defined as a lack of motivation towards goal-directed behavior, is a common neuropsychiatric symptom in Alzheimer's (AD) and Parkinson's (PD) disease. However, the mechanism underlying apathy is still unclear. Studies have postulated that the degeneration of frontal cortical and subcortical structures may play a major role in the mechanism of apathy. This study investigates whether associations between degeneration in structural and functional connectivity between frontal and subcortical regions contributes to the development of apathetic behavior and whether these associations differ by diseases. Forty-four patients, 8 with AD, 14 amnestic mild cognitive impairment (aMCI), and 22 PD, received MRI brain scans, a decision-making behavioral task, cognitive and psychosocial assessments including the dimensional apathy scale (DAS). We quantified functional connectivity and white matter tract integrity for a set of frontal and subcortical regions of interest, and examined the associations among fronto-subcortical connectivity, behavioral measures, and the DAS. These associations were tested for patient group interactions. Combining AD and aMCI into one patient group, the AD/aMCI group showed worse apathy than PD in terms of the total, the executive, and the behavioral/cognitive subscores (see Table 1), while the DAS emotional subscore was not different between the two groups. For the decision-making task, the proportion of trial acceptance was similar between the groups, but AD/aMCI had slower decision latency than PD. Group interaction with brain measures was observed in the association between DAS total score and the functional connectivity between the right pars triangularis in the inferior frontal gyrus and the caudate (See Figure 1; interaction effect: beta = -.367, p = .0422 FDR corrected). The white matter tract connecting the right pars triangularis to subcortical regions also showed a group interaction with DAS total score but at an uncorrected statistical level (Figure 2; beta = 3.61, p = .0454, uncorrected). Our preliminary analyses exposed phenotypic differences in apathy profiles and decision-making behavior between AD and PD. Furthermore, the observed functional and structural neurodegenerative changes associated with higher apathy severity may also differ between the two diseases. Future analyses in a larger cohort will examine distinct neurodegeneration patterns between the two diseases.

Hippocampus‐associated tract degradation follows differential DTI patterns and is influenced by amyloid in MCI patients

AbstractBackgroundDiffusion tensor imaging (DTI) has been leveraged to understand microstructural alterations to limbic and cortico‐cortical tracts in Alzheimer’s disease (AD). However, investigation into the key changes and patterns of fractional anisotropy (FA) and mean diffusivity (MD) metrics in the early stages of MCI has not been widely investigated. This study aimed to establish whether the early DTI white matter tract changes in MCI patients are decoupled and whether amyloid positivity (Aβ+/Aβ‐) is associated with early tract degradation.Method171 participants (103 MCI & 73 CN) were recruited from the AD Neuroimaging Initiative (ADNI; adni.loni.usc.edu) database. For each participant, FA and MD maps were obtained at their baseline scan and voxel wise analysis was carried out using FSL (https://fsl.fmrib.ox.ac.uk/fsl/) and Tract‐Based Spatial Statistics (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/TBSS). Students t‐tests were conducted on the FA and MD changes in hippocampal WM tracts, previously identified as areas of potential early degradation. Comparisons between CN and MCI groups were made along Aβ+ and Aβ‐ groups.ResultWe found evidence for WM degradation, indicated by lower FA scores in MCI participants compared with controls, in the specific regions of interest of the fornix (p = 0.004) and tapetum (p = 0.012). Mean diffusivity was increased in the MCI group compared to CN in areas of the fornix (p < 0.001), consistent with FA alterations, yet differed from areas identified in FA changes owing to changes in the uncinate fasciculus (p = 0.022) and cingulum (p = 0.003). Comparison of DTI metrics in the fornix between amyloid status groups revealed that Aβ+ participants had significantly lower FA compared to Aβ‐ participants (p = 0.047), but MD did not significantly differ.ConclusionThese results confirm the notion that WM tract integrity degradation in the tract apparatus surrounding the hippocampus occur early in the AD trajectory. However, results indicate that FA alterations occur in different patterns to that of MD and that amyloid may influence these patterns. This supports the idea that efforts to develop therapeutics which maintain WM tract integrity early may be key to slowing AD progression.

Medial Temporal Lobe White Matter Integrity is Related to Memory and Amyloid‐Beta Pathology in Aging

AbstractBackgroundDamage to white matter (WM) within the medial temporal lobe (MTL) may underlie memory decline in aging and Alzheimer’s disease (AD). We measured MTL WM tract integrity through diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging (NODDI). We tested WM integrity associations with memory performance and amyloid‐ß pathology in cognitively normal older adults.Method105 cognitively normal older adults (70.8 years old, 65% female) with diffusion MRI were processed with MRtrix3. Standard diffusion metrics of fractional anisotropy (FA) and mean diffusivity (MD) were calculated. NODDI MDT was used to generate the neurite density index (NDI), representing number of voxels with unhindered diffusion, and the orientation dispersion index (ODI), representing the variability of neurite orientation. We calculated these measures for MTL tracts from the JHU WM Atlas: cingulum‐hippocampus, fornix column/body, and fornix/stria terminalis. Participants received 18F‐florbetapir (FBP) to measure Aß pathology (n = 94), and global FBP SUVR was calculated. Memory was measured with the Rey Auditory Verbal Learning Test delayed recall score (RAVLT, n = 81). Analyses covaried for age and/or education.ResultBetter memory was associated with lower ODI in the fornix column/body (r = ‐0.27, p = 0.018), with trends for higher FA (r = 0.021, p = 0.06) and lower NDI (r = ‐0.19, p = 0.09). Better memory was also associated with higher MD in the cingulum‐hippocampus (right: r = 0.23, p = 0.04; left: r = 0.25, p = 0.03), with trends for lower ODI (right: r = ‐.20, p = 0.08; left: r = ‐0.20, p = 0.09). Higher FBP SUVR was associated with increased FA in the fornix column/body (r = 0.31, p = 0.003) and a trend in the left cingulum hippocampus (r = 0.20, p = 0.054). Memory or FBP SUVR was not significantly related to integrity of the fornix/stria terminalis.ConclusionIntegrity of fornix column/body and cingulum‐hippocampus were related to both memory performance and Aß pathology. Our results suggest that using a combination of NODDI as well as diffusion tensor metrics provided a more robust understanding of memory impacts in aging.

Thalamo-dorsolateral prefrontal cortex tract integrity correlates with residual consciousness in patient with prolonged disorders of consciousness

Thalamo-dorsolateral prefrontal cortex tract integrity correlates with residual consciousness in patient with prolonged disorders of consciousness

The association between microbiome and white matter integrity in the elderly with youthful memory in superaging

AbstractBackgroundAging‐related cognitive decline has been regarded as a normal consequence of aging. However, previous research on ‘SuperAgers’ suggests that such decline is not inevitable. The purpose of this study was to investigate the relationship between the microbiome and white matter integrity in SuperAgers, which may help us understand the mechanism that preserves memory function in these individuals.MethodWe enrolled a total of 115 elderly individuals aged 60 years or older with normal cognitive function, which was defined as scoring one standard deviation or more above the population norm on tests of memory, attention, language, visuospatial ability, and frontal function in the Seoul Neuropsychological Screening Battery. SuperAgers were defined based on their delayed recall scores compared to middle‐aged adults (45 years old) in both the Seoul Verbal Learning Test and the Rey‐Osterrieth Complex Figure Test. Diffusion tensor images were analyzed using tract‐based spatial statistics (TBSS). Parameters related to diffusion tensors were calculated at the voxel level to generate fractional anisotropy (FA) images using the DTIFit. FA values, a diffusion tensor parameter reflecting white matter fiber tract integrity, were measured and compared between SuperAgers and typical agers using the FSL randomise program. For microbiome analysis, EZ biocloud was used to perform alpha diversity, taxonomic hierarchy, and taxonomic composition analysis for each subject analysis. Group analysis was also conducted using the taxonomic composition values, and further group analysis was carried out using ACE, Chao1, and Jacknife, which are indicators of species richness. Statistical analyses were conducted using Statistical Package for Social Science 19.ResultCompared to typical agers, superagers showed a higher number of Firmicutes and Actinobacteria, which have been associated with higher cognitive function. However, there was no significant difference between superagers and typical agers. Additionally, an analysis of the association between p_firmicutes, c_mollicutes, o_lactobacilales and f_erysipelotrichaceae with white matter integrity showed no significant association.ConclusionBased on these results, it can be inferred that superagers may have a correlation with microbiome strains that are closely related to cognitive function, as well as white matter in the brain

An Overview of Transcranial Magnetic Stimulation and Its Application in Multiple Sclerosis

Transcranial magnetic stimulation (TMS) is a flexible, non-invasive technique that involves the production of a brief magnetic field to stimulate the conductive structures of the brain. When TMS is specifically employed as a single- or paired-pulse over the motor cortex, the function and integrity of the descending motor pathways can be assessed through the generation of a motor evoked potential (MEP). Important MEP-derived measures include the motor threshold, MEP amplitude and latency, central motor conduction time, silent period, intracortical inhibition, and intracortical facilitation. These functional measures may have use in individuals with multiple sclerosis (MS), a common chronic autoimmune disorder of the central nervous system, due to their useful diagnostic and prognostic implications. As a representation of excitability and conductivity, TMS measures may have the potential to serve as objective markers of corticospinal tract integrity, which is a major aspect of clinical disability in MS. Additionally, TMS may be employed to help monitor and provide insight on the effects of therapies for patients with MS over a longitudinal timeframe. In this review, we focus on the application of TMS in the context of MS, with an emphasis on the relationship between TMS measures and widely used clinical assessment measures used for patients with MS.

The importance of pyramidal tract integrity for cortical plasticity and related functionality in patients with multiple sclerosis

The importance of pyramidal tract integrity for cortical plasticity and related functionality in patients with multiple sclerosis

Effect of the duration of hypertension on white matter structure and its link with cognition

The relation between hypertension (HTN) and cognition has been reported inclusive results, which may be affected by disease duration. Our study aimed to examine the influence of HTN duration on cognition and its underlying white matter (WM) changes including macrostructural WM hyperintensities (WMH) and microstructural WM integrity. A total of 1218 patients aged ≥55 years with neuropsychological assessment and a subgroup of 233 people with imaging data were recruited and divided into 3 groups (short duration: <5 years, medium duration: 5–20 years, long duration: >20 years). We found that greater HTN duration was preferentially related to worse executive function (EF), processing speed (PS), and more severe WMH, which became more significant during long duration stage. The reductions in WM integrity were evident at the early stage especially in long-range association fibers and then scattered through the whole brain. Increasing WMH and decreasing integrity of specific tracts consistently undermined EF. Furthermore, free water imaging method greatly enhanced the sensitivity in detecting HTN-related WM alterations. These findings supported that the neurological damaging effects of HTN is cumulative and neuroimaging markers of WM at macro- and microstructural level underlie the progressive effect of HTN on cognition.

Cortical volume alteration in the superior parietal region mediates the relationship between childhood abuse and PTSD avoidance symptoms: A complementary multimodal neuroimaging study

BackgroundAdverse childhood experiences (ACE), which can be separated into abuse and neglect, contribute to the development of post-traumatic stress symptoms (PTSS). However, which brain structures are mainly affected by ACE as well as the mediating role these brain structures play in ACE and PTSS relationship are still being investigated. The current study tested the effect of ACE on brain structure and investigated the latter's mediating role in ACE-PTSS relationship. MethodsA total of 78 adults with self-reported ACE were included in this study. Participants completed the childhood trauma questionnaire (CTQ) and a Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) to ascertain ACE history and PTSS, respectively. T1w images and diffusion MRI scans were then acquired to assess cortical morphometry and white matter (WM) integrity in fibre tracts connecting key areas where ACE-related cortical volume alterations were observed. ResultsThe combined effect of ACE was negatively associated with total grey matter volume and local cortical area in the right superior parietal region (rSP). Childhood abuse was negatively related to right superior parietal volume after controlling for neglect and overall psychological burden. The right superior parietal volume significantly mediated the relationship between childhood abuse and avoidance-related PTSS. Post-hoc analyses showed that the indirect relation was subsequently moderated by dissociative symptoms. Lastly, a complementary examination of the WM tracts connected to abuse-associated cortical GM regions shows that abuse was negatively related to the normalised fibre density of WM tracts connected to the right superior parietal region. ConclusionWe provide multimodal structural evidence that ACE in the first years of life is related to alterations in the right superior brain region, which plays a crucial role in spatial processing and attentional functioning. Additionally, we highlight that the cortical volume alteration in this region may play a role in explaining the relationship between childhood abuse and avoidance symptoms.

42 White matter injury is driven by HIV duration, immune and vascular factors in virally suppressed people living with HIV: a longitudinal diffusion imaging study

Objective:The aim of the current longitudinal study was to use improved brain white matter integrity outcomes (better at resolving white matter complexity, hence with improved biological significance compared to traditional diffusion tensor imaging - DTI outcomes) while considering baseline age, cardiovascular diseases (CVD), and HIV disease markers impacts on the health of major white matter tracts in virally suppressed people Living with HIV infection (PLHIV) versus demographically, geographically, and life-style comparable HIVnegative controls. Furthermore, white-matter hyperintensity (WMH) and normal-appearing white matter (NAWM) volumes and microstructure were considered.Participants and Methods:At baseline 48 HIV-controls and 84 virally suppressed PLHIV (mean age 55), and at 24-month follow-up, 40 HIV-controls and 75 virally suppressed PLHIV underwent an MRI scan (3T Phillips) collecting a high-resolution anatomical MRI, FLAIR, and a 32-direction diffusion imaging. The diffusion data were processed using mrtrix and intra-cranial volume-corrected outcomes included fibre density (FD), fibre cross-section (log was used; logFC) and a composite fibre density and cross-section (FDC). The volumetric data was first processed in Freesurfer 6.0, and WMH were segmented using the “pgs” U-Net neural network. Using mixed models, we examine the longitudinal mrtrix outcomes across major white matter tracts by HIV status, and associations with CVD (sum of the scaled scores of total cholesterol, HDL, Systolic BP, current smoking, and diabetes) and HIV disease (HIV duration, historical AIDS, nadir CD4, baseline CD4) markers. Additionally, we assessed the volume, and FDC in the periventricular and deep WMH, as well as NAWM, and the associations with CVD and HIV disease markers. We used FDR control procedure (alpha = 0.05), and all p-values reported are FDR adjusted.Results:Relative to controls, PLHIV showed significant reductions (p&lt;.05 - p&lt;.01) of FC, and FDC to a lesser extent, in multiple long cortical association tracts, and within striatal- and thalamic-frontoparietal connections. A small HIV by age interaction was only detected for FC of inferior longitudinal fasciculus (Beta = -0.004, SE = 0.002 p&lt;.04). However, HIV duration (corrected for baseline age) was associated with worse FDC across multiple tracts (p&lt;03 -p&lt;.001). Baseline CD4 counts associated with lower FD in frontal association tracts (p&lt;.05 -p&lt;.005). Furthermore, WMH increased in size with time, age, and higher CVD risk factors, but not HIV status. In PLHIV, deep WMH and NAWM microstructure were both associated with worse CVD but not HIV disease markers.Conclusions:The fine integrity of major white matter tracts is impacted by HIV status, HIV duration and baseline CD4, whereas WMH and NAWM volumes and microstructure are affected by CVD. Our study provides further evidence of the immuno-vascular underpinning of HIV neuropathogenesis in virally suppressed PLHIV. The convergence of these effects in aging PLHIV may lead to early neurodegeneration. Hence, improving CVD health and maintaining high CD4 is critical.

Structural and connectivity parameters reveal spared connectivity in young patients with non-progressive compared to slow-progressive cerebellar ataxia.

Within Pediatric Cerebellar Ataxias (PCAs), patients with non-progressive ataxia (NonP) surprisingly show postural motor behavior comparable to that of healthy controls, differently to slow-progressive ataxia patients (SlowP). This difference may depend on the building of compensatory strategies of the intact areas in NonP brain network. Eleven PCAs patients were recruited: five with NonP and six with SlowP. We assessed volumetric and axonal bundles alterations with a multimodal approach to investigate whether eventual spared connectivity between basal ganglia and cerebellum explains the different postural motor behavior of NonP and SlowP patients. Cerebellar lobules were smaller in SlowP patients. NonP patients showed a lower number of streamlines in the cerebello-thalamo-cortical tracts but a generalized higher integrity of white matter tracts connecting the cortex and the basal ganglia with the cerebellum. This work reveals that the axonal bundles connecting the cerebellum with basal ganglia and cortex demonstrate a higher integrity in NonP patients. This evidence highlights the importance of the cerebellum-basal ganglia connectivity to explain the different postural motor behavior of NonP and SlowP patients and support the possible compensatory role of basal ganglia in patients with stable cerebellar malformation.

A prospective study of MRI biomarkers in the brain and lower limb muscles for prediction of lower limb motor recovery following stroke.

The aim of this prospective observational longitudinal study was to explore and decipher the predictive value of prospective MRI biomarkers in the brain and lower limb muscles for 3-month lower limb motor recovery following stroke. In the brain, we measured the integrity of the corticospinal tract (fractional anisotropy/"FA"). In the muscles, we measured volume, fatty replacement (fat fraction analysis and proton spectroscopy) and oedema. Measurements were taken at two time points: (1) within 4 weeks of stroke (baseline measurement, clinical and imaging) and (2) 3 months following stroke (follow up measurement, clinical only). Clinical measurements consisted of assessments of functional ability and strength (Fugl-Meyer score, motor NIHSS, Functional Ambulation Category/"FAC", and muscle dynamometry). Twenty-three patients completed imaging and clinical assessments at baseline and follow-up; five patients had partial imaging assessment. The results provided some evidence that damage to the corticospinal tract would result in less motor recovery: recovery of the Fugl-Meyer score and dynamometric ankle plantarflexion, ankle dorsiflexion, and knee extension correlated positively and significantly with fractional anisotropy (0.406-0.457; p = 0.034-p = 0.016). However, fractional anisotropy demonstrated a negative correlation with recovery of the Functional Ambulation Category (-0.359, p = 0.046). For the muscle imaging, significant inverse correlation was observed between vastus lateralis fat fraction vs. NIHSS recovery (-0.401, p = 0.04), and a strong positive correlation was observed between ratio of intra- to extra-myocellular lipid concentrations and the recovery of knee flexion (0.709, p = 0.007). This study supports previous literature indicating a positive correlation between the integrity of the corticospinal tract and motor recovery post-stroke, expanding the limited available literature describing this relationship specifically for the lower limb. However, recovery of functional ambulation behaved differently to other clinical recovery markers by demonstrating an inverse relationship with corticospinal tract integrity. The study also introduces some muscle imaging biomarkers as potentially valuable in the prediction of 3-month lower limb motor recovery following stroke.