White Matter Structural Changes Research Articles

Causal Relationship between Aging and Anorexia Nervosa: A White-Matter-Microstructure-Mediated Mendelian Randomization Analysis.

This study employed a two-step Mendelian randomization analysis to explore the causal relationship between telomere length, as a marker of aging, and anorexia nervosa and to evaluate the mediating role of changes in the white matter microstructure across different brain regions. We selected genetic variants associated with 675 diffusion magnetic resonance imaging phenotypes representing changes in brain white matter. F-statistics confirmed the validity of the instruments, ensuring robust causal inference. Sensitivity analyses, including heterogeneity tests, horizontal pleiotropy tests, and leave-one-out tests, validated the results. The results show that telomere length is significantly negatively correlated with anorexia nervosa in a unidirectional manner (p = 0.017). Additionally, changes in specific white matter structures, such as the internal capsule, corona radiata, posterior thalamic radiation, left cingulate gyrus, left longitudinal fasciculus, and left forceps minor (p < 0.05), were identified as mediators. These findings enhance our understanding of the neural mechanisms, underlying the exacerbation of anorexia nervosa with aging; emphasize the role of brain functional networks in disease progression; and provide potential biological targets for future therapeutic interventions.

Genetic influence on microstructure integrity and motor progression in Parkinson's disease

BackgroundUp to 10 % of Parkinson's disease (PD) populations carry a genetic risk variant, which may not only increase one's chance of developing PD but also affect disease presentation and progression. We hypothesize motor impairment in genetic carriers of PD correlate to different patterns of microstructural changes over time. Design/methodsData were accessed from the Parkinson's Progression Markers Initiative (PPMI) project. Connectometry analyses were performed for GBA1+ PD, LRRK2+ PD, and sporadic PD correlating white matter structural changes, as measured by quantitative anisotropy (QA), with motor impairment, as measured by MDS-UPDRS III. ResultsThere was a negative correlation between QA and MDS-UPDRS III in all 3 cohorts at 48 months. In GBA1+ PD (n = 12), the white matter tracts identified were cortical and subcortical, while in the LRRK2+ PD (n = 18) and sporadic PD (n = 45) cohorts white tracts identified were primarily subcortical and within the brainstem. ConclusionsOur findings highlight the association between motor symptom progrerssion and structural connectivity in individuals with GBA1+ PD, LRRK2+ PD, and sporadic PD. Due to the small sample size, larger studies are needed in the future to confirm the findings.

Altered thalamocortical tract trajectory growth with undisrupted thalamic parcellation pattern in human lissencephaly brain at mid-gestational stage

Proper topographically organized neural connections between the thalamus and the cerebral cortex are mandatory for thalamus function. Thalamocortical (TC) fiber growth begins during the embryonic period and completes by the third trimester of gestation, so that human neonates at birth have a thalamus with a near-facsimile of adult functional parcellation. Whether congenital neocortical anomaly (e.g., lissencephaly) affects TC connection in humans is unknown. Here, via diffusion MRI fiber-tractography analysis of long-term formalin-fixed postmortem fetal brain diagnosed as lissencephaly in comparison with an age-matched normal one, we found similar topological patterns of thalamic subregions and of internal capsule parcellated by TC fibers. However, lissencephaly fetal brain showed white matter structural changes, including fewer/less organized TC fibers and optic radiations, and much less cortical plate invasion by TC fibers — particularly around the shallow central sulcus. Diffusion MRI fiber tractography of normal fetal brains at 15, 23, and 26 gestational weeks (GW) revealed dynamic volumetric change of each parcellated thalamic subregion, suggesting coupled developmental progress of the thalamus with the corresponding cortex. Moreover, from GW23 and GW26 normal fetal brains, TC endings in the cortical plate could be delineated to reflect cumulative progressive TC invasion of cortical plate. By contrast, lissencephaly brain showed a dramatic decrease in TC invasion of the cortical plate. Our study thus shows the feasibility of diffusion MRI fiber tractography in postmortem long-term formalin-fixed fetal brains to disclose the developmental progress of TC tracts coordinating with thalamic and neocortical growth both in normal and lissencephaly fetal brains at mid-gestational stage.

P.023 Review of imaging changes, cognitive decline, and dementia risk in cancer survivors after chemotherapy

Background: Cancer survival rates in Canada have been improving, leading to a steady increase in the number of survivors entering the typical ages of dementia onset. Yet, some cancer treatments (e.g. chemotherapy) are neurotoxic and adversely affect normal brain functioning. We conducted a review to examine changes observed in brain imaging and cognitive measures in survivorship, and long-term risk of dementia among cancer survivors. Methods: 91 Primary studies were selected from PubMed. Inclusion criteria were studies investigating the changes in brain imaging, cognition, and future dementia risk among adult survivors who received chemotherapy. Study quality was assessed based on 1) prospective, controlled design, 2) sample size, and 3) validated imaging and cognitive metrics. Results: Imaging studies identified MRI-based structural grey and white matter changes and functional network changes among survivors. Cognitive studies reported heterogeneous impairments in attention, memory, and executive function. In studies that examined dementia risk among cancer survivors, 67% reported lower risk of dementia, while 33% reported no association or a higher risk. Conclusions: While short-term cognitive impairment with associated changes on brain imaging is widely reported, findings concerning future or long-term cognitive impairment are mixed. Studies are warranted to identify potential connections between short-term and long-term cognitive function after cancer treatment.

Brain perfusion changes in beta-thalassemia

BackgroundBrain injury in hereditary hemoglobinopathies is commonly attributed to anemia-related relative hypoperfusion in terms of impaired oxygen blood supply. Supratentorial and infratentorial vascular watershed regions seem to be especially vulnerable, but data are very scarce.AimsWe investigated a large beta-thalassemia sample with arterial spin labeling in order to characterize regional perfusion changes and their correlation with phenotype and anemia severity.MethodsWe performed a multicenter single-scanner cross-sectional 3T-MRI study analyzing non-invasively the brain perfusion in 54 transfusion-dependent thalassemia (TDT), 23 non-transfusion-dependent thalassemia (NTDT) patients and 56 Healthy Controls (HC). Age, hemoglobin levels, and cognitive functioning were recorded.ResultsBoth TDT and NTDT patients showed globally increased brain perfusion values compared to healthy controls, while no difference was found between patient subgroups. Using age and sex as covariates and scaling the perfusion maps for the global cerebral blood flow, beta-thalassemia patients showed relative hyperperfusion in supratentorial/infratentorial watershed regions. Perfusion changes correlated with hemoglobin levels (p = 0.013) and were not observed in the less severely anemic patients (hemoglobin level > 9.5 g/dL). In the hyperperfused regions, white matter density was significantly decreased (p = 0.0003) in both patient subgroups vs. HC. In NTDT, white matter density changes correlated inversely with full-scale Intelligence Quotient (p = 0.007) while in TDT no correlation was found.ConclusionRelative hyperperfusion of watershed territories represents a hemodynamic hallmark of beta-thalassemia anemia challenging previous hypotheses of brain injury in hereditary anemias. A careful management of anemia severity might be crucial for preventing structural white matter changes and subsequent long-term cognitive impairment.

Superagers Resist Typical Age-Related White Matter Structural Changes.

Superagers are elderly individuals with the memory ability of people 30 years younger and provide evidence that age-related cognitive decline is not inevitable. In a sample of 64 superagers (mean age, 81.9; 59% women) and 55 typical older adults (mean age, 82.4; 64% women) from the Vallecas Project, we studied, cross-sectionally and longitudinally over 5 years with yearly follow-ups, the global cerebral white matter status as well as region-specific white matter microstructure assessment derived from diffusivity measures. Superagers and typical older adults showed no difference in global white matter health (total white matter volume, Fazekas score, and lesions volume) cross-sectionally or longitudinally. However, analyses of diffusion parameters revealed the better white matter microstructure in superagers than in typical older adults. Cross-sectional differences showed higher fractional anisotropy (FA) in superagers mostly in frontal fibers and lower mean diffusivity (MD) in most white matter tracts, expressed as an anteroposterior gradient with greater group differences in anterior tracts. FA decrease over time is slower in superagers than in typical older adults in all white matter tracts assessed, which is mirrored by MD increases over time being slower in superagers than in typical older adults in all white matter tracts except for the corticospinal tract, the uncinate fasciculus, and the forceps minor. The better preservation of white matter microstructure in superagers relative to typical older adults supports resistance to age-related brain structural changes as a mechanism underpinning the remarkable memory capacity of superagers, while their regional aging pattern is in line with the last-in-first-out hypothesis.

Association between homotopic connectivity and clinical symptoms in first-episode schizophrenia

BackgroundAbnormal functional connectivity (FC) in the brain has been observed in schizophrenia patients. However, studies on FC between homotopic brain regions are limited, and the results of these studies are inconsistent. The aim of this study was to compare homotopic connectivity between first-episode schizophrenia (FES) patients and healthy subjects and assess its correlation with clinical symptoms. MethodsThirty-one FES patients and thirty-three healthy controls (HC) were included in the study. The voxel-mirrored homotopic connectivity (VMHC) method of resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyse the changes in homotopic connectivity between the two groups. The 5-factor PANSS model was used to quantitatively evaluate the severity of symptoms in FES patients. Partial correlation analysis was used to assess the correlation between homotopic connectivity changes and clinical symptoms. ResultsCompared to those in the HC group, VMHC values were decreased in the paracentral lobule (PL), thalamus, and superior temporal gyrus (STG) in the FES group (P < 0.05, FDR correction). No significant differences in white matter volume (WMV) within the subregion of the corpus callosum or in brain regions associated with reduced VMHC were observed between the two groups. Partial correlation analyses revealed that VMHC in the bilateral STG of FES patients was positively correlated with negative symptoms (rleft = 0.46, p < 0.05; rright = 0.47, p < 0.05), and VMHC in the right thalamus was negatively correlated with disorganized/concrete symptoms (rright = 0.45, p < 0.05). ConclusionOur study revealed that homotopic connectivity is altered in the resting-state brain of FES patients and correlates with the severity of negative symptoms; this change may be independent of structural changes in white matter. These findings may contribute to the development of the abnormal connectivity hypothesis in schizophrenia patients.

Resting State Brain Networks under Inverse Agonist versus Complete Knockout of the Cannabinoid Receptor 1.

The cannabinoid receptor 1 (CB1) is famous as the target of Δ9-tetrahydrocannabinol (THC), which is the active ingredient of marijuana. Suppression of CB1 is frequently suggested as a drug target or gene therapy for many conditions (e.g., obesity, Parkinson's disease). However, brain networks affected by CB1 remain elusive, and unanticipated psychological effects in a clinical trial had dire consequences. To better understand the whole brain effects of CB1 suppression we performed in vivo imaging on mice under complete knockout of the gene for CB1 (cnr1-/-) and also under the CB1 inverse agonist rimonabant. We examined white matter structural changes and brain function (network activity and directional uniformity) in cnr1-/- mice. In cnr1-/- mice, white matter (in both sexes) and functional directional uniformity (in male mice) were altered across the brain but network activity was largely unaltered. Conversely, under rimonabant, functional directional uniformity was not altered but network activity was altered in cortical regions, primarily in networks known to be altered by THC (e.g., neocortex, hippocampal formation). However, rimonabant did not alter many brain regions found in both our cnr1-/- results and previous behavioral studies of cnr1-/- mice (e.g., thalamus, infralimbic area). This suggests that chronic loss of cnr1 is substantially different from short-term suppression, subtly rewiring the brain but largely maintaining the network activity. Our results help explain why pathological mutations in CB1 (e.g., chronic pain) do not always provide insight into the side effects of CB1 suppression (e.g., clinical depression), and thus urge more preclinical studies for any drugs that suppress CB1.

White adipose tissue distribution and amount are associated with increased white matter connectivity.

Obesity represents a significant public health concern and is linked to various comorbidities and cognitive impairments. Previous research indicates that elevated body mass index (BMI) is associated with structural changes in white matter (WM). However, a deeper characterization of body composition is required, especially considering the links between abdominal obesity and metabolic dysfunction. This study aims to enhance our understanding of the relationship between obesity and WM connectivity by directly assessing the amount and distribution of fat tissue. Whole-body magnetic resonance imaging (MRI) was employed to evaluate total adipose tissue (TAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT), while MR liver spectroscopy measured liver fat content in 63 normal-weight, overweight, and obese males. WM connectivity was quantified using microstructure-informed tractography. Connectome-based predictive modeling was used to predict body composition metrics based on WM connectomes. Our analysis revealed a positive dependency between BMI, TAT, SAT, and WM connectivity in brain regions involved in reward processing and appetite regulation, such as the insula, nucleus accumbens, and orbitofrontal cortex. Increased connectivity was also observed in cognitive control and inhibition networks, including the middle frontal gyrus and anterior cingulate cortex. No significant associations were found between WM connectivity and VAT or liver fat. Our findings suggest that altered neural communication between these brain regions may affect cognitive processes, emotional regulation, and reward perception in individuals with obesity, potentially contributing to weight gain. While our study did not identify a link between WM connectivity and VAT or liver fat, further investigation of the role of various fat depots and metabolic factors in brain networks is required to advance obesity prevention and treatment approaches.

White matter structural changes before and after microvascular decompression for hemifacial spasm.

Hemifacial spasm (HFS) is a syndrome characterized by involuntary contractions of the facial muscles innervated by the ipsilateral facial nerve. Currently, microvascular decompression (MVD) is an effective treatment for HFS. Diffusion weighted imaging (DWI) is a non-invasive advanced magnetic resonance technique that allows us to reconstruct white matter (WM) virtually based on water diffusion direction. This enables us to model the human brain as a complex network using graph theory. In our study, we recruited 32 patients with HFS and 32 healthy controls to analyze and compare the topological organization of whole-brain white matter networks between the groups. We also explored the potential relationships between altered topological properties and clinical outcomes. Compared to the HC group, the white matter network was disrupted in both preoperative and postoperative groups of HFS patients, mainly located in the somatomotor network, limbic network, and default network (All P < 0.05, FDR corrected). There was no significant difference between the preoperative and postoperative groups (P > 0.05, FDR corrected). There was a correlation between the altered topological properties and clinical outcomes in the postoperative group of patients (All P < 0.05, FDR corrected). Our findings indicate that in HFS, the white matter structural network was disrupted before and after MVD, and that these alterations in the postoperative group were correlated with the clinical outcomes. White matter alteration here described may subserve as potential biomarkers for HFS and may help us identify patients with HFS who can benefit from MVD and thus can help us make a proper surgical patient selection.

Differential influences of rest tremor on brain fiber architecture in essential tremor and Parkinson's disease

BackgroundRest tremor is a movement disorder commonly found in diseases like Parkinson's disease (PD) and essential tremor (ET). Rest tremor typically shows slower progression in PD, but more severe progression in ET. However, the underlying white matter organization of rest tremor behind PD and ET remains unclear. MethodsThis study included 57 ET patients (40 without rest tremor (ETWR), 17 with rest tremor (ETRT)), 68 PD patients (34 without rest tremor (PDWR), 34 with rest tremor (PDRT)), and 62 normal controls (NC). Fixel-based analysis was used to evaluate the structural changes of white matter in rest tremor in these different diseases. ResultsThe fiber-bundle cross-section (FC) of the right non-decussating dentato-rubro-thalamic tract and several fibers outside the dentato-rubro-thalamic pathway in ETWR were significantly higher than that in NC. The fiber density and cross-section of the left nigro-pallidal in PDWR is significantly lower than that in NC, while the FC of bilateral nigro-pallidal in PDRT is significantly lower than that in NC. ConclusionET patients with pure action tremor showed over-activation of fiber tracts. However, when superimposed with rest tremor, ET patients no longer exhibited over-activation of fiber tracts, but rather showed a trend of fiber tract damage. Except for the nigro-pallidal degeneration in all PD, PDRT will not experience further deterioration in fiber organization. These results provide important insights into the unique effects of rest tremor on brain fiber architecture in ET and PD.

Corpus callosum and cerebellum participate in semantic dysfunction of Parkinson's disease: a diffusion tensor imaging-based cross-sectional study.

Language dysfunction is common in Parkinson's disease (PD) patients, among which, the decline of semantic fluency is usually observed. This study aims to explore the relationship between white matter (WM) alterations and semantic fluency changes in PD patients. 127 PD patients from the Parkinson's Progression Markers Initiative cohort who received diffusion tensor imaging scanning, clinical assessment and semantic fluency test (SFT) were included. Tract-based special statistics, automated fiber quantification, graph-theoretical and network-based analyses were performed to analyze the correlation between WM structural changes, brain network features and semantic fluency in PD patients. Fractional anisotropy of corpus callosum, anterior thalamic radiation, inferior front-occipital fasciculus, and uncinate fasciculus, were positively correlated with SFT scores, while a negative correlation was identified between radial diffusion of the corpus callosum, inferior longitudinal fasciculus, and SFT scores. Automatic fiber quantification identified similar alterations with more details in these WM tracts. Brain network analysis positively correlated SFT scores with nodal efficiency of cerebellar lobule VIII, and nodal local efficiency of cerebellar lobule X. WM integrity and myelin integrity in the corpus callosum and several other language-related WM tracts may influence the semantic function in PD patients. Damage to the cerebellum lobule VIII and lobule X may also be involved in semantic dysfunction in PD patients.

Alterations in white matter fiber tracts and their correlation with flying cadet behavior.

An increasing number of studies have shown that flight training alters the human brain structure; however, most studies have focused on gray matter, and the exploration of white matter structure has been largely neglected. This study aimed to investigate the changes in white matter structure induced by flight training and estimate the correlation between such changes and psychomotor and flight performance. Diffusion tensor imaging data were obtained from 25 flying cadets and 24 general college students. Data were collected in 2019 and 2022 and analyzed using automated fiber quantification. This study found no significant changes in the flight group in 2019. However, in 2022, the flight group exhibited significant alterations in the diffusion tensor imaging of the right anterior thalamic radiation, left cingulum cingulate, bilateral superior longitudinal fasciculus, and left arcuate fasciculus. These changes occurred within local nodes of the fiber tracts. In addition, we found that changes in fiber tracts in the 2022 flight group were correlated with the reaction time of the psychomotor test task and flight duration. These findings may help improve flight training programs and provide new ideas for the selection of excellent pilots.

N-acetylcysteine during critical neurodevelopmental periods prevents behavioral and neurochemical deficits in the Poly I:C rat model of schizophrenia

Schizophrenia is a chronic neurodevelopmental disorder with an inflammatory/prooxidant component. N-acetylcysteine (NAC) has been evaluated in schizophrenia as an adjuvant to antipsychotics, but its role as a preventive strategy has not been sufficiently explored. We aimed to evaluate the potential of NAC administration in two-time windows before the onset of symptoms in a schizophrenia-like maternal immune stimulation (MIS) rat model. Pregnant Wistar rats were injected with Poly I:C or Saline on gestational day (GD) 15. Three different preventive approaches were evaluated: 1) NAC treatment during periadolescence in the offspring (from postnatal day [PND] 35 to 49); 2) NAC treatment during pregnancy after MIS challenge until delivery (GD15–21); and 3) NAC treatment throughout all pregnancy (GD1–21). At postnatal day (PND) 70, prepulse inhibition (PPI) and anxiety levels were evaluated. In vivo magnetic resonance (MR) imaging was acquired on PND100 to assess structural changes in gray and white matter, and brain metabolite concentrations. Additionally, inflammation and oxidative stress (IOS) markers were measured ex vivo in selected brain regions. MIS offspring showed behavioral, neuroanatomical, and biochemical alterations. Interestingly, NAC treatment during periadolescence prevented PPI deficits and partially counteracted some biochemical imbalances. Moreover, NAC treatments during pregnancy not only replicated the beneficial outcomes reported by the treatment in periadolescence, but also prevented some neuroanatomical deficits, including reductions in hippocampal and corpus callosum volumes. This study suggests that early reduction of inflammation and prooxidation could help prevent the onset of schizophrenia-like symptoms, supporting the importance of anti-IOS compounds in ameliorating this disorder.

Neurophysiological, balance and motion evidence in adolescent idiopathic scoliosis: A systematic review.

Adolescent idiopathic scoliosis (AIS) is a spinal deformity that affects approximately 4% of the world's population. Several hypotheses regarding the etiology of AIS have been investigated. In the last decades, impaired visual-spatial perception, alterations in spatial body orientation and sensory integration deficits have been documented. We aimed to summarize the neurophysiological, balance, and motion evidence related to AIS published in the last fifteen years, between January 2008 and April 2023. Both observational and interventional studies were considered. Only studies using quantitative assessment methods, such as electroencephalography (EEG), electromyography (EMG), magnetic resonance imaging (MRI), somatosensory evoked potentials, force platform, or motion capture, were included. 1250 eligible records identified from online database searching were filtered by duplicate removal, title and abstract screening, and qualitative analysis. 61 articles met the inclusion criteria (i.e., Cobb range 10°-35°, age range 10-18 years) and were summarized. We found significant evidence of impaired standing balance in individuals with AIS who greatly rely on visual and proprioceptive information to stay upright. EMG studies frequently reported an increased activity on the convex side of the intrinsic spinae muscles. EEG data show increased delta and theta power, higher alpha peak frequencies, and significant suppression in the alpha and beta bands in subjects with AIS during standing tasks. MRI studies report changes in white matter structures, differences in the vestibular system, and abnormal cortical activations over motor-related areas in subjects with AIS. Bracing appears to be an effective treatment for AIS, leading to improvements in static balance and gait. Methodological issues prevent reliable conclusions about the effects of other treatment options. This review underscores the importance of quantitative assessment methods to explore the etiology and pathophysiology of AIS. Further research is needed to measure the impact of physical therapy and orthotic treatments on the neurophysiological mechanisms of the disease.

What clinical parameter strongly associates white matter tract alterations in a Multiple Sclerosis population with voiding dysfunction? A prospective exploratory study.

To correlate clinical and urodynamics parameters in Multiple Sclerosis patients (MS) presenting Lower Urinary Tract Symptoms (LUTS) with both Expanded Disability Status Scale (EDSS) and changes in white matter integrity as seen on Diffusion Tensor Images (DTI). LUTS worsen throughout MS, as does lesion burden. We investigated which symptoms correlated best with structural changes in white matter structure. Ten adult women >18 years were recruited with stable MS for ≥3 months and voiding dysfunction defined as %PVR/BV > 20%. Patients participated in a clinical Urodynamic Study (UDS) and completed several questionnaires (i.e., HAM, AUASS, NBS-QoL). DTI images were acquired using a 7-Tesla Siemens MAGNETOM Terra MRI scanner. DTI maps were constructed, and individual patients were co-registered with the ICBM-DTI-81 white matter atlas to extract fractional anisotropy (FA) and mean diffusivity (MD). Pearson's correlation test was performed between each WMT and clinical parameters and between clinical parameters and the EDSS score as well. P-values < 0.05 were considered significant. Of the clinical parameters, %PVR/BV obtained from the average of multiple un-instrumented uroflow assessments had significant correlations to the greatest number of WMTs. Furthermore, we observed that in all recorded clinical parameters, %PVR/BV was the only significant parameter correlated to the EDSS score. This study demonstrates that %PVR/BV can be used as an objective parameter to gauge WMT changes and disease progression in MS patients. Future studies are needed to refine this model.

Bridging Reduced Grip Strength and Altered Executive Function: Specific Brain White Matter Structural Changes in Patients with Alzheimer's Disease.

To investigate the correlation between specific fiber tracts and grip strength and cognitive function in patients with Alzheimer's disease (AD) by fixel-based analysis (FBA). AD patients were divided into AD with low grip strength (AD-LGS, n=29) and AD without low grip strength (AD-nLGS, n=25), along with 31 normal controls (NC). General data, neuropsychological tests, grip strength and cranial magnetic resonance imaging (MRI) scans were collected. FBA evaluated white matter (WM) fiber metrics, including fiber density (FD), fiber cross-sectional (FC), and fiber density and cross-sectional area (FDC). The mean fiber indicators of the fiber tracts of interest (TOI) were extracted in cerebral region of significant statistical differences in FBA to further compare the differences between groups and analyze the correlation between fiber properties and neuropsychological test scores. Compared to AD-nLGS group, AD-LGS group showed significant reductions in FDC in several cerebral regions. In AD patients, FDC values of bilateral uncinate fasciculus and left superior longitudinal fasciculus were positively correlated with Clock Drawing Test scores, while FDC of splenium of corpus callosum, bilateral anterior cingulate tracts, forceps major, and bilateral inferior longitudinal fasciculus were positively correlated with the Executive Factor Score of Memory and Executive Screening scale scores. Reduced grip strength in AD patients is associated with extensive impairment of WM structural integrity. Changes in FDC of specific WM fiber tracts related to executive function play a significant mediating role in the reduction of grip strength in AD patients.

Cortical Network Disruption Is Minimal in Early Stages of Psychosis.

Schizophrenia is associated with white matter disruption and topological reorganization of cortical connectivity but the trajectory of these changes, from the first psychotic episode to established illness, is poorly understood. Current studies in first-episode psychosis (FEP) patients using diffusion magnetic resonance imaging (dMRI) suggest such disruption may be detectable at the onset of psychosis, but specific results vary widely, and few reports have contextualized their findings with direct comparison to young adults with established illness. Diffusion and T1-weighted 7T MR scans were obtained from N = 112 individuals (58 with untreated FEP, 17 with established schizophrenia, 37 healthy controls) recruited from London, Ontario. Voxel- and network-based analyses were used to detect changes in diffusion microstructural parameters. Graph theory metrics were used to probe changes in the cortical network hierarchy and to assess the vulnerability of hub regions to disruption. The analysis was replicated with N = 111 (57 patients, 54 controls) from the Human Connectome Project-Early Psychosis (HCP-EP) dataset. Widespread microstructural changes were found in people with established illness, but changes in FEP patients were minimal. Unlike the established illness group, no appreciable topological changes in the cortical network were observed in FEP patients. These results were replicated in the early psychosis patients of the HCP-EP datasets, which were indistinguishable from controls in most metrics. The white matter structural changes observed in established schizophrenia are not a prominent feature in the early stages of this illness.

Diffusion tensor imaging in photosensitive and nonphotosensitive juvenile myoclonic epilepsy

Introduction/backgroundJuvenile myoclonic epilepsy (JME) syndrome is known to cause alterations in brain structure and white matter integrity. The study aimed to determine structural white matter changes in patients with JME and to reveal the differences between the photosensitive (PS) and nonphotosensitive (NPS) subgroups by diffusion tensor imaging (DTI) using the tract-based spatial statistics (TBSS) method. MethodsThis study included data from 16 PS, 15 NPS patients with JME, and 41 healthy participants. The mean fractional anisotropy (FA) values of these groups were calculated, and comparisons were made via the TBSS method over FA values in the whole-brain and 81 regions of interest (ROI) obtained from the John Hopkins University White Matter Atlas. ResultsIn the whole-brain TBSS analysis, no significant differences in FA values were observed in pairwise comparisons of JME patient group and subgroups with healthy controls (HCs) and in comparison between JME subgroups. In ROI-based TBSS analysis, an increase in FA values of right anterior corona radiata and left corticospinal pathways was found in JME patient group compared with HC group. When comparing JME-PS patients with HCs, an FA increase was observed in the bilateral anterior corona radiata region, whereas when comparing JME-NPS patients with HCs, an FA increase was observed in bilateral corticospinal pathway. Moreover, in subgroup comparison, an increase in FA values was noted in corpus callosum genu region in JME-PS compared with JME-NPS. ConclusionsOur results support the disruption in thalamofrontal white matter integrity in JME, and subgroups and highlight the importance of using different analysis methods to show the underlying microstructural changes.

Modifiers of Individual Differences and Within‐person Changes in the Aging White Matter

AbstractMy talk will focus on: 1) longitudinal changes and plasticity, and 2) lifestyle and health modifiers of white matter (WM) health in aging.First, individual differences in changes in WM microstructure may be key for identifying preclinical stages of dementia, opening new opportunities for early interventions. I will present the outcomes from a meta‐analysis and systematic review (Colmenares et al., in preparation) based on 28 diffusion tensor imaging (DTI) studies in healthy adults from the past 10 years, addressing the following questions: Over what time periods can decline in WM microstructure be detected using MRI? Do within‐person changes accelerate with age and vary by brain region? What are the modifiers of within‐person changes in WM? Also, for decades, adult WM has been perceived as a “passive” (i.e., only relaying electrical signals) and “static” (i.e., not capable of or involved in neuroplasticity). Despite emerging evidence in rodents on short‐term structural WM changes, evidence for such experience‐induced plasticity in adult humans remains inconclusive. Thus, I summarize evidence from clinical studies to discuss whether the adult WM microstructure is malleable with experience, and what interventions may be the most promising in inducing a change. I will also present our findings on exercise‐induced WM plasticity in older age, using DTI and T1/T2 ratio imaging (Colmenares et al., 2021, Burzynska et al., 2017).Second, lack of physical activity (PA) and sedentary lifestyles are independently associated with increased risk of metabolic and cardiovascular diseases, mortality, and ADRD. Regular PA decreases inflammation and improves vascular function and perfusion. In contrast, insufficient PA and/or excessive sedentary behaviors is known to upregulate markers of metabolic stress and inflammation. I will briefly review our past work relating sensor‐measured PA with WM health, measured with DTI. Then, I will present our ongoing work using quantitative MRI, such as Myelin Water Imaging and Neurite Orientation Dispersion and Density Imaging. For example, I will present associations between systemic health (i.e., BMI, waist circumference, blood pressure, blood glucose and cholesterol), sensor‐measured physical activity (i.e., time spend sedentary and in light, moderate or vigorous physical activity), and myelin and axonal content in healthy adults.