Fornix white matter microstructure differentially predicts false recollection rates in older and younger adults.
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ABSTRACT:
SUBMITTER: Chamberlain JD
PROVIDER: S-EPMC8674925 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The fornix is the main tract between the medial temporal lobe (MTL) and medial diencephalon, both of which are critical for episodic memory. The precise involvement of the fornix in memory, however, has been difficult to ascertain since damage to this tract in human amnesics is invariably accompanied by atrophy to surrounding structures. We used diffusion-weighted imaging to investigate whether individual differences in fornix white matter microstructure in neurologically healthy participants were related to differences in memory as assessed by two recognition tasks. Higher microstructural integrity in the fornix tail was found to be associated with significantly better recollection memory. In contrast, there was no significant correlation between fornix microstructure and familiarity memory or performance on two non-mnemonic tasks. Our findings support the idea that there are distinct MTL-diencephalon pathways that subserve differing memory processes.
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Project description:The fornix is a white matter bundle located in the center of the hippocampaldiencephalic limbic circuit that controls memory and executive functions, yet its genetic architectures and involvement in brain disorders remain largely unknown. We carried out a genome-wide association analysis of 30,832 UK Biobank individuals of the six fornix diffusion magnetic resonance imaging (dMRI) traits. The post-GWAS analysis allowed us to identify causal genetic variants in phenotypes at the single nucleotide polymorphisms (SNP), locus, and gene levels, as well as genetic overlap with brain health-related traits. We further generalized our GWAS in adolescent brain cognitive development (ABCD) cohort. The GWAS identified 63 independent significant variants within 20 genomic loci associated (P < 8.33 × 10-9) with the six fornix dMRI traits. Geminin coiled-coil domain containing (GMNC) and NUAK family SNF1-like kinase 1 (NUAK1) gene were highlighted, which were found in UKB and replicated in ABCD. The heritability of the six traits ranged from 10% to 27%. Gene mapping strategies identified 213 genes, where 11 were supported by all of four methods. Gene-based analyses revealed pathways relating to cell development and differentiation, with astrocytes found to be significantly enriched. Pleiotropy analyses with eight neurological and psychiatric disorders revealed shared variants, especially with schizophrenia under the conjFDR threshold of 0.05. These findings advance our understanding of the complex genetic architectures of fornix and their relevance in neurological and psychiatric disorders.
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Project description:Unveiling the details of white matter (WM) maturation throughout ageing is a fundamental question for understanding the ageing brain. In an extensive comparison of brain age predictions and age-associations of WM features from different diffusion approaches, we analyzed UK Biobank diffusion magnetic resonance imaging (dMRI) data across midlife and older age (N = 35,749, 44.6-82.8 years of age). Conventional and advanced dMRI approaches were consistent in predicting brain age. WM-age associations indicate a steady microstructure degeneration with increasing age from midlife to older ages. Brain age was estimated best when combining diffusion approaches, showing different aspects of WM contributing to brain age. Fornix was found as the central region for brain age predictions across diffusion approaches in complement to forceps minor as another important region. These regions exhibited a general pattern of positive associations with age for intra axonal water fractions, axial, radial diffusivities, and negative relationships with age for mean diffusivities, fractional anisotropy, kurtosis. We encourage the application of multiple dMRI approaches for detailed insights into WM, and the further investigation of fornix and forceps as potential biomarkers of brain age and ageing.
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Project description:Chronic back pain (CBP) has extensive clinical and social implications for its sufferers and is a major source of disability. Chronic pain has previously been shown to have central neural factors underpinning it, including the loss of white matter (WM), however traditional methods of analyzing WM microstructure have produced mixed and unclear results. To better understand these factors, we assessed the WM microstructure of 50 patients and 40 healthy controls (HC) using diffusion-weighted imaging. The data were analyzed using fixel-based analysis (FBA), a higher-order diffusion modelling technique applied to CBP for the first time here. Subjects also answered questionnaires relating to pain, disability, catastrophizing, and mood disorders, to establish the relationship between fixelwise metrics and clinical symptoms. FBA determined that, compared to HC, CBP patients had: 1) lower fibre density (FD) in several tracts, specifically the right anterior and bilateral superior thalamic radiations, right spinothalamic tract, right middle cerebellar peduncle, and the body and splenium of corpus callosum; 2) higher FD in the genu of corpus callosum; and 3) lower FDC - a combined fibre density and cross-section measure - in the bilateral spinothalamic tracts and right anterior thalamic radiation. Exploratory correlations showed strong negative relationships between fixelwise metrics and clinical questionnaire scores, especially pain catastrophizing. These results have important implications for the intake and processing of sensory data in CBP that warrant further investigation.
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Project description:The neurobiological underpinnings of anorexia nervosa (AN) are unclear. White matter deficits have been described in the illness, but findings are inconsistent between studies. The aim of this study was to investigate differences in white matter microstructure in AN using diffusion-weighted imaging (DWI). It was hypothesised that people with AN, relative to a healthy control (HC) group, would show decreased functional anisotropy (FA) and increased mean diffusivity (MD) in the fornix and superior longitudinal fasciculus, consistent with previous literature. Analyses were conducted on 23 females with AN and 26 age- and gender-matched HCs using tract-based spatial statistics (TBSS). The results revealed widespread FA decreases and MD increases in the AN group. Our hypothesis was largely supported, although FA differences were not specifically found in the fornix. The findings suggest extensive differences in white matter structure in AN, which may contribute to AN pathophysiology.
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Project description:Background In neonates with single ventricle, smaller ascending aorta diameter is associated with cerebral white matter ( WM ) microstructural abnormalities. We sought to determine whether this association persists into adolescence. Methods and Results Ascending aorta Z scores were obtained from first postnatal echocardiogram. Brain magnetic resonance imaging with diffusion tensor imaging was acquired in adolescence and used to obtain fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity in 33 WM tract regions of interest. Partial Pearson correlation coefficients were evaluated for associations between ascending aorta Z scores and WM microstructure measures, adjusting for sex, age at magnetic resonance imaging, scanner field strength, and Norwood status. Among 42 single ventricle patients aged 10 to 19 years, 31 had undergone the Norwood procedure as neonates. Lower ascending aorta Z scores were associated with lower fractional anisotropy in bilateral pontine crossing tracts ( P=0.02), inferior fronto-occipital fasciculus ( P=0.02), and inferior longitudinal fasciculus ( P=0.01); left cingulum-cingulate bundle ( P=0.01), superior longitudinal fasciculus ( P=0.04), and superior longitudinal fasciculus-temporal component ( P=0.01); and right cingulum-hippocampal bundle (P=0.009) and inferior cerebellar peduncle ( P=0.01). Lower ascending aorta Z scores were associated with higher radial diffusivity and mean diffusivity in a similar regional pattern but not with axial diffusivity. Conclusions In adolescents with single ventricle, smaller aorta diameter at birth is associated with abnormalities of WM microstructure in a subset of WM tracts, mostly those located in deeper brain regions. Our findings suggest that despite multiple intervening medical or surgical procedures, prenatal cerebral blood flow may have a lasting influence on WM microstructure in single-ventricle patients.
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Project description:We examined the relationship between white matter microstructure in schizophrenia using diffusion tensor imaging (DTI) and cognitive improvements induced by 70h (~16weeks) of cognitive training. We measured anatomical connectivity in 48 patients with schizophrenia (SZ) and 28 healthy control participants (HC) at baseline, and then examined the relationship between anatomical connectivity at baseline and training-induced cognitive gains in 30 SZ who performed diffusion imaging after completing 70h of training. Compared with healthy control participants, individuals with schizophrenia showed reduced white matter integrity at baseline, as indexed by fractional anisotropy metrics, in bilateral posterior corona radiata, bilateral retrolenticular internal capsules, bilateral posterior thalamic radiation, left anterior corona radiata, left superior longitudinal fasciculus, left sagittal stratum, right cerebral peduncle and the genu and splenium of the corpus callosum. After training, schizophrenia participants showed significant gains in attention/vigilance, speed of processing, verbal learning, visual learning and executive functioning. White matter integrity within the right fronto-occipital fasciculus predicted training-induced improvements in attention/vigilance, while white matter integrity within the right corticospinal tract and bilateral medial lemnisci predicted cognitive training-induced improvements in executive functioning, areas that did not show white matter tract deficits at baseline. These findings suggest that preserved white matter integrity connecting long-range prefrontal-thalamic-sensorimotor areas may be an important determinant for training-induced neurocognitive plasticity.
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Project description:Accumulating evidence suggests associations between cerebrovascular disease (CVD) and Alzheimer's disease (AD). White matter hyperintensities of presumed vascular origin (WMHs) are increased in subjects with mild cognitive impairment (MCI) and AD, but the exact pathomechanistic link is unknown. The current study investigated effects of amyloid dysmetabolism on the microstructure of WMHs in subjects with MCI or subjective cognitive decline (N?=?51), dichotomized according to pathological or normal levels of amyloid-? peptide (A?42) in cerebrospinal fluid (CSF). Thirty-one subjects with low CSF A?42 (A?+) and 20 subjects with normal CSF A?42 (A?-) were assessed with magnetic resonance diffusion tensor imaging (DTI), and fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA), and mean diffusivity (MD) were determined. There were no significant differences in WMH volume or distribution between the groups, and neither age nor WMH volume had significant impact on the DTI indices. Nevertheless, there were significantly higher DA, DR, and MD in WMHs in A?+ relative to A?-; however, no differences in FA were found. The present results suggest that amyloid accumulation is associated with impaired structural integrity (e.g. relating to more extensive demyelination and loss of axons) in WMHs putatively adding to effects of ischemia.
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Project description:Aging leads to gray and white matter decline but their causation remains unclear. We explored two classes of models of age and dementia risk related brain changes. The first class of models emphasises the importance of gray matter: age and risk-related processes cause neurodegeneration and this causes damage in associated white matter tracts. The second class of models reverses the direction of causation: aging and risk factors cause white matter damage and this leads to gray matter damage. We compared these models with linear mediation analysis and quantitative MRI indices (from diffusion, quantitative magnetization transfer and relaxometry imaging) of tissue properties in two limbic structures implicated in age-related memory decline: the hippocampus and the fornix in 166 asymptomatic individuals (aged 38-71 years). Aging was associated with apparent glia but not neurite density damage in the fornix and the hippocampus. Mediation analysis supported white matter damage causing gray matter decline; controlling for fornix glia damage, the correlations between age and hippocampal damage disappear, but not vice versa. Fornix and hippocampal differences were both associated with reductions in episodic memory performance. These results suggest that fornix white matter glia damage may cause hippocampal gray matter damage during age-dependent limbic decline.
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Project description:Children are becoming increasingly inactive, unfit, and overweight, yet there is relatively little causal evidence regarding the effects of physical activity on brain health during childhood. The present study examined the effects of an after-school physical activity program (FITKids2) on the microstructure of white matter tracts in 7- to 9-year-old children. We measured the microstructural properties of white matter via diffusion tensor imaging in 143 children before and after random assignment to either a 9-month after-school physical activity program (N = 76, mean age = 8.7 years) or a wait list control group (N = 67, mean age = 8.7 years). Our results demonstrate that children who participated in the physical activity program showed increased white matter microstructure in the genu of the corpus callosum, with no changes in white matter microstructure in the wait list control group which reflects typical development. Specifically, children in the physical activity program showed increases in fractional anisotropy (FA) and decreases in radial diffusivity (RD) in the genu from pre- to post-test, thereby suggesting more tightly bundled and structurally compact fibers (FA) and increased myelination (RD), with no changes in estimates of axonal fiber diameter (axial diffusivity, AD). The corpus callosum integrates cognitive, motor, and sensory information between the left and right hemispheres of the brain, and the white matter tract plays a role in cognition and behavior. Our findings reinforce the importance of physical activity for brain health during child development.
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