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JAMA Network Open Oct 2022Vision loss and depression are common conditions with major health implications. However, mechanisms of the association of visual health (across the full acuity...
IMPORTANCE
Vision loss and depression are common conditions with major health implications. However, mechanisms of the association of visual health (across the full acuity spectrum) with depression remain unclear.
OBJECTIVE
To characterize the association between visual health and depression and investigate the association between depression and brain microstructure and macrostructure in subgroups divided by visual acuity.
DESIGN, SETTING, AND PARTICIPANTS
In the UK Biobank Study cohort, 114 583 volunteers were included at baseline from March to June 2006 to July 2010. Habitual distance visual acuity was examined using the logarithm of the minimum angle of resolution (LogMAR) characters. Depression was identified based on Patient Health Questionnaire (PHQ) or through an interview-based psychiatric diagnosis. Subgroup participants completed multimodal magnetic resonance imaging (MRI) of the brain and PHQ evaluation during the imaging visit after 2014. Data were analyzed from May 5 to August 9, 2022.
MAIN OUTCOMES AND MEASURES
Depression, depressive symptoms, and imaging-derived phenotypes from T1-weighted and diffusion MRI.
RESULTS
Of the 114 583 participants from the UK Biobank Study, 62 401 (54.5%) were women, and the mean (SD) age was 56.8 (8.1) years (range, 39-72 years). A 1-line worse visual acuity (0.1 LogMAR increase) was associated with 5% higher odds of depression (odds ratio, 1.05 [95% CI, 1.04-1.07]) after adjustment for age, sex, race and ethnicity, Townsend index, educational qualifications, smoking, alcohol consumption, obesity, physical activity, history of hypertension, diabetes, hyperlipidemia, and family history of depression. Of the 7844 participants eligible for MRI analysis, there were linear associations between PHQ score and the left volume of gray matter in supracalcarine cortex (coefficient, 7.61 [95% CI, 3.90-11.31]) and mean isotropic volume fraction (ISOVF) in the right fornix (cres) and/or stria terminalis (coefficient, 0.003 [95% CI, 0.001-0.004]) after correction for multiple comparison. In addition, their association could be moderated by visual acuity, whereby increased PHQ score was associated with higher ISOVF levels only among those with poorer visual acuity (P = .02 for interaction).
CONCLUSIONS AND RELEVANCE
This study suggests an association between visual health and depression and that the diffusion characteristic of ISOVF in the fornix (cres) and/or stria terminalis is associated with depressive symptoms in participants with poorer visual acuity.
Topics: Brain; Depression; Female; Humans; Male; Neuroimaging; Phenotype; Vision Disorders; Visual Acuity
PubMed: 36201210
DOI: 10.1001/jamanetworkopen.2022.35017 -
Translational Psychiatry May 2023The fornix is a white matter bundle located in the center of the hippocampaldiencephalic limbic circuit that controls memory and executive functions, yet its genetic...
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) 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.
Topics: Humans; Genetic Predisposition to Disease; Genome-Wide Association Study; White Matter; Phenotype; Schizophrenia; Polymorphism, Single Nucleotide; Protein Kinases; Repressor Proteins
PubMed: 37236919
DOI: 10.1038/s41398-023-02475-6 -
Cureus Apr 2024Background The aim of this study is to evaluate the clinical and radiological findings of metastatic tumors and primary brain tumors affecting the fornix. Methods ...
Background The aim of this study is to evaluate the clinical and radiological findings of metastatic tumors and primary brain tumors affecting the fornix. Methods Between January 2015 and March 2023, we retrospectively evaluated 1087 patients of both sexes who underwent cranial magnetic resonance imaging (MRI) for a preliminary diagnosis of intracranial malignancy in the radiology department of our hospital. Two radiologists with six and 10 years of experience in MRI examination assessed the relationship between primary and metastatic tumors and the fornix. Results Involvement of the fornix was diagnosed in 29 of the 1087 patients (2.66%), of which fornix was affected by metastatic lesions in 14 patients (48.2%) and primary tumors in 15 patients (51.7%). The majority of metastatic lesions were from lung and breast cancers, with other tumor types including osteosarcoma, renal cell carcinoma, pancreatic adenocarcinoma, pleomorphic sarcoma, and diffuse large B-cell lymphoma. Among all primary tumors, glioblastoma was the most common primary brain tumor invading the fornix, with other diagnoses including diffuse astrocytoma, medulloblastoma, and anaplastic oligodendroglioma. Metastatic and primary brain tumors affecting the fornix were detected over a broad timeline, from the time of diagnosis up to 120 months after diagnosis. A retrospective evaluation of medical records revealed memory deficits in four patients. Conclusion The fornix can be affected by both metastatic and primary brain tumors. It is crucial to understand the relevant neuroanatomical relationships when evaluating lesions that affect the fornix.
PubMed: 38689678
DOI: 10.7759/cureus.57612 -
Cerebral Cortex (New York, N.Y. : 1991) Nov 2022Episodic memory relies on the coordination of widespread brain regions that reconstruct spatiotemporal details of an episode. These topologically dispersed brain regions...
Episodic memory relies on the coordination of widespread brain regions that reconstruct spatiotemporal details of an episode. These topologically dispersed brain regions can rapidly communicate through structural pathways. Research in animal and human lesion studies implicate the fornix-the major output pathway of the hippocampus-in supporting various aspects of episodic memory. Because episodic memory undergoes marked changes in early childhood, we tested the link between the fornix and episodic memory in an age window of robust memory development (ages 4-8 years). Children were tested on the stories subtest from the Children's Memory Scale, a temporal order memory task, and a source memory task. Fornix streamlines were reconstructed using probabilistic tractography to estimate fornix microstructure. In addition, we measured fornix macrostructure and computed free water. To assess selectivity of our findings, we also reconstructed the uncinate fasciculus. Findings show that children's memory increases from ages 4 to 8 and that fornix micro- and macrostructure increases between ages 4 and 8. Children's memory performance across nearly every memory task correlated with individual differences in fornix, but not uncinate fasciculus, white matter. These findings suggest that the fornix plays an important role in supporting the development of episodic memory, and potentially semantic memory, in early childhood.
Topics: Child; Humans; Child, Preschool; Memory, Episodic; Fornix, Brain; White Matter; Nerve Net; Brain
PubMed: 35169831
DOI: 10.1093/cercor/bhac022 -
Frontiers in Aging Neuroscience 2014Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. Researchers have long been focused on the cortical pathology of AD, since the most... (Review)
Review
Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. Researchers have long been focused on the cortical pathology of AD, since the most important pathologic features are the senile plaques found in the cortex, and the neurofibrillary tangles and neuronal loss that begin in the entorhinal cortex and the hippocampus. In addition to these gray matter (GM) structures, histopathological studies indicate that the white matter (WM) is also a good target for both the early diagnosis of AD and for monitoring disease progression. The fornix is a WM bundle that constitutes a core element of the limbic circuits, and is one of the most important anatomical structures related to memory. Functional and anatomical features of the fornix have naturally captured researchers' attention as possible diagnostic and prognostic markers of AD. Indeed, neurodegeneration of the fornix has been histologically observed in AD, and growing evidence indicates that the alterations seen in the fornix are potentially a good marker to predict future conversion from mild cognitive impairment (MCI) to AD, and even from cognitively normal individuals to AD. The degree of alteration is correlated with the degree of memory impairment, indicating the potential for the use of the fornix as a functional marker. Moreover, there have been attempts to stimulate the fornix using deep brain stimulation (DBS) to augment cognitive function in AD, and ongoing research has suggested positive effects of DBS on brain glucose metabolism in AD patients. On the other hand, disease specificity for fornix degeneration, methodologies to evaluate fornix degeneration, and the clinical significance of the fornix DBS, especially for the long-term impact on the quality of life, are mostly unknown and need to be elucidated.
PubMed: 25309426
DOI: 10.3389/fnagi.2014.00241 -
NeuroImage May 2022Ageing displays a low-grade pro-inflammatory profile in blood and the brain. Accumulation of pro-inflammatory cytokines, microglia activation and volumetric changes in...
Ageing displays a low-grade pro-inflammatory profile in blood and the brain. Accumulation of pro-inflammatory cytokines, microglia activation and volumetric changes in the brain correlate with cognitive decline in ageing models. However, the interplay between them is not totally understood. Here, we aimed to globally identify an age-dependent pro-inflammatory profile and microglia morphological plasticity that favors major volume changes in the brain associated with cognitive decline. Cluster analysis of behavioral data obtained from 2-,12- and 20-month-old male C57BL/6 mice revealed age-dependent cognitive decline after the Y-maze, Barnes maze, object recognition (NORT) and object location tests (OLT). Global magnetic resonance imageing (MRI) analysis by deformation-based morphometry (DBM) in the brain identified a volume increase in the fornix and a decrease in the left medial entorhinal cortex (MEntC) during ageing. Notably, the fornix shows an increase in the accumulation of pro-inflammatory cytokines, whereas the left MEntC displays a decrease. Morphological assessment of microglia also confirms an active and dystrophic phenotype in the fornix and a surveillance phenotype in the left MEntC. Finally, biological modeling revealed that age-related volume increase in the fornix was associated with dystrophic microglia and cognitive impairment, as evidenced by failure on tasks examining memory of object location and novelty. Our results propose that the morphological plasticity of microglia might contribute to volumetric changes in brain regions associated with cognitive decline during physiological ageing.
Topics: Aging; Animals; Cognitive Dysfunction; Cytokines; Humans; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Microglia; Spatial Memory
PubMed: 35227858
DOI: 10.1016/j.neuroimage.2022.119039 -
Journal of Neurology, Neurosurgery, and... May 2020The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres, which connects various nodes of a limbic circuitry and is believed to play... (Review)
Review
The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres, which connects various nodes of a limbic circuitry and is believed to play a key role in cognition and episodic memory recall. As the most prevalent cause of dementia, Alzheimer's disease (AD) dramatically impairs the quality of life of patients and imposes a significant societal burden on the healthcare system. As an established treatment for movement disorders, deep brain stimulation (DBS) is currently being investigated in preclinical and clinical studies for treatment of memory impairment in AD by modulating fornix activity. Optimal target and stimulation parameters to potentially rescue memory deficits have yet to be determined. The aim of this review is to consolidate the structural and functional aspects of the fornix in the context of neuromodulation for memory deficits. We first present an anatomical and functional overview of the fibres and structures interconnected by the fornix. Recent evidence from preclinical models suggests that the fornix is subdivided into two distinct functional axes: a septohippocampal pathway and a subiculothalamic pathway. Each pathway's target and origin structures are presented, followed by a discussion of their oscillatory dynamics and functional connectivity. Overall, neuromodulation of each pathway of the fornix is discussed in the context of evidence-based forniceal DBS strategies. It is not yet known whether driving fornix activity can enhance cognition-optimal target and stimulation parameters to rescue memory deficits have yet to be determined.
Topics: Alzheimer Disease; Deep Brain Stimulation; Fornix, Brain; Humans; Memory Disorders; Neural Pathways
PubMed: 32132227
DOI: 10.1136/jnnp-2019-322375 -
Brain Imaging and Behavior Oct 2019Both white and grey matter atrophy with age, but it is still unclear how decline in white matter relates to decline in grey matter, and how this relationship varies with...
Both white and grey matter atrophy with age, but it is still unclear how decline in white matter relates to decline in grey matter, and how this relationship varies with age. In a group of healthy adults from 20 to 80 years old, divided into three age groups by tertiles, we cross-sectionally examined the white-to-grey matter associations in the fornix and the hippocampus, and tested if and how the fornix-to-hippocampus relationship differs across the age groups. Both structures were also tested as predictors for performance on a memory test, the Selective Reminding Task (SRT). Participants were imaged with T1-weighted magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI), from which the hippocampal volume, fractional anisotropy (FA), and mean diffusivity (MD) for the bilateral crus and body of the fornix were calculated. Our data showed that even after accounting for age, sex, and motion parameters, fornix integrity predicted hippocampal volume in the two older age groups (middle and old age) for the crus of the fornix, and only in the oldest age group for the body of the fornix. Furthermore, fornix integrity significantly predicted SRT performance, whereas hippocampal volume did not; this relationship was also observed only in the oldest age group, and absent in the two younger age groups. The age specificity of the relationships suggests that the fornix-to-hippocampus relationship only manifests once brain structures begin to atrophy in old age, and that fornix integrity is a more sensitive measure for episodic memory than is hippocampal volume.
Topics: Adult; Aged; Aged, 80 and over; Aging; Anisotropy; Diffusion Tensor Imaging; Female; Fornix, Brain; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Memory, Episodic; Middle Aged; Neuropsychological Tests; White Matter; Young Adult
PubMed: 30187206
DOI: 10.1007/s11682-018-9958-1 -
AJNR. American Journal of Neuroradiology Mar 2022The fornix-fimbria complex is mainly involved in emotions and memory. In brain MR imaging studies of young children, we have occasionally noted DWI hyperintensity in...
BACKGROUND AND PURPOSE
The fornix-fimbria complex is mainly involved in emotions and memory. In brain MR imaging studies of young children, we have occasionally noted DWI hyperintensity in this region. The significance of this finding remains unclear. This study evaluated the DWI signal in the fornix-fimbria complex of children 0-2 years of age, including the frequency of signal hyperintensity and clinical context.
MATERIALS AND METHODS
Brain MR imaging of 714 children 0-2 years of age (mean, 11 months), performed between September 2018 and May 2021, was reviewed and evaluated for DWI signal changes in the fornix-fimbria. All children with available MR imaging studies including DWI were included. Children with poor image quality, poor visualization of the fornix-fimbria region, and missing medical data were excluded. Additional imaging findings were also evaluated. Demographic data were retrieved from the medical files. We compared the ADC values of the fimbria and fornix between children with and without signal changes. The unpaired 2-tailed Student test and χ test were used for statistical analysis.
RESULTS
DWI signal hyperintensity of the Fornix-fimbria complex was noted in 53 (7.4%) children (mean age, 10 months). Their mean ADC values were significantly lower than those of the children with normal DWI findings (< .05). About half of the children had otherwise normal MR imaging findings. When detected, the most common abnormality was parenchymal volume loss (15%). The most common indication for imaging was seizures (26.5%).
CONCLUSIONS
DWI hyperintensity in the fornix-fimbria complex was detected in 7.4% of children 0-2 years of age. The etiology is not entirely clear, possibly reflecting a transient phenomenon.
Topics: Brain; Child; Child, Preschool; Diffusion Magnetic Resonance Imaging; Fornix, Brain; Humans; Infant; Magnetic Resonance Imaging
PubMed: 35210274
DOI: 10.3174/ajnr.A7437 -
Human Brain Mapping Jul 2023Unveiling the details of white matter (WM) maturation throughout ageing is a fundamental question for understanding the ageing brain. In an extensive comparison of brain...
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.
Topics: Humans; White Matter; Brain; Diffusion Magnetic Resonance Imaging; Aging; Corpus Callosum
PubMed: 37195079
DOI: 10.1002/hbm.26333