scholarly journals The role of the fornix in human navigational learning

2018 ◽  
Author(s):  
Carl J. Hodgetts ◽  
Martina Stefani ◽  
Angharad N. Williams ◽  
Branden S. Kolarik ◽  
Andrew P. Yonelinas ◽  
...  

AbstractStudies in rodents have demonstrated that transecting the white matter pathway linking the hippocampus and anterior thalamic nuclei - the fornix - impairs flexible navigational learning in the Morris Water Maze (MWM), as well as similar spatial learning tasks. While diffusion MRI studies in humans have linked fornix microstructure to scene discrimination and memory, its role in human navigation is currently unknown. We used high-angular resolution diffusion MRI to ask whether inter-individual differences in fornix microstructure would be associated with spatial learning in a virtual MWM task. To increase sensitivity to individual learning across trials, we adopted a novel curve fitting approach to estimate a single index of learning rate. We found a significant correlation between learning rate and the microstructure (mean diffusivity) of the fornix, but not that of a control tract linking occipital and anterior temporal cortices (the inferior longitudinal fasciculus, ILF). Further, this correlation remained significant when controlling for hippocampal volume. These findings extend previous animal studies by demonstrating the functional relevance of the fornix for human navigational learning, and highlight the importance of a distributed neuroanatomical network, underpinned by key white matter pathways, such as the fornix, in complex spatial behaviour.

2018 ◽  
Author(s):  
Farshid Sepehrband ◽  
Ryan P Cabeen ◽  
Jeiran Choupan ◽  
Giuseppe Barisano ◽  
Meng Law ◽  
...  

AbstractDiffusion tensor imaging (DTI) has been extensively used to map changes in brain tissue related to neurological disorders. Among the most widespread DTI findings are increased mean diffusivity and decreased fractional anisotropy of white matter tissue in neurodegenerative diseases. Here we utilize multi-shell diffusion imaging to separate diffusion signal of the brain parenchyma from fluid within the white matter. We show that unincorporated anisotropic water in perivascular space (PVS) significantly, and systematically, biases DTI measures, casting new light on the biological validity of many previously reported findings. Despite the challenge this poses for interpreting these past findings, our results suggest that multi-shell diffusion MRI provides a new opportunity for incorporating the PVS contribution, ultimately strengthening the clinical and scientific value of diffusion MRI.HighlightsPerivascular space (PVS) fluid significantly contributes to diffusion tensor imaging metricsIncreased PVS fluid results in increased mean diffusivity and decreased fractional anisotropyPVS contribution to diffusion signal is overlooked and demands further investigation


2021 ◽  
Vol 15 ◽  
Author(s):  
Ami Tsuchida ◽  
Alexandre Laurent ◽  
Fabrice Crivello ◽  
Laurent Petit ◽  
Antonietta Pepe ◽  
...  

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilized to study white matter changes during development and aging. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18–26. We assessed the age and sex dependence of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterized by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. These findings emphasize the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.


2021 ◽  
pp. 1-15
Author(s):  
Takahiro Koinuma ◽  
Taku Hatano ◽  
Koji Kamagata ◽  
Christina Andica ◽  
Akio Mori ◽  
...  

Background: Although pathological studies usually indicate pure dopaminergic neuronal degeneration in patients with parkin (PRKN) mutations, there is no evidence to date regarding white matter (WM) pathology. A previous diffusion MRI study has revealed WM microstructural alterations caused by systemic oxidative stress in idiopathic Parkinson’s disease (PD), and we found that PRKN patients have systemic oxidative stress in serum biomarker studies. Thus, we hypothesized that PRKN mutations might lead to WM abnormalities. Objective: To investigate whether there are WM microstructural abnormalities in early-onset PD patients with PRKN mutations using diffusion tensor imaging (DTI). Methods: Nine PRKN patients and 19 age- and sex-matched healthy controls were recruited. DTI measures were acquired on a 3T MR scanner using a b value of 1,000 s/mm2 along 32 isotropic diffusion gradients. The DTI measures were compared between groups using tract-based spatial statistics (TBSS) analysis. Correlation analysis was also performed between the DTI parameters and several serum oxidative stress markers obtained in a previously conducted metabolomic analysis. Results: Although the WM volumes were not significantly different, the TBSS analysis revealed a corresponding decrease in fractional anisotropy and an increase in mean diffusivity and radial diffusivity in WM areas, such as the anterior and superior corona radiata and uncinate fasciculus, in PRKN patients compared with controls. Furthermore, 9-hydroxystearate, an oxidative stress marker, and disease duration were positively correlated with several parameters in PRKN patients. Conclusion: This pilot study suggests that WM microstructural impairments occur in PRKN patients and are associated with disease duration and oxidative stress.


2016 ◽  
Author(s):  
Lee B Reid ◽  
Martin V Sale ◽  
Ross Cunnington ◽  
Jason B Mattingley ◽  
Stephen E Rose

AbstractWe have reported reliable changes in behaviour, brain structure and function in 24 healthy right-handed adults who practiced a finger-thumb opposition sequence task with their left hand for 10 mins daily, over four weeks. Here we extend these findings by employing diffusion MRI to investigate white-matter changes in the corticospinal tract, basal-ganglia, and connections of the dorsolateral prefrontal cortex. Twenty-three participant datasets were available with pre-training and post-training scans. Task performance improved in all participants (mean: 52.8%, SD: 20.0%; group p<0.01 FWE) and widespread microstructural changes were detected across the motor system of the ‘trained’ hemisphere. Specifically, region-of-interest based analyses of diffusion MRI (n=21) revealed significantly increased fractional anisotropy in the right caudate nucleus (4.9%; p<0.05 FWE), and decreased mean diffusivity in the left nucleus accumbens (-1.3%; p<0.05 FWE). Diffusion MRI tractography (n=22), seeded by sensorimotor cortex fMRI activation, also revealed increased fractional anisotropy in the right corticomotor tract (mean 3.28%; p<0.05 FWE) predominantly reflecting decreased radial diffusivity. These changes were consistent throughout the entire length of the tract. The left corticomotor tract did not show any changes. FA also increased in white matter connections between the right middle frontal gyrus and both right caudate nucleus (17/22 participants; p<0.05 FWE) and right supplementary motor area (18/22 participants; p<0.05 FWE). Equivalent changes in FA were not seen in the left (‘non-trained’) hemisphere. In combination with our functional and structural findings, this study provides detailed, multifocal evidence for widespread neuroplastic changes in the human brain resulting from motor training.


2020 ◽  
Author(s):  
Erica F. Barry ◽  
John P. Loftus ◽  
Wen-Ming Luh ◽  
Mony J. de Leon ◽  
Sumit N. Niogi ◽  
...  

AbstractWhite matter dysfunction and degeneration have been a topic of great interest in healthy and pathological aging. While ex vivo studies have investigated age-related changes in canines, little in vivo canine aging research exists. Quantitative diffusion MRI such as diffusion tensor imaging (DTI) has demonstrated aging and neurodegenerative white matter changes in humans. However, this method has not been applied and adapted in vivo to canine populations. This study aimed to test the hypothesis that white matter diffusion changes frequently reported in human aging are also found in aged canines. The study used Tract Based Spatial Statistics (TBSS) and a region of interest (ROI) approach to investigate age related changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). The results show that, compared to younger animals, aged canines have significant decreases in FA in parietal and temporal regions as well as the corpus callosum and fornix. Additionally, AxD decreases were observed in parietal, frontal and midbrain regions. Similarly, an age-related increase in RD was observed in the right parietal lobe while MD decreases were found in the midbrain. These findings suggest that canine samples offer a model for healthy human aging as they exhibit similar white matter diffusion tensor changes with age.


2021 ◽  
Author(s):  
Thomas Veale ◽  
Ian B Malone ◽  
Teresa Poole ◽  
Thomas D Parker ◽  
Catherine F Slattery ◽  
...  

Pathological involvement of cerebral white matter in Alzheimer's disease has been shown using diffusion tensor imaging. Superficial white matter (SWM) changes have been relatively understudied despite their importance in cortico-cortical connections. Measuring SWM degeneration using diffusion tensor imaging is challenging due to its complex structure and proximity to the cortex. To overcome this we investigated diffusion MRI changes in young-onset Alzheimer's disease using standard diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging to distinguish between disease-related changes that are due to degeneration (e.g. loss of myelinated fibres) and those due to reorganisation (e.g. increased fibre dispersion). Twenty-nine young-onset Alzheimer's disease patients and 22 healthy controls had both single-shell and multi-shell diffusion MRI. We calculated fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index and tissue fraction (1-free water fraction). Diffusion metrics were sampled in 15 a priori regions of interest at four points along the cortical profile: cortical grey matter, the grey/white boundary, SWM (1mm below grey/white boundary) and SWM/deeper white matter (2mm below grey/white boundary). To estimate cross-sectional group differences, we used average marginal effects from linear mixed effect models of participants' diffusion metrics along the cortical profile. The SWM of young-onset Alzheimer's disease individuals had lower neurite density index compared to controls in five regions (superior and inferior parietal, precuneus, entorhinal and parahippocampus) (all P<0.05), and higher orientation dispersion index in three regions (fusiform, entorhinal and parahippocampus) (all P<0.05). Young-onset Alzheimer's disease individuals had lower fractional anisotropy in the SWM of two regions (entorhinal and parahippocampus) (both P<0.05) and higher fractional anisotropy within the postcentral region (P<0.05). Mean diffusivity in SWM was higher in the young-onset Alzheimer's disease group in the parahippocampal region (P<0.05) and lower in three regions (postcentral, precentral and superior temporal) (all P<0.05). In the overlying grey matter, disease-related changes were largely consistent with SWM findings when using neurite density index and fractional anisotropy, but appeared at odds with orientation dispersion and mean diffusivity SWM changes. Tissue fraction was significantly lower across all grey matter regions in young-onset Alzheimer's disease individuals (all P<0.001) but group differences reduced in magnitude and coverage when moving towards the SWM. These results show that microstructural changes occur within SWM and along the cortical profile in individuals with young-onset Alzheimer's disease. Lower neurite density and higher orientation dispersion suggests underlying SWM fibres undergo neurodegeneration and reorganisation, two effects previously indiscernible using standard diffusion tensor metrics in SWM.


2020 ◽  
Author(s):  
Nira Cedres ◽  
Patricia Diaz-Galvan ◽  
Lucio Diaz-Flores ◽  
J-Sebastian Muehlboeck ◽  
Yaiza Molina ◽  
...  

Abstract AIMS: To investigate the interplay between gray matter (GM) and white matter (WM) neurodegeneration in subjective cognitive decline (SCD), including thickness across the whole cortical mantle, hippocampal volume, and integrity across the whole WM. METHODS: We included 225 cognitively unimpaired individuals from a community-based cohort, of whom 123 endorsed one or more subjective cognitive complaints. GM neurodegeneration was assessed through measures of cortical thickness across the whole mantle and hippocampal volume. WM neurodegeneration was assessed through measures of mean diffusivity (MD) across the whole WM skeleton. Mediation analysis and multiple linear regression were conducted to investigate the interplay between the measures of GM and WM neurodegeneration.RESULTS: A higher number of complaints was associated with reduced hippocampal volume, cortical thinning in several frontal and temporal areas and the insula, and higher MD across the WM skeleton, with a tendency to spare the occipital lobe. SCD-related cortical thinning and increased MD were associated with each other and jointly contributed to the complaints, but the contribution of cortical thinning to SCD was stronger.CONCLUSIONS: Neurodegeneration processes affecting the GM and WM seem to be associated with each other in SCD and include brain areas other than those typically targeted by Alzheimer’s disease (AD). Our findings suggest that SCD may be a sensitive behavioral marker of heterogeneous brain pathologies in individuals recruited from the community.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S88-S89
Author(s):  
Tzung-Jeng Hwang ◽  
Yu-Hung Tung ◽  
Chang-Le Chen ◽  
Li-Ying Yang ◽  
Yung-Chin Hsu ◽  
...  

Abstract Background Current diffusion MRI studies of schizophrenia are limited by methodology and sample size. With normative models and the largest single-site cohort, we aimed to delineate a comprehensive profile of tract alteration in unaffected siblings, first-episode schizophrenia (FES), and chronic schizophrenia. Methods A total of 277 patients with schizophrenia, 81 unaffected siblings, and 1023 healthy people underwent diffusion-weighted imaging on the same 3T scanner. Generalized fractional anisotropy (GFA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were sampled along 45 major neural tracts. A normative model was built from the images of 1023 healthy people; Z scores represented the normalized deviation of the index value from that of the age- and sex-matched healthy population. Results Widespread involvement of neural tracts was found in patients with FES, and the tracts connecting the prefrontal lobe were the most severely affected. In patients with chronic schizophrenia, virtually all neural tracts were altered, with the tracts connecting the sensorimotor cortex the least affected. A significant negative correlation was observed between GFA alterations and the duration of illness. In unaffected siblings, scattered tracts were involved in GFA, but not in MD or RD. Discussion The study revealed widespread white matter involvement in the early stages of schizophrenia. The alteration continues to progress from the neural tracts connecting the prefrontal lobe to the entire brain. Compared to a large sample of normal controls, the attenuated peak and rapid decline of white matter GFA across the lifespan suggest that schizophrenia is associated with neurodevelopmental and neurodegenerative abnormalities of white matter.


2020 ◽  
Author(s):  
Elizabeth Huber ◽  
Aviv Mezer ◽  
Jason D. Yeatman

AbstractHuman white matter is remarkably plastic. Yet it is challenging to infer the biological underpinnings of this plasticity using non-invasive measurements like diffusion MRI. Here we capitalize on metrics derived from diffusion kurtosis imaging (DKI) to interpret previously reported changes in mean diffusivity throughout the white matter during an 8-week, intensive reading intervention. We then use an independent quantitative MRI measurement of R1 (1/T1 relaxation time) in the same white matter regions; since R1 closely tracks variation in myelin content, it provides complementary information about white matter microstructure. Behavioral measures, multi-shell diffusion MRI data, and quantitative T1 data were collected at regular intervals during the intervention in a group of 33 children with reading difficulties (7-12 years old), and over the same period in an age-matched non-intervention control group. Changes in DKI parameters modeled over the intervention were consistent with increased hindrance in the extra-axonal space, rather than a large-scale change in axon density and/or myelination. Supporting this interpretation, analysis of R1 values did not suggest a change in myelin, although R1 estimates were correlated with individual differences in reading skill. Together, these results suggest that large-scale changes in diffusivity observed over a short timescale during an intensive educational experience are most likely to reflect changes occurring in the extra-axonal space, in line with recent work highlighting the role of glial cells in experience-dependent plasticity and learning.


2014 ◽  
Vol 45 (4) ◽  
pp. 865-874 ◽  
Author(s):  
T. Bracht ◽  
A. N. Doidge ◽  
P. A. Keedwell ◽  
D. K. Jones

Background.The medial forebrain bundle (MFB) is an important pathway of the reward system. Two branches have been described using diffusion magnetic resonance imaging (MRI)-based tractography: the infero-medial MFB (imMFB) and the supero-lateral MFB (slMFB). Previous studies point to white-matter microstructural alterations of the slMFB in major depressive disorder (MDD) during acute episodes. To extend this finding, this study investigates whether white-matter microstructure is also altered in MDD patients that are in remission. Further, we explore associations between diffusion MRI-based metrics of white-matter microstructure of imMFB, slMFB and hedonic tone, the ability to derive pleasure.Method.Eighteen remitted depressed (RD) and 22 never depressed (ND) participants underwent high angular resolution diffusion-weighted imaging (HARDI) scans. To reconstruct the two pathways of the MFB (imMFB and slMFB) we used the damped Richardson–Lucy (dRL) algorithm. Mean fractional anisotropy (FA) was sampled along the tracts.Results.Mean FA of imMFB, slMFB and a comparison tract (the middle cerebellar peduncle) did not differ between ND and RD participants. Hedonic capacity correlated negatively with mean FA of the left slMFB, explaining 21% of the variance.Conclusions.Diffusion MRI-based metrics of white-matter microstructure of the MFB in RD do not differ from ND. Hedonic capacity is associated with altered white-matter microstructure of the slMFB.


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