scholarly journals Altered White Matter Organization in the TUBB3 E410K Syndrome

2018 ◽  
Vol 29 (8) ◽  
pp. 3561-3576 ◽  
Author(s):  
P Ellen Grant ◽  
Kiho Im ◽  
Banu Ahtam ◽  
Cynthia T Laurentys ◽  
Wai-Man Chan ◽  
...  

Abstract Seven unrelated individuals (four pediatric, three adults) with the TUBB3 E410K syndrome, harboring identical de novo heterozygous TUBB3 c.1228 G>A mutations, underwent neuropsychological testing and neuroimaging. Despite the absence of cortical malformations, they have intellectual and social disabilities. To search for potential etiologies for these deficits, we compared their brain's structural and white matter organization to 22 controls using structural and diffusion magnetic resonance imaging. Diffusion images were processed to calculate fractional anisotropy (FA) and perform tract reconstructions. Cortical parcellation-based network analysis and gyral topology-based FA analyses were performed. Major interhemispheric, projection and intrahemispheric tracts were manually segmented. Subjects had decreased corpus callosum volume and decreased network efficiency. While only pediatric subjects had diffuse decreases in FA predominantly affecting mid- and long-range tracts, only adult subjects had white matter volume loss associated with decreased cortical surface area. All subjects showed aberrant corticospinal tract trajectory and bilateral absence of the dorsal language network long segment. Furthermore, pediatric subjects had more tracts with decreased FA compared with controls than did adult subjects. These findings define a TUBB3 E410K neuroimaging endophenotype and lead to the hypothesis that the age-related changes are due to microscopic intrahemispheric misguided axons that are pruned during maturation.

Author(s):  
Marissa A. Gogniat ◽  
Catherine M. Mewborn ◽  
Talia L. Robinson ◽  
Kharine R. Jean ◽  
L. Stephen Miller

The population of older adults is increasing, indicating a need to examine factors that may prevent or mitigate age-related cognitive decline. The current study examined whether microstructural white matter characteristics mediated the relation between physical activity and executive function in older adults without any self-reported psychiatric and neurological disorders or cognitive impairment (N = 43, mean age = 73 y). Physical activity was measured by average intensity and number of steps via accelerometry. Diffusion tensor imaging was used to examine microstructural white matter characteristics, and neuropsychological testing was used to examine executive functioning. Parallel mediation models were analyzed using microstructural white matter regions of interest as mediators of the association between physical activity and executive function. Results indicated that average steps was significantly related to executive function (β = 0.0003, t = 2.829, P = .007), while moderate to vigorous physical activity was not (β = 0.0007, t = 1.772, P = .08). White matter metrics did not mediate any associations. This suggests that microstructural white matter characteristics alone may not be the mechanism by which physical activity impacts executive function in aging.


2018 ◽  
Author(s):  
Ayan Dey ◽  
Vessela Stamenova ◽  
Agnes Bacopulos ◽  
Nivethika Jeyakumar ◽  
Gary R. Turner ◽  
...  

Some degree of ischemic injury to white matter tracts occurs naturally with age and is visible on magnetic resonance imaging as focal or confluent white matter hyperintensities (WMHs). Its relationship to cognition, however, remains unclear. To explore this, community-dwelling adults between the ages 55-80 years old completed structural imaging, neuropsychological testing, and questionnaires to provide objective measures and subjective experience of executive functioning. Volumetric lesion burden derived from structural MRI identified those with significant WMH burden (~10 cubic cm). Half of those recruited met this criterion and were designated as the cerebral small vessel disease (CSVD) group. Subjective complaints but not objective test scores differentiated adults with and without CSVD. Hierarchical clustering revealed two CSVD subgroups that differentiated those with impaired versus preserved executive function relative to controls. Overall these results provide some explanation for behavioural heterogeneity often observed in studies of age-related white matter changes. They also support the use of questionnaires to assess subjective complaints that may be able to detect subtle effects of pathology not evident on standardized cognitive scores.


2020 ◽  
Vol 31 (1) ◽  
pp. 396-409
Author(s):  
Alexandrine Morand ◽  
Shailendra Segobin ◽  
Grégory Lecouvey ◽  
Julie Gonneaud ◽  
Francis Eustache ◽  
...  

Abstract Time-based prospective memory (TBPM) allows us to remember to perform intended actions at a specific time in the future. TBPM is sensitive to the effects of age, but the neural substrates of this decline are still poorly understood. The aim of the present study was thus to better characterize the brain substrates of the age-related decline in TBPM, focusing on macrostructural gray matter and microstructural white matter integrity. We administered a TBPM task to 22 healthy young (26 ± 5.2 years) and 23 older (63 ± 5.9 years) participants, who also underwent volumetric magnetic resonance imaging and diffusion tensor imaging scans. Neuroimaging analyses revealed lower gray matter volumes in several brain areas in older participants, but these did not correlate with TBPM performance. By contrast, an age-related decline in fractional anisotropy in several white-matter tracts connecting frontal and occipital regions did correlate with TBPM performance, whereas there was no significant correlation in healthy young subjects. According to the literature, these tracts are connected to the anterior prefrontal cortex and the thalamus, 2 structures involved in TBPM. These results confirm the view that a disconnection process occurs in aging and contributes to cognitive decline.


2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Vanja Kljajevic

AbstractThe relevance of anatomical connectivity for understanding of the neural basis of language was recognized in the 19th century, and yet this topic has only recently become the subject of wider research interest. In this paper, I review recent findings on white matter tracts implicated in language: the arcuate fasciculus, superior longitudinal fasciculus, extreme capsule, uncinate fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. The reviewed findings on these tracts were reported in studies that used a variety of methods, from post-mortem dissection and diffusion imaging to intraoperative electrostimulation with awake surgery patients. The emerging picture suggests that there is currently no consensus with regard to the exact number and identity of the tracts supporting language, their origins, trajectories, and terminations, as well as their functional interpretation.


2021 ◽  
Author(s):  
John D Lewis ◽  
Christian O’Reilly ◽  
Elizabeth Bock ◽  
Rebecca J Theilmann ◽  
Jeanne Townsend

Abstract There is substantial evidence of age-related declines in anatomical connectivity during adulthood, with associated alterations in functional connectivity. But the relation of those functional alterations to the structural reductions is unclear. The complexities of both the structural and the functional connectomes make it difficult to determine such relationships. We pursue this question with methods, based on animal research, that specifically target the interhemispheric connections between the visual cortices. We collect t1- and diffusion-weighted imaging data from which we assess the integrity of the white matter interconnecting the bilateral visual cortices. Functional connectivity between the visual cortices is measured with electroencephalography during the presentation of drifting sinusoidal gratings that agree or conflict across hemifields. Our results show age-related reductions in the integrity of the white matter interconnecting the visual cortices, and age-related increases in the difference in functional interhemispheric lagged coherence between agreeing versus disagreeing visual stimuli. We show that integrity of the white matter in the splenium of the corpus callosum predicts the differences in lagged coherence for the agreeing versus disagreeing stimuli; and that this relationship is mediated by age. These results give new insight into the causal relationship between age and functional connectivity.


2006 ◽  
Vol 2 ◽  
pp. S683-S683
Author(s):  
Norbert Schuff ◽  
Yu Zhang ◽  
Antao Du ◽  
Susanne Mueller ◽  
Jennifer Hlavin ◽  
...  

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