SYT1 Gene-Wide Analysis on White Matter Microstructure in Adulthood ADHD

Abstract The Synaptotagmin-1 encoding gene (SYT1) is a key regulator of neurotransmitter release and is associated with cognitive and psychiatric phenotypes in GWAS, and with ADHD in single-gene studies, raising the need for dissecting possible cross-trait effects on clinical and brain phenotypes. Inferences about white matter microstructure can be made by diffusion-tensor imaging (DTI), which makes this method a promising tool in the understanding of biological changes that underpin cognitive functions and brain disorders. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects multiple functioning domains, highly overlapping with other psychiatric disorders, and known to involve white matter abnormalities and neurotransmission dysfunction. Using a set-based analysis, the present study investigates how genetic variants within SYT1 might affect brain white matter at a cellular level using DTI in adults with ADHD (n = 85). The combined effect of all measured variations in the gene (i.e., 468 variants) was evaluated concerning specific white matter tracts. Set-based analysis was performed in PLINK software and followed by in silico analysis of all variants included in the study. SYT1 gene was nominally associated with white matter changes in two important tracts: forceps major and inferior fronto-occipital fasciculus. In addition, two regions within the SYT1 have more consistent associations with different white matter tracts. These findings endorse the involvement of SYT1 on psychiatric phenotypes and suggest that white matter tracts underlie this complex relationship.

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Association between breastfeeding during infancy and white matter microstructure in early childhood

10.1101/2021.01.05.425482 ◽

2021 ◽

Author(s):

Preeti Kar ◽

Jess E. Reynolds ◽

Melody N. Grohs ◽

Rhonda C. Bell ◽

Megan Jarman ◽

...

Keyword(s):

Early Childhood ◽

White Matter ◽

Diffusion Tensor ◽

Total Duration ◽

Sociodemographic Factors ◽

Typically Developing ◽

Brain White Matter ◽

White Matter Microstructure ◽

White Matter Development ◽

Exclusive Or

Introduction: Associations between breastfeeding and brain development, in the context of child, perinatal, and sociodemographic variables, remain unclear. This study investigates whether exclusive breastfeeding for the first 6 months and total duration of any breastfeeding are associated with brain white matter microstructure in young children. Methods: This study included a sample of 83 mothers and 85 typically developing children (42 males). Children underwent their first diffusion tensor imaging scan between ages 2.34-6.97 years; some children returned multiple times, providing a total of 331 datasets. Feeding information was collected from the mothers at 3, 6, and 12 months postpartum and at their child's scan to calculate breastfeeding status at 6 months (exclusive or not) as well as total duration of any breastfeeding. Linear regression was used to investigate associations between breastfeeding exclusivity/duration and fractional anisotropy (FA, a measure sensitive to myelination/axonal packing/fibre coherence) for the whole brain and 10 individual white matter tracts. Results: Breastfeeding exclusivity and duration were associated with global and regional white matter microstructure, even after controlling for perinatal and sociodemographic factors. Greater exclusivity was associated with higher FA in females and lower FA in males. Conclusions: These findings suggest white matter differences associated with breastfeeding that differ by sex. These may stem from different trajectories in white matter development between males and females in early childhood and suggest possible long-term white matter differences associated with breastfeeding.

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Scalp acupuncture plus low-frequency rTMS promotes repair of brain white matter tracts in hemiplegic patients with stroke: A diffusion tensor imaging study

Journal of Integrative Neuroscience ◽

10.31083/jin-170043 ◽

2018 ◽

Vol 17 (1) ◽

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Low Frequency ◽

Imaging Study ◽

Scalp Acupuncture ◽

White Matter Tracts ◽

Brain White Matter ◽

Low Frequency Rtms ◽

Diffusion Tensor Imaging Study

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Microstructure of Strategic White Matter Tracts and Cognition in Memory Clinic Patients with Vascular Brain Injury

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000485376 ◽

2017 ◽

Vol 44 (5-6) ◽

pp. 268-282 ◽

Cited By ~ 5

Author(s):

J. Matthijs Biesbroek ◽

Alexander Leemans ◽

Hanna den Bakker ◽

Marco Duering ◽

Benno Gesierich ◽

...

Keyword(s):

Brain Injury ◽

White Matter ◽

Executive Functioning ◽

Diffusion Tensor ◽

Added Value ◽

Memory Clinic ◽

Whole Brain ◽

White Matter Tracts ◽

Conventional Mri ◽

Brain White Matter

Background: White matter injury is an important factor for cognitive impairment in memory clinic patients. We determined the added value of diffusion tensor imaging (DTI) of strategic white matter tracts in explaining variance in cognition in memory clinic patients with vascular brain injury. Methods: We included 159 patients. Conventional MRI markers (white matter hyperintensity volume, lacunes, nonlacunar infarcts, brain atrophy, and microbleeds), and fractional anisotropy and mean diffusivity (MD) of the whole brain white matter and of 18 white matter tracts were related to cognition using linear regression and Bayesian network analysis. Results: On top of all conventional MRI markers combined, MD of the whole brain white matter explained an additional 3.4% (p = 0.014), 7.8% (p < 0.001), and 1.2% (p = 0.119) variance in executive functioning, speed, and memory, respectively. The Bayesian analyses of regional DTI measures identified strategic tracts for executive functioning (right superior longitudinal fasciculus), speed (left corticospinal tract), and memory (left uncinate fasciculus). MD within these tracts explained an additional 3.4% (p = 0.012), 3.8% (p = 0.007), and 2.1% (p = 0.041) variance in executive functioning, speed, and memory, respectively, on top of all conventional MRI and global DTI markers combined. Conclusion: In memory clinic patients with vascular brain injury, DTI of strategic white matter tracts has a significant added value in explaining variance in cognitive functioning.

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Mapping the human brain white matter tracts relative to cortical and deep gray matter using diffusion tensor imaging at high spatial resolution

Magnetic Resonance Imaging ◽

10.1016/j.mri.2008.10.007 ◽

2009 ◽

Vol 27 (5) ◽

pp. 631-636 ◽

Cited By ~ 25

Author(s):

Khader M. Hasan ◽

Arash Kamali ◽

Larry A. Kramer

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Human Brain ◽

Spatial Resolution ◽

Gray Matter ◽

High Spatial Resolution ◽

Diffusion Tensor ◽

White Matter Tracts ◽

Brain White Matter ◽

Deep Gray Matter

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Widespread White Matter Microstructure Alterations Based on Diffusion Tensor Imaging and Diffusion Kurtosis Imaging in Patients With Pontine Infarction

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.758236 ◽

2021 ◽

Vol 13 ◽

Author(s):

Ying Wei ◽

Caihong Wang ◽

Jingchun Liu ◽

Peifang Miao ◽

Sen Wei ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Diffusion Kurtosis Imaging ◽

White Matter Tracts ◽

Microstructure Changes ◽

Diffusion Parameters ◽

White Matter Microstructure ◽

Pontine Infarction ◽

Diffusion Kurtosis

Neurological deficits after stroke are closely related to white matter microstructure damage. However, secondary changes in white matter microstructure after pontine infarction (PI) in the whole brain remain unclear. This study aimed to investigate the correlation of diffusion kurtosis imaging (DKI)-derived diffusion and kurtosis parameters of abnormal white matter tracts with behavioral function in patients with chronic PI. Overall, 60 patients with unilateral chronic PI (33 patients with left PI and 27 patients with right PI) and 30 normal subjects were recruited and underwent DKI scans. Diffusion parameters derived from diffusion tensor imaging (DTI) and DKI and kurtosis parameters derived from DKI were obtained. Between-group differences in multiple parameters were analyzed to assess the changes in abnormal white matter microstructure. Moreover, we also calculated the sensitivities of different diffusion and kurtosis parameters of DTI and DKI for identifying abnormal white matter tracts. Correlations between the DKI-derived parameters in secondary microstructure changes and behavioral scores in the PI were analyzed. Compared with the NC group, both left PI and right PI groups showed more extensive perilesional and remote white matter microstructure changes. The DKI-derived diffusion parameters showed higher sensitivities than did the DTI-derived parameters. Further, DKI-derived diffusion and kurtosis parameters in abnormal white matter regions were correlated with impaired motor and cognitive function in patients with PI. In conclusion, PI could lead to extensive white matter tracts impairment in perilesional and remote regions. Further, the diffusion and kurtosis parameters could be complementary for identifying comprehensive tissue microstructural damage after PI.

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Brain White Matter Microstructure as a Risk Factor for Cognitive Decline After Chemotherapy for Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.21.00627 ◽

2021 ◽

Author(s):

Michiel B. de Ruiter ◽

Liesbeth Reneman ◽

Jacobien M. Kieffer ◽

Hester S. A. Oldenburg ◽

Sanne B. Schagen

Keyword(s):

Breast Cancer ◽

Risk Factor ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Cognitive Decline ◽

Diffusion Tensor ◽

Improve Patient Care ◽

Brain White Matter ◽

White Matter Microstructure ◽

Premorbid Intelligence

PURPOSE Cognitive decline is frequently observed after chemotherapy. As chemotherapy is associated with changes in brain white matter microstructure, we investigated whether white matter microstructure before chemotherapy is a risk factor for cognitive decline after chemotherapy. METHODS Neuropsychologic tests were administered before and 6 months (n = 49), 2 years (n = 32), and 3 years (n = 32) after chemotherapy in patients with breast cancer receiving anthracycline-based chemotherapy (BC + CT group), at matched intervals to patients with BC who did not receive systemic therapy (BC – CT group: n = 39, 23, and 19, respectively) and to no-cancer controls (NC group: n = 37, 29, and 28, respectively). Using multivariate normative comparison, we evaluated to what extent the cognitive profiles of patients deviated from those of controls. Fractional anisotropy (FA), derived from magnetic resonance diffusion tensor imaging, was used to measure white matter microstructure before treatment. FA was evaluated as a risk factor for cognitive decline, in addition to baseline age, fatigue, cognitive complaints, and premorbid intelligence quotient. We subsequently ran voxel-wise diffusion tensor imaging analyses to investigate white matter microstructure in specific nerve tracts. RESULTS Low FA independently predicted cognitive decline early (6 months, P = .013) and late (3 years, P < .001) after chemotherapy. FA did not predict cognitive decline in the BC – CT and NC groups. Voxel-wise analysis indicated involvement of white matter tracts essential for cognitive functioning. CONCLUSION Low FA may reflect low white matter reserve. This may be a risk factor for cognitive decline after chemotherapy for BC. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy.

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Transient changes in white matter microstructure during general anesthesia

PLoS ONE ◽

10.1371/journal.pone.0247678 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247678

Author(s):

Cheuk Y. Tang ◽

Victoria X. Wang ◽

Min Yin Lun ◽

Joshua S. Mincer ◽

Johnny C. Ng ◽

...

Keyword(s):

White Matter ◽

General Anesthesia ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

The Elderly ◽

Volumetric Analysis ◽

Sevoflurane Anesthesia ◽

Transient Effects ◽

Brain White Matter ◽

White Matter Microstructure

Cognitive dysfunction after surgery under general anesthesia is a well-recognized clinical phenomenon in the elderly. Physiological effects of various anesthetic agents have been studied at length. Very little is known about potential effects of anesthesia on brain structure. In this study we used Diffusion Tensor Imaging to compare the white matter microstructure of healthy control subjects under sevoflurane anesthesia with their awake state. Fractional Anisotropy, a white mater integrity index, transiently decreases throughout the brain during sevoflurane anesthesia and then returns back to baseline. Other DTI metrics such as mean diffusivity, axial diffusivity and radial diffusivity were increased under sevoflurane anesthesia. Although DTI metrics are age dependent, the transient changes due to sevoflurane were independent of age and sex. Volumetric analysis shows various white matter volumes decreased whereas some gray matter volumes increased during sevoflurane anesthesia. These results suggest that sevoflurane anesthesia has a significant, but transient, effect on white matter microstructure. In spite of the transient effects of sevoflurane anesthesia there were no measurable effects on brain white matter as determined by the DTI metrics at 2 days and 7 days following anesthesia. The role of white matter in the loss of consciousness under anesthesia will need to be studied and MRI studies with subjects under anesthesia will need to take these results into account.

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Evidence of Genetic Overlap Between Circadian Preference and Brain White Matter Microstructure

Twin Research and Human Genetics ◽

10.1017/thg.2021.4 ◽

2021 ◽

Vol 24 (1) ◽

pp. 1-6

Author(s):

Luis M. García-Marín ◽

Sarael Alcauter ◽

Adrian I. Campos ◽

Aoibhe Mulcahy ◽

Pik-Fang Kho ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Genetic Correlations ◽

Mean Diffusivity ◽

Causal Association ◽

Posterior Limb ◽

Brain White Matter ◽

White Matter Microstructure ◽

Genetic Overlap ◽

Circadian Preference

AbstractSeveral neuroimaging studies have reported associations between brain white matter microstructure and chronotype. However, it is unclear whether those phenotypic relationships are causal or underlined by genetic factors. In the present study, we use genetic data to examine the genetic overlap and infer causal relationships between chronotype and diffusion tensor imaging (DTI) measures. We identify 29 significant pairwise genetic correlations, of which 13 also show evidence for a causal association. Genetic correlations were identified between chronotype and brain-wide mean, axial and radial diffusivities. When exploring individual tracts, 10 genetic correlations were observed with mean diffusivity, 10 with axial diffusivity, 4 with radial diffusivity and 2 with mode of anisotropy. We found evidence for a possible causal association of eveningness with white matter microstructure measures in individual tracts including the posterior limb and the retrolenticular part of the internal capsule; the genu and splenium of the corpus callosum and the posterior, superior and anterior regions of the corona radiata. Our findings contribute to the understanding of how genes influence circadian preference and brain white matter and provide a new avenue for investigating the role of chronotype in health and disease.

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Brain white matter after pediatric mild traumatic brain injury: a diffusion tensor and neurite orientation and dispersion imaging study

10.1101/2021.09.09.21263356 ◽

2021 ◽

Author(s):

Ayushi Shukla ◽

Ashley L Ware ◽

Sunny Guo ◽

Bradley Gooodyear ◽

Miriam H Beauchamp ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Diffusion Tensor ◽

Univariate Analysis ◽

Significant Group ◽

Brain White Matter ◽

Orthopedic Injury ◽

White Matter Microstructure

Background: Pediatric mild traumatic brain injury (mTBI) affects millions of children annually. Diffusion tensor imaging (DTI) is sensitive to axonal injuries and white matter microstructure and has been used to characterize the brain changes associated with mild traumatic brain injury (mTBI). Neurite orientation dispersion and density imaging (NODDI) is a diffusion model that can provide additional insight beyond traditional DTI metrics, but has not been examined in pediatric mTBI. The goal of this study was to employ DTI and NODDI to gain added insight into white matter alterations in children with mTBI compared to children with mild orthopedic injury (OI). Methods: Children (mTBI n=320, OI n=176) aged 8-16.99 years (12.39 ± 2.32 years) were recruited from emergency departments at five hospitals across Canada and underwent 3T MRI on average 11 days post-injury. DTI and NODDI metrics were calculated for seven major white matter tracts and compared between groups using univariate analysis of covariance controlling for age, sex, and scanner type. False discovery rate (FDR) was used to correct for multiple comparisons. Results: Univariate analysis revealed no significant group main effects or interactions in DTI or NODDI metrics. Fractional anisotropy and neurite density index in all tracts exhibited a significant positive association with age and mean diffusivity in all tracts exhibited a significant negative association with age in the whole sample. Conclusions: Overall, there were no differences between mTBI and OI groups in brain white matter microstructure from either DTI or NODDI in the seven tracts. This indicates that mTBI is associated with only relatively minor white matter differences, if any, at the post-acute stage. Brain differences may evolve at later stages of injury, so longitudinal studies with long-term follow-up are needed.

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