Advancement of PD Is Reflected by White Matter Changes in Olfactory Areas: A Pilot Study

Loss of sense of smell is a well-known non-motor symptom of Parkinson’s disease (PD). Here, we present insight into the association between PD advancement and equivalents of smell loss in olfactory-eloquent brain areas, such as the posterior cortex and orbitofrontal cortex. Twelve PD patients in different Hoehn and Yahr stages and 12 healthy normosmic individuals were examined with diffusion tensor imaging. Tract-based spatial statistics were used to analyze microstructural changes in white matter adjacent to the bilateral posterior and orbitofrontal cortex. Axial diffusivity, mean diffusivity, and radial diffusivity were significantly higher in olfactory ROIs in advanced PD patients. The results of this preliminary study indicate that PD advancement is associated with progressive neurodegeneration in olfactory-related brain areas.

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Arterial Stiffness Is Associated with White Matter Disruption and Cognitive Impairment: A Community-Based Cohort Study

Journal of Alzheimer s Disease ◽

10.3233/jad-201424 ◽

2021 ◽

Vol 80 (2) ◽

pp. 567-576

Author(s):

Fei Han ◽

Fei-Fei Zhai ◽

Ming-Li Li ◽

Li-Xin Zhou ◽

Jun Ni ◽

...

Keyword(s):

Cognitive Function ◽

White Matter ◽

Arterial Stiffness ◽

Cognitive Decline ◽

Sex Education ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

White Matter Injury ◽

White Matter Integrity ◽

Cross Sectional

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

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White matter network damage mediates association between cerebrovascular disease and cognition

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x21990980 ◽

2021 ◽

pp. 0271678X2199098

Author(s):

Saima Hilal ◽

Siwei Liu ◽

Tien Yin Wong ◽

Henri Vrooman ◽

Ching-Yu Cheng ◽

...

Keyword(s):

White Matter ◽

Cerebrovascular Disease ◽

Verbal Memory ◽

Visual Memory ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Domain Specific ◽

Epidemiology Of Dementia ◽

Z Scores ◽

White Matter Connectivity

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores. Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers. Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.

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White Matter Integrity Predicts Delay Discounting Behavior in 9- to 23-Year-Olds: A Diffusion Tensor Imaging Study

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2009.21107 ◽

2009 ◽

Vol 21 (7) ◽

pp. 1406-1421 ◽

Cited By ~ 119

Author(s):

Elizabeth A. Olson ◽

Paul F. Collins ◽

Catalina J. Hooper ◽

Ryan Muetzel ◽

Kelvin O. Lim ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Delay Discounting ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Study ◽

Temporal Lobes ◽

Brain White Matter ◽

Independent Effects ◽

Age Range

Healthy participants (n = 79), ages 9–23, completed a delay discounting task assessing the extent to which the value of a monetary reward declines as the delay to its receipt increases. Diffusion tensor imaging (DTI) was used to evaluate how individual differences in delay discounting relate to variation in fractional anisotropy (FA) and mean diffusivity (MD) within whole-brain white matter using voxel-based regressions. Given that rapid prefrontal lobe development is occurring during this age range and that functional imaging studies have implicated the prefrontal cortex in discounting behavior, we hypothesized that differences in FA and MD would be associated with alterations in the discounting rate. The analyses revealed a number of clusters where less impulsive performance on the delay discounting task was associated with higher FA and lower MD. The clusters were located primarily in bilateral frontal and temporal lobes and were localized within white matter tracts, including portions of the inferior and superior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and splenium of the corpus callosum. FA increased and MD decreased with age in the majority of these regions. Some, but not all, of the discounting/DTI associations remained significant after controlling for age. Findings are discussed in terms of both developmental and age-independent effects of white matter organization on discounting behavior.

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White matter differences between essential tremor and Parkinson disease

Neurology ◽

10.1212/wnl.0000000000006694 ◽

2018 ◽

Vol 92 (1) ◽

pp. e30-e39 ◽

Cited By ~ 5

Author(s):

Meher R. Juttukonda ◽

Giulia Franco ◽

Dario J. Englot ◽

Ya-Chen Lin ◽

Kalen J. Petersen ◽

...

Keyword(s):

White Matter ◽

Parkinson Disease ◽

Essential Tremor ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Superior Cerebellar Peduncle ◽

Radial Diffusivity ◽

Cerebellar Peduncles ◽

Cerebellar Peduncle

ObjectiveTo assess white matter integrity in patients with essential tremor (ET) and Parkinson disease (PD) with moderate to severe motor impairment.MethodsSedated participants with ET (n = 57) or PD (n = 99) underwent diffusion tensor imaging (DTI) and fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values were computed. White matter tracts were defined using 3 well-described atlases. To determine candidate white matter regions that differ between ET and PD groups, a bootstrapping analysis was applied using the least absolute shrinkage and selection operator. Linear regression was applied to assess magnitude and direction of differences in DTI metrics between ET and PD populations in the candidate regions.ResultsFractional anisotropy values that differentiate ET from PD localize primarily to thalamic and visual-related pathways, while diffusivity differences localized to the cerebellar peduncles. Patients with ET exhibited lower fractional anisotropy values than patients with PD in the lateral geniculate body (p < 0.01), sagittal stratum (p = 0.01), forceps major (p = 0.02), pontine crossing tract (p = 0.03), and retrolenticular internal capsule (p = 0.04). Patients with ET exhibited greater radial diffusivity values than patients with PD in the superior cerebellar peduncle (p < 0.01), middle cerebellar peduncle (p = 0.05), and inferior cerebellar peduncle (p = 0.05).ConclusionsRegionally, distinctive white matter microstructural values in patients with ET localize to the cerebellar peduncles and thalamo-cortical visual pathways. These findings complement recent functional imaging studies in ET but also extend our understanding of putative physiologic features that account for distinctions between ET and PD.

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White matter abnormalities in the corpus callosum with cognitive impairment in Parkinson disease

Neurology ◽

10.1212/wnl.0000000000006646 ◽

2018 ◽

Vol 91 (24) ◽

pp. e2244-e2255 ◽

Cited By ~ 16

Author(s):

Ian O. Bledsoe ◽

Glenn T. Stebbins ◽

Doug Merkitch ◽

Jennifer G. Goldman

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Corpus Callosum ◽

Parkinson Disease ◽

Information Transfer ◽

Diffusion Tensor ◽

Anterior Segment ◽

Mean Diffusivity ◽

Cognitive Domain ◽

White Matter Abnormalities

ObjectiveTo evaluate microstructural characteristics of the corpus callosum using diffusion tensor imaging (DTI) and their relationships to cognitive impairment in Parkinson disease (PD).MethodsSeventy-five participants with PD and 24 healthy control (HC) participants underwent structural MRI brain scans including DTI sequences and clinical and neuropsychological evaluations. Using Movement Disorder Society criteria, PD participants were classified as having normal cognition (PD-NC, n = 23), mild cognitive impairment (PD-MCI, n = 35), or dementia (PDD, n = 17). Cognitive domain (attention/working memory, executive function, language, memory, visuospatial function) z scores were calculated. DTI scalar values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were established for 5 callosal segments on a midsagittal plane, single slice using a topographically derived parcellation method. Scalar values were compared among participant groups. Regression analyses were performed on cognitive domain z scores and DTI metrics.ResultsParticipants with PD showed increased AD values in the anterior 3 callosal segments compared to healthy controls. Participants with PDD had significantly increased AD, MD, and RD in the anterior 2 segments compared to participants with PD-NC and most anterior segment compared to participants with PD-MCI. FA values did not differ significantly between participants with PD and participants with HC or among PD cognitive groups. The strongest associations for the DTI metrics and cognitive performance occurred in the most anterior and most posterior callosal segments, and also reflected fronto-striatal and posterior cortical type cognitive deficits, respectively.ConclusionsMicrostructural white matter abnormalities of the corpus callosum, as measured by DTI, may contribute to PD cognitive impairment by disrupting information transfer across interhemispheric and callosal–cortical projections.

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Discrimination of epileptogenic lesions and perilesional white matter using diffusion tensor magnetic resonance imaging

The Neuroradiology Journal ◽

10.1177/1971400918813991 ◽

2018 ◽

Vol 32 (1) ◽

pp. 10-16

Author(s):

Alexander Rau ◽

Elias Kellner ◽

Niels A Foit ◽

Niklas Lützen ◽

Dieter H Heiland ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Focal Cortical Dysplasia ◽

Mean Diffusivity ◽

Area Under The Curve ◽

P Value ◽

Radial Diffusivity ◽

Normal Appearing White Matter ◽

Diffusion Parameters

The aim of this study was to evaluate whether ganglioglioma (GGL), dysembryoplastic neuroepithelial tumour (DNET) and FCD (focal cortical dysplasia) are distinguishable through diffusion tensor imaging. Additionally, it was investigated whether the diffusion measures differed in the perilesional (pNAWM) and in the contralateral normal appearing white matter (cNAWM). Six GGLs, eight DNETs and seven FCDs were included in this study. Quantitative diffusion measures, that is, axial, radial and mean diffusivity and fractional anisotropy, were determined in the lesion identified on isotropic T2 or FLAIR-weighted images and in pNAWM and cNAWM, respectively. DNET differed from FCD in mean diffusivity, and GGL from FCD in radial diffusivity. Both types of glioneuronal tumours were different from pNAWM in fractional anisotropy and radial diffusivity. For identifying the tumour edges, threshold values for tumour-free tissue were investigated with receiver operating characteristic analyses: tumour could be separated from pNAWM at a threshold ≤ 0.32 (fractional anisotropy) or ≥ 0.56 (radial diffusivity) *10–3 mm2/s (area under the curve 0.995 and 0.990 respectively). While diffusion parameters of FCDs differed from cNAWM (radial diffusivity (*10–3 mm/s2): 0.74 ± 0.19 vs. 0.43 ± 0.05; corrected p-value < 0.001), the pNAWM could not be differentiated from the FCD.

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In Vivo Characterization of Cortical and White Matter Microstructural Pathology in Growth Hormone-Secreting Pituitary Adenoma

Frontiers in Oncology ◽

10.3389/fonc.2021.641359 ◽

2021 ◽

Vol 11 ◽

Author(s):

Taoyang Yuan ◽

Jianyou Ying ◽

Chuzhong Li ◽

Lu Jin ◽

Jie Kang ◽

...

Keyword(s):

Growth Hormone ◽

Pituitary Adenoma ◽

White Matter ◽

Diffusion Tensor ◽

Critical Role ◽

Mean Diffusivity ◽

Occipital Cortex ◽

Test Surface ◽

Neuropsychological Dysfunction

BackgroundThe growth hormone (GH) and insulin-like-growth factor 1 (IGF-1) axis has long been recognized for its critical role in brain growth, development. This study was designed to investigate microstructural pathology in the cortex and white matter in growth hormone-secreting pituitary adenoma, which characterized by excessive secretion of GH and IGF-1.Methods29 patients with growth hormone-secreting pituitary adenoma (acromegaly) and 31 patients with non-functional pituitary adenoma as controls were recruited and assessed using neuropsychological test, surface-based morphometry, T1/T2-weighted myelin-sensitive magnetic resonance imaging, neurite orientation dispersion and density imaging, and diffusion tensor imaging.ResultsCompared to controls, we found 1) acromegaly had significantly increased cortical thickness throughout the bilateral cortex (pFDR < 0.05). 2) T1/T2-weighted ratio in the cortex were decreased in the bilateral occipital cortex and pre/postcentral central gyri but increased in the bilateral fusiform, insular, and superior temporal gyri in acromegaly (pFDR < 0.05). 3) T1/T2-weighted ratio were decreased in most bundles, and only a few areas showed increases in acromegaly (pFDR < 0.05). 4) Neurite density index (NDI) was significantly lower throughout the cortex and bundles in acromegaly (pTFCE < 0.05). 5) lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in extensive bundles in acromegaly (pTFCE < 0.05). 6) microstructural pathology in the cortex and white matter were associated with neuropsychological dysfunction in acromegaly.ConclusionsOur findings suggested that long-term persistent and excess serum GH/IGF-1 levels alter the microstructure in the cortex and white matter in acromegaly, which may be responsible for neuropsychological dysfunction.

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Diffusion tensor imaging of cerebral white matter in patients with myotonic dystrophy

Acta Radiologica ◽

10.1080/02841850510015974 ◽

2005 ◽

Vol 46 (1) ◽

pp. 104-109 ◽

Cited By ~ 23

Author(s):

H. Fukuda ◽

J. Horiguchi ◽

C. Ono ◽

T. Ohshita ◽

J. Takaba ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Myotonic Dystrophy ◽

Normal Control ◽

Diffusion Tensor ◽

Age At Onset ◽

Mean Diffusivity ◽

Magnetic Resonance Images ◽

Microstructural Changes ◽

Control Subjects

Purpose: To determine whether myotonic dystrophy (MyD) patients have diffusion tensor abnormalities suggestive of microstructural changes in normal‐appearing white matter (NAWM). Material and Methods: Conventional and diffusion tensor magnetic resonance images of the brain were obtained in 19 MyD patients and 19 age‐matched normal control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in white matter lesions (WMLs) and NAWM in MyD patients and in the white matter of normal control subjects. Differences between WML and NAWM values and between MyD patient and control subject values were analyzed statistically. Results: Significantly lower FA and higher MD values were found in all regions of interest in the NAWM of MyD patients than in the white matter of control subjects ( P<0.01), as well as significantly lower FA and higher MD values in WMLs than in NAWM of MyD patients ( P<0.05). There was no significant correlation of mean FA or MD values in NAWM with patient age, age at onset, or duration of illness ( P>0.1). Conclusion: Diffusion tensor imaging analysis suggests the presence of diffuse microstructural changes in NAWM of MyD patients that may play an important role in the development of disability.

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Repeated Sport-Related Concussion Shows Only Minimal White Matter Differences Many Years After Playing High School Football

Journal of the International Neuropsychological Society ◽

10.1017/s1355617719000754 ◽

2019 ◽

Vol 25 (09) ◽

pp. 950-960 ◽

Cited By ~ 2

Author(s):

Douglas P. Terry ◽

Catherine M. Mewborn ◽

L. Stephen Miller

Keyword(s):

High School ◽

White Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Region Of Interest ◽

Internal Capsule ◽

Later Life ◽

Cognitive Outcomes ◽

High School Football ◽

Former Athletes

AbstractObjective: Multiple concussions sustained in youth sport may be associated with later-life brain changes and worse cognitive outcomes. We examined the association between two or more concussions during high school football and later-life white matter (WM) microstructure (i.e., 22–47 years following football retirement) using diffusion tensor imaging (DTI). Method: Forty former high school football players aged 40–65 who received 2+ concussions during high school football (N = 20), or denied concussive events (N = 20) were recruited. Participants underwent neurocognitive testing and DTI scanning. Results: Groups did not statistically differ on age, education, or estimated pre-morbid intelligence. Tract-based Spatial Statistics (TBSS) correcting for Family-Wise Error (FWE)(p < .05) did not yield differences between groups at the whole-brain level. Region of interest analyses showed higher mean diffusivity (MD) in the anterior limb of the internal capsule (ALIC) in the concussed group compared to the non-concussed former players. More liberal analyses (i.e., p < .001, uncorrected for multiple comparisons, ≥8 voxels) also revealed that former players endorsing 2+ concussions had higher MD in the ALIC. Analyses that covaried for age did not reveal differences at either threshold. Concussive histories were not associated with worse cognitive functioning, nor did it impact the relationship between neuropsychological scores and DTI metrics. Discussion: Results suggest only minimal neuroanatomical brain differences in former athletes many years following original concussive injuries compared to controls.

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Dysmature superficial white matter microstructure in developmental focal epilepsy

Brain Communications ◽

10.1093/braincomms/fcz002 ◽

2019 ◽

Vol 1 (1) ◽

Cited By ~ 3

Author(s):

Lauren M Ostrowski ◽

Daniel Y Song ◽

Emily L Thorn ◽

Erin E Ross ◽

Sally M Stoyell ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Fine Motor ◽

Epilepsy Syndrome ◽

Healthy Controls ◽

Deep White Matter ◽

White Matter Microstructure ◽

Benign Epilepsy

Abstract Benign epilepsy with centrotemporal spikes is a common childhood epilepsy syndrome that predominantly affects boys, characterized by self-limited focal seizures arising from the perirolandic cortex and fine motor abnormalities. Concurrent with the age-specific presentation of this syndrome, the brain undergoes a developmentally choreographed sequence of white matter microstructural changes, including maturation of association u-fibres abutting the cortex. These short fibres mediate local cortico-cortical communication and provide an age-sensitive structural substrate that could support a focal disease process. To test this hypothesis, we evaluated the microstructural properties of superficial white matter in regions corresponding to u-fibres underlying the perirolandic seizure onset zone in children with this epilepsy syndrome compared with healthy controls. To verify the spatial specificity of these features, we characterized global superficial and deep white matter properties. We further evaluated the characteristics of the perirolandic white matter in relation to performance on a fine motor task, gender and abnormalities observed on EEG. Children with benign epilepsy with centrotemporal spikes (n = 20) and healthy controls (n = 14) underwent multimodal testing with high-resolution MRI including diffusion tensor imaging sequences, sleep EEG recordings and fine motor assessment. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region. We found distinct abnormalities corresponding to the perirolandic u-fibre region, with increased axial, radial and mean diffusivity and fractional anisotropy values in children with epilepsy (P = 0.039, P = 0.035, P = 0.042 and P = 0.017, respectively). Increased fractional anisotropy in this region, consistent with decreased integrity of crossing sensorimotor u-fibres, correlated with inferior fine motor performance (P = 0.029). There were gender-specific differences in white matter microstructure in the perirolandic region; males and females with epilepsy and healthy males had higher diffusion and fractional anisotropy values than healthy females (P ≤ 0.035 for all measures), suggesting that typical patterns of white matter development disproportionately predispose boys to this developmental epilepsy syndrome. Perirolandic white matter microstructure showed no relationship to epilepsy duration, duration seizure free, or epileptiform burden. There were no group differences in diffusivity or fractional anisotropy in superficial white matter outside of the perirolandic region. Children with epilepsy had increased radial diffusivity (P = 0.022) and decreased fractional anisotropy (P = 0.027) in deep white matter, consistent with a global delay in white matter maturation. These data provide evidence that atypical maturation of white matter microstructure is a basic feature in benign epilepsy with centrotemporal spikes and may contribute to the epilepsy, male predisposition and clinical comorbidities observed in this disorder.

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