Frontal Lobe White Matter Research Articles

Frontal White Matter Hyperintensities and Executive Functioning Performance in Older Adults.

Frontal lobe structures decline faster than most other brain regions in older adults. Age-related change in the frontal lobe is associated with poorer executive function (e.g., working memory, switching/set-shifting, and inhibitory control). The effects and presence of frontal lobe white matter hyperintensities (WMH) on executive function in normal aging is relatively unknown. The current study assessed relationships between region-specific frontal WMH load and cognitive performance in healthy older adults using three executive function tasks from the NIH Toolbox (NIHTB) Cognition Battery. A cohort of 279 healthy older adults ages 65–88 completed NIHTB and 3T T1-weighted and FLAIR MRI. Lesion Segmentation Toolbox quantified WMH volume and generated lesion probability maps. Individual lesion maps were registered to the Desikan-Killiany atlas in FreeSurfer 6.0 to define regions of interest (ROI). Independent linear regressions assessed relationships between executive function performance and region-specific WMH in frontal lobe ROIs. All models included age, sex, education, estimated total intracranial volume, multi-site scanner differences, and cardiovascular disease risk using Framingham criteria as covariates. Poorer set-shifting performance was associated with greater WMH load in three frontal ROIs including bilateral superior frontal (left β = −0.18, FDR-p = 0.02; right β = −0.20, FDR-p = 0.01) and right medial orbitofrontal (β = −0.17, FDR-p = 0.02). Poorer inhibitory performance associated with higher WMH load in one frontal ROI, the right superior frontal (right β = −0.21, FDR-p = 0.01). There were no significant associations between working memory and WMH in frontal ROIs. Our study demonstrates that location and pattern of frontal WMH may be important to assess when examining age-related differences in cognitive functions involving switching/set-shifting and inhibition. On the other hand, working memory performance was not related to presence of frontal WMH in this sample. These data suggest that WMH may contribute selectively to age-related declines in executive function. Findings emerged beyond predictors known to be associated with WMH presence, including age and cardiovascular disease risk. The spread of WMH within the frontal lobes may play a key role in the neuropsychological profile of cognitive aging. Further research should explore whether early intervention on modifiable vascular factors or cognitive interventions targeted for executive abilities may help mitigate the effect of frontal WMH on executive function.

Study on hemodynamics of high altitude polycythemia by 3D-ASL combined with CT cerebral perfusion

Objective To investigate the changes of CT cerebral perfusion (CTP) and the application value of nuclear magnetic resonance proton spin labeling (3D-ASL) and to conduct a comparative study. Methods Multi-slice spiral CT(MDCT) was used to study the changes of CTP in 22 patients with HAPC. Comparison of CT whole-brain perfusion technique and nuclear magnetic resonance proton spin labeling technique (3D-ASL) in hemodynamic changes of the brain in plateau polycythemia. Results With the aggravation of HAPC, CBF of cerebral cortex and white matter showed a downward trend. Except the white matter of frontal lobe and temporal lobe, the difference of HAPC among different diseases was statistically significant ( P < 0.05). Along with the aggravation of, each part of the brain cortex and white matter CBV increase, white matter, and each part CBV difference had statistical significance between different condition ( P < 0.05). With the aggravation of the disease, the MTT of cortex and white matter in all parts of the brain increased significantly, and the difference of MTT between different parts of the disease was statistically significant ( P < 0.05). HAPC patients along with the aggravation of different level, rCBF is reduced, in addition to the parietal cortex, temporal and occipital white matter, white matter rCBF differences between different parts of different condition have statistical significance ( P < 0.05). ROC curve was used to evaluate the diagnostic value of CTP and ASL. The two curves were close to each other, and CTP was slightly better than ASL. Conclusion With the progression of HAPC, cerebral blood flow decreased, blood volume increased, and average blood flow time prolonged in patients with different degrees of HAPC. CTP and ASL had similar effects, and the former had slightly better value. 摘要： 目的 研宄高原红细胞增多症(HAPC)CT脑灌注 (CTP) 的变化/核磁共振质子自旋标记技术 (3D-ASL) 的应用 价值并进行对比研宄。 方法 用多层螺旋 CT(MDCT) 研宄 22 例不同程度高原红细胞增多症患者的 CT 脑灌注的变 化; CT 全脑灌注技术与核磁共振质子自旋标记技术 (3D-ASL) 在高原红细胞增多症脑部血流动力学改变中的应用价 值的比较。 结果 HAPC 随病情加重, 大脑皮质和白质均脑血流量 (CBF) 呈下降趋势, 除额叶白质和颞叶白质外, 余部 位不同病情间差异均有统计学意义 ( P < 0.05); 随病情加重, 大脑各部位皮质和白质脑血容量 (CBV) 增加, 白质更为显 著, 且各部位不同病情间 CBV 差异均有统计学意义 ( P < 0.05); 随病情加重, 大脑各部位皮质和白质平均通过时间 (MTT) 均显著增加, 各部位不同病情间 MTT 差异均有统计学意义 ( P < 0.05); 不同程度 HAPC 患者随病情加重 ( P <0.05), 相对脑血流量(rCBF)降低, 除顶叶皮质、颞叶白质和枕叶白质外, 各部位不同病情间rCBF差异均有统计学意 义;通过 ROC 曲线来评价 CTP 和ASL两者的诊断价值, 两条曲线接近, CTP 略优于 ASL。 结论 不同程度HAPC患 者随着病情进展, 脑血流减低;血容量增加;血流平均通过时间延长; CTP 与 ASL 两种方法效果接近, 前者价值略优。

Longitudinal Assessment of Enhancing Foci of Abnormal Signal Intensity in Neurofibromatosis Type 1

Patients with neurofibromatosis 1 are at increased risk of developing brain tumors, and differentiation from contrast-enhancing foci of abnormal signal intensity can be challenging. We aimed to longitudinally characterize rare, enhancing foci of abnormal signal intensity based on location and demographics. A total of 109 MR imaging datasets from 19 consecutive patients (7 male; mean age, 8.6 years; range, 2.3-16.8 years) with neurofibromatosis 1 and a total of 23 contrast-enhancing parenchymal lesions initially classified as foci of abnormal signal intensity were included. The mean follow-up period was 6.5 years (range, 1-13.8 years). Enhancing foci of abnormal signal intensity were followed up with respect to presence, location, and volume. Linear regression analysis was performed. Location, mean peak volume, and decrease in enhancing volume over time of the 23 lesions were as follows: 10 splenium of the corpus callosum (295 mm3, 5 decreasing, 3 completely resolving, 2 surgical intervention for change in imaging appearance later confirmed to be gangliocytoma and astrocytoma WHO II), 1 body of the corpus callosum (44 mm3, decreasing), 2 frontal lobe white matter (32 mm3, 1 completely resolving), 3 globus pallidus (50 mm3, all completely resolving), 6 cerebellum (206 mm3, 3 decreasing, 1 completely resolving), and 1 midbrain (34 mm3). On average, splenium lesions began to decrease in size at 12.2 years, posterior fossa lesions at 17.1 years, and other locations at 9.4 years of age. Albeit very rare, contrast-enhancing lesions in patients with neurofibromatosis 1 may regress over time. Follow-up MR imaging aids in ascertaining regression. The development of atypical features should prompt further evaluation for underlying tumors.

Diffusion tensor magnetic resonance imaging: is it valuable in the detection of brain microstructural changes in patients having migraine without aura?

PurposeThe aim of this study is to assess the diagnostic value of diffusion tensor magnetic resonance imaging (MRI) in the detection of brain microstructural changes in patients having migraine without aura.Material and methodsOur prospective study included 33 patients having migraine without aura and 15 volunteers with matched age and sex, who underwent brain MRI with diffusion tensor imaging (DTI). The fractional anisotropy (FA) and mean diffusivity (MD) of selected grey and white matter regions on both sides were measured and correlated with the neurological clinical examination.ResultsSignificant differences were detected in MD values in the thalamus, globus pallidus, and hippocampus head on the right side of patients versus controls. Also, significant differences of the FA values were detected in the thalamus, globus pallidus, and hippocampus head on the right side of patients versus controls. Regarding the FA values of the same regions on the left side, a significant difference in the FA value was detected only in the hippocampus head. There was a statistically significant difference in the FA values on both sides of the white matter of the frontal lobes, posterior limbs of the internal capsules, and cerebellar hemispheres in patients compared to controls. There was a statistically significant difference in MD values in the white matter of both frontal lobes, posterior limb of the right internal capsule, and both cerebellar hemispheres in patients compared to controls.ConclusionsDTI can detect microstructural changes of the grey and white matter in patients having migraine without aura that could not be detected by conventional MRI.

Fetal İzole Ilımlı Ventrikülomegali Manyetik Rezonans Görüntülemede Bölgesel ADC Değerlerinde Farklılık Yaratır mı?

Objective: Ventriculomegaly may not only develop secondary to a process,but it may also be in the form of isolated ventriculomegaly with no specific reason. MRI is performed to show the presence of accompanying pathologies.In this study, we measured ADC values in mild ventriculomegaly cases and aimed to investigate the role of ADC value measurements in predicting neurological prognosis in isolated mild ventriculomegaly during MRI. Methods: In our study, ADC values were measured of 37 patients detected to be present with mild ventriculomegaly and 17 fetuses in the control group who had no additional central nervous system patology. For the measurement, ROI was placed in differtent brain regions (frontal lobe white matter,occipital lobe white matter, basal ganglia, thalamus, cerebellum and pons). The analysis of the data obtained was performed using the SPSS (20th version) program. MannWhitney U test was applied. Statistical significance level was set as p&lt;0.05. Results: There was no statistically significant difference between the isolated mild ventriculomegaly and the control group in terms of the mean maternal age (p=0.160). Also, no statistically significant difference was observed between the mean gestational age in the ventriculomegaly group and the control group (p=0.890). There was also no statistically significant difference between ADC measurements in different brain regions in the isolated mild ventriculomegaly and the control group (p=0.807). Conclusion: In order to determine the prognosis in isolated mild ventriculomegaly, other quantitative parameters such as ADC measurement, beyond morphological evaluation and diameter measurement should be determined, and also we need more studies comprising more cases in this field.

Altered neurochemistry in the anterior white matter of bipolar children and adolescents: a multivoxel 1H MRS study.

Abnormalities within frontal lobe grey and white matter of bipolar disorder (BD) patients have been consistently reported in adult and pediatric studies, yet little is known about the neurochemistry of the anterior white matter (AWM) in pediatric BD and how medication status may affect it. The present cross-sectional 3T 1H MRS study is the first to use a multivoxel approach to study the AWM of BD youth. Absolute metabolite levels from four bilateral AWM voxels were collected from 49 subjects between the ages of eight and eighteen (25 healthy controls (HC); 24 BD) and quantified. Our study found BD subjects to have lower levels of N-acetylaspartate (NAA) and glycerophosphocholine plus phosphocholine (GPC+PC), metabolites that are markers of neuronal viability and phospholipid metabolism and have also been implicated in adult BD. Further analysis indicated that the observed patterns were mostly driven by BD subjects who were medicated at the time of scanning and had an ADHD diagnosis. Although limited by possible confounding effects of mood state, medication, and other mood comorbidities, these findings serve as evidence of altered neurochemistry in BD youth that is sensitive to medication status and ADHD comorbidity.

NIMG-60. ATYPICAL POSTERIOR REVERSIBLE LEUKOENCEPHALOPATHY SYNDROME MIMICKING TUMOR IN 1ST TRIMESTER PREGNANCY-’DON’T BELIEVE EVERYTHING YOU SEE’

Abstract Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiographic diagnosis characterized by headache, confusion, visual disturbances, seizures and most commonly bilateral vasogenic edema. PRES during first trimester gestation is exceptional and in our report mimicking CNS tumor. An 18-year-old G1P0 Hispanic woman was admitted with headache, left-sided hemiparesis and left-sided visual loss for 4 days. Exam was consistent for drowsiness, dysarthria, left homonymous hemianopia, left facial droop and left hemiplegia with left hemi-sensory loss. By pelvic ultrasound she had a single 9-week intrauterine pregnancy with no detectable fetal heart tone. MRI brain: large area of increased T2 signal in the right parietal occipital and upper temporal and posterior right frontal lobe white matter with mass effect of 6mm midline shift and no evidence of hemorrhage. There was high suspicion for a glial neoplasm. MRA of head and neck and EEG were unremarkable. IR cerebral angiogram had no evidence of vascular abnormalities. Eventual MR spectroscopy, choline/NAA ratio was (&amp;lt; 2/1), elevated lactate/fat peak suggestive of inflammatory versus infectious process. She had D&amp;C for missed abortion and pathology was negative for malignancy. Further brain biopsy on day 5 demonstrated reactive astrogliosis with microglial activation, scattered macrophages with white matter vacuolation. Biopsy specimen was negative for infections. TPO Ab, NMO/AQP4, Ttg IgA and rheumatologic panel were negative. The pathology was most compatible with PRES. Repeat MRI had decreasing mass effect and increased patchy subcortical restricted diffusion in the right occipital and temporo-parietal lobes. She had inpatient rehabilitation leading to complete recovery.

Loss of capillary pericytes and the blood-brain barrier in white matter in poststroke and vascular dementias and Alzheimer's disease.

White matter (WM) disease is associated with disruption of the gliovascular unit, which involves breach of the blood–brain barrier (BBB). We quantified pericytes as components of the gliovascular unit and assessed their status in vascular and other common dementias. Immunohistochemical and immunofluorescent methods were developed to assess the distribution and quantification of pericytes connected to the frontal lobe WM capillaries. Pericytes with a nucleus were identified by collagen 4 (COL4) and platelet‐derived growth factor receptor‐β (PDGFR‐β) antibodies with further verification using PDGFR‐β‐specific ELISA. We evaluated a total of 124 post‐mortem brains from subjects with post‐stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), AD‐VaD (Mixed) and post‐stroke non‐demented (PSND) stroke survivors as well as normal aging controls. COL4 and PDGFR‐β reactive pericytes adopted the characteristic “crescent” or nodule‐like shapes around capillary walls. We estimated densities of pericyte somata to be 225 ±38 and 200 ±13 (SEM) per COL4 mm2 area or 2.0 ± 0.1 and 1.7 ± 0.1 per mm capillary length in young and older aging controls. Remarkably, WM pericytes were reduced by ~35%–45% in the frontal lobe of PSD, VaD, Mixed and AD subjects compared to PSND and controls subjects (P < 0.001). We also found pericyte numbers were correlated with PDGFR‐β reactivity in the WM. Our results first demonstrate a reliable method to quantify COL4‐positive pericytes and then, indicate that deep WM pericytes are decreased across different dementias including PSD, VaD, Mixed and AD. Our findings suggest that downregulation of pericytes is associated with the disruption of the BBB in the deep WM in several aging‐related dementias.

Characteristics of diffusion tensor imaging of central nervous system in children with tourette's disease.

To investigate the characteristics of diffusion tensor imaging (DTI) of the central nervous system in children with Tourette syndrome (TS).Fifteen children with TS (TS group) and 15 normal children (control group) were studied, and all of them underwent DTI. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) parameters were calculated using the DTIStudio software. The region of interest was delineated manually. The ADC and FA values of the bilateral caudate nucleus, bilateral globus pallidus, bilateral putamen, bilateral thalamus, and bilateral frontal lobe white matter were measured using the region of interest editor software. The differences of FA values and ADC values between the same brain areas were compared. The associations between ADC, FA values and Yale Global Tic Severity Scale (YGTSS) scores were evaluated by Pearson correlation analyses.The FA values of left globus pallidus and left thalamus were significantly lower in the TS group than in the control group (P < .05), while the ADC values of the right caudate nucleus and bilateral thalamus were significantly higher in the TS group than in the control group (P < .05). The decrease in FA in the left thalamus significantly correlated with the YGTSS score (r = 0.692; P < .05). No correlation was found between FA and ADC values in other brain regions and the YGTSS score (P > .05).After the DTI analyses, abnormalities were found in the left globus pallidus, right caudate nucleus, and bilateral thalamus in children with TS. Especially the changes in the left thalamus structure was crucial in the pathophysiological clock of TS.

Role of T1 mapping to evaluate brain aging in a healthy population

PurposeTo investigate the relationship between healthy brain aging and T1 relaxation time obtained by T1 mapping. Materials and methodsA total of 211 (102 males, 109 females; age range: 20–89 years; mean age: 54 years) healthy volunteers underwent T1 mapping between July 2018 and January 2019. Regions of interest (ROIs) were placed on T1 maps in different anatomical regions, including the thalamus, putamen, globus pallidus, head of the caudate nucleus, nucleus accumbens, genu of the corpus callosum, and frontal lobe white matter (WM). Additionally, linear and quadratic regression analyses of ROIs were performed. ResultsThere were significant quadratic and negative linear correlations between T1 relaxation times in the thalamus, putamen, and age (p < .001). Although the nucleus accumbens did not show a significant relationship between T1 relaxation times and age by linear regression (p = .624), a statistically significant relationship was obtained by quadratic regression (p < .001). For the globus pallidus, head of the caudate nucleus, genu of the corpus callosum and frontal lobe WM the quadratic regression analysis showed a better relationship than the linear correlation analysis. ConclusionAge-related changes in T1 relaxation time vary by location in GM and WM.

Non epileptogenic Rasmussen`s encephalitis: a case report

Rasmussen's encephalitis (RE) is a very rare chronic inflammatory unilateral encephalopathy with still unknown etiology. It predominantly affects children under the age of 10, but can also affect adolescents and adults. Current evidence on possible etiologies are divided in two main theories. The first one is based on brain inflammation caused by a reaction to a foreign antigen. The second one is based on an autoimmune disease that is limited to a single hemisphere of the brain. The common presentation is intractable and frequent focal motor seizures, often associated with progressive neurological decline, and progressive unilateral focal cortical atrophy. Progression of the inflammatory process in MRI is considered a good biomarker in RE. Objectives: Report a rare case of a female infant presenting atypical manifestations of uncommon symptoms without seizures caused by Rasmussen's encephalitis. Case Report: A ten-year-old right-handed female presented to the emergency department with sudden onset of abnormal involuntary movements of the right upper and lower limbs, face paresia of the same side and loss of attention without loss of consciousness. The involuntary contractions were brief, random, irregular, and worsened with activity, along with a positive milkmaid grip sign. She also displayed reduced movement speed and hyperactive biceps, triceps, patellar and ankle jerk reflexes. Associated with the motor abnormalities, the girl presented with a recent but progressive decrease in cognitive functions, which caused a decline in school performance and impaired reasoning, and affective blunting. She had no sign of previous neuropsychomotor development abnormality. She was taken to a quaternary hospital where a MRI and a CT of the brain were performed. MRI showed atrophy of the left cerebral hemisphere, predominantly in the operculum and head of the caudate nucleus, hypersignal in the insular cortex and adjacent white matter. CT presented with hypoattenuation of the left frontal lobe and parieto-occipital white matter associated with atrophy of the head of the caudate nucleus of the same side and enlargement of the adjacent fissures and sulcus. A subsequent PET-CT showed a left cerebral hemisphere hypometabolism, predominantly in the basal ganglia, temporal, frontal and insular lobes. Functional evaluation detected diffuse unilateral disorganization of brain electric activity, but no epileptic paroxysmal discharges were found on the electroencephalogram. After hospitalization, human immunoglobulin at the dose 2g/kg/day was used for five days. The girl remained stable, with no complications. After sixteen days, she was discharged with a rehabilitation program and follow-up care.

Novel gene mutation of molybdenum cofactor deficiency

Molybdenum cofactor deficiency is a rare metabolic condition characterized by brain dysfunction (encephalopathy) that worsens over time. Molybdenum cofactor deficiency is caused by mutations in the ΜΟSC1, ΜΟSC2, or GPHN gene. There are three forms of the disorder, named types A, B, and C. The forms have the same signs and symptoms but are distinguished by their genetic cause: ΜΟSC1 gene mutations cause type A, ΜΟSC2 gene mutations cause type B, and GPHN gene mutations cause type C. Herein we are reporting a 2 months old child who presented to our hospitals with seizure disorders, post cardiac arrest. After clinical evaluation, and thorough investigations, uric acid was undetectable. MRI brain showed periventricular leukomalacia- HIE picture, with bilateral frontal lobe white matter loss with extensive cystic formation and thinning of corpus callosum. Molecular genetic testing showed pathogenic deletion c.604_624del p.( Gly202_glu208del) in exon 4 of MOCS1 gene in homozygous state. to best of our knowledge this variant was not yet reported in any literature yet.

A Cluster of Cyclic Esotropia: White Matter Changes on MRI and Surgical Outcomes.

To report a series of patients with cyclic esotropia, their surgical outcomes, and incidental findings. The medical records of five patients with cyclic esotropia presenting over 17 months were reviewed. Age at onset, ocular and motility examinations, brain magnetic resonance imaging (MRI), acetylcholine receptor antibodies, thyroid hormone levels and antibodies, calendars documenting phases, surgical treatments, postoperative alignment, and fusion were documented. Three boys and two girls presented at 3 to 4 years old in 2015-2016. Typical periodicity followed a 48-hour cycle. Duration of cycling varied from 1 to 9 weeks. Mean maximum deviation was 37 prism diopters (PD) of esotropia (range: 35 to 40 PD of esotropia). All patients had normal laboratory studies. MRIs showed an abnormal white matter signal in the frontal lobes in 2 patients and were normal in the others. Bilateral medial rectus recessions for the maximum angle were successful in 4 patients at a minimum follow-up of 13 months; the other patient required reoperation for a residual esotropia. Fusion was present in 4 patients preoperatively and all postoperatively. Stereopsis was stable or improved in all postoperatively. This is the first report of frontal white matter changes occurring in the setting of cyclic esotropia. MRI with attention to frontal lobe white matter might be considered in the work-up of cyclic esotropia to determine if this is a common finding. Bilateral medial rectus recessions can restore fusion in these patients. [J Pediatr Ophthalmol Strabismus. 2019;56(3):178-182.].

Detecting microstructural white matter abnormalities of frontal pathways in children with ADHD using advanced diffusion models.

Studies using diffusion tensor imaging (DTI) have documented alterations in the attention and executive system in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). While abnormalities in the frontal lobe have also been reported, the associated white matter fiber bundles have not been investigated comprehensively due to the complexity in tracing them through fiber crossings. Furthermore, most studies have used a non-specific DTI model to understand white matter abnormalities. We present results from a first study that uses a multi-shell diffusion MRI (dMRI) data set coupled with an advanced multi-fiber tractography algorithm to probe microstructural measures related to axonal/cellular density and volume of fronto-striato-thalamic pathways in children with ADHD (N = 30) and healthy controls (N = 28). Head motion was firstly examined as a priority in order to assure that no group difference existed. We investigated 45 different white matter fiber bundles in the brain. After correcting for multiple comparisons, we found lower axonal/cellular packing density and volume in ADHD children in 8 of the 45 fiber bundles, primarily in the right hemisphere as follows: 1) Superior longitudinal fasciculus-II (SLF-II) (right), 2) Thalamus to precentral gyrus (right), 3) Thalamus to superior-frontal gyrus (right), 4) Caudate to medial orbitofrontal gyrus (right), 5) Caudate to precentral gyrus (right), 6) Thalamus to paracentral gyrus (left), 7) Caudate to caudal middlefrontal gyrus (left), and 8) Cingulum (bilateral). Our results demonstrate reduced axonal/cellular density and volume in certain frontal lobe white matter fiber tracts, which sub-serve the attention function and executive control systems. Further, our work shows specific microstructural abnormalities in the striato-thalamo-cortical connections, which have not been previously reported in children with ADHD.

White matter capillaries in vascular and neurodegenerative dementias

Previous studies suggest white matter (WM) integrity is vulnerable to chronic hypoperfusion during brain ageing. We assessed ~ 0.7 million capillary profiles in the frontal lobe WM across several dementias comprising Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease with dementia, vascular dementia, mixed dementias, post-stroke dementia as well as post-stroke no dementia and similar age ageing and young controls without significant brain pathology. Standard histopathological methods were used to determine microvascular pathology and capillary width and densities in 153 subjects using markers of the basement membrane (collagen IV; COL4) and endothelium (glucose transporter-1; GLUT-1). Variable microvascular pathology including coiled, tortuous, collapsed and degenerated capillaries as well as occasional microaneurysms was present in all dementias. As expected, WM microvascular densities were 20–49% lower than in the overlying cortex. This differential in density between WM and cortex was clearly demonstrated by COL4, which was highly correlated with GLUT-1 densities (Spearman’s rho = 0.79, P = 0.000). WM COL4 immunopositive microvascular densities were decreased by ~ 18% across the neurodegenerative dementias. However, we found WM COL4 densities were increased by ~ 57% in post-stroke dementia versus ageing and young controls and other dementias. Using three different methods to measure capillary diameters, we found WM capillaries to be significantly wider by 19–45% compared to those in overlying neocortex apparent with both COL4 and GLUT-1. Remarkably, WM capillary widths were increased by ~ 20% across all dementias compared to ageing and young controls (P < 0.01). We also noted mean WM pathology scores incorporating myelin loss, arteriolosclerosis and perivascular spacing were correlated with COL4 immunopositive capillary widths (Pearson’s r = 0.71, P = 0.032). Our key finding indicates that WM capillaries are wider compared to those in the overlying neocortex in controls but they dilate further during dementia pathogenesis. We suggest capillaries undergo restructuring in the deep WM in different dementias. This reflects compensatory changes to retain WM perfusion and integrity during hypoperfusive states in ageing-related dementias.

Identifying early diffusion imaging biomarkers of regional white matter injury as indicators of executive function decline following brain radiotherapy: A prospective clinical trial in primary brain tumor patients

Background and purposeExecutive function (EF) decline is common after brain radiation therapy (RT), yet the etiology is unclear. We analyzed the association between longitudinal changes in frontal lobe white matter microstructure and decline in EF following RT in brain tumor patients on a prospective clinical trial. Materials and methodsDiffusion tensor imaging was obtained on 22 patients with brain tumors prior to RT, as well as 3- and 6-months post-RT, in a prospective, observational trial. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated within the superficial white matter (SWM) of the anterior cingulate (AC) and dorsolateral prefrontal cortex. Measures of cognitive flexibility, verbal fluency, and verbal set-shifting were obtained pre- and post-RT. Reliable change indices were calculated to determine significant baseline to 6-month EF changes. ResultsDecreases in FA and increases in MD were observed in the caudal AC (CAC) at 3-months post-RT. CAC changes were characterized by increased RD bilaterally. From baseline to 6-months post-RT, decreased FA and increased MD and RD of the CAC was associated with decline in verbal set-shifting ability, whereas increased MD in the CAC was associated with a decline in cognitive flexibility. ConclusionWhite matter underlying the AC may be particularly vulnerable to radiation effects. Early microstructural loss within AC SWM represents an important biomarker for EF decline, and dose reduction in this region may represent a possibility for cognitive preservation for patients receiving radiotherapy.

Aberrant interhemispheric functional connectivity in first-episode, drug-naïve major depressive disorder.

Many studies have indicated that depression is associated with impairment of the topological organization of the brain functional network, which may lead to disruption of mood and cognition in depressive patients. The abnormality of homotopic connectivity provides a basis for the clinical manifestations of depression, such as emotional and cognitive disorders. Several studies have investigated the abnormal imbalance of homotopic regions between the hemispheres in depressive patients. However, the reported findings are inconsistent. Additionally, the published studies have focused on only the grey matter when investigating functional connectivity abnormalities of the bilateral cerebral hemispheres in major depressive disorder (MDD). The aim of this study is to investigate functional connectivity abnormalities of the bilateral cerebral hemispheres in patients with first-episode, drug-naïve MDD using a voxel-mirrored homotopic connectivity (VMHC) method. Based on DSM-IV diagnostic criteria, 23 first-episode, drug-naïve MDD patients were recruited, together with 20 gender- and age-matched healthy normal controls. A Philips Achieva 3.0T MRI scanner was used to acquire brain functional images at resting state as well as high-resolution structural images. The functional images were preprocessed by using Data Processing Assistant for Resting-State Functional MR Imaging toolkit and SPM8.VMHC between the bilateral hemispheres was computed and compared between the MDD and control groups. The correlation between the VMHC values of the abnormal homotopy function areas and the Hamilton Depression Rating Scale (HAMD) was evaluated in the MDD patients. Compared with the control group, the MDD patients showed significantly decreased VMHC values in the bilateral brain regions including the insular, putamen, and frontal white matter. The MDD patients did not exhibit increased VMHC values in any brain regions compared with the normal controls. In addition, a negative correlation was observed between the VMHC value in the frontal lobe white-matter and the HAMD in the MDD patients. Abnormalities in brain homotopic functional connectivity observed in this study may indicate abnormal neural circuits related to aberrant cognition and emotional processing in MDD. Although the physiological significance underlaying abnormal VMHC in white matter in the frontal lobe needs further research, our study new angle to investigate the role of white-matter abnormalities in MDD as well as other psychiatric disorders.

Differences in gray and white matter 18F-THK5351 uptake between behavioral-variant frontotemporal dementia and other dementias.

We investigated the regional distribution of 18F-THK5351 uptake in gray (GM) and white matter (WM) in patients with behavioral-variant frontotemporal dementia (bvFTD) and compared it with that in patients with Alzheimer's disease (AD) or semantic dementia (SD). 18F-THK-5351 positron emission tomography (PET), 18F-florbetaben PET, magnetic resonance imaging, and neuropsychological testing were performed in 103 subjects including 30, 24, 9, and 8 patients with mild cognitive impairment, AD, bvFTD, and SD, respectively, and 32 normal subjects. Standardized uptake value ratios (SUVRs) of 18F-THK-5351 PET images were measured from six GM and WM regions using cerebellar GM as reference. GM and WM SUVRs and WM/GM ratios, the relationship between GM SUVR and WM/GM ratio, and correlation between SUVR and cognitive function were compared. In AD, both parietal GM (p < 0.001) and WM (p < 0.001) SUVRs were higher than in bvFTD. In AD and SD, the WM/GM ratio decreased as the GM SUVR increased, regardless of lobar region. In AD, memory function correlated with parietal GM (ρ = -0.74, p < 0.001) and WM (ρ = -0.53, p < 0.001) SUVR. In SD, language function correlated with temporal GM SUVR (ρ = -0.69, p = 0.006). The frontal WM SUVR was higher in bvFTD than in AD (p = 0.003) or SD (p = 0.017). The frontal WM/GM ratio was higher in bvFTD than in AD (p < 0.001). In bvFTD, the WM/GM ratio increased more prominently than the GM SUVR only in the frontal lobe (R2 = 0.026). In bvFTD, executive function correlated with frontal WM SUVR (ρ = -0.64, p = 0.014). Frontal WM 18F-THK5351 uptake was higher in bvFTD than in other dementias. The increase in frontal WM uptake was greater than the increase in GM uptake and correlated with executive function. This suggests that frontal lobe WM 18F-THK5351 uptake reflects neuropathological differences between bvFTD and other dementias.

Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression.

Uric acid is a non-enzymatic antioxidant associated with depression. Despite its known protective role in other brain disorders, little is known about its influence on the structural characteristics of brains of patients with major depressive disorder (MDD). This study explored the association between uric acid and characteristics of white matter (WM) in patients with MDD.A total of 32 patients with MDD and 23 healthy controls (HCs) were examined. All participants were scored based on the Beck Depression Inventory and Beck Anxiety Inventory at baseline. All patients were also rated with the Hamilton Depression Rating Scale. We collected blood samples from all participants immediately after their enrollment and before the initiation of antidepressants in case of patients. Tract-based spatial statistics were used for all imaging analyses.Lower fractional anisotropy (FA) and higher radial diffusivity (RD) values were found in the MDD group than in the HC group. Voxelwise correlation analysis revealed that the serum uric acid levels positively correlated with the FA and negatively with the RD in WM regions that previously showed significant group differences in the MDD group. The correlated areas were located in the left anterior corona radiata, left frontal lobe WM, and left anterior cingulate cortex WM.The present study suggests a significant association between altered WM connectivity and serum uric acid levels in patients with MDD, possibly through demyelination.

White matter correlates of temporal discounting in older adults.

Temporal discounting, the tendency to select a smaller reward offered sooner over a larger reward offered at a later time, has been associated with a number of real-world decision-making outcomes important for health and wellbeing. Neurobiological mechanisms supporting temporal discounting have been explored among younger participants, and these have considered white matter integrity. However, the white matter correlates of temporal discounting in older adults are unclear. We hypothesized that greater temporal discounting would be associated with poorer white matter integrity measures, more specifically lower fractional anisotropy and higher trace, in older adults. Participants were 302 older persons without dementia (mean age = 81.38, mean years of education = 15.75, 75.5% female, mean MMSE = 28.29) from the Rush Memory and Aging Project, a community-based longitudinal study of aging. Temporal discounting was assessed using standard elicitation questions. White matter integrity was assessed with diffusion tensor imaging (DTI). Regression models were adjusted for the effects of age, sex, education, and white matter lesions. Secondary models further adjusted for global cognition. Results revealed significant associations between temporal discounting and white matter integrity measures (FA and trace) in bilateral frontal, frontostriatal, and temporal-parietal lobe white matter tracts, and results remained significant after further accounting for global cognition. These results suggest that temporal discounting is inversely associated with white matter integrity in old age and that this association is independent of global cognition.