A diffusion tensor imaging white matter atlas of the domestic canine brain.

There is increasing reliance on magnetic resonance imaging (MRI) techniques in both research and clinical settings. However, few standardized methods exist to permit comparative studies of brain pathology and function. To help facilitate these studies, we have created a detailed, MRI-based white matter atlas of the canine brain using diffusion tensor imaging. This technique, which relies on the movement properties of water, permits the creation of a three-dimensional diffusivity map of white matter brain regions that can be used to predict major axonal tracts. To generate an atlas of white matter tracts, thirty neurologically and clinically normal dogs underwent MRI imaging under anesthesia. High-resolution, three-dimensional T1-weighted sequences were collected and averaged to create a population average template. Diffusion-weighted imaging sequences were collected and used to generate diffusivity maps, which were then registered to the T1-weighted template. Using these diffusivity maps, individual white matter tracts-including association, projection, commissural, brainstem, olfactory, and cerebellar tracts-were identified with reference to previous canine brain atlas sources. To enable the use of this atlas, we created downloadable overlay files for each white matter tract identified using manual segmentation software. In addition, using diffusion tensor imaging tractography, we created tract files to delineate major projection pathways. This comprehensive white matter atlas serves as a standard reference to aid in the interpretation of quantitative changes in brain structure and function in clinical and research settings.

Variability of Intraoperative Electrostimulation Parameters in Conscious Individuals: Language Fasciculi.

OBJECTIVE: The authors analyzed the current-intensity thresholds for electrostimulation of language fasciculi and the possible consequences of threshold variability on brain mapping. METHODS: A prospective protocol of subcortical electrostimulation was used in 50 patients undergoing brain mapping, directly stimulating presumed language fasciculi identified by diffusion tensor imaging. RESULTS: The stimulation-intensity thresholds for identification of language fasciculi varied among patients (mean minimum current intensity of 4.4 mA, range = 1.5-10 mA, standard deviation = 1.1 mA), and 23% of fascicular interferences were detected only above 5 mA. Repeated stimulation of the same site with the same intensity led to different types of interferences in 20% of patients, and a higher current intensity led to changes in the type of response in 27%. The mean minimum stimulation intensities did not differ significantly between different fasciculi, between the different types of interference obtained, or with age, sex, or type of tumor. Positive results on cortical mapping were significantly associated with positive results on subcortical mapping (P < 0.001). Subcortical intensity thresholds were slightly lower than cortical ones (mean = 4.43 vs. 5.25 mA, P = 0.034). In 23 of 50 subcortical mappings, fascicular stimulation produced no language interference. CONCLUSIONS: Individual variability of minimum stimulation-intensity thresholds for identification of language fasciculi is frequent. Nevertheless, even when a high current intensity was used, many stimulations on language fasciculi remained negative for various hypothetic reasons. Finding the optimal current intensity for identifying language fasciculi is of paramount importance to refine the clinical results and scientific data derived from brain mapping.

Left and Right Arcuate Fasciculi Are Uniquely Related to Word Reading Skills in Chinese-English Bilingual Children.

Whether reading in different writing systems recruits language-unique or language-universal neural processes is a long-standing debate. Many studies have shown the left arcuate fasciculus (AF) to be involved in phonological and reading processes. In contrast, little is known about the role of the right AF in reading, but some have suggested that it may play a role in visual spatial aspects of reading or the prosodic components of language. The right AF may be more important for reading in Chinese due to its logographic and tonal properties, but this hypothesis has yet to be tested. We recruited a group of Chinese-English bilingual children (8.2 to 12.0 years old) to explore the common and unique relation of reading skill in English and Chinese to fractional anisotropy (FA) in the bilateral AF. We found that both English and Chinese reading skills were positively correlated with FA in the rostral part of the left AF-direct segment. Additionally, English reading skill was positively correlated with FA in the caudal part of the left AF-direct segment, which was also positively correlated with phonological awareness. In contrast, Chinese reading skill was positively correlated with FA in certain segments of the right AF, which was positively correlated with visual spatial ability, but not tone discrimination ability. Our results suggest that there are language universal substrates of reading across languages, but that certain left AF nodes support phonological mechanisms important for reading in English, whereas certain right AF nodes support visual spatial mechanisms important for reading in Chinese.

Axonal quantification of the white matter association fasciculi in cerebral hemispheres of cow (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus).

BACKGROUND: Cerebral white matter consists mainly of axons surrounded by myelin sheaths, which are grouped to form association, commissural, and projection fasciculi. The aim of our work was to quantify and compare under the microscope the axons of the white matter association fasciculi in the cerebral hemispheres of cow (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus) indirectly by identification of their myelin sheaths. MATERIALS AND METHODS: The samples were taken from 30 cerebral hemispheres: 10 cow, 10 pig and 10 rabbit (15 right and 15 left). They were obtained following a protocol based on the Talairach-Tournoux coordinate system for human and primate brains. The slides were stained with Luxol Fast Blue, observed by optical microscopy, and photographed at 600×. Samples were also prepared for observation in scanning transmission electron microscopy with osmium tetroxide. The myelin sheaths/axons were counted with the ImageJ software. RESULTS: Statistically significant differences in the number of myelin sheaths per 410 µm² were found in the inferior and superior longitudinal fasciculi between the left and right hemispheres of cows, with predominance of the right hemisphere; and in the inferior occipitofrontal fasciculus of the rabbit with predominance of the left hemisphere. CONCLUSIONS: The use of animal models for experiments in the cerebral fasciculi, especially pig, could give us a greater understanding of the behaviour of demyelinating and neurodegenerative diseases in humans.

Intrinsic Well-Demarcated Midline Brainstem Lesion Successfully Resected through a Midline Pontine Splitting Approach.

INTRODUCTION: Surgical approaches to intrinsic pontine lesions are technically difficult and prone to complications. The surgical approach to the brainstem through midline pontine splitting is regarded as safe since there are no crossing vital fibers in the midline between the abducens nuclei at the facial colliculi in the pons and the oculomotor nucleus in the midbrain, although its actual utilization has not been reported previously. CASE PRESENTATION: A 6-year-old boy presented with a large intrinsic cystic lesion in the pons. We successfully achieved gross total removal via the median sulcus of the fourth ventricle. The fixation in adduction and limitation of abduction were newly observed in the left eye after surgery. DISCUSSION: The advantage of the surgical approach through the median sulcus is the longer line of dissection in an axial direction and the gain of a wider operative view. On the other hand, the disadvantage of this approach is the limited orientation and view toward lateral side and a possible impairment of the medial longitudinal fasciculi and paramedian pontine reticular formation, which are located lateral to the midline sulcus bilaterally and are easily affected via the median sulcus of the fourth ventricular floor. Ongoing developments in intraoperative neuro-monitoring and navigation systems are expected to enhance this promising approach, resulting in a safer and less complicated procedure in the future. CONCLUSION: The surgical approach through midline pontine splitting is suitable for midline and deep locations of relatively large pontine lesions that necessitate a wider surgical window.

Dissection of white matter association fasciculi in bovine (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus) brains.

The cerebral fasciculi (association, commissural and projection) pass through the cerebral white matter in organized groups connecting regions, hemispheres, gyri, areas and brain lobes to each other. The study can be done in vivo through diffusion tensor imaging (DTI) but presenting some technical problems. The post-mortem study by dissection allows to have a clearer view of its location, path and connections. In this work, we dissect, identify and compare the fasciculi of association of the white matter of the dorsolateral face of bovine hemispheres (Bos taurus), pig hemispheres (Sus scrofa domesticus) and rabbit hemispheres (Oryctolagus cuniculus), applying the Klingler´s technique. In 30 cerebral hemispheres (10 of each species, five right and five left), we applied the Klingler technique to identify and isolate the occipitofrontal fasciculus, uncinate fasciculus, inferior longitudinal fasciculus and superior longitudinal fasciculus; we established its location by fixing landmarks, and determined the difference in its length and width between the right and left hemispheres as well as between species using the statistical tests of t-student and one-way ANOVA. We identify the gyri, sulci and fasciculi of the dorsolateral surface of the cerebral hemispheres of the three species. We found statistically significant differences in several fasciculi between species principally in the occipitofrontal fasciculus. The preparation of the brains through the modified Klingler technique allowed a successful identification of the fascicules of association of the dorsolateral face of the cerebral hemispheres and the empowerment of these animal models for future research work in this field.

Long-Term Results of Deep Brain Stimulation of the Mamillotegmental Fasciculus in Chronic Cluster Headache.

BACKGROUND: Deep brain stimulation (DBS) and the proper target for chronic cluster headache (CCH) are still subjects of controversy. OBJECTIVES: We present our long-term results of analysis of the target and its structural connectivity. METHODS: Fifteen patients with drug-resistant CCH underwent DBS in coordinates 4 mm lateral to the III ventricular wall and 2 mm behind and 5 mm below the intercommissural point. The clinical parameters recorded were the number of weekly attacks, pain intensity, and duration of the headache. Structural connectivity was studied using 3-T MR diffusion tensor imaging (DTI). RESULTS: All of our patients improved from a mean of 39 attacks/week to 2; pain intensity decreased from 9 to 3 out of 10, and the mean cephalalgia duration decreased from 53 to 8 min. The mean stereotactic coordinates of the effective contact location were 6.1 mm lateral to the midcommissural point and 1.2 mm behind and 4.0 mm below the intercommissural point. DTI analysis showed that this target was connected to tracts and nuclei of the posterior mesencephalic tegmentum, specifically the dorsal longitudinal and mamillotegmental fasciculi. CONCLUSIONS: Our data showed DBS to be a safe and useful procedure for the treatment of drug-resistant CCH; the rate of improvement was higher than those found in other series. Although these are promising results, larger series targeting those fasciculi with a longer follow-up are needed.

Atlasing the frontal lobe connections and their variability due to age and education: a spherical deconvolution tractography study.

In neuroscience, there is a growing consensus that higher cognitive functions may be supported by distributed networks involving different cerebral regions, rather than by single brain areas. Communication within these networks is mediated by white matter tracts and is particularly prominent in the frontal lobes for the control and integration of information. However, the detailed mapping of frontal connections remains incomplete, albeit crucial to an increased understanding of these cognitive functions. Based on 47 high-resolution diffusion-weighted imaging datasets (age range 22-71 years), we built a statistical normative atlas of the frontal lobe connections in stereotaxic space, using state-of-the-art spherical deconvolution tractography. We dissected 55 tracts including U-shaped fibers. We further characterized these tracts by measuring their correlation with age and education level. We reported age-related differences in the microstructural organization of several, specific frontal fiber tracts, but found no correlation with education level. Future voxel-based analyses, such as voxel-based morphometry or tract-based spatial statistics studies, may benefit from our atlas by identifying the tracts and networks involved in frontal functions. Our atlas will also build the capacity of clinicians to further understand the mechanisms involved in brain recovery and plasticity, as well as assist clinicians in the diagnosis of disconnection or abnormality within specific tracts of individual patients with various brain diseases.

Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults.

The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. NTRK3 variants are putative risk factors for schizophrenia, bipolar disorder, and obsessive-compulsive disorder hoarding, suggesting that some NTRK3 variants may affect the brain. To test this, we scanned 392 healthy adult twins and their siblings (mean age, 23.6 ± 2.2 years; range: 20-29 years) with 105-gradient 4-Tesla diffusion tensor imaging (DTI). We identified 18 single nucleotide polymorphisms (SNPs) in the NTRK3 gene that have been associated with neuropsychiatric disorders. We used a multi-SNP model, adjusting for family relatedness, age, and sex, to relate these variants to voxelwise fractional anisotropy (FA) - a DTI measure of white matter integrity. FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders.

White matter integrity affected by depressive symptoms in migraine without aura: a tract-based spatial statistics study.

Previous studies have proven that migraine and depression are bidirectionally linked. However, few studies have investigated white matter (WM) integrity affected by depressive symptoms in patients suffering from migraine without aura (MWoA). Forty patients with MWoA were divided into two groups according to their self-rating depression scale (SDS) score in the present study, including 20 in the SDS (+) (SDS > 49) group and 20 in the SDS (-) (SDS ≤ 49) group. Forty healthy participants were also recruited as the control group. Tract-based spatial statistics analyses with multiple diffusion tensor imaging-derived indices [fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)] were employed collectively to investigate WM integrity between all patients with MWoA and all healthy controls, between each subgroup (SDS (-) group and SDS (+) group) and healthy controls, and between the SDS (-) and SDS (+) groups. Compared with healthy controls, decreased AD was shown in several WM tracts of the whole MWoA group, SDS (-) group and SDS (+) group. In addition, compared with the SDS (-) group, the SDS (+) group showed decreased FA and increased MD and RD, with conserved AD, including the genu, body and splenium of the corpus callosum, bilateral superior longitudinal fasciculi, the right anterior corona radiata and some other WM tracts, similar to previous findings in depression disorder. Furthermore, mean FA and RD in some of the above-mentioned WM tracts in the SDS (+) group were correlated significantly with SDS scores, including the genu and splenium of the corpus callosum, the right anterior corona radiata and the superior longitudinal fasciculi. Our results suggest that WM integrity may be affected by both depression symptoms (more sensitive as RD) and migraine (more sensitive as AD). The findings may serve as a sensitive biomarker of depression severity in MWoA.