大鼠大脑白质无髓神经纤维老年改变的机制探讨

目的 运用体视学方法研究大鼠大脑白质无髓神经纤维的老年性改变,探讨导致老年白质有髓神经纤维总长度降低的确切原因,并探讨性别因素在老年大脑改变中所起的作用.方法 6～8月龄Long-Evans大鼠9只和18月龄同种大鼠8只.用电镜技术及相应的体视学方法计算白质内无髓神经纤维的体积密度、长度密度和白质内无髓神经纤维的总体积和总长度.结果 雄性和雌性大鼠大脑白质无髓神经纤维总长度均无显著的老年性降低.白质内无髓神经纤维总体积在雌性组存在显著的老年性降低,从年轻组的平均32.79mm3下降到了老年组的平均18.60mm3.雄性大鼠无髓神经纤维总体积老年性降低虽无显著性,但也从年轻组的平均34.79mm3下降到老年组的平均24.02mm3.降低高达31%.年轻组与老年组的各项指标中雄性与雌性动物间均不存在显著的性差别. 结论老年大鼠大脑白质存在大直径无髓神经纤维的显著件丢失,同时存在的细小直径的有髓神经纤维脱髓鞘改变,在一定程度上掩盖了老年白质内小直径无髓神经纤维的丢失.     

大鼠大脑白质及白质内有髓神经纤维老年性改变的体视学研究

目的 探讨老年大鼠大脑白质及白质内有髓神经纤维的改变.方法 运用透射电子显微镜和体视学方法分别对年轻组和老年组Long-Evans大鼠大脑白质及其内有髓神经纤维进行定量研究.结果 老年组大鼠大脑白质总体积,有髓神经纤维总长度分别下降了24.1%和41%;老年组大鼠有髓神经纤维体积密度、髓鞘体积密度和纤维直径分别增加了30%、23.9%和31%,具有统计学意义.但是有髓神经纤维长度密度、有髓神经纤维总体积和髓鞘的总体积没有显著老年性改变.结论 正常老年大脑的萎缩主要是由白质体积的下降引起的.正常老年大脑白质的有髓神经纤维总长度显著性降低,并且主要是由于白质内细小直径的有髓神经纤维丢失所造成的.     

Stereological Methods for Estimating the Myelin Sheaths of the Myelinated Fibers in White Matter

In the present study, efficient and unbiased stereological techniques to investigate the myelin sheaths of the myelinated fibers in rat white matter were established. In the present design, four tissue blocks were obtained from the entire white matter of rat brain in a uniform, random fashion. Isotropic, uniform random (IUR) sections were ensured by the use of the isector technique. One section with the thickness of 60 nm was cut from the center of each epon block. Eight to 10 fields of vision were randomly photographed under a transmission electron microscope. The total length of the myelinated fibers and the total volume of the myelin sheaths in the white matter were the products of the length density, volume density, and the volume of the white matter obtained with the Cavalieri principle. The mean areas of the myelinated fibers profiles and myelin sheaths were estimated with the point counting technique. The inner and outer perimeters of the myelin sheaths were estimated by the use of a line grid, and the thickness of the myelin sheaths was estimated by direct orthogonal measurements in uniform, random locations. The described methods will provide very useful tools for future quantitative studies of changes in the myelin sheaths of white matter in various experimental conditions and in various neurodegenerative diseases. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

大脑白质有髓神经纤维髓鞘超微结构定量研究的体视学方法

目的:运用新的体视学方法研究大鼠白质有髓神经纤维髓鞘超微结构,以期为以后各种有关髓鞘超微结构的相关研究提供可靠的方法学依据.方法:6～8月龄雌性Long-Evans大鼠.运用电镜技术及相应的体视学方法计算白质内有髓神经纤维的总长度、有髓神经纤维髓鞘总体积、有髓神经纤维及轴突直径、髓鞘断面面积、髓鞘内外周长、髓鞘平均厚度.结果:获得了正常6～8月龄雌性Long-Evans大鼠有髓神经纤维总长度及髓鞘超微结构的各项数据,两种不同方法得到的髓鞘平均厚度并没有显著性差异.结论:把新的体视学方法和电子显微镜结合起来定量研究了大鼠大脑白质有髓神经纤维髓鞘超微结构,所描述的方法为以后进行髓鞘超微结构的定量研究提供了有用的工具.     

Demyelination Induces the Decline of the Myelinated Fiber Length in Aged Rat White Matter

To determine the exact reason for the age‐related decline of the myelinated fiber length in white matter, we performed this study. In middle‐aged rats, there was age‐related loss of the unmyelinated fibers with large diameters. The demyelination of the myelinated fibers with small diameters in middle‐aged rat white matter might make the age‐related decrease of the unmyelinated fibers with small diameters in the white matter unnoticeable. However, in old‐aged female rats, the unmyelinated fibers with large and small diameters significantly degenerated together and that the unmyelinated fibers formed from the demyelination of the myelinated fibers could not replenish the age‐related loss of the unmyelinated fibers in the white matter. In conclusion, this study suggested that demyelination of myelinated fibers with small diameters in aged white matter might be the key mechanism of the significant decline of the myelinated fiber length in aged white matter. Anat Rec, 292:528–535, 2009. © 2009 Wiley‐Liss, Inc.     

No change in total length of white matter fibers in Alzheimer's disease

White matter changes have been reported as part of Alzheimer dementia. To investigate this, the total subcortical myelinated nerve fiber length was estimated in postmortem brains from eight females (age 79-88 years) with severe Alzheimer's disease (AD) and compared with brains from 10 female control subjects (age 74-92 years). A stereological method for estimating myelinated brain fibers includes sampling systematically, randomly from the white matter, and counting fibers in unbiased counting frames using light microscopy at approximately 6000x magnification. The diameter of each counted fiber was measured to obtain the diameter distribution of myelinated fibers in both groups. The mean total myelinated fiber length was 81,554 km in the AD group and 78,896 km in the control group (P=0.63). All other measured parameters were also unaffected in the AD brains: The mean fiber length density was 248 km/cm3 in the AD group and 247 km/cm3 in the control group; the volume of white matter was 329 cm3 (AD) and 321 cm3 (control) and the volume density of myelinated fibers to white matter tissue volume was 0.30 in AD group and 0.31 in the control group. This is the first study of subcortical brain white matter fiber length using a stereological method on postmortem brains from AD patients and control subjects.     

Anatibant,a selective non-peptide bradykinin B2 receptor antagonist,reduces intracranial hypertension and histopathological damage after experimental traumatic brain injury

Bradykinin, the main metabolite of the kallikrein-kinin system and one of the first mediators released during inflammation, is well known to increase the permeability of the blood brain barrier (BBB) by activation of kinin B₂ receptors and hence promote brain edema formation following traumatic brain injury (TBI). Anatibant^® (LF 16-0687), a selective non-peptide bradykinin B₂ receptor antagonist, reduces brain edema after experimental TBI, however, so far no data are available if Anatibant^® reduces also the sequels of brain edema formation, i.e. morphological brain damage. Therefore, we investigated the effect of Anatibant (3.0 mg/kg b.w.) on intracranial pressure (ICP) and contusion volume after experimental TBI. Male C57/Bl6 mice (25–28 g) were subjected to Controlled Cortical Impact trauma (CCI). Anatibant^® was administrated as a subcutaneous bolus 15 min and 8 h after TBI. ICP was measured 3, 6, and 10 h after injury and contusion volume was quantified 24 h after trauma. Our data demonstrate a significant reduction of ICP (16.6 ± 1.67 mmHg vs. 24.40 ± 3.58 mmHg; n = 6; p = 0.002) and of contusion volume 24 h after trauma (28.28 ± 5.18 mm³ vs. 35.0 ± 3.32 mm³n = 7; p = 0.003) in treated mice. Therefore we conclude, that inhibition of bradykinin B₂ receptors seems to be a promising treatment option, and might therefore be investigated in clinical trails for the treatment of TBI.     

短期丰富生存环境对老年雄性大鼠大脑白质及白质内有髓神经纤维的影响

目的 探讨短期丰富生存环境干预对老年雄性大鼠大脑白质及白质内有髓神经纤维的影响.方法 将20只24月龄雄性SD大鼠分别在丰富生存环境条件和普通标准环境下饲养4个月后,从每组随机抽取4只大鼠,用透射电子显微镜和体视学方法比较两组大鼠大脑白质及白质内有髓神经纤维的改变. 结果 丰富生存环境组大鼠的白质总体积,白质内有髓神经纤维总长度和总体积,有髓神经纤维轴突总体积分别较标准对照组显著增大,但有髓神经纤维平均内径、外径、髓鞘总体积、髓鞘平均厚度、髓鞘平均内、外周长、有髓神经纤维断面面积、髓鞘断面面积及轴突断面面积较对照组均无明显差异. 结论 短期丰富生存环境干预对24月龄雄性大鼠的大脑白质和白质内有髓神经纤维均有明显的影响.提示短期丰富生存环境可能促使老年雄性大鼠白质内已经发生脱髓鞘改变的有髓神经纤维出现髓鞘再生.     

Excitatory actions of mushroom poison (acromelic acid) on unmyelinated muscular afferents in the rat

Ingestion of a poisonous mushroom, Clitocybe acromelalga, results in strong and long-lasting allodynia, burning pain, redness and swelling in the periphery of the body. Acromelic acid (ACRO), a kainate analogue isolated from the mushroom, is assumed to be involved in the poisoning. ACRO has two isomers, ACRO-A and ACRO-B. The potency of ACRO-A is a million times higher than that of ACRO-B for induction of allodynia when intrathecally administered in mice. The effect of ACRO on the primary afferents of somatic tissues remains largely unknown. The aim of the present study was to examine the effect of ACRO-A on the response behavior of unmyelinated afferents in the skeletal muscle. For this purpose single fiber recordings of C-afferents were made from rat extensor digitorum longus (EDL) muscle-common peroneal nerve preparations in vitro. Intramuscular injections of ACRO-A at three different concentrations (10⁻¹², 10⁻¹⁰ and 10⁻⁸ M, 5 μl over 5 s) near the receptive field in the EDL muscle elicited excitation of C-afferents (12%, 50% and 44%, respectively). ACRO-A at the concentration of 10⁻¹⁰ M induced the strongest excitation. The incidence of ACRO-A responsive fibers at the concentration of 10⁻¹⁰ and 10⁻⁸ M was significantly higher than that at 10⁻¹² M. The responses to mechanical and heat stimulations did not differ between ACRO-A sensitive and insensitive fibers. These results clearly demonstrated the powerful excitatory action of ACRO-A on mechanosensitive unmyelinated afferents in the rat skeletal muscle.     

In vivo micro-CT imaging of rat brain glioma: A comparison with 3 T MRI and histology

The aim of this study was to evaluate the potential of a novel micro-CT system to image in vivo the extent of tumor in a rat model of malignant glioma compared to 3 T magnetic resonance imaging (MRI) and histology. Fourteen animals underwent double dose contrast-enhanced imaging with micro-CT and 3 T MRI using a clinical machine at day 10 after stereotactic F98 glioma cell implantation. Calculation of the volume of the contrast-uptaking part of the tumor was done by manually outlining the tumor contours by two experienced neuroradiologists. The micro-CT- and MRI-derived tumor volumes were compared to histology as gold standard (hematoxylin and eosin staining and fluorescence staining). There was high interobserver reability regarding the tumor volumes (Crombach's α > 0.81). Also, there was good correlation of micro-CT- and high-field MRI-derived tumor volumes compared to histology: 72 ± 21 mm³ and 69 ± 23 mm³ compared to 81 ± 14 mm³, respectively (r > 0.76). Both the micro-CT- and MRI-derived tumor volumes were not significantly smaller compared to histology (P > 0.14). In conclusion, micro-CT allows in vivo imaging of the contrast-enhancing part of experimental gliomas with an accuracy comparable to high-field MRI.     

Brain atrophy and cognition: Interaction with cerebrovascular pathology?

We examined the interaction of brain atrophy and white matter lesions (WML) with cognitive functioning in 605 patients (mean age, 58 ± 10; 76% men) with atherosclerotic disease from the Second Manifestations of ARTerial disease-MR substudy (SMART-MR study). Automated brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid, and WML on MRI. Total brain, ventricular, and cortical gray matter volume were divided by intracranial volume (ICV). Neuropsychological tests assessing executive functioning and memory performance were performed and composite scores were calculated. We observed that smaller total brain volume, larger ventricular volume, and smaller cortical gray matter volume (all as % of ICV) were associated with worse executive performance and that this association became stronger with presence of brain infarcts or severe WML volume (P-values for interaction <0.05). No interaction between measures of brain volume and cerebrovascular pathology on memory performance was observed. Our findings suggest that patients with cerebrovascular pathology on MRI may be more vulnerable to impairment in executive functioning related to global as well as focal brain atrophy.     

Design-based stereological study of the guinea-pig (Cavia porcellus) cerebellum

Guinea pigs have proved useful as experimental animal models in studying cerebellar anatomical and structural alterations in human neurological disease; however, they are also currently acquiring increasing veterinary interest as companion animals. The morphometric features of the normal cerebellum in guinea pigs have not been previously investigated using stereology. The objective of the present work was to establish normal volumetric and quantitative stereological parameters for cerebellar tissues in guinea pigs, by means of unbiased design-based stereology. Cerebellar total volume, gray and white matter volume fractions, molecular and granular layers volume fractions, cerebellar surface area, Purkinje cellular and nuclear volumes, and the Purkinje cell total count were stereologically estimated. For this purpose, cerebellar hemispheres from six adult male guinea pigs were employed. Isotropic, uniform random sections were obtained by applying the orientator method, and subsequently processed for light microscopy. The cerebellar total volume, the white and grey matter volume fractions, and the molecular and granular layer volumes were estimated using the Cavalieri's principle and the point counting system. The cerebellar surface area was estimated through the use of test lines; Purkinje cellular and nuclear volumes were analysed using the nucleator technique, whereas the Purkinje cell total count was obtained by means of the optical disector technique. The mean ± standard deviation total volume of a guinea-pig cerebellar hemisphere was 0.11 ± 0.01 cm³. The mean volumetric proportions occupied by the gray and white matters were, respectively, 78.0 ± 2.6% and 22.0 ± 2.6%, whereas their mean absolute volumes were found to be 0.21 ± 0.02 cm³ and 0.059 ± 0.006 cm³. The volumes of the molecular and granular layers were estimated at 112.4 ± 20.6 mm³ and 104.4 ± 7.3 mm³, whereas their mean thicknesses were calculated to be 0.184 ± 0.020 mm and 0.17 ± 0.02 mm. The molecular and granular layers accounted for 40.7 ± 3.9% and 37.4 ± 1.8% of total cerebellar volume respectively. The surface area of the cerebellum measured 611.4 ± 96.8 mm². Purkinje cells with a cellular volume of 3210.1 µm³ and with a nuclear volume of 470.9 µm³ had a higher incidence of occurrence. The mean total number of Purkinje cells for a cerebellar hemisphere was calculated to be 253,090 ± 34,754. The morphometric data emerging from the present study provide a set of reference data which might prove valuable as basic anatomical contribution for practical applications in veterinary neurology.     

Association between symptom severity and internal capsule volume in obsessive-compulsive disorder

Neurobiological models support an involvement of white matter tracts in the pathophysiology of obsessive-compulsive disorder (OCD), but there has been little systematic evaluation of white matter volumes in OCD using magnetic resonance imaging (MRI). We investigated potential differences in the volume of the cingulum bundle (CB) and anterior limb of internal capsule (ALIC) in OCD patients (n = 19) relative to asymptomatic control subjects (n = 15). White matter volumes were assessed using a 1.5T MRI scanner. Between-group comparisons were carried out after spatial normalization and image segmentation using optimized voxel-based morphometry. Correlations between regional white matter volumes in OCD subjects and symptom severity ratings were also investigated. We found significant global white matter reductions in OCD patients compared to control subjects. The voxel-based search for regional abnormalities (with covariance for total white matter volumes) showed no specific white matter volume deficits in brain portions predicted a priori to be affected in OCD (CB and ALIC). However, large clusters of significant positive correlation with OCD severity scores were found bilaterally on the ALIC. These findings provide evidence of OCD-related ALIC abnormalities and suggest a connectivity dysfunction within frontal-striatal-thalamic-cortical circuits. Further studies are warranted to better define the role of such white matter alterations in the pathophysiology of OCD, and may provide clues for a more effectively targeting of neurosurgical treatments for OCD.     

Brain tissue phantoms for optical near infrared imaging

In this study, solid, stable, and cost-effective optical phantoms of scalp–skull, white matter and grey matter are developed by inverse method. To begin with, to obtain a range of optical parameters, absorption and reduced scattering coefficients (μ_a and respectively), 20 homogeneous phantoms were made of paraffin wax by using optically contrast black and highly scattering white colouring materials in different combination. By comparing the measured reflectance values for each phantom got from the four channel reflectometer with that obtained from steady-state diffusion equation, the values of μ_a and were determined. Next, phantoms which exhibit specific optical properties of scalp–skull, white and grey matter are developed iteratively by comparing actual reflectance measurements got by adjusting the colour concentration with the predicted reflectance values from the diffusion equation. This is done as follows: to obtain μ_a of 0.04 mm⁻¹ for scalp–skull, 9.5 mg of black dye per 100 ml of wax added since more attenuation of light occurs in bone tissue. To obtain a 6.0 mm⁻¹ for white matter in brain tissue, 190 mg of white dye per 100 ml of wax was used to facilitate more scatter of light. The colour concentrations of phantoms were then adjusted to obtain the predetermined values of optical parameters for scalp–skull, grey and white matter.     

G-CSF enhances stem cell proliferation in rat hippocampus after transient middle cerebral artery occlusion

Granulocyte colony-stimulating factor (G-CSF) enhances the survival and stimulates the proliferation of neutrophil progenitors. Recently, the neurogenerative effect of G-CSF has been intensely investigated. In this study, we explored the possibility that G-CSF enhanced the cell proliferation in the rat dentate gyrus (DG) after focal cerebral ischemia, using a rat transient middle cerebral artery occlusion (tMCAO) model. At 7 days after tMCAO, the number of 5-bromodeoxyuridine (BrdU)-positive cells in the G-CSF-treated group was significantly increased compared with that in the vehicle-treated group in the ipsilateral SGZ (16.6 ± 5.5/mm² in the vehicle-treated group versus 33.0 ± 7.2/mm² in the G-CSF-treated group, **p < 0.01) and in the ipsilateral GCL (14.2 ± 2.8/mm² in the vehicle-treated group versus 21.0 ± 3.8/mm² in the G-CSF-treated group, *p < 0.05). This result showed the possibility of a neurogenerative role of G-CSF after tMCAO in rats.     

Uridine 5′-triphosphate (UTP) protects against cerebral ischemia reperfusion injury in rats

Aims: To test the hypothesis that uridine 5′-triphosphate (UTP) had a protective effect on cerebral ischemia reperfusion (IR) injury in rats. Methods: Ischemia was induced by intraluminal suture of middle cerebral artery occlusion (MCAO). UTP solution was delivered through an indwelling tail venous catheter via microinfusion pump 30 min after the occlusion of MCA at a rate of 0.5 ml/100 g/min. Neurological deficit score (NDS) and brain water content were determined 24 h after reperfusion. Infarct volume was determined by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and magnetic resonance imaging (MRI), and nerve cell death was studied under an electron microscope. Results: There was a dose-dependent relationship among 10, 30 and 90 μg/kg UTP. The 90 μg/kg UTP had the best protective effect among the 3 groups. We compared 90 μg/kg UTP group with normal saline group and found that UTP had a protective effect on cerebral IR by the results of TTC staining (15.9% vs 30.5%, P < 0.01). MRI at 6, 30 and 54 h after reperfusion showed smaller infarct volume in 90 μg/kg group compared with 0 μg/kg group (283.5, 352.1, 367.45 mm³ vs 401.36, 576.75 and 677.11 mm³, respectively), and electron microscope showed less nerve cell death in 90 μg/kg group compared with 0 μg/kg group. Conclusion: UTP has a dose-dependent protective effect on cerebral IR.     

Side differences of the age-related changes in the white matter and the myelinated nerve fibers in the white matter of female rats

The present study tested if there were side differences of the white matter and the myelinated fibers in the white matter of female rats, and if there were side differences in the age-related changes of the white matter and the myelinated fibers in the white matter of female rats. Five young, five middle-aged and five aged female Long-Evans rats were quantitatively investigated using electron microscopic technique and stereological methods. We found no side differences of the white matter volume, the total volume, total length and mean diameter of the myelinated fibers in the white matter of young, middle-aged, and aged female rats. When compared to middle-aged female rats, the total length of the myelinated fibers in the white matter of the left hemisphere in aged female rats was decreased significantly, but the total length of the myelinated fibers in the white matter of the right hemisphere in aged female rats was non-significantly decreased. Our data indicated that there were no significant side differences in the white matter and the myelinated fibers in the white matter in young, middle-aged, and aged female rats. However, we demonstrated that the aged-related changes of the myelinated fibers in the white matter of the left hemisphere and right hemisphere were different. The results obtained in the present study will provide biological basis for the understanding of the asymmetry of cerebral functions.     

Direct quantitative estimation of Paneth and total cell populations in the jejunal glands of Lieberkühn

Direct morphometric estimation of the number of intestinal crypts per 10 mm length of jejunum, the total number of cells per crypt, and the number of Paneth cells per crypt was performed using Zenker-fixed, serially sectioned small intestines from adult BALB/c mice. The mean volume of a crypt cell was estimated to be in the order of 6.6 ± 0.1 × 10^?4 mm³, while the total volume of all cells in a single crypt was 1.833 ± 0.02 × 10^?1 mm³. The cell population per crypt was 278 ± 7 cells, of which 44 ± 10 were Paneth cells. It was estimated further that 265 ± 30 crypts per 10 mm length of jejunum contained 7.4 ± 0.1 × 10⁴ cells, including 1.2 ± 0.24 × 10³ Paneth cells. The volume of all crypt and Paneth cells per 10 mm length of jejunum was in the order of 49 ± 1.2 and 8 ± 1.8 mm³, respectively. The volume of the tunica muscularis and the surface area of the crypt's lumina were estimated to be 33.5 ± 2.2 mm³ and 118 ± 19 mm², respectively.     

雄性大鼠大脑半球白质及其内有髓神经纤维老年改变的侧别差异

目的 探讨雄性大鼠左右大脑半球白质及其内有髓神经纤维是否存在显著性差异,以及每侧大脑半球白质及其内有髓神经纤维的老年性改变是否一致.方法运用透射电子显微镜和体视学方法分别对5只年轻(6～8月龄)和4只老年(18月龄)雄性Long-Evans大鼠左侧、右侧大脑半球白质体积及白质内有髓神经纤维体积、长度和直径进行定量研究.结果年轻组大鼠和老年组大鼠左右大脑半球白质体积及白质内有髓神经纤维体积、长度和直径均不存在显著性差异.每侧大脑半球白质及其内有髓神经纤维总长度和总体积均随年龄增加而降低,右侧半球白质体积、右侧半球白质内有髓神经纤维总体积和左侧半球白质内有髓神经纤维总长度随年龄增长分别显著性降低32.9%、28.6%和49.3%.结论正常年轻和老年雄性Tong-Evans大鼠两侧大脑半球的白质及其内有髓神经纤维均不存在显著性侧别差异.老年雄性Long-Evans大鼠右侧大脑半球白质体积、右侧大脑半球白质内有髓神经纤维的总体积和左侧大脑半球白质内有髓神经纤维总长度存在显著老年性改变.     

Diffusion tensor imaging in studying white matter complexity: A gap junction hypothesis

The role of the prefrontal cortex as an executive oversight of posterior brain regions raises the question of the extent to which the anterior regions of the brain interconnect with the posterior regions. The aim of this study is to test the complexity of rostral white matter tracts, which connect anterior and posterior brain regions, in comparison to caudal white matter tracts and the corpus callosum. Diffusion tensor imaging (DTI) is a modality that measures fractional anisotropy (FA). Higher white matter complexity could result in a decrease of FA, possibly through denser intersection of fiber tracts. DTI was used to determine regional FA in 9 healthy bonnet macaques (Macaca radiata). Four regions of interest were included: anterior and posterior limbs of the internal capsule, the occipital lobe white matter, and the corpus callosum. FA of the anterior limbs of the internal capsule was lowest compared to all other regions of interest (Newman–Keuls (N–K); p < 0.0001), whereas FA of the corpus callosum was highest (N–K; p < 0.0001). The posterior limbs of the internal capsule and the occipital white matter were not distinguishable but exhibited intermediate FA in comparison to the former (N–K; p < 0.0001) and the latter (N–K; p < 0.0001). The current study demonstrates that FA, a measure of white matter complexity, can vary markedly as a function of region of interest. Moreover, validation of these findings using neurohistological studies and replication in human samples appears warranted.