A comparative study of bone marrow mesenchymal stem cell functionality in C57BL and mdx mice

Abnormalities of the white matter (WM) tracts integrity in brain areas involved in emotional regulation have been postulated in major depressive disorder (MDD). However, there is no diffusion tensor imaging (DTI) study in patients with treatment-responsive MDD at present. DTI scans were performed on 22 patients with treatment-responsive MDD and 19 well-matched healthy subjects. Tract-based spatial statistics (TBSS) approach was employed to analyze the scans. Voxel-wise statistics revealed four brain WM tracts with lower fractional anisotropy (FA) in patients compared to healthy subjects: the bilateral internal capsule, the genu of corpus callosum, the bilateral anterior corona radiata, and the right external capsule. FA values were nowhere higher in patients compared to healthy subjects. Our findings demonstrate that the abnormalities of the WM tracts, major in the projection fibers and corpus callosum, may contribute to the pathogenesis of treatment-responsive MDD.     

Diffusion tensor imaging of two unrelated Chinese men with hereditary spastic paraplegia associated with thin corpus callosum

Hereditary spastic paraplegia (HSP) associated with thin corpus callosum is a rare autosomal recessive neurodegenerative disorder characterized by an abnormally thin corpus callosum, normal motor development, slowly progressive spastic paraparesis and cognitive deterioration. To investigate and localize abnormalities in the brains of two Chinese patients with HSP-TCC, with mutations in the spatacsin gene. Diffusion tensor imaging (DTI) was used to determine the mean diffusion (MD) and fractional anisotropy (FA) in the brains of the patients in comparison to 20 healthy subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values were performed using statistical parametric mapping (SPM). Significant changes with MD increase and FA reduction were found in the already known lesions including the corpus callosum, cerebellum and thalamus. In addition, changes were also found in regions that appear to be normal in conventional MRI, such as the brain stem, internal capsule, cingulum and subcortical white matter including superior longitudinal fascicle and inferior longitudinal fascicle. Neither increase in FA nor reduction in MD was detected in the brain. Our study provides clear in vivo MR imaging evidence of a more widespread brain involvement of HSP-TCC. MD is more sensitive than FA in detecting lesions in thalamus and subcortical white matter, suggesting that MD may be a better marker of the disease progression.     

Diffusion tensor imaging and Tract-Based Spatial Statistics in Alzheimer's disease and mild cognitive impairment

We aimed to explore the changes in fractional anisotropy (FA) in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by analyzing diffusion tensor imaging (DTI) data using the Tract-Based Spatial Statistics (TBSS). DTI data were collected from 17 AD patients, 27 MCI subjects and 19 healthy controls. Voxel-based analysis with TBSS was used to compare FA among the three groups. Additionally, guided by TBSS findings, a region of interest (ROI)-based analysis along the TBSS skeleton was performed on group-level and the accuracy of the method was assessed by the back-projection of ROIs to the native space FA. Neurofiber tracts with decreased FA included: the parahippocampal white matter, cingulum, uncinate fasciculus, inferior and superior longitudinal fasciculus, corpus callosum, fornix, tracts in brain stem, and cerebellar tracts. Quantitative ROI-analysis further demonstrated the significant decrease on FA values in AD patients relative to controls whereas FA values of MCI patients were found in between the controls and AD patients. We conclude that TBSS is a promising method in examining the degeneration of neurofiber tracts in MCI and AD patients.     

基于不同FA模板的全脑体素分析方法可靠性的研究

比较基于两种不同FA模板的全脑体素分析(VBA)方法的结果,了解该方法的可靠性,以期为脑白质的功能研究和相关疾病的诊治提供基础信息。选择27例健康成年志愿者,分为青年组(14例)和老年组(13例),行磁共振弥散张量成像扫描。首先使用DTIStudio软件对图像进行自动配准和张量计算,获取部分各向异性(FA)图,然后利用统计参数图(SPM8)软件对FA图进行配准、归一化、平滑等预处理,最后分别基于SPM8软件下产生的专用FA模板和本实验室自主开发的正常中国人FA模板,对两组间的脑白质FA值进行全脑体素分析比较。以纤维束示踪的空间统计学(TBSS)方法和相关文献结果为标准,对以上比较结果进行验证。在基于SPM8产生的专用FA模板下,与青年组对比,老年组的双侧内囊前、后肢,左外囊,左额上回,左枕叶,右放射冠,右大脑脚底,右额中、下回,右小脑中脚的FA值显著下降(P<0.05,簇错误率校正);在基于正常中国人FA模板下,老年组的左内囊后肢,左外囊,左额上回,左颞中回,左枕叶,右放射冠,右内囊前、后肢,右大脑脚底,右额中、下回和胼胝体膝部的FA值相对于青年组显著下降(P<0.05,簇错误率校正);两种模板结果的不一致区域共有4个,即:左内囊前肢、右小脑中脚和左颞中回、胼胝体膝部,前两个区域出现在第一个模板中,后两个区域出现在第二个模板中,根据TBSS方法的激活区结果可得出左内囊前肢、右小脑中脚是假阳性,TBSS方法和相关文献结果支持第二个模板的结论。在采用VBA方法对脑白质进行分析时,基于正常中国人FA模板有助于提高结果的客观性和可靠性。     

Diffusional kurtosis imaging and white matter microstructure modeling in a clinical study of major depressive disorder

Major depressive disorder (MDD) is a globally prevalent psychiatric disorder that results from disruption of multiple neural circuits involved in emotional regulation. Although previous studies using diffusion tensor imaging (DTI) found smaller values of fractional anisotropy (FA) in the white matter, predominantly in the frontal lobe, of patients with MDD, studies using diffusion kurtosis imaging (DKI) are scarce. Here, we used DKI whole‐brain analysis with tract‐based spatial statistics (TBSS) to investigate the brain microstructural abnormalities in MDD. Twenty‐six patients with MDD and 42 age‐ and sex‐matched control subjects were enrolled. To investigate the microstructural pathology underlying the observations in DKI, a compartment model analysis was conducted focusing on the corpus callosum. In TBSS, the patients with MDD showed significantly smaller values of FA in the genu and frontal portion of the body of the corpus callosum. The patients also had smaller values of mean kurtosis (MK) and radial kurtosis (RK), but MK and RK abnormalities were distributed more widely compared with FA, predominantly in the frontal lobe but also in the parietal, occipital, and temporal lobes. Within the callosum, the regions with smaller MK and RK were located more posteriorly than the region with smaller FA. Model analysis suggested significantly smaller values of intra‐neurite signal fraction in the body of the callosum and greater fiber dispersion in the genu, which were compatible with the existing literature of white matter pathology in MDD. Our results show that DKI is capable of demonstrating microstructural alterations in the brains of patients with MDD that cannot be fully depicted by conventional DTI. Though the issues of model validation and parameter estimation still remain, it is suggested that diffusion MRI combined with a biophysical model is a promising approach for investigation of the pathophysiology of MDD.     

Efferent fiber projections of the habenula and the interpeduncular nucleus. An experimental study in the opossum and cat

Summary A study of efferent fiber connections of the habenula and the inter-peduncular nucleus was conducted using anterograde degeneration techniques. Lesions were placed in the habenula of the opossum and the habenula and interpeduncular nucleus of the cat. Degeneration was studied by means of the Nauta and Fink-Heimer techniques.Fibers from the habenular nucleus of the opossum extended caudally and were traced bilaterally to the interpeduncular nucleus, dorsal tegmental nucleus of Gudden, deep (ventral) tegmental nucleus of Gudden, nucleus centralis superior and nucleus reticularis tegmenti pontis. Rostrally fibers were traced to the preoptic and septal region and the anterior and lateral hypothalamus.The medial and lateral habenular nuclei of the cat projected differentially to portions of the interpeduncular nucleus and the tegmental nuclei of Gudden. The medial habenular nucleus sent fibers to the paramedian subnucleus of the interpeduncular nucleus and to the deep tegmental nucleus; whereas the lateral habenular nucleus distributed to the apical and central subnuclei of the interpeduncular nucleus and the dorsal tegmental nucleus.Fibers from both the medial and lateral habenular nuclei were found to project bilaterally to the nucleus paraventricularis anterior, nucleus ventralis anterior, anterior medialis and anterior dorsalis of the thalamus, and the septal area.Fibers from the interpeduncular nucleus of the cat were represented bilaterally. Those passing rostral went to the lateral habenular nucleus, nucleus centromedianus and parafascicularis of the thalamus, and to the septal area. Those directed caudally projected to the nucleus centralis superior, and the dorsal and deep tegmental nucleus of Gudden.Abbreviations AC anterior commissure - AD nucleus anterior dorsalis - AM nucleus anterior medialis - AV nucleus anterior ventralis - BC brachium conjunctivum - CC corpus callosum - CD caudate nucleus - CI internal capsule - CL nucleus centralis lateralis - CM nucleus centromedianus - CP cerebral peduncle - DT dorsal tegmental nucleus (of Gudden) - EN entopeduncular nucleus - Fx fornix - GC central gray - GL lateral geniculate nucleus - GM medial geniculate nucleus - GP globus pallidus - HbPt habenulopeduncular tract - HVM ventromedial hypothalamic nucleus - IC inferior colliculus - IP interpeduncular nucleus - LHb lateral habenular nucleus - LL lateral lemniscus - LMN lateral mammillary nucleus - LP nucleus lateralis posterior - MD nucleus medialis dorsalis - MHb medial habenular nucleus - ML medial lemniscus - MMN medial mammillary nucleus - MP mammillary peduncle - NCM nucleus centralis medialis - OC optic chiasm - OT optic tract - Pf nucleus parafascicularis - Pul pulvinar - PUT putamen - RE nucleus reuniens - RN red nucleus - RPO preoptic area - RTP nucleus reticularis tegmenti pontisv (von Bechterew) - S stria medullaris - SC superior colliculus - SN substantia nigra - SPT septal area - VA nucleus ventralis anterior - VL nucleus ventralis lateralis - VM nucleus ventralis medialis - VPL nucleus ventralis posterolateralis - VPM nucleus ventralis posteromedialis - VT deep tegmental nucleus (of Gudden) - II optic nerve     

The cingular vocalization pathway in the squirrel monkey

Summary In 39 squirrel monkeys (Saimiri sciureus), the effects of various brain lesions on vocalizations elicited from the precallosal cingulate gyrus were tested. It was found that lesions abolishing the cingular vocalization completely can be traced from the stimulation site continuously down to the laryngeal motoneurons in the nucleus ambiguus. The pathway thus determined (Fig. 4) travels from the precallosal cingulate gyrus through the frontal white matter and enters the internal capsule from a dorsolateral position. The pathway then follows this structure in a medio-caudal direction down to the caudal diencephalon. Here, the effective lesions leave the corticospinal tract and ascend dorsally into the periaqueductal grey. The pathway follows this structure to its end where it sweeps lateral through the parabrachial area and then descends through the lateral pons and ventrolateral medulla to the nucleus ambiguus.In nine of the animals, in addition, the effects of bilateral anterior cingular lesions on vocalizations elicited in other brain areas were tested. It was found that the only vocalization-eliciting area which becomes ineffective after destruction of the anterior cingulate gyrus is the postero-medial orbital cortex.Abbreviations a nucl. accumbens - aa area anterior amygdalae - ab nucl. basalis amygdalae - ac nucl. centralis amygdalae - al nucl. lateralis amygdalae - am nucl. medialis amygdalae - an nucl. anterior thalami - aq griseum centralis - bc brachium conjunctivum - ca caudatum - cb cerebellum - cc corpus callosum - cen nucl. centralis superior Bechterew - ci capsula interna - cin cingulum - cl claustrum - coa commissura anterior - coli colliculus inferior - cols colliculus superior - cop commissura posterior - cr corpus restiforme - csp tractus corticospinalis - db fasciculus diagonalis Brocae - dbc decussatio brachii conjunctivi - f fornix - gc gyrus cinguli - gl geniculatum laterale - gm geniculatum mediale - gp globus pallidus - gr gyrus rectus - gs gyrus subcallosus - h area tegmentalis (Forel) - ha habenula - hi tractus habenulo-interpeduncularis - hip hippocampus - hya hypothalamus anterior - hyv hypothalamus ventromedialis - in nucl. interpeduncularis - lap nucl. lateralis posterior thalami - lem lemniscus medialis - lm fasciculus longitudinalis medialis - m nucl. mammillaris - md nucl. medialis dorsalis thalami - mt tractus mammillothalamicus - nst nucl. striae terminalis - nts nucl. solitarius - oi oliva inferior - ol fasciculus olfactorius (Zuckerkandl) - os oliva superior - p pedunculus cerebri - pmc brachium pontis - po griseum pontis - pro area praeoptica - pu nucl. pulvinaris - put putamen - re formatio reticularis mesencephali - rep nucl. reticularis tegmenti pontis - rl nucl. reticularis lateralis - rub nucl. ruber - s septum - sm stria medullaris - sn substantia nigra - st stria terminalis - sto stria olfactoria lateralis - tec tractus tegmentalis centralis - trz corpus trapezoideum - va nucl. ventralis anterior thalami - ves nucl. vestibularis - vpl nucl. ventralis posterior lateralis th. - vpm nucl. ventralis posterior medialis th. - zi zona incerta - II tractus opticus - IIchde chiasma n. opticorum - III nucl. n. oculomotorii and n. oculomotorius - IV nucl. n. trochlearis - VI n. abducens - VII nucl. n. facialis and n. facialis - VIII n. acusticus - XII nucl. n. hypoglossi     

Abnormal integrity of corticocortical tracts in mild cognitive impairment: a diffusion tensor imaging study

Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders.     

Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system--II. Immunohistochemical analysis

The distribution of neuropeptide Y-like immunoreactivity in the rat brain and spinal cord was investigated by means of the peroxidase-antiperoxidase procedure of Sternberger using a rabbit anti-neuropeptide Y serum. A widespread distribution of immunostained cells and fibres was detected with moderate to large numbers of cells in the following regions: olfactory bulb, anterior olfactory nucleus, olfactory tubercle, striatum, nucleus accumbens, all parts of the neocortex and the corpus callosum, septum including the anterior hippocampal rudiment, ventral pallidum, horizontal limb of the diagonal band, amygdaloid complex. Ammon's horn, dentate gyrus, subiculum, pre- and parasubiculum, lateral thalamic nucleus (intergeniculate leaflet), bed nucleus of the stria terminalis, medial preoptic area, lateral hypothalamus, mediobasal hypothalamus, supramammillary nucleus, pericentral and external nuclei of the inferior colliculus, interpeduncular nucleus, periaqueductal central gray, locus coeruleus, dorsal tegmental nucleus of Gudden, lateral superior olive, lateral reticular nucleus, medial longitudinal fasciculus, prepositus hypoglossal nucleus, nucleus of the solitary tract and spinal nucleus of the trigeminal nerve. In the spinal cord cells were found in the substantia gelatinosa at all levels, the dorsolateral funiculus and dorsal gray commissure in lumbosacral cord. The pattern of staining was found to be similar to that observed with antisera to avian and bovine pancreatic polypeptide, but to differ in some respects from that observed with antisera to molluscan cardioexcitatory peptide. The presence of neuropeptide Y immunoreactive fibres in tracts such as the corpus callosum, anterior commissure, lateral olfactory tract, fimbria, medial corticohypothalamic tract, medial forebrain bundle, stria terminalis, dorsal periventricular bundle and other periventricular areas, indicated that in addition to the localisation of neuropeptide Y-like peptide(s) in interneurons in the forebrain, neuropeptide Y may be found in long neuronal pathways throughout the brain.     

Normal aging in the central nervous system: quantitative MR diffusion-tensor analysis

The purpose of this study is to elucidate changes in mean diffusivity (ADC) and fractional anisotropy (FA) using MR diffusion tensor imaging (DTI) in the central nervous system during normal aging. We studied 50 normal volunteers (30 men, 20 women; mean age 44.8 +/- 14.0; age range, 21-69 years) without disorders affecting the central nervous system. The frontal, parietal white matter, lentiform nucleus, posterior limb of internal capsule, thalamus, genu and splenium of the corpus callosum were selected for investigation. There was no significant difference in ADC or FA between male and female or between the right and left hemisphere. A significant ADC increase with advancing age was observed in frontal white matter (P = 0.010) and lentiform nucleus (P = 0.022). A significant FA decline was found only in the genu of the corpus callosum (P < 0.001) with advancing age. Quantitative diffusion tensor analysis correlate with normal aging and may help in assessing normal age-related changes and serve as a standard for comparison with neurodegenerative disorders.     

Evidence for a ventral septal projection to the hippocampal formation of the rat

Summary In a series of experiments in which the known projections of the septal complex to the hippocampal formation have been transected, we have used both anterograde and retrograde tracing techniques in an attempt to demonstrate a ventral septo-hippocampal pathway. In cases where transections of the fimbria, dorsal fornix and supracallosal stria were complete, injections of the retrograde tracers wheat germ agglutinin-conjugated horseradish peroxidase or Fast blue, resulted in labeled cells in the ipsilateral septal complex, primarily in the nucleus of the diagonal band. The number of cells labeled in these experiments was approximately 5–10% of that seen in experiments in animals with intact dorsal pathways who had received similar injections. The presence of a ventral pathway was confirmed in anterograde labeling experiments in which injections of ³H-amino acids were made into the septal complex. The autoradiogfaphs demonstrated that the projection terminates most heavily in the entorhinal cortex and to a lesser extent in the ventral subicular complex; there may be an additional minor projection to the temporal half of the hippocampus and dentate gyrus. Finally, using double labeling procedures, we were able to demonstrate that at least a portion of the cell population that gives rise to the ventral pathway demonstrates choline acetyltransferase immunoreactivity and is presumably cholinergic.Abbreviations ac Anterior commissure - ACB Nucleus accumbens - AH Anterior hypothalamic nucleus - AHA Amygdalo-hippocampal area - BL Basolateral nucleus (amygdala) - BM Basomedial nucleus (amygdala) - c Cingulum bundle - CE Central nucleus (amygdala) - cc Corpus callosum - CIN Cingulate cortex - CO Cortical nucleus (amygdala) - CP Caudate-putamen - df Dorsal fornix - DG Dentate gyrus - EN Endopiriform nucleus - f Fimbria-fornix - GP Globus pallidus - Hb Habenular nuclei - ic Internal capsule - L Lateral nucleus (amygdala) - LEC Lateral entorhinal cortex - LH Lateral hypothalamic area - LS Lateral septal nucleus - ME Medial nucleus (amygdala) - MEC Medial entorhinal cortex - mfb Medial forebrain bundle - MMN Medial mamillary nucleus - MS Medial septal nucleus - NDB Nucleus of the diagonal band - OLF Olfactory cortex - ot Optic tract - PAC Periamygdaloid cortex - PV Paraventricular nucleus (thalamus) - RI Regio inferior (hippocampus) - RS Regio superior (hippocampus) - rs Rhinal sulcus - S Subiculum - scs Supracallosal striae - sm Stria medullaris - SUM Supramamillary nucleus - TU Olfactory tubercle - V Ventricle - VMH Ventromedial hypothalamic nucleus     

Distribution of the omega-conotoxin receptor in rat brain. An autoradiographic mapping

The distribution of [125I]omega-conotoxin GVIA binding sites, the putative voltage-sensitive calcium channels, was studied by an autoradiographic method in the rat brain. The toxin binding sites were distributed throughout the brain in a highly heterogeneous manner. The highest density of the binding sites was observed in the cerebral cortex, hippocampus, amygdaloid complex, substantia nigra, caudate putamen, superior colliculus, nucleus of the solitary tract, and the dorsal horn of the cervical spine. The glomerular layer of the olfactory bulb, molecular layer of the cerebellar cortex, and posterior lobe of the hypophysis showed intermediate density but the density was higher than in the surrounding areas. The globus pallidus, thalamic areas, inferior olive, and pontine nuclei showed low density, while no binding sites were observed in the white matter tract regions such as the internal and external capsule, corpus callosum, fimbria of the hippocampus, fornix, stria medullaris of the thalamus, and fasciculus retroflexus. This distribution of omega-conotoxin binding sites indicates that the toxin binding sites are localized in those areas of the brain enriched in synaptic connections. This distribution pattern resembles that reported for voltage-sensitive sodium channels but it differs from that of the binding sites of dihydropyridines and verapamil. These results suggest that omega-conotoxin recognizes different molecules from organic calcium channel antagonist binding sites and that omega-conotoxin-sensitive voltage-sensitive calcium channels are concentrated in the synaptic zones and play a key role in the excitation-secretion coupling of neurotransmitters.     

Diffusion tensor imaging of diffuse axonal injury in a rat brain trauma model

Diffusion tensor imaging (DTI) was used to study traumatic brain injury. The impact-acceleration trauma model was used in rats. Here, in addition to diffusivities (mean, axial and radial), fractional anisotropy (FA) was used, in particular, as a parameter to characterize the cerebral tissue early after trauma. DTI was implemented at 7 T using fast spiral k-space sampling and the twice-refocused spin echo radiofrequency sequence for eddy current minimization. The method was carefully validated on different phantom measurements. DTI of a trauma group (n = 5), as well as a sham group (n = 5), was performed at different time points during 6 h following traumatic brain injury. Two cerebral regions, the cortex and corpus callosum, were analyzed carefully. A significant decrease in diffusivity in the trauma group versus the sham group was observed, suggesting the predominance of cellular edema in both cerebral regions. No significant FA change was detected in the cortex. In the corpus callosum of the trauma group, the FA indices were significantly lower. A net discontinuity in fiber reconstructions in the corpus callosum was observed by fiber tracking using DTI. Histological analysis using Hoechst, myelin basic protein and Bielschowsky staining showed fiber disorganization in the corpus callosum in the brains of the trauma group. On the basis of our histology results and the characteristics of the impact-acceleration model responsible for the presence of diffuse axonal injury, the detection of low FA caused by a drastic reduction in axial diffusivity and the presence of fiber disconnections of the DTI track in the corpus callosum were considered to be related to the presence of diffuse axonal injury.     

Major depressive disorder and white matter abnormalities: A diffusion tensor imaging study with tract-based spatial statistics

BackgroundA few diffusion tensor imaging (DTI) studies have shown abnormalities in areas of white matter tracts involved in mood regulation in geriatric depressive patients, using a region-of-interest technique. A voxel-based morphometry DTI study of young depressive patients reported similar results. In this study, we explored the structure of the white matter of the whole brain with DTI in middle-aged major depressive disorder (MDD) patients, using novel tract-based spatial statistics.MethodsSixteen MDD patients and 20 controls underwent DTI. An automated tract-based spatial method (TBSS) was used to analyze the scans.ResultsCompared with controls, the MDD patients showed a trend for lower values of fractional anisotropy (FA) in the left sagittal stratum, and suggestive decreased FA in the right cingulate cortex and posterior body of corpus callosum. Regressing out the duration and severity of disorder in the model did not change the finding in the sagittal stratum, but dissipated the decrease of FA in latter regions.LimitationsPossibly by reason of a relatively small study sample for a TBSS, the results are suggestive, and should be replicated in further studies.ConclusionsA novel observer-independent DTI method showed decreased FA in the middle-aged MDD patients in white matter regions that have previously connected to the emotional regulation. Lower FA might imply underlying structural abnormalities that contribute to the dysfunction detected in the limbic-cortical network of depressive patients.     

Right lateralized white matter abnormalities in first-episode,drug-naive paranoid schizophrenia

Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia.     

High-resolution diffusion tensor imaging of fixed brain in a mouse model of Pelizaeus-Merzbacher disease: comparison with quantitative measures of white matter pathology

Diffusion tensor imaging (DTI) is a powerful technique for the noninvasive assessment of the central nervous system. To facilitate the application of this technique to in vivo studies, we characterised a mouse model of the leukodystrophy, Pelizaeus-Merzbacher disease (PMD), comparing high-resolution ex vivo DTI findings with quantitative histological analysis of selected areas of the brain. The mice used in this study (Plp1-transgenic) carry transgenic copies of the Plp1 gene and are models for PMD as a result of gene duplication. Plp1 transgenic mice display a mild ataxia and experience frequent seizures around the time at which they were imaged. Axial (λ(1) ) and radial (RD) diffusivities and fractional anisotropy (FA) data were analysed using an exploratory whole-brain voxel-based method, a voxel-based approach using tract-based spatial statistics (TBSS), and by application of conventional region of interest (ROI) analyses to selected white matter tracts. Raw t value maps and TBSS analyses indicated widespread changes throughout the brain of Plp1-transgenic mice compared with the wild-type. ROI analyses of the corpus callosum, anterior commissure and hippocampal fimbria showed that FA was reduced significantly, whereas λ(1) and RD were increased significantly, in Plp1-transgenic mice compared with the wild-type. The DTI data derived from ROI analyses were subsequently compared with histological measures taken in the same regions. These revealed an almost complete absence of myelin, preservation of axons, marked astrocytosis and increased or unchanged cell densities. These data contribute to our growing understanding of the basis of anisotropic water diffusion in the normal and diseased nervous system.     

Spatiotemporal microstructural white matter changes in diffusion tensor imaging after transient focal ischemic stroke in rats

Structural reorganization in white matter (WM) after stroke is a potential contributor to substitute or to newly establish the functional field on the injured brain in nature. Diffusion tensor imaging (DTI) is an imaging modality that can be used to evaluate damage and recovery within the brain. This method of imaging allows for in vivo assessment of the restricted movements of water molecules in WM and provides a detailed look at structural connectivity in the brain. For longitudinal DTI studies after a stroke, the conventional region of interest method and voxel‐based analysis are highly dependent on the user‐hypothesis and parameter settings for implementation. In contrast, tract‐based spatial statistics (TBSS) allows for reliable voxel‐wise analysis via the projection of diffusion‐derived parameters onto an alignment‐invariant WM skeleton. In this study, spatiotemporal WM changes were examined with DTI‐derived parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, DA; radial diffusivity, RD) using TBSS 2 h to 6 weeks after experimental focal ischemic stroke in rats (N = 6). FA values remained unchanged 2–4 h after the stroke, followed by a continuous decrease in the ipsilesional hemisphere from 24 h to 2 weeks post‐stroke and gradual recovery from the ipsilesional corpus callosum to the external capsule until 6 weeks post‐stroke. In particular, the fibers in these areas were extended toward the striatum of the ischemic boundary region at 6 weeks on tractography. The alterations of the other parameters in the ipsilesional hemisphere showed patterns of a decrease at the early stage, a subsequent pseudo‐normalization of MD and DA, a rapid reduction of RD, and a progressive increase in MD, DA and RD with a decreased extent in the injured area at later stages. The findings of this study may reflect the ongoing processes on tissue damage and spontaneous recovery after stroke.     

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.     

Acetylcholinesterase histochemistry of the habenulo-interpeduncular pathway in the rat and the effects of electrolytic and kainic acid lesions

Summary The histochemical distribution of acetylcholinesterase (AChE) was studied in the habenulo-interpeduncular pathway of normal rats and after electrolytic and kainic acid lesions of the habenular nuclei. From these combined observations it appears that the AChE-rich projection to the interpeduncular nucleus derives from both the medial and the lateral habenular nuclei. The lateral nucleus of the habenula is the main source of AChE-rich fibres in the fasciculus retroflexus, and a number of stained fibres also derive from the stria medullaris. While total habenular lesions completely deprived the fasciculus retroflexus of AChE-stained fibres, a direct effect on the enzyme distribution in the interpeduncular nucleus was only apparent at its rostral pole. In the remainder of the nucleus the AChE distribution did not undergo obvious changes in comparison with the normal pattern, except for a moderate decrease in overall reaction intensity in cases with subtotal habenular lesions bilaterally.The above results are consistent with the observations derived from experiments involving kainic acid injection into the habenula. The neurotoxic effect of kainic acid was highly selective for specific types of neurons in the lateral habenula, while the neurons of the medial habenula were completely unaffected. The existence of an AChE-rich projection from the lateral habenula to the interpeduncular nucleus was supported by a corresponding decrease in enzyme activity in the lateral habenula and fasciculus retroflexus after kainic acid treatment.     

Reinforcing concomitants of electrically elicited vocalizations

Summary In 38 squirrel monkeys 251 vocalization-producing electrode positions were tested for their positive and negative reinforcing properties. Two groups of vocalization-producing brain areas could be distinguished: One group in which the electrically elicited vocalization was independent of the accompanying reinforcement effect, and a second group in which vocalization and reinforcement effect were correlated. The first group included the anterior cingulate gyrus, the adjacent supplementary motor area, gyrus rectus, ventromedial edge of the capsula interna, caudal periaqueductal gray and adjacent parabrachial region. The second group consisted of the caudatum, septum, substantia innominata, amygdala, inferior thalamic peduncle, stria terminalis, midline thalamus, ventral and periventricular hypothalamus, substantia nigra, rostral periaqueductal gray, dorsolateral midbrain tegmentum and lateral medulla. It is hypothesized that the first group contains predominantly or exclusively primary vocalization subtrates; the second group is thought to be composed mainly of structures whose stimulation yields vocalization secondarily due to stimulus induced motivational changes.Abbreviations a nucl. accumbens - aa area anterior amygdalae - ab nucl. basalis amygdalae - ac nucl. centralis amygdalae - al nucl. lateralis amygdalae - an nucl. anterior thalami - anl ansa lenticularis - aq substantia grisea centralis - bc brachium conjunctivum - ca nucl. caudatus - cc corpus callosum - cen nucl. centralis superior tegmenti - cent centrum medianum - ci capsula interna - cin cingulum - cl claustrum - coa commissura anterior - coli colliculus inferior - cols colliculus superior - csp tractus cortico-spinalis - db fasciculus diagonalis Brocae - dbc decussatio brachii conjunctivii - f fornix - gc gyrus cinguli - gl corpus geniculatum laterale - gm corpus geniculatum mediale - gp globus pallidus - gr gyrus rectus - gs gyrus subcallosus - h campus Foreli - ha nucl. habenularis - hi tractus habenulo-interpeduncularis - hip hippocampus - hya area hypothalamica anterior - hyl area hypothalamica lateralis - hyv nucl. ventromedialis hypothalami - in nucl. interpeduncularis - lap nucl. lateralis posterior thalami - lav nucl. ventralis lateralis thalami - le lemniscus lateralis - lem lemniscus medialis - lm fasciculus longitudinalis medialis - m corpus mamillare - md nucl. medialis dorsalis thalami - mt tractus mamillo-thalamicus - nst nucl. striae terminalis - oi nucl. olivaris inferior - ol fasciculus olfactorius Zuckerkandl - os nucl. olivaris superior - p pedunculus cerebri - pmc brachium pontis - po griseum pontis - pro area praeoptica - pu nucl. pulvinaris thalami - put putamen - re formatio reticularis - rep nucl. reticularis tegmenti pontis - rub nucl. ruber - s septum - sm stria medullaris - sn substantia nigra - st stria terminalis - sto tria olfactoria lateralis - subt subthalamus - tec tractus tegmentalis centralis - trz corpus trapezoideum - va nucl. ventralis anterior thalami - vpl nucl. ventralis postero-lateralis - vpm nucl. ventralis postero-medialis - zi zona incerta - II tractus opticus - IIch chiasma nervorum opticorum - III n. oculomotorius and nucl. n. oculomotorii - IV n. and nucl. n. trochlearis - VI n. abducens and nucl. n. abducentis - VII nucl. n. facialis - VIII nucl. cochlearis - IX n. hypoglossus