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1

Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2  

PubMed Central

Recent genetic studies have implicated a number of candidate genes in the pathogenesis of Autism Spectrum Disorder (ASD). Polymorphisms of CNTNAP2 (contactin-associated like protein-2), a member of the neurexin family, have already been implicated as a susceptibility gene for autism by at least 3 separate studies. We investigated variation in white and grey matter morphology using structural MRI and diffusion tensor imaging. We compared volumetric differences in white and grey matter and fractional anisotropy values in control subjects characterised by genotype at rs7794745, a single nucleotide polymorphism in CNTNAP2. Homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation. Thus a risk allele for autism results in significant cerebral morphological variation, despite the absence of overt symptoms or behavioural abnormalities. The results are consistent with accumulating evidence of CNTNAP2's function in neuronal development. The finding suggests the possibility that the heterogeneous manifestations of ASD can be aetiologically characterised into distinct subtypes through genetic-morphological analysis.

Tan, Geoffrey C.Y.; Doke, Thomas F.; Ashburner, John; Wood, Nicholas W.; Frackowiak, Richard S.J.

2010-01-01

2

Role of Frontotemporal Fiber Tract Integrity in Task-Switching Performance of Healthy Controls and Patients with Temporal Lobe Epilepsy  

PubMed Central

The objective of this study is to investigate the relationships among frontotemporal fiber tract compromise and task-switching performance in healthy controls and patients with temporal lobe epilepsy (TLE). We performed diffusion tensor imaging (DTI) on 30 controls and 32 patients with TLE (15 left TLE). Fractional anisotropy (FA) was calculated for four fiber tracts [uncinate fasciculus (UncF), arcuate fasciculus (ArcF), dorsal cingulum (CING), and inferior fronto-occipital fasciculus (IFOF)]. Participants completed the Trail Making Test-B (TMT-B) and Verbal Fluency Category Switching (VFCS) test. Multivariate analyses of variances (MANOVAs) were performed to investigate group differences in fiber FA and set-shifting performances. Canonical correlations were used to examine the overall patterns of structural-cognitive relationships and were followed by within-group bivariate correlations. We found a significant canonical correlation between fiber FA and task-switching performance. In controls, TMT-B correlated with left IFOF, whereas VFCS correlated with FA of left ArcF and left UncF. These correlations were not significant in patients with TLE. We report significant correlations between frontotemporal fiber tract integrity and set-shifting performance in healthy controls that appear to be absent or attenuated in patients with TLE. These findings suggest a breakdown of typical structure-function relationships in TLE that may reflect aberrant developmental or degenerative processes.

Kucukboyaci, N. Erkut; Girard, H.M.; Hagler, D.J.; Kuperman, J.; Tecoma, E.S.; Iragui, V.J.; Halgren, E.; McDonald, C.R.

2012-01-01

3

Role of frontotemporal fiber tract integrity in task-switching performance of healthy controls and patients with temporal lobe epilepsy.  

PubMed

The objective of this study is to investigate the relationships among frontotemporal fiber tract compromise and task-switching performance in healthy controls and patients with temporal lobe epilepsy (TLE). We performed diffusion tensor imaging (DTI) on 30 controls and 32 patients with TLE (15 left TLE). Fractional anisotropy (FA) was calculated for four fiber tracts [uncinate fasciculus (UncF), arcuate fasciculus (ArcF), dorsal cingulum (CING), and inferior fronto-occipital fasciculus (IFOF)]. Participants completed the Trail Making Test-B (TMT-B) and Verbal Fluency Category Switching (VFCS) test. Multivariate analyses of variances (MANOVAs) were performed to investigate group differences in fiber FA and set-shifting performances. Canonical correlations were used to examine the overall patterns of structural-cognitive relationships and were followed by within-group bivariate correlations. We found a significant canonical correlation between fiber FA and task-switching performance. In controls, TMT-B correlated with left IFOF, whereas VFCS correlated with FA of left ArcF and left UncF. These correlations were not significant in patients with TLE. We report significant correlations between frontotemporal fiber tract integrity and set-shifting performance in healthy controls that appear to be absent or attenuated in patients with TLE. These findings suggest a breakdown of typical structure-function relationships in TLE that may reflect aberrant developmental or degenerative processes. PMID:22014246

Kucukboyaci, N Erkut; Girard, H M; Hagler, D J; Kuperman, J; Tecoma, E S; Iragui, V J; Halgren, E; McDonald, C R

2011-10-12

4

Altered Microstructure Within Social-Cognitive Brain Networks During Childhood in Williams Syndrome.  

PubMed

Williams syndrome (WS) is a neurodevelopmental condition caused by a hemizygous deletion of ?26-28 genes on chromosome 7q11.23. WS is associated with a distinctive pattern of social cognition. Accordingly, neuroimaging studies show that WS is associated with structural alterations of key brain regions involved in social cognition during adulthood. However, very little is currently known regarding the neuroanatomical structure of social cognitive brain networks during childhood in WS. This study used diffusion tensor imaging to investigate the structural integrity of a specific set of white matter pathways (inferior fronto-occipital fasciculus [IFOF] and uncinate fasciculus [UF]) and associated brain regions [fusiform gyrus (FG), amygdala, hippocampus, medial orbitofrontal gyrus (MOG)] known to be involved in social cognition in children with WS and a typically developing (TD) control group. Children with WS exhibited higher fractional anisotropy (FA) and axial diffusivity values and lower radial diffusivity and apparent diffusion coefficient (ADC) values within the IFOF and UF, higher FA values within the FG, amygdala, and hippocampus and lower ADC values within the FG and MOG compared to controls. These findings provide evidence that the WS genetic deletion affects the development of key white matter pathways and brain regions important for social cognition. PMID:23709644

Haas, Brian W; Barnea-Goraly, Naama; Sheau, Kristen E; Yamagata, Bun; Ullas, Shruti; Reiss, Allan L

2013-05-24

5

Cortex-sparing fiber dissection: an improved method for the study of white matter anatomy in the human brain  

PubMed Central

Classical fiber dissection of post mortem human brains enables us to isolate a fiber tract by removing the cortex and overlying white matter. In the current work, a modification of the dissection methodology is presented that preserves the cortex and the relationships within the brain during all stages of dissection, i.e. ‘cortex-sparing fiber dissection’. Thirty post mortem human hemispheres (15 right side and 15 left side) were dissected using cortex-sparing fiber dissection. Magnetic resonance imaging study of a healthy brain was analyzed using diffusion tensor imaging (DTI)-based tractography software. DTI fiber tract reconstructions were compared with cortex-sparing fiber dissection results. The fibers of the superior longitudinal fasciculus (SLF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF) were isolated so as to enable identification of their cortical terminations. Two segments of the SLF were identified: first, an indirect and superficial component composed of a horizontal and vertical segment; and second, a direct and deep component or arcuate fasciculus. The IFOF runs within the insula, temporal stem and sagittal stratum, and connects the frontal operculum with the occipital, parietal and temporo-basal cortex. The UF crosses the limen insulae and connects the orbito-frontal gyri with the anterior temporal lobe. Finally, a portion of the ILF was isolated connecting the fusiform gyrus with the occipital gyri. These results indicate that cortex-sparing fiber dissection facilitates study of the 3D anatomy of human brain tracts, enabling the tracing of fibers to their terminations in the cortex. Consequently, it is an important tool for neurosurgical training and neuroanatomical research.

Martino, Juan; De Witt Hamer, Philip C; Vergani, Francesco; Brogna, Christian; de Lucas, Enrique Marco; Vazquez-Barquero, Alfonso; Garcia-Porrero, Juan A; Duffau, Hugues

2011-01-01

6

Tractography of the uncinate fasciculus and the posterior cingulate fasciculus in patients with mild cognitive impairment and Alzheimer disease.  

PubMed

INTRODUCTION: Brain tractography is a non-invasive medical imaging technique which enables in vivo visualisation and various types of quantitative studies of white matter fibre tracts connecting different parts of the brain. We completed a quantitative study using brain tractography with diffusion tensor imaging in patients with mild cognitive impairment, patients with Alzheimer disease, and normal controls, in order to analyse the reproducibility and validity of the results. SUBJECTS AND METHODS: Fractional anisotropy (FA) and mean diffusivity (MD) were measured across the uncinate fasciculus and the posterior cingulate fasciculus in images, obtained from a database and a research centre, representing 52 subjects distributed among the 3 study groups. Two observers took the measurements twice in order to evaluate intra- and inter-observer reproducibility. RESULTS: Measurements of FA and MD of the uncinate fasciculus delivered an intraclass correlation coefficient above 0.9; ICC was above 0.68 for the posterior cingulate fasciculus. Patients with Alzheimer disease showed lower values of FA and higher MD values in the right uncinate fasciculus in images from the research centre. A comparison of the measurements from the 2 centres revealed significant differences. CONCLUSION: We established a reproducible methodology for performing tractography of the tracts in question. FA and MD indexes may serve as early indicators of Alzheimer disease. The type of equipment and the method used to acquire images must be considered because they may alter results as shown by comparing the 2 data sets in this study. PMID:23582374

Larroza, A; Moratal, D; D'ocón Alcañiz, V; Arana, E

2013-04-10

7

The Role of the Arcuate Fasciculus in Conduction Aphasia  

ERIC Educational Resources Information Center

|In aphasia literature, it has been considered that a speech repetition defect represents the main constituent of conduction aphasia. Conduction aphasia has frequently been interpreted as a language impairment due to lesions of the arcuate fasciculus (AF) that disconnect receptive language areas from expressive ones. Modern neuroradiological…

Bernal, Byron; Ardila, Alfredo

2009-01-01

8

MR Imaging of the Temporal Stem: Anatomic Dissection Tractography of the Uncinate Fasciculus, Inferior Occipitofrontal Fasciculus, and Meyer's Loop of the Optic Radiation  

Microsoft Academic Search

BACKGROUND AND PURPOSE: The MR anatomy of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop of the optic radiation, which traverse the temporal stem, is not well known. The purpose of this investigation was to study these structures in the anterior temporal lobe and the external and extreme capsules and to correlate the dissected anatomy with the cross-sectional MR

E. Leon Kier; Lawrence H. Staib; Lawrence M. Davis; Richard A. Bronen

9

Brain white matter microstructure is associated with susceptibility to motion-induced nausea.  

PubMed

Nausea is associated with significant morbidity, and there is a wide range in the propensity of individuals to experience nausea. The neural basis of the heterogeneity in nausea susceptibility is poorly understood. Our previous functional magnetic resonance imaging (fMRI) study in healthy adults showed that a visual motion stimulus caused activation in the right MT+/V5 area, and that increased sensation of nausea due to this stimulus was associated with increased activation in the right anterior insula. For the current study, we hypothesized that individual differences in visual motion-induced nausea are due to microstructural differences in the inferior fronto-occipital fasciculus (IFOF), the white matter tract connecting the right visual motion processing area (MT+/V5) and right anterior insula. To test this hypothesis, we acquired diffusion tensor imaging data from 30 healthy adults who were subsequently dichotomized into high and low nausea susceptibility groups based on the Motion Sickness Susceptibility Scale. We quantified diffusion along the IFOF for each subject based on axial diffusivity (AD); radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA), and evaluated between-group differences in these diffusion metrics. Subjects with high susceptibility to nausea rated significantly (P < 0.001) higher nausea intensity to visual motion stimuli and had significantly (P < 0.05) lower AD and MD along the right IFOF compared to subjects with low susceptibility to nausea. This result suggests that differences in white matter microstructure within tracts connecting visual motion and nausea-processing brain areas may contribute to nausea susceptibility or may have resulted from an increased history of nausea episodes. PMID:23360260

Napadow, V; Sheehan, J; Kim, J; Dassatti, A; Thurler, A H; Surjanhata, B; Vangel, M; Makris, N; Schaechter, J D; Kuo, B

2013-01-29

10

Evidence of frontotemporal structural hypoconnectivity in social anxiety disorder: A quantitative fiber tractography study.  

PubMed

Investigation of the brain's white matter fiber tracts in social anxiety disorder (SAD) may provide insight into the underlying pathophysiology. Because models of pathological anxiety posit altered frontolimbic interactions, the uncinate fasciculus (UF) connecting (orbito-) frontal and temporal areas including the amygdala is of particular interest. Microstructural alterations in parts of the UF have been reported previously, whereas examination of the UF as discrete fiber tract with regard to more large-scale properties is still lacking. Diffusion tensor imaging was applied in 25 patients with generalized SAD and 25 healthy control subjects matched by age and gender. By means of fiber tractography, the UF was reconstructed for each participant. The inferior fronto-occipital fasciculus (IFOF), originating from the frontal cortex similarly to the UF, was additionally included as control tract. Volume and fractional anisotropy (FA) were compared between the groups for both tracts. Volume of left and right UF was reduced in patients with SAD, reaching statistical significance for the left UF. Bilateral IFOF volume was not different between groups. A similar pattern was observed for FA. Reduced volume of the left UF in SAD fits well into pathophysiological models of anxiety, as it suggests deficient structural connectivity between higher-level control areas in the orbitofrontal cortex and more basal limbic areas like the amygdala. The results point to a specific role of the left UF with regard to altered white matter volume in SAD. However, results should be replicated and functional correlates of altered UF volume be determined in future studies. PMID:22076860

Baur, Volker; Brühl, Annette Beatrix; Herwig, Uwe; Eberle, Tanja; Rufer, Michael; Delsignore, Aba; Jäncke, Lutz; Hänggi, Jürgen

2011-11-11

11

Does the left inferior longitudinal fasciculus play a role in language? A brain stimulation study  

Microsoft Academic Search

Although advances in diffusion tensor imaging have enabled us to better study the anatomy of the inferior long- itudinal fasciculus (ILF), its function remains poorly understood. Recently, it was suggested that the subcortical network subserving the language semantics could be constituted, in parallel with the inferior occipitofrontal fasciculus, by the left ILF, joining the posterior occipitotemporal regions to the temporal

Emmanuel Mandonnet; Aurelien Nouet; Peggy Gatignol; Laurent Capelle; Hugues Duffau

2007-01-01

12

Does the Left Inferior Longitudinal Fasciculus Play a Role in Language? A Brain Stimulation Study  

ERIC Educational Resources Information Center

|Although advances in diffusion tensor imaging have enabled us to better study the anatomy of the inferior longitudinal fasciculus (ILF), its function remains poorly understood. Recently, it was suggested that the subcortical network subserving the language semantics could be constituted, in parallel with the inferior occipitofrontal fasciculus,…

Mandonnet, Emmanuel; Nouet, Aurelien; Gatignol, Peggy; Capelle, Laurent; Duffau, Hugues

2007-01-01

13

Asymmetries of the Arcuate Fasciculus in Monozygotic Twins: Genetic and Nongenetic Influences  

PubMed Central

We assessed cerebral asymmetry for language in 35 monozygotic twin pairs. Using DTI, we reconstructed the arcuate fasciculus in each twin. Among the male twins, right-handed pairs showed greater left-sided asymmetry of connectivity in the arcuate fasciculus than did those with discordant handedness, and within the discordant group the right-handers had greater left-sided volume asymmetry of the arcuate fasciculus than did their left-handed co-twins. There were no such effects in the female twins. Cerebral asymmetry for language showed more consistent results, with the more left-cerebrally dominant twins also showing more leftward asymmetry of high anisotropic fibers in the arcuate fasciculus, a result applying equally to female as to male twins. Reversals of arcuate fasciculus asymmetry were restricted to pairs discordant for language dominance, with the left-cerebrally dominant twins showing leftward and the right-cerebrally dominant twins rightward asymmetry of anisotropic diffusion in the arcuate fasciculus. Because monozygotic twin pairs share the same genotype, our results indicate a strong nongenetic component in arcuate fasciculus asymmetry, particularly in those discordant for cerebral asymmetry.

Haberling, Isabelle S.; Badzakova-Trajkov, Gjurgjica; Corballis, Michael C.

2013-01-01

14

Reading impairment in a patient with missing arcuate fasciculus  

PubMed Central

We describe the case of a child (“S”) who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. S was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive abilities and performed diffusion tensor imaging (DTI) to measure cerebral white matter pathways. Diffuse white matter differences were evident in T1-weighted, T2-weighted, diffusion anisotropy, and mean diffusivity measures in S compared to a group of 28 normal female controls. In addition, we found specific white matter pathway deficits by comparing tensor orientation directions in S’s brain with those of the control brains. While her principal diffusion direction maps appeared consistent with those of controls over most of the brain, there were tensor orientation abnormalities in the fiber tracts that form the superior longitudinal fasciculus (SLF) in both hemispheres. Tractography analysis indicated that the left and right arcuate fasciculus (AF), as well as other tracts within the SLF, were missing in S. Other major white matter tracts, such as the corticospinal and inferior occipitofrontal pathways, were intact. Functional MRI measurements indicated left-hemisphere dominanance for language with a normal activation pattern. Despite the left AF abnormality, S had preserved oral language with average sentence repetition skills. In addition to profound dyslexia, S exhibited visuospatial, calculation, and rapid naming deficits and was impaired in both auditory and spatial working memory. We propose that the reading and visuospatial deficits were due to the abnormal left and right SLF pathways, respectively. These results advance our understanding of the functional significance of the SLF and are the first to link radiation necrosis with selective damage to a specific set of fiber tracts.

Rauschecker, Andreas M.; Deutsch, Gayle K.; Ben-Shachar, Michal; Schwartzman, Armin; Perry, Lee M.; Dougherty, Robert F.

2009-01-01

15

Learning to Read Improves the Structure of the Arcuate Fasciculus.  

PubMed

The acquisition of literacy results from an effortful learning process that leads to functional changes in several cortical regions. We explored whether learning to read also leads to anatomical changes within the left intrahemispheric white matter pathways that interconnect these regions. Using diffusion tensor imaging tractography, we compared illiterates with ex-illiterates who learned to read during adulthood and literates who learned to read during their childhood. Literacy related to an increase in fractional anisotropy and a decrease in perpendicular diffusivity in the temporo-parietal portion of the left arcuate fasciculus. The microstructure within this pathway correlated with the reading performance and the degree of functional activation within 2 dominant brain regions involved in reading: The Visual Word Form Area in response to letter strings, and the posterior superior temporal cortex in response to spoken language. Thus, the acquisition of literacy is associated with a reinforcement of left temporo-parietal connections whose microstructure predicts overall reading performance and the functional specialization of the Visual Word Form Area. This anatomical magnetic resonance imaging marker may be useful to predict developmental reading disorders. PMID:23236205

Thiebaut de Schotten, Michel; Cohen, Laurent; Amemiya, Eduardo; Braga, Lucia W; Dehaene, Stanislas

2012-12-12

16

A tractography study in dyslexia: neuroanatomic correlates of orthographic, phonological and speech processing.  

PubMed

Diffusion tensor imaging tractography is a structural magnetic resonance imaging technique allowing reconstruction and assessment of the integrity of three dimensional white matter tracts, as indexed by their fractional anisotropy. It is assumed that the left arcuate fasciculus plays a crucial role for reading development, as it connects two regions of the reading network, the left temporoparietal region and the left inferior frontal gyrus, for which atypical functional activation and lower fractional anisotropy values have been reported in dyslexic readers. In addition, we explored the potential role of the left inferior fronto-occipital fasciculus, which might connect a third region of the reading network, the left ventral occipitotemporal region with the left inferior frontal gyrus. In the present study, 20 adults with dyslexia and 20 typical reading adults were scanned using diffusion tensor imaging, and the bilateral arcuate fasciculus and the left inferior fronto-occipital fasciculus were delineated. Group comparisons show a significantly reduced fractional anisotropy in the left arcuate fasciculus of adults with dyslexia, in particular in the segment that directly connects posterior temporal and frontal areas. This fractional anisotropy reduction might reflect a lower degree of myelination in the dyslexic sample, as it co-occurred with a group difference in radial diffusivity. In contrast, no significant group differences in fractional anisotropy were found in the right arcuate fasciculus or in the left inferior fronto-occipital fasciculus. Correlational analyses (controlled for reading status) demonstrated a specific relation between performance on phoneme awareness and speech perception and the integrity of left arcuate fasciculus as indexed by fractional anisotropy, and between orthographic processing and fractional anisotropy values in left inferior fronto-occipital fasciculus. The present study reveals structural anomalies in the left arcuate fasciculus in adults with dyslexia. This finding corroborates current hypotheses of dyslexia as a disorder of network connections. In addition, our study demonstrates a correlational double dissociation, which might reflect neuroanatomical correlates of the dual route reading model: the left arcuate fasciculus seems to sustain the dorsal phonological route underlying grapheme-phoneme decoding, while the left inferior fronto-occipital fasciculus seems to sustain the ventral orthographic route underlying reading by direct word access. PMID:22327793

Vandermosten, Maaike; Boets, Bart; Poelmans, Hanne; Sunaert, Stefan; Wouters, Jan; Ghesquière, Pol

2012-02-10

17

Uncinate Fasciculus Findings in Schizophrenia: A Magnetic Resonance Diffusion Tensor Imaging Study  

PubMed Central

Objective Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. Method Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. Results Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. Conclusions These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.

Kubicki, Marek; Westin, Carl-Fredrik; Maier, Stephan E.; Frumin, Melissa; Nestor, Paul G.; Salisbury, Dean F.; Kikinis, Ron; Jolesz, Ferenc A.; McCarley, Robert W.; Shenton, Martha E.

2009-01-01

18

Damage to the anterior arcuate fasciculus predicts non-fluent speech production in aphasia.  

PubMed

Non-fluent aphasia implies a relatively straightforward neurological condition characterized by limited speech output. However, it is an umbrella term for different underlying impairments affecting speech production. Several studies have sought the critical lesion location that gives rise to non-fluent aphasia. The results have been mixed but typically implicate anterior cortical regions such as Broca's area, the left anterior insula, and deep white matter regions. To provide a clearer picture of cortical damage in non-fluent aphasia, the current study examined brain damage that negatively influences speech fluency in patients with aphasia. It controlled for some basic speech and language comprehension factors in order to better isolate the contribution of different mechanisms to fluency, or its lack. Cortical damage was related to overall speech fluency, as estimated by clinical judgements using the Western Aphasia Battery speech fluency scale, diadochokinetic rate, rudimentary auditory language comprehension, and executive functioning (scores on a matrix reasoning test) in 64 patients with chronic left hemisphere stroke. A region of interest analysis that included brain regions typically implicated in speech and language processing revealed that non-fluency in aphasia is primarily predicted by damage to the anterior segment of the left arcuate fasciculus. An improved prediction model also included the left uncinate fasciculus, a white matter tract connecting the middle and anterior temporal lobe with frontal lobe regions, including the pars triangularis. Models that controlled for diadochokinetic rate, picture-word recognition, or executive functioning also revealed a strong relationship between anterior segment involvement and speech fluency. Whole brain analyses corroborated the findings from the region of interest analyses. An additional exploratory analysis revealed that involvement of the uncinate fasciculus adjudicated between Broca's and global aphasia, the two most common kinds of non-fluent aphasia. In summary, the current results suggest that the anterior segment of the left arcuate fasciculus, a white matter tract that lies deep to posterior portions of Broca's area and the sensory-motor cortex, is a robust predictor of impaired speech fluency in aphasic patients, even when motor speech, lexical processing, and executive functioning are included as co-factors. Simply put, damage to those regions results in non-fluent aphasic speech; when they are undamaged, fluent aphasias result. PMID:24131592

Fridriksson, Julius; Guo, Dazhou; Fillmore, Paul; Holland, Audrey; Rorden, Chris

2013-10-15

19

A Combined fMRI and DTI Examination of Functional Language Lateralization and Arcuate Fasciculus Structure: Effects of Degree versus Direction of Hand Preference  

ERIC Educational Resources Information Center

|The present study examined the relationship between hand preference degree and direction, functional language lateralization in Broca's and Wernicke's areas, and structural measures of the arcuate fasciculus. Results revealed an effect of degree of hand preference on arcuate fasciculus structure, such that consistently-handed individuals,…

Propper, Ruthe E.; O'Donnell, Lauren J.; Whalen, Stephen; Tie, Yanmei; Norton, Isaiah H.; Suarez, Ralph O.; Zollei, Lilla; Radmanesh, Alireza; Golby, Alexandra J.

2010-01-01

20

Preliminary Evidence of White Matter Abnormality in the Uncinate Fasciculus in Generalized Social Anxiety Disorder  

PubMed Central

Background Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala’s response to threat. The goal of this study was to investigate brain frontal WM abnormalities by using diffusion tensor imaging (DTI) in patients with social anxiety disorder. Method A Turboprop DTI sequence was used to acquire diffusion tensor images in thirty patients with GSAD and thirty matched healthy controls. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects and an automated voxel-based, whole-brain method was used to analyze group differences. Results Compared to healthy controls, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. Conclusions These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness.

Phan, K. Luan; Orlichenko, Anton; Boyd, Erin; Angstadt, Mike; Coccaro, Emil F.; Liberzon, Israel; Arfanakis, Konstantinos

2009-01-01

21

Predicting Behavioral Deficits in Pediatric Traumatic Brain Injury Through Uncinate Fasciculus Integrity  

PubMed Central

Behavioral dysregulation is a common and detrimental consequence of traumatic brain injury (TBI) in children that contributes to poor academic achievement and deficits in social development. Unfortunately, behavioral dysregulation is difficult to predict from either injury severity or early neuropsychological evaluation. The uncinate fasciculus (UF) connects orbitofrontal and anterior temporal lobes, which are commonly implicated in emotional and behavioral regulation. Using probabilistic diffusion tensor tractography (DTT), we examined the relationship between the integrity of the UF 3 months post-injury and ratings of executive functions 12 months post-injury in children with moderate to severe TBI and a comparison group with orthopedic injuries. As expected, fractional anisotropy of the UF was lower in the TBI group relative to the orthopedic injury group. DTT metrics from the UF served as a biomarker and predicted ratings of emotional and behavior regulation, but not metacognition. In contrast, the Glasgow Coma Scale score was not related to either UF integrity or to executive function outcomes. Neuroanatomical biomarkers like the uncinate fasciculus may allow for early identification of behavioral problems and allow for investigation into the relationship of frontotemporal networks to brain-behavior relationships.

Johnson, Chad P.; Juranek, Jenifer; Kramer, Larry A.; Prasad, Mary R.; Swank, Paul R.; Ewing-Cobbs, Linda

2013-01-01

22

Disynaptic excitation from the medial longitudinal fasciculus to lumbosacral motoneurons: modulation by repetitive activation, descending pathways, and locomotion  

Microsoft Academic Search

Short-latency excitatory postsynaptic potentials (EPSPs) evoked by stimulation in the medial longitudinal fasciculus (MLF) were recorded intracellularly from motoneurons in the cat lumbosacral spinal cord. Monosynaptic and disynaptic EPSPs occurred in most flexor and extensor motoneurons studied. These EPSPs resulted from the activation of fast (> 100 m\\/s) descending axons from the MLF to the spinal cord. Several features distinguished

M. K. Floeter; G. N. Sholomenko; J.-P. Gossard; R. E. Burke

1993-01-01

23

Vertical gaze palsy and selective unilateral infarction of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)  

Microsoft Academic Search

We report a clinico-pathological correlation study in a patient with basilar artery thrombosis, who developed tetraplegia and combined up- and downgaze palsy involving voluntary saccades and visually-guided movements, but sparing the oculocephalic responses. At necropsy, apart from bilateral infarction in the basis pontis, there was a single unilateral infarct selectively destroying the rostral interstitial nucleus of the medial longitudinal fasciculus

J Bogousslavsky; J Miklossy; F Regli; R Janzer

1990-01-01

24

Dissociation of Behavioral Changes in Rats Resulting From Lesions of the Habenula Versus Fasciculus Retroflexus and Their Possible Anatomical Substrates  

Microsoft Academic Search

Lesions in either the habenula or its primary efferent pathway, the fasciculus retroflexus (FR), impaired avoidance responding. However, lesions of only the FR provided a persistent elevation of locomotor activity. Immunocytochemical study of the interpeduncular nucleus (IPN) through injection of retrograde tracers into the IPN and the overlying ventral tegmental area indicated that habenular lesions spared both rostral habenula and

Everard W. Thornton; Marion Murray; Theresa Connors-Eckenrode; Forrest Haun

1994-01-01

25

Evidence of slow maturation of the superior longitudinal fasciculus in early childhood by diffusion tensor imaging.  

PubMed

While the majority of axonal organization is established by birth in mammalian brains, axonal wiring and pruning processes, as well as myelination, are known to extend to the postnatal periods, where environmental stimuli often play a major role. Normal axonal and myelin development of individual white matter tracts of human in this period is poorly understood and may have a major role in cognitive development of human. In this study, we applied diffusion tensor imaging and normalization-based population analyses to 44 preteen children and 30 adult images. We observed highly significant changes of fiber orientations at regions that correspond to the superior longitudinal fasciculus during the first 5 years. The result is attributed to slow axonal and/or myelin maturation of this tract, which is believed to be involved in language functions. PMID:17826183

Zhang, Jiangyang; Evans, Alan; Hermoye, Laurent; Lee, Seung-Koo; Wakana, Setsu; Zhang, Weihong; Donohue, Pamela; Miller, Michael I; Huang, Hao; Wang, Xiaoqing; van Zijl, Peter C M; Mori, Susumu

2007-08-08

26

Is the term "fasciculus opticus cerebralis" more justifiable than the term "optic nerve"?  

PubMed

The terminology of the optic nerve had already been changed three times, since 1895 until 1955 when the term "nervus opticus" was introduced in the "Terminologia Anatomica". Following our study we claim that, from the aspect of phylogenetic evolution of binocular vision development as well as optical embryogenesis where opticus is evidently presented as a product of diencephalic structures, the addition of the term "nervus" to opticus is not adequate and justified. From the clinical aspect the term "nervus opticus" is also inadequate, both as a "nerve" that has no functional regenerative properties, unlike other cranial nerves, as well as from a pedagogical and didactical aspect of educating future physicians. We suggest that the term "Fasciculus Opticus Cerebralis" should be used as it much better explains the origin as well as its affiliation to the central nervous system. PMID:23837214

Vojnikovi?, Bojo; Bajek, Snjezana; Bajek, Goran; Strenja-Lini?, Ines; Grubesi?, Aron

2013-04-01

27

Relatively normal repetition performance despite severe disruption of the left arcuate fasciculus  

PubMed Central

The arcuate fasciculus (AF) is believed to be fundamental to the neural circuitry behind many important cognitive processes. Connecting Wernicke’s and Broca’s area, these fibers are thought to be especially important for repetition. In this case study we present evidence from a patient that set doubt on these assumptions. We present structural imaging, diffusion tensor imaging, and language data on a patient with a large left-sided stroke and severely damaged left AF who showed intact word repetition and relatively intact sentence repetition performance. Specifically, his sentence repetition is more fluent and grammatical, with less hesitation than spontaneous speech, and with rare omissions only during the longest sentences. These results challenge classical theories that maintain the left AF is the dominant language processing pathway or mechanism for repetition.

Epstein-Peterson, Zachary; Faria, Andreia Vasconcellos; Mori, Susumu; Hillis, Argye E.; Tsapkini, Kyrana

2012-01-01

28

A Combined fMRI and DTI Examination of Functional Language Lateralization and Arcuate Fasciculus Structure: Effects of Degree Versus Direction of Hand Preference  

PubMed Central

The present study examined the relationship between hand preference degree and direction, functional language lateralization in Broca's and Wernicke's areas, and structural measures of the arcuate fasciculus. Results revealed an effect of degree of hand preference on arcuate fasciculus structure, such that consistently-handed individuals, regardless of the direction of hand preference, demonstrated the most asymmetric arcuate fasciculus, with larger left versus right arcuate, as measured by DTI. Functional language lateralization in Wernicke's area, measured via fMRI, was related to arcuate fasciculus volume in consistent-left-handers only, and only in people who were not right hemisphere lateralized for language; given the small sample size for this finding, future investigation is warranted. Results suggest handedness degree may be an important variable to investigate in the context of neuroanatomical asymmetries.

Propper, Ruth E.; O'Donnell, Lauren J.; Whalen, Stephen; Tie, Yanmei; Norton, Isaiah H.; Suarez, Ralph O.; Zollei, Lilla; Radmanesh, Alireza; Golby, Alexandra J.

2010-01-01

29

Long-term Cognitive and Behavioral Therapies, Combined with Augmentative Communication, are Related to Uncinate Fasciculus Integrity in Autism  

Microsoft Academic Search

Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging,\\u000a we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed\\u000a to long-term augmentative and alternative communication, combined with sessions of cognitive and behavioral therapy. Uncinate\\u000a fasciculus structural properties correlated significantly with therapy length and early onset, as

Matteo Pardini; Maurizio Elia; Francesco G. Garaci; Silvia Guida; Filadelfo Coniglione; Frank Krueger; Francesca Benassi; Leonardo Emberti Gialloreti

30

The anatomical characteristics of superior longitudinal fasciculus I in human brain: Diffusion tensor tractography study.  

PubMed

The superior longitudinal fasciculus (SLF) I is known to be involved in regulation of higher aspects of motor function. Using diffusion tensor imaging (DTI), we attempted to identify the SLF I and to investigate the anatomical characteristics of the SLF I in the human brain. We recruited 30 healthy subjects for this study. The SLF I was obtained using the FMRIB Software Library. The seed region of interest (ROI) was given at the superior parietal lobule (SPL) and the target ROI was the supplementary motor area (SMA) along with the dorsal part of the premotor area (PMA). Values of fractional anisotropy (FA), mean diffusivity (MD), and tract volume were measured. The SLF I originated from the SPL and medial parietal cortex, passed through the white matter of the SPL and superior frontal gyrus, and then terminated in the SMA and dorsal PMA. There were no significant differences between hemispheres in terms of the FA, MD, and tract volume. We present with the anatomical characteristics of the SLF I in the human brain using DTI. We think that the methodology and results of this study would be helpful to researchers in this field. PMID:22085696

Jang, Sung Ho; Hong, Ji Heon

2011-11-06

31

Midbrain vs. pontine medial longitudinal fasciculus lesions: the utilization of masseter and blink reflexes.  

PubMed

Masseter (MR) and blink reflexes (BL) were investigated in 51 patients with internuclear ophthalmoplegia (INO) due to multiple sclerosis (28) and lacunar infarction (23). The MR was abnormal in 20 of 23 cases with bilateral INO and in 21 of 28 with unilateral INO. The R1 component of the BL (BL-R1) was abnormal in 7 of 23 patients with bilateral INO and 10 of 28 with unilateral INO. Combined MR and BL-R1 changes occurred in 8 of 28 cases with unilateral INO and 7 of 23 with bilateral INO. The findings provide evidence for a rostral/caudal localization of lesions within the medial longitudinal fasciculus causing INO on the basis of MR and BL-R1 abnormalities. An abnormality limited to MR suggests a midbrain location in 58.8% of patients while abnormal BL-R1 with or without an associated MR change suggests a rostral pontine location in 35.3%. PMID:2027350

Hopf, H C; Thömke, F; Gutmann, L

1991-04-01

32

Neural injury of uncinate fasciculus in patients with diffuse axonal injury.  

PubMed

The recent development of diffusion tensor imaging (DTI) allows visualization and estimation of the uncinate fasciculus (UF). We investigated injuries of the UF in patients with diffuse axonal injury (DAI) who showed no specific lesions except for DAI lesions on conventional brain MRI. Twenty-one chronic patients with DAI, and 21 age- and sex-matched normal control subjects were recruited for this study. Diffusion tensor images were acquired using a sensitivity-encoding head coil at 1.5 T and the UF was reconstructed using DTI-Studio software. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) value, and fiber number of the UF were measured. In the DAI group, the FA values and fiber numbers were significantly decreased compared to those of the control group (P< 0.05). The FA value and fiber number decreased 8.4% and 26.5% in the DAI group compared to those of the control group. By contrast, the ADC value did not show any difference between the DAI and control groups (P> 0.05). Changes in the DTI parameters of the DAI group appeared to indicate neural injury of the UF. We believe that DTI can be a useful evaluation tool for detecting hidden neural injuries of UF in patients with DAI. PMID:22672947

Seo, Jeong Pyo; Kim, Oh Lyong; Kim, Seong Ho; Chang, Min Cheol; Kim, Min-Su; Son, Su Min; Jang, Sung Ho

2012-01-01

33

Effects of practice and experience on the arcuate fasciculus: comparing singers, instrumentalists, and non-musicians.  

PubMed

Structure and function of the human brain are affected by training in both linguistic and musical domains. Individuals with intensive vocal musical training provide a useful model for investigating neural adaptations of learning in the vocal-motor domain and can be compared with learning in a more general musical domain. Here we confirm general differences in macrostructure (tract volume) and microstructure (fractional anisotropy, FA) of the arcuate fasciculus (AF), a prominent white-matter tract connecting temporal and frontal brain regions, between singers, instrumentalists, and non-musicians. Both groups of musicians differed from non-musicians in having larger tract volume and higher FA values of the right and left AF. The AF was then subdivided in a dorsal (superior) branch connecting the superior temporal gyrus and the inferior frontal gyrus (STG???IFG), and ventral (inferior) branch connecting the middle temporal gyrus and the inferior frontal gyrus (MTG???IFG). Relative to instrumental musicians, singers had a larger tract volume but lower FA values in the left dorsal AF (STG???IFG), and a similar trend in the left ventral AF (MTG???IFG). This between-group comparison controls for the general effects of musical training, although FA was still higher in singers compared to non-musicians. Both musician groups had higher tract volumes in the right dorsal and ventral tracts compared to non-musicians, but did not show a significant difference between each other. Furthermore, in the singers' group, FA in the left dorsal branch of the AF was inversely correlated with the number of years of participants' vocal training. Our findings suggest that long-term vocal-motor training might lead to an increase in volume and microstructural complexity of specific white-matter tracts connecting regions that are fundamental to sound perception, production, and its feedforward and feedback control which can be differentiated from a more general musician effect. PMID:21779271

Halwani, Gus F; Loui, Psyche; Rüber, Theodor; Schlaug, Gottfried

2011-07-07

34

Correlation between uncinate fasciculus and memory tasks in healthy individual using diffusion tensor tractography.  

PubMed

Tractography is a procedure that can track and demonstrate the 3D neural tracts of the white matter of the brain. The images of the brain are obtained by analyzing the diffusion tensor, identification of which can provide the anatomical connections of the brain. Studying these connections is integral to the understanding of the brain function. Specifically, the uncinate fasciculus (UF), which is the white matter in the human brain, is said to be related to cognitive function. The UF tractography is calculated using diffusion tensor imaging (DTI) parameter. Studies have shown that the DTI parameter of dementia patients is lower than that of healthy individuals. It is also suggested that the DTI parameter of healthy individuals decreases with age. In addition, the WMS-R score, which is indicative of general memory, verbal memory and other cognitive functions, of the elderly are lower than of the young. However, there is no report yet that has holistically investigated DTI parameter and the memory functions. Thus, in this research, we have calculated the correlation coefficient between the DTI parameter of UF and WMS-R score. Our result shows that the correlation coefficient of diffusivity of the fiber direction and visual memory of a left UF is -0.226 at the maximum. Correlation between DTI measurement and memory performance suggests the relationships between the UF and function in memory tasks lateralization. Our finding matches previous reports on the correlation between FA in the left, or L1 in the right UF, and performance on visual memory. PMID:23365919

Sato, T; Maruyama, N; Hoshida, T; Minato, K

2012-01-01

35

Aberrations in the arcuate fasciculus are associated with auditory verbal hallucinations in psychotic and in non-psychotic individuals.  

PubMed

The pathophysiology of auditory verbal hallucinations (AVH) is still unclear. Cognitive as well as electrophysiological studies indicate that a defect in sensory feedback (corollary discharge) may contribute to the experience of AVH. This could result from disruption of the arcuate fasciculus, the major tract connecting frontal and temporo-parietal language areas. Previous diffusion tensor imaging studies indeed demonstrated abnormalities of this tract in schizophrenia patients with AVH. It is, however, difficult to disentangle specific associations with AVH in this patient group as many other factors, such as other positive and negative symptoms, medication or halted education could likewise have affected tract integrity. We therefore investigated AVH in relative isolation and studied a group of non-psychotic individuals with AVH as well as patients with AVH and non-hallucinating matched controls. We compared tract integrity of the arcuate fasiculus and of three other control tracts, between 35 non-psychotic individuals with AVH, 35 schizophrenia patients with AVH, and 36 controls using diffusion tensor imaging and magnetization transfer imaging. Both groups with AVH showed an increase in magnetization transfer ratio (MTR) in the arcuate fasciculus, but not in the other control tracts. In addition, a general decrease in fractional anisotropy (FA) for almost all bundles was observed in the patient group, but not in the non-psychotic individuals with AVH. As increased MTR in the arcuate fasciculus was present in both hallucinating groups, a specific association with AVH seems plausible. Decreases in FA, on the other hand, seem to be related to other disease processes of schizophrenia. PMID:22109992

de Weijer, Antoin D; Neggers, Sebastiaan F W; Diederen, Kelly M S; Mandl, René C W; Kahn, René S; Hulshoff Pol, Hilleke E; Sommer, Iris E

2011-11-23

36

Horizontal portion of arcuate fasciculus fibers track to pars opercularis, not pars triangularis, in right and left hemispheres: A DTI study  

Microsoft Academic Search

The arcuate fasciculus (AF) is a white matter pathway traditionally considered to connect left Broca's area with posterior language zones. We utilized diffusion tensor imaging (DTI) in eight healthy subjects (5 M) to track pathways in the horizontal mid-portion of the AF (hAF) to subregions of Broca's area — pars triangularis (PTr) and pars opercularis (POp); and to ventral premotor

Elina Kaplan; Margaret A. Naeser; Paula I. Martin; Michael Ho; Yunyan Wang; Errol Baker; Alvaro Pascual-Leone

2010-01-01

37

Selective neurotoxic effects of nicotine on axons in fasciculus retroflexus further support evidence that this a weak link in brain across multiple drugs of abuse  

Microsoft Academic Search

When administered continuously for several days at relatively low plasma levels, a variety of drugs of abuse with strong dopaminergic actions induce degeneration in axons traveling from the lateral habenula through the sheath of fasciculus retroflexus to midbrain monoaminergic nuclei. With some of these drugs, such as cocaine, this is virtually the only degeneration induced in brain. Nicotine given continuously

Janice Carlson; Brian Armstrong; Robert C. Switzer III; Gaylord Ellison

2000-01-01

38

Neural degeneration following chronic stimulant abuse reveals a weak link in brain, fasciculus retroflexus, implying the loss of forebrain control circuitry  

Microsoft Academic Search

There is increasing evidence that the fasciculus retroflexus (FR) represents a ‘weak link’ following the continuous administration of drugs of abuse. A variety of drugs which predominantly potentiate dopamine, including d-amphetamine, methamphetamine, MDMA, cocaine, and cathinone, all induce degeneration in axons from lateral habenula, through the sheath of FR, to midbrain cells such as SN, VTA, and raphe. For some

Gaylord Ellison

2002-01-01

39

Vertical gaze palsy and selective unilateral infarction of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF).  

PubMed Central

We report a clinico-pathological correlation study in a patient with basilar artery thrombosis, who developed tetraplegia and combined up- and downgaze palsy involving voluntary saccades and visually-guided movements, but sparing the oculocephalic responses. At necropsy, apart from bilateral infarction in the basis pontis, there was a single unilateral infarct selectively destroying the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) on the right. The posterior commissure and its nucleus, the nucleus of Cajal, the nucleus of Darkschewitsch and the pontine tegmentum were spared. We suggest that the unilateral riMLF lesion may have disrupted bilateral upgaze excitatory and inhibitory inputs and unilateral downgaze excitatory inputs. The functional anatomy of inhibitory and excitatory vertical gaze circuitry, which remains speculative, may explain why a unilateral lesion of the upper midbrain tegmentum may be sufficient to generate an upgaze palsy or a combined up- and downgaze palsy, while an isolated downgaze palsy requires bilateral lesions. Images

Bogousslavsky, J; Miklossy, J; Regli, F; Janzer, R

1990-01-01

40

Abnormal Language Pathway in Children with Angelman Syndrome  

PubMed Central

Angelman Syndrome is a genetic disorder characterized by pervasive developmental disability with failure to develop speech. We examined the basis for severe language delay in Angelman Syndrome patients using diffusion tensor imaging. Magnetic Resonance Imaging/diffusion tensor imaging was performed in seven genetically confirmed Angelman Syndrome children (age:70±26 months, five males) and four age-matched controls to investigate the microstructural integrity of arcuate fasciculus and other major association tracts. Six of seven Angelman Syndrome children had unidentifiable left arcuate fasciculus while all controls had identifiable arcuate fasciculus. The right arcuate fasciculus was absent in six of seven Angelman Syndrome children and one of four controls. Diffusion tensor imaging color map suggested aberrant morphology of the arcuate fasciculus region. Other association tracts, including uncinate fasciculus, inferior-fronto-occipital fasciculus, inferior-longitudinal fasciculus, and corticospinal tract, were identifiable but showed decreased fractional anisotropy in Angelman Syndrome children. Increased apparent diffusion coefficient was seen in all tracts except uncinate fasciculus when compared to controls. Angelman Syndrome patients have global impairment of white matter integrity in association tracts, particularly, the arcuate fasciculus which shows severe morphological changes. This could be due to a potential problem with axon guidance during brain development possibly due to loss of UBE3A gene expression.

Wilson, Benjamin J.; Sundaram, Senthil K.; Huq, AHM; Jeong, Jeong-Won; Halverson, Stacey R.; Behen, Michael E.; Bui, Duy Q.; Chugani, Harry T.

2011-01-01

41

Deficits in torsional and vertical rapid eye movements and shift of Listing's plane after uni- and bilateral lesions of the rostral interstitial nucleus of the medial longitudinal fasciculus  

Microsoft Academic Search

The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) contains burst neurons whose activity precedes rapid eye movements with a vertical and\\/or torsional component. To ascertain their causal role in the generation of conjugate eye movements, we placed uni- and bilateral kainic acid lesions in that region. Unilateral inactivation of the riMLF leads to a loss of all rapid

Y. Suzuki; J. A. Biittner-Ennever; D. Straumann; K. Hepp; B. J. M. Hess; V. Henn

1995-01-01

42

The anterior glenohumeral joint capsule: macroscopic and MRI anatomy of the fasciculus obliquus or so-called ligamentum glenohumerale spirale.  

PubMed

The purpose of this study was to demonstrate the macroscopic and MRI anatomy of the fasciculus obliquus, otherwise known as the ligamentum glenohumerale spirale or spiral GHL of the anterior shoulder joint capsule. Conventional and MR arthrography (1.5-T device Somatom Symphony, Siemens with shoulder coil) images in standard planes were compared with gross anatomic dissection findings in six fresh shoulder specimens from three cadavers. The MR imaging protocol included T1, PD and DESS 3D WI sequences. The macroscopically recognisable band-the spiral GHL-was identified by anatomic dissection and MRI in all the specimens. It was best visualised by MR arthrography on axial and oblique sagittal planes (T1; PD WI) and appeared as a low signal intensity stripe within the superficial layer of the anterior joint capsule. The absence of the variable middle glenohumeral ligament did not influence the anatomic properties and the MR imaging of the spiral GHL. Diagnostic visualisation of the normal anatomic structures is a prerequisite to distinguish between normal and pathologic conditions. Anatomy of the spiral GHL can be used by radiologists for more detailed interpretation of the anterior shoulder joint capsule ligaments on MR images. PMID:15022012

Merila, M; Leibecke, T; Gehl, H-B; Busch, L-C; Russlies, M; Eller, A; Haviko, T; Kolts, I

2004-03-12

43

Changes in maps of language function and the integrity of the arcuate fasciculus after therapy for chronic aphasia  

PubMed Central

A patient with chronic aphasia secondary to unilateral stroke in the left hemisphere underwent language testing, diffusion tensor imaging (DTI), and functional imaging using magnetoencephalography (MEG) at four time points: 3 weeks prior to, immediately prior to, immediately after, and 3 months after Constraint Induced Language Therapy (CILT). Performance on language tests involving visual naming and repetition of spoken sentences improved between the immediately prior to and immediately after CILT testing sessions, but not between the pre-CILT sessions. MEG activation in putative pre-morbid language areas of the left hemisphere and homotopic areas of the right hemisphere increased immediately after therapy, as did integrity within the arcuate fasciculus bilaterally. These changes were not evident between the two pre-CILT sessions. While some of these functional, neurophysiological and structural changes had regressed 3 months after therapy, all remained at or above baseline levels. Results provide evidence for an association between improvement in functional status and the increased integrity within a white matter tract known to be involved in language function and its contralateral homologue, as well as increased neurophysiological activity in areas that have the potential to subserve language function bilaterally.

Breier, Joshua I.; Juranek, Jenifer; Papanicolaou, Andrew C.

2012-01-01

44

Sustained attention is associated with right superior longitudinal fasciculus and superior parietal white matter microstructure in children.  

PubMed

Sustained attention develops during childhood and has been linked to the right fronto-parietal cortices in functional imaging studies; however, less is known about its relation to white matter (WM) characteristics. Here we investigated whether the microstructure of the WM underlying and connecting the right fronto-parietal cortices was associated with sustained attention performance in a group of 76 typically developing children aged 7-13 years. Sustained attention was assessed using a rapid visual information processing paradigm. The two behavioral measures of interest were the sensitivity index d' and the coefficient of variation in reaction times (RTCV ). Diffusion-weighted imaging was performed. Mean fractional anisotropy (FA) was extracted from the WM underlying right dorsolateral prefrontal (DLPFC) and parietal cortex (PC), and the right superior longitudinal fasciculus (SLF), as well as equivalent anatomical regions-of-interest (ROIs) in the left hemisphere and mean global WM FA. When analyzed collectively, right hemisphere ROIs FA was significantly associated with d' independently of age. Follow-up analyses revealed that only FA of right SLF and the superior part of the right PC contributed significantly to this association. RTCV was significantly associated with right superior PC FA, but not with right SLF FA. Observed associations remained significant after controlling for FA of equivalent left hemisphere ROIs or global mean FA. In conclusion, better sustained attention performance was associated with higher FA of WM in regions connecting right frontal and parietal cortices. Further studies are needed to clarify to which extent these associations are driven by maturational processes, stable characteristics and/or experience. Hum Brain Mapp 34:3216-3232, 2013. © 2012 Wiley Periodicals, Inc. PMID:22806938

Klarborg, Brith; Skak Madsen, Kathrine; Vestergaard, Martin; Skimminge, Arnold; Jernigan, Terry L; Baaré, William F C

2012-07-17

45

White matter structural connectivity underlying semantic processing: evidence from brain damaged patients.  

PubMed

Widely distributed brain regions in temporal, parietal and frontal cortex have been found to be involved in semantic processing, but the anatomical connections supporting the semantic system are not well understood. In a group of 76 right-handed brain-damaged patients, we tested the relationship between the integrity of major white matter tracts and the presence of semantic deficits. The integrity of white matter tracts was measured by percentage of lesion voxels obtained in structural imaging and mean fractional anisotropy values obtained in diffusion tensor imaging. Semantic deficits were assessed by jointly considering the performance on three semantic tasks that vary in the modalities of input (visual and auditory stimuli) and output (oral naming and associative judgement). We found that the lesion volume and fractional anisotropy value of the left inferior fronto-occipital fasciculus, left anterior thalamic radiation, and left uncinate fasciculus significantly correlated with severity of impairment in all three semantic tasks. These associations remained significant even when we controlled for a wide range of potential confounding variables, including overall cognitive state, whole lesion volume, or type of brain damage. The effects of these three white matter tracts could not be explained by potential involvement of relevant grey matter, and were (relatively) specific to object semantic processing, as no correlation with performance on non-object semantic control tasks (oral repetition and number processing tasks) was observed. These results underscore the causal role of left inferior fronto-occipital fasciculus, left anterior thalamic radiation, and left uncinate fasciculus in semantic processing, providing direct evidence for (part of) the anatomical skeleton of the semantic network. PMID:23975453

Han, Zaizhu; Ma, Yujun; Gong, Gaolang; He, Yong; Caramazza, Alfonso; Bi, Yanchao

2013-08-23

46

Lateralization of the arcuate fasciculus and its differential correlation with reading ability between young learners and experienced readers: a diffusion tensor tractography study in a Chinese cohort.  

PubMed

As Chinese reading engages a different neural network from alphabetic language reading, we investigate whether leftward lateralization of the arcuate fasciculus (AF), as observed in the Western population, is also present in the Chinese population and if it does, whether it is associated with better reading ability. Diffusion tensor tractography analysis on 75 Chinese subjects of three age groups (first graders, fourth graders, and college students) showed that 70-83% of them had leftward lateralization of the AF. The pattern of lateralization did not differ significantly among the three groups, suggesting that lateralization of the AF is formed at an early age and before one enters first grade. Among the first graders, who had just started to learn to read, subjects with strongly leftward lateralized AF scored significantly higher than those with other defined lateralization patterns in Chinese (P = 0.001) and English (P = 0.036) reading tasks. This association was not observed among the fourth graders and college students who were experienced Chinese readers. Among the fourth graders, females were found to obtain significantly higher Chinese (P = 0.033) and English reading scores than males (P = 0.002). Our study suggests a differential effect of leftward lateralization of the AF on reading ability at different stages of reading development in the Chinese population. PMID:21259386

Qiu, Deqiang; Tan, Li-Hai; Siok, Wai-Ting; Zhou, Ke; Khong, Pek-Lan

2011-01-21

47

Downbeat nystagmus associated with damage to the medial longitudinal fasciculus of the pons: a vestibular balance control mechanism via the lower brainstem paramedian tract neurons.  

PubMed

The paramedian tract (PMT) neurons, a group of neurons associated with eye movement that project into the cerebellar flocculus, are present in or near the medial longitudinal fasciculus (MLF) in the paramedian region of the lower brainstem. A 66-year-old man with multiple sclerosis in whom downbeat nystagmus appeared along with right MLF syndrome due to a unilateral pontomedullary lesion is described. In light of these findings, a possible schema for the vestibular balance control mechanism circuit of the PMT neurons via the flocculus is presented. Damage to the PMT neurons impaired the elective inhibitory control mechanism of the anterior semicircular canal neural pathway by the flocculus. This resulted in the appearance of anterior semicircular canal-dominant vestibular imbalance and the formation of downbeat nystagmus. From the pathogenesis of this vertical vestibular nystagmus, the action of the PMT neurons in the vestibular eye movement neuronal pathway to maintain vestibular balance was conjectured to be as follows. PMT neurons transmit vestibular information from the anterior semicircular canals to the cerebellum, forming a cerebellum/brainstem feedback loop. Vestibular information from that loop is integrated in the cerebellum, inhibiting only the anterior semicircular canal neuronal pathway via the flocculus and controlling vestibular balance. PMID:23510567

Nakamagoe, Kiyotaka; Fujizuka, Natsu; Koganezawa, Tadachika; Yamaguchi, Tetsuto; Tamaoka, Akira

2013-03-16

48

Anatomical substrates of cognitive and clinical dimensions in first episode schizophrenia.  

PubMed

OBJECTIVE: To explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first-episode schizophrenia (FES). METHOD: Nineteen patients with first episode of non-affective psychosis and 18 controls underwent a magnetic resonance voxel-based morphometry. Additionally, WM fractional anisotropy (FA) was calculated. For correlative analysis, symptoms and neuropsychological performances were scored by PANSS and by a comprehensive neuropsychological assessment respectively. RESULTS: Patients showed significantly decreased volume of left temporal lobe and disarray of all major WM tracts. Disorganized PANSS factor was inversely related to left cerebellar GM volume (corrected P = 0.03) and to WM FA of the left cerebellum, inferior fronto-occipital fasciculi (IFOF), and inferior longitudinal fasciculi (corrected P < 0.05). PANSS negative factor was inversely related to FA in the IFOF and superior longitudinal fasciculi (corrected P < 0.05). Impairment in facial emotion identification showed associations with temporo-occipital GM volume decrease (corrected P = 0.003) and WM disarray of superior and middle temporal gyri, anterior thalamic radiation, and superior longitudinal fasciculi (corrected P < 0.05). Speed of processing and visual memory correlated with WM abnormalities in fronto-temporal tracts. CONCLUSION: These results confirm how the structural development of key brain regions is related to neuropsychopathological dysfunction in FES, consistently with a neurodevelopmentally derived misconnection syndrome. PMID:23216145

Rigucci, S; Rossi-Espagnet, C; Ferracuti, S; De Carolis, A; Corigliano, V; Carducci, F; Mancinelli, I; Cicone, F; Tatarelli, R; Bozzao, A; Girardi, P; Comparelli, A

2012-12-01

49

Mean diffusivity and fractional anisotropy as indicators of disease and genetic liability to schizophrenia  

PubMed Central

The goals of this study were to first determine whether the fractional anisotropy (FA) and mean diffusivity (MD) of major white matter pathways associate with schizophrenia, and secondly to characterize the extent to which differences in these metrics might reflect a genetic predisposition to schizophrenia. Differences in FA and MD were identified using a comprehensive atlas-based tract mapping approach using diffusion tensor imaging and high resolution structural data from 35 patients, 28 unaffected first-degree relatives of patients, 29 community controls, and 14 first-degree relatives of controls. Schizophrenia patients had significantly higher MD in the following tracts compared to controls: the right anterior thalamic radiations, the forceps minor, the bilateral inferior fronto-occipital fasciculus (IFO), the temporal component of the left superior longitudinal fasciculus (tSLF), and the bilateral uncinate. FA showed schizophrenia effects and a linear relationship to genetic liability (represented by schizophrenia patients, first-degree relatives, and controls) for the bilateral IFO, the left inferior longitudinal fasciculus (ILF), and the left tSLF. Diffusion tensor imaging studies have previously identified white matter abnormalities in all three of these tracts in schizophrenia; however, this study is the first to identify a significant genetic liability. Thus, FA of these three tracts may serve as biomarkers for studies seeking to identify how genes influence brain structure predisposing to schizophrenia. However, differences in FA and MD in frontal and temporal white matter pathways may be additionally driven by state variables that involve processes associated with the disease.

Clark, Kristi A.; Nuechterlein, Keith H.; Asarnow, Robert F.; Hamilton, Liberty S.; Phillips, Owen R.; Hageman, Nathan S.; Woods, Roger P.; Alger, Jeffry R.; Toga, Arthur W.; Narr, Katherine L.

2011-01-01

50

Effects of aging and calorie restriction on white matter in rhesus macaques.  

PubMed

Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of caloric restriction likely include reductions in age-related inflammation and oxidative damage. Oligodendrocytes are particularly susceptible to inflammation and oxidative stress, therefore, we hypothesized that CR would have a beneficial effect on brain white matter and would attenuate age-related decline in this tissue. CR monkeys and controls underwent diffusion tensor imaging (DTI). A beneficial effect of CR indexed by DTI was observed in superior longitudinal fasciculus, fronto-occipital fasciculus, external capsule, and brainstem. Aging effects were observed in several regions, although CR appeared to attenuate age-related alterations in superior longitudinal fasciculus, frontal white matter, external capsule, right parahippocampal white matter, and dorsal occipital bundle. The results, however, were regionally specific and also suggested that CR is not salutary across all white matter. Further evaluation of this unique cohort of elderly primates to mortality will shed light on the ultimate benefits of an adult-onset, moderate CR diet for deferring brain aging. PMID:20541839

Bendlin, B B; Canu, E; Willette, A; Kastman, E K; McLaren, D G; Kosmatka, K J; Xu, G; Field, A S; Colman, R J; Coe, C L; Weindruch, R H; Alexander, A L; Johnson, S C

2010-06-11

51

White Matter Integrity and Behavioral Activation in Healthy Subjects  

PubMed Central

Individual differences in behavioral inhibition and behavioral activation may place certain people at greater risk for neuropsychiatric disorders and engagement in risky behaviors. Therefore, studying the neural correlates of behavioral inhibition and activation may help us understand neural mechanisms underlying risk behaviors in both clinical and non-clinical populations. To investigate, we assessed the relationships between white matter integrity and measures of behavioral inhibition and behavioral activation in 51 healthy participants using diffusion tensor imaging (DTI) and the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale. Scores on the Fun-Seeking subscale of the BAS positively correlated with DTI fractional anisotropy (FA) in the left corona radiata and adjacent superior longitudinal fasciculus, and with mean diffusivity (MD) in the left inferior longitudinal fasciculus and inferior fronto-occipital fasciculus after controlling for age, gender, and education. These findings suggest that the integrity of white matter connecting extensive brain regions implicated in self-control and the processing of rewards and emotions are associated with individual differences in the motivation for seeking and participating in fun and novel experiences.

Xu, Jiansong; Kober, Hedy; Carroll, Kathleen M.; Rounsaville, Bruce J.; Pearlson, Godfrey D.; Potenza, Marc N.

2011-01-01

52

White matter integrity and behavioral activation in healthy subjects.  

PubMed

Individual differences in behavioral inhibition and behavioral activation may place certain people at greater risk for neuropsychiatric disorders and engagement in risky behaviors. Therefore, studying the neural correlates of behavioral inhibition and activation may help us understand neural mechanisms underlying risk behaviors in both clinical and non-clinical populations. To investigate, we assessed the relationships between white matter integrity and measures of behavioral inhibition and behavioral activation in 51 healthy participants using diffusion tensor imaging (DTI) and the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale. Scores on the Fun-Seeking subscale of the BAS positively correlated with DTI fractional anisotropy in the left corona radiata and adjacent superior longitudinal fasciculus, and with mean diffusivity in the left inferior longitudinal fasciculus and inferior fronto-occipital fasciculus after controlling for age, gender, and education. These findings suggest that the integrity of white matter connecting extensive brain regions implicated in self-control and the processing of rewards and emotions are associated with individual differences in the motivation for seeking and participating in fun and novel experiences. PMID:21618658

Xu, Jiansong; Kober, Hedy; Carroll, Kathleen M; Rounsaville, Bruce J; Pearlson, Godfrey D; Potenza, Marc N

2011-05-26

53

Fiber Dissection and DTI Tractography Study of the Temporo-parietal Fiber Intersection Area.  

PubMed

BACKGROUND:: Lesion studies and recent surgical series report important sequelae when damaging the inferior parietal lobe and posterior temporal lobe. Millions of axons cross through the white matter underlying these cortical areas; however, little is known about the complex organization of these connections. OBJECTIVE:: To analyze the subcortical anatomy of a specific region within the parietal and temporal lobes where seven long-distances tracts intersect, i.e. the temporo-parietal fiber intersection area (TPFIA). METHODS:: Four postmortem human hemispheres were dissected, and four healthy hemispheres were analyzed using DTI-based tractography software. The different tracts that intersect at the posterior temporal and parietal lobes were isolated and the relations with the surrounding structures analyzed. RESULTS:: Seven tracts pass through the TPFIA: horizontal portion of the superior longitudinal fasciculus, arcuate fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, optic radiations, and tapetum. The TPFIA was located deep to the angular gyrus, posterior portion of the supramarginal gyrus, and posterior portion of the superior, middle, and inferior temporal gyri. CONCLUSION:: The TPFIA is a critical neural crossroad, as it is traversed by seven white matter tracts that connect multiple areas of the ipsilateral and contralateral hemisphere. It is also a vulnerable part of the network, as a lesion within this area will produce multiple disconnections. This is valuable information when planning a surgical approach through the parieto-temporo-occipital junction. In order to decrease the surgical risks, a detailed DTI tractography reconstruction of the TPFIA should be performed and intraoperative electrical stimulation should be strongly considered. PMID:23037819

Martino, Juan; da Silva-Feritas, Rousinelle; Caballero, Hugo; Marco de Lucas, Enrique; García-Porrero, Juan A; Vázquez-Barquero, Alfonso

2012-10-01

54

Brain connectivity in body dysmorphic disorder compared with controls: a diffusion tensor imaging study.  

PubMed

BACKGROUND: Several neuroimaging studies have investigated brain grey matter in people with body dysmorphic disorder (BDD), showing possible abnormalities in the limbic system, orbitofrontal cortex, caudate nuclei and temporal lobes. This study takes these findings forward by investigating white matter properties in BDD compared with controls using diffusion tensor imaging. It was hypothesized that the BDD sample would have widespread significantly reduced white matter connectivity as characterized by fractional anisotropy (FA). Method A total of 20 participants with BDD and 20 healthy controls matched on age, gender and handedness underwent diffusion tensor imaging. FA, a measure of water diffusion within a voxel, was compared between groups on a voxel-by-voxel basis across the brain using tract-based spatial statistics within the FSL package. RESULTS: Results showed that, compared with healthy controls, BDD patients demonstrated significantly lower FA (p < 0.05) in most major white matter tracts throughout the brain, including in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus and corpus callosum. Lower FA levels could be accounted for by increased radial diffusivity as characterized by eigenvalues 2 and 3. No area of higher FA was found in BDD. CONCLUSIONS: This study provided the first evidence of compromised white matter integrity within BDD patients. This suggests that there are inefficient connections between different brain areas, which may explain the cognitive and emotion regulation deficits within BDD patients. PMID:23473554

Buchanan, B G; Rossell, S L; Maller, J J; Toh, W L; Brennan, S; Castle, D J

2013-03-11

55

White matter microstructure in body dysmorphic disorder and its clinical correlates.  

PubMed

Body dysmorphic disorder (BDD) is characterized by an often-delusional preoccupation with misperceived defects of appearance, causing significant distress and disability. Although previous studies have found functional abnormalities in visual processing, frontostriatal, and limbic systems, no study to date has investigated the microstructure of white matter connecting these systems in BDD. Participants comprised 14 medication-free individuals with BDD and 16 healthy controls who were scanned using diffusion-weighted magnetic resonance imaging (MRI). We utilized probabilistic tractography to reconstruct tracts of interest, and tract-based spatial statistics to investigate whole brain white matter. To estimate white matter microstructure, we used fractional anisotropy (FA), mean diffusivity (MD), and linear and planar anisotropy (c(l) and c(p)). We correlated diffusion measures with clinical measures of symptom severity and poor insight/delusionality. Poor insight negatively correlated with FA and c(l) and positively correlated with MD in the inferior longitudinal fasciculus (ILF) and the forceps major (FM). FA and c(l) were lower in the ILF and the inferior fronto-occipital fasciculus and higher in the FM in the BDD group, but differences were nonsignificant. This is the first diffusion-weighted MR investigation of white matter in BDD. Results suggest a relationship between impairments in insight, a clinically important phenotype, and fiber disorganization in tracts connecting visual with emotion/memory processing systems. PMID:23375265

Feusner, Jamie D; Arienzo, Donatello; Li, Wei; Zhan, Liang; Gadelkarim, Johnson; Thompson, Paul M; Leow, Alex D

2013-02-01

56

Sex differences in white matter development during adolescence: A DTI study  

PubMed Central

Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Our results suggest that boys (13–18 years) continued to demonstrate white matter maturation, whereas girls appeared to reach mature levels earlier. In addition, we identified significant positive correlations between FA and full-scale intelligence quotient (IQ) in the right inferior fronto-occipital fasciculus when both sexes were looked at together. Only girls showed significant positive correlations between FA and verbal IQ in the left cortico-spinal tract and superior longitudinal fasciculus. The preliminary evidence presented in this study supports that boys and girls have different developmental trajectories in white matter microstructure.

Wang, Yingying; Adamson, Chris; Yuan, Weihong; Altaye, Mekibib; Rajagopal, Akila; Byars, Anna W.; Holland, Scott K.

2012-01-01

57

Decreased white matter integrity before the onset of delusions in patients with Alzheimer's disease: diffusion tensor imaging  

PubMed Central

Background The pathology of delusions in patients with Alzheimer’s disease (AD) associated with white matter (WM) abnormalities is poorly understood. In addition, whether the abnormalities in WM integrity that underlie the delusions develop before the onset of the delusions remains unclear. In this study, we used a diffusion tensor imaging approach to examine the existence of baseline abnormalities in WM integrity in AD patients who developed delusions and AD patients who did not develop delusions. Methods Using the Neuropsychiatric Inventory, we identified patients with AD who exhibit delusions during a 1-year period. All the patients underwent a magnetic resonance imaging (MRI) examination at baseline. We conducted fractional anisotropy using tract-based spatial statistics software and compared the results of AD patients who developed delusions with those who did not develop delusions. Results Compared with the AD patients who did not develop delusions (n = 15), the AD patients who developed delusions (n = 10) exhibited two relatively large clusters and one minimal cluster of significantly lower fractional anisotropy results. The first cluster was located in the left parieto-occipital region and included several fibers: the left inferior longitudinal fasciculus, the inferior fronto-occipital fasciculus, the posterior corona radiate, and the forceps major of the corpus callosum. The second cluster was located on the body of the corpus callosum. A third minimal cluster was located on the superior temporal gyrus white matter. Conclusion Abnormalities in WM integrity involving several fibers may be crucial to the development of delusions in AD patients.

Nakaaki, Shutaro; Sato, Junko; Torii, Katsuyoshi; Oka, Mizuki; Negi, Atsushi; Nakamae, Takashi; Narumoto, Jin; Miyata, Jun; Furukawa, Toshi A; Mimura, Masaru

2013-01-01

58

Emerging Structure-Function Relations in the Developing Face Processing System.  

PubMed

To evaluate emerging structure-function relations in a neural circuit that mediates complex behavior, we investigated age-related differences among cortical regions that support face recognition behavior and the fiber tracts through which they transmit and receive signals using functional neuroimaging and diffusion tensor imaging. In a large sample of human participants (aged 6-23 years), we derived the microstructural and volumetric properties of the inferior longitudinal fasciculus (ILF), the inferior fronto-occipital fasciculus, and control tracts, using independently defined anatomical markers. We also determined the functional characteristics of core face- and place-selective regions that are distributed along the trajectory of the pathways of interest. We observed disproportionately large age-related differences in the volume, fractional anisotropy, and mean and radial, but not axial, diffusivities of the ILF. Critically, these differences in the structural properties of the ILF were tightly and specifically linked with an age-related increase in the size of a key face-selective functional region, the fusiform face area. This dynamic association between emerging structural and functional architecture in the developing brain may provide important clues about the mechanisms by which neural circuits become organized and optimized in the human cortex. PMID:23765156

Suzanne Scherf, K; Thomas, Cibu; Doyle, Jaime; Behrmann, Marlene

2013-06-13

59

Magnetic resonance imaging correlates of first-episode psychosis in young adult male patients: combined analysis of grey and white matter  

PubMed Central

Background Several patterns of grey and white matter changes have been separately described in young adults with first-episode psychosis. Concomitant investigation of grey and white matter densities in patients with first-episode psychosis without other psychiatric comorbidities that include all relevant imaging markers could provide clues to the neurodevelopmental hypothesis in schizophrenia. Methods We recruited patients with first-episode psychosis diagnosed according to the DSM-IV-TR and matched controls. All participants underwent magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis and mean diffusivity voxel-based analysis (VBA) were used for grey matter data. Fractional anisotropy and axial, radial and mean diffusivity were analyzed using tract-based spatial statistics (TBSS) for white matter data. Results We included 15 patients and 16 controls. The mean diffusivity VBA showed significantly greater mean diffusivity in the first-episode psychosis than in the control group in the lingual gyrus bilaterally, the occipital fusiform gyrus bilaterally, the right lateral occipital gyrus and the right inferior temporal gyrus. Moreover, the TBSS analysis revealed a lower fractional anisotropy in the first-episode psychosis than in the control group in the genu of the corpus callosum, minor forceps, corticospinal tract, right superior longitudinal fasciculus, left middle cerebellar peduncle, left inferior longitudinal fasciculus and the posterior part of the fronto-occipital fasciculus. This analysis also revealed greater radial diffusivity in the first-episode psychosis than in the control group in the right corticospinal tract, right superior longitudinal fasciculus and left middle cerebellar peduncle. Limitations The modest sample size and the absence of women in our series could limit the impact of our results. Conclusion Our results highlight the structural vulnerability of grey matter in posterior areas of the brain among young adult male patients with first-episode psychosis. Moreover, the concomitant greater radial diffusivity within several regions already revealed by the fractional anisotropy analysis supports the idea of a late myelination in patients with first-episode psychosis.

Ruef, Anne; Curtis, Logos; Moy, Guenael; Bessero, Severine; Ba, Maryse Badan; Lazeyras, Francois; Lovblad, Karl-Olof; Haller, Sven; Malafosse, Alain; Giannakopoulos, Panteleimon; Merlo, Marco

2012-01-01

60

White matter integrity, language, and childhood onset schizophrenia  

PubMed Central

Background The heterogeneity of symptoms and cognitive deficits in schizophrenia can be explained by abnormal connectivity between brain regions. Childhood-onset schizophrenia (COS) is a particularly severe form of schizophrenia, with an onset during a key time period for both cerebral pruning and myelination. Methods Diffusion tensor images were acquired from 18 children and adolescents with COS and 25 controls. The COS group was divided into two sub-groups--one with linguistic impairment (LI) and the other without (NLI). The fractional anisotropy (FA), axial (AD), and radial diffusivity (RD) data from the two COS sub-groups were compared to each other and to the controls using tract-based spatial statistics (TBSS) analyses, which is a voxel-based method used to identify regions of white matter abnormalities. Results TBSS identified several regions in the left hemisphere where the LI group had increased AD and RD relative to the NLI and the control groups. These areas primarily localized to linguistic tracts: left superior longitudinal fasciculus and left inferior longitudinal fasciculus/inferior fronto-occipital fasciculus. Regions of increased RD overlapped regions of increased AD, with the former showing more pronounced effects. Conclusions Studies of adult-onset schizophrenia typically identify areas of higher RD but unchanged AD; however, normal development studies have shown that while RD decreases are pronounced over this age range, smaller decreases in AD can also be detected. The observed increases in both RD and AD suggest that developmental disturbances affecting the structural connectivity of these pathways are more severe in COS accompanied by severe linguistic impairments.

Clark, Kristi; Narr, Katherine L.; O'Neill, Joseph; Levitt, Jennifer; Siddarth, Prabha; Phillips, Owen; Toga, Arthur; Caplan, Rochelle

2012-01-01

61

BDNF GENE EFFECTS ON BRAIN CIRCUITRY REPLICATED IN 455 TWINS  

PubMed Central

Brain-derived neurotrophic factor (BDNF) plays a key role in learning and memory, but its effects on the fiber architecture of the living brain are unknown. We genotyped 455 healthy adult twins and their non-twin siblings (188 males/267 females; age: 23.7±2.1 years, mean±SD) and scanned them with high angular resolution diffusion tensor imaging (DTI), to assess how the BDNF Val66Met polymorphism affects white matter microstructure. By applying genetic association analysis to every 3D point in the brain images, we found that the Val-BDNF genetic variant was associated with lower white matter integrity in the splenium of the corpus callosum, left optic radiation, inferior fronto-occipital fasciculus, and superior corona radiata. Normal BDNF variation influenced the association between subjects’ performance intellectual ability (as measured by Object Assembly subtest) and fiber integrity (as measured by fractional anisotropy; FA) in the callosal splenium, and pons. The BDNF gene may affect intellectual performance by modulating white matter development. This combination of genetic association analysis and large-scale diffusion imaging directly relates a specific gene to the fiber microstructure of the living brain and to human intelligence.

Chiang, Ming-Chang; Barysheva, Marina; Toga, Arthur W.; Medland, Sarah E.; Hansell, Narelle K.; James, Michael R.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.

2011-01-01

62

White matter integrity and vulnerability to Alzheimer's disease: Preliminary findings and future directions  

PubMed Central

Neuroimaging biomarkers that precede cognitive decline have the potential to aid early diagnosis of Alzheimer's disease (AD). A body of diffusion tensor imaging (DTI) work has demonstrated declines in white matter (WM) microstructure in AD and its typical prodromal state, amnestic mild cognitive impairment. The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline. The available data suggest that AD-risk is associated with WM integrity declines in a subset of tracts showing decline in symptomatic AD. Specifically, AD-risk has been associated with WM integrity declines in tracts that connect grey matter structures associated with memory function. These tracts include parahippocampal WM, the cinglum, the inferior fronto-occipital fasciculus, and the splenium of the corpus callosum. Preliminary evidence suggests that some AD-risk declines are characterized by increases of radial diffusivity, raising the possibility that a myelin-related pathology may contribute to AD onset. These findings justify future research aimed at a more complete understanding of the neurobiological bases of DTI-based declines in AD. With continued refinement of imaging methods, DTI holds promise as a method to aid identification of presymptomatic AD.

Gold, Brian T.; Johnson, Nathan F.; Powell, David K.; Smith, Charles D.

2011-01-01

63

BDNF gene effects on brain circuitry replicated in 455 twins.  

PubMed

Brain-derived neurotrophic factor (BDNF) plays a key role in learning and memory, but its effects on the fiber architecture of the living brain are unknown. We genotyped 455 healthy adult twins and their non-twin siblings (188 males/267 females; age: 23.7±2.1 years, mean±SD) and scanned them with high angular resolution diffusion tensor imaging (DTI), to assess how the BDNF Val66Met polymorphism affects white matter microstructure. By applying genetic association analysis to every 3D point in the brain images, we found that the Val-BDNF genetic variant was associated with lower white matter integrity in the splenium of the corpus callosum, left optic radiation, inferior fronto-occipital fasciculus, and superior corona radiata. Normal BDNF variation influenced the association between subjects' performance intellectual ability (as measured by Object Assembly subtest) and fiber integrity (as measured by fractional anisotropy; FA) in the callosal splenium, and pons. BDNF gene may affect the intellectual performance by modulating the white matter development. This combination of genetic association analysis and large-scale diffusion imaging directly relates a specific gene to the fiber microstructure of the living brain and to human intelligence. PMID:21195196

Chiang, Ming-Chang; Barysheva, Marina; Toga, Arthur W; Medland, Sarah E; Hansell, Narelle K; James, Michael R; McMahon, Katie L; de Zubicaray, Greig I; Martin, Nicholas G; Wright, Margaret J; Thompson, Paul M

2010-12-30

64

Sex-linked white matter microstructure of the social and analytic brain.  

PubMed

Sexual dimorphism in the brain is known to underpin sex differences in neuropsychological behaviors. The white matter (WM) microstructure appears to be coupled with cognitive performances. However, the issues concerning sex differences in WM remains to be determined. This study used the tract-based spatial statistics on diffusion tensor imaging concurrently with the assessments of Empathizing Quotient (EQ) and Systemizing Quotient (SQ) in forty healthy female and forty male adults. Females exhibited greater fractional anisotropy (FA) in the fronto-occipital fasciculus, body of the corpus callosum, and WM underlying the parahippocampal gyrus. Males exhibited larger FA in the bilateral internal capsule, WM underlying the medial frontal gyrus, fusiform gyrus, hippocampus, insula, postcentral gyrus, frontal and temporal lobe. Interestingly, the interaction analysis of dispositional measures by sex showed that females had a positive correlation between FA of the WM underlying the inferior parietal lobule and superior temporal gyrus and EQ but a negative correlation between FA of the occipital and postcentral gyrus and SQ. Males displayed the opposite effect. The findings indicate a sexual dimorphism of WM microstructure. Divergent correlations of WM microstructure and neuropsychological behaviors between sexes may account for the higher prevalence of autism spectrum disorders in males. PMID:20633662

Chou, Kun-Hsien; Cheng, Yawei; Chen, I-Yun; Lin, Ching-Po; Chu, Woei-Chyn

2010-07-12

65

Covert face recognition without the fusiform-temporal pathways.  

PubMed

Patients with prosopagnosia are unable to recognize faces consciously, but when tested indirectly they can reveal residual identification abilities. The neural circuitry underlying this covert recognition is still unknown. One candidate for this function is the partial survival of a pathway linking the fusiform face area (FFA) and anterior-inferior temporal (AIT) cortex, which has been shown to be essential for conscious face identification. Here we performed functional magnetic, and diffusion tensor imaging in FE, a patient with severe prosopagnosia, with the goal of identifying the neural substrates of his robust covert face recognition. FE presented massive bilateral lesions in the fusiform gyri that eliminated both FFAs, and also disrupted the fibers within the inferior longitudinal fasciculi that link the visual areas with the AITs and medial temporal lobes. Therefore participation of the fusiform-temporal pathway in his covert recognition was precluded. However, face-selective activations were found bilaterally in his occipital gyri and in his extended face system (posterior cingulate and orbitofrontal areas), the latter with larger responses for previously-known faces than for faces of strangers. In the right hemisphere, these surviving face selective-areas were connected via a partially persevered inferior fronto-occipital fasciculus. This suggests an alternative occipito-frontal pathway, absent from current models of face processing, that could explain the patient's covert recognition while also playing a role in unconscious processing during normal cognition. PMID:21570471

Valdés-Sosa, Mitchell; Bobes, Maria A; Quiñones, Ileana; Garcia, Lorna; Valdes-Hernandez, Pedro A; Iturria, Yasser; Melie-Garcia, Lester; Lopera, Francisco; Asencio, José

2011-05-04

66

GENETIC INFLUENCES ON BRAIN ASYMMETRY: A DTI STUDY OF 374 TWINS AND SIBLINGS  

PubMed Central

Brain asymmetry, or the structural and functional specialization of each brain hemisphere, has fascinated neuroscientists for over a century. Even so, genetic and environmental factors that influence brain asymmetry are largely unknown. Diffusion tensor imaging (DTI) now allows asymmetry to be studied at a microscopic scale by examining differences in fiber characteristics across hemispheres rather than differences in structure shapes and volumes. Here we analyzed 4 Tesla DTI scans from 374 healthy adults, including 60 monozygotic twin pairs, 45 same-sex dizygotic pairs, and 164 mixed-sex DZ twins and their siblings; mean age: 24.4 years +/? 1.9SD). All DTI scans were nonlinearly aligned to a geometrically-symmetric, population-based image template. We computed voxel-wise maps of significant asymmetries (left/right differences) for common diffusion measures that reflect fiber integrity (fractional and geodesic anisotropy; FA, GA and mean diffusivity, MD). In quantitative genetic models computed from all same-sex twin pairs (N=210 subjects), genetic factors accounted for 33% of the variance in asymmetry for the inferior fronto-occipital fasciculus, 37% for the anterior thalamic radiation, and 20% for the forceps major and uncinate fasciculus (all L>R). Shared environmental factors accounted for around 15% of the variance in asymmetry for the cortico-spinal tract (R>L) and about 10% for the forceps minor (L>R). Sex differences in asymmetry (men > women) were significant, and were greatest in regions with prominent FA asymmetries. These maps identify heritable DTI-derived features, and may empower genome-wide searches for genetic polymorphisms that influence brain asymmetry.

Jahanshad, Neda; Lee, Agatha D.; Barysheva, Marina; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Toga, Arthur W.; Thompson, Paul M.

2011-01-01

67

Genetic influences on brain asymmetry: a DTI study of 374 twins and siblings.  

PubMed

Brain asymmetry, or the structural and functional specialization of each brain hemisphere, has fascinated neuroscientists for over a century. Even so, genetic and environmental factors that influence brain asymmetry are largely unknown. Diffusion tensor imaging (DTI) now allows asymmetry to be studied at a microscopic scale by examining differences in fiber characteristics across hemispheres rather than differences in structure shapes and volumes. Here we analyzed 4Tesla DTI scans from 374 healthy adults, including 60 monozygotic twin pairs, 45 same-sex dizygotic pairs, and 164 mixed-sex DZ twins and their siblings; mean age: 24.4years+/-1.9 SD). All DTI scans were nonlinearly aligned to a geometrically-symmetric, population-based image template. We computed voxel-wise maps of significant asymmetries (left/right differences) for common diffusion measures that reflect fiber integrity (fractional and geodesic anisotropy; FA, GA and mean diffusivity, MD). In quantitative genetic models computed from all same-sex twin pairs (N=210 subjects), genetic factors accounted for 33% of the variance in asymmetry for the inferior fronto-occipital fasciculus, 37% for the anterior thalamic radiation, and 20% for the forceps major and uncinate fasciculus (all L>R). Shared environmental factors accounted for around 15% of the variance in asymmetry for the cortico-spinal tract (R>L) and about 10% for the forceps minor (L>R). Sex differences in asymmetry (men>women) were significant, and were greatest in regions with prominent FA asymmetries. These maps identify heritable DTI-derived features, and may empower genome-wide searches for genetic polymorphisms that influence brain asymmetry. PMID:20430102

Jahanshad, Neda; Lee, Agatha D; Barysheva, Marina; McMahon, Katie L; de Zubicaray, Greig I; Martin, Nicholas G; Wright, Margaret J; Toga, Arthur W; Thompson, Paul M

2010-04-27

68

Relationship of a variant in the NTRK1 gene to white matter microstructure in young adults.  

PubMed

The NTRK1 gene (also known as TRKA) encodes a high-affinity receptor for NGF, a neurotrophin involved in nervous system development and myelination. NTRK1 has been implicated in neurological function via links between the T allele at rs6336 (NTRK1-T) and schizophrenia risk. A variant in the neurotrophin gene, BDNF, was previously associated with white matter integrity in young adults, highlighting the importance of neurotrophins to white matter development. We hypothesized that NTRK1-T would relate to lower fractional anisotropy in healthy adults. We scanned 391 healthy adult human twins and their siblings (mean age: 23.6 ± 2.2 years; 31 NTRK1-T carriers, 360 non-carriers) using 105-gradient diffusion tensor imaging at 4 tesla. We evaluated in brain white matter how NTRK1-T and NTRK1 rs4661063 allele A (rs4661063-A, which is in moderate linkage disequilibrium with rs6336) related to voxelwise fractional anisotropy-a common diffusion tensor imaging measure of white matter microstructure. We used mixed-model regression to control for family relatedness, age, and sex. The sample was split in half to test reproducibility of results. The false discovery rate method corrected for voxelwise multiple comparisons. NTRK1-T and rs4661063-A correlated with lower white matter fractional anisotropy, independent of age and sex (multiple-comparisons corrected: false discovery rate critical p = 0.038 for NTRK1-T and 0.013 for rs4661063-A). In each half-sample, the NTRK1-T effect was replicated in the cingulum, corpus callosum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculus, superior corona radiata, and uncinate fasciculus. Our results suggest that NTRK1-T is important for developing white matter microstructure. PMID:22539856

Braskie, Meredith N; Jahanshad, Neda; Stein, Jason L; Barysheva, Marina; Johnson, Kori; McMahon, Katie L; de Zubicaray, Greig I; Martin, Nicholas G; Wright, Margaret J; Ringman, John M; Toga, Arthur W; Thompson, Paul M

2012-04-25

69

Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression  

PubMed Central

Background Relatives of patients with major depressive disorder (MDD) and people who experienced early-life adversity are at risk for MDD. The aim of our study was to investigate whether unaffected first-degree healthy relatives (UHRs) of patients with MDD show changes in white matter fibre connections compared with healthy controls and whether there are interactions between early-life adversity and these microstructural changes. Methods Unaffected, healthy first-degree relatives of patients with MDD and healthy controls without any family history for a psychiatric disease underwent high angular resolution diffusion imaging with 61 diffusion directions. Data were analyzed with tract-based spatial statistics, and findings were confirmed with tractography. Results Twenty-one UHRs and 24 controls participated in our study. The UHRs showed greater fractional anisotropy than controls in the body and splenium of the corpus callosum, inferior fronto-occipital fasciculus (IFO), left superior longitudinal fasciculus (SLF) and right fornix. The UHRs who experienced more early-life adversity had greater fractional anisotropy than those with less early-life adversity in the splenium of the corpus callosum, fornix, IFO and SLF; in controls, early-life adversity was found to be associated with decreased fractional anisotropy in these fibre tracts. Limitations Studying participants’ strategies for coping with early-life adversity would have been helpful. Crossing fibres in tracts are a general limitation of the method used. Conclusion Altogether, our findings provide evidence for greater fractional anisotropy in UHRs and for interaction between early-life adversity and family risk on white matter tracts involved in cognitive–emotional processes. Whether stronger neural fibre connections are associated with more resilience against depression needs to be addressed in future studies.

Frodl, Thomas; Carballedo, Angela; Fagan, Andrew J.; Lisiecka, Danuta; Ferguson, Yolande; Meaney, James F.

2012-01-01

70

White matter microstructure in untreated first episode bipolar disorder with psychosis: comparison with schizophrenia  

PubMed Central

Objectives White matter abnormalities have been reported in bipolar disorder. The present study aimed to investigate white matter integrity in untreated first episode patients with psychotic bipolar disorder using diffusion tensor imaging, and to compare observations with those from untreated first episode schizophrenia patients. Methods Fractional anisotropy and mean diffusivity were measured in first episode psychotic patients with bipolar disorder (n = 13) or schizophrenia (n = 21) and healthy individuals (n = 18). Group differences were evaluated using voxel based morphometry. Axial and radial diffusivity were examined in regions with altered fractional anisotropy in post-hoc analyses. Results Patients with bipolar disorder showed lower fractional anisotropy than healthy controls in several white matter tracts. Compared with schizophrenia patients, bipolar disorder patients showed lower fractional anisotropy in the cingulum, internal capsule, posterior corpus callosum, tapetum, and occipital white matter including posterior thalamic radiation and inferior longitudinal fasciculus/inferior fronto-occipital fasciculus. Lower fractional anisotropy in bipolar disorder was characterized by increased radial diffusion rather than axial diffusion along the orientation of fiber tracts. Across several white matter tracts, both patient groups showed greater mean diffusivity than healthy individuals. Conclusions Selectively increased radial diffusivity in bipolar disorder patients suggests structural disorganization in fiber tract coherence of neurodevelopmental origin or alterations in myelin sheaths along fiber tracts. In contrast, increased isotropic diffusion along white matter tracts in schizophrenia patients with alterations in both radial and axial diffusivity suggests increased water content outside of axonal space. Thus, the present results suggest that different pathophysiological mechanisms may underlie white matter microstructural abnormalities in bipolar disorder and schizophrenia.

Lu, Lisa H; Zhou, Xiaohong Joe; Keedy, Sarah K; Reilly, James L; Sweeney, John A

2012-01-01

71

White matter integrity, substance use, and risk taking in adolescence.  

PubMed

White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n = 47) and demographically similar nonusers (n = 49) received diffusion tensor imaging at baseline (ages 16-19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17-20). Brain regions of interest were the fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance-using youth (n = 47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (?R2 = 10-12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (?R2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic-system fibers and future substance-use frequency. Subcortical white matter coherence, along with an imbalance between the maturation levels in cognitive control and reward systems, may disadvantage the resistance to engage in risk taking behaviors during adolescence. PMID:22564204

Jacobus, Joanna; Thayer, Rachel E; Trim, Ryan S; Bava, Sunita; Frank, Lawrence R; Tapert, Susan F

2012-05-07

72

Repeating with the right hemisphere: reduced interactions between phonological and lexical-semantic systems in crossed aphasia?  

PubMed Central

Knowledge on the patterns of repetition amongst individuals who develop language deficits in association with right hemisphere lesions (crossed aphasia) is very limited. Available data indicate that repetition in some crossed aphasics experiencing phonological processing deficits is not heavily influenced by lexical-semantic variables (lexicality, imageability, and frequency) as is regularly reported in phonologically-impaired cases with left hemisphere damage. Moreover, in view of the fact that crossed aphasia is rare, information on the role of right cortical areas and white matter tracts underpinning language repetition deficits is scarce. In this study, repetition performance was assessed in two patients with crossed conduction aphasia and striatal/capsular vascular lesions encompassing the right arcuate fasciculus (AF) and inferior frontal-occipital fasciculus (IFOF), the temporal stem and the white matter underneath the supramarginal gyrus. Both patients showed lexicality effects repeating better words than non-words, but manipulation of other lexical-semantic variables exerted less influence on repetition performance. Imageability and frequency effects, production of meaning-based paraphrases during sentence repetition, or better performance on repeating novel sentences than overlearned clichés were hardly ever observed in these two patients. In one patient, diffusion tensor imaging disclosed damage to the right long direct segment of the AF and IFOF with relative sparing of the anterior indirect and posterior segments of the AF, together with fully developed left perisylvian white matter pathways. These findings suggest that striatal/capsular lesions extending into the right AF and IFOF in some individuals with right hemisphere language dominance are associated with atypical repetition patterns which might reflect reduced interactions between phonological and lexical-semantic processes.

De-Torres, Irene; Davila, Guadalupe; Berthier, Marcelo L.; Walsh, Sean Froudist; Moreno-Torres, Ignacio; Ruiz-Cruces, Rafael

2013-01-01

73

Repeating with the right hemisphere: reduced interactions between phonological and lexical-semantic systems in crossed aphasia?  

PubMed

Knowledge on the patterns of repetition amongst individuals who develop language deficits in association with right hemisphere lesions (crossed aphasia) is very limited. Available data indicate that repetition in some crossed aphasics experiencing phonological processing deficits is not heavily influenced by lexical-semantic variables (lexicality, imageability, and frequency) as is regularly reported in phonologically-impaired cases with left hemisphere damage. Moreover, in view of the fact that crossed aphasia is rare, information on the role of right cortical areas and white matter tracts underpinning language repetition deficits is scarce. In this study, repetition performance was assessed in two patients with crossed conduction aphasia and striatal/capsular vascular lesions encompassing the right arcuate fasciculus (AF) and inferior frontal-occipital fasciculus (IFOF), the temporal stem and the white matter underneath the supramarginal gyrus. Both patients showed lexicality effects repeating better words than non-words, but manipulation of other lexical-semantic variables exerted less influence on repetition performance. Imageability and frequency effects, production of meaning-based paraphrases during sentence repetition, or better performance on repeating novel sentences than overlearned clichés were hardly ever observed in these two patients. In one patient, diffusion tensor imaging disclosed damage to the right long direct segment of the AF and IFOF with relative sparing of the anterior indirect and posterior segments of the AF, together with fully developed left perisylvian white matter pathways. These findings suggest that striatal/capsular lesions extending into the right AF and IFOF in some individuals with right hemisphere language dominance are associated with atypical repetition patterns which might reflect reduced interactions between phonological and lexical-semantic processes. PMID:24151460

De-Torres, Irene; Dávila, Guadalupe; Berthier, Marcelo L; Walsh, Seán Froudist; Moreno-Torres, Ignacio; Ruiz-Cruces, Rafael

2013-10-18

74

Word learning is mediated by the left arcuate fasciculus.  

PubMed

Human language requires constant learning of new words, leading to the acquisition of an average vocabulary of more than 30,000 words in adult life. The ability to learn new words is highly variable and may rely on the integration between auditory and motor information. Here, we combined diffusion imaging tractography and functional MRI to study whether the strength of anatomical and functional connectivity between auditory and motor language networks is associated with word learning ability. Our results showed that performance in word learning correlates with microstructural properties and strength of functional connectivity of the direct connections between Broca's and Wernicke's territories in the left hemisphere. This study suggests that our ability to learn new words relies on an efficient and fast communication between temporal and frontal areas. The absence of these connections in other animals may explain the unique ability of learning words in humans. PMID:23884655

López-Barroso, Diana; Catani, Marco; Ripollés, Pablo; Dell'Acqua, Flavio; Rodríguez-Fornells, Antoni; de Diego-Balaguer, Ruth

2013-07-24

75

Reading Impairment in a Patient with Missing Arcuate Fasciculus  

ERIC Educational Resources Information Center

|We describe the case of a child ("S") who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. "S" was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive…

Rauschecker, Andreas M.; Deutsch, Gayle K.; Ben-Shachar, Michal; Schwartzman, Armin; Perry, Lee M.; Dougherty, Robert F.

2009-01-01

76

Prediction of post-surgical seizure outcome in left mesial temporal lobe epilepsy?  

PubMed Central

Mesial temporal lobe epilepsy is the most common type of focal epilepsy and in its course often becomes refractory to anticonvulsant pharmacotherapy. A resection of the mesial temporal lobe structures is a promising option in these cases. However, approximately 30% of all patients remain with persistent seizures after surgery. In other words, reliable criteria for patients' outcome prediction are absent. To address this limitation, we investigated pre-surgical brain morphology of patients with unilateral left mesial temporal lobe epilepsy who underwent a selective amygdalohippocampectomy. Using support vector classification, we aimed to predict the post-surgical seizure outcome of each patient based on the pre-surgical T1-weighted structural brain images. Due to morphological gender differences and the evidence that men and women differ in onset, prevalence and symptomology in most neurological diseases, we investigated male and female patients separately. Thus, we benefitted from the capability to validate the reliability of our method in two independent samples. Notably, we were able to accurately predict the individual patients' outcome in the male (94% balanced accuracy) as well as in the female (96% balanced accuracy) group. In the male cohort relatively larger white matter volumes in the favorable as compared to the non-favorable outcome group were identified bilaterally in the cingulum bundle, fronto-occipital fasciculus and both caudate nuclei, whereas the left inferior longitudinal fasciculus showed relatively larger white matter volume in the non-favorable group. While relatively larger white matter volumes in the female cohort in the left inferior and right middle longitudinal fasciculus were associated with the favorable outcome, relatively larger white matter volumes in the non-favorable outcome group were identified bilaterally in the superior longitudinal fasciculi I and II. Here, we observed a clear lateralization and distinction of structures involved in the classification in men as compared to women with men exhibiting more alterations in the hemisphere contralateral to the seizure focus. In conclusion, individual post-surgical outcome predictions based on a single T1-weighted magnetic resonance image seem plausible and may thus support the routine pre-surgical workup of epilepsy patients.

Feis, Delia-Lisa; Schoene-Bake, Jan-Christoph; Elger, Christian; Wagner, Jan; Tittgemeyer, Marc; Weber, Bernd

2013-01-01

77

The cholinergic system in mild cognitive impairment and Alzheimer's disease: an in vivo MRI and DTI study.  

PubMed

Few studies have investigated in vivo changes of the cholinergic basal forebrain in Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), an at risk stage of AD. Even less is known about alterations of cortical projecting fiber tracts associated with basal forebrain atrophy. In this study, we determined regional atrophy within the basal forebrain in 21 patients with AD and 16 subjects with MCI compared to 20 healthy elderly subjects using deformation-based morphometry of MRI scans. We assessed effects of basal forebrain atrophy on fiber tracts derived from high-resolution diffusion tensor imaging (DTI) using tract-based spatial statistics. We localized significant effects relative to a map of cholinergic nuclei in MRI standard space as determined from a postmortem brain. Patients with AD and MCI subjects showed reduced volumes in basal forebrain areas corresponding to anterior medial and lateral, intermediate and posterior nuclei of the Nucleus basalis of Meynert (NbM) as well as in the diagonal band of Broca nuclei (P < 0.01). Effects in MCI subjects were spatially more restricted than in AD, but occurred at similar locations. The volume of the right antero-lateral NbM nucleus was correlated with intracortical projecting fiber tract integrity such as the corpus callosum, cingulate, and the superior longitudinal, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculus (P < 0.05, corrected for multiple comparisons). Our findings suggest that a multimodal MRI-DTI approach is supportive to determine atrophy of cholinergic nuclei and its effect on intracortical projecting fiber tracts in AD. PMID:20672311

Teipel, Stefan J; Meindl, Thomas; Grinberg, Lea; Grothe, Michel; Cantero, Jose L; Reiser, Maximilian F; Möller, Hans-Jürgen; Heinsen, Helmut; Hampel, Harald

2010-07-29

78

The "frontal syndrome" revisited: lessons from electrostimulation mapping studies.  

PubMed

For a long time, in a localizationist view of brain functioning, a combination of symptoms called "frontal syndrome" has been interpreted as the direct result of damages involving the frontal lobe(s). The goal of this review is to challenge this view, that is, to move to a hodotopical approach to lesion mapping, on the basis of new insights provided by intraoperative electrostimulation mapping investigations in patients who underwent awake surgery for cerebral tumors. These original data reported in the last decade break with the traditional dogma of a modular and fixed organization of the central nervous system, by switching to the concepts of cerebral connectivity and plasticity - i.e., a brain organization based on dynamic interrelationships between parallel distributed networks. According to this revisited model, "frontal symptoms" can be generated by tumor or electrostimulation not only of the frontal lobes, but also of cortical and subcortical (white matter pathways/deep gray nuclei) structures outside the frontal lobes: especially, stimulation of the superior longitudinal fascicle may elicit speech production disorders, syntactic disturbances, involuntary language switching or phonemic paraphasia (arcuate fascicle), stimulation of the inferior fronto-occipital fascicle can generate semantic paraphasia or deficit of cross-modal judgment, stimulation of the subcallosal fasciculus may elicit transcortical motor aphasia, while stimulation of the striatum induces preservations. On the other hand, it is also possible to perform extensive right or left frontal lobectomy in patients who continue to have a normal familial, social and professional life, without "frontal syndrome". Therefore, this provocative approach may open the door to a renewal in the modeling of brain processing as well as in its clinical applications, especially in the fields of cerebral surgery and functional rehabilitation. These findings illustrate well the need to reinforce links between cognitive neuroscience and clinical neurology/neurosurgery. PMID:21621762

Duffau, Hugues

2011-05-07

79

White Matter Abnormalities in Pediatric Obsessive-Compulsive Disorder  

PubMed Central

Obsessive-compulsive disorder (OCD) is a prevalent and often severely disabling illness with onset generally in childhood or adolescence. Although white matter deficits have been implicated in the neurobiology of OCD, few studies have been conducted in pediatric patients when the brain is still developing and have examined their functional correlates. In this study, 23 pediatric OCD patients and 23 healthy volunteers, between the ages of 9 and 17 years, matched for sex, age, handedness, and IQ, received a diffusion tensor imaging exam on a 3T GE system and a brief neuropsychological battery tapping executive functions. Patient symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Patients with OCD exhibited significantly greater fractional anisotropy compared to matched controls in the left dorsal cingulum bundle, splenium of the corpus callosum, right corticospinal tract, and left inferior fronto-occipital fasciculus. There were no regions of significantly lower fractional anisotropy in patients compared to controls. Higher fractional anisotropy in the splenium was significantly correlated with greater obsession severity on the CY-BOCS in the subgroup of psychotropic drug-naïve patients. Among patients, there was a significant association between greater fractional anisotropy in the dorsal cingulum bundle and better performance on measures of response inhibition and cognitive control. The overall findings suggest a pattern of greater directional coherence of white matter tracts in OCD very early in the course of illness, which may serve a compensatory mechanism, at least for response inhibition functions typically subserved by the cingulum bundle.

Gruner, Patricia; Vo, An; Ikuta, Toshikazu; Mahon, Katie; Peters, Bart D; Malhotra, Anil K; Ulug, Aziz M; Szeszko, Philip R

2012-01-01

80

Genetics of brain fiber architecture and intellectual performance.  

PubMed

The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a(2)=0.55, p=0.04, left; a(2)=0.74, p=0.006, right), bilateral parietal (a(2)=0.85, p<0.001, left; a(2)=0.84, p<0.001, right), and left occipital (a(2)=0.76, p=0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto-occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p=0.04 for FIQ and p=0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition. PMID:19228974

Chiang, Ming-Chang; Barysheva, Marina; Shattuck, David W; Lee, Agatha D; Madsen, Sarah K; Avedissian, Christina; Klunder, Andrea D; Toga, Arthur W; McMahon, Katie L; de Zubicaray, Greig I; Wright, Margaret J; Srivastava, Anuj; Balov, Nikolay; Thompson, Paul M

2009-02-18

81

Fiber tract-specific white matter lesion severity Findings in late-life depression and by AGTR1 A1166C genotype.  

PubMed

Past work demonstrated that late-life depression is associated with greater severity of ischemic cerebral hyperintense white matter lesions, particularly frontal lesions. However, these lesions are also associated with other neuropsychiatric deficits, so these clinical relationships may depend on which fiber tracts are damaged. We examined the ratio of lesion to nonlesioned white matter tissue within multiple fiber tracts between depressed and nondepressed elders. We also sought to determine if the AGTR1 A1166C and BDNF Val66Met polymorphisms contributed to vulnerability to lesion development in discrete tracts. The 3T structural MR images and blood samples for genetic analyses were acquired on 54 depressed and 37 nondepressed elders. Lesion maps were created through an automated tissue segmentation process and applied to a probabilistic white matter fiber tract atlas allowing for identification of the fraction of the tract occupied by lesion. The depressed cohort exhibited a significantly greater lesion ratio only in the left upper cingulum near the cingulate gyrus (F((1,86)) = 4.62, P = 0.0344), supporting past work implicating cingulate dysfunction in the pathogenesis of depression. In the 62 Caucasian subjects with genetic data, AGTR1 C1166 carriers exhibited greater lesion ratios across multiple tracts including the anterior thalamic radiation and inferior fronto-occipital fasciculus. In contrast, BDNF Met allele carriers exhibited greater lesion ratios only in the frontal corpus callosum. Although these findings did not survive correction for multiple comparisons, this study supports our hypothesis and provides preliminary evidence that genetic differences related to vascular disease may increase lesion vulnerability differentially across fiber tracts. PMID:22021115

Taylor, Warren D; Zhao, Zheen; Ashley-Koch, Allison; Payne, Martha E; Steffens, David C; Krishnan, Ranga R; Hauser, Elizabeth; MacFall, James R

2011-10-22

82

Abnormal White Matter Integrity in Adolescents with Internet Addiction Disorder: A Tract-Based Spatial Statistics Study  

PubMed Central

Background Internet addiction disorder (IAD) is currently becoming a serious mental health issue around the globe. Previous studies regarding IAD were mainly focused on associated psychological examinations. However, there are few studies on brain structure and function about IAD. In this study, we used diffusion tensor imaging (DTI) to investigate white matter integrity in adolescents with IAD. Methodology/Principal Findings Seventeen IAD subjects and sixteen healthy controls without IAD participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA) was performed by tract-based spatial statistics (TBSS) to localize abnormal white matter regions between groups. TBSS demonstrated that IAD had significantly lower FA than controls throughout the brain, including the orbito-frontal white matter, corpus callosum, cingulum, inferior fronto-occipital fasciculus, and corona radiation, internal and external capsules, while exhibiting no areas of higher FA. Volume-of-interest (VOI) analysis was used to detect changes of diffusivity indices in the regions showing FA abnormalities. In most VOIs, FA reductions were caused by an increase in radial diffusivity while no changes in axial diffusivity. Correlation analysis was performed to assess the relationship between FA and behavioral measures within the IAD group. Significantly negative correlations were found between FA values in the left genu of the corpus callosum and the Screen for Child Anxiety Related Emotional Disorders, and between FA values in the left external capsule and the Young's Internet addiction scale. Conclusions Our findings suggest that IAD demonstrated widespread reductions of FA in major white matter pathways and such abnormal white matter structure may be linked to some behavioral impairments. In addition, white matter integrity may serve as a potential new treatment target and FA may be as a qualified biomarker to understand the underlying neural mechanisms of injury or to assess the effectiveness of specific early interventions in IAD.

Qin, Lindi; Zhao, Zhimin; Xu, Jianrong; Lei, Hao

2012-01-01

83

Cerebral correlates of visuospatial neglect: A direct cerebral stimulation study.  

PubMed

OBJECTIVE.: To assess the role of the superior longitudinal fascicle, the inferior fronto-occipital fascicle, and the posterior parietal lobe in visuospatial attention in humans during awake brain surgery. EXPERIMENTAL DESIGN.: Seven patients with hemispheric gliomas (six in the right hemisphere) entered the study. During surgery in asleep/awake anesthesia, guided by Diffusion Tensor Imaging Fiber Tractography, visuospatial neglect was assessed during direct electrical stimulation by computerized line bisection. PRINCIPAL OBSERVATIONS.: A rightward deviation, indicating left visuospatial neglect, was induced in six of seven patients by stimulation of the parietofrontal connections, in a location consistent with the trajectory of the second branch of the superior longitudinal fascicle. Stimulation of the medial and dorsal white matter of the superior parietal lobule (corresponding to the first branch of the superior longitudinal fascicle), of the ventral and lateral white matter of the supramarginal gyrus (corresponding to the third branch of the superior longitudinal fascicle), and of the inferior occipitofrontal fasciculus, was largely ineffective. Stimulation of the superior parietal lobule (Brodmann's area 7) caused a marked rightward deviation in all of the six assessed patients, while stimulation of Brodmann's areas 5 and 19 was ineffective. CONCLUSIONS.: The parietofrontal connections of the dorso-lateral fibers of the superior longitudinal fascicle (i.e., the second branch of the fascicle), and the posterior superior parietal lobe (Brodmann's area 7) are involved in the orientation of spatial attention. Spatial neglect should be assessed systematically during awake brain surgery, particularly when the right parietal lobe may be involved by the neurosurgical procedure. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc. PMID:23417885

Vallar, Giuseppe; Bello, Lorenzo; Bricolo, Emanuela; Castellano, Antonella; Casarotti, Alessandra; Falini, Andrea; Riva, Marco; Fava, Enrica; Papagno, Costanza

2013-02-18

84

Normal cerebral asymmetry in familial and non-familial schizophrenic probands and their unaffected relatives  

Microsoft Academic Search

Loss of normal fronto-occipital cerebral asymmetry has been reported in patients with schizophrenia and also in their well relatives from multiply affected families, suggesting a relationship with susceptibility genes. We sought to confirm this relationship in a family study of patients with schizophrenia and their unaffected relatives of presumed differing genetic risk. MRI scans were carried out on 25 probands

Ben Chapple; Anton Grech; Pak Sham; Timothea Toulopoulou; Muriel Walshe; Katja Schulze; Kevin Morgan; Robin M. Murray; Colm McDonald

2004-01-01

85

Beyond the Arcuate Fasciculus: Consensus and Controversy in the Connectional Anatomy of Language  

ERIC Educational Resources Information Center

|The growing consensus that language is distributed into large-scale cortical and subcortical networks has brought with it an increasing focus on the connectional anatomy of language, or how particular fibre pathways connect regions within the language network. Understanding connectivity of the language network could provide critical insights into…

Dick, Anthony Steven; Tremblay, Pascale

2012-01-01

86

White Matter Microstructure in Superior Longitudinal Fasciculus Associated with Spatial Working Memory Performance in Children  

ERIC Educational Resources Information Center

|During childhood and adolescence, ongoing white matter maturation in the fronto-parietal cortices and connecting fiber tracts is measurable with diffusion-weighted imaging. Important questions remain, however, about the links between these changes and developing cognitive functions. Spatial working memory (SWM) performance improves significantly…

Vestergaard, Martin; Madsen, Kathrine Skak; Baare, William F. C.; Skimminge, Arnold; Ejersbo, Lisser Rye; Ramsoy, Thomas Z.; Gerlach, Christian; Akeson, Per; Paulson, Olaf B.; Jernigan, Terry L.

2011-01-01

87

White Matter Microstructure in Superior Longitudinal Fasciculus Associated with Spatial Working Memory Performance in Children  

ERIC Educational Resources Information Center

During childhood and adolescence, ongoing white matter maturation in the fronto-parietal cortices and connecting fiber tracts is measurable with diffusion-weighted imaging. Important questions remain, however, about the links between these changes and developing cognitive functions. Spatial working memory (SWM) performance improves significantly…

Vestergaard, Martin; Madsen, Kathrine Skak; Baare, William F. C.; Skimminge, Arnold; Ejersbo, Lisser Rye; Ramsoy, Thomas Z.; Gerlach, Christian; Akeson, Per; Paulson, Olaf B.; Jernigan, Terry L.

2011-01-01

88

Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study  

Microsoft Academic Search

BackgroundEvidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia

Marek Kubicki; Carl-Fredrik Westin; Paul G. Nestor; Cynthia G. Wible; Melissa Frumin; Stephan E. Maier; Ron Kikinis; Ferenc A. Jolesz; Robert W. McCarley; Martha E. Shenton

2003-01-01

89

Aberrant Diffusion and Geometric Properties in the Left Arcuate Fasciculus of Developmentally Delayed Children: A Diffusion Tensor Imaging Study  

PubMed Central

BACKGROUND AND PURPOSE One of the neurologic substrates of poor language in children with DD is the abnormal development of perisylvian language networks. We sought to determine whether this manifests as aberrant regional changes in diffusivity or geometry of the left AF. MATERIALS AND METHODS We performed DTI studies in 16 young (age, 55.4 ± 18.95 months) patients with DD and 11 age- and sex-matched TD children (age, 60.09 ± 21.27 months). All children were right-handed. To detect the malformation of left AF structure in native or standard space, we proposed new methodology consisting of 2 complementary approaches, principal fiber orientation quantification in color-coded anisotropic maps and tract-based morphometry analysis. RESULTS Patients with DD did not show the typical pattern of age-related maturity of the AP and ML pathways passing through the left AF (R2 of the AP pathway: DD versus TD = 0.002 versus 0.4542; R2 of the ML pathway: DD versus TD = 0.002 versus 0.4154). In addition, the patients with DD showed significantly reduced FA in the temporal portion of the AF (mean FA of DD versus TD = 0.37 ± 0.11 versus 0.48 ± 0.06, P < .001), and the AF showed higher curvatures in the parietotemporal junction, resulting in sharper bends to the Wernicke area (mean curvature of DD versus TD = 0.12 ± 0.03 versus 0.06 ± 0.02, P < .001). CONCLUSIONS The proposed methods successfully revealed regional abnormalities in the axonal integrity of the left AF in the patients with DD. These abnormalities support the notion that the perisylvian language network is malformed in children with DD.

Jeong, J.-W.; Sundaram, S.K.; Kumar, A.; Chugani, D.C.; Chugani, H.T.

2011-01-01

90

Long-Term Cognitive and Behavioral Therapies, Combined with Augmentative Communication, Are Related to Uncinate Fasciculus Integrity in Autism  

ERIC Educational Resources Information Center

|Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging, we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed to long-term augmentative and alternative communication, combined with sessions of…

Pardini, Matteo; Elia, Maurizio; Garaci, Francesco G.; Guida, Silvia; Coniglione, Filadelfo; Krueger, Frank; Benassi, Francesca; Gialloreti, Leonardo Emberti

2012-01-01

91

Convergent effects on alpha motoneurones from the vestibulospinal tract and a pathway descending in the medial longitudinal fasciculus  

Microsoft Academic Search

1.Convergence of effects from the vestibulospinal tract and the pathway descending in the MLF on the same motoneurones has been investigated with intracellular recording in the lumbosacral spinal cord. The following effects from the MLP pathway are described: a) Monosynaptic EPSPs are common in knee, ankle and toe flexors as well as in hip and toe extensors. b) Disynaptic IPSPs

S. Grillner; T. Hongo; S. Lund

1971-01-01

92

Fetal cerebral biometry: normal parenchymal findings and ventricular size.  

PubMed

Assessing fetal cerebral biometry is one means of ascertaining that the development of the fetal central nervous system is normal. Norms have been established on large cohorts of fetuses by sonographic and neurofetopathological studies. Biometric standards have been established in MR in much smaller cohorts. The purpose of this paper is to analyse methods of measuring a few parameters in MR [biparietal diameter (BPD), fronto-occipital diameter (FOD), length of the corpus callosum (LCC), atrial diameter, transverse cerebellar diameter, height, anteroposterior diameter and surface of the vermis] and to compare US and MR in the assessment of fetal cerebral biometry. PMID:15726378

Garel, C

2005-02-22

93

A Sensitive Diffusion Tensor Imaging Quantification Method to Detect Language Laterality in Children: Correlation With the Wada Test  

Microsoft Academic Search

Using diffusion tensor imaging tractography and color-coded anisotropy map quantification, we investigated asymmetry of the arcuate fasciculus to determine language laterality in children and compared it with the Wada test. Arcuate fasciculus volume and fractional anisotropy were measured after tractography. We also quantified the fiber orientation distribution in the arcuate fasciculus region, ie, the fraction of arcuate fasciculus fibers oriented

Vijay Narayan Tiwari; Jeong-Won Jeong; Eishi Asano; Robert Rothermel; Csaba Juhasz; Harry T. Chugani

2011-01-01

94

9 CFR 303.1 - Exemptions.  

Code of Federal Regulations, 2013 CFR

...establishment, all facilities and equipment in the official establishment...sanitizing of utensils and equipment, a sink with not fewer than...national or international amateur sports competition (but only if...of athletic facilities or equipment), or for the...

2013-01-01

95

24 CFR 26.41 - Default.  

Code of Federal Regulations, 2013 CFR

...motion, for failure to file a timely response to the Government's complaint. The motion...expiration of the time for filing a response to the default motion. If...of all facts alleged in the Government's complaint and a...

2013-04-01

96

Fiber density asymmetry of the arcuate fasciculus in relation to functional hemispheric language lateralization in both right- and left-handed healthy subjects: A combined fMRI and DTI study  

Microsoft Academic Search

Previously reported leftward asymmetry in language-related gray and white matter areas of the brain has been proposed as a structural correlate of left-sided functional hemispheric language lateralization. However, structural asymmetry in non-left-sided functional language lateralization has as yet not been studied. Furthermore, the neuroanatomical basis of the reported volumetric white matter asymmetry is not fully understood. In 20 healthy volunteers,

M. W. Vernooij; M. Smits; P. A. Wielopolski; G. C. Houston; G. P. Krestin; A. van der Lugt

2007-01-01

97

Damage to the Upper Portion of Area 19 and the Deep White Matter in the Left Inferior Parietal Lobe, Including the Superior Longitudinal Fasciculus, Results in Alexia with Agraphia  

Microsoft Academic Search

Analysis of lesions and symptoms in patients with brain tumors combined with information from diffusion tensor imaging provides direct evidence of the anatomical localization of brain function. Using these methods, we evaluated 8 patients who underwent surgery for metastatic brain tumors located in the left occipital lobes between 2007 and 2009. Preoperatively, 4 patients (cases 1–4) had alexia with agraphia

Nobusada Shinoura; Toshiyuki Onodera; Kotoyo Kurokawa; Masanobu Tsukada; Ryozi Yamada; Yusuke Tabei; Tomoyuki Koizumi; Kazuo Yagi

2010-01-01

98

Heritability of regional and global brain structure at the onset of puberty: a magnetic resonance imaging study in 9-year-old twin pairs.  

PubMed

Puberty represents the phase of sexual maturity, signaling the change from childhood into adulthood. During childhood and adolescence, prominent changes take place in the brain. Recently, variation in frontal, temporal, and parietal areas was found to be under varying genetic control between 5 and 19 years of age. However, at the onset of puberty, the extent to which variation in brain structures is influenced by genetic factors (heritability) is not known. Moreover, whether a direct link between human pubertal development and brain structure exists has not been studied. Here, we studied the heritability of brain structures at 9 years of age in 107 monozygotic and dizygotic twin pairs (N = 210 individuals) using volumetric MRI and voxel-based morphometry. Children showing the first signs of secondary sexual characteristics (N = 47 individuals) were compared with children without these signs, based on Tanner-stages. High heritabilities of intracranial, total brain, cerebellum, and gray and white matter volumes (up to 91%) were found. Regionally, the posterior fronto-occipital, corpus callosum, and superior longitudinal fascicles (up to 93%), and the amygdala, superior frontal and middle temporal cortices (up to 83%) were significantly heritable. The onset of secondary sexual characteristics of puberty was associated with decreased frontal and parietal gray matter densities. Thus, in 9-year-old children, global brain volumes, white matter density in fronto-occipital and superior longitudinal fascicles, and gray matter density of (pre-)frontal and temporal areas are highly heritable. Pubertal development may be directly involved in the decreases in gray matter areas that accompany the transition of our brains from childhood into adulthood. PMID:19294640

Peper, Jiska S; Schnack, Hugo G; Brouwer, Rachel M; Van Baal, G Caroline M; Pjetri, Eneda; Székely, Eszter; van Leeuwen, Marieke; van den Berg, Stéphanie M; Collins, D Louis; Evans, Alan C; Boomsma, Dorret I; Kahn, René S; Hulshoff Pol, Hilleke E

2009-07-01

99

20 CFR 404.335 - How do I become entitled to widow's or widower's benefits?  

Code of Federal Regulations, 2010 CFR

...was accidental. The death is accidental if...of these injuries, death occurred not later...intentional and voluntary suicide will not be considered an accidental death. (ii) At the...reasonably expected to live for 9 months...marriage to the insured due to mental...

2010-04-01

100

20 CFR 404.335 - How do I become entitled to widow's or widower's benefits?  

Code of Federal Regulations, 2010 CFR

...was accidental. The death is accidental if...of these injuries, death occurred not later...intentional and voluntary suicide will not be considered an accidental death. (ii) At the...reasonably expected to live for 9 months...marriage to the insured due to mental...

2009-04-01

101

26 CFR 1.692-1 - Abatement of income taxes of certain members of the Armed Forces of the United States upon death.  

Code of Federal Regulations, 2013 CFR

...the Armed Forces of the United States upon death. 1.692-1 Section 1.692-1...the Armed Forces of the United States upon death. (a)(1) This section applies if...of the United States, and (ii) His death occurs while he is serving in a...

2013-04-01

102

9 CFR 381.10 - Exemptions for specified operations.  

Code of Federal Regulations, 2013 CFR

...sanitizing of utensils and equipment, a sink with not fewer than...permit the accommodation of the equipment and utensils, and each compartment...national or international amateur sports competition (but only if...of athletic facilities or equipment), or for the...

2013-01-01

103

42 CFR 136.12 - Persons to whom services will be provided.  

Code of Federal Regulations, 2011 CFR

...Indian's household if the medical officer in charge determines...control acute infectious disease or a public health hazard...the Indian health and medical service program if...of the program, the medical officer in charge...If the applicant's condition is such that...

2011-10-01

104

DTI Tractography of the Human Brain's Language Pathways  

Microsoft Academic Search

Diffusion Tensor Imaging (DTI) tractography has been used to detect leftward asymmetries in the arcuate fasciculus, a pathway that links temporal and inferior frontal language cortices. In this study, we more specifically define this asymmetry with respect to both anatomy and function. Twenty right-handed male subjects were scanned with DTI, and the arcuate fasciculus was reconstructed using deterministic tractography. The

Matthew F. Glasser; James K. Rilling

2008-01-01

105

Prediction of brain-computer interface aptitude from individual brain structure.  

PubMed

Objective: Brain-computer interface (BCI) provide a non-muscular communication channel for patients with impairments of the motor system. A significant number of BCI users is unable to obtain voluntary control of a BCI-system in proper time. This makes methods that can be used to determine the aptitude of a user necessary. Methods: We hypothesized that integrity and connectivity of involved white matter connections may serve as a predictor of individual BCI-performance. Therefore, we analyzed structural data from anatomical scans and DTI of motor imagery BCI-users differentiated into high and low BCI-aptitude groups based on their overall performance. Results: Using a machine learning classification method we identified discriminating structural brain trait features and correlated the best features with a continuous measure of individual BCI-performance. Prediction of the aptitude group of each participant was possible with near perfect accuracy (one error). Conclusions: Tissue volumetric analysis yielded only poor classification results. In contrast, the structural integrity and myelination quality of deep white matter structures such as the Corpus Callosum, Cingulum, and Superior Fronto-Occipital Fascicle were positively correlated with individual BCI-performance. Significance: This confirms that structural brain traits contribute to individual performance in BCI use. PMID:23565083

Halder, S; Varkuti, B; Bogdan, M; Kübler, A; Rosenstiel, W; Sitaram, R; Birbaumer, N

2013-04-02

106

Longitudinal anthropometric measurements in patients with growth hormone deficiency. Effect of human growth hormone treatment.  

PubMed

The effect of human growth hormone (6IU/m2 twice weekly i.m.) on standing, sitting, and subischial leg height, on arm length, head circumference, fronto-occipital and biparietal head diameter, bi-iliac (pelvis) and bihumeral (shoulder) width, body weight, triceps and subscapular skinfold thickness, and upper arm and calf circumferences was studied longitudinally over a period of 2 years in 37 prepubertal growth hormone deficient patients (29 boys, 8 girls). Thirteen of them had isolated growth hormone deficiency, 18 combined defects with other anterior pituitary hormone deficiencies, and 6 had been operated for a craniopharyngioma. The most retarded height and length measurements were influenced most markedly by treatment in the fashion of a characteristic catch-up growth, while head circumference, which was less retarded initially, increased more slowly. With exception of craniopharyngioma patients, who became slightly eunuchoid, both proportions (sitting height versus subischial leg height) were not changed by treatment. The disproportions of shoulder and hip width (relatively wide pelvis, narrow shoulders before treatment) tended to be normalized. The results in patients with operated craniopharyngioma were not as good as in those with idiopathic growth hormone deficiency. PMID:7075625

Sorgo, W; Zachmann, M; Tassinari, D; Fernandez, F; Prader, A

1982-02-01

107

Functional Bimodality in the Brain Networks of Preterm and Term Human Newborns.  

PubMed

The spontaneous brain activity exhibits long-range spatial correlations detected using functional magnetic resonance imaging (fMRI) signals in newborns when (1) long neuronal pathways are still developing, and (2) the electrical brain activity consists of developmentally unique, intermittent events believed to guide activity-dependent brain wiring. We studied this spontaneous electrical brain activity using multichannel electroencephalography (EEG) of premature and fullterm babies during sleep to assess the development of spatial integration during last months of gestation. Correlations of frequency-specific amplitudes were found to follow a robust bimodality: During low amplitudes (low mode), brain activity exhibited very weak spatial correlations. In contrast, the developmentally essential high-amplitude events (high mode) showed strong spatial correlations. There were no clear spatial patterns in the early preterm, but clear frontal and parieto-occipital modules at term age. A significant fronto-occipital gradient was also seen in the development of the graph measure clustering coefficient. Strikingly, no bimodality was found in the fMRI recordings of the fullterm babies, suggesting that early EEG activity and fMRI signal reflect different mechanisms of spatial coordination. The results are compatible with the idea that early developing human brain exhibits intermittent long-range spatial connections that likely provide the endogenous guidance for early activity-dependent development of brain networks. PMID:23650289

Omidvarnia, Amir; Fransson, Peter; Metsäranta, Marjo; Vanhatalo, Sampsa

2013-05-01

108

Quantitative evaluation of changes in the selected white matter tracts using diffusion tensor imaging in patients with Alzheimer's disease and mild cognitive impairment.  

PubMed

This study evaluated the damage to the extensive range of white matter tracts in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Thirty-four patients with AD (mean age 71.5 yrs, MMSE 17.6), 23 patients with MCI (mean age 66 yrs, MMSE 27.4) and 15 normal controls (mean age 69 yrs, MMSE 29.8) were enrolled. Diffusion tensor imaging (DTI) was performed in 25 directions on 1.5 T MR scanner. Fractional anisotropy (FA) values were obtained with a small ROI method in several association tracts including posterior cingulum fibers, in commissural tracts (genu and splenium of corpus callosum) and projection tracts (middle cerebellar peduncles and posterior limbs of internal capsules). In MCI significant reductions of FA were found in the inferior longitudinal fascicles, left superior longitudinal fascicle and posterior cingulum fibers compared to normal controls. In AD significantly decreased FA values were detected in the same fascicles as in MCI and additionally in inferior fronto-occipital tracts and commissural tracts. In both AD and MCI the most severe changes were found within posterior cingulum fibers. No abnormalities were detected in projection tracts in both groups. Accuracy of DTI in detecting AD and MCI reached 0.95 and 0.79, respectively. FA measurements strongly correlated with neuropsychological tests. DTI is capable of depicting microstructural changes within white matter fiber tracts in dementia and may aid the differential diagnosis of AD and MCI. PMID:24028982

Zimny, A; Szewczyk, P; Bladowska, J; Trypka, E; Wojtynska, R; Leszek, J; Sasiadek, M

2012-06-26

109

Results of extremely low birth weight infants randomized to receive extra enteral calcium supply  

PubMed Central

Background Bone mineral deficiency continues to occur in extremely low birth weight (ELBW) infants despite formulas enriched in Ca and P. Objective This study tested whether extra enteral Ca supplementation increases bone mineral content (BMC) and prevents dolichocephalic head flattening and myopia in ELBW infants. Study design Infants 401–1000 birth weight receiving enteral feeds were randomized to receive feeds supplemented with Ca-gluconate powder, or pure standard feeds. Main outcome measures were the excretion of Ca and P by weekly spot urine measurements, the degree of dolichocephalic deformation (fronto-occipital to biparietal diameter ratio, FOD/BPD) at 36 weeks postmenstrual age and the BMC (by dual-energy x-ray absorptiometry) at discharge. Cycloplegic refraction was measured at 18–22 months corrected age. Results Ninety-nine ELBW infants with a gestational age of 26 weeks (23–31) [Median (minimum-maximum)] were randomized at a postnatal age of 12 days (5–23) weighing 790g (440–1700). Urinary Ca excretion increased, P excretion decreased in the Ca supplemented group. Total body BMC was 89.9 ± 2.4 g (mean ± SE) in the supplemented group and 85.2 ± 2.6 g in the control group (p= 0.19). The FOD/BPD was 1.50 (1.13–1.69, mean ± SD) and 1.47 (1.18–1.64) in the supplemented and control groups, and the refraction 0.98 ± 1.23 and 1.40 ± 1.33 dpt. (p=0.68), respectively in 64 ELBW infants (79% of survivors) at 2-year-follow-up. Conclusions Extra enteral Ca supplementation did not change BMC, head shape or refraction. The decreased P excretion may reflect P deficiency in infants receiving extra Ca, preventing improved bone mineral accretion.

Carroll, William F.; Fabres, Jorge; Nagy, Tim R.; Frazier, Marcela; Roane, Claire; Pohlandt, Frank; Carlo, Waldemar A.; Thome, Ulrich H.

2011-01-01

110

Neuroanatomical Dissections of Unilateral Visual Neglect Symptoms: ALE Meta-Analysis of Lesion-Symptom Mapping  

PubMed Central

Unilateral visual neglect is commonly defined as impaired ability to attend to stimuli presented on the side of visual space contralateral to the brain lesion. However, behavioral analyses indicate that different neglect symptoms can dissociate. The neuroanatomy of the syndrome has been hotly debated. Some groups have argued that the syndrome is linked to posterior parietal cortex lesions, while others report damage within regions including the superior temporal gyrus, insula, and basal ganglia. Several recent neuroimaging studies provide evidence that heterogeneity in the behavioral symptoms of neglect can be matched by variations in the brain lesions, and that some of the discrepancies across earlier findings might have resulted from the use of different neuropsychological tests and/or varied measures within the same task for diagnosing neglect. In this paper, we review the evidence for dissociations between both the symptoms and the neural substrates of unilateral visual neglect, drawing on ALE (anatomic likelihood estimation) meta-analyses of lesion-symptom mapping studies. Specifically, we examine dissociations between neglect symptoms associated with impaired control of attention across space (in an egocentric frame of reference) and within objects (in an allocentric frame of reference). Results of ALE meta-analyses indicated that, while egocentric symptoms are associated with damage within perisylvian network (pre- and postcentral, supramarginal, and superior temporal gyri) and damage within sub-cortical structures, more posterior lesions including the angular, middle temporal, and middle occipital gyri are associated with allocentric symptoms. Furthermore, there was high concurrence in deficits associated with white matter lesions within long association (superior longitudinal, inferior fronto-occipital, and inferior longitudinal fasciculi) and projection (corona radiata and thalamic radiation) pathways, supporting a disconnection account of the syndrome. Using this evidence we argue that different forms of neglect link to both distinct and common patterns of gray and white matter lesions. The findings are discussed in terms of functional accounts of neglect and theoretical models based on computational studies of both normal and impaired attention functions.

Chechlacz, Magdalena; Rotshtein, Pia; Humphreys, Glyn W.

2012-01-01

111

A Diffusion Tensor Imaging Study on the White Matter Skeleton in Individuals with Sports-Related Concussion  

PubMed Central

Abstract Recognizing and managing the effects of cerebral concussion is very challenging, given the discrete symptomatology. Most individuals with sports-related concussion will not score below 15 on the Glasgow Coma Scale, but will present with rapid onset of short-lived neurological impairment, demonstrating no structural changes on traditional magnetic resonance imaging (MRI) and computed tomography (CT) scans. The return-to-play decision is one of the most difficult responsibilities facing the physician, and so far this decision has been primarily based on neurological examination, symptom checklists, and neuropsychological (NP) testing. Diffusion tensor imaging (DTI) may be a more objective tool to assess the severity and recovery of function after concussion. We assessed white matter (WM) fiber tract integrity in varsity level college athletes with sports-related concussion without loss of consciousness, who experienced protracted symptoms for at least 1 month after injury. Evaluation of fractional anisotropy (FA) and mean diffusivity (MD) of the WM skeleton using tract-based spatial statistics (TBSS) revealed a large cluster of significantly increased MD for concussed subjects in several WM fiber tracts in the left hemisphere, including parts of the inferior/superior longitudinal and fronto-occipital fasciculi, the retrolenticular part of the internal capsule, and posterior thalamic and acoustic radiations. Qualitative comparison of average FA and MD suggests that with increasing level of injury severity (ranging from sports-related concussion to severe traumatic brain injury), MD might be more sensitive at detecting mild injury, whereas FA captures more severe injuries. In conclusion, the TBSS analysis used to evaluate diffuse axonal injury of the WM skeleton seems sensitive enough to detect structural changes in sports-related concussion.

Cubon, Valerie A.; Putukian, Margot; Boyer, Cynthia

2011-01-01

112

EEG oscillatory activity associated to monetary gain and loss signals in a learning task: effects of attentional impulsivity and learning ability.  

PubMed

This study investigated the influence of individual differences in attentional impulsivity (Att-Imp), learning ability, and learning practice on oscillatory activity and phase synchrony responses to monetary gain and loss signals during an instrumental-learning task in healthy women. We used a trial-by-trial wavelet-based time-frequency analysis of the electroencephalographic (EEG) signal to provide amplitude and inter-site phase synchrony measures from 30 electrodes in theta (4-8 Hz, 350-500 ms), alpha (8-12 Hz, 100-200 ms), beta (13-25 Hz, 100-200 ms), and gamma (30-40 Hz, 350-450 ms) time-frequency ranges. Oscillatory amplitude and inter-site phase synchrony were both greater following loss signals as compared to gain signals in theta, beta, and gamma frequency bands. Low Att-Imp subjects had higher theta activity within a 350-500 ms time window over frontocentral, and centroparietal sites than high Att-Imp subjects. Monetary gain signals elicited higher theta and gamma activities in high Att-Imp individuals and loss signals elicited higher activities to loss signals in low Att-Imp individuals. Good learners showed enhanced intrahemispheric theta synchrony between frontoparietal, and fronto-occipital sites to monetary loss compared to gain signals. In good learners, monetary loss produced an increase of gamma synchrony that enhanced in the second stage of learning. In low Att-Imp individuals, there was a reduction of theta synchrony during the second stage, as compared with the first stage of learning, between temporal, parietal and fronto-parietal brain regions. These findings may offer valuable clues to understand outcome processing, attentional impulsivity, and learning ability. We propose that the punishment-related theta and gamma waves play a leading role in learning process. PMID:21704660

De Pascalis, Vilfredo; Varriale, Vincenzo; Rotonda, Marco

2011-06-24

113

White Matter Fractional Anisotropy Correlates With Speed of Processing and Motor Speed in Young Childhood Cancer Survivors  

SciTech Connect

Purpose: To determine whether childhood medulloblastoma and acute lymphoblastic leukemia (ALL) survivors have decreased white matter fractional anisotropy (WMFA) and whether WMFA is related to the speed of processing and motor speed. Methods and Materials: For this study, 17 patients (6 medulloblastoma, 5 ALL treated with high-dose methotrexate (MTX) (4 x 5 g/m{sup 2}) and 6 with low-dose MTX (3 x 2 g/m{sup 2})) and 17 age-matched controls participated. On a 3.0-T magnetic resonance imaging (MRI) scanner, diffusion tensor imaging (DTI) was performed, and WMFA values were calculated, including specific regions of interest (ROIs), and correlated with the speed of processing and motor speed. Results: Mean WMFA in the patient group, mean age 14 years (range 8.9 - 16.9), was decreased compared with the control group (p = 0.01), as well as WMFA in the right inferior fronto-occipital fasciliculus (IFO) (p = 0.03) and in the genu of the corpus callosum (gCC) (p = 0.01). Based on neurocognitive results, significant positive correlations were present between processing speed and WMFA in the splenium (sCC) (r = 0.53, p = 0.03) and the body of the corpus callosum (bCC) (r = 0.52, p = 0.03), whereas the right IFO WMFA was related to motor speed (r = 0.49, p < 0.05). Conclusions: White matter tracts, using a 3.0-T MRI scanner, show impairment in childhood cancer survivors, medulloblastoma survivors, and also those treated with high doses of MTX. In particular, white matter tracts in the sCC, bCC and right IFO are positively correlated with speed of processing and motor speed.

Aukema, Eline J. [Pediatric Psychosocial Department, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands)], E-mail: e.j.aukema@amc.uva.nl; Caan, Matthan W.A. [Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Delft University of Technology, Delft (Netherlands); Oudhuis, Nienke [Pediatric Psychosocial Department, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands); Majoie, Charles [Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Vos, Frans M. [Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Delft University of Technology, Delft (Netherlands); Reneman, Liesbeth [Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Last, Bob F. [Pediatric Psychosocial Department, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands); Department of Developmental Psychology, Free University of Amsterdam, Amsterdam (Netherlands); Grootenhuis, Martha A. [Pediatric Psychosocial Department, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands); Schouten-van Meeteren, Antoinette Y.N. [Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands)

2009-07-01

114

A diffusion tensor imaging study on the white matter skeleton in individuals with sports-related concussion.  

PubMed

Recognizing and managing the effects of cerebral concussion is very challenging, given the discrete symptomatology. Most individuals with sports-related concussion will not score below 15 on the Glasgow Coma Scale, but will present with rapid onset of short-lived neurological impairment, demonstrating no structural changes on traditional magnetic resonance imaging (MRI) and computed tomography (CT) scans. The return-to-play decision is one of the most difficult responsibilities facing the physician, and so far this decision has been primarily based on neurological examination, symptom checklists, and neuropsychological (NP) testing. Diffusion tensor imaging (DTI) may be a more objective tool to assess the severity and recovery of function after concussion. We assessed white matter (WM) fiber tract integrity in varsity level college athletes with sports-related concussion without loss of consciousness, who experienced protracted symptoms for at least 1 month after injury. Evaluation of fractional anisotropy (FA) and mean diffusivity (MD) of the WM skeleton using tract-based spatial statistics (TBSS) revealed a large cluster of significantly increased MD for concussed subjects in several WM fiber tracts in the left hemisphere, including parts of the inferior/superior longitudinal and fronto-occipital fasciculi, the retrolenticular part of the internal capsule, and posterior thalamic and acoustic radiations. Qualitative comparison of average FA and MD suggests that with increasing level of injury severity (ranging from sports-related concussion to severe traumatic brain injury), MD might be more sensitive at detecting mild injury, whereas FA captures more severe injuries. In conclusion, the TBSS analysis used to evaluate diffuse axonal injury of the WM skeleton seems sensitive enough to detect structural changes in sports-related concussion. PMID:21083414

Cubon, Valerie A; Putukian, Margot; Boyer, Cynthia; Dettwiler, Annegret

2011-01-27

115

Multivariate searchlight classification of structural MRI in children and adolescents with autism  

PubMed Central

Background Autism spectrum disorders (ASD) are neurodevelopmental disorders with a prevalence of nearly 1:100. Structural imaging studies point to disruptions in multiple brain areas, yet the precise neuroanatomical nature of these disruptions remains unclear. Characterization of brain structural differences in children with ASD is critical for development of biomarkers that may eventually be used to improve diagnosis and monitor response to treatment. Methods We use voxel-based morphometry (VBM) along with a novel multivariate pattern analysis (MPA) approach and searchlight algorithm to classify structural magnetic resonance imaging data acquired from 24 children and adolescents with autism and 24 age-, gender-, and IQ-matched neurotypical participants. Results Despite modest VBM differences, MPA revealed that the groups could be distinguished with accuracies of around 90% based on gray matter in the posterior cingulate cortex (PCC), medial prefrontal cortex, and bilateral medial temporal lobes, all regions within the default mode network (DMN). Abnormalities in the PCC were associated with impaired ADI-R communication scores. Gray matter in additional prefrontal, lateral temporal, and subcortical structures also discriminated between the two groups with accuracies between 81-90%. White matter in the inferior fronto-occipital and superior longitudinal fasciculi, and the genu and splenium of the corpus callosum, achieved up to 85% classification accuracy. Conclusions Multiple brain regions, including those belonging to the DMN, exhibit aberrant structural organization in children with autism. Brain-based biomarkers derived from structural MRI data may eventually contribute to identification of the neuroanatomical basis of symptom heterogeneity and to the development of more targeted early intervention.

Uddin, Lucina Q.; Menon, Vinod; Young, Christina B.; Ryali, Srikanth; Chen, Tianwen; Khouzam, Amirah; Minshew, Nancy J.; Hardan, Antonio Y.

2011-01-01

116

Associations between white matter hyperintensities and ? amyloid on integrity of projection, association, and limbic fiber tracts measured with diffusion tensor MRI.  

PubMed

The goal of this study was to assess the relationship between A? deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78±7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0-0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume >0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between A? deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. A? deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where A? deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE ?4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue. PMID:23762308

Chao, Linda L; Decarli, Charles; Kriger, Stephen; Truran, Diana; Zhang, Yu; Laxamana, Joel; Villeneuve, Sylvia; Jagust, William J; Sanossian, Nerses; Mack, Wendy J; Chui, Helena C; Weiner, Michael W

2013-06-06

117

Effects of NG-nitro-L-arginine and L-arginine on regional cerebral blood flow in the cat.  

PubMed Central

1. We studied the effects of NG-nitro-L-arginine (NOLA), a potent inhibitor of the L-arginine-nitric oxide pathway, and L-arginine, the precursor of nitric oxide, on regional cerebral blood flow, electrocortical activity and ex vivo cerebrovascular reactivity in the cat. Flow was measured via radiolabelled microspheres, and vascular responses were studied by measuring isometric tension of isolated middle cerebral arterial rings. 2. NOLA (30 mg kg-1 bolus followed by 1 mg kg-1 min-1 infusion) caused an approximately 40 mmHg elevation in the mean arterial blood pressure, a regionally heterogenous increase of the regional cerebrovascular resistance and a decrease in the regional cerebral blood flow 15 and 40 min after the start of its administration. In contrast L-arginine (30 mg kg-1 bolus followed by 10 mg kg-1 min-1 infusion) did not alter blood pressure, cerebrovascular resistance nor regional cerebral blood flow 15 min after the start of its administration. The NOLA-induced changes in tissue flow were the most pronounced in the cerebellum, pituitary and medulla oblongata, whereas there was no decrease in the flow of the cortex and white matter. 3. NOLA caused characteristic changes in total fronto-occipital EEG power and in power spectra which were unlikely to have been due to cerebral ischaemia. In addition, the ex vivo reactivity of the middle cerebral arteries showed signs of impaired endothelial nitric oxide synthesis: there were enhanced noradrenaline-induced contractions and N-ethoxycarbonyl-3-morpholino-sydnonimine (SIN-1)-induced relaxations and markedly attenuated acetylcholine- and ATP-induced relaxations after NOLA treatment. 4. The present data indicate that resting cerebral blood flow and cerebrovascular resistance are regulated by nitric oxide derived from L-arginine in a regionally heterogenous way and that exogenous L-arginine availability is not a limiting factor in this nitric oxide generation. Possibly, both the vascular endothelium and the neurons contribute to this basal nitric oxide release.

Kovach, A G; Szabo, C; Benyo, Z; Csaki, C; Greenberg, J H; Reivich, M

1992-01-01

118

Role of diffusion tensor magnetic resonance tractography in predicting the extent of resection in glioma surgery.  

PubMed

Diffusion tensor imaging (DTI) tractography enables the in vivo visualization of the course of white matter tracts inside or around a tumor, and it provides the surgeon with important information in resection planning. This study is aimed at assessing the ability of preoperative DTI tractography in predicting the extent of the resection achievable in surgical removal of gliomas. Patients with low-grade gliomas (LGGs; 46) and high-grade gliomas (HGGs; 27) were studied using a 3T scanner according to a protocol including a morphological study (T2, fluid-attenuated inversion-recovery, T1 sequences) and DTI acquisitions (b = 1000 s/mm(2), 32 gradient directions). Preoperative tractography was performed off-line on the basis of a streamline algorithm, by reconstructing the inferior fronto-occipital (IFO), the superior longitudinal fascicle (SLF), and the corticospinal tract (CST). For each patient, the relationship between each bundle reconstructed and the lesion was analyzed. Initial and residual tumor volumes were measured on preoperative and postoperative 3D fluid-attenuated inversion-recovery images for LGGs and postcontrast T1-weighted scans for HGGs. The presence of intact fascicles was predictive of a better surgical outcome, because these cases showed a higher probability of total resection than did subtotal and partial resection. The presence of infiltrated or displaced CST or infiltrated IFO was predictive of a lower probability of total resection, especially for tumors with preoperative volume <100 cm(3). DTI tractography can thus be considered to be a promising tool for estimating preoperatively the degree of radicality to be reached by surgical resection. This information will aid clinicians in identifying patients who will mostly benefit from surgery. PMID:22015596

Castellano, Antonella; Bello, Lorenzo; Michelozzi, Caterina; Gallucci, Marcello; Fava, Enrica; Iadanza, Antonella; Riva, Marco; Casaceli, Giuseppe; Falini, Andrea

2011-10-20

119

Multiple DTI index analysis in normal aging, amnestic MCI and AD. Relationship with neuropsychological performance.  

PubMed

White matter (WM) damage has been reported in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in diffusion tensor imaging (DTI) studies. It is, however, unknown how the investigation of multiple tensor indexes in the same patients, can differentiate them from normal aging or relate to patients cognition. Forty-six individuals (15 healthy, 16 a-MCI and 15 AD) were included. Voxel-based tract based spatial-statistics (TBSS) was used to obtain whole-brain maps of main WM bundles for fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA) and mean diffusivity (MD). FA reductions were evidenced among AD patients with posterior predominance. A-MCI patients displayed reduced mean FA in these critical regions, compared to healthy elders. MD increases were widespread in both groups of patients. Interestingly, a-MCI patients exhibited DR increases in overlapping areas of FA shrinkages in AD, whereas DA increases were only observed in AD. Gray matter atrophy explained most DTI differences, except those regarding MD in both groups as well as DR increases in posterior associative pathways among a-MCI cases. FA values were the only DTI measure significantly related to memory performance among patients. Present findings suggest that most DTI-derived changes in AD and a-MCI are largely secondary to gray matter atrophy. Notably however, specific DR signal increases in posterior parts of the inferior fronto-occipital and longitudinal fasciculi may reflect early WM compromise in preclinical dementia, which is independent of atrophy. Finally, global measures of integrity, particularly orientation coherence (FA) of diffusion, appear to be more closely related to the cognitive profile of our patients than indexes reflecting water movement parallel (DA) and perpendicular (DR) to the primary diffusion direction. PMID:20371138

Bosch, Beatriz; Arenaza-Urquijo, Eider M; Rami, Lorena; Sala-Llonch, Roser; Junqué, Carme; Solé-Padullés, Cristina; Peña-Gómez, Cleofé; Bargalló, Núria; Molinuevo, José Luis; Bartrés-Faz, David

2010-04-03

120

Frontotemporal anatomical connectivity and working-relational memory performance predict everyday functioning in schizophrenia.  

PubMed

Hippocampal (relational memory) and prefrontal cortex (PFC; working memory) impairments have been found in patients with schizophrenia (SP), possibly due to a dysfunctional connection between structures. Neuroanatomical studies that describe reduced fractional anisotropy (FA) in the uncinate fasciculus support this idea. The dysconnection hypothesis in SP was investigated by examining frontotemporal anatomical connectivity (uncinate fasciculus FA) and PFC-hippocampal memory and their relationship with each other and everyday functioning. PFC-hippocampal memory was examined with two working-relational memory tasks: transverse patterning and a virtual Morris water task. SP exhibited a performance deficit on both tasks and had lower FA in bilateral uncinate fasciculus than healthy volunteers. Lower frontotemporal anatomical connectivity was related to lower working-relational memory performance, and both predicted worse everyday functioning. PMID:22882287

Hanlon, Faith M; Houck, Jon M; Klimaj, Stefan D; Caprihan, Arvind; Mayer, Andrew R; Weisend, Michael P; Bustillo, Juan R; Hamilton, Derek A; Tesche, Claudia D

2012-08-06

121

Patterns of cortical reorganization in the adult marmoset after a cervical spinal cord injury.  

PubMed

In the present study, we used microelectrode recordings of multiunit responses to evaluate patterns of the reactivation of somatosensory cortex after sensory loss produced by spinal cord lesions in the common marmoset (Callithrix jacchus). These New World monkeys have become a popular model in studies of cortical organization and function. Primary somatosensory cortex and adjoining somatosensory areas can become extensively deactivated by lesions of somatosensory afferents as they ascend in the dorsal columns of the cervical spinal cord. Six to 7 weeks after complete lesions of the cuneate fasciculus subserving the forelimb at cervical levels 5-6, the hand region in contralateral areas 3b and 1 was reactivated by inputs from the forelimb, but excluded representations of some or all digits. In a similar manner, recording sites from the forelimb region of areas 2-5 responded to parts of the forelimb but not to digits after an extensive lesion of the contralateral cuneate fasciculus at C5-C6. Lesions that damaged only the gracile fasciculus or a small percentage of the cuneate fasciculus did not produce changes in the gross hand representation in contralateral areas 3b, 3a, 1, and 2. Finally, a complete but lower lesion of the cuneate fasciculus at C8 produced some abnormalities in the reactivation, but the digits were represented. The results indicate that areas 3a, 3b, 1, and 2-5 of the somatosensory cortex are extensively reactivated after large, apparently complete lesions of the contralateral cuneate fasciculus, but afferents from the digits may not contribute to their reactivation. J. Comp. Neurol. 521:3451-3463, 2013. © 2013 Wiley Periodicals, Inc. PMID:23681952

Bowes, Charnese; Burish, Mark; Cerkevich, Christina; Kaas, Jon

2013-10-01

122

DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity  

PubMed Central

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to localize and to specify further DTI abnormalities in schizophrenia by combining DTI with magnetization transfer imaging (MTI), a technique sensitive to myelin and axonal alterations in order to increase specificity of DTI findings. 21 chronic schizophrenics and 26 controls were scanned using Line-Scan-Diffusion-Imaging and T1-weighted techniques with and without a saturation pulse (MT). Diffusion information was used to normalize co-registered maps of fractional anisotropy (FA) and magnetization transfer ratio (MTR) to a study-specific template, using the multi-channel daemon algorithm, designed specifically to deal with multi-directional tensor information. Diffusion anisotropy was decreased in schizophrenia in the following brain regions: the fornix, the corpus callosum, bilaterally in the cingulum bundle, bilaterally in the superior occipito-frontal fasciculus, bilaterally in the internal capsule, in the right inferior occipito-frontal fasciculus and the left arcuate fasciculus. MTR maps demonstrated changes in the corpus callosum, fornix, right internal capsule, and the superior occipito-frontal fasciculus bilaterally; however, no changes were noted in the anterior cingulum bundle, the left internal capsule, the arcuate fasciculus, or inferior occipito-frontal fasciculus. In addition, the right posterior cingulum bundle showed MTR but not FA changes in schizophrenia. These findings suggest that, while some of the diffusion abnormalities in schizophrenia are likely due to abnormal coherence, or organization of the fiber tracts, some of these abnormalities may, in fact, be attributed to or coincide with myelin/axonal disruption.

Kubicki, M.; Park, H.; Westin, C.F.; Nestor, P.G.; Mulkern, R.V.; Maier, S.E.; Niznikiewicz, M.; Connor, E.E.; Levitt, J.J.; Frumin, M.; Kikinis, R.; Jolesz, F.A.; McCarley, R.W.; Shenton, M.E.

2009-01-01

123

The longitudinal growth of the neuromeres and the resulting brain in the human embryo.  

PubMed

The growth of the human brain during the embryonic period was assessed in terms of longitudinal measurements in staged embryos. Precise graphic reconstructions prepared by the onerous point-plotting method were considered to be the most reliable, and 23 were examined in detail. A distinction is necessary between measurements of the brain (cerebral diameters) and those of the skull (osseous diameters), and also between those of the folded brain in situ, studied here, and the later relatively straightened brain. Longitudinal measurements were made of individual neuromeres and their successors in steps (neuromeric lengths). The sum of the neuromeric measurements at any given stage provides the total neuromeric length (TNL) of the folded brain in situ at that stage and it increases in keeping with the greatest length (GL) of the embryo. At stages 16-19, however, the neuromeric length of the brain may exceed the GL. From stage 20 onwards the body length increases more rapidly compared with the length of the brain. The most cephalic neuromere is the telencephalon medium, abbreviated T1 here. The cerebral hemispheres are derived from it, although they are not neuromeres. The hemispheres soon extend rostrally beyond the limit of T1 by an amount that is here designated T2, and that indicates the growth of the telencephalon rostral to the commissural plate, which is the site of the future corpus callosum. Further laterally, the hemispheric length (future fronto-occipital diameter) increases rapidly, as does also the bitemporal (biparietal) diameter. At the end of the embryonic period these diameters are one fourth to one fifth of the head circumference. Additional neuromeric information becomes manifest when the measurements are calculated as percentages of the total length of the brain. The rhombencephalon decreases considerably, diencephalon 2 increases greatly, whereas diencephalon 1 diminishes, and the cerebral hemispheres enlarge massively. In addition, specific neuromeres or subdivisions come to occupy relatively more or relatively less of the total. Three periods were found during which individual neuromeres acquire their maximal or minimal lengths: the maximal absolute lengths were in period 3, whereas the maximal and minimal percentage lengths were in periods 1 and 3. The various neuromeric changes are considered to be related to alterations in functional development. Finally, in furtherance of establishing continuity in prenatal data, comparisons were effected between embryonic and fetal measurements. PMID:23183269

O'Rahilly, Ronan; Müller, Fabiola

2012-11-24

124

Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study  

PubMed Central

Summary Background Previous studies have identified effects of age and vascular risk factors on brain injury in elderly individuals. We aimed to establish whether the effects of high blood pressure in the brain are evident as early as the fifth decade of life. Methods In an investigation of the third generation of the Framingham Heart Study, we approached all participants in 2009 to ask whether they would be willing to undergo MRI. Consenting patients underwent clinical assessment and cerebral MRI that included T1-weighted and diffusion tensor imaging to obtain estimates of fractional anisotropy, mean diffusivity, and grey-matter volumes. All images were coregistered to a common minimum deformation template for voxel-based linear regressions relating fractional anisotropy, mean diffusivity, and grey-matter volumes to age and systolic blood pressure, with adjustment for potential confounders. Findings 579 (14·1%) of 4095 participants in the third-generation cohort (mean age 39·2 years, SD 8·4) underwent brain MRI between June, 2009 and June, 2010. Age was associated with decreased fractional anisotropy and increased mean diffusivity in almost all cerebral white-matter voxels. Age was also independently associated with reduced grey-matter volumes. Increased systolic blood pressure was linearly associated with decreased regional fractional anisotropy and increased mean diffusivity, especially in the anterior corpus callosum, the inferior fronto-occipital fasciculi, and the fibres that project from the thalamus to the superior frontal gyrus. It was also strongly associated with reduced grey-matter volumes, particularly in Brodmann’s area 48 on the medial surface of the temporal lobe and Brodmann’s area 21 of the middle temporal gyrus. Interpretation Our results suggest that subtle vascular brain injury develops insidiously during life, with discernible effects even in young adults. These findings emphasise the need for early and optimum control of blood pressure. Funding National Institutes of Health and National Heart, Lung, and Blood Institute; National Institute on Aging; and National Institute of Neurological Disorders and Stroke.

Maillard, Pauline; Seshadri, Sudha; Beiser, Alexa; Himali, Jayandra J; Au, Rhoda; Fletcher, Evan; Carmichael, Owen; Wolf, Philip A; DeCarli, Charles

2012-01-01

125

Atypical conduction aphasia and the right hemisphere: Cross-hemispheric plasticity of phonology in a developmentally dyslexic and dysgraphic patient with early left frontal damage  

Microsoft Academic Search

We report the rare case of a patient, JNR, with history of mixed handedness, developmental dyslexia, dysgraphia, and attentional deficits associated with a Klippel–Trènaunay syndrome and a small subcortical frontal lesion involving the left arcuate fasciculus. In adulthood, he suffered a large right perisylvian stroke and developed atypical conduction aphasia with deficits in input and output phonological processing and poor

Marcelo L. Berthier; Guadalupe Dávila; Natalia García-Casares; Cristina Green; Rocío Juárez; Rafael Ruiz-Cruces; J. Pablo Lara; M. A. Barbancho

2011-01-01

126

White matter tract signatures of the progressive aphasias.  

PubMed

The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity. PMID:23312804

Mahoney, Colin J; Malone, Ian B; Ridgway, Gerard R; Buckley, Aisling H; Downey, Laura E; Golden, Hannah L; Ryan, Natalie S; Ourselin, Sebastien; Schott, Jonathan M; Rossor, Martin N; Fox, Nick C; Warren, Jason D

2013-01-09

127

White matter tract signatures of the progressive aphasias  

PubMed Central

The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity.

Mahoney, Colin J.; Malone, Ian B.; Ridgway, Gerard R.; Buckley, Aisling H.; Downey, Laura E.; Golden, Hannah L.; Ryan, Natalie S.; Ourselin, Sebastien; Schott, Jonathan M.; Rossor, Martin N.; Fox, Nick C.; Warren, Jason D.

2013-01-01

128

Brain regions underlying repetition and auditory-verbal short-term memory deficits in aphasia: Evidence from voxel-based lesion symptom mapping  

Microsoft Academic Search

Background: A deficit in the ability to repeat auditory-verbal information is common among individuals with aphasia. The neural basis of this deficit has traditionally been attributed to the disconnection of left posterior and anterior language regions via damage to a white matter pathway, the arcuate fasciculus. However, a number of lesion and imaging studies have called this notion into question.Aims:

Juliana V. Baldo; Shira Katseff; Nina F. Dronkers

2012-01-01

129

Brain regions underlying repetition and auditory-verbal short-term memory deficits in aphasia: Evidence from voxel-based lesion symptom mapping  

Microsoft Academic Search

Background: A deficit in the ability to repeat auditory-verbal information is common among individuals with aphasia. The neural basis of this deficit has traditionally been attributed to the disconnection of left posterior and anterior language regions via damage to a white matter pathway, the arcuate fasciculus. However, a number of lesion and imaging studies have called this notion into question.Aims:

Juliana V. Baldo; Shira Katseff; Nina F. Dronkers

2011-01-01

130

Progress of myelination in the human fetal spinal nerve roots, spinal cord and brainstem with myelin basic protein immunohistochemistry  

Microsoft Academic Search

The early progress of myelination was studied, by means of myelin basic protein (MBP) immunohistochemistry and luxol-fast-blue (LFB) staining, in the spinal cord, spinal nerve roots and brainstem of 66 fetuses and neonates. The degree of myelination was classified from 1 (slight) to 4 (mature). MBP immunoreactivity exhibited slight LFB positivity. Myelination first occurred in the medial longitudinal fasciculus at

Soichiro Tanaka; Takashi Mito; Sachio Takashima

1995-01-01

131

Artificial control of swimming in goldfish by brain stimulation: Confirmation of the midbrain nuclei as the swimming center  

Microsoft Academic Search

The midbrain locomotor region including the nucleus of the medial longitudinal fasciculus (Nflm) was electrically stimulated in free-moving goldfish. Stimulation of sites on the midline induced forward movement, whereas that of sites off midline induced turning toward the stimulated side. The closer the site of stimulation to Nflm, the lower the threshold stimulus intensity required to evoke locomotor movement. Using

Nobutaka Kobayashi; Masayuki Yoshida; Noritaka Matsumoto; Kazumasa Uematsu

2009-01-01

132

Perisylvian white matter connectivity in the human right hemisphere  

Microsoft Academic Search

BACKGROUND: By using diffusion tensor magnetic resonance imaging (DTI) and subsequent tractography, a perisylvian language network in the human left hemisphere recently has been identified connecting Brocas's and Wernicke's areas directly (arcuate fasciculus) and indirectly by a pathway through the inferior parietal cortex. RESULTS: Applying DTI tractography in the present study, we found a similar three-way pathway in the right

Alireza Gharabaghi; Frank Kunath; Michael Erb; Ralf Saur; Stefan Heckl; Marcos Tatagiba; Wolfgang Grodd; Hans-Otto Karnath

2009-01-01

133

Neuropsychological Correlates of Diffusion Tensor Imaging in Schizophrenia  

Microsoft Academic Search

Patients with schizophrenia (n = 41) and healthy comparison participants (n = 46) completed neuropsychological measures of intelligence, memory, and executive function. A subset of each group also completed magnetic resonance diffusion tensor imaging (DTI) studies (fractional anisotropy and cross-sectional area) of the uncinate fasciculus (UF) and cingulate bundle (CB). Patients with schizophrenia showed reduced levels of functioning across all

Paul G. Nestor; Marek Kubicki; Ronald J. Gurrera; Margaret Niznikiewicz; Melissa Frumin; Robert W. McCarley; Martha E. Shenton

2004-01-01

134

Extrastriatal dopaminergic innervation of human basal ganglia  

Microsoft Academic Search

A tyrosine-hydroxylase immunohistochemical analysis of the brains of normal human individuals has revealed nigrostriatal axons providing collaterals that arborize in the pallidum and subthalamic nucleus. These thin and varicose collaterals emerge from thick and smooth axons that course backward along the main output pathways of the basal ganglia, including the ansa lenticularis, the lenticular fasciculus and Wilson’s pencils. Many of

Martine Cossette; Martin Lévesque; André Parent

1999-01-01

135

Regeneration of descending projections to the spinal motor neurons after spinal hemisection in the goldfish  

Microsoft Academic Search

Following spinal transection, descending spinal projections from goldfish brainstem neurons spontaneously regenerate beyond the lesion site. The nucleus of the medial longitudinal fasciculus (nFLM), which has a critical role in swimming, also sends regenerated axons over a long distance to the ipsilateral spinal cord. To examine whether regenerated axons re-innervate the appropriate targets, we injected rhodamine dextran amine (RDA) into

Akihito Takeda; Richard C. Goris; Kengo Funakoshi

2007-01-01

136

Paraphasias in Multilingual Conduction Aphasia: A Single Case Study  

ERIC Educational Resources Information Center

|Conduction aphasia is a type of fluent aphasia, which is caused due to the damage to the supramarginal gyrus and arcuate fasciculus resulting in repetition disturbance. It has been speculated that linguistic system in bilingual aphasics can breakdown in different ways across languages. There is a lack of detailed linguistic studies in specific…

Hegde, Medha; Bhat, Sapna

2007-01-01

137

Structural white matter asymmetries in relation to functional asymmetries during speech perception and production.  

PubMed

Functional hemispheric asymmetries of speech production and perception are a key feature of the human language system, but their neurophysiological basis is still poorly understood. Using a combined fMRI and tract-based spatial statistics approach, we investigated the relation of microstructural asymmetries in language-relevant white matter pathways and functional activation asymmetries during silent verb generation and passive listening to spoken words. Tract-based spatial statistics revealed several leftward asymmetric clusters in the arcuate fasciculus and uncinate fasciculus that were differentially related to activation asymmetries in the two functional tasks. Frontal and temporal activation asymmetries during silent verb generation were positively related to the strength of specific microstructural white matter asymmetries in the arcuate fasciculus. In contrast, microstructural uncinate fasciculus asymmetries were related to temporal activation asymmetries during passive listening. These findings suggest that white matter asymmetries may indeed be one of the factors underlying functional hemispheric asymmetries. Moreover, they also show that specific localized white matter asymmetries might be of greater relevance for functional activation asymmetries than microstructural features of whole pathways. PMID:23921095

Ocklenburg, Sebastian; Hugdahl, Kenneth; Westerhausen, René

2013-08-03

138

White matter tract integrity and intelligence in patients with mental retardation and healthy adults  

Microsoft Academic Search

It is well known that brain structures correlate with intelligence but the association between the integrity of brain white matter tracts and intelligence in patients with mental retardation (MR) and healthy adults remains unknown. The aims of this study are to investigate whether the integrity of corpus callosum (CC), cingulum, uncinate fasciculus (UF), optic radiation (OR) and corticospinal tract (CST)

Chunshui Yu; Jun Li; Yong Liu; Wen Qin; Yonghui Li; Ni Shu; Tianzi Jiang; Kuncheng Li

2008-01-01

139

Altered connections on the road to psychopathy  

Microsoft Academic Search

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and\\/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore,

M C Craig; M Catani; Q Deeley; R Latham; E Daly; R Kanaan; M Picchioni; P K McGuire; T Fahy; D G M Murphy

2009-01-01

140

Comparison of white matter integrity between autism spectrum disorder subjects and typically developing individuals: a meta-analysis of diffusion tensor imaging tractography studies  

PubMed Central

Background Aberrant brain connectivity, especially with long-distance underconnectivity, has been recognized as a candidate pathophysiology of autism spectrum disorders. However, a number of diffusion tensor imaging studies investigating people with autism spectrum disorders have yielded inconsistent results. Methods To test the long-distance underconnectivity hypothesis, we performed a systematic review and meta-analysis of diffusion tensor imaging studies in subjects with autism spectrum disorder. Diffusion tensor imaging studies comparing individuals with autism spectrum disorders with typically developing individuals were searched using MEDLINE, Web of Science and EMBASE from 1980 through 1 August 2012. Standardized mean differences were calculated as an effect size of the tracts. Results A comprehensive literature search identified 25 relevant diffusion tensor imaging studies comparing autism spectrum disorders and typical development with regions-of-interest methods. Among these, 14 studies examining regions of interest with suprathreshold sample sizes were included in the meta-analysis. A random-effects model demonstrated significant fractional anisotropy reductions in the corpus callosum (P = 0.023, n = 387 (autism spectrum disorders/typically developing individuals: 208/179)), left uncinate fasciculus (P = 0.011, n = 242 (117/125)), and left superior longitudinal fasciculus (P = 0.016, n = 182 (96/86)), and significant increases of mean diffusivity in the corpus callosum (P = 0.006, n = 254 (129/125)) and superior longitudinal fasciculus bilaterally (P = 0.031 and 0.011, left and right, respectively, n = 109 (51/58)), in subjects with autism spectrum disorders compared with typically developing individuals with no significant publication bias. Conclusion The current meta-analysis of diffusion tensor imaging studies in subjects with autism spectrum disorders emphasizes important roles of the superior longitudinal fasciculus, uncinate fasciculus, and corpus callosum in the pathophysiology of autism spectrum disorders and supports the long-distance underconnectivity hypothesis.

2013-01-01

141

Diffusion tensor tractography findings in schizophrenia across the adult lifespan.  

PubMed

In healthy adult individuals, late life is a dynamic time of change with respect to the microstructural integrity of white matter tracts. Yet, elderly individuals are generally excluded from diffusion tensor imaging studies in schizophrenia. Therefore, we examined microstructural integrity of frontotemporal and interhemispheric white matter tracts in schizophrenia across the adult lifespan. Diffusion tensor imaging data from 25 younger schizophrenic patients (< or = 55 years), 25 younger controls, 25 older schizophrenic patients (> or = 56 years) and 25 older controls were analysed. Patients with schizophrenia in each group were individually matched to controls. Whole-brain tractography and clustering segmentation were employed to isolate white matter tracts. Groups were compared using repeated measures analysis of variance with 12 within-group measures of fractional anisotropy: (left and right) uncinate fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, inferior occipito-frontal fasciculus, cingulum bundle, and genu and splenium of the corpus callosum. For each white matter tract, fractional anisotropy was then regressed against age in patients and controls, and correlation coefficients compared. The main effect of group (F(3,92) = 12.2, P < 0.001), and group by tract interactions (F(26,832) = 1.68, P = 0.018) were evident for fractional anisotropy values. Younger patients had significantly lower fractional anisotropy than younger controls (Bonferroni-corrected alpha = 0.0042) in the left uncinate fasciculus (t(48) = 3.7, P = 0.001) and right cingulum bundle (t(48) = 3.6, P = 0.001), with considerable effect size, but the older groups did not differ. Schizophrenic patients did not demonstrate accelerated age-related decline compared with healthy controls in any white matter tract. To our knowledge, this is the first study to examine the microstructural integrity of frontotemporal white matter tracts across the adult lifespan in schizophrenia. The left uncinate fasciculus and right cingulum bundle are disrupted in younger chronic patients with schizophrenia compared with matched controls, suggesting that these white matter tracts are related to frontotemporal disconnectivity. The absence of accelerated age-related decline, or differences between older community-dwelling patients and controls, suggests that these patients may possess resilience to white matter disruption. PMID:20237131

Voineskos, Aristotle N; Lobaugh, Nancy J; Bouix, Sylvain; Rajji, Tarek K; Miranda, Dielle; Kennedy, James L; Mulsant, Benoit H; Pollock, Bruce G; Shenton, Martha E

2010-03-17

142

Gray and white matter water diffusion in the syndromic variants of frontotemporal dementia  

PubMed Central

Objective: To use diffusion tensor imaging (DTI) to assess gray matter and white matter tract diffusion in behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SMD), and progressive nonfluent aphasia (PNFA). Methods: This was a case-control study where 16 subjects with bvFTD, 7 with PNFA, and 4 with SMD were identified and matched by age and gender to 19 controls. All subjects had 3-T head MRI with a DTI sequence with diffusion encoding in 21 directions. Gray matter mean diffusivity (MD) was assessed using a region-of-interest (ROI) and voxel-level approach, and voxel-based morphometry was used to assess patterns of gray matter loss. White matter tract diffusivity (fractional anisotropy and radial diffusivity) was assessed by placing ROIs on tracts of interest. Results: In bvFTD, increased gray matter MD and gray matter loss were identified bilaterally throughout frontal and temporal lobes, with abnormal diffusivity observed in white matter tracts that connect to these regions. In SMD, gray matter loss and increased MD were identified predominantly in the left temporal lobe, with tract abnormalities observed in the inferior longitudinal fasciculus and uncinate fasciculus. In PNFA, gray matter loss and increased MD were observed in left inferior frontal lobe, insula, and supplemental motor area, with tract abnormalities observed in the superior longitudinal fasciculus. Conclusions: The diffusivity of gray matter is increased in regions that are atrophic in frontotemporal dementia, suggesting disruption of the cytoarchitecture of remaining tissue. Furthermore, damage was identified in white matter tracts that interconnect these regions, supporting the hypothesis that these diseases involve different and specific brain networks. GLOSSARY AAL = automated anatomic labeling; AC = anterior cingulate; ADRC = Alzheimer's Disease Research Center; ADPR = Alzheimer's Disease Patient Registry; AOS = apraxia of speech; bvFTD = behavioral variant frontotemporal dementia; CV = coefficient of variation; DA = axial diffusivity; DR = radial diffusivity; DTI = diffusion tensor imaging; FA = fractional anisotropy; FDR = false discovery rate; FOV = field of view; FTD = frontotemporal dementia; FWHM = full-width at half-maximum; GCC = genu of the corpus callosum; HDW = high-dimensional warping; ILF = inferior longitudinal fasciculus; MD = mean diffusivity; MPRAGE = magnetization prepared rapid acquisition gradient echo; PC = posterior cingulate; PNFA = progressive nonfluent aphasia; PVC = partial volume correction; ROI = region of interest; SLF = superior longitudinal fasciculus; SMD = semantic dementia; UNC = uncinate fasciculus.

Whitwell, J.L.; Avula, R.; Senjem, M.L.; Kantarci, K.; Weigand, S.D.; Samikoglu, A.; Edmonson, H.A.; Vemuri, P.; Knopman, D.S.; Boeve, B.F.; Petersen, R.C.; Josephs, K.A.; Jack, C.R.

2010-01-01

143

Neural pathways for language in autism: the potential for music-based treatments  

PubMed Central

Language deficits represent the core diagnostic characteristics of autism, and some of these individuals never develop functional speech. The language deficits in autism may be due to structural and functional abnormalities in certain language regions (e.g., frontal and temporal), or due to altered connectivity between these brain regions. In particular, a number of anatomical pathways that connect auditory and motor brain regions (e.g., the arcuate fasciculus, the uncinate fasciculus and the extreme capsule) may be altered in individuals with autism. These pathways may also provide targets for experimental treatments to facilitate communication skills in autism. We propose that music-based interventions (e.g., auditory–motor mapping training) would take advantage of the musical strengths of these children, and are likely to engage, and possibly strengthen, the connections between frontal and temporal regions bilaterally. Such treatments have important clinical potential in facilitating expressive language in nonverbal children with autism.

Wan, Catherine Y; Schlaug, Gottfried

2010-01-01

144

Minor head trauma and isolated unilateral internuclear ophthalmoplegia.  

PubMed

Internuclear ophthalmoplegia is a syndrome that develops due to a lesion of the medial longitudinal fasciculus. This lesion is mostly caused by multiple sclerosis (usually bilaterally), and only rarely by head injury. A case is presented of unilateral internuclear ophthalmoplegia as an isolated sequel of minor head trauma, which eventually resolved. A 40-year-old woman with isolated internuclear ophthalmoplegia secondary to closed head trauma with anatomical lesions of the mesencephalon in the region of medial longitudinal fasciculus is described. A minor contusion was detected by magnetic resonance imaging. Diplopia resolved in 5 months. In conclusion, internuclear ophthalmoplegia should be considered in the differential diagnosis in patients with recent head injuries showing adduction impairment. The connection between the clinical picture and anatomical lesions is visualized by magnetic resonance imaging. PMID:17044578

Cerovski, Branimir; Vidovi?, Tomislav; Papa, Jurica; Cerovski, Jasenka; Boji?, Lovro

2006-08-01

145

Continuity, Divergence, and the Evolution of Brain Language Pathways  

PubMed Central

Recently, the assumption of evolutionary continuity between humans and non-human primates has been used to bolster the hypothesis that human language is mediated especially by the ventral extreme capsule pathway that mediates auditory object recognition in macaques. Here, we argue for the importance of evolutionary divergence in understanding brain language evolution. We present new comparative data reinforcing our previous conclusion that the dorsal arcuate fasciculus pathway was more significantly modified than the ventral extreme capsule pathway in human evolution. Twenty-six adult human and twenty-six adult chimpanzees were imaged with diffusion-weighted MRI and probabilistic tractography was used to track and compare the dorsal and ventral language pathways. Based on these and other data, we argue that the arcuate fasciculus is likely to be the pathway most essential for higher-order aspects of human language such as syntax and lexical–semantics.

Rilling, James K.; Glasser, Matthew F.; Jbabdi, Saad; Andersson, Jesper; Preuss, Todd M.

2011-01-01

146

Assessing White Matter Integrity as a Function of Abstinence Duration in Former Cocaine-Dependent Individuals  

PubMed Central

Current cocaine-dependent users show reductions in white matter (WM) integrity, especially in cortical regions associated with cognitive control that have been associated with inhibitory dysfunction. A key question is whether these white matter differences are present following abstinence from drug use. To address this, WM integrity was examined using diffusion tensor imaging (DTI) obtained on 43 cocaine abstinent patients (abstinence duration ranged between five days and 102 weeks) and 43 non-using controls. Additionally, a cross-sectional comparison separated the patients into three groups (short-term, mid-term and long-term) based upon duration of cocaine abstinence. The 43 cocaine abstinent patients showed lower fractional anisotropy (FA) in the left anterior callosal fibers, left genu of the corpus callosum, right superior longitudinal fasciculus, right callosal fibers and the superior corona radiata bilaterally when compared against non-using controls. Higher FA in the cocaine abstinent patients was observed in the splenium of the corpus callosum and right superior longitudinal fasciculus. Differences between the cocaine abstinent groups were observed bilaterally in the inferior longitudinal fasciculus, right anterior thalamic radiation, right ventral posterolateral nucleus of the thalamus, left superior corona radiata, superior longitudinal fasciculus bilaterally, right cingulum and the WM of the right precentral gyrus. The results identified WM differences between cocaine abstinent patients and controls as well as distinct differences between abstinent subgroups. The findings suggest that specific white matter differences persist throughout abstinence while other, spatially distinct, differences discriminate as a function of abstinence duration. These differences may, therefore, represent brain changes that mark recovery from addiction.

Bell, Ryan P.; Foxe, John J.; Nierenberg, Jay; Hoptman, Matthew J.; Garavan, Hugh

2010-01-01

147

Isolated unilateral post-traumatic internuclear ophthalmoplegia.  

PubMed

A patient developed an isolated unilateral internuclear ophthalmoplegia (INO) after head trauma. An uncommon complication of closed head trauma, INO usually occurs bilaterally and is often associated with other neurologic deficits. The mechanism may be shear injury caused by angular acceleration leading to downward displacement of the posterior brainstem downward, stretching of the nerve fibers of the medial longitudinal fasciculus, or compression and tearing of its arterial supply. PMID:11725189

Chan, J W

2001-09-01

148

Ocular vestibular evoked myogenic potentials are abnormal in internuclear ophthalmoplegia  

Microsoft Academic Search

ObjectiveThe cervical vestibular evoked myogenic potential (cVEMP) is sensitive to lower brainstem lesions affecting the vestibulo-collic pathway. We wished to determine whether the ocular VEMP (oVEMP), a recently-described otolith–ocular reflex, is also abnormal in patients with brainstem lesions. We tested patients with internuclear ophthalmoplegia (INO), caused by a brainstem lesion in the medial longitudinal fasciculus (MLF), to investigate whether the

S. M. Rosengren; J. G. Colebatch

2011-01-01

149

Localization and Distribution Patterns of Nicotinamide Adenine Dinucleotide Phosphate Diaphorase Exhibiting Axons in the White Matter of the Spinal Cord of the Rabbit  

Microsoft Academic Search

The funicular distribution of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-exhibiting axons was examined in the white matter of the rabbit spinal cord by using horizontal, parasaggital, and transverse sections. Four morphologically distinct kinds of NADPHd-exhibiting axons (2.5–3.5 µm in diameter) were identified in the sulcomarginal fasciculus as a part of the ventral column in the cervical and upper thoracic segments

Jozef Maršala; Martin Maršala; Nadežda Luká?ová; Toshizo Ishikawa; Dáša ?ížková

2003-01-01

150

Microstructural White Matter Changes, Not Hippocampal Atrophy, Detect Early Amnestic Mild Cognitive Impairment  

PubMed Central

Background Alzheimer’s disease (AD) is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI), a prodromal stage of AD. Methods We studied 155 cognitively normal (CN) and 27 ‘late’ aMCI individuals with stable diagnosis over 2 years, and 39 ‘early’ aMCI individuals who had converted from CN to aMCI at 2-year follow up. Diffusion tensor imaging (DTI) tractography was used to reconstruct six white matter tracts three limbic tracts critical for episodic memory function - the fornix, the parahippocampal cingulum, and the uncinate fasciculus; two cortico-cortical association fiber tracts - superior longitudinal fasciculus and inferior longitudinal fasciculus; and one projection fiber tract - corticospinal tract. Microstructural integrity as measured by fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) was assessed for these tracts. Results Compared with CN, late aMCI had lower white matter integrity in the fornix, the parahippocampal cingulum, and the uncinate fasciculus, while early aMCI showed white matter damage in the fornix. In addition, fornical measures were correlated with hippocampal atrophy in late aMCI, whereas abnormality of the fornix in early aMCI occurred in the absence of hippocampal atrophy and did not correlate with hippocampal volumes. Conclusions Limbic white matter tracts are preferentially affected in the early stages of cognitive dysfunction. Microstructural degradation of the fornix preceding hippocampal atrophy may serve as a novel imaging marker for aMCI at an early stage.

Zhuang, Lin; Sachdev, Perminder S.; Trollor, Julian N.; Reppermund, Simone; Kochan, Nicole A.; Brodaty, Henry; Wen, Wei

2013-01-01

151

Conduction Aphasia in a 3YearOld with a Left Posterior Cortical\\/Subcortical Abscess  

Microsoft Academic Search

A 3-year-old, right-handed girl developed a conduction-type aphasia following a second generalized seizure in the setting of a developing abscess involving left subcortical and cortical angular gyrus and arcuate fasciculus, and the posterior corpus callosum. The language disorder was fluent, characterized by age appropriate mean length of utterance and syntax, but with markedly reduced spontaneity of output, rapid rate of

Ruth Nass; Fern Leventhal; Beth Levine; Diana Lebron; Carol Maxfield; Patricia McCaul; Ajax George; Jeffrey Allen

1998-01-01

152

Existence of Different Subtypes of Nicotinic Acetylcholine Receptors in the Rat Habenulo-interpeduncular System  

Microsoft Academic Search

Neuronal nicotinic ACh receptors (nAChRs) are present in the rat medial habenula (MHB) and interpeduncular nucleus (IPN), two brain regions connected through the fasciculus retroflexus (FR). The goal of the present study was to com- pare the electrophysiological and pharmacological charac- teristics of nAChRs located at pre- and postsynaptic sites within the MHB-IPN system. nAChRs located on the soma of

Christophe Mulle; Catherine Vidal; Pierre Benoit; Jean-Pierre Changeux

1991-01-01

153

White matter microstructural abnormalities in the frontal lobe of adults with antisocial personality disorder  

Microsoft Academic Search

IntroductionAntisocial personality disorder (ASPD) and psychopathy involve significant interpersonal and behavioural impairments. However, little is known about their underlying neurobiology and in particular, abnormalities in white matter (WM) microstructure. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of adult psychopaths employing tractography revealed abnormalities in the right uncinate fasciculus (UF) (Craig et al., 2009), indicating fronto-limbic disconnectivity. However, it is

Frederick Sundram; Quinton Deeley; Sagari Sarkar; Eileen Daly; Richard Latham; Michael Craig; Tom Fahy; Marco Picchioni; Gareth J. Barker; Declan G. M. Murphy

154

Association between Subcortical Vascular Lesion Location and Cognition: A Voxel-Based and Tract-Based Lesion-Symptom Mapping Study. The SMART-MR Study  

PubMed Central

Introduction Lacunar lesions (LLs) and white matter lesions (WMLs) affect cognition. We assessed whether lesions located in specific white matter tracts were associated with cognitive performance taking into account total lesion burden. Methods Within the Second Manifestations of ARTerial disease Magnetic Resonance (SMART-MR) study, cross-sectional analyses were performed on 516 patients with manifest arterial disease. We applied an assumption-free voxel-based lesion-symptom mapping approach to investigate the relation between LL and WML locations on 1.5 Tesla brain MRI and compound scores of executive functioning, memory and processing speed. Secondly, a multivariable linear regression model was used to relate the regional volume of LLs and WMLs within specific white matter tracts to cognitive functioning. Results Voxel-based lesion-symptom mapping identified several clusters of voxels with a significant correlation between WMLs and executive functioning, mostly located within the superior longitudinal fasciculus and anterior thalamic radiation. In the multivariable linear regression model, a statistically significant association was found between regional LL volume within the superior longitudinal fasciculus and anterior thalamic radiation and executive functioning after adjustment for total LL and WML burden. Conclusion These findings identify the superior longitudinal fasciculus and anterior thalamic radiation as key anatomical structures in executive functioning and emphasize the role of strategically located vascular lesions in vascular cognitive impairment.

Biesbroek, J. Matthijs; Kuijf, Hugo J.; van der Graaf, Yolanda; Vincken, Koen L.; Postma, Albert; Mali, Willem P. T. M.; Biessels, Geert J.; Geerlings, Mirjam I.

2013-01-01

155

The neural circuitry of visual artistic production and appreciation: A proposition  

PubMed Central

The nondominant inferior parietal lobule is probably a major “store house” of artistic creativity. The ventromedial prefrontal lobe (VMPFL) is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL) in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF), relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo–amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit) is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously.

Chakravarty, Ambar

2012-01-01

156

Asymmetry, sex differences and age-related changes in the white matter in the healthy elderly: a tract-based study  

PubMed Central

Background Hemispherical asymmetry, sex differences and age-related changes have been reported for the human brain. Meanwhile it was still unclear the presence of the asymmetry or sex differences in the human brain occurred whether as a normal development or as consequences of any pathological changes. The aim of this study was to investigate hemispherical asymmetry, sex differences and age-related changes by using a tract-based analysis in the nerve bundles. Methods 40 healthy elderly subjects underwent magnetic resonance diffusion tensor imaging, and we calculated fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values along the major white matter bundles. Results We identified hemispherical asymmetry in the ADC values for the cingulate fasciculus in the total subject set and in males, and a sex difference in the FA values for the right uncinate fasciculus. For age-related changes, we demonstrated a significant increase in ADC values with advancing age in the right cingulum, left temporal white matter, and a significant decrease in FA values in the right superior longitudinal fasciculus. Conclusion In this study, we found hemispherical asymmetry, sex differences and age-related changes in particular regions of the white matter in the healthy elderly. Our results suggest considering these differences can be important in imaging studies.

2011-01-01

157

Gender Differences in White Matter Microstructure  

PubMed Central

Background Sexual dimorphism in human brain structure is well recognised, but little is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore differences in fractional anisotropy (FA), an index of microstructural integrity. Methods A whole brain analysis of 135 matched subjects (90 men and 45 women) using a 1.5 T scanner. A region of interest (ROI) analysis was used to confirm those results where proximity to CSF raised the possibility of partial-volume artefact. Results Men had higher fractional anisotropy (FA) in cerebellar white matter and in the left superior longitudinal fasciculus; women had higher FA in the corpus callosum, confirmed by ROI. Discussion The size of the differences was substantial - of the same order as that attributed to some pathology – suggesting gender may be a potentially significant confound in unbalanced clinical studies. There are several previous reports of difference in the corpus callosum, though they disagree on the direction of difference; our findings in the cerebellum and the superior longitudinal fasciculus have not previously been noted. The higher FA in women may reflect greater efficiency of a smaller corpus callosum. The relatively increased superior longitudinal fasciculus and cerebellar FA in men may reflect their increased language lateralisation and enhanced motor development, respectively.

Kanaan, Richard A.; Allin, Matthew; Picchioni, Marco; Barker, Gareth J.; Daly, Eileen; Shergill, Sukhwinder S.; Woolley, James; McGuire, Philip K.

2012-01-01

158

White Matter Integrity and Prediction of Social and Role Functioning in Subjects at Ultra-High Risk for Psychosis  

PubMed Central

Background White matter microstructural disruptions have been observed in patients with schizophrenia. However, whether changes exist prior to disease onset or in high-risk individuals is unclear. Here we investigated white matter integrity, as assessed by diffusion tensor imaging (DTI), in individuals at ultra high risk for psychosis (UHR), relative to healthy controls (HC), and the relationship between baseline DTI measures and functional outcome over time. Methods Thirty-six UHR participants and 25 HC’s completed baseline DTI scans. Subjects also completed clinical follow-up assessments approximately 6 (26 subjects) and 15 months (13 subjects) later. We used a rigorous registration approach (Tract-Based Spatial Statistics (TBSS) to examine fractional anisotropy (FA) in six major white matter tracts. Results Relative to the HC group, UHR subjects showed lower baseline FA in the superior longitudinal fasciculus, the major frontal-parietal white matter connection. Cross-sectional analyses demonstrated that UHR youth failed to show the same age-associated increases in FA in the hippocampus and inferior longitudinal fasciculus as HCs. Finally, lower baseline FA in the hippocampus and inferior longitudinal fasciculus predicted deterioration in social and role functioning in UHR participants at 15-month follow-up. Conclusions This is the first investigation of white matter microstructural alterations in a clinical high-risk sample. Our findings indicate that white matter development may be altered in youth at risk for psychosis, possibly due to disrupted developmental mechanisms, and further, that white matter integrity may be predictive of functional outcome.

Karlsgodt, Katherine H.; Niendam, Tara A.; Bearden, Carrie E.; Cannon, Tyrone D.

2009-01-01

159

Anatomy of the Temporal Lobe  

PubMed Central

Only primates have temporal lobes, which are largest in man, accommodating 17% of the cerebral cortex and including areas with auditory, olfactory, vestibular, visual and linguistic functions. The hippocampal formation, on the medial side of the lobe, includes the parahippocampal gyrus, subiculum, hippocampus, dentate gyrus, and associated white matter, notably the fimbria, whose fibres continue into the fornix. The hippocampus is an inrolled gyrus that bulges into the temporal horn of the lateral ventricle. Association fibres connect all parts of the cerebral cortex with the parahippocampal gyrus and subiculum, which in turn project to the dentate gyrus. The largest efferent projection of the subiculum and hippocampus is through the fornix to the hypothalamus. The choroid fissure, alongside the fimbria, separates the temporal lobe from the optic tract, hypothalamus and midbrain. The amygdala comprises several nuclei on the medial aspect of the temporal lobe, mostly anterior the hippocampus and indenting the tip of the temporal horn. The amygdala receives input from the olfactory bulb and from association cortex for other modalities of sensation. Its major projections are to the septal area and prefrontal cortex, mediating emotional responses to sensory stimuli. The temporal lobe contains much subcortical white matter, with such named bundles as the anterior commissure, arcuate fasciculus, inferior longitudinal fasciculus and uncinate fasciculus, and Meyer's loop of the geniculocalcarine tract. This article also reviews arterial supply, venous drainage, and anatomical relations of the temporal lobe to adjacent intracranial and tympanic structures.

Kiernan, J. A.

2012-01-01

160

Light-induced short-term adaptation mechanisms under redox control in the PS II-LHCII supercomplex: LHC II state transitions and PS II repair cycle  

NASA Astrophysics Data System (ADS)

Oxygenic photosynthesis takes place in the thylakoid membranes of cyanobacteria, algae and higher plants. While cyanobacteria have adapted to relatively constant environments, higher plants had to evolve mechanisms to adapt to continuous environmental changes. These include changes in light intensity, temperature and availability of water. One of the great challenges in plant cell biology is therefore to determine the regulatory mechanisms employed by higher plants and some algae to adapt to these constant environmental changes. The particular emphasis of this review is the description and characterisation of light-induced redox-controlled processes regulating the photosynthetic reactions, which involves maintaining maximal electron transport flow through the PS II-Cytb6f-PS I-FoF1ATPase electron transport chain and minimising light-induced oxidative damage to PS II which drives the highly oxidising water-splitting reaction. Two of the mechanisms involved in such short-term regulation processes are known as light harvesting complex II (LHC II) state transitions and photosystem II (PS II) repair cycle. They are followed by, and indeed may be a precondition in order to establish, the onset of the subsequent long-term mechanisms of regulation. In particular, the redox control of LHC II state transitions by reversible phosphorylation has been in the focus of many investigations, leading to many new results demonstrating the complexity of thylakoid-associated redox control mechanisms.

Kruse, Olaf

2001-05-01

161

The topology of dermatomal projection in the medial lemniscal system  

PubMed Central

1. The topographic organization of first order afferent fibres in the lumbar, sacral and coccygeal dorsal roots, and in the fasciculus gracilis was studied in squirrel monkeys. 2. At the entry zone, progressing from caudal to rostral, dorsal root filaments receive fibres from tail and hind-limb receptive fields which serially overlap and describe a spiral-shaped trajectory. The latter starts with tail, progresses post-axially towards the foot, crosses the foot from lateral to medial, and ascends the preaxial leg. 3. In the fasciculus gracilis, this arrangement of fibres at the dorsal root entry zone is preserved in its entirety. It assumes the form of a fibre lamination, with the most caudal dorsal root fibres occupying a dorso-medial location; further rostral dorsal root fibres come to lie more ventrolaterally. 4. Dorsum and sole of foot project in an overlapping and interdigitating manner to the fibre lamina of the 7th lumber dermatome in the fasciculus gracilis. Thereby, dorsum and sole of foot behave in the projection as if they were one and the same surface. 5. The argument is presented that the foot and its projection on to the cross-sectional plane of the dorsal funiculus are topologically equivalent and that the hind-limb as a whole and its projection are not. On the other hand, homotopic mapping of the foot together with the sequential fibre organization in the dorsal funiculus enable many more types of closed curves on the body surface to remain arc-wise connected in the projection than would otherwise be possible. ImagesPlate 1

Werner, Gerhard; Whitsel, Barry L.

1967-01-01

162

Testing the white matter retrogenesis hypothesis of cognitive aging.  

PubMed

The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimer's disease, it has not been tested systematically in normal cognitive aging. In the current study, we examined the retrogenesis hypothesis in a group (n = 282) of cognitively normal individuals, ranging in age from 7 to 87 years, from the Brain Resource International Database. Participants were evaluated with a comprehensive neuropsychological battery and were imaged with diffusion tensor imaging. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (DA), measures of white matter coherence, were computed in 2 prototypical early-myelinated fiber tracts (posterior limb of the internal capsule, cerebral peduncles) and 2 prototypical late-myelinated fiber tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus) chosen to parallel previous studies; mean summary values were also computed for other early- and late-myelinated fiber tracts. We examined age-associated differences in FA, RD, and DA in the developmental trajectory (ages 7-30 years) and degenerative trajectory (ages 31-87 years), and tested whether the measures of white matter coherence mediated age-related cognitive decline in the older group. FA and DA values were greater for early-myelinated fibers than for late-myelinated fibers, and RD values were lower for early-myelinated than late-myelinated fibers. There were age-associated differences in FA, RD, and DA across early- and late-myelinated fiber tracts in the younger group, but the magnitude of differences did not vary as a function of early or late myelinating status. FA and RD in most fiber tracts showed reliable age-associated differences in the older age group, but the magnitudes were greatest for the late-myelinated tract summary measure, inferior longitudinal fasciculus (late fiber tract), and cerebral peduncles (early fiber tract). Finally, FA in the inferior longitudinal fasciculus and cerebral peduncles and RD in the cerebral peduncles mediated age-associated differences in an executive functioning factor. Taken together, the findings highlight the importance of white matter coherence in cognitive aging and provide some, but not complete, support for the white matter retrogenesis hypothesis in normal cognitive aging. PMID:21783280

Brickman, Adam M; Meier, Irene B; Korgaonkar, Mayuresh S; Provenzano, Frank A; Grieve, Stuart M; Siedlecki, Karen L; Wasserman, Ben T; Williams, Leanne M; Zimmerman, Molly E

2011-07-23

163

Internuclear ophthalmoplegia of abduction: clinical and electrophysiological data on the existence of an abduction paresis of prenuclear origin.  

PubMed Central

Three patients showed unilateral and five bilateral abduction paresis. Five had associated adduction nystagmus of the contralateral eye. Electrophysiological testing of masseter and blink reflexes indicated an ipsilateral rostral pontine or mesencephalic lesion, and excluded a lesion of the infranuclear portion of the abducens nerve. Abduction paresis was attributed to impaired inhibition of the tonic resting activity of the antagonistic medial rectus muscle. The prenuclear origin of the disorder is based on morphological and neurophysiological evidence of an ipsilateral inhibitory connection between the paramedian pontine reticular formation and the oculomotor nucleus running close to but separated from the medial longitudinal fasciculus. Images

Thomke, F; Hopf, H C; Kramer, G

1992-01-01

164

Experimental internuclear ophthalmoplegia.  

PubMed Central

A midline experimental lesion separating the medial longitudinal fasciculi at and below the level of the abducens nuclei without damaging either fasciculus at the level of the nuclei has produced defects of ocular motility resembling those of clinical internuclear ophthalmoplegia. Electromyographic recordings during lateral gaze demonstrate: (1) lack of inhibition of the lateral rectus muscle in the adducting eye, (2) delayed inhibition of the medial rectus muscle in the abducting eye, and (3) occasional evidence of excitation of the medial rectus muscle of the abducting eye probably associated with pupillary constriction. The presumed physiologic mechanisms involved in conjugate gaze movements are discussed in the light of the experimental findings. Images

Burde, R. M.; Lehman, R. A.; Roper-Hall, G.; Brooks, J.; Keltner, J. L.

1977-01-01

165

[A case of brainstem and cerebellar infarctions related to basilar impression].  

PubMed

We report a 30-year-old man presenting with medial longitudinal fasciculus (MLF) syndrome after an afternoon nap. Magnetic resonance imaging revealed a right medial pontine tegmental infarction and right cerebellar infarctions. This patient was complicated with basilar impression detected on cervical X-ray and MRI. Three-dimensional CT angiography disclosed that the odontoid process migrated into the posterior fossa, thrusting the bilateral vertebral arteries postero-laterally. The mechanical stress on the bilateral vertebral arteries may have caused infarctions in the territories of the posterior circulation of this patient with basilar impression. PMID:15233275

Kasai, Takashi; Yoshikawa, Kenji; Tachibana, Shunji; Taniguchi, Takuya; Nakagawa, Masanori

2004-03-01

166

Investigating musical disorders with diffusion tensor imaging: a comparison of imaging parameters.  

PubMed

The arcuate fasciculus (AF) is a bundle of white matter traditionally thought to be responsible for language function. However, its role in music is not known. Here we investigate the connectivity of the AF using diffusion tensor imaging (DTI) and show that musically tone-deaf individuals, who show impairments in pitch discrimination, have reduced connectivity in the AF relative to musically normal-functioning control subjects. Results were robust to variations in imaging parameters and emphasize the importance of brain connectivity in para-linguistic processes, such as music. PMID:19673766

Loui, Psyche; Schlaug, Gottfried

2009-07-01

167

Leonardo da Vinci and Kethem-Kiveris vena.  

PubMed

In the drawing of coitus by Leonardo da Vinci are pictured the contemporary hypotheses regarding this act. The authors analyze the mamillaruteral connection depicted by the artist and grow up to believe that this is a hypothetical kiveris vena, female vein described by Anatomist Master Nicolai Physicus from the Salerno School. The Hebrew roots were found in the name. The connection is described also by Mondino in The Anathomia. The same connection can be found in the picture of the pregnant woman in Fasciculus Medicinæ by Johannes De Ketham. PMID:23391978

Dolezal, Antonín; Skorepova-Honzlova, Zita; Jelen, Karel

2012-01-01

168

Progressive supranuclear palsy: a brief personalized history.  

PubMed Central

Progressive supranuclear palsy (PSP) was originally described in 1964. Although some contended it was merely a variant of Parkinson's disease, a specific electron microscopic finding of straight, rather than twisted, filaments in the neurofibrillary tangles established PSP as a distinct entity. The almost pathognomonic early clinical finding of paralysis of downward gaze is due to lesions involving the lateral portions of the rostral interstitial nucleus of the medial longitudinal fasciculus. Recent neurochemical studies have identified both a decrease in central dopamine and acetylcholine. The etiology of PSP is unknown, and the therapy is generally ineffective.

Daroff, R. B.

1987-01-01

169

Neural systems predicting long-term outcome in dyslexia  

PubMed Central

Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25) or without dyslexia (n = 20) to discover whether initial behavioral or brain measures, including functional MRI (fMRI) and diffusion tensor imaging (DTI), can predict future long-term reading gains in dyslexia. No behavioral measure, including widely used and standardized reading and language tests, reliably predicted future reading gains in dyslexia. Greater right prefrontal activation during a reading task that demanded phonological awareness and right superior longitudinal fasciculus (including arcuate fasciculus) white-matter organization significantly predicted future reading gains in dyslexia. Multivariate pattern analysis (MVPA) of these two brain measures, using linear support vector machine (SVM) and cross-validation, predicted significantly above chance (72% accuracy) which particular child would or would not improve reading skills (behavioral measures were at chance). MVPA of whole-brain activation pattern during phonological processing predicted which children with dyslexia would improve reading skills 2.5 y later with >90% accuracy. These findings identify right prefrontal brain mechanisms that may be critical for reading improvement in dyslexia and that may differ from typical reading development. Brain measures that predict future behavioral outcomes (neuroprognosis) may be more accurate, in some cases, than available behavioral measures.

Hoeft, Fumiko; McCandliss, Bruce D.; Black, Jessica M.; Gantman, Alexander; Zakerani, Nahal; Hulme, Charles; Lyytinen, Heikki; Whitfield-Gabrieli, Susan; Glover, Gary H.; Reiss, Allan L.; Gabrieli, John D. E.

2010-01-01

170

Eel calcitonin binding site distribution and antinociceptive activity in rats  

SciTech Connect

The distribution of binding site for (/sup 125/I)-eel-calcitonin (ECT) to rat central nervous system, studied by an autoradiographic technique, showed concentrations of binding in the diencephalon, the brain stem and the spinal cord. Large accumulations of grains were seen in the hypothalamus, the amygdala, in the fasciculus medialis prosencephali, in the fasciculus longitudinalis medialis, in the ventrolateral part of the periventricular gray matter, in the lemniscus medialis and in the raphe nuclei. The density of grains in the reticular formation and in the nucleus tractus spinalis nervi trigemini was more moderate. In the spinal cord, grains were scattered throughout the dorsal horns. Binding of the ligand was displaced equally by cold ECT and by salmon CT(sCT), indicating that both peptides bind to the same receptors. Human CT was much weaker than sCT in displacing (/sup 125/I)-ECT binding. The administration of ECT into the brain ventricles of rats dose-dependently induced a significant and long-lasting enhancement of hot-plate latencies comparable with that obtained with sCT. The antinociceptive activity induced by ECT is compatible with the topographical distribution of binding sites for the peptide and is a further indication that fish CTs are active in the mammalian brain.

Guidobono, F.; Netti, C.; Sibilia, V.; Villa, I.; Zamboni, A.; Pecile, A.

1986-03-01

171

Neuropathology of chronic vitamine E deficiency in fatal familial intrahepatic cholestasis.  

PubMed

A progressive neuromuscular syndrome developed in a girl suffering from fatal familial intrahepatic cholestasis (Byler disease). The neuromuscular syndrome included muscular wasting of the legs, pes cavus, areflexia, decreased vibratory sensation, cerebellar symptoms, ophthalmoplegia, and visual disturbance with retinitis pigmentosa. The serum vitamin E level was extremely low. Postmortem neuropathologic study revealed the following lesions: (1) Systemic axonopathy involving the peripheral nerves and proximal axons of the dorsal root ganglia and posterior roots as well as the distal axons of the central nervous system (CNS) (2) Neuronal loss in the sensory and oculomotor nuclei of the brain stem, basal ganglia, Clarke's column, posterior horn, and dorsal root ganglia. (3) Neuronal lipofuscinosis. Axonopathy was severer in the more distal axonal segments, although the cuneate fasciculus was more affected than the gracile fasciculus. The severity of neuronal lipofuscinosis was not correlated with that of neuronal disintegration. The electron-dense bodies in the dystrophic swollen axons resembled lipofuscin granules. These neuropathologic lesions were considered to be the sequelae to chronic vitamin E deficiency. PMID:7158298

Saito, K; Yokoyama, T; Okaniwa, M; Kamoshita, S

1982-01-01

172

Understanding higher level gait disturbances in mild dementia in order to improve rehabilitation: 'last in-first out'.  

PubMed

Predicting and anticipating disturbances in higher level gait is particularly relevant for patients with dementia as higher level gait appears to be closely related to higher level cognitive functioning. A phenomenon that could contribute to the understanding and prediction of disturbances in higher level gait and gait-related motor activity in the various subtypes of dementia is paraphrased as 'last in-first out'. 'Last in-first out' refers to the principle that neural circuits that mature late in development are the most vulnerable to neurodegeneration. The strength of relating symptoms to the 'last in-first out' principle is that a future symptom can be predicted and anticipated in a therapeutic way, even if the disease process has not already started. Therefore, the aim of this review is to provide new strategies for rehabilitation of higher level gait disturbances in dementia based upon the 'last in-first out' principle. These new strategies emerge from five neural networks: the superior longitudinal fasciculus, the uncinate fasciculus, the fronto-cerebellar and fronto-striatal connections, and the cingulum. PMID:20833200

Scherder, Erik; Eggermont, Laura; Visscher, Chris; Scheltens, Philip; Swaab, Dick

2010-09-15

173

White Matter Integrity and Five-Factor Personality Measures in Healthy Adults  

PubMed Central

The five-factor model organizes personality traits into five factors: Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Measures of these personality traits predict people’s behaviors and important outcomes of their lives. Therefore, understanding the neural correlates of these personality traits is important. This study assessed the relationships between white matter (WM) integrity and personality traits among 51 healthy participants using diffusion tensor imaging (DTI) and the revised NEO Personality Inventory (NEO-PI-R). Neuroticism correlated positively while Openness and Agreeableness correlated negatively with DTI mean diffusivity (MD) in the corona radiata and superior longitudinal fasciculus, tracts which interconnect prefrontal cortex (PFC), parietal cortex, and subcortical structures. Furthermore, Neuroticism correlated positively with MD in the anterior cingulum and uncinate fasciculus, tracts interconnecting PFC and amygdala. Openness correlated negatively with MD of WM adjacent to the dorsolateral PFC in both hemispheres. These findings suggest that greater Neuroticism associates with worse integrity of WM interconnecting extensive cortical and subcortical structures including the PFC and amygdala and that greater Openness associates with better integrity of WM interconnecting extensive cortical and subcortical structures including the dorsolateral PFC.

Xu, Jiansong; Potenza, Marc N.

2011-01-01

174

A Method for Clustering White Matter Fiber Tracts  

PubMed Central

BACKGROUND/PURPOSE Despite its potential for visualizing white matter fiber tracts in vivo, diffusion tensor tractography has found only limited applications in clinical research in which specific anatomic connections between distant regions need to be evaluated. We introduce a robust method for fiber clustering that guides the separation of anatomically distinct fiber tracts and enables further estimation of anatomic connectivity between distant brain regions. METHODS Line scanning diffusion tensor images (LSDTI) were acquired on a 1.5T magnet. Regions of interest for several anatomically distinct fiber tracts were manually drawn; then, white matter tractography was performed by using the Runge-Kutta method to interpolate paths (fiber traces) following the major directions of diffusion, in which traces were seeded only within the defined regions of interest. Next, a fully automatic procedure was applied to fiber traces, grouping them according to a pairwise similarity function that takes into account the shapes of the fibers and their spatial locations. RESULTS We demonstrated the ability of the clustering algorithm to separate several fiber tracts which are otherwise difficult to define (left and right fornix, uncinate fasciculus and inferior occipitofrontal fasciculus, and corpus callosum fibers). CONCLUSION This method successfully delineates fiber tracts that can be further analyzed for clinical research purposes. Hypotheses regarding specific fiber connections and their abnormalities in various neuropsychiatric disorders can now be tested.

O'Donnell, L.J.; Kubicki, M.; Shenton, M.E.; Dreusicke, M.H.; Grimson, W.E.L.; Westin, C.F.

2009-01-01

175

Dorsal fronto-parietal connections of the human brain: a fiber dissection study of their composition and anatomical relationships.  

PubMed

The goal of this study was to detail the composition of dorsal fronto-parietal connections in the human brain, focusing on the dorsal component of superior longitudinal fasciculus (SLF), short association fibers, their three-dimensional organization, and relationships with adjacent projection and commissural fibers. Ten human cerebral hemispheres (five left and five right) were obtained from necropsy specimens. The technique for specimen preparation was adapted from that previously described by Ludwig and Klingler for spreading groups of white matter fibers, rendering tracts visible and dissectible. Near the superior border of the hemisphere, we observed an overall organization consisting of a succession of "U" fibers in both sides of a narrow and irregular intermediary layer of white matter. Dissection of the core fibers leads to the corona radiata (intermingled with the callosal radiations) on the lateral aspect and to the callosal radiations at the medial aspect of the hemisphere. Based on our findings, the fiber dissection technique does not provide evidence of the presence of long horizontal association fibers in such location, as suggested by brain imaging techniques. The results of this study lead us to hypothesize that dorsal regions of the frontal and parietal lobes superior to the level of the cingulate sulcus are connected by a succession of short association pathways. Dissectible long association fibers are only encountered in a zone restricted to a lower and deeper portion of the superior parietal lobule. These fibers are clearly integrated in the lower portions of the SLF/arcuate fasciculus complex. PMID:22190345

Maldonado, Igor L; Mandonnet, Emmanuel; Duffau, Hugues

2011-12-20

176

Stereotactic disconnection of hypothalamic hamartoma to control seizure and behavior disturbance: case report and literature review.  

PubMed

An 18-year-old boy with refractory epilepsy and aggressiveness associated to a hypothalamic hamartoma was submitted to a stereotactically guided lesion by thermocoagulation. The target was based on magnetic resonance (MR) images merged with computed tomography scan images taken on the day of surgery while patient was on a stereotactic frame. In order to reveal structures not discernible in MR images, the Schaltenbrand digital brain atlas was merged onto the patient's images. Target and trajectory of the depth electrode were chosen based on three-dimensional imaging reconstructions. A surgical plan was devised to disconnect the hypothalamic hamartoma from the hypothalamus, medial forebrain bundle, fasciculus princeps, and dorsal longitudinal fasciculus. Our target was placed at the inferior portion of the posterolateral component of the hamartoma, bordering the normal hypothalamus. The patient evolved with marked lessening of aggressiveness. Seizure frequency was reduced from several seizures per day to less than one tonic-clonic seizure during sleep per month and only two episodes suggestive of partial complex seizures during daytime. These results have remained consistent over a 24-month postoperative follow-up. Functional neuroanatomy of hypothalamic connections involved in seizure propagation and aggressive behavior was reviewed. PMID:18443834

de Almeida, Antonio Nogueira; Fonoff, Erich Talamoni; Ballester, Gerson; Teixeira, Manoel Jacobsen; Marino, Raul

2008-04-29

177

Diffusion tensor imaging (DTI) and colored fractional anisotropy (FA) mapping of the subthalamic nucleus (STN) and the globus pallidus interna (GPi)  

PubMed Central

Introduction The subthalamic nucleus (STN) and the globus pallidus internus (GPi) are the most common surgical targets for the treatment of Parkinson’s disease. We studied directionally colored fractional anisotropy (FA) and diffusion tensor imaging (DTI) sequences to better target these anatomical regions. Methods Four patients undergoing stereotactic surgery for movement disorders were studied. Stereotactic targets and fiber tractography were determined on MRIs using the Schaltenbrand–Wahren atlas for definition in the iPlan software. In addition, post-operative imaging was fused to preoperative FA sequences for end-result identification. Axial, sagittal, and coronal images of the FA sequence were studied. DTI parameters used ranged from 2 to 4 mm for voxel size in the x/y/z planes, fiber length was kept constant at 15 mm and FA threshold of 0.25. Results Colored FA maps resulted in a key signature in and around the STN and GPi. Regions identified include, but were not limited to: the internal capsule, nigral projections, the thalamic fasciculus, Forel’s fields H1 and H2, zona incerta, suthalamic fasciculus, tegmental tracts, and cerebello-rubro-thalamic tract. Conclusions Colored FA maps allow a potential method to identify the STN and GPi accurately. DTI has proven to be a powerful tool that can be used to augment identification of the STN nucleus and GPi used for stereotactic surgery.

Gorgulho, Alessandra; Bari, Ausaf; Behnke, Eric; Frew, Andrew; Gevorkyan, Inga; Pouratian, Nader; DeSalles, Antonio

2010-01-01

178

Alterations of mean diffusivity in brain white matter and deep gray matter in Parkinson's disease.  

PubMed

Although Parkinson's disease is a neurodegenerative disease primarily involving basal ganglia and midbrain, the deficit of white matter is also involved during the disease progression. As the diffusion tensor imaging method is sensitive to the microstructural changes, we investigated the microstructural alterations in white matter and deep gray matter in patients with Parkinson's disease. Brain images of 64 patients and sex- and age-matched 64 healthy controls were obtained from a 3T MRI scanner. Tract-based spatial statistics were used to compare the mean diffusivity of the white matter tract between the groups. Voxel-based analysis was used to compare the mean diffusivity of the subcortical gray matter between the groups. There were white matter deficits in the corticofugal tract, cingulum, uncinate fasciculus, crus of fornix or stria terminalis, corpus callosum, external capsule, superior longitudinal fasciculus, posterior thalamic radiation including optic radiation, and the tracts adjacent to the precuneus and supramarginal gyrus, as indicated by higher mean diffusivity in Parkinson's disease patients than in controls. There were also deficits in the left putamen, pallidum, thalamus, and caudate as indicated by higher mean diffusivity in Parkinson's disease patients than in controls. Using diffusion tensor imaging and multi-methods of image analysis, we successfully characterized and visualized brain white matter and deep gray matter areas with microstructural deficits in Parkinson's disease patients. PMID:23831353

Kim, Hengjun J; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Kim, Namkug; Han, Seungbong; Jang, Eun Hye; Chung, Sun J; Lee, Chong Sik

2013-07-03

179

Age-related decline in white matter tract integrity and cognitive performance: A DTI tractography and structural equation modeling study  

PubMed Central

Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) set-shifting/flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial construction; and posterior fibers (i.e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging.

Voineskos, Aristotle N.; Rajji, Tarek K.; Lobaugh, Nancy J.; Miranda, Dielle; Shenton, Martha E.; Kennedy, James L.; Pollock, Bruce G.; Mulsant, Benoit H.

2010-01-01

180

Brn3a and Nurr1 mediate a gene regulatory pathway for habenula development  

PubMed Central

The habenula is a dorsal diencephalic structure consisting of medial and lateral subnuclei and a principal output tract, the fasciculus retroflexus, which together form a link between the limbic forebrain and ventral midbrain. Here we have used microarray and bioinformatic approaches in the mouse to show that the habenula is a distinctive molecular territory of the CNS, with a unique profile of neurotransmitter, ion channel, and regulatory factor expression. Neurons of the medial habenula and part of the lateral habenula express the transcription factor Brn3a/Pou4f1, and Brn3a-expressing habenular neurons project exclusively to the interpeduncular nucleus in the ventral midbrain. In Brn3a mutant embryos the fasciculus retroflexus is directed appropriately, but habenular neurons fail to innervate their targets. Microarray analysis of Brn3anull embryos shows that this factor regulates an extensive program of habenula-enriched genes, but not generic neural properties. The orphan nuclear receptor Nurr1/Nr4a2 is co-expressed with Brn3a in the developing habenula, is downstream of Brn3a, and mediates expression of a subset of Brn3a regulated transcripts. Together these findings begin to define a gene regulatory pathway for habenula development in mammals.

Quina, Lely A.; Wang, Shirong; Ng, Lydia; Turner, Eric E.

2009-01-01

181

Functional and structural amygdala - Anterior cingulate connectivity correlates with attentional bias to masked fearful faces.  

PubMed

An attentional bias to threat has been causally related to anxiety. Recent research has linked nonconscious attentional bias to threat with variability in the integrity of the amygdala - anterior cingulate pathway, which sheds light on the neuroanatomical basis for a behavioral precursor to anxiety. However, the extent to which structural variability in amygdala - anterior cingulate integrity relates to the functional connectivity within this pathway and how such functional connectivity may relate to attention bias behavior, remain critical missing pieces of the puzzle. In 15 individuals we measured the structural integrity of the amygdala - prefrontal pathway with diffusion tensor-weighted MRI (magnetic resonance imaging), amygdala-seeded intrinsic functional connectivity to the anterior cingulate, and attentional bias toward backward masked fearful faces with a dot-probe task. We found that greater biases in attention to threat predicted greater levels of uncinate fasciculus integrity, greater positive amygdala - anterior cingulate functional connectivity, and greater amygdala coupling with a broader social perception network including the superior temporal sulcus, tempoparietal junction (TPJ), and somatosensory cortex. Additionally, greater levels of uncinate fasciculus integrity correlated with greater levels of amygdala - anterior cingulate intrinsic functional connectivity. Thus, high bias individuals displayed a heightened degree of amygdala - anterior cingulate connectivity during basal conditions, which we believe predisposes these individuals to focus their attention on signals of threat within their environment. PMID:23954317

Carlson, Joshua M; Cha, Jiook; Mujica-Parodi, Lilianne R

2013-07-20

182

Different patterns of white matter degeneration using multiple diffusion indices and volumetric data in mild cognitive impairment and Alzheimer patients.  

PubMed

Alzheime?s disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia. PMID:23300797

Alves, Gilberto Sousa; O'Dwyer, Laurence; Jurcoane, Alina; Oertel-Knöchel, Viola; Knöchel, Christian; Prvulovic, David; Sudo, Felipe; Alves, Carlos Eduardo; Valente, Letice; Moreira, Denise; Fu?er, Fabian; Karakaya, Tarik; Pantel, Johannes; Engelhardt, Eliasz; Laks, Jerson

2012-12-31

183

Gestures, Vocalizations, and Memory in Language Origins  

PubMed Central

This article discusses the possible homologies between the human language networks and comparable auditory projection systems in the macaque brain, in an attempt to reconcile two existing views on language evolution: one that emphasizes hand control and gestures, and the other that emphasizes auditory–vocal mechanisms. The capacity for language is based on relatively well defined neural substrates whose rudiments have been traced in the non-human primate brain. At its core, this circuit constitutes an auditory–vocal sensorimotor circuit with two main components, a “ventral pathway” connecting anterior auditory regions with anterior ventrolateral prefrontal areas, and a “dorsal pathway” connecting auditory areas with parietal areas and with posterior ventrolateral prefrontal areas via the arcuate fasciculus and the superior longitudinal fasciculus. In humans, the dorsal circuit is especially important for phonological processing and phonological working memory, capacities that are critical for language acquisition and for complex syntax processing. In the macaque, the homolog of the dorsal circuit overlaps with an inferior parietal–premotor network for hand and gesture selection that is under voluntary control, while vocalizations are largely fixed and involuntary. The recruitment of the dorsal component for vocalization behavior in the human lineage, together with a direct cortical control of the subcortical vocalizing system, are proposed to represent a fundamental innovation in human evolution, generating an inflection point that permitted the explosion of vocal language and human communication. In this context, vocal communication and gesturing have a common history in primate communication.

Aboitiz, Francisco

2011-01-01

184

Neural systems for speech and song in autism  

PubMed Central

Despite language disabilities in autism, music abilities are frequently preserved. Paradoxically, brain regions associated with these functions typically overlap, enabling investigation of neural organization supporting speech and song in autism. Neural systems sensitive to speech and song were compared in low-functioning autistic and age-matched control children using passive auditory stimulation during functional magnetic resonance and diffusion tensor imaging. Activation in left inferior frontal gyrus was reduced in autistic children relative to controls during speech stimulation, but was greater than controls during song stimulation. Functional connectivity for song relative to speech was also increased between left inferior frontal gyrus and superior temporal gyrus in autism, and large-scale connectivity showed increased frontal–posterior connections. Although fractional anisotropy of the left arcuate fasciculus was decreased in autistic children relative to controls, structural terminations of the arcuate fasciculus in inferior frontal gyrus were indistinguishable between autistic and control groups. Fractional anisotropy correlated with activity in left inferior frontal gyrus for both speech and song conditions. Together, these findings indicate that in autism, functional systems that process speech and song were more effectively engaged for song than for speech and projections of structural pathways associated with these functions were not distinguishable from controls.

Pantazatos, Spiro P.; Schneider, Harry

2012-01-01

185

Structural correlates of cognitive domains in normal aging with diffusion tensor imaging.  

PubMed

The involvement of brain structures in specific cognitive functions is not straightforward. In order to characterize the brain micro-structural correlates of cognitive domains, 52 healthy subjects, age 25-82 years, completed a computerized neuropsychological battery and were scanned using magnetic resonance diffusion tensor imaging. Factor analysis of 44 different cognitive scores was performed, isolating three cognitive domains-executive function, information processing speed and memory. Partial correlation was conducted between DTI parameters and each of the three cognitive domains controlling for age and motor function. Regions showing significant correlations with cognitive domains are domain-specific and are consistent with previous knowledge. While executive function was correlated with diffusion tensor imaging (DTI) parameters in frontal white matter and in the superior longitudinal fasciculus, information processing speed was correlated with DTI parameters in the cingulum, corona radiata, inferior longitudinal fasciculus, parietal white matter and in the thalamus. Memory performance was correlated with DTI measures in temporal and frontal gray matter and white matter regions, including the cingulate cortex and the parahippocampus. Thus, inter-subject variability in cognitive performance and tissue morphology, as expressed by diffusion tensor magnetic resonance imaging, can be used to relate tissue microstructure with cognitive performance and to provide information to corroborate other functional localization techniques. PMID:21909706

Sasson, Efrat; Doniger, Glen M; Pasternak, Ofer; Tarrasch, Ricardo; Assaf, Yaniv

2011-09-10

186

Gestures, vocalizations, and memory in language origins.  

PubMed

THIS ARTICLE DISCUSSES THE POSSIBLE HOMOLOGIES BETWEEN THE HUMAN LANGUAGE NETWORKS AND COMPARABLE AUDITORY PROJECTION SYSTEMS IN THE MACAQUE BRAIN, IN AN ATTEMPT TO RECONCILE TWO EXISTING VIEWS ON LANGUAGE EVOLUTION: one that emphasizes hand control and gestures, and the other that emphasizes auditory-vocal mechanisms. The capacity for language is based on relatively well defined neural substrates whose rudiments have been traced in the non-human primate brain. At its core, this circuit constitutes an auditory-vocal sensorimotor circuit with two main components, a "ventral pathway" connecting anterior auditory regions with anterior ventrolateral prefrontal areas, and a "dorsal pathway" connecting auditory areas with parietal areas and with posterior ventrolateral prefrontal areas via the arcuate fasciculus and the superior longitudinal fasciculus. In humans, the dorsal circuit is especially important for phonological processing and phonological working memory, capacities that are critical for language acquisition and for complex syntax processing. In the macaque, the homolog of the dorsal circuit overlaps with an inferior parietal-premotor network for hand and gesture selection that is under voluntary control, while vocalizations are largely fixed and involuntary. The recruitment of the dorsal component for vocalization behavior in the human lineage, together with a direct cortical control of the subcortical vocalizing system, are proposed to represent a fundamental innovation in human evolution, generating an inflection point that permitted the explosion of vocal language and human communication. In this context, vocal communication and gesturing have a common history in primate communication. PMID:22347184

Aboitiz, Francisco

2012-02-01

187

Spinal cord magnetic resonance imaging demonstrates sensory neuronal involvement and clinical severity in neuronopathy associated with Sj?gren's syndrome  

PubMed Central

OBJECTIVES—To determine spinal cord MRI findings in neuronopathy associated with Sjögren's syndrome and their correlation with severity of sensory impairment.?METHODS—Clinical and electrophysiological features, pathological findings in the sural nerve, and hyperintensity on T2* weighted MRI in the spinal dorsal columns were evaluated in 14 patients with neuronopathy associated with Sjögren's syndrome.?RESULTS—Of 14 patients, 12 showed high intensity by T2* weighted MRI in the posterior columns of the cervical cord. High intensity areas were seen in both the fasciculus cuneatus and gracilis in nine patients, who showed severe and widespread sensory deficits in the limbs and trunk; these patients also had a high frequency of autonomic symptoms. Somatosensory evoked potentials often could not be elicited. Hyperintensity restricted to the fasciculus gracilis was seen in three patients, who showed sensory deficits restricted to lower limbs without trunk involvement, or with only partial limb involvement; no autonomic symptoms were noted. The two patients who did not show high intensity areas in the dorsal columns showed restricted sensory involvement in the limbs. All patients showed axonal loss predominantly affecting large fibres, without axonal sprouting.?CONCLUSIONS—High intensity areas on T2* weighted MRI in the spinal dorsal columns reflect the degree of sensory neuronal involvement in neuronopathy associated with Sjögren's syndrome; this finding could also be a helpful marker for estimating severity of this neuronopathy.??

Mori, K; Koike, H; Misu, K; Hattori, N; Ichimura, M; Sobue, G

2001-01-01

188

[Localization of level of lesions in internuclear ophthalmoplegia through assessment of masseter and blink reflex].  

PubMed

The masseter and blink reflexes were investigated in 100 patients with internuclear ophthalmoplegia due to multiple sclerosis (58 patients) or lacunar brainstem infarction (42 patients). In unilateral internuclear ophthalmoplegia, 38 of 60 patients (63.3%) had masseter reflex abnormalities, two patients (3.3%) showed changes of the blink reflex R1 component, and 13 patients (21.7%) combined alterations of the masseter reflex and the blink reflex R1 component. 46 (86.8%) of these 53 patients with electrophysiological abnormalities had unilateral changes, which were ipsilateral to the medial longitudinal fasciculus lesion in 42 patients (91.3%). In bilateral internuclear ophthalmoplegia, 24 of 40 patients (60.0%) had abnormalities of the masseter reflex, two (5.0%) showed changes of the blink reflex R1, and nine (22.5%) combined alterations of the masseter reflex and the blink reflex R1 component. 20 (57.1%) of these 35 patients with electrophysiological abnormalities had bilateral changes. Thus, masseter reflex abnormalities indicating midbrain lesions were seen in 63.3% and 60.0%, respectively, of unilateral and bilateral internuclear ophthalmoplegia. Blink reflex R1 component changes with or without impairment of the masseter reflex indicating rostral pontine to midpontine lesions occurred in 25.0% and 27.5%, respectively. These figures correspond to the results of postmortem examinations and to theoretical considerations based on the length of the medial longitudinal fasciculus. PMID:1462069

Thömke, F; Hopf, H C

1992-12-01

189

Abnormal Integrity of Corticocortical Tracts in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study  

PubMed Central

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.

Cho, Hyun; Shon, Young Min; Kim, Beum Saeng; Kim, Yeong In; Choi, Young Bin; Lee, Kwang Soo; Shim, Yong Soo; Yoon, Bora; Kim, Woojin; Ahn, Kook Jin

2008-01-01

190

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

PubMed

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. PMID:18583886

Cho, Hyun; Yang, Dong Won; Shon, Young Min; Kim, Beum Saeng; Kim, Yeong In; Choi, Young Bin; Lee, Kwang Soo; Shim, Yong Soo; Yoon, Bora; Kim, Woojin; Ahn, Kook Jin

2008-06-01

191

Different Patterns of White Matter Degeneration Using Multiple Diffusion Indices and Volumetric Data in Mild Cognitive Impairment and Alzheimer Patients  

PubMed Central

Alzheime?s disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.

Alves, Gilberto Sousa; O'Dwyer, Laurence; Jurcoane, Alina; Oertel-Knochel, Viola; Knochel, Christian; Prvulovic, David; Sudo, Felipe; Alves, Carlos Eduardo; Valente, Letice; Moreira, Denise; Fu?er, Fabian; Karakaya, Tarik; Pantel, Johannes; Engelhardt, Eliasz; Laks, Jerson

2012-01-01

192

Effect of the COMT val158met polymorphism on white matter connectivity in patients with major depressive disorder.  

PubMed

Cortico-limbic network dysfunction and genetic polymorphism are considered to be associated with major depressive disorder (MDD). Using diffusion tensor imaging (DTI), we investigated the relationship between catechol-O-methyltransferase (COMT) gene polymorphisms and white matter tract integrity in patients with MDD. Eighty-six patients with MDD and 62 healthy controls participated in this study. DTI and genotyping for the COMT val158met gene (rs4680) polymorphism were conducted to determine the impact of COMT polymorphisms on white matter changes in patients with MDD. Voxel-wise statistical analyses of fractional anisotropy (FA) were performed using tract-based spatial statistics (TBSS). FAs of the MDD patient group were significantly decreased in bilateral frontal forceps minor, bilateral anterior cingulum, genu of corpus callosum, left posterior cingulum, right superior longitudinal fasciculus, and right posterior thalamic radiation compared with those of healthy controls. In the MDD patient group, mean FA in subjects with the GG allele was significantly decreased in left inferior longitudinal fasciculus, bilateral middle temporal gyrus, right frontal gyrus, and right cingulum bundle area compared with subjects with the AA/AG allele. These findings suggest cortico-limbic network dysfunction in MDD. Specifically, further FA reduction was evident in MDD patients with the valine homozygote group of the COMT gene. MDD may be associated with dysfunctional white matter changes, and the valine homozygote of COMT gene may contribute to further abnormalities in these pathological changes. PMID:23618651

Seok, Jeong-Ho; Choi, Sunyoung; Lim, Hyun Kook; Lee, Sang-Hyuk; Kim, InSeong; Ham, Byung-Joo

2013-04-22

193

Gender differences in the relationship between white matter organization and adolescent substance use disorders  

PubMed Central

Few studies have focused on the neurobiological correlates of adolescent-onset substance use disorders (SUDs), particularly with respect to white matter development and organization. This study investigated microstructural white matter characteristics associated with SUDs during the adolescent developmental period. Twenty-four case adolescents (ages 14-18) entering treatment for SUDs and 12 sex- and age-matched control adolescents with no psychopathology were compared. Diffusion tensor imaging data were collected and analyzed using the whole brain, tract-based spatial statistics (TBSS) method. In order to comprehensively characterize diffusivity characteristics, we first studied fractional anisotropy (FA), and within regions that differed in FA, other indicators of microstructure, including the axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). A large cluster of significantly lower FA values was found in cases compared to controls in the superior longitudinal fasciculus (SLF). Within this cluster, AD and RD were also significantly different between the groups, while MD was not significantly different. For FA, a significant group by sex interaction was found; females with SUD exhibited lower FA than males with SUD, while control females exhibited higher FA than control males. These results indicated significantly lower white matter integrity in the superior longitudinal fasciculus region of association cortex, and assessed using multiple indicators of diffusion. These findings suggest that the disruption of normal white matter development due to substance exposure may be more severe in females than in males.

Thatcher, Dawn L.; Pajtek, Stefan; Chung, Tammy; Terwilliger, Robert A.; Clark, Duncan B.

2011-01-01

194

Modeling the mechanisms of Uhthoff's phenomenon in MS patients with internuclear ophthalmoparesis.  

PubMed

Internuclear ophthalmoparesis (INO) is the most common saccadic eye movement disorder observed in patients with multiple sclerosis (MS). It is characterized by slowing of the adducting eye during horizontal saccades, and most commonly results from a demyelinating lesion in the medial longitudinal fasciculus (MLF) within the midline tegmentum of the pons (ventral to the fourth ventricle) or midbrain (ventral to the cerebral aqueduct). Recent research has demonstrated that adduction velocity in MS-related INO, as measured by infrared eye movement recording techniques, is further reduced by a systematic increase in core body temperature (utilizing tube-lined water infusion suits in conjunction with an ingestible temperature probe and transabdominal telemetry) and reversed to baseline with active cooling. These results suggest that INO may represent a model syndrome by which we can carefully study the Uhthoff's phenomenon and objectively test therapeutic agents for its prevention. PMID:21951010

Frohman, Teresa C; Davis, Scott L; Frohman, Elliot M

2011-09-01

195

Progressive bulbar paralysis associated with neural deafness. A nosological entity.  

PubMed

A complete autopsy verification of progressive bulbar palsy associated with neural deafness was performed. Hearing loss and speech difficulties developed in a five-year-old girl. When she was 24 years old, clinical examination demonstrated deafness and bulbopontine paralysis together with retinitis pigmentosa, peripheral amyotrophies, pyramidal signs, and ataxia. The patients died at 27 years and the autopsy disclosed degenerative changes characterized by simple atrophy and loss of neurons accompanied by gliosis and loss of myelinated fibers. The structures principally affected were the anterior horns and the motor nuclei of the brain stem together with the eighth cranial nerve nuclei. Loss of myelinated fibers was found in the spinocerebellar and pyramidal tracts and in the fasciculus gracilis. Our study suggests that progressive bulbar paralysis with neural deafness should be considered as a nosological entity. PMID:7362486

Alberca, R; Montero, C; Ibañez, A; Segura, D I; Miranda-Nieves, G

1980-04-01

196

Process versus product in social learning: comparative diffusion tensor imaging of neural systems for action execution-observation matching in macaques, chimpanzees, and humans.  

PubMed

Social learning varies among primate species. Macaques only copy the product of observed actions, or emulate, while humans and chimpanzees also copy the process, or imitate. In humans, imitation is linked to the mirror system. Here we compare mirror system connectivity across these species using diffusion tensor imaging. In macaques and chimpanzees, the preponderance of this circuitry consists of frontal-temporal connections via the extreme/external capsules. In contrast, humans have more substantial temporal-parietal and frontal-parietal connections via the middle/inferior longitudinal fasciculi and the third branch of the superior longitudinal fasciculus. In chimpanzees and humans, but not in macaques, this circuitry includes connections with inferior temporal cortex. In humans alone, connections with superior parietal cortex were also detected. We suggest a model linking species differences in mirror system connectivity and responsivity with species differences in behavior, including adaptations for imitation and social learning of tool use. PMID:22539611

Hecht, Erin E; Gutman, David A; Preuss, Todd M; Sanchez, Mar M; Parr, Lisa A; Rilling, James K

2012-04-25

197

Eight and a Half Syndrome with Hemiparesis and Hemihypesthesia: The Nine Syndrome?  

PubMed

"Eight-and-a-half" syndrome is "one-and-a-half" syndrome (conjugated horizontal gaze palsy and internuclear ophthalmoplegia) plus ipsilateral fascicular cranial nerve seventh palsy. This rare condition, particularly when isolated, is caused by circumscribed lesions of the pontine tegmentum involving the abducens nucleus, the ipsilateral medial longitudinal fasciculus, and the adjacent facial colliculus. Its recognition is therefore of considerable diagnostic value. We report a 71-year-old man who presented with eight and a half syndrome associated with contralateral hemiparesis and hemihypesthesia, in which brain magnetic resonance imaging scans revealed a lacunar pontine infarction also involving the corticospinal tract and medial lemniscus. These features could widen the spectrum of pontine infarctions, configuring a possible "nine" syndrome. PMID:23434442

Rosini, Francesca; Pretegiani, Elena; Guideri, Francesca; Cerase, Alfonso; Rufa, Alessandra

2013-02-20

198

[Bilateral medial medullary infarction presenting as vertical gaze palsy].  

PubMed

A 79-year old man noticed paresthesia in all 4 limbs, quadriplegia and dysarthria, and then developed respiratory arrest requiring mechanical ventilation. After level of consciousness was improved, vertical gaze palsy, left hemifacial palsy (central type) and quadriplegia were noted. Brain magnetic resonance imaging (MRI) on day 9 revealed bilateral upper medial medullary infarction. In general, the vertical gaze center is thought to be present in the midbrain, including the rostral interstitial nucleus of the medial longitudinal fasciculus, posterior commissure and interstitial nucleus of Cajal. Few reports have described vertical gaze palsy due to medullary lesions. The upper medial medullary lesions, particularly the paramedian tract in the medulla, may have been responsible for vertical gaze palsy in this patient. PMID:16541794

Jikumaru, Mika; Masuda, Teruaki; Ueyama, Hidetsugu; Sannomiya, Kunihiro; Kumamoto, Toshihide

2006-01-01

199

[A case presenting vertical one-and-a-half syndrome and seesaw nystagmus due to thalamomesencephalic infarction].  

PubMed

A 58-year-old woman presented, conjugate upgaze palsy and monocular paresis of downward gaze in the ipsilateral eye (vertical one-and-a-half syndrome; VOHS) as well as seesaw nystagmus (SSN). Vertical oculocephalic response and conjugate horizontal gaze were preserved. Magnetic resonance imaging revealed a right thalamo-mesencephalic infarction including the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal. On the 22nd hospital day SSN was disappeared, and then on the 32nd day VOHS was improved. The lesions of VOHS may have affected the efferent tracts of riMLF and the descending fibres to the ipsilateral subnucleus of the inferior rectus and contralateral subnucleus of the superior oblique. Furthermore, it was assumed that SSN was caused simultaneously by a lesion in the interstitial nucleus of Cajal existing in the adjacent area of riMLF. PMID:13677304

Sekine, Shigeo; Utsumi, Hiroya; Kaku, Hiroi; Otsuka, Takao; Harukawa, Hajime; Horiguchi, Satoshi

2003-08-01

200

Effects of unilateral midbrain lesions on gaze (eye and head) movements.  

PubMed

The rostral midbrain, especially the rostral interstitial nucleus of the medial longitudinal fasciculus (RIMLF) and the interstitial nucleus of Cajal (INC), plays an important role in the control of eye movements. Although the effect of midbrain lesions on eye movements is well investigated, little is known about its effect on head movements. In this study, we measured eye and head (gaze) movements in five patients with unilateral, acute midbrain lesions and nine healthy controls. In all patients, vertical eye velocity was reduced as a result of the lesion compared to healthy subjects, whereas peak head velocity was not affected. Further, most patients displayed an increased contralesional torsion in peripheral head positions, independently of whether they presented a head tilt in the straight-ahead position or not. Our results indicate that midbrain lesions affect the control of eye and head differently and independently. PMID:21950978

Kremmyda, Olympia; Glasauer, Stefan; Guerrasio, Lorenzo; Büttner, Ulrich

2011-09-01

201

Unilateral midbrain infarction causing upward and downward gaze palsy.  

PubMed

We report on a 47-year-old-woman who developed sudden complete loss of vertical saccades, smooth pursuit, and vestibular eye movements bilaterally. MRI revealed a unilateral midbrain infarct involving the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (INC) and spared the posterior commissure (PC). The lesion is presumed to have interrupted the pathways involved in vertical gaze just before they decussate, inducing an anatomically unilateral but functionally bilateral lesion. Previous reports of bidirectional vertical gaze palsy have shown lesions involving the PC or both riMLFs. This case is the first to show that a unilateral lesion of the riMLF and the INC that spares the PC may cause complete bidirectional vertical gaze palsy. PMID:16966933

Alemdar, Murat; Kamaci, Senol; Budak, Faik

2006-09-01

202

Wall-eyed bilateral internuclear ophthalmoplegia in central nervous system cryptococcosis.  

PubMed

Only one case of wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) has been described in central nervous system cryptococcosis. The disorder was initially unilateral, then became bilateral with skew deviation and vertical upgaze deficit. We report a case of WEBINO in central nervous system cryptococcosis in a patient with acquired immune deficiency syndrome. Magnetic resonance imaging revealed high signal on T2 images in the right midbrain, left frontal vertex, left splenium, and cerebellum. With treatment, the internuclear ophthalmoplegia improved; however, the convergence insufficiency remained. Disruption of input from cortical supranuclear locations or the region of the rostral interstitial nucleus of the medial longitudinal fasciculus has been proposed as a mechanism in the absence of convergence. This correlates in our patient with the lesions seen on magnetic resonance images. PMID:10380136

Fay, P M; Strominger, M B

1999-06-01

203

Wall-eyed bilateral internuclear ophthalmoplegia in a patient with progressive supranuclear palsy.  

PubMed

Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is a rare disorder consisting of a bilateral adduction deficit and primary gaze position exotropia. Associated with bilateral medial longitudinal fasciculus lesions, it has been mostly reported in patients with multiple sclerosis and brainstem stroke. A 72-year-old man with characteristic clinical features of progressive supranuclear palsy (PSP) later developed WEBINO. Brain MRI revealed atrophy of the midbrain tegmentum. Caloric irrigation revealed intact horizontal eye movements in both eyes. We believe this to be the first report of WEBINO in PSP. The preservation of vestibulo-ocular horizontal eye movements supports the notion that the WEBINO in this condition was caused by a supranuclear rather than a nuclear lesion and suggests the possibility that even in other causes of WEBINO, the lesion is supranuclear and not in the medial rectus subnucleus as is often suggested. PMID:18562838

Ushio, Munetaka; Iwasaki, Shinichi; Chihara, Yasuhiro; Murofushi, Toshihisa

2008-06-01

204

Changes in descending motor pathway connectivity after corticospinal tract lesion in macaque monkey  

PubMed Central

Damage to the corticospinal tract is a leading cause of motor disability, for example in stroke or spinal cord injury. Some function usually recovers, but whether plasticity of undamaged ipsilaterally descending corticospinal axons and/or brainstem pathways such as the reticulospinal tract contributes to recovery is unknown. Here, we examined the connectivity in these pathways to motor neurons after recovery from corticospinal lesions. Extensive unilateral lesions of the medullary corticospinal fibres in the pyramidal tract were made in three adult macaque monkeys. After an initial contralateral flaccid paralysis, motor function rapidly recovered, after which all animals were capable of climbing and supporting their weight by gripping the cage bars with the contralesional hand. In one animal where experimental testing was carried out, there was (as expected) no recovery of fine independent finger movements. Around 6 months post-lesion, intracellular recordings were made from 167 motor neurons innervating hand and forearm muscles. Synaptic responses evoked by stimulating the unlesioned ipsilateral pyramidal tract and the medial longitudinal fasciculus were recorded and compared with control responses in 207 motor neurons from six unlesioned animals. Input from the ipsilateral pyramidal tract was rare and weak in both lesioned and control animals, suggesting a limited role for this pathway in functional recovery. In contrast, mono- and disynaptic excitatory post-synaptic potentials elicited from the medial longitudinal fasciculus significantly increased in average size after recovery, but only in motor neurons innervating forearm flexor and intrinsic hand muscles, not in forearm extensor motor neurons. We conclude that reticulospinal systems sub-serve some of the functional recovery after corticospinal lesions. The imbalanced strengthening of connections to flexor, but not extensor, motor neurons mirrors the extensor weakness and flexor spasm which in neurological experience is a common limitation to recovery in stroke survivors.

Zaaimi, Boubker; Edgley, Steve A.; Soteropoulos, Demetris S.

2012-01-01

205

Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer's disease supports retrogenesis  

PubMed Central

The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM) degeneration follows a pattern that is the reverse of myelogenesis. Using diffusion tensor imaging (DTI) to test this model, we predicted greater loss of microstructural integrity in late-myelinating WM fiber pathways in AD patients than in healthy older adults, whereas differences in early-myelinating WM fiber pathways were not expected. We compared 16 AD patients and 14 demographically-matched healthy older adults with a whole-brain approach via tract-based spatial statistics (TBSS), and a region of interest (ROI) approach targeting early-myelinating (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported the retrogenesis model. There was significantly lower fractional anisotropy (FA) in AD patients compared to healthy older adults in late-myelinating but not early-myelinating pathways. These group differences appeared to be driven by loss of myelin integrity based on our finding of greater radial diffusion in AD than in healthy elderly. ROI analyses were generally in agreement with whole-brain findings, with significantly lower FA and increased radial diffusion in the ILF in the AD group. Consistent with the retrogenesis model, AD patients showed demonstrable changes in late-myelinating WM fiber pathways. Given greater change in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may also be a contributing mechanism. Knowledge of the pattern of WM microstructural changes in AD and its underlying mechanisms may contribute to earlier detection and intervention in at-risk groups.

Stricker, N.H.; Schweinsburg, B.C.; Delano-Wood, L.; Wierenga, C.E.; Bangen, K.J.; Haaland, K.Y.; Frank, L.R.; Salmon, D.P.; Bondi, M.W.

2009-01-01

206

The Neural Architecture of the Language Comprehension Network: Converging Evidence from Lesion and Connectivity Analyses  

PubMed Central

While traditional models of language comprehension have focused on the left posterior temporal cortex as the neurological basis for language comprehension, lesion and functional imaging studies indicate the involvement of an extensive network of cortical regions. However, the full extent of this network and the white matter pathways that contribute to it remain to be characterized. In an earlier voxel-based lesion-symptom mapping analysis of data from aphasic patients (Dronkers et al., 2004), several brain regions in the left hemisphere were found to be critical for language comprehension: the left posterior middle temporal gyrus, the anterior part of Brodmann's area 22 in the superior temporal gyrus (anterior STG/BA22), the posterior superior temporal sulcus (STS) extending into Brodmann's area 39 (STS/BA39), the orbital part of the inferior frontal gyrus (BA47), and the middle frontal gyrus (BA46). Here, we investigated the white matter pathways associated with these regions using diffusion tensor imaging from healthy subjects. We also used resting-state functional magnetic resonance imaging data to assess the functional connectivity profiles of these regions. Fiber tractography and functional connectivity analyses indicated that the left MTG, anterior STG/BA22, STS/BA39, and BA47 are part of a richly interconnected network that extends to additional frontal, parietal, and temporal regions in the two hemispheres. The inferior occipito-frontal fasciculus, the arcuate fasciculus, and the middle and inferior longitudinal fasciculi, as well as transcallosal projections via the tapetum were found to be the most prominent white matter pathways bridging the regions important for language comprehension. The left MTG showed a particularly extensive structural and functional connectivity pattern which is consistent with the severity of the impairments associated with MTG lesions and which suggests a central role for this region in language comprehension.

Turken, And U.; Dronkers, Nina F.

2011-01-01

207

Diagnosing disconjugate eye movements  

PubMed Central

Background: Saccades are fast eye movements that conjugately shift the point of fixation between distant features of interest in the visual environment. Several disorders, affecting sites from brainstem to extraocular muscle, may cause horizontal saccades to become disconjugate. Prior techniques for detection of saccadic disconjugacy, especially in internuclear ophthalmoparesis (INO), have compared only one point in abducting vs adducting saccades, such as peak velocity. Methods: We applied a phase-plane technique that compared each eye’s velocity as a function of change in position (normalized displacement) in 22 patients with disease variously affecting the brainstem reticular formation, the abducens nucleus, the medial longitudinal fasciculus, the oculomotor nerve, the abducens nerve, the neuromuscular junction, or the extraocular muscles; 10 age-matched subjects served as controls. Results: We found three different patterns of disconjugacy throughout the course of horizontal saccades: early abnormal velocity disconjugacy during the first 10% of the displacement in patients with INO, oculomotor or abducens nerve palsy, and advanced extraocular muscle disease; late disconjugacy in patients with disease affecting the neuromuscular junction; and variable middle-course disconjugacy in patients with pontine lesions. When normal subjects made disconjugate saccades between two targets aligned on one eye, the initial part of the movement remained conjugate. Conclusions: Along with conventional measures of saccades, such as peak velocity, phase planes provide a useful tool to determine the site, extent, and pathogenesis of disconjugacy. We hypothesize that the pale global extraocular muscle fibers, which drive the high-acceleration component of saccades, receive a neural command that ensures initial ocular conjugacy. GLOSSARY Abd. = abducens; CN = cranial nerve; CPEO = chronic progressive external ophthalmoplegia; EM = eye movement; H = horizontal; INO = internuclear ophthalmoparesis; MG = myasthenia gravis; MLF = medial longitudinal fasciculus; MS = multiple sclerosis; P = patient; PI = prediction interval; PPRF = paramedian pontine reticular formation; RIP = raphe interpositus; V = vertical.

Serra, Alessandro; Liao, Ke; Matta, Manuela; Leigh, R John

2008-01-01

208

White matter fiber compromise contributes differentially to attention and emotion processing impairment in alcoholism, HIV-infection, and their comorbidity  

PubMed Central

Alcoholism (ALC) and HIV-1 infection (HIV) each affects emotional and attentional processes and integrity of brain white matter fibers likely contributing to functional compromise. The highly prevalent ALC+HIV comorbidity may exacerbate compromise. We used diffusion tensor imaging (DTI) and an emotional Stroop Match-to-Sample task in 19 ALC, 16 HIV, 15 ALC+HIV, and 15 control participants to investigate whether disruption of fiber system integrity accounts for compromised attentional and emotional processing. The task required matching a cue color to that of an emotional word with faces appearing between the color cue and the Stroop word in half of the trials. Nonmatched cue-word color pairs assessed selective attention, and face-word pairs assessed emotion. Relative to controls, DTI-based fiber tracking revealed lower inferior longitudinal fasciculus (ilf) integrity in HIV and ALC+HIV and lower uncinate fasciculus (uf) integrity in all three patient groups. Controls exhibited Stroop effects to positive face-word emotion, and greater interference was related to greater callosal, cingulum and ilf integrity. By contrast, HIV showed greater interference from negative Stroop words during color-nonmatch trials, correlating with greater uf compromise. For face trials, ALC and ALC+HIV showed greater Stroop-word interference, correlating with lower cingulate and callosal integrity. Thus, in HIV, conflict resolution was diminished when challenging conditions usurped resources needed to manage interference from negative emotion and to disengage attention from wrongly cued colors (nonmatch). In ALC and ALC+HIV, poorer callosal integrity was related to enhanced emotional interference suggesting curtailed interhemispheric exchange needed between preferentially right-hemispheric emotion and left-hemispheric Stroop-word functions.

Schulte, T.; Muller-Oehring, E.M.; Sullivan, E.V.; Pfefferbaum, A.

2012-01-01

209

White matter abnormalities correlating with memory and depression in heroin users under methadone maintenance treatment.  

PubMed

Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT. PMID:22496768

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chien-Chih; Huang, Chu-Chung; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Wang, Ya-Ling; Cheng, Yu-Fan; Lin, Ching-Po

2012-04-09

210

Reduced fractional anisotropy in the visual limbic pathway of young adults witnessing domestic violence in childhood.  

PubMed

Witnessing domestic violence (WDV) is a traumatic childhood experience associated with increased risk for depression, posttraumatic stress disorder and reduced IQ scores. Specific affects of WDV on brain development have not been assessed. We sought to ascertain whether WDV was associated with abnormalities in white matter (WM) tract integrity using diffusion tensor imaging (DTI). Twenty subjects who witnessed domestic violence (16F/4M, mean age 22.4 ± 2.48 years) but were not physically or sexually abused were compared to 27 healthy controls (19F/8M, 21.9 ± 1.97 years) without exposure to trauma or Axis I and II disorders. DTI images were acquired with a 3T Siemens Trio scanner. Group differences in fractional anisotropy (FA), covaried by age, gender, parental education, perceived financial sufficiency, IQ and degree of exposure to parental verbal aggression were assessed using tract-based spatial statistics (TBSS), which projects FA values onto an alignment-invariant fiber tract representation. FA values in the inferior longitudinal fasciculus of left lateral occipital lobe were significantly lower (P<0.05 corrected for multiple comparison) in the WDV group. FA values correlated inversely with ratings of depression, anxiety, somatization, 'limbic irritability' and neuropsychological measures of processing speed. Measures of radial but not axial diffusivity were affected suggesting alterations in myelination. Degree of FA reduction was associated with duration of witnessing interparental verbal aggression and with exposure between ages 7 and 13 years. The inferior longitudinal fasciculus connects occipital and temporal cortex and is the main component of the visual-limbic pathway that subserves emotional, learning and memory functions that are modality specific to vision. This finding is consistent with the hypothesis that exposure to childhood maltreatment is associated with alterations in fiber pathways that convey the adverse experience to frontal, temporal or limbic regions. PMID:21985907

Choi, Jeewook; Jeong, Bumseok; Polcari, Ann; Rohan, Michael L; Teicher, Martin H

2011-10-01

211

Dorsal column nuclei in a prosimian primate (Galago senegalensis). II. Cuneate and lateral cuneate nuclei: morphology and primary afferent fibers from cervical and upper thoracic spinal segments.  

PubMed

The morphology and brachial cord primary afferent projections of the cuneate and lateral cuneate nuclei have been studied in the lesser bushbaby. The cuneate nucleus was divided into three regions. From caudal to rostral these were the large cell, cell column and rostral regions. Primary afferents from C2, C4, C6, C7, C8, T1 and T3 terminated within distinct partially overlapping terminal zones in the ipsilateral large cell and cell column regions of the cuneate nucleus (CN) and the lateral cuneate nucleus (LCN). Segmentotopic was the greatest in the rostal region of the CN due to a more diffuse projection pattern. In the LCN, the transverse terminal fields appeared as curved mediolaterally oriented laminae. In each case, ascending fibers of passage from C4, C6, and C7 in the cuneate fasciculus were organized so that two distinct fiber laminae were present. The separation of fibers and the formation of the two ascending laminae were completed either within two segments rostral to their respective level of entry (for C6 and C7 lesions) or in the caudal medulla (for C4 lesion). For each of these segments, the laminae consisted of a small dorsomedial one and a large lateral one. The organization of primary afferents from one segment into two ascending fiber laminae in the cuneate fasciculus was reflected in a differential termination pattern within both the CN and LCN. The results of this study were discussed relative to earlier anatomical and physiological studies on the DCN in other animals. PMID:687970

Albright, B C; Haines, D E

1978-01-01

212

Characterizing white matter damage in rat spinal cord with quantitative MRI and histology.  

PubMed

ABSTRACT Diffusion tensor imaging (DTI) and quantitative T(2) magnetic resonance imaging (MRI) were used to characterize ex vivo the white matter damage at 3 and 8 weeks following dorsal column transection (DC Tx) injury at the cervical level C5 of rat spinal cords. Luxol Fast Blue (LFB) and myelin basic protein (MBP) staining was used to assess myelin damage, and neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining was used to assess axonal damage. Average values of myelin water fraction (MWF), fractional anisotropy (FA), longitudinal diffusivity (D(long)), transverse diffusivity (D(trans)), and average diffusivity (D(ave)) were calculated in the fasciculus gracilis, fasciculus cuneatus, and the dorsal corticospinal tract (CST) 5 mm cranial, as well as 5 and 10 mm caudal to injury and correlated with histology. These tracts were selected as these contain bundles of parallel ascending and descending axons in very circumscribed areas with little intermingling of other axonal populations. Axonal and myelin degeneration occur cranial to injury in the funiculus gracilis and caudal to injury in the CST. Both MWF and D(trans) showed significant correlation with LFB staining at 3 weeks (0.64 and -0.49, respectively) and 8 weeks post-injury (0.88 and -0.71, respectively). Both D(long) and FA correlated significantly with NF/Tub staining at 3 weeks post-injury (0.78 and 0.64, respectively), while only D(long) displayed significant correlation 8 weeks post-injury (0.58 and 0.33, respectively). This study demonstrates that quantitative MRI can accurately characterize white matter damage in DC Tx model of injury in rat spinal cord. PMID:18578635

Kozlowski, Piotr; Raj, Disha; Liu, Jie; Lam, Clarrie; Yung, Andrew C; Tetzlaff, Wolfram

2008-06-01

213

Diffusion tensor imaging and cognitive function in older adults with no dementia  

PubMed Central

Objective: To determine the patterns of diffusivity associated with cognitive domain functions in older adults without dementia. Methods: We studied older adults without dementia (n = 220) who underwent neuropsychometric testing and a diffusion tensor imaging (DTI) examination at 3 T in a cross-sectional study. Memory, language, attention/executive function, and visual-spatial processing domains were assessed within 4 months of the MRI examination. A fluid-attenuated inversion recovery–based DTI sequence that enabled uncontaminated cortical diffusion measurements was performed. Associations between cortical mean diffusivity (MD) and cognitive function were tested using voxel-based regression analysis. Association between tract diffusivity and cognitive function was tested with regions of interest drawn on color-coded fractional anisotropy (FA) maps. Results: Memory function was associated with the medial temporal lobe cortical MD on voxel-based analysis (p < 0.001, corrected for multiple comparisons), and inferior longitudinal fasciculus and posterior and anterior cingulum FA on tract-based analysis (p < 0.001). Language function was associated with the left temporal lobe cortical MD (p < 0.001, corrected for multiple comparisons), inferior longitudinal fasciculus, fornix, and posterior cingulum FA (p < 0.05). Attention and executive function was associated with the posterior and anterior cingulum FA, and visual-spatial function was associated with posterior cingulum FA (p < 0.01). Conclusion: Specific cognitive domain functions are associated with distinct patterns of cortical and white matter diffusivity in elderly with no dementia. Posterior cingulum tract FA was associated with all 4 cognitive domain functions, in agreement with the hypothesis that the posterior cingulate cortex is the main connectivity hub for cognitive brain networks. Microstructural changes identified on DTI may be associated with neurodegenerative pathologies underlying cognitive changes in older adults without dementia.

Senjem, M.L.; Avula, R.; Zhang, B.; Samikoglu, A.R.; Weigand, S.D.; Przybelski, S.A.; Edmonson, H.A.; Vemuri, P.; Knopman, D.S.; Boeve, B.F.; Ivnik, R.J.; Smith, G.E.; Petersen, R.C.; Jack, C.R.

2011-01-01

214

White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals  

PubMed Central

Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4=529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.

Gongvatana, Assawin; Schweinsburg, Brian C; Taylor, Michael J; Theilmann, Rebecca J; Letendre, Scott L; Alhassoon, Omar M; Jacobus, Joanna; Woods, Steven P; Jernigan, Terry L; Ellis, Ronald J; Frank, Lawrence R; Grant, Igor

2011-01-01

215

White matter lateralization and interhemispheric coherence to auditory modulations in normal reading and dyslexic adults.  

PubMed

Neural activation of slow acoustic variations that are important for syllable identification is more lateralized to the right hemisphere than activation of fast acoustic changes that are important for phoneme identification. It has been suggested that this complementary function at different hemispheres is rooted in a different degree of white matter myelination in the left versus right hemisphere. The present study will investigate this structure-function relationship with Diffusion Tensor Imaging (DTI) and Auditory Steady-State Responses (ASSR), respectively. With DTI we examined white matter lateralization in the cortical auditory and language regions (i.e. posterior region of the superior temporal gyrus and the arcuate fasciculus) and white matter integrity in the splenium of the corpus callosum. With ASSR we examined interhemispheric coherence to slow, syllabic-rate (i.e. 4Hz) and fast, phonemic-rate (i.e. 20Hz) modulations. These structural and functional techniques were applied in a group of normal reading adults and a group of dyslexic adults for whom previously reduced functional interhemispheric connectivity at 20Hz has been reported (Poelmans et al. (2012). Ear and Hearing, 33, 134-143). This sample was chosen since it is hypothesized that in dyslexic readers insufficient hemispheric asymmetry in myelination might relate to their auditory and phonological problems. Results demonstrate reduced white matter lateralization in the posterior superior temporal gyrus and the arcuate fasciculus in the dyslexic readers. Additionally, white matter lateralization in the posterior superior temporal gyrus and white matter integrity in the splenium of the corpus callosum related to interhemispheric coherence to phonemic-rate modulations (i.e. 20Hz). Interestingly, this correlation pattern was opposite in normal versus dyslexic readers. These results might imply that less pronounced left white matter dominance in dyslexic adults might relate to their problems to process phonemic-rate acoustic information and to integrate them into the phonological system. PMID:23872049

Vandermosten, Maaike; Poelmans, Hanne; Sunaert, Stefan; Ghesquière, Pol; Wouters, Jan

2013-07-18

216

Impaired Anatomical Connectivity and Related Executive Functions: Differentiating Vulnerability and Disease Marker in Bipolar Disorder.  

PubMed

BACKGROUND: Bipolar 1 disorder (BD1) has been associated with impaired set shifting, increased risk taking, and impaired integrity of frontolimbic white matter. However, it remains unknown to what extent these findings are related to each other and whether these abnormalities represent risk factors or consequences of the illness. METHODS: We addressed the first question by comparing 19 patients with BD1 and 19 healthy control subjects (sample 1) with diffusion tensor imaging, the Intra-Extra Dimensional Set Shift Task, and the Cambridge Gambling Task. The second question we approached by applying the same protocol to 22 healthy first-degree relatives of patients with BD1 and 22 persons without a family history of mental disorders (sample 2). RESULTS: In comparison with their control groups, BD1 patients and healthy first-degree relatives of patients with BD1 showed significantly reduced fractional anisotropy (FA) in the right anterior limb of the internal capsule and right uncinate fasciculus. White matter integrity in corpus callosum was reduced in BD1 patients only. In addition, reduced FA in anterior limb of the internal capsule correlated significantly with an increased number of errors during set shifting and increased risk taking and reduced FA in uncinate fasciculus correlated significantly with increased risk taking. CONCLUSIONS: Similar white matter alterations in BD1 patients and healthy relatives of BD1 patients are associated with comparable behavioral abnormalities. Further, results indicate that altered frontolimbic and frontothalamic connectivity and corresponding behavioral abnormalities might be a trait and vulnerability marker of BD1, whereas interhemispheric connectivity appears to be a disease marker. PMID:23684382

Linke, Julia; King, Andrea V; Poupon, Cyril; Hennerici, Michael G; Gass, Achim; Wessa, Michèle

2013-05-16

217

A prospective diffusion tensor imaging study in mild traumatic brain injury  

PubMed Central

Objectives: Only a handful of studies have investigated the nature, functional significance, and course of white matter abnormalities associated with mild traumatic brain injury (mTBI) during the semi-acute stage of injury. The present study used diffusion tensor imaging (DTI) to investigate white matter integrity and compared the accuracy of traditional anatomic scans, neuropsychological testing, and DTI for objectively classifying mTBI patients from controls. Methods: Twenty-two patients with semi-acute mTBI (mean = 12 days postinjury), 21 matched healthy controls, and a larger sample (n = 32) of healthy controls were studied with an extensive imaging and clinical battery. A subset of participants was examined longitudinally 3–5 months after their initial visit. Results: mTBI patients did not differ from controls on clinical imaging scans or neuropsychological performance, although effect sizes were consistent with literature values. In contrast, mTBI patients demonstrated significantly greater fractional anisotropy as a result of reduced radial diffusivity in the corpus callosum and several left hemisphere tracts. DTI measures were more accurate than traditional clinical measures in classifying patients from controls. Longitudinal data provided preliminary evidence of partial normalization of DTI values in several white matter tracts. Conclusions: Current findings of white matter abnormalities suggest that cytotoxic edema may be present during the semi-acute phase of mild traumatic brain injury (mTBI). Initial mechanical damage to axons disrupts ionic homeostasis and the ratio of intracellular and extracellular water, primarily affecting diffusion perpendicular to axons. Diffusion tensor imaging measurement may have utility for objectively classifying mTBI, and may serve as a potential biomarker of recovery. GLOSSARY ADC = apparent diffusion coefficient; CC = corpus callosum; CCI = cortical impact injury model; CR = corona radiata; DTI = diffusion tensor imaging; EC = external capsule; FA = fractional anisotropy; FPI = fluid percussion injury model; HC = healthy controls; IC = internal capsule; JHU = Johns Hopkins University; MANCOVA = multivariate analysis of covariance; mTBI = mild traumatic brain injury; RD = radial diffusivity; ROI = region of interest; SCR = superior corona radiata; SLF = superior longitudinal fasciculus; UF = uncinate fasciculus.

Mayer, A. R.; Ling, J.; Mannell, M. V.; Gasparovic, C.; Phillips, J. P.; Doezema, D.; Reichard, R.; Yeo, R. A.

2010-01-01

218

A Comprehensive Reliability Assessment of Quantitative Diffusion Tensor Tractography  

PubMed Central

Diffusion tensor tractography is increasingly used to examine structural connectivity in the brain in various conditions, but its test-retest reliability is understudied. The main purposes of this study were to evaluate 1) the reliability of quantitative measurements of diffusion tensor tractography and 2) the effect on reliability of the number of gradient sampling directions and scan repetition. Images were acquired from ten healthy participants. Ten fiber regions of nine major fiber tracts were reconstructed and quantified using six fiber variables. Intra- and inter-session reliabilities were estimated using intraclass correlation coefficient (ICC) and coefficient of variation (CV), and compared to pinpoint major error sources. Additional pairwise comparisons were made between the reliability of images with 30 directions and NEX 2 (DTI30-2), 30 directions and NEX 1 (DTI30-1), and 15 directions and NEX 2 (DTI15-2) to determine whether increasing gradient directions and scan repetition improved reliability. Of the 60 tractography measurements, 43 showed intersession CV ? 10%, ICC ? .70, or both for DTI30-2, 40 measurements for DTI30-1, and 37 for DTI15-2. Most of the reliable measurements were associated with the tracts corpus callosum, cingulum, cerebral peduncular fibers, uncinate fasciculus, and arcuate fasciculus. These reliable measurements included factional anisotropy (FA) and mean diffusivity of all 10 fiber regions. Intersession reliability was significantly worse than intra-session reliability for FA, mean length, and tract volume measurements from DTI15-2, indicating that the combination of MRI signal variation and physiological noise/change over time was the major error source for this sequence. Increasing the number of gradient directions from 15 to 30 while controlling the scan time, significantly affected values for all six variables and reduced intersession variability for mean length and tract volume measurements. Additionally, while increasing scan repetition from 1 to 2 had no significant effect on the reliability for DTI with 30 directions, this significantly reduced the upward bias in FA values from all 10 fiber regions and fiber count, mean length, and tract volume measurements from 5-7 fiber regions. In conclusion, diffusion tensor tractography provided many measurements with high test-retest reliability across different fiber variables and various fiber tracts even for images with 15 directions (NEX 2). Increasing the number of gradient directions from 15 to 30 with equivalent scan time reduced variability whereas increasing repetition from 1 to 2 for 30-direction DTI improved the accuracy of tractography measurements.

Wang, Jun Yi; Abdi, Herve; Bakhadirov, Khamid; Diaz-Arrastia, Ramon; Devous, Michael D.

2012-01-01

219

Altered white matter microstructure in adolescent substance users.  

PubMed

Chronic marijuana use during adolescence is frequently comorbid with heavy alcohol consumption and associated with CNS alterations, yet the influence of early cannabis and alcohol use on microstructural white matter integrity is unclear. Building on evidence that cannabinoid receptors are present in myelin precursors and affect glial cell processing, and that excessive ethanol exposure is associated with persistently impaired myelination, we used diffusion tensor imaging (DTI) to characterize white matter integrity in heavy substance using and non-using adolescents. We evaluated 36 marijuana and alcohol-using (MJ+ALC) adolescents (ages 16-19) and 36 demographically similar non-using controls with DTI. The diffusion parameters fractional anisotropy (FA) and mean diffusivity (MD) were subjected to whole-brain voxelwise group comparisons using tract-based spatial statistics (Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Mackay, C.E., Watkins, K.E., Ciccarelli, O., Cader, M.Z., Matthews, P.M., Behrens, T.E., 2006. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31, 1487-1505). MJ+ALC teens had significantly lower FA than controls in 10 regions, including left superior longitudinal fasciculus (SLF), left postcentral gyrus, bilateral crus cerebri, and inferior frontal and temporal white matter tracts. These diminutions occurred in the context of increased FA in right occipital, internal capsule, and SLF regions. Changes in MD were less distributed, but increased MD was evident in the right occipital lobe, whereas the left inferior longitudinal fasciculus showed lower MD in MJ+ALC users. Findings suggest that fronto-parietal circuitry may be particularly impacted in adolescent users of the most prevalent intoxicants: marijuana and alcohol. Disruptions to white matter in this young group could indicate aberrant axonal and myelin maturation with resultant compromise of fiber integrity. Findings of increased anisotropic diffusion in alternate brain regions suggest possible neuroadaptive processes and can be examined in future studies of connectivity to determine how aberrancies in specific tracts might influence efficient cognitive processing. PMID:19699064

Bava, Sunita; Frank, Lawrence R; McQueeny, Tim; Schweinsburg, Brian C; Schweinsburg, Alecia D; Tapert, Susan F

2009-08-20

220

Distinguishing rat brainstem reticulospinal nuclei by their neuronal morphology. I. Medullary nuclei.  

PubMed

While cytoarchitectonic and hodological investigations suggest that the brainstem reticulospinal nuclei (BRN) are complexly organized, previous Golgi studies claimed that BRN comprise a homogeneous population with respect to neuronal morphology. To determine whether this is indeed the case, neurons of the various BRN of adult albino or hooded rats were either backfilled with horseradish peroxidase (HRP) from spinal injections, stained with a Nissl method or impregnated with a Golgi-Kopsch variant. The results suggest that at least thirteen BRN can be distinguished in the medulla. Some medullary BRN contain neurons whose dendritic arborizations (DA) are radially symmetric (e.g., nucleus reticularis (NR) ventralis pars beta (RVb), NR gigantocellularis (RGc) and nucleus raphe magnus (RaM]. Some BRN contain neurons whose DA exhibit a pronounced dorsomedial to ventrolateral slant (e.g., NR dorsalis (RD) and NR parvocellularis (RPc). The DA of NR paragigantocellularis dorsalis (RPgcd) neurons tend to course dorsally. The DA of nucleus raphe obscurus (RaO) neurons course vertically, while those of NR magnocellularis pars alpha (RMca) and NR magnocellularis pars beta (RMcb) course horizontally. The DA of NR ventralis pars alpha (RVa) may be oriented horizontally also, but sometimes slant from dorsolateral to ventromedial. The DA of NR paramedianus neurons (RPm) are cruciform. The neurons of NR paragigantocellularis lateralis (RPgcl) and of the nucleus raphe pallidus (RaP) exhibit a variety of DA patterns. The neurons of RD, RVa, RMcb and RMca project to the spinal cord with a strong ipsilateral predominance, while those of RVb, RPgcl and RGc project to the spinal cord with a weak ipsilateral predominance. The axons of RPc, RaO, RaP, and RaM neurons exhibit no lateral predominance. RPm neurons project to the cord with a weak contralateral predominance, and RPgcd neurons project to the cord with a strong contralateral predominance. Most medullary BRN project to the spinal cord via the medial longitudinal fasciculus (mlf) and sulcomarginal fasciculus. However, RPgcl, RMca and RMcb also project to the spinal cord via the lateral funiculus. The neurons of RD, RPm and RaM project to the spinal cord exclusively via the lateral or dorsolateral funiculus. Since the various medullary BRN are distinguishable on the basis of neuronal morphology, they may play distinct roles in brainstem modulation of spinal motor, sensory or autonomic activity. PMID:2410489

Newman, D B

1985-01-01

221

White matter structures associated with emotional intelligence: evidence from diffusion tensor imaging.  

PubMed

Previous studies of brain lesions, functional activity, and gray matter structures have suggested that emotional intelligence (EI) is associated with regions involved in the network of social cognition (SCN) and in somatic marker circuitry (SMC). Our new study is the first to investigate the association between white matter (WM) integrity and EI. We examined this relationship in the brain of healthy young adult men [n = 74, mean age = 21.5 years, standard deviation (SD) = 1.6] and women (n = 44, mean age = 21.9 years, SD = 1.4). We performed a voxel-based analysis of fractional anisotropy, which is an indicator of WM integrity, using diffusion tensor imaging and used a questionnaire (EI Scale) for measuring EI to identify the correlation of WM integrity with individual EI factor (intrapersonal, interpersonal, and situation management factors). Our results showed that (a) the intrapersonal factor of EI was positively correlated with WM integrity in the right anterior insula, and (b) the interpersonal factor of EI was associated with WM integrity in a part of the right inferior longitudinal fasciculus (ILF). The right anterior insula is one of the important nodes of the SMC, whereas the ILF connects the visual cortex and areas related to SCN, and thus, is a part of the SCN. Our findings further support the notion that the brain regions involved in the SCN and in the SMC are associated with EI. PMID:22139821

Takeuchi, Hikaru; Taki, Yasuyuki; Sassa, Yuko; Hashizume, Hiroshi; Sekiguchi, Atsushi; Nagase, Tomomi; Nouchi, Rui; Fukushima, Ai; Kawashima, Ryuta

2011-12-03

222

White Matter Development in Early Puberty: A Longitudinal Volumetric and Diffusion Tensor Imaging Twin Study  

PubMed Central

White matter microstructure and volume show synchronous developmental patterns in children. White matter volume increases considerably during development. Fractional anisotropy, a measure for white matter microstructural directionality, also increases with age. Development of white matter volume and development of white matter microstructure seem to go hand in hand. The extent to which the same or different genetic and/or environmental factors drive these two aspects of white matter maturation is currently unknown. We mapped changes in white matter volume, surface area and diffusion parameters in mono- and dizygotic twins who were scanned at age 9 (203 individuals) and again at age 12 (126 individuals). Over the three-year interval, white matter volume (+6.0%) and surface area (+1.7%) increased, fiber bundles expanded (most pronounced in the left arcuate fasciculus and splenium), and fractional anisotropy increased (+3.0%). Genes influenced white matter volume (heritability ?85%), surface area (?85%), and fractional anisotropy (locally 7% to 50%) at both ages. Finally, volumetric white matter growth was negatively correlated with fractional anisotropy increase (r?=?–0.62) and this relationship was driven by environmental factors. In children who showed the most pronounced white matter growth, fractional anisotropy increased the least and vice-versa. Thus, white matter development in childhood may reflect a process of both expansion and fiber optimization.

Brouwer, Rachel M.; Mandl, Rene C. W.; Schnack, Hugo G.; van Soelen, Inge L. C.; van Baal, G. Caroline; Peper, Jiska S.; Kahn, Rene S.; Boomsma, Dorret I.; Pol, H. E. Hulshoff

2012-01-01

223

Convergence of Pyramidal and Medial Brain Stem Descending Pathways Onto Macaque Cervical Spinal Interneurons  

PubMed Central

We investigated the control of spinal interneurons by corticospinal and medial brain stem descending tracts in two macaque monkeys. Stimulating electrodes were implanted in the left pyramidal tract (PT), and the right medial longitudinal fasciculus (MLF), which contains reticulospinal, vestibulospinal, and some tectospinal fibers. Single unit discharge was recorded from 163 interneurons in the intermediate zone of the right spinal cord (segmental levels C6–C8) in the awake state; inputs from descending pathways were assessed from the responses to stimulation through the PT and MLF electrodes. Convergent input from both pathways was the most common finding (71/163 cells); responses to PT and MLF stimulation were of similar amplitude. Interneuron discharge was also recorded while the animal performed a reach and grasp task with the right hand; the output connections of the recorded cells were determined by delivering intraspinal microstimulation (ISMS) at the recording sites. Convergent input from MLF/PT stimulation was also common when analysis was restricted to cells that increased their rate during grasp (14/23 cells) or to cells recorded at sites where ISMS elicited finger or wrist movements (23/57 cells). We conclude that medial brain stem and corticospinal descending pathways have largely overlapping effects on spinal interneurons, including those involved in the control of the hand. This may imply a more important role for the brain stem in coordinating hand movements in primates than commonly assumed; brain stem pathways could contribute to the restoration of function seen after lesions to the corticospinal tract.

Riddle, C. Nicholas

2010-01-01

224

Temporal association tracts and the breakdown of episodic memory in mild cognitive impairment  

PubMed Central

Objective: To examine the pattern of association between microstructure of temporal lobe connections and the breakdown of episodic memory that is a core feature of mild cognitive impairment (MCI). Methods: Twenty-five individuals with MCI and 20 matched controls underwent diffusion MRI and cognitive assessment. Three temporal pathways were reconstructed by tractography: fornix, parahippocampal cingulum (PHC), and uncinate fasciculus. Tissue volume fraction—a tract-specific measure of atrophy—and microstructural measures were derived for each tract. To test specificity of associations, a comparison tract (corticospinal tract) and control cognitive domains were also examined. Results: In MCI, tissue volume fraction was reduced in the fornix. Axial and radial diffusivity were increased in uncinate and PHC implying more subtle microstructural change. In controls, tissue volume fraction in the fornix was the predominant correlate of free recall. In contrast, in MCI, the strongest relationship was with left PHC. Microstructure of uncinate and PHC also correlated with recognition memory, and recognition confidence, in MCI. Conclusions: Episodic memory in MCI is related to the structure of multiple temporal association pathways. These associations are not confined to the fornix, as they are in healthy young and older adults. In MCI, because of a compromised fornix, alternative pathways may contribute disproportionally to episodic memory performance.

Metzler-Baddeley, Claudia; Hunt, Sarah; Jones, Derek K.; Leemans, Alexander; Aggleton, John P.

2012-01-01

225

A new method to investigate brain stem structural-functional correlations using digital post-processing MRI--reliability in ischemic internuclear ophthalmoplegia.  

PubMed

We investigated the reliability of a new digital post-processing magnetic resonance imaging (MRI) technique in ischemic brain stem lesions to identify relations of the lesion to anatomical brain stem structures. The target was a medial longitudinal fasciculus (MLF) lesion, which was evident from ipsilateral internuclear ophthalmoplegia (INO). Sixteen patients with acute unilateral INO and an isolated acute brain stem lesion in T2- and EPI-diffusion weighted MRI within 2 days after the onset of symptoms were studied. The MRI slice direction was parallel and perpendicular to a slice selection of a stereotactic anatomical atlas. The individual slices were normalized and projected in the digitalized atlas. The eye movement disorder was monitored by electro-oculography. In all patients with clinical or subclinical electro-oculographically documented INO and MRI proven brain stem infarction the lesion covered or at least partially overlapped the ipsilateral MLF at one or more atlas levels. We conclude that digital post-processing MRI with normalizing and projecting brain stem lesions in an anatomical atlas is a reliable method to demonstrate the anatomical structures involved by the lesion. Combined with electrophysiological brain stem testing, this method may be a useful tool to identify incompletely understood pathways mediating brain stem reflexes or the generators of evoked potentials. PMID:11554915

Marx, J J; Thoemke, F; Fitzek, S; Vucurevic, G; Fitzek, C; Mika-Gruettner, A; Urban, P P; Stoeter, P; Hopf, H C

2001-09-01

226

Topodiagnostic value of blink reflex R1 changes: a digital postprocessing MRI correlation study.  

PubMed

The aim of the study was to investigate the relation of the blink reflex R1 arc to known anatomical brainstem structures. Acute vascular brainstem lesions as identified by magnetic resonance imaging (MRI) of patients with isolated R1 pathology were superimposed into a stereotactic anatomical atlas using a new method of digital postprocessing. Isolated acute brainstem lesions were documented by diffusion-weighted MRI in 12 of 24 patients with unilateral R1 pathology. The lesions were located in the ipsilateral mid- to lower pons. In three patients only, the lesion had partial contact with the principal sensory nucleus of the trigeminal nerve (PSN) on at least one level. In two patients, the lesion involved the medial longitudinal fasciculus. Most lesions were located medially and ventrally to the PSN on transverse slices. Our results underline the high localizing value of changes in the R1 component of the blink reflex in patients with ipsilateral pontine functional deficits. Although available physiological evidence suggests that the R1 component of the blink reflex traverses an oligosynaptic pathway, this MRI study does not support the view that synaptic transmission in the PSN subserves R1. The reflex arc probably descends more medially and ventrally on its course to the facial nucleus. PMID:11562912

Marx, J J; Thoemke, F; Fitzek, S; Vucurevic, G; Fitzek, C; Mika-Gruettner, A; Urban, P P; Stoeter, P; Hopf, H C

2001-10-01

227

Asymmetric tonic seizures with bilateral parietal lesions resembling frontal lobe epilepsy.  

PubMed

We performed long-term video/ EEG monitoring and a single photon emission computed tomographic (SPECT) study to clarify generating mechanism of bilateral tonic motor seizures resembling seizures generated by the supplementary motor area (SMA), in patients with bilateral parietal lesions. We describe 2 patients (age 24 and 32 years), with bilateral parietal lesions. Clinically, seizures were preceded by lightning sensation in the body, followed by asymmetric tonic posturing of both hands and thrashing movements of the feet, lasting for less than 1 min. Ictal rhythmic (7-15 Hz) activity at the vertex was observed on the EEG in 1 patient. Interictal SPECT in 2 patients showed decreased blood flow in both parietal areas, consistent with bilateral parietal abnormalities on T2- and T1-weighted MRIs. Ictal SPECT in 1 patient showed increased blood flow in the right parietal and frontopolar areas. The present 2 patients had clinically asymmetric tonic seizures, most likely resulting from spreading of the ictal activity from the parietal lesions via the superior longitudinal fasciculus to the SMA. Bilateral, homologous lesions in the parietal area might cause disinhibition on the unilateral epileptogenic side. PMID:11313218

Ikeda, A; Matsumoto, R; Ohara, S; Kunieda, T; Shirakashi, Y; Kaji, R; Fukuyama, H; Shibasaki, H

228

F-Spondin/spon1b Expression Patterns in Developing and Adult Zebrafish  

PubMed Central

F-spondin, an extracellular matrix protein, is an important player in embryonic morphogenesis and CNS development, but its presence and role later in life remains largely unknown. We generated a transgenic zebrafish in which GFP is expressed under the control of the F-spondin (spon1b) promoter, and used it in combination with complementary techniques to undertake a detailed characterization of the expression patterns of F-spondin in developing and adult brain and periphery. We found that F-spondin is often associated with structures forming long neuronal tracts, including retinal ganglion cells, the olfactory bulb, the habenula, and the nucleus of the medial longitudinal fasciculus (nMLF). F-spondin expression coincides with zones of adult neurogenesis and is abundant in CSF-contacting secretory neurons, especially those in the hypothalamus. Use of this new transgenic model also revealed F-spondin expression patterns in the peripheral CNS, notably in enteric neurons, and in peripheral tissues involved in active patterning or proliferation in adults, including the endoskeleton of zebrafish fins and the continuously regenerating pharyngeal teeth. Moreover, patterning of the regenerating caudal fin following fin amputation in adult zebrafish was associated with F-spondin expression in the blastema, a proliferative region critical for tissue reconstitution. Together, these findings suggest major roles for F-spondin in the CNS and periphery of the developing and adult vertebrate.

Akle, Veronica; Guelin, Emmanuel; Yu, Lili; Brassard-Giordano, Helena; Slack, Barbara E.; Zhdanova, Irina V.

2012-01-01

229

Is there a pathway in the posterior funiculus that signals visceral pain?  

PubMed Central

Summary The present report provides evidence that axons in the medial part of the posterior column at T10 convey ascending nociceptive signals from pelvic visceral organs. This evidence was obtained from human surgical case studies and histological verification of the lesion in one of these cases, along with neuroanatomical and neurophysiological findings in animal experiments. A restricted lesion in this area can virtually eliminate pelvic pain due to cancer. The results remain excellent even in cases in which somatic structures of the pelvic body wall are involved. Following this procedure, neurological testing reveals no additional neurological deficit. There is no analgesia to pinprick stimuli applied to the body surface, despite the relief of the visceral pain. Since it is reasonable to attribute the favorable results of limited midline myelotomies to the interruption of axons of visceral nociceptive projection neurons in the posterior column, we have performed experiments in rats to test this hypothesis. The results in rats indicate that the dorsal column does indeed include a nociceptive component that signals pelvic visceral pain. The pathway includes neurons of the postsynaptic dorsal column pathway at the L6-S1 segmental level, axons of these neurons in the fasciculus gracilis, and neurons of the nucleus gracilis and the ventral posterolateral nucleus of the thalamus.

Hirshberg, R.M.; AI-Chaer, E.D.; Lawand, N.B.; Westlund, K.N.; Willis, W.D.

2011-01-01

230

Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. II. Gaze palsy and internuclear ophthalmoplegia.  

PubMed Central

The site of lesions responsible for horizontal gaze palsy and various types of internuclear ophthalmoplegia (INO) was established by identifying the common areas where the abnormal MRI signals from patients with a given ocular-motor disorder overlapped. Patients with unilateral gaze palsy had lesions in the paramedian area of the pons, including the abducens nucleus, the lateral part of the nucleus reticularis pontis caudalis and the nucleus reticularis pontis oralis. Patients with abducens nucleus lesions showed additional clinical signs of lateral rectus weakness. Lesions responsible for bilateral gaze palsy involved the pontine tegmental raphe. Since this region contains the saccadic omnipause neurons, this finding suggests that damage to omnipause cells produces slowing of saccades rather than opsoclonus, as previously proposed. All INOs, regardless of the presence of impaired abduction or convergence, had similar MRI appearances. Frequently the lesions in patients with INO, were not confined to the medial longitudinal fasciculus (MLF) but also involved neighbouring structures at the pontine and mid-brain levels. There was a statistically significant association between the clinical severity of the INO and the presence of abnormal abduction or convergence. The findings suggest that the lesions outside the MLF, which may affect abducens, gaze or convergence pathways, are responsible for the presence of features additional to INO, depending on the magnitude of functional disruption they produce. Images

Bronstein, A M; Rudge, P; Gresty, M A; Du Boulay, G; Morris, J

1990-01-01

231

Neurophysiology of Nicotine Addiction  

PubMed Central

Tobacco use is a major health problem, and nicotine is the main addictive component. Nicotine binds to nicotinic acetylcholine receptors (nAChR) to produce its initial effects. The nAChRs subtypes are composed of five subunits that can form in numerous combinations with varied functional and pharmacological characteristics. Diverse psychopharmacological effects contribute to the overall process of nicotine addiction, but two general neural systems are emerging as critical for the initiation and maintenance of tobacco use. Mesocorticolimbic circuitry that includes the dopaminergic pathway originating in the ventral tegmental area and projecting to the nucleus accumbens is recognized as vital for reinforcing behaviors during the initiation of nicotine addiction. In this neural system ?2, ?4, and ?6 are the most important nAChR subunits underlying the rewarding aspects of nicotine and nicotine self-administration. On the other hand, the epithalamic habenular complex and the interpeduncular nucleus, which are connected via the fasciculus retroflexus, are critical contributors regulating nicotine dosing and withdrawal symptoms. In this case, the ?5 and ?4 nAChR subunits have critical roles in combination with other subunits. In both of these neural systems, particular nAChR subtypes have roles that contribute to the overall nicotine addiction process

Dani, John A.; Jenson, Daniel; Broussard, John I.; De Biasi, Mariella

2012-01-01

232

Neurophysiology of Nicotine Addiction.  

PubMed

Tobacco use is a major health problem, and nicotine is the main addictive component. Nicotine binds to nicotinic acetylcholine receptors (nAChR) to produce its initial effects. The nAChRs subtypes are composed of five subunits that can form in numerous combinations with varied functional and pharmacological characteristics. Diverse psychopharmacological effects contribute to the overall process of nicotine addiction, but two general neural systems are emerging as critical for the initiation and maintenance of tobacco use. Mesocorticolimbic circuitry that includes the dopaminergic pathway originating in the ventral tegmental area and projecting to the nucleus accumbens is recognized as vital for reinforcing behaviors during the initiation of nicotine addiction. In this neural system ?2, ?4, and ?6 are the most important nAChR subunits underlying the rewarding aspects of nicotine and nicotine self-administration. On the other hand, the epithalamic habenular complex and the interpeduncular nucleus, which are connected via the fasciculus retroflexus, are critical contributors regulating nicotine dosing and withdrawal symptoms. In this case, the ?5 and ?4 nAChR subunits have critical roles in combination with other subunits. In both of these neural systems, particular nAChR subtypes have roles that contribute to the overall nicotine addiction process. PMID:22454789

Dani, John A; Jenson, Daniel; Broussard, John I; De Biasi, Mariella

2011-04-20

233

Is there a critical lesion site for unilateral spatial neglect? A meta-analysis using activation likelihood estimation  

PubMed Central

The critical lesion site responsible for the syndrome of unilateral spatial neglect has been debated for more than a decade. Here we performed an activation likelihood estimation (ALE) to provide for the first time an objective quantitative index of the consistency of lesion sites across anatomical group studies of spatial neglect. The analysis revealed several distinct regions in which damage has consistently been associated with spatial neglect symptoms. Lesioned clusters were located in several cortical and subcortical regions of the right hemisphere, including the middle and superior temporal gyrus, inferior parietal lobule, intraparietal sulcus, precuneus, middle occipital gyrus, caudate nucleus, and posterior insula, as well as in the white matter pathway corresponding to the posterior part of the superior longitudinal fasciculus. Further analyses suggested that separate lesion sites are associated with impairments in different behavioral tests, such as line bisection and target cancellation. Similarly, specific subcomponents of the heterogeneous neglect syndrome, such as extinction and allocentric and personal neglect, are associated with distinct lesion sites. Future progress in delineating the neuropathological correlates of spatial neglect will depend upon the development of more refined measures of perceptual and cognitive functions than those currently available in the clinical setting.

Molenberghs, Pascal; Sale, Martin V.; Mattingley, Jason B.

2012-01-01

234

Patient-Specific Model-Based Investigation of Speech Intelligibility and Movement during Deep Brain Stimulation  

PubMed Central

Background/Aims Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson's disease. The aim of this study was to investigate the anatomical aspects of the electric field in relation to effects on speech and movement during DBS in the subthalamic nucleus. Methods Patient-specific finite element models of DBS were developed for simulation of the electric field in 10 patients. In each patient, speech intelligibility and movement were assessed during 2 electrical settings, i.e. 4 V (high) and 2 V (low). The electric field was simulated for each electrical setting. Results Movement was improved in all patients for both high and low electrical settings. In general, high-amplitude stimulation was more consistent in improving the motor scores than low-amplitude stimulation. In 6 cases, speech intelligibility was impaired during high-amplitude electrical settings. Stimulation of part of the fasciculus cerebellothalamicus from electrodes positioned medial and/or posterior to the center of the subthalamic nucleus was recognized as a possible cause of the stimulation-induced dysarthria. Conclusion Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus.

Astrom, Mattias; Tripoliti, Elina; Hariz, Marwan I.; Zrinzo, Ludvic U.; Martinez-Torres, Irene; Limousin, Patricia; Wardell, Karin

2010-01-01

235

Research with rTMS in the treatment of aphasia  

PubMed Central

This review of our research with rTMS to treat aphasia contains four parts: Part 1 reviews functional brain imaging studies related to recovery of language in aphasia with emphasis on nonfluent aphasia. Part 2 presents the rationale for using rTMS to treat nonfluent aphasia patients (based on results from functional imaging studies). Part 2 also reviews our current rTMS treatment protocol used with nonfluent aphasia patients, and our functional imaging results from overt naming fMRI scans, obtained pre- and post- a series of rTMS treatments. Part 3 presents results from a pilot study where rTMS treatments were followed immediately by constraint-induced language therapy (CILT). Part 4 reviews our diffusion tensor imaging (DTI) study that examined white matter connections between the horizontal, midportion of the arcuate fasciculus (hAF) to different parts within Broca’s area (pars triangularis, PTr; pars opercularis, POp), and the ventral premotor cortex (vPMC) in the RH and in the LH. Part 4 also addresses some of the possible mechanisms involved with improved naming and speech, following rTMS with nonfluent aphasia patients.

Naeser, Margaret A.; Martin, Paula I; Treglia, Ethan; Ho, Michael; Kaplan, Elina; Bashir, Shahid; Hamilton, Roy; Coslett, H. Branch; Pascual-Leone, Alvaro

2013-01-01

236

Development of Tectal Connectivity across Metamorphosis in the Bullfrog (Rana catesbeiana)  

PubMed Central

In the bullfrog (Rana catesbeiana), the process of metamorphosis culminates in the appearance of new visual and visuomotor behaviors reflective of the emergence of binocular vision and visually-guided prey capture behaviors as the animal transitions to life on land. Using several different neuroanatomical tracers, we examined the substrates that may underlie these behavioral changes by tracing the afferent and efferent connectivity of the midbrain optic tectum across metamorphic development. Intratectal, tectotoral, tectotegmental, tectobulbar, and tecto-thalamic tracts exhibit similar trajectories of neurobiotin fiber label across the developmental span from early larval tadpoles to adults. Developmental variability was apparent primarily in intensity and distribution of cell and puncta label in target nuclei. Combined injections of cholera toxin subunit ? and Phaseolus vulgaris leucoagglutinin consistently label cell bodies, puncta, or fiber segments bilaterally in midbrain targets including the pretectal gray, laminar nucleus of the torus semicircularis, and the nucleus of the medial longitudinal fasciculus. Developmentally stable label was observed bilaterally in medullary targets including the medial vestibular nucleus, lateral vestibular nucleus, and reticular gray, and in forebrain targets including the posterior and ventromedial nuclei of the thalamus. The nucleus isthmi, cerebellum, lateral line nuclei, medial septum, ventral striatum, and medial pallium show more developmentally variable patterns of connectivity. Our results suggest that even during larval development, the optic tectum contains substrates for integration of visual with auditory, vestibular, and somatosensory cues, as well as for guidance of motivated behaviors.

Horowitz, Seth S.; Simmons, Andrea Megela

2011-01-01

237

Impaired language pathways in tuberous sclerosis complex patients with autism spectrum disorders.  

PubMed

The purpose of this study was to examine the relationship between language pathways and autism spectrum disorders (ASDs) in patients with tuberous sclerosis complex (TSC). An advanced diffusion-weighted magnetic resonance imaging (MRI) was performed on 42 patients with TSC and 42 age-matched controls. Using a validated automatic method, white matter language pathways were identified and microstructural characteristics were extracted, including fractional anisotropy (FA) and mean diffusivity (MD). Among 42 patients with TSC, 12 had ASD (29%). After controlling for age, TSC patients without ASD had a lower FA than controls in the arcuate fasciculus (AF); TSC patients with ASD had even a smaller FA, lower than the FA for those without ASD. Similarly, TSC patients without ASD had a greater MD than controls in the AF; TSC patients with ASD had even a higher MD, greater than the MD in those without ASD. It remains unclear why some patients with TSC develop ASD, while others have better language and socio-behavioral outcomes. Our results suggest that language pathway microstructure may serve as a marker of the risk of ASD in TSC patients. Impaired microstructure in language pathways of TSC patients may indicate the development of ASD, although prospective studies of language pathway development and ASD diagnosis in TSC remain essential. PMID:22661408

Lewis, William W; Sahin, Mustafa; Scherrer, Benoit; Peters, Jurriaan M; Suarez, Ralph O; Vogel-Farley, Vanessa K; Jeste, Shafali S; Gregas, Matthew C; Prabhu, Sanjay P; Nelson, Charles A; Warfield, Simon K

2012-06-01

238

Age-related brain trajectories in schizophrenia: A systematic review of structural MRI studies.  

PubMed

Using the Pubmed database, we performed a detailed literature search for structural magnetic resonance imaging studies on patients with schizophrenia, investigating the relationship between macroscopic and microscopic structural parameters and age, to delineate an age-related trajectory. Twenty-six studies were considered for the review, from January 2000 to June 2012. Research results are heterogeneous because of the multifactorial features of schizophrenia and the multiplicity of the methodological approaches adopted. Some areas, within the amygdala-hippocampus complex, which are affected early in life by schizophrenia, age in a physiological way. Other regions, such as the superior temporal gyrus, appear already impaired at the onset of symptoms, undergo a worsening in the acute phase but later stabilize, progressing physiologically over years. Finally, there are regions, such as the uncinate fasciculus, which are not altered early in life, but are affected around the onset of schizophrenia, with their impairment continuously worsening over time. Further extensive longitudinal studies are needed to understand the timing and the possible degenerative characteristics of structural impairment associated with schizophrenia. PMID:23972726

Chiapponi, Chiara; Piras, Fabrizio; Fagioli, Sabrina; Piras, Federica; Caltagirone, Carlo; Spalletta, Gianfranco

2013-08-21

239

Tone-deafness - a new disconnection syndrome?  

PubMed Central

Communicating with one’s environment requires efficient neural interaction between action and perception. Neural substrates ofsound perception and production are connected by the arcuate fasciculus (AF). While AF is known to be involved in language, its roles in non-linguistic functions are unexplored. Here we show that tone-deaf people, with impaired sound perception and production, have reduced AF connectivity. Diffusion tensor tractography and psychophysics were assessed in tone-deaf individuals and matched controls. Abnormally-reduced AF connectivity was observed in the tone-deaf. Furthermore, we observed relationships between AF and auditory-motor behavior: superior and inferior AF branches predict psychophysically-assessed pitch-discrimination and sound production-perception abilities respectively. This neural abnormality suggests that tone-deafness leads to a reduction in connectivity resulting in pitch-related impairments. Results support a dual-stream anatomy of sound production and perception implicated in vocal communications. By identifying white-matter differences and their psychophysical correlates, results contribute to our understanding of how neural connectivity subserves behavior.

Loui, Psyche; Alsop, David; Schlaug, Gottfried

2009-01-01

240

Evidence for Plasticity in White Matter Tracts of Chronic Aphasic Patients Undergoing Intense Intonation-based Speech Therapy  

PubMed Central

Recovery from aphasia can be achieved through recruitment of either peri-lesional brain regions in the affected hemisphere or homologous language regions in the non-lesional hemisphere. For patients with large left-hemisphere lesions, recovery through the right hemisphere may be the only possible path. The right hemisphere regions most likely to play a role in this recovery process are the superior temporal lobe (important for auditory feedback control), premotor regions/posterior inferior frontal gyrus (important for planning and sequencing of motor actions and for auditory-motor mapping) and the primary motor cortex (important for execution of vocal motor actions). These regions are connected reciprocally via a major fiber tract called the arcuate fasciculus (AF), but this tract is usually not as well developed in the non-dominant right hemisphere. We tested whether an intonation-based speech therapy (i.e., Melodic Intonation Therapy) which is typically administered in an intense fashion with 75–80 daily therapy sessions, would lead to changes in white matter tracts, particularly the AF. Using diffusion tensor imaging (DTI), we found a significant increase in the number of AF fibers and AF volume comparing post with pre-treatment assessments in 6 patients that could not be attributed to scan-to-scan variability. This suggests that intense, long-term Melodic Intonation Therapy leads to remodeling of the right AF and may provide an explanation for the sustained therapy effects that were seen in these 6 patients.

Schlaug, Gottfried; Marchina, Sarah; Norton, Andrea

2009-01-01

241

Structural connectivity of the frontal lobe in children with drug-resistant partial epilepsy  

PubMed Central

The superior longitudinal fasciculus (SLF) II and cingulum are two white matter tracts important for attention and other frontal lobe functions. These functions are often disturbed in children with drug-resistant (DR) partial epilepsy even when no abnormalities are seen on conventional MRI. We set out to determine whether abnormalities in these structures might be depicted on diffusion tensor imaging (DTI) studies in the absence of abnormalities on conventional MRI. We compared the DTI findings of 12 children with DR-partial epilepsy to those of 12 age- and gender-matched controls. We found that the fractional anisotropy (FA) values in the SLF II of the patients were significantly lower than those of the controls (mean: 0.398±0.057, 0.443±0.059, p=0.002). Similarly apparent diffusion coefficient (ADC) and parallel diffusivity values of the SLF II were also significantly lower in the patients. There were no differences in the FA and ADC values of the cingulum. Our findings are consistent with abnormal structural connectivity of the frontal lobe in children with DR-partial epilepsy and provide a possible explanation for the previously reported functional abnormalities related to the SLF II in these patients.

Holt, Rebecca L.; Provenzale, James M.; Veerapandiyan, Aravindhan; Moon, Won-Jin; De Bellis, Michael D.; Leonard, Soren; Gallentine, William B.; Grant, Gerald A.; Egger, Helen; Song, Allen W.; Mikati, Mohamad A.

2011-01-01

242

Early maturation of the linguistic dorsal pathway in human infants.  

PubMed

Human infants, unlike even closely related primates, exhibit a remarkable capacity for language learning. Yet how the underlying anatomical network matures remains largely unknown. The classical view is that of a largely immature brain comprising only a few islands of maturity in primary cortices. This view has favored a description of learning based on bottom-up algorithms and has tended to discard the role of frontal regions, which were assumed to be barely functional early on. Here, using an index based on the normalized T2-weighted magnetic resonance signal, we have quantified maturation within the linguistic network in fourteen 1- to 4-month-old infants. Our results show first that the ventral superior temporal sulcus (STS), and not the inferior frontal area, is the less mature perisylvian region. A significant difference of maturation in the STS favoring the right side is an early testimony of the distinctive left-right development of this structure observed during the whole life. Second, asymmetries of maturation in Broca's area were correlated with asymmetries in the posterior STS and in the parietal segment of the arcuate fasciculus, suggesting that an efficient frontotemporal dorsal pathway might provide infants with a phonological loop circuitry much earlier than expected. PMID:21273434

Leroy, François; Glasel, Hervé; Dubois, Jessica; Hertz-Pannier, Lucie; Thirion, Bertrand; Mangin, Jean-François; Dehaene-Lambertz, Ghislaine

2011-01-26

243

Vasoactive intestinal peptide binding sites and fibers in the brain of the pigeon Columba livia: An autoradiographic and immunohistochemical study  

SciTech Connect

The distribution of vasoactive intestinal peptide (VIP) binding sites in the pigeon brain was examined by in vitro autoradiography on slide-mounted sections. A fully characterized monoiodinated form of VIP, which maintains the biological activity of the native peptide, was used throughout this study. The highest densities of binding sites were observed in the hyperstriatum dorsale, archistriatum, auditory field L of neostriatum, area corticoidea dorsolateralis and temporo-parieto-occipitalis, area parahippocampalis, tectum opticum, nucleus dorsomedialis anterior thalami, and in the periventricular area of the hypothalamus. Lower densities of specific binding occurred in the neostriatum, hyperstriatum ventrale and nucleus septi lateralis, dorsolateral area of the thalamus, and lateral and posteromedial hypothalamus. Very low to background levels of VIP binding were detected in the ectostriatum, paleostriatum primitivum, paleostriatum augmentatum, lobus parolfactorius, nucleus accumbens, most of the brainstem, and the cerebellum. The distribution of VIP-containing fibers and terminals was examined by indirect immunofluorescence using a polyclonal antibody against porcine VIP. Fibers and terminals were observed in the area corticoidea dorsolateralis, area parahippocampalis, hippocampus, hyperstriatum accessorium, hyperstriatum dorsale, archistriatum, tuberculum olfactorium, nuclei dorsolateralis and dorsomedialis of the thalamus, and throughout the hypothalamus and the median eminence. Long projecting fibers were visualized in the tractus septohippocampalis. In the brainstem VIP immunoreactive fibers and terminals were observed mainly in the substantia grisea centralis, fasciculus longitudinalis medialis, lemniscus lateralis, and in the area surrounding the nuclei of the 7th, 9th, and 10th cranial nerves.

Hof, P.R.; Dietl, M.M.; Charnay, Y.; Martin, J.L.; Bouras, C.; Palacios, J.M.; Magistretti, P.J. (Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY (USA))

1991-03-15

244

A crucial role for the cortico-striato-cortical loop in the pathogenesis of stroke-related neurogenic stuttering.  

PubMed

Neurogenic stuttering is an acquired speech disorder characterized by the occurrence of stuttering-like dysfluencies following brain damage. Because the onset of stuttering in these patients is associated with brain lesions, this condition provides a unique opportunity to study the neural processes underlying speech dysfluencies. Lesion localizations of 20 stroke subjects with neurogenic stuttering and 17 control subjects were compared using voxel-based lesion symptom mapping. The results showed nine left-hemisphere areas associated with the presence of neurogenic stuttering. These areas were largely overlapping with the cortico-basal ganglia-cortical network comprising the inferior frontal cortex, superior temporal cortex, intraparietal cortex, basal ganglia, and their white matter interconnections through the superior longitudinal fasciculus and internal capsule. These results indicated that stroke-induced neurogenic stuttering is not associated with neural dysfunction in one specific brain area but can occur following one or more lesion throughout the cortico-basal ganglia-cortical network. It is suggested that the onset of neurogenic stuttering in stroke subjects results from a disintegration of neural functions necessary for fluent speech. PMID:22451328

Theys, Catherine; De Nil, Luc; Thijs, Vincent; van Wieringen, Astrid; Sunaert, Stefan

2012-03-25

245

Projections from Gudden's tegmental nuclei to the mammillary body region in the cynomolgus monkey (Macaca fascicularis).  

PubMed

Gudden's tegmental nuclei provide major inputs to the rodent mammillary bodies, where they are thought to be important for learning and navigation. Comparable projections have yet to be described in the primate brain, where part of the problem has been in effectively delineating these nuclei. Immunohistochemical staining of tissue from a series of macaque monkeys (Macaca mulatta) showed that cells in the region of both the ventral and dorsal tegmental nuclei selectively stain for parvalbumin, thus helping to reveal these nuclei. These same tegmental nuclei were not selectively revealed when tissue was stained for SMI32, acetylcholinesterase, calbindin, or calretinin. In a parallel study, horseradish peroxidase was injected into the mammillary bodies of five cynomolgus monkeys (Macaca fascicularis). Retrogradely labeled neurons were consistently found in the three subdivisions of the ventral tegmental nucleus of Gudden, which are located immediately below, within, and above the medial longitudinal fasciculus. Further projections to the mammillary body region arose from cells in the anterior tegmental nucleus, which appears to be a rostral continuation of the infrafascicular part of the ventral tegmental nucleus. In the dorsal tegmental nucleus of Gudden, labeled cells were most evident when the tracer injection was more laterally placed in the mammillary bodies, consistent with a projection to the lateral mammillary nucleus. The present study not only demonstrates that the primate mammillary bodies receive parallel inputs from the dorsal and ventral tegmental nuclei of Gudden, but also helps to confirm the extent of these poorly distinguished nuclei in the monkey brain. PMID:21830220

Saunders, Richard C; Vann, Seralynne D; Aggleton, John P

2012-04-15

246

Tyrosine hydroxylase (TH)- and aromatic-L-amino acid decarboxylase (AADC)-immunoreactive neurons of the common marmoset (Callithrix jacchus) brain: an immunohistochemical analysis.  

PubMed

From the perspective of comparative morphology, the distribution of non-monoaminergic neurons in the common marmoset (Callithrix jacchus) was investigated using an immunohistochemical method with specific antibodies to tyrosine hydroxylase (TH) and aromatic-L-amino acid decarboxylase (AADC).TH-immunoreactive (IR) neurons (but not AADC-IR) neurons were observed in the olfactory tubercle, preoptic suprachiasmatic nucleus, periventricular hypothalamic nucleus, arcuate nucleus, paraventricular nucleus, periaqueductal gray matter, medial longitudinal fasciculus, substantia nigra, and nucleus solitaris. In contrast, AADC-IR (but not TH-IR), small, oval and spindle-shaped neurons were sparsely distributed in the following areas: the hypothalamus from the anterior nucleus to the lateral nucleus, the dorsomedial nucleus, the dorsomedial area of the medial mammillary nucleus and the arcuate nucleus; the midbrain, including the stria medullaris and substantia nigra; and the medulla oblongata, including the dorsal area of the nucleus solitaris and the medullary reticular nucleus. The distribution of AADC-IR neurons was not as extensive in the marmoset as it is in rats. However, these neurons were located in the marmoset, but not the rat substantia nigra. Furthermore, AADC-IR neurons that are present in the human striatum were absent in that of the marmoset. The present results indicate that the distribution of non-monoaminergic neurons in the brain of the common marmoset is unique and different from that in humans and rodents. PMID:17653300

Karasawa, Nobuyuki; Hayashi, Motoharu; Yamada, Keiki; Nagatsu, Ikuko; Iwasa, Mineo; Takeuchi, Terumi; Uematsu, Mitsutoshi; Watanabe, Kazuko; Onozuka, Minoru

2007-07-01

247

Study of the rostral midbrain atrophy in progressive supranuclear palsy.  

PubMed

Rostral midbrain atrophy in progressive supranuclear palsy (PSP) is detected by mid-sagittal plain magnetic resonance imaging (MRI). The shape of the atrophy looks like the bill of a hummingbird (hummingbird sign). We studied this sign to elucidate the nature of midbrain atrophy in PSP. Eight patients with PSP, 12 with Parkinson's disease (PD), and 10 normal controls were studied. Using mid-sagittal plain MRI, we measured the rostral and caudal midbrain tegmentum (MT), superior and inferior colliculus, pontine base, and tegmentum. We compared the length of the interpeduncular fossa, which is posterior to the mammillary body, to the diameter of the midbrain tegmentum. The multiple comparison method was used for the statistical analysis. The hummingbird sign was demonstrated in all of the PSP patients studied, and it was not observed in PD patients nor in normal controls. The hummingbird sign in the PSP patients was due to the atrophy of the midbrain tegmentum (rostral and caudal) and to a relative increase in the length of the interpeduncular fossa over that of the anteroposterior diameter of the midbrain tegmentum. The hummingbird sign, which represents the atrophy of the rostral midbrain tegmentum, strongly suggests the involvement of the rostral interstitial nucleus of the medial longitudinal fasciculus in patients with PSP. Demonstration of a hummingbird sign on MRI is thought to be useful for a diagnosis of PSP. PMID:12736089

Kato, Naoko; Arai, Kimihito; Hattori, Takamichi

2003-06-15

248

Possible ctenophoran affinities of the Precambrian "sea-pen" Rangea.  

PubMed

The Namibian Kuibis Quartzite fossils of Rangea are preserved three-dimensionally owing to incomplete collapse of the soft tissues under the load of instantaneously deposited sand. The process of fossilization did not reproduce the original external morphology of the organism but rather the inner surface of collapsed organs, presumably a system of sacs connected by a medial canal. The body of Rangea had tetraradial symmetry, a body plan shared also by the White Sea Russian fossil Bomakellia and possibly some other Precambrian frond-like fossils. They all had a complex internal anatomy, smooth surface of the body, and radial membranes, making their alleged colonial nature unlikely. Despite a different style of preservation, the Middle Cambrian Burgess Shale frond-like Thaumaptilon shows several anatomical similarities to Rangea. The body plan of the Burgess Shale ctenophore Fasciculus, with its numerous, pinnately arranged comb organs, is in many respects transitional between Thaumaptilon and the Early Cambrian ctenophore Maotianoascus from the Chengjiang fauna of South China. It is proposed that the irregularly distributed dark spots on the fusiform units of the petaloid of Thaumaptilon represent a kind of macrocilia and that the units are homologous with the ctenophoran comb organs. These superficial structures were underlain by the complex serial organs, well represented in the fossils of Rangea. The Precambrian "sea-pens" were thus probably sedentary ancestors of the ctenophores. PMID:11948678

Dzik, Jerzy

2002-06-01

249

New Burgess shale type fauna in the Middle Cambrian Stephen Formation on Mt. Stephen, British Columbia  

SciTech Connect

Excavation of a fossil locality discovered in 1981 on Mount Stephen, 5 km south of the Burgess shale site on Mount Wapta, has yielded about 1000 specimens of a new soft-bodied and lightly-sclerotized fauna. The fauna includes the trilobite, Glossopleura, which is characteristic of the lower part of the Stephen Formation, 100 m or more stratigraphically below the level of the Burgess shale fauna. The arthropod, Alalcomenaeus, a genus extremely rare in the Burgess shale, is by far the most numerous, followed by a new, fishlike arthropod with prominent eyes, and Branchiocaris, another extremely rare Burgess shale arthropod. Many Burgess shale animals are present, although the most common, Marrella, is absent. They include the arthropods Canadaspis, Naraoia, Plenocaris and Tuzoia, the worms Ottoia and Burgessochaeta, the onychophoran Aysheaia, the sponge Leptomitus, Wiwaxia of unknown affinities, and Fasciculus, a possible ctenophore. The Glossopleura fauna thus adds extant and extinct invertebrate groups to those already known in the Middle Cambrian epoch, mostly from the Burgess shale. It also demonstrates that the animals preserved in the Stephen Formation are evolutionarily stable.

Collins, D.H.

1985-01-01

250

White-matter microstructure and language lateralization in left-handers: a whole-brain MRI analysis.  

PubMed

Most people are left-hemisphere dominant for language. However the neuroanatomy of language lateralization is not fully understood. By combining functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), we studied whether language lateralization is associated with cerebral white-matter (WM) microstructure. Sixteen healthy, left-handed women aged 20-25 were included in the study. Left-handers were targeted in order to increase the chances of involving subjects with atypical language lateralization. Language lateralization was determined by fMRI using a verbal fluency paradigm. Tract-based spatial statistics analysis of DTI data was applied to test for WM microstructural correlates of language lateralization across the whole brain. Fractional anisotropy and mean diffusivity were used as indicators of WM microstructural organization. Right-hemispheric language dominance was associated with reduced microstructural integrity of the left superior longitudinal fasciculus and left-sided parietal lobe WM. In left-handed women, reduced integrity of the left-sided language related tracts may be closely linked to the development of right hemispheric language dominance. Our results may offer new insights into language lateralization and structure-function relationships in human language system. PMID:23792788

Perlaki, Gabor; Horvath, Reka; Orsi, Gergely; Aradi, Mihaly; Auer, Tibor; Varga, Eszter; Kantor, Gyongyi; Altbäcker, Anna; John, Flora; Doczi, Tamas; Komoly, Samuel; Kovacs, Norbert; Schwarcz, Attila; Janszky, Jozsef

2013-06-21

251

Neuronavigation-guided endoscopic and hodotopic approach to an arachnoid cyst  

PubMed Central

Background: Arachnoid cysts are intraarachnoid benign cystic lesions filled with cerebrospinal fluid and should be treated without incurring further morbidity to the patients. Case Description: The authors present a case of a 68-year-old elderly female with a large right fronto-parieto-temporal arachnoid cyst who has been suffering from mild left hemiparesis for the past 4 years and presented with sudden onset of seizures. The 3 Tesla MR system with diffusion tensor imaging (DTI) and MR tractography of the brain showed a large right fronto-parieto-temporal cystic lesion measuring 7 × 5 × 5 cm with a midline shift of 1 cm, suggestive of an arachnoid cyst with surrounding ipsilateral white matter projection pathways and inferior occipito-frontal fasciculus or inferior longitudinal white matter tracts. The cyst was successfully treated with neuronavigation-guided endoscopic and hodotopical approach to fenestrate the arachnoid cyst into the sylvian cistern, avoiding inadvertent injury to major white matter tracts portrayed by DTI. Postoperatively, a repeated computed tomography (CT) scan of the brain revealed a smaller arachnoid cyst with correction of the midline shift. The patient was weaned off from the ventilator and her hemiplegia improved gradually. Conclusion: This case report emphasizes the value of neuronavigation-guided endoscopic and hodotopic approach to fenestrate the intra-axial arachnoid cyst.

Idris, Zamzuri; Nandrajog, Puneet; Abdullah, Jafri M.; Ghani, Rahman I; Idris, Badrisyah

2013-01-01

252

Altered fronto-cerebellar connectivity in alcohol-na?ve youth with a family history of alcoholism  

PubMed Central

Fronto-cerebellar connections are thought to be involved in higher-order cognitive functioning. It is suspected that damage to this network may contribute to cognitive deficits in chronic alcoholics. However, it remains to be elucidated if fronto-cerebellar circuitry is altered in high-risk individuals even prior to alcohol use onset. The current study used functional connectivity MRI (fcMRI) to examine fronto-cerebellar circuitry in 13 alcohol-naïve, at-risk youth with a family history of alcoholism (FH+) and 14 age-matched controls. In addition, we examined how white matter microstructure, as evidenced by fractional anisotropy (FA) related to fcMRI. FH+ youth showed significantly reduced functional connectivity between bilateral anterior prefrontal cortices and contralateral cerebellar seed regions compared to controls. We found that this reduction in connectivity significantly correlated with reduced FA in the anterior limb of the internal capsule and the superior longitudinal fasciculus. Taken together, our findings reflect associated aberrant functional and structural connectivity in substance-naïve FH+ adolescents, perhaps suggesting an identifiable neurophenotypic precursor to substance use. Given the role of frontal and cerebellar brain regions in subserving executive functioning, the presence of premorbid abnormalities in fronto-cerebellar circuitry may heighten the risk for developing an alcohol use disorder in FH+ youth through atypical control processing.

Herting, Megan M.; Fair, Damien; Nagel, Bonnie J.

2011-01-01

253

Tissue distribution of neurturin, persephin and artemin in the human brainstem at fetal, neonatal and adult age.  

PubMed

The occurrence of the glial cell line-derived neurotrophic factor (GDNF) family ligands neurturin (NTN), persephin (PSP), and artemin (ART) was examined by immunohistochemistry in the normal human brainstem at pre-, perinatal and adult age. Immunolabelled neurons were unevenly distributed and each trophin had a consistent distribution pattern. As a rule, the NTN antiserum produced the most abundant and diffuse tissue labelling, whereas the lowest density of positive elements was observed after ART immunostaining. Labelling for NTN, PSP, and ART occurred at all examined ages. For each trophin, neuronal perikarya were observed within sensory and motor nuclei of cranial nerves, dorsal column nuclei, olivary nuclear complex, reticular formation, pontine nuclei, locus caeruleus, raphe nuclei, substantia nigra, and quadrigeminal plate. Nerve fibers occurred within gracile and cuneate fasciculi, trigeminal spinal tract and nucleus, oculomotor and facial nerves, solitary tract, vestibular nerve, medial longitudinal fasciculus, medial and lateral lemnisci, and inferior and superior cerebellar peduncles. Age changes were detected in the distribution pattern for each trophin. On the whole, in the grey matter, labelled perikarya were more frequently observed in pre- and perinatal than in adult specimens; on the other hand, in discrete regions, nerve fibers and terminals were abundant and showed a definite arrangement only in adult tissue; finally, distinct fiber systems in the white matter were immunolabelled only at pre- and perinatal ages. The results support the concept of a trophic involvement of NTN, PSP, and ART in the development, functional activity and maintenance of a variety of human brainstem neuronal systems. PMID:17316574

Quartu, Marina; Serra, Maria Pina; Boi, Marianna; Sestu, Natascia; Lai, Maria Letizia; Del Fiacco, Marina

2007-01-26

254

More insights into early brain development through statistical analyses of eigen-structural elements of diffusion tensor imaging using multivariate adaptive regression splines.  

PubMed

The aim of this study was to characterize the maturational changes of the three eigenvalues (?1 ? ?2 ? ?3) of diffusion tensor imaging (DTI) during early postnatal life for more insights into early brain development. In order to overcome the limitations of using presumed growth trajectories for regression analysis, we employed Multivariate Adaptive Regression Splines (MARS) to derive data-driven growth trajectories for the three eigenvalues. We further employed Generalized Estimating Equations (GEE) to carry out statistical inferences on the growth trajectories obtained with MARS. With a total of 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects, we found that the growth velocities of the three eigenvalues were highly correlated, but significantly different from each other. This paradox suggested the existence of mechanisms coordinating the maturations of the three eigenvalues even though different physiological origins may be responsible for their temporal evolutions. Furthermore, our results revealed the limitations of using the average of ?2 and ?3 as the radial diffusivity in interpreting DTI findings during early brain development because these two eigenvalues had significantly different growth velocities even in central white matter. In addition, based upon the three eigenvalues, we have documented the growth trajectory differences between central and peripheral white matter, between anterior and posterior limbs of internal capsule, and between inferior and superior longitudinal fasciculus. Taken together, we have demonstrated that more insights into early brain maturation can be gained through analyzing eigen-structural elements of DTI. PMID:23455648

Chen, Yasheng; Zhu, Hongtu; An, Hongyu; Armao, Diane; Shen, Dinggang; Gilmore, John H; Lin, Weili

2013-03-01

255

WEBINO and the return of the King's Speech.  

PubMed

We present a 69 year-old man with hypertension who developed the sudden onset of horizontal binocular diplopia and stuttering of speech. On examination, bilateral exotropia (i.e. 'wall-eyed') was observed in the primary position. Attempted horizontal saccades revealed bilateral internuclear ophthalmoplegia; all consistent with the wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome. Convergence, vertical saccades and vestibular ocular reflexes were likewise impaired. Pupillary and levator palpebrae superioris functions were intact. Mild left-sided dysmetria, intention tremor and dysdiadochokinesia were elicited. Conspicuously, further characterization of the patient's history revealed that he had stuttered as a child, but it had resolved in adolescence. Brain MRI revealed an acute infarction of the mesencephalic and upper pontine tegmentum involving the periaqueductal gray region and the medial longitudinal fasciculus bilaterally with greater involvement of the left. Like the WEBINO syndrome, re-emergent developmental stuttering is a rare neurologic phenomenon. To our knowledge, this is the first case report of a mesencephalic and upper pontine infarction causing both syndromes. We discuss the pathobiological underpinnings of the WEBINO syndrome and neurogenic stuttering and in relationship to this unusual case. PMID:22178081

Beh, Shin C; Frohman, Elliot M

2011-12-15

256

Morphometry and connectivity of the fronto-parietal verbal working memory network in development.  

PubMed

Two distinctly different maturational processes - cortical thinning and white matter maturation - take place in the brain as we mature from late childhood to adulthood. To what extent does each contribute to the development of complex cognitive functions like working memory? The independent and joint contributions of cortical thickness of regions of the left fronto-parietal network and the diffusion characteristics of the connecting pathway of the left superior longitudinal fasciculus (SLF) in accounting for verbal working memory performance were investigated, using a predefined regions of interest-approach. 108 healthy participants aged 8-19 years underwent MRI, including anatomical and diffusion tensor imaging (DTI), as well as cognitive testing using a digit span task. Radial diffusivity of the SLF, as well as cortical thickness of supramarginal gyrus and rostral middle frontal cortex, were negatively related to digit span forwards performance, independently of age. Radial diffusivity of the SLF was also negatively related to digit span backwards. A multi-modal analysis showed that cortical thickness and SLF microstructure were complementary in explaining working memory span. Furthermore, SLF microstructure and cortical thickness had different impact on working memory performance during the developmental period, suggesting a complex developmental interplay. The results indicate that cortical and white matter maturation each play unique roles in the development of working memory. PMID:22001853

Østby, Ylva; Tamnes, Christian K; Fjell, Anders M; Walhovd, Kristine B

2011-10-06

257

Relation between brain lesion location and clinical outcome in patients with severe traumatic brain injury: a diffusion tensor imaging study using voxel-based approaches.  

PubMed

The early prediction of consciousness recovery from traumatic brain injury (TBI) is crucial to make decisions about the appropriate use of prolonged intensive care. Diffusion tensor imaging (DTI) has been proposed as a biomarker of white matter injury that could be used in a classification purpose. Instead of region-of-interest-based approach, we applied voxel-based approaches (voxel-based DTI and tract-based spatial statistics) on 30 patients with TBI to identify, without any prior, the brain regions that were specifically damaged in unfavorable 1-year outcome group compared to the favorable one. DTI were acquired at mean 23 days (5-53 days) and two DTI-derived indices, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), were tested. Our results showed that (1) ADC is not a relevant biomarker for early 1-year outcome prognosis; (2) FA measured in inferior longitudinal fasciculus, in cerebral peduncle, in posterior limb of the internal capsule, and in posterior corpus callosum is specifically decreased in unfavorable outcome group compare to the favorable one; (3) a linear discriminant analysis using the FA measured in these four regions showed good classification performance (sensitivity = 86% and specificity = 86%). These findings confirm the relevance of the use of DTI as biomarkers for consciousness recovery after TBI and support the possible use of these biomarkers for early classification of patients. PMID:19507154

Perlbarg, Vincent; Puybasset, Louis; Tollard, Eléonore; Lehéricy, Stéphane; Benali, Habib; Galanaud, Damien

2009-12-01

258

A Golgi study on neuronal morphology of the ventral lateral geniculate nucleus of the lizard.  

PubMed

The architecture and cellular morphology of the ventral geniculate nucleus (vLGN) of Lacerta sicula (Rafinesque) were investigated by means of classical neuroanatomical methods (Bodian, Klüver-Barrera, Cresyl-violet, and rapid Golgi impregnation). The vLGN of L. sicula is located in the laterodorsal portion of the diencephalon throughout the ventral thalamus. It appears sickle-shaped in cross section and contains a) a lateral neuropil, close to the marginal optic tract; b) a medial cell plate and c) an internal neuropil. Golgi preparations show a diffuse population of multipolar, "tufted" and bipolar neurons together with scattered glial cells in the lateral neuropil of vLGN. In the cell plate, two or three rows of cells of medium size, largely corresponding to the so called "cellule a doppio pennacchio" (Beccari, 1923) are found. These cells are endowed with two dendritic trunks, extending respectively into the internal neuropil and toward the optic tract. This latter process shows a quite complex arborization, closely intermingling with the retinal fibres arising from the marginal optic tract. The axons of these cells contribute to the fasciculus geniculatus descendens, the main efferent system of the vLGN. PMID:7130675

Franzoni, M F; Fasolo, A

1982-01-01

259

A Brain Network Processing the Age of Faces  

PubMed Central

Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.

Homola, Gyorgy A.; Jbabdi, Saad; Beckmann, Christian F.; Bartsch, Andreas J.

2012-01-01

260

Limb apraxia in a patient with cerebral infarct: diffusion tensor tractography study.  

PubMed

We report on a patient with ideomotor apraxia (IMA) and limb-kinetic apraxia (LKA) following cerebral infarct, which demonstrated neural tract injuries by diffusion tensor tractography (DTT). A 67-year-old male was diagnosed as cerebral infarct in the left frontal cortex (anterior portion of the precentral gyrus and prefrontal cortex) and centrum semiovale. The patient presented with severe paralysis of the right upper extremity and mild weakness of the right lower extremity at onset. At the time of DTT scanning (5 months after onset), the patient was able to move all joint muscles of the right upper extremity against gravity, except for the finger extensors, which he could extend partially against gravity. The patient showed intact ideational plan for motor performance; however, his movements were slow, clumsy, and mutilated when executing grasp-release movements of his affected hand. The patient's score on the ideomotor apraxia test was 20 (cut-off score < 32). DTTs for premotor cortex fibers, supplementary motor area fibers, and superior longitudinal fasciculus of the left hemisphere showed partial injuries, compared with those of the right side, and these injuries appeared to be responsible for IMA and LKA in this patient. PMID:22672938

Hong, Ji Heon; Lee, Jun; Cho, Yoon Woo; Byun, Woo Mok; Cho, Hee Kyung; Son, Su Min; Jang, Sung Ho

2012-01-01

261

Alexithymia and reduced white matter integrity in schizophrenia: a diffusion tensor imaging study on impaired emotional self-awareness.  

PubMed

Alexithymia is characterized by deficits in emotional self-awareness. A number of previous studies have revealed impaired emotional self-awareness in schizophrenia. Although the pathology of schizophrenia is thought to involve disrupted white matter integrity, its relationship with alexithymia remains unclear. The present study investigated associations between alexithymia and white matter integrity, to seek the neural basis of impaired emotional self-awareness in schizophrenia. Forty-four patients with schizophrenia and 44 age-, gender- and predicted IQ level-matched healthy controls underwent diffusion-weighted imaging. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20). We applied tract-based spatial statistics to investigate the correlation between the TAS-20 total score and white matter fractional anisotropy (FA). TAS-20 scores were significantly higher in patients than in controls. In the patient group only, FA was negatively correlated with the TAS-20 total score in the corpus callosum, mostly the left part of the superior and inferior longitudinal fasciculi, the inferior occipito-frontal fasciculus, the anterior and posterior thalamic radiation, and the precuneus white matter. These results suggest that schizophrenia is associated with alexithymia, and that reduced white matter integrity within these regions constitutes an important pathology underlying impaired self-emotional awareness in schizophrenia. PMID:22986045

Kubota, Manabu; Miyata, Jun; Sasamoto, Akihiko; Kawada, Ryosaku; Fujimoto, Shinsuke; Tanaka, Yusuke; Sawamoto, Nobukatsu; Fukuyama, Hidenao; Takahashi, Hidehiko; Murai, Toshiya

2012-09-15

262

Angular smoothing and radial regularization of ODF fields: application on deterministic crossing fiber tractography.  

PubMed

The advent of high angular resolution diffusion imaging (HARDI) has opened up new perspectives for the delineation of crossing and branching fiber pathways. However, image acquisition under clinical conditions with limited measurement time faces the problem of poor spatial and angular resolution and the technique's high susceptibility to noise. In this paper we present a straightforward spatial filter for ODF fields that uses the data-inherent structural information around a voxel as part of a directionally selective method for angular smoothing and radial regularization (ASRR). Especially in regions where fibers cross (multimodal voxels), the method allows us to reduce noise, improve the accuracy of ODF diffusion peaks, and strengthen signals of non-dominant fibers. Moreover, we propose a dynamic scheme in which regularization is applied only to ODFs classified as multimodal. The approach is quantitatively evaluated on synthetic datasets of various configurations. With an in vivo dataset of a human subject, measured under clinical imaging conditions, we demonstrate the method's ability to improve tractography of non-dominant transcallosal fiber pathways and the long fibers of the superior longitudinal fasciculus. PMID:22051017

Otto, K M; Ehricke, H-H; Kumar, V; Klose, U

2011-11-02

263

Mapping joint grey and white matter reductions in Alzheimer's disease using joint independent component analysis.  

PubMed

Alzheimer's disease (AD) is a neurodegenerative disease concomitant with grey and white matter damages. However, the interrelationship of volumetric changes between grey and white matter remains poorly understood in AD. Using joint independent component analysis, this study identified joint grey and white matter volume reductions based on structural magnetic resonance imaging data to construct the covariant networks in twelve AD patients and fourteen normal controls (NC). We found that three networks showed significant volume reductions in joint grey-white matter sources in AD patients, including (1) frontal/parietal/temporal-superior longitudinal fasciculus/corpus callosum, (2) temporal/parietal/occipital-frontal/occipital, and (3) temporal-precentral/postcentral. The corresponding expression scores distinguished AD patients from NC with 85.7%, 100% and 85.7% sensitivity for joint sources 1, 2 and 3, respectively; 75.0%, 66.7% and 75.0% specificity for joint sources 1, 2 and 3, respectively. Furthermore, the combined source of three significant joint sources best predicted the AD/NC group membership with 92.9% sensitivity and 83.3% specificity. Our findings revealed joint grey and white matter loss in AD patients, and these results can help elucidate the mechanism of grey and white matter reductions in the development of AD. PMID:23123779

Guo, Xiaojuan; Han, Yuan; Chen, Kewei; Wang, Yan; Yao, Li

2012-11-02

264

Six is enough? Comparison of diffusion parameters measured using six or more diffusion-encoding gradient directions with deterministic tractography.  

PubMed

Diffusion tensor imaging tractography is commonly used to quantify white matter tracts in the human brain via parameters such as fractional anisotropy and mean diffusivity. Simulation studies recommend the use of more than six directions for robust parameter estimates; however, no study has examined the impact of the number of gradient directions on deterministic tractography-derived diffusion parameters in human brain. Here, for 10 major white matter tracts in 11 healthy volunteers at 1.5 T, six-direction diffusion tensor imaging data were compared to 30- or 60-direction data, keeping scan time and number of b = 0 images constant within each test. Mean diffusivity was systematically lower for six-direction protocols (20/40 comparisons); six-direction data had higher fractional anisotropy in the superior longitudinal fasciculus and smaller tract volume for the genu of the corpus callosum. In general, parameter differences due to the number of directions were smaller than those from intersubject variation or signal-to-noise ratio. Despite some absolute differences, standard deviations were significantly different for only one of 160 comparisons. Thus, six-direction data provide diffusion measures with comparable robustness to 30- or 60-direction data and yield appropriate parameter values for most white matter tracts, although there are clear advantages in acquiring higher angular resolution data. PMID:22162075

Lebel, Catherine; Benner, Thomas; Beaulieu, Christian

2011-12-12

265

ADRB2, brain white matter integrity and cognitive ageing in the Lothian Birth Cohort 1936.  

PubMed

The non-synonymous mutations arg16gly (rs1042713) and gln27glu (rs1042714) in the adrenergic ?-2 receptor gene (ADRB2) have been associated with cognitive function and brain white matter integrity. The current study aimed to replicate these findings and expand them to a broader range of cognitive and brain phenotypes. The sample used is a community-dwelling group of older people, the Lothian Birth Cohort 1936. They had been assessed cognitively at age 11 years, and undertook further cognitive assessments and brain diffusion MRI tractography in older age. The sample size range for cognitive function variables was N = 686-765, and for neuroimaging variables was N = 488-587. Previously-reported findings with these genetic variants did not replicate in this cohort. Novel, nominally significant associations were observed; notably, the integrity of the left arcuate fasciculus mediated the association between rs1042714 and the Digit Symbol Coding test of information processing speed. No significant associations of cognitive and brain phenotypes with ADRB2 variants survived correction for false discovery rate. Previous findings may therefore have been subject to type 1 error. Further study into links between ADRB2, cognitive function and brain white matter integrity is required. PMID:23229623

Lyall, Donald M; Lopez, Lorna M; Bastin, Mark E; Maniega, Susana Muñoz; Penke, Lars; Valdés Hernández, Maria del C; Royle, Natalie A; Starr, John M; Porteous, David J; Wardlaw, Joanna M; Deary, Ian J

2012-12-11

266

Axon tracts guide zebrafish facial branchiomotor neuron migration through the hindbrain.  

PubMed

Appropriate localization of neurons within the brain is a crucial component of the establishment of neural circuitry. In the zebrafish hindbrain, the facial branchiomotor neurons (FBMNs) undergo a chain-like tangential migration from their birthplace in rhombomere (r) 4 to their final destination in r6/r7. Here, we report that ablation of either the cell body or the trailing axon of the leading FBMN, or 'pioneer' neuron, blocks the migration of follower FBMNs into r5. This demonstrates that the pioneer neuron and its axon are crucial to the early migration of FBMNs. Later migration from r5 to r6 is not dependent on pioneer neurons but on the medial longitudinal fasciculus (MLF), a bundle of axons lying ventral to the FBMNs. We find that MLF axons enter r5 only after the pioneer neuron has led several followers into this region; the MLF is then contacted by projections from the FBMNs. The interactions between FBMNs and the MLF are important for migration from r5 to r6, as blocking MLF axons from entering the hindbrain can stall FBMN migration in r5. Finally, we have found that the adhesion molecule Cdh2 (N-cadherin) is important for interactions between the MLF and FBMNs, as well as for interactions between the trailing axon of the pioneer neuron and follower FBMNs. Interestingly, migration of pioneer neurons is independent of both the MLF and Cdh2, suggesting pioneer migration relies on independent cues. PMID:23325758

Wanner, Sarah J; Prince, Victoria E

2013-01-16

267

Brain regional lesion burden and impaired mobility in the elderly.  

PubMed

This study investigated the relationship of brain white matter (WM) lesions affecting specific neural networks with decreased mobility in ninety-nine healthy community-dwelling subjects ?75 years old prospectively enrolled by age and mobility status. We assessed lesion burden in the genu, body and splenium of corpus callosum; anterior, superior and posterior corona radiata; anterior and posterior limbs of internal capsule; corticospinal tract; and superior longitudinal fasciculus. Burden in the splenium of corpus callosum (SCC) demonstrated the highest correlation particularly with walking speed (r=0.4, p<10(-4)), and in logistic regression it was the best regional predictor of low mobility performance. We also found that independent of mobility, corona radiata has the largest lesion burden with anterior (ACR) and posterior (PCR) aspects being the most frequently affected. The results suggest that compromised inter-hemispheric integration of visuospatial information through the SCC plays an important role in mobility impairment in the elderly. The relatively high lesion susceptibility of ACR and PCR in all subjects may obscure the importance of these lesions in mobility impairment. PMID:19428145

Moscufo, Nicola; Guttmann, Charles R G; Meier, Dominik; Csapo, Istvan; Hildenbrand, Peter G; Healy, Brian C; Schmidt, Julia A; Wolfson, Leslie

2009-05-09

268

Multiple Indices of Diffusion Identifies White Matter Damage in Mild Cognitive Impairment and Alzheimer's Disease  

PubMed Central

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa.

O'Dwyer, Laurence; Lamberton, Franck; Bokde, Arun L. W.; Ewers, Michael; Faluyi, Yetunde O.; Tanner, Colby; Mazoyer, Bernard; O'Neill, Des; Bartley, Mairead; Collins, D. Ronan; Coughlan, Tara; Prvulovic, David; Hampel, Harald

2011-01-01

269

Internuclear ophthalmoplegia: recovery and plasticity.  

PubMed

We studied refixational eye movements of a patient during the gradual resolution of an internuclear ophthalmoplegia (secondary to head trauma) in an attempt to determine the relative contributions of both medial longitudinal fasciculus (MLF) recovery and secondary central plastic changes. Adduction-refixational eye movements in the affected eye consisted of an initial fast (saccadic) portion followed by a slow drift toward the new intended eye position. The fast and slow components of the movements reflected, respectively, the pulse and step increases in neural innervation. Shortly after the traumatic insult, the affected eye exhibited low adduction gain (pulse gain 0.34; step gain 0.37) and slow saccades with peak velocities of 55% and durations of 278%, normalized for achieved, rather than intended, amplitudes. Several months later the pulse and step gains, peak velocities, and durations of the saccades improved to 0.81, 0.92, 87%, and 145%, respectively. The increased gains and faster velocity were accomplished by increases in the firing frequency of the pulse and step, reflecting recovery of MLF axons, rather than saccadic system plasticity, which would have resulted in increased duration of the saccadic pulse. PMID:7440105

Doslak, M J; Kline, L B; Dell'Osso, L F; Daroff, R B

1980-12-01

270

Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey  

SciTech Connect

The projections to the frontal cortex that originate from the various areas of the superior temporal region of the rhesus monkey were investigated with the autoradiographic technique. The results demonstrated that the rostral part of the superior temporal gyrus (areas Pro, Ts1, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus.

Petrides, M.; Pandya, D.N.

1988-07-01

271

Longitudinal changes in patients with traumatic brain injury assessed with diffusion tensor and volumetric imaging  

PubMed Central

Traumatic brain injury (TBI) is associated with brain volume loss, but there is little information on the regional gray matter (GM) and white matter (WM) changes that contribute to overall loss. Since axonal injury is a common occurrence in TBI, imaging methods that are sensitive to WM damage such as diffusion-tensor imaging (DTI) may be useful for characterizing microstructural brain injury contributing to regional WM loss in TBI. High-resolution T1-weighted imaging and DTI were used to evaluate regional changes in TBI patients compared to matched controls. Patients received neuropsychological testing and were imaged approximately 2 months and 12.7 months post injury. Paradoxically, neuropsychological function improved from Visit 1 to Visit 2, while voxel-based analyses of fractional anisotropy (FA), and mean diffusivity (MD) from the DTI images, and voxel-based analyses of the GM and WM probability maps from the T1-weighted images, mainly revealed significantly greater deleterious GM and WM change over time in patients compared to controls. Cross-sectional comparisons of the DTI measures indicated that patients have decreased FA and increased MD compared to controls over large regions of the brain. TBI affected virtually all of the major fiber bundles in the brain including the corpus callosum, cingulum, the superior and inferior longitudinal fascicules, the uncinate fasciculus, and brain stem fiber tracts. The results indicate that both GM and WM degeneration are significant contributors to brain volume loss in the months following brain injury, and also suggest that DTI measures may be more useful than high-resolution anatomical images in assessment of group differences.

Bendlin, Barbara; Ries, Michele L.; Lazar, Mariana; Alexander, Andrew L.; Dempsey, Robert J.; Rowley, Howard A.; Sherman, Jack E.; Johnson, Sterling C.

2008-01-01

272

Aortic pulse wave velocity predicts focal white matter hyperintensities in a biracial cohort of older adults.  

PubMed

Although the cross-sectional relationship of arterial stiffness with cerebral small vessel disease is consistently shown in middle-aged and young-old adults, it is less clear whether these associations remain significant over time in very old adults. We hypothesize that arterial stiffness is longitudinally associated with white matter characteristics, and associations are stronger within watershed areas. Neuroimaging was obtained in 2006-2008 from 303 elderly (mean age 82.9 years, 59% women, 41% black) with pulse wave velocity (PWV) measures in 1997-1998. Multivariable regression models estimated the coefficients for PWV (cm/sec) in relationship to presence, severity, and spatial distribution of white matter hyperintensities (WMH), gray matter volume, and fractional anisotropy from diffusion tensor, adjusting for demographic, cardiovascular risk factors, and diseases from 1997-1998 to 2006-2008. Higher PWV in 1997-1998 was associated with greater WMH volume in 2006-2008 within the left superior longitudinal fasciculus (age and total brain WMH adjusted, P=0.023), but not with WMH in other tracts or with fractional anisotropy or gray matter volume from total brain (P>0.2). Associations were stronger in blacks than in whites, remaining significant in fully adjusted models. Elderly with WMH in tracts related to processing speed and memory are more likely to have had higher PWV values 10 years prior, before neuroimaging data being available. Future studies should address whether arterial stiffness can serve as an early biomarker of covert brain structural abnormalities and whether early arterial stiffness control can promote successful brain aging, especially in black elderly. PMID:23172923

Rosano, Caterina; Watson, Nora; Chang, Yuefang; Newman, Anne B; Aizenstein, Howard J; Du, Yan; Venkatraman, Vijay; Harris, Tamara B; Barinas-Mitchell, Emma; Sutton-Tyrrell, Kim

2012-11-19

273

Exposure to Parental Verbal Abuse is Associated with Increased Gray Matter Volume in Superior Temporal Gyrus  

PubMed Central

Objective Exposure to parental verbal aggression (PVA) during childhood increases risk for the development of psychopathology, particularly mood and anxiety disorders. Other forms of childhood abuse have been found to be associated with alterations in brain structure. The aim of this study was to ascertain whether exposure to PVA was associated with discernible effects on brain morphology. Methods Optimized voxel based morphometry was performed on 21 unmedicated, right-handed subjects (18–25 years) with histories of PVA and 19 psychiatrically healthy controls of comparable age and gender. Group differences in gray matter volume (GMV) – covaried by age, gender, parental education, financial stress, and total GMV – were assessed using high-resolution, T1-weighted, volumetric MRI data sets (Siemens 3T trio scanner). Results GMV was increased by 14.1% in the left superior temporal gyrus (STG, BA 22) (P = 0.004, corrected cluster level). GMV in this cluster was associated most strongly with levels of maternal (? = 0.544, P < 0.0001) and paternal (? = 0.300, P < 0.02) verbal aggression and inversely associated with parental education (? = ?0.577, P < 0.0001). Conclusion Previous studies have demonstrated an increase in STG GMV in children with abuse histories, and found a reduction in fractional anisotropy in the arcuate fasciculus connecting Wernicke’s and frontal areas in young adults exposed to PVA. These findings and the present results suggest that the development of auditory association cortex involved in language processing may be affected by exposure to early stress and/or emotionally-abusive language.

Tomoda, Akemi; Sheu, Yi-Shin; Rabi, Keren; Suzuki, Hanako; Navalta, Carryl P.; Polcari, Ann; Teicher, Martin H.

2010-01-01

274

Orexin-A inputs onto visuomotor cell groups in the monkey brainstem  

PubMed Central

Orexin-A, synthesized by neurons of the lateral hypothalamus, helps to maintain wakefulness through excitatory projections to nuclei involved in arousal. Obvious changes in eye movements, eyelid position and pupil reactions seen in the transition to sleep led to the investigation of orexin-A projections to visuomotor cell groups to determine whether direct pathways exist that may modify visuomotor behaviors during the sleep/wake cycle. Histological markers were used to define these specific visuomotor cell groups in monkey brainstem sections and combined with orexin-A immunostaining. The dense supply by orexin-A boutons around adjacent neurons in the dorsal raphe nucleus served as a control standard for a strong orexin-A input. The quantitative analysis assessing various functional cell groups of the oculomotor system revealed that almost no input from orexin-A terminals reached motoneurons supplying the singly-innervated muscle fibers of the extraocular muscles in the oculomotor nucleus, the omnipause neurons in the nucleus raphe interpositus and the premotor neurons in the rostral interstitial nucleus of the medial longitudinal fasciculus. In contrast, the motoneurons supplying the multiply-innervated muscle fibers of the extraocular muscles, the motoneurons of the levator palpebrae muscle in the central caudal nucleus, and especially the preganglionic neurons supplying the ciliary ganglion received a strong orexin input. We interpret these results as evidence that orexin-A does modulate pupil size, lid position, and possibly convergence and eye alignment via the motoneurons of multiply-innervated muscle fibres. However orexin-A does not directly modulate premotor pathways for saccades or the SIF motoneurons.

Schreyer, Sarah; Buttner-Ennever, Jean A.; Tang, Xiaofang; Mustari, Michael J.; Horn, Anja K. E.

2009-01-01

275

Longitudinal diffusion tensor imaging and neuropsychological correlates in traumatic brain injury patients.  

PubMed

Traumatic brain injury (TBI) often involves focal cortical injury and white matter (WM) damage that can be measured shortly after injury. Additionally, slowly evolving WM change can be observed but there is a paucity of research on the duration and spatial pattern of long-term changes several years post-injury. The current study utilized diffusion tensor imaging to identify regional WM changes in 12 TBI patients and nine healthy controls at three time points over a four year period. Neuropsychological testing was also administered to each participant at each time point. Results indicate that TBI patients exhibit longitudinal changes to WM indexed by reductions in fractional anisotropy (FA) in the corpus callosum, as well as FA increases in bilateral regions of the superior longitudinal fasciculus (SLF) and portions of the optic radiation (OR). FA changes appear to be driven by changes in radial (not axial) diffusivity, suggesting that observed longitudinal FA changes may be related to changes in myelin rather than to axons. Neuropsychological correlations indicate that regional FA values in the corpus callosum and sagittal stratum (SS) correlate with performance on finger tapping and visuomotor speed tasks (respectively) in TBI patients, and that longitudinal increases in FA in the SS, SLF, and OR correlate with improved performance on the visuomotor speed (SS) task as well as a derived measure of cognitive control (SLF, OR). The results of this study showing progressive WM deterioration for several years post-injury contribute to a growing literature supporting the hypothesis that TBI should be viewed not as an isolated incident but as a prolonged disease state. The observations of long-term neurological and functional improvement provide evidence that some ameliorative change may be occurring concurrently with progressive degeneration. PMID:22723773

Farbota, Kimberly D; Bendlin, Barbara B; Alexander, Andrew L; Rowley, Howard A; Dempsey, Robert J; Johnson, Sterling C

2012-06-19

276

Validating Serum S100B and Neuron-Specific Enolase as Biomarkers for the Human Brain - A Combined Serum, Gene Expression and MRI Study  

PubMed Central

Introduction Former studies have investigated the potential of serum biomarkers for diseases affecting the human brain. In particular the glial protein S100B, a neuro- and gliotrophin inducing plasticity, seems to be involved in the pathogenesis and treatment of psychiatric diseases such as major depression and schizophrenia. Neuron-specific enolase (NSE) is a specific serum marker for neuronal damage. However, the specificity of these biomarkers for cell type and brain region has not been investigated in vivo until now. Methods We acquired two magnetic resonance imaging parameters sensitive to changes in gray and white matter (T1-weighted/diffusion tensor imaging) and obtained serum S100B and NSE levels of 41 healthy subjects. Additionally, we analyzed whole brain gene expressions of S100B in another male cohort of three subjects using the Allen Brain Atlas. Furthermore, a female post mortal brain was investigated using double immunofluorescence labelling with oligodendrocyte markers. Results We show that S100B is specifically related to white matter structures, namely the corpus callosum, anterior forceps and superior longitudinal fasciculus in female subjects. This effect was observed in fractional anisotropy and radial diffusivity – the latest an indicator of myelin changes. Histological data confirmed a co-localization of S100B with oligodendrocyte markers in the human corpus callosum. S100B was most abundantly expressed in the corpus callosum according to the whole genome Allen Human Brain Atlas. In addition, NSE was related to gray matter structures, namely the amygdala. This effect was detected across sexes. Conclusion Our data demonstrates a very high S100B expression in white matter tracts, in particular in human corpus callosum. Our study is the first in vivo study validating the specificity of the glial marker S100B for the human brain, and supporting the assumption that radial diffusivity represents a myelin marker. Our results open a new perspective for future studies investigating major neuropsychiatric disorders.

Streitburger, Daniel-Paolo; Arelin, Katrin; Kratzsch, Jurgen; Thiery, Joachim; Steiner, Johann; Villringer, Arno

2012-01-01

277

Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans  

PubMed Central

Mild traumatic brain injury (TBI) is a common source of morbidity from the wars in Iraq and Afghanistan. With no overt lesions on structural MRI, diagnosis of chronic mild TBI in military veterans relies on obtaining an accurate history and assessment of behavioral symptoms that are also associated with frequent comorbid disorders, particularly posttraumatic stress disorder (PTSD) and depression. Military veterans from Iraq and Afghanistan with mild TBI (n=30) with comorbid PTSD and depression and non-TBI participants from primary (n=42) and confirmatory (n=28) control groups were assessed with high angular resolution diffusion imaging (HARDI). White matter-specific registration followed by whole-brain voxelwise analysis of crossing fibers provided separate partial volume fractions reflecting the integrity of primary fibers and secondary (crossing) fibers. Loss of white matter integrity in primary fibers (p < .05; corrected) was associated with chronic mild TBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including the corpus callosum (genu, body, splenium), forceps minor, forceps major, superior and posterior corona radiata, internal capsule, superior longitudinal fasciculus, and others. Distributed loss of white matter integrity correlated with duration of loss of consciousness and most notably with “feeling dazed or confused,” but not diagnosis of PTSD or depressive symptoms. This widespread spatial extent of white matter damage has typically been reported in moderate to severe TBI. The diffuse loss of white matter integrity appears consistent with systemic mechanisms of damage shared by blast- and impact-related mild TBI that involves a cascade of inflammatory and neurochemical events.

Morey, Rajendra A.; Haswell, Courtney C.; Selgrade, Elizabeth S.; Massoglia, Dino; Liu, Chunlei; Weiner, Jonathan; Marx, Christine E.; Cernak, Ibolja; McCarthy, Gregory

2013-01-01

278

Mechanism of the antinociceptive action of mesaconitine: participation of brain stem and lumbar enlargement.  

PubMed Central

The antinociceptive action of mesaconitine (MA) microinjected into the nucleus reticularis gigantocellularis (NRGC), the nucleus reticularis paragigantocellularis (NRPG), the periaqueductal gray (PAG) or the lumbar enlargement was investigated in rats by use of the tail immersion test. In addition, the effects of beta-adrenoceptor antagonists and an alpha-adrenoceptor antagonist administered intrathecally (i.t.) on the antinociceptive action of MA given into the NRPG were also examined by the tail immersion test. MA (50, 100 ng per rat) microinjected into the NRGC, the NRPG, and PAG and the lumbar enlargement increased the response latency in rats in a dose-dependent fashion. MA (50 ng per rat) microinjected into neighbouring sites, the nucleus reticularis parvocellularis, the nucleus originis nervi abducentis and the fasciculus longitudinalis medialis, elicited no significant effect. Intrathecally administered propranolol (1 and 5 micrograms per rat), atenolol (1 and 5 micrograms per rat) and IPS-339 (1 and 5 micrograms per rat) remarkably inhibited the increase of the response latency induced by MA (50 ng per rat) given into the NRPG. Intrathecally administered phenoxybenzamine (1 and 5 micrograms per rat) inhibited the increase of the response latency induced by MA (50 ng per rat) injected into the NRPG but to a lesser extent than the beta-adrenoceptor antagonists. It is concluded that the NRGC, the NRPG, the PAG and the lumbar enlargement are involved in the sites of the antinociceptive action of MA and that the antinociceptive effect of MA administered into NRPG is elicited by activation of the inhibitory noradrenergic neurones from the NRPG in particularly via beta-receptor-mediated effects of noradrenaline.

Hikino, H.; Murayama, M.

1985-01-01

279

Gene network effects on brain microstructure and intellectual performance identified in 472 twins.  

PubMed

A major challenge in neuroscience is finding which genes affect brain integrity, connectivity, and intellectual function. Discovering influential genes holds vast promise for neuroscience, but typical genome-wide searches assess approximately one million genetic variants one-by-one, leading to intractable false positive rates, even with vast samples of subjects. Even more intractable is the question of which genes interact and how they work together to affect brain connectivity. Here, we report a novel approach that discovers which genes contribute to brain wiring and fiber integrity at all pairs of points in a brain scan. We studied genetic correlations between thousands of points in human brain images from 472 twins and their nontwin siblings (mean age: 23.7 ± 2.1 SD years; 193 male/279 female). We combined clustering with genome-wide scanning to find brain systems with common genetic determination. We then filtered the image in a new way to boost power to find causal genes. Using network analysis, we found a network of genes that affect brain wiring in healthy young adults. Our new strategy makes it computationally more tractable to discover genes that affect brain integrity. The gene network showed small-world and scale-free topologies, suggesting efficiency in genetic interactions and resilience to network disruption. Genetic variants at hubs of the network influence intellectual performance by modulating associations between performance intelligence quotient and the integrity of major white matter tracts, such as the callosal genu and splenium, cingulum, optic radiations, and the superior longitudinal fasciculus. PMID:22723713

Chiang, Ming-Chang; Barysheva, Marina; McMahon, Katie L; de Zubicaray, Greig I; Johnson, Kori; Montgomery, Grant W; Martin, Nicholas G; Toga, Arthur W; Wright, Margaret J; Shapshak, Paul; Thompson, Paul M

2012-06-20

280

Spatiotemporal Expression of Repulsive Guidance Molecules (RGMs) and Their Receptor Neogenin in the Mouse Brain  

PubMed Central

Neogenin has been implicated in a variety of developmental processes such as neurogenesis, neuronal differentiation, apoptosis, migration and axon guidance. Binding of repulsive guidance molecules (RGMs) to Neogenin inhibits axon outgrowth of different neuronal populations. This effect requires Neogenin to interact with co-receptors of the uncoordinated locomotion-5 (Unc5) family to activate downstream Rho signaling. Although previous studies have reported RGM, Neogenin, and/or Unc5 expression, a systematic comparison of RGM and Neogenin expression in the developing nervous system is lacking, especially at later developmental stages. Furthermore, information on RGM and Neogenin expression at the protein level is limited. To fill this void and to gain further insight into the role of RGM-Neogenin signaling during mouse neural development, we studied the expression of RGMa, RGMb, Neogenin and Unc5A-D using in situ hybridization, immunohistochemistry and RGMa section binding. Expression patterns in the primary olfactory system, cortex, hippocampus, habenula, and cerebellum were studied in more detail. Characteristic cell layer-specific expression patterns were detected for RGMa, RGMb, Neogenin and Unc5A-D. Furthermore, strong expression of RGMa, RGMb and Neogenin protein was found on several major axon tracts such as the primary olfactory projections, anterior commissure and fasciculus retroflexus. These data not only hint at a role for RGM-Neogenin signaling during the development of different neuronal systems, but also suggest that Neogenin partners with different Unc5 family members in different systems. Overall, the results presented here will serve as a framework for further dissection of the role of RGM-Neogenin signaling during neural development.

van den Heuvel, Dianne M. A.; Hellemons, Anita J. C. G. M.; Pasterkamp, R. Jeroen

2013-01-01

281

Coexpression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer axons during pathfinding in the developing rat forebrain.  

PubMed

Precise axon pathfinding is crucial for establishment of the initial neuronal network during development. Pioneer axons navigate without the help of preexisting axons and pave the way for follower axons that project later. Voltage-gated ion channels make up the intrinsic electrical activity of pioneer axons and regulate axon pathfinding. To elucidate which channel molecules are present in pioneer axons, immunohistochemical analysis was performed to examine 14 voltage-gated ion channels (Kv1.1-Kv1.3, Kv3.1-Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2, Nav1.2, Nav1.6, and Nav1.9) in nine axonal tracts in the developing rat forebrain, including the optic nerve, corpus callosum, corticofugal fibers, thalamocortical axons, lateral olfactory tract, hippocamposeptal projection, anterior commissure, hippocampal commissure, and medial longitudinal fasciculus. We found A-type K? channel Kv3.4 in both pioneer axons and early follower axons and L-type Ca²? channel Cav1.2 in pioneer axons and early and late follower axons. Spatially, Kv3.4 and Cav1.2 were colocalized with markers of pioneer neurons and pioneer axons, such as deleted in colorectal cancer (DCC), in most fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in most fiber tracts during axon pathfinding but were downregulated beginning in synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1) and Nav channels (e.g., Nav1.2) were absent from these fiber tracts (except for the corpus callosum) during pathfinding of pioneer axons. These data suggest that Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to control Ca²? -dependent electrical activity of pioneer axons and play important roles during axon pathfinding. PMID:22473424

Huang, Chia-Yi; Chu, Dachen; Hwang, Wei-Chao; Tsaur, Meei-Ling

2012-11-01

282

Autoradiographic localization of putative nicotinic receptors in the rat brain using sup 125 I-neuronal bungarotoxin  

SciTech Connect

Neuronal bungarotoxin (NBT), a snake venom neurotoxin, selectively blocks nicotinic receptors in many peripheral and central neuronal preparations. alpha-Bungarotoxin (alpha BT), on the other hand, a second toxin isolated from the venom of the same snake, is an ineffective nicotinic antagonist in most vertebrate neuronal preparations studied thus far. To examine central nicotinic receptors recognized by NBT, we have characterized the binding of 125I-labeled NBT (125I-NBT) to rat brain membranes and have mapped the distribution of 125I-NBT binding in brain sections using quantitative light microscopic autoradiography. The binding of 125I-NBT was found to be saturable, of high affinity, and heterogeneously distributed in the brain. Pharmacological studies suggested that more than one population of sites is labeled by 125I-NBT. For example, one component of 125I-NBT binding was also recognized by alpha BT, while a second component, not recognized by alpha BT, was recognized by the nicotinic agonist nicotine. The highest densities of these alpha BT-insensitive, nicotine-sensitive sites were found in the fasciculus retroflexus, the lateral geniculate nucleus, the medial terminal nucleus of the accessory optic tract, and the olivary pretectal nucleus. alpha BT-sensitive NBT binding sites were found in highest density in the lateral geniculate nucleus, the subthalamic nucleus, the dorsal tegmental nucleus, and the medial mammillary nucleus (lateral part). The number of brain regions with a high density of 125I-NBT binding sites, blocked either by alpha BT or by nicotine, is low when compared with results obtained using other approaches to studying the central distribution of nicotinic receptors, such as labeling with 3H-nicotine or labeling with cDNA probes to mRNAs coding for putative receptor subunits.

Schulz, D.W.; Loring, R.H.; Aizenman, E.; Zigmond, R.E. (Harvard Medical School, Boston, MA (USA))

1991-01-01

283

White matter is altered with parental family history of Alzheimer's disease  

PubMed Central

Background Brain alterations in structure and function have been identified in people with risk factors for sporadic type Alzheimer’s disease (AD), suggesting that alterations can be detected decades before AD diagnosis. While the effect of Apolipoprotein E (ApoE) ?4 on the brain is well studied, less is known about the effect of family history of AD. We examined the main effects of family history and ApoE ?4 on brain integrity, in addition to assessing possible additive effects of these two risk factors. Methods Diffusion tensor imaging was performed in 136 middle-aged asymptomatic participants stratified on family history and ApoE ?4. Mean diffusivity and fractional anisotropy (FA) were entered in factorial analyses to test the effect of AD risk on microstructural brain integrity. We performed a post hoc analysis of the three principle diffusivities (?1, ?2, ?3) to provide potential additional insight on underlying tissue differences. Results Parental family history of AD was associated with lower FA in regions of the brain known to be affected by AD, including cingulum, corpus callosum, tapetum, uncinate fasciculus, hippocampus, and adjacent white matter. Contrary to previous reports there was no main effect of ApoE ?4; however, there was an additive effect of family history and ApoE ?4 where family history positive participants who were also ApoE ?4 carriers had the lowest FA compared to the other groups. Conclusions The data indicate that unknown risk factors contained in family history are associated with changes in microstructural brain integrity in areas of the brain known be affected by AD. Importantly, the results provide further evidence that AD pathology may be detected prior to cognitive changes, perhaps decades before disease onset.

Bendlin, B. B.; Ries, M. L.; Canu, E.; Sodhi, A.; Lazar, M.; Alexander, A. L.; Carlsson, C. M.; Sager, M. A.; Asthana, S.; Johnson, S. C.

2009-01-01

284

Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans.  

PubMed

Mild traumatic brain injury (TBI) is a common source of morbidity from the wars in Iraq and Afghanistan. With no overt lesions on structural MRI, diagnosis of chronic mild TBI in military veterans relies on obtaining an accurate history and assessment of behavioral symptoms that are also associated with frequent comorbid disorders, particularly posttraumatic stress disorder (PTSD) and depression. Military veterans from Iraq and Afghanistan with mild TBI (n = 30) with comorbid PTSD and depression and non-TBI participants from primary (n = 42) and confirmatory (n = 28) control groups were assessed with high angular resolution diffusion imaging (HARDI). White matter-specific registration followed by whole-brain voxelwise analysis of crossing fibers provided separate partial volume fractions reflecting the integrity of primary fibers and secondary (crossing) fibers. Loss of white matter integrity in primary fibers (P < 0.05; corrected) was associated with chronic mild TBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including the corpus callosum (genu, body, and splenium), forceps minor, forceps major, superior and posterior corona radiata, internal capsule, superior longitudinal fasciculus, and others. Distributed loss of white matter integrity correlated with duration of loss of consciousness and most notably with "feeling dazed or confused," but not diagnosis of PTSD or depressive symptoms. This widespread spatial extent of white matter damage has typically been reported in moderate to severe TBI. The diffuse loss of white matter integrity appears consistent with systemic mechanisms of damage shared by blast- and impact-related mild TBI that involves a cascade of inflammatory and neurochemical events. Hum Brain Mapp 34:2986-2999, 2013. © 2012 Wiley Periodicals, Inc. PMID:22706988

Morey, Rajendra A; Haswell, Courtney C; Selgrade, Elizabeth S; Massoglia, Dino; Liu, Chunlei; Weiner, Jonathan; Marx, Christine E; Cernak, Ibolja; McCarthy, Gregory

2012-06-15

285

Subject-Specific Changes in Brain White Matter on Diffusion Tensor Imaging After Sports-Related Concussion  

PubMed Central

Background and Purpose Current approaches to diffusion tensor imaging (DTI) analysis do not permit identification of individual-level changes in DTI indices. We investigated the ability of wild bootstrapping analysis to detect subject-specific changes in brain white matter (WM) before and after sports-related concussion. Materials and Methods A prospective cohort study was performed in 9 high school athletes engaged in hockey or football, and 6 controls. Subjects underwent DTI pre- and post-season within a 3-month interval. One athlete was diagnosed with concussion (scanned within 72 hours) and 8 suffered between 26 and 399 sub-concussive head blows. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in each white matter voxel. Bootstrap samples were generated and a permuted t test used to compare voxel-wise FA/MD changes in each subject pre- vs. post-season. Results The percentage of WM voxels with significant (p<0.05) pre-post FA changes was highest for the concussion subject (3.2%), intermediary for those with sub-concussive head blows (mean 1.05±.15%) and lowest for controls (mean 0.28±.01%). Similarly, the percentage of WM voxels with significant MD changes was highest for the concussion subject (3.44%), intermediary for those with sub-concussive head blows (mean 1.48±.17%) and lowest for controls (mean 0.48±.05%). Significantly changed FA and MD voxels co-localized in the concussion subject to the right corona radiata and right inferior longitudinal fasciculus. Conclusions Wild bootstrap analysis detected significantly changed WM in a single concussed athlete. Athletes with multiple sub-concussive head blows had significant changes in a percentage of their WM that was over 3 times higher than controls. Efforts to understand the significance of these WM changes, and their relationship to head impact forces appear warranted.

Zhu, Tong; Blyth, Brian; Borrino, Allyson; Zhong, Jianhui

2011-01-01

286

Habenula and thalamus cell transplants restore normal sleep behaviors disrupted by denervation of the interpeduncular nucleus.  

PubMed

The preceding companion study (Eckenrode et al., 1992) showed that cell suspension transplants of fetal habenula cells placed near the interpeduncular nucleus (IPN) following lesions of the fasciculus retroflexus (FR) restore the normal pattern of substance P (SP) staining in habenular target subnuclei of the IPN in both perinatal and adult hosts, and restore ChAT staining in the IPN of perinatal hosts. Similarly placed transplants of fetal thalamus cells only restore ChAT staining in the IPN of adult hosts. In this study, we examined the functional significance of these restored staining patterns. We used a behavioral measure of the integrity of REM-stage and non-REM-stage sleep, the "flower pot" test, and assayed (1) normal adult rats, (2) FR-lesioned control animals (neonatal or adult operates), (3) animals receiving FR lesions and transplants of fetal habenula cells (perinatal or adult hosts), and (4) animals receiving FR lesions and transplants of fetal thalamus cells (adult hosts). FR lesions decrease markedly the muscle atonia component of REM sleep and reduce duration of sleep episodes. Transplants that restore SP staining in the IPN (habenular transplants into either perinatal or adult lesion hosts) restore normal frequency of REM atonia; transplants that restore ChAT staining (habenular transplants into perinatal hosts or thalamic transplants into adult hosts) restore normal duration of sleep episodes. The number of SP-immunoreactive cells in the transplants predicts recovery of REM atonia, and the number of ChAT cells in habenular (but not thalamic) transplants predicts restoration of sleep duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1494957

Haun, F; Eckenrode, T C; Murray, M

1992-08-01

287

Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use  

PubMed Central

Background There is growing evidence that adolescence is a key period for neuronal maturation. Despite the high prevalence of marijuana use among adolescents and young adults in the United States and internationally, very little is known about its impact on the developing brain. Based on neuroimaging literature on normal brain developmental during adolescence, we hypothesized that individuals with heavy cannabis use (HCU) would have brain structure abnormalities in similar brain regions that undergo development during late adolescence, particularly the fronto-temporal connection. Method Fourteen young adult males in residential treatment for cannabis dependence and 14 age-matched healthy male control subjects were recruited. Patients had a history of HCU throughout adolescence; 5 had concurrent alcohol abuse. Subjects underwent structural and diffusion tensor magnetic resonance imaging. White matter integrity was compared between subject groups using voxelwise and fiber tractography analysis. Results Voxelwise and tractography analyses revealed that adolescents with HCU had reduced fractional anisotropy, increased radial diffusivity, and increased trace in the homologous areas known to be involved in ongoing development during late adolescence, particularly in the fronto-temporal connection via arcuate fasciculus. Conclusions Our results support the hypothesis that heavy cannabis use during adolescence may affect the trajectory of normal brain maturation. Due to concurrent alcohol consumption in five HCU subjects, conclusions from this study should be considered preliminary, as the DTI findings reported here may be reflective of the combination of alcohol and marijuana use. Further research in larger samples, longitudinal in nature, and controlling for alcohol consumption is needed to better understand the pathophysiology of the effect of cannabis on the developing brain.

Cervellione, Kelly; Cottone, John; Ardekani, Babak A.; Kumra, Sanjiv

2012-01-01

288

Delay discounting behavior and white matter microstructure abnormalities in youth with a family history of alcoholism  

PubMed Central

Background Youth with family history of alcohol abuse have a greater risk of developing an alcohol use disorder (AUD). Brain and behavior differences may underlie this increased vulnerability. The current study examined delay discounting behavior and white matter microstructure in youth at high-risk for alcohol abuse, as determined by a family history of alcoholism (FH+), and youth without such family history (FH?). Methods Thirty-three healthy youth (FH+ = 15, FH? = 18), ages 11 to 15 years, completed a delay discounting task and underwent diffusion tensor imaging (DTI). Tract Based Spatial Statistics (Smith et al., 2006), as well as follow-up region-of-interest analyses, were performed in order to compare fractional anisotropy (FA) between FH+ and FH? youth. Results FH+ youth showed a trend toward increased discounting behavior and had significantly slower reaction times on the delay discounting paradigm compared to FH? youth. Group differences in FA were seen in several white matter tracts. Furthermore, lower FA in the left inferior longitudinal fasciculus and the right optic radiation statistically mediated the relationship between FH status and slower reaction times on the delay discounting task. Conclusion Youth with a family history of substance abuse have disrupted white matter microstructure, which likely contributes to less efficient cortical processing, and may act as an intrinsic risk-factor contributing to an increased susceptibility of developing AUD. In addition, FHP youth showed a trend toward greater impulsive decision making, possibly representing an inherent personal characteristic that may facilitate substance use onset and abuse in high-risk youth.

Herting, Megan M.; Schwartz, Daniel; Mitchell, Suzanne H.; Nagel, Bonnie J.

2011-01-01

289

Discriminating Schizophrenia and Bipolar Disorder by Fusing FMRI and DTI in A Multimodal CCA+ Joint ICA Model  

PubMed Central

Diverse structural and functional brain alterations have been identified in both schizophrenia and bipolar disorder, but with variable replicability, significant overlap and often in limited number of subjects. In this paper, we aimed to clarify differences between bipolar disorder and schizophrenia by combining fMRI (collected during an auditory oddball task) and diffusion tensor imaging (DTI) data. We proposed a fusion method, “multimodal CCA+ joint ICA’, which increases flexibility in statistical assumptions beyond existing approaches and can achieve higher estimation accuracy. The data collected from 164 participants (62 healthy controls, 54 schizophrenia and 48 bipolar) were extracted into “features” (contrast maps for fMRI and fractional anisotropy (FA) for DTI) and analyzed in multiple facets to investigate the group differences for each pair-wised groups and each modality. Specifically, both patient groups shared significant dysfunction in dorsolateral prefrontal cortex and thalamus, as well as reduced white matter (WM) integrity in anterior thalamic radiation and uncinate fasciculus. Schizophrenia and bipolar subjects were separated by functional differences in medial frontal and visual cortex, as well as WM tracts associated with occipital and frontal lobes. Both patients and controls showed similar spatial distributions in motor and parietal regions, but exhibited significant variations in temporal lobe. Furthermore, there were different group trends for age effects on loading parameters in motor cortex and multiple WM regions, suggesting brain dysfunction and WM disruptions occurred in identified regions for both disorders. Most importantly, we can visualize an underlying function-structure network by evaluating the joint components with strong links between DTI and fMRI. Our findings suggest that although the two patient groups showed several distinct brain patterns from each other and healthy controls, they also shared common abnormalities in prefrontal thalamic WM integrity and in frontal brain mechanisms.

Sui, Jing; Pearlson, Godfrey; Adali, Tulay; Kiehl, Kent A.; Caprihan, Arvind; Liu, Jingyu; Yamamoto, Jeremy; Calhoun, Vince D.

2011-01-01

290

Bulbospinal control of spinal cord pathways generating locomotor extensor activities in the cat  

PubMed Central

Intracellular recording of lumbosacral motoneurones in the decerebrate and partially spinalized cat injected with nialamide and L-dihydroxyphenylalanine (l-DOPA) was used to investigate the interneuronal convergence of two bulbospinal pathways and of the segmental pathways involved with the generation of extensor activities during locomotion. Deiter's nucleus (DN) or the medial longitudinal fasciculus (MLF) was stimulated in alternation with, and in combination with, stimulation of group I afferents from extensor muscles or of contralateral flexor reflex afferents (coFRA). The evoked polysynaptic EPSPs were recorded in extensor motoneurones when long-latency, long-lasting discharges were evoked by the stimulation of coFRA and when the group I autogenetic inhibition in extensors was reversed to polysynaptic excitation. Spatial facilitation was inferred when the amplitude of the EPSPs evoked by the combined stimuli was notably larger than the algebraic sum of the EPSPs evoked by individual stimulation. Both DN (16 motoneurones) and MLF inputs (8 motoneurones) showed spatial facilitation when preceded by coFRA stimuli and both could reset the rhythm of fictive stepping by triggering a precocious extensor phase. MLF showed spatial facilitation with extensor group I inputs in 69 % of trials but DN failed to show spatial facilitation in any cells. These results indicate that DN and MLF project to the coFRA pathways of the extensor half-centre for locomotion and MLF, but not DN, converge on segmental interneurones of the extensor group I pathways. The implications of such convergence patterns on the functional organization of the extensor half-centre are discussed.

Leblond, Hugues; Menard, Ariane; Gossard, Jean-Pierre

2000-01-01

291

Selective asymmetry in a conserved forebrain to midbrain projection.  

PubMed

How the left and right sides of the brain acquire anatomical and functional specializations is not well understood. The zebrafish has proven to be a useful model to explore the genetic basis of neuroanatomical asymmetry in the developing forebrain. The dorsal diencephalon or epithalamus consists of the asymmetric pineal complex and adjacent paired nuclei, the left and right medial habenulae, which in zebrafish larvae, exhibit differences in their size, neuropil density and patterns of gene expression. In all vertebrates, axons from the medial habenular nuclei project within a prominent fiber bundle, the fasciculus retroflexus, to a shared midbrain target, the interpeduncular nucleus of the ventral tegmentum. However, in zebrafish, projections from the left habenula innervate the dorsal and ventral regions of the target nucleus, whereas right habenular efferents project only to the ventral region. A similar dorsoventral difference in habenular connectivity is found in another teleost species, the highly derived southern flounder, Paralichthys lethostima. In this flatfish, directional asymmetry of the habenular projection appears to be independent of the left-right morphology and orientation that an individual adopts post-metamorphosis. Comparative anterograde labeling of the brains of salamanders, frogs and mice reveals that axons emanating from the left and right medial habenulae do not project to different domains, but rather, they traverse the target nucleus in a complementary mirror image pattern. Thus, although the habenulo-interpeduncular conduction system is highly conserved in the vertebrate brain, the stereotypic dorsoventral topography of left-right connections appears to be a feature that is specific to teleosts. PMID:17592620

Kuan, Yung-Shu; Gamse, Joshua T; Schreiber, Alexander M; Halpern, Marnie E

2007-09-15

292

Tissue distribution of Ret, GFRalpha-1, GFRalpha-2 and GFRalpha-3 receptors in the human brainstem at fetal, neonatal and adult age.  

PubMed

Occurrence and localization of receptor components of the glial cell line-derived neurotrophic factor (GDNF) family ligands, the Ret receptor tyrosine kinase and the GDNF family receptor (GFR) alpha-1 to -3, were examined by immunohistochemistry in the normal human brainstem at fetal, neonatal, and adult age. Immunoreactive elements were detectable at all examined ages with uneven distribution and consistent pattern for each receptor. As a rule, the GFRalpha-1 and GFRalpha-2 antisera produced the most abundant and diffuse tissue labelling. Immunoreactive perikarya were observed within sensory and motor nuclei of cranial nerves, dorsal column nuclei, olivary nuclear complex, reticular formation, pontine nuclei, locus caeruleus, raphe nuclei, substantia nigra, and quadrigeminal plate. Nerve fibers occurred within gracile and cuneate fasciculi, trigeminal spinal tract and nucleus, facial, trigeminal, vestibular and oculomotor nerves, solitary tract, medial longitudinal fasciculus, medial lemniscus, and inferior and superior cerebellar peduncles. Occasionally, glial cells were stained. Age changes were appreciable in the distribution pattern of each receptor. On the whole, in the grey matter, labelled perikarya were more frequently observed in pre- and perinatal than in adult specimens; on the other hand, in discrete regions, nerve fibers and terminals were abundant and showed a plexiform arrangement only in adult tissue; finally, distinct fiber systems in the white matter were immunolabelled only at pre- and perinatal ages. The results obtained suggest the involvement of Ret and GFRalpha receptors signalling in processes subserving both the organization of discrete brainstem neuronal systems during development and their functional activity and maintenance in adult life. PMID:17825269

Quartu, Marina; Serra, Maria Pina; Boi, Marianna; Ferretti, Maria Teresa; Lai, Maria Letizia; Del Fiacco, Marina

2007-08-09

293

Altered Development of White Matter in Youth at High Familial Risk for Bipolar Disorder: A Diffusion Tensor Imaging Study  

PubMed Central

Objective To study WM development in youth at high familial risk for BD. White matter (WM) alterations are reported in youth and adults with bipolar disorder (BD). WM undergoes important maturational changes in adolescence. The authors compared age-related changes in WM microstructure using diffusion tensor imaging (DTI) with tract-based spatial statistics in healthy offspring having a parent with BD and healthy controls. Method A total of 45 offspring participated, including 20 healthy offspring with a parent diagnosed with BD (HBO) and 25 healthy control offspring of healthy parents (CONT). All were free of medical and psychiatric disorders. Mean fractional anisotropy (FA), radial diffusivity (RD), and longitudinal diffusivity (L1) were examined using wholebrain analyses, covarying for age. Results Group by age interactions revealed a linear increase in FA, and linear decrease in RD, in CONT in left corpus callosum (CC) and right inferior longitudinal fasciculus (ILF). In HBO, there was a linear decrease in FA and increase in RD, with age in left CC, and no relationship between FA, or RD, and age in right ILF. Curve fitting confirmed linear, and revealed non-linear, relationships between FA, and RD, with age in the above regions in CONT and HBO. Conclusions This is the first study to examine WM in healthy offspring at high familial risk for BD. Results from this cross-sectional study suggest altered development of WM in HBO relative to CONT in CC and temporal associative tracts, which may represent vulnerability markers for future BD and other psychiatric disorders in HBO.

Versace, Amelia; Ladouceur, Cecile D.; Romero, Soledad; Birmaher, Boris; Axelson, David A.; Kupfer, David J.; Phillips, Mary L.

2010-01-01

294

Structure Tensor Informed Fiber Tractography (STIFT) by combining gradient echo MRI and diffusion weighted imaging.  

PubMed

Structural connectivity research in the human brain in vivo relies heavily on fiber tractography in diffusion-weighted MRI (DWI). The accurate mapping of white matter pathways would gain from images with a higher resolution than the typical ~2mm isotropic DWI voxel size. Recently, high field gradient echo MRI (GE) has attracted considerable attention for its detailed anatomical contrast even within the white and gray matter. Susceptibility differences between various fiber bundles give a contrast that might provide a useful representation of white matter architecture complementary to that offered by DWI. In this paper, Structure Tensor Informed Fiber Tractography (STIFT) is proposed as a method to combine DWI and GE. A data-adaptive structure tensor is calculated from the GE image to describe the morphology of fiber bundles. The structure tensor is incorporated in a tractography algorithm to modify the DWI-based tracking direction according to the contrast in the GE image. This GE structure tensor was shown to be informative for tractography. From closely spaced seedpoints (0.5mm) on both sides of the border of 1) the optic radiation and inferior longitudinal fasciculus 2) the cingulum and corpus callosum, STIFT fiber bundles were clearly separated in white matter and terminated in the anatomically correct areas. Reconstruction of the optic radiation with STIFT showed a larger anterior extent of Meyer's loop compared to a standard tractography alternative. STIFT in multifiber voxels yielded a reduction in crossing-over of streamlines from the cingulum to the adjacent corpus callosum, while tracking through the fiber crossings of the centrum semiovale was unaffected. The STIFT method improves the anatomical accuracy of tractography of various fiber tracts, such as the optic radiation and cingulum. Furthermore, it has been demonstrated that STIFT can differentiate between kissing and crossing fiber configurations. Future investigations are required to establish the applicability in more white matter pathways. PMID:22056460

Kleinnijenhuis, Michiel; Barth, Markus; Alexander, Daniel C; van Cappellen van Walsum, Anne-Marie; Norris, David G

2011-10-28

295

Improved sensitivity to cerebral white matter abnormalities in Alzheimer's disease with spherical deconvolution based tractography.  

PubMed

Diffusion tensor imaging (DTI) based fiber tractography (FT) is the most popular approach for investigating white matter tracts in vivo, despite its inability to reconstruct fiber pathways in regions with "crossing fibers." Recently, constrained spherical deconvolution (CSD) has been developed to mitigate the adverse effects of "crossing fibers" on DTI based FT. Notwithstanding the methodological benefit, the clinical relevance of CSD based FT for the assessment of white matter abnormalities remains unclear. In this work, we evaluated the applicability of a hybrid framework, in which CSD based FT is combined with conventional DTI metrics to assess white matter abnormalities in 25 patients with early Alzheimer's disease. Both CSD and DTI based FT were used to reconstruct two white matter tracts: one with regions of "crossing fibers," i.e., the superior longitudinal fasciculus (SLF) and one which contains only one fiber orientation, i.e. the midsagittal section of the corpus callosum (CC). The DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), obtained from these tracts were related to memory function. Our results show that in the tract with "crossing fibers" the relation between FA/MD and memory was stronger with CSD than with DTI based FT. By contrast, in the fiber bundle where one fiber population predominates, the relation between FA/MD and memory was comparable between both tractography methods. Importantly, these associations were most pronounced after adjustment for the planar diffusion coefficient, a measure reflecting the degree of fiber organization complexity. These findings indicate that compared to conventionally applied DTI based FT, CSD based FT combined with DTI metrics can increase the sensitivity to detect functionally significant white matter abnormalities in tracts with complex white matter architecture. PMID:22952880

Reijmer, Yael D; Leemans, Alexander; Heringa, Sophie M; Wielaard, Ilse; Jeurissen, Ben; Koek, Huiberdina L; Biessels, Geert Jan

2012-08-31

296

Associations between white matter microstructure and infants' working memory.  

PubMed

Working memory emerges in infancy and plays a privileged role in subsequent adaptive cognitive development. The neural networks important for the development of working memory during infancy remain unknown. We used diffusion tensor imaging (DTI) and deterministic fiber tracking to characterize the microstructure of white matter fiber bundles hypothesized to support working memory in 12-month-old infants (n=73). Here we show robust associations between infants' visuospatial working memory performance and microstructural characteristics of widespread white matter. Significant associations were found for white matter tracts that connect brain regions known to support working memory in older children and adults (genu, anterior and superior thalamic radiations, anterior cingulum, arcuate fasciculus, and the temporal-parietal segment). Better working memory scores were associated with higher FA and lower RD values in these selected white matter tracts. These tract-specific brain-behavior relationships accounted for a significant amount of individual variation above and beyond infants' gestational age and developmental level, as measured with the Mullen Scales of Early Learning. Working memory was not associated with global measures of brain volume, as expected, and few associations were found between working memory and control white matter tracts. To our knowledge, this study is among the first demonstrations of brain-behavior associations in infants using quantitative tractography. The ability to characterize subtle individual differences in infant brain development associated with complex cognitive functions holds promise for improving our understanding of normative development, biomarkers of risk, experience-dependent learning and neuro-cognitive periods of developmental plasticity. PMID:22989623

Short, Sarah J; Elison, Jed T; Goldman, Barbara Davis; Styner, Martin; Gu, Hongbin; Connelly, Mark; Maltbie, Eric; Woolson, Sandra; Lin, Weili; Gerig, Guido; Reznick, J Steven; Gilmore, John H

2012-09-16

297

Prediction of individual subject's age across the human lifespan using diffusion tensor imaging: a machine learning approach.  

PubMed

Diffusion tensor imaging has the potential to be used as a neuroimaging marker of natural ageing and assist in elucidating trajectories of cerebral maturation and ageing. In this study, we applied a multivariate technique relevance vector regression (RVR) to predict individual subject's age using whole brain fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) from a cohort of 188 subjects aged 4-85 years. High prediction accuracy as derived from Pearson correlation coefficient of actual versus predicted age (FA - r=0.870 p<0.0001; MD - r=0.896 p<0.0001; AD - r=0.895 p<0.0001; RD - r=0.899 p<0.0001) was achieved. Cerebral white-matter regions that contributed to these predictions include; corpus callosum, cingulum bundles, posterior longitudinal fasciculus and the cerebral peduncle. A post-hoc analysis of these regions showed that FA follows a nonlinear rational-quadratic trajectory across the lifespan peaking at approximately 21.8 years. The MD, RD and AD volumes were particularly useful for making predictions using grey matter cerebral regions. These results suggest that diffusion tensor imaging measurements can reliably predict individual subject's age and demonstrate that FA cerebral maturation and ageing patterns follow a non-linear trajectory with a noteworthy peaking age. These data will contribute to the understanding of neurobiology of cerebral maturation and ageing. Most notably, from a neuropsychiatric perspective our results may allow differentiation of cerebral changes that may occur due to natural maturation and ageing, and those due to developmental or neuropsychiatric disorders. PMID:23501046

Mwangi, Benson; Hasan, Khader M; Soares, Jair C

2013-03-14

298

Anatomical basis for the fastigial pressor response.  

PubMed

Electrical stimulation of rostromedial portion of cerebellar fastigial nucleus elicits integrated cardiovascular effects, which are neurally and humorally mediated. In this study, we sought to demonstrate the anatomical substrates of the fastigial pressor response (FPR) in the rat. The response was electrophysiologically localized in anesthetized, paralyzed-ventilated rats. Anterograde transport techniques were used to study the efferent projections of the fastigial pressor area; the distribution of efferent projection cells were then mapped by injecting retrograde tracers into anterogradely labeled sites. Electrolytic lesions were then placed bilaterally in selected brainstem areas in the attempt to block the pressor response. Sites of cerebellar stimulation and of brainstem lesions were subsequently histologically identified. The following lesions abolished the FPR: in nine animals lesions involved portions of the nucleus gigantocellularis dorsalis (NGCd), paramedian reticular formation (PMN) and the nucleus tractus solitarii (NTS) (in two animals fairly selectively the caudal NTS); in two other animals lesions destroyed the rostral ventrolateral medulla (C1 area) and in one animal the area encompassing the dorsal convexity of the superior cerebellar peduncle bordering the locus coeruleus-lateral parabrachial complex; partially effective were unilateral lesions of NGCd and NTS (three), bilateral lesions confined to NGCd and PMN (two), to vestibular complex and uncinate fasciculus (UF) (three), to UF and locus coeruleus (three) and to nucleus reticularis ventralis (two). Ineffective lesions involved A1 area, the nucleus gigantocellularis ventralis (NGCv), the spinal trigeminal nucleus and nucleus reticularis parvocellularis, the A5 area of the ventrolateral pons, the central gray and lateral mesencephalic tegmentum. It seems therefore that the pressor response elicited by stimulation of the cerebellar fastigial nucleus utilizes central specific pathways, as lesions involving other brainstem regions also known to participate in cardiovascular control do not affect the response. Furthermore, the FPR persisted after midbrain decerebration, thus demonstrating that it is organized beneath the midbrain. PMID:12875480

Giuditta, Marianna; Ruggiero, David A; Del Bo, Alberto

2003-01-01

299

Nuclear, internuclear, and supranuclear ocular motor disorders.  

PubMed

In the brainstem, lateral and vertical eye movements are controlled by separate structures, the former mainly in the pons and the latter in the midbrain. The abducens nucleus (VI) in the pons controls all ipsilateral eye movements, i.e., ipsilateral saccades as well as the horizontal vestibulo-ocular reflex (VOR). This nucleus contains the abduction motoneurons, but also the internuclear neurons involved in adduction, passing through the contralateral medial longitudinal fasciculus (MLF) before relaying in the third-nerve nucleus in the midbrain. Lesions affecting the abducens nucleus result in complete ipsilateral eye movement paralysis, and lesions damaging the MLF result in internuclear ophthalmoplegia, whereas an association of these two lesions leads to the "one-and-a-half" syndrome. Ipsilateral saccades are controlled by the ipsilateral paramedian pontine reticular formation located close to the sixth nucleus, whereas the ipsilateral VOR is controlled by the contralateral medial vestibular nucleus. Vertical eye movements are controlled by the third- and fourth-nerve nuclei in the midbrain. A lesion unilaterally affecting the third-nerve nucleus results in an ipsilateral third-nerve paralysis and a contralateral upgaze paralysis because of the decussation of the superior rectus motoneurons, at the level of the third-nerve nuclei. Vertical saccades are controlled by the rostral interstitial nucleus of the MLF (riMLF) located close to the third-nerve nucleus. Downward and upward saccade paralysis results from bilateral riMLF damage whereas upgaze paralysis usually results from a unilateral lesion affecting the region of the posterior commissure, suggesting that the suprareticular control of these two types of vertical saccade is distinct. PMID:21601072

Pierrot-Deseilligny, Charles

2011-01-01

300

[Bilateral internuclear ophthalmoplegia in association with basilar artery occlusive disease].  

PubMed

A 56 year-old man presented with vertigo and the right sided weakness. Neurological examination revealed a lethargic man with good orientation to three spheres. His neck was supple. He had anisocoria, the right pupil being larger than the left by 1.5 mm with sluggish light reaction bilaterally. He had exotropia of the right eye in primary gaze. The abduction of both eyes were full with terminal horizontal nystagmus. The adduction of both eyes were quite limited in each eye. He had a limited upward gaze with poor convergence. These were interpreted as the syndrome of the medial longitudinal fasciculus (MLF) bilaterally. He had a depressed gag reflex on the right side with tongue deviation to the right. He had a mild weakness of the right side limb and also had the right sided hemihyperesthesia including his face to pain and temperature. Twenty four hours after the onset, the left brachial angiography revealed a complete occlusion of the rostral portion of the basilar artery without visualization of the posterior cerebral and superior cerebellar arteries bilaterally. CT scans three days after the onset revealed a low density area in the mid pons with extension rostrally up to the mesencephalon. Four days later he became quadriplegic with bilateral horizontal gaze palsy. No more internuclear ophthalmoplegia is noted on both sides. The midline location of the MLF in the pons, and the separate blood supplies by different paramedian branches of the basilar artery, form the anatomical explanation for the frequent unilaterality of vascular and bilaterality of demyelinating lesions. Bilateral MLF syndrome has been considered almost pathognomonic of multiple sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2350928

Kataoka, S; Hirose, G; Tukada, K; Michishita, H; Yoshikawa, H

1990-02-01

301

TAR DNA-binding protein 43 pathology in a case clinically diagnosed with facial-onset sensory and motor neuronopathy syndrome: an autopsied case report and a review of the literature.  

PubMed

We report an autopsy case of a 48-year-old female clinically diagnosed with facial-onset sensory and motor neuronopathy (FOSMN) syndrome with TAR DNA-binding protein 43 (TDP-43) pathology. She developed paresthesia involving her whole face, right upper extremity and the right side of her upper trunk, followed by dysphagia, dysarthria, muscle atrophy and weakness with fasciculation in both upper extremities. Her symptoms showed a marked cranial and right-sided dominancy. She had anti-sulfoglucuronyl paragloboside (SGPG) IgG and anti-myelin-associated glycoprotein (MAG) IgG, and repeatedly showed limited response to immunotherapies. Her disease was essentially progressive, culminating in death due to respiratory failure three and a half years after onset. The autopsy revealed severe degeneration of the nuclei of the right trigeminal nerve and right facial nerve and widespread TDP-43-positive glial inclusions in the brainstem tegmentum. Neurons in the hypoglossal nerve nuclei were also shrunken and lost, with TDP-43-positive neuronal inclusions. Neuronal loss and gliosis in the anterior horn, predominantly in the cervical cord, were prominent with TDP-43-positive skein-like inclusions. Bilateral ventral roots were obviously atrophic. Spinal tract degeneration was also prominent in the ventral columns, essentially sparing the anterior corticospinal tracts at the cervical cord level. Additionally there was severe myelin pallor in the right spinal trigeminal tract and right fasciculus cuneatus of the cervical cord. The right spinal root ganglion showed numerous Nageotte's nodules and focal lymphocytic infiltration. The present case manifested FOSMN syndrome clinically, while the pathological findings suggested a motor neuron disease like TDP-43 proteinopathy and a possible involvement of immune-mediated neuropathy. PMID:23849263

Sonoda, Keita; Sasaki, Kensuke; Tateishi, Takahisa; Yamasaki, Ryo; Hayashi, Shintaro; Sakae, Nobutaka; Ohyagi, Yasumasa; Iwaki, Toru; Kira, Jun-ichi

2013-07-09

302

Grey and white matter abnormalities in temporal lobe epilepsy with and without mesial temporal sclerosis.  

PubMed

Temporal lobe epilepsy with (TLE-mts) and without (TLE-no) mesial temporal sclerosis display different patterns of cortical neuronal loss, suggesting that the distribution of white matter damage may also differ between the sub-groups. The purpose of this study was to examine patterns of white matter damage in TLE-mts and TLE-no and to determine if identified changes are related to neuronal loss at the presumed seizure focus. The 4 T diffusion tensor imaging (DTI) and T1-weighted data were acquired for 22 TLE-mts, 21 TLE-no and 31 healthy controls. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) maps and voxel-based morphometry (VBM) was used to identify grey matter (GM) volume atrophy. Correlation analysis was conducted between the FA maps and neuronal loss at the presumed seizure focus. In TLE-mts, reduced FA was identified in the genu, body and splenium of the corpus callosum, bilateral corona radiata, cingulum, external capsule, ipsilateral internal capsule and uncinate fasciculus. In TLE-no, FA decreases were identified in the genu, the body of the corpus callosum and ipsilateral anterior corona radiata. The FA positively correlated with ipsilateral hippocampal volume. Widespread extra-focal GM atrophy was associated with both sub-groups. Despite widespread and extensive GM atrophy displaying different anatomical patterns in both sub-groups, TLE-mts demonstrated more extensive FA abnormalities than TLE-no. The microstructural organization in the corpus callosum was related to hippocampal volume in both patients and healthy subjects demonstrating the association of these distal regions. PMID:23754695

Scanlon, Cathy; Mueller, Susanne G; Cheong, Ian; Hartig, Miriam; Weiner, Michael W; Laxer, Kenneth D

2013-06-11

303

Reproducibility and biases in high field brain diffusion MRI: An evaluation of acquisition and analysis variables.  

PubMed

Diffusion tensor imaging (DTI) of in-vivo human brain provides insights into white matter anatomical connectivity, but little is known about measurement difference biases and reliability of data obtained with last generation high field scanners (>3T) as function of MRI acquisition and analyses variables. Here we assess the impact of acquisition (voxel size: 1.8×1.8×1.8, 2×2×2 and 2.5×2.5×2.5mm(3), b-value: 700, 1000 and 1300s/mm(2)) and analysis variables (within-session averaging and co-registration methods) on biases and test-retest reproducibility of some common tensor derived quantities like fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity in a group of healthy subjects at 4T in three regions: arcuate fasciculus, corpus callosum and cingulum. Averaging effects are also evaluated on a full-brain voxel based approach. The main results are: i) group FA and MD reproducibility errors across scan sessions are on average double of those found in within-session repetitions (?1.3 %), regardless of acquisition protocol and region; ii) within-session averaging of two DTI acquisitions does not improve reproducibility of any of the quantities across sessions at the group level, regardless of acquisition protocol; iii) increasing voxel size biased MD, axial and radial diffusivities to higher values and FA to lower values; iv) increasing b-value biased all quantities to lower values, axial diffusivity showing the strongest effects; v) the two co-registration methods evaluated gave similar bias and reproducibility results. Altogether these results show that reproducibility of FA and MD is comparable to that found at lower fields, not significantly dependent on pre-processing and acquisition protocol manipulations, but that the specific choice of acquisition parameters can significantly bias the group measures of FA, MD, axial and radial diffusivities. PMID:23623031

Papinutto, Nico Dario; Maule, Francesca; Jovicich, Jorge

2013-04-24

304

GENE NETWORK EFFECTS ON BRAIN MICROSTRUCTURE AND INTELLECTUAL PERFORMANCE IDENTIFIED IN 472 TWINS  

PubMed Central

A major challenge in neuroscience is finding which genes affect brain integrity, connectivity, and intellectual function. Discovering influential genes holds vast promise for neuroscience, but typical genome-wide searches assess around one million genetic variants one-by-one, leading to intractable false positive rates, even with vast samples of subjects. Even more intractable is the question of which genes interact and how they work together to affect brain connectivity. Here we report a novel approach that discovers which genes contribute to brain wiring and fiber integrity at all pairs of points in a brain scan. We studied genetic correlations between thousands of points in human brain images from 472 twins and their non-twin siblings (mean age: 23.7±2.1 SD years; 193 M/279 F). We combined clustering with genome-wide scanning to find brain systems with common genetic determination. We then filtered the image in a new way to boost power to find causal genes. Using network analysis, we found a network of genes that affect brain wiring in healthy young adults. Our new strategy makes it more computationally tractable to discover genes that affect brain integrity. The gene network showed small-world and scale-free topologies, suggesting efficiency in genetic interactions, and resilience to network disruption. Genetic variants at hubs of the network influence intellectual performance by modulating associations between performance intelligence quotient (IQ) and the integrity of major white matter tracts, such as the callosal genu and splenium, cingulum, optic radiations, and the superior longitudinal fasciculus.

Chiang, Ming-Chang; Barysheva, Marina; McMahon, Katie L.; de Zubicaray, Greig I.; Johnson, Kori; Montgomery, Grant W.; Martin, Nicholas G.; Toga, Arthur W.; Wright, Margaret J.; Shapshak, Paul; Thompson, Paul M.

2012-01-01

305

Neuropathology of chronic GM2 gangliosidosis due to hexosaminidase A deficiency.  

PubMed

Autopsy studies of late-onset GM2 gangliosidosis are sparse and only one adult case is on record. The case of partial Hex A deficiency presented here started in childhood as spinal muscular atrophy which progressed slowly over 4 decades. Cognitive function remained intact throughout the entire course, but during the last few years of life allodynia supervened. The patient died at 44 years of age. In good correlation with clinical observations the autopsy findings showed the most severe accumulation of lipid and consequent regressive change in the anterior horns of the spinal cord. Extensive but less severe storage was found in other spinal cord neurons, brain stem and selected basal ganglia. Cerebral cortex was virtually spared by storage but was the site of excessive formation of lipofuscin which was also present in many other neurons in the CNS. Marked storage and ganglionic loss was also found in the dorsal root ganglia, and the fasciculus gracilis was severely depleted of myelinated fibers. Electron microscopy showed accumulated gangliosides almost exclusively in the form of single and coalescing zebra bodies. In conclusion, the pathology in this case of chronic GM2 gangliosidosis, though in part conforming with previous observations, differed in several aspects. First, the cerebral cortex was--with only a few exceptions--free of ganglioside storage. Also spared was the cerebellum. In addition, homogeneous accumulation of zebra bodies contrasted with heterogeneity of neuronal inclusions found in other chronic cases. Finally, the involvement of sensory neurons was prominent and potentially related to allodynia. Molecular study of HEXA gene in this patient showed an TATC1278/? genotype. PMID:18808061

Kornfeld, M

306

Evidence for fractional anisotropy and mean diffusivity white matter abnormalities in the internal capsule and cingulum in patients with obsessive-compulsive disorder  

PubMed Central

Background There is evidence to suggest that obsessive–compulsive disorder (OCD) is associated with structural abnormalities in cortico–striato–thalamic circuits, yet the extent of white matter abnormalities is not well established. In this study, we used diffusion tensor imaging (DTI) to examine white matter integrity in specific regions of interest (ROIs) in patients with OCD. Methods Patients with OCD and sex-, age- and IQ-matched healthy controls underwent DTI. The primary objective was to explore whether patients with OCD had white matter abnormalities in the anterior limb of the internal capsule (ALIC), the uncinate fasciculus, the genu of the corpus callosum and the cingulum. The secondary objective was to evaluate the relation between fractional anisotropy and mean diffusivity in these ROIs and other clinical variables (including age at onset of OCD, OCD severity and levels of depressive and anxiety symptomatology) in patients with OCD. Results There were 15 patients and 17 controls enrolled in our study. Compared with healthy controls, patients with OCD showed increased fractional anisotropy in bilateral regions of the ALIC adjacent to the body of the caudate, as well as decreased fractional anisotropy in the right anterior limb near the head of the caudate. Patients also had decreased mean diffusivity in the body of the right cingulum and the left anterior cingulum compared with controls. Correlational analyses revealed significant associations of fractional anisotropy and mean diffusivity in select circuits with OCD, depression and anxiety severity scores. Limitations Inclusion of patients with OCD receiving pharmacotherapy may have been a limitation. In addition, the patients were heterogeneous in terms of their obsessive–compulsive symptom profiles; we did not distinguish between different obsessive–compulsive symptom dimensions. Conclusion The study results provide further evidence for OCD-related white matter abnormalities in the ALIC and cingulum, consistent with a corticostriatal model of OCD.

Lochner, Christine; Fouche, Jean-Paul; du Plessis, Stefan; Spottiswoode, Bruce; Seedat, Soraya; (Psych), MMed; Fineberg, Naomi; Chamberlain, Samuel R.; Stein, Dan J.

2012-01-01

307

Mobility decline in the elderly relates to lesion accrual in the splenium of the corpus callosum.  

PubMed

In a previous cross-sectional study on baseline data, we demonstrated that the volume of brain white matter hyperintensities (WMH) in the splenium of corpus callosum (SCC) predicted the current mobility function of older persons. The primary aim of this follow-up study was to determine the relation of WMH volume change in SCC (SCC-?WMH) with change in mobility measures. A secondary aim was to characterize the global and regional progression of WMH. Mobility function and WMH burden were evaluated at baseline and at 2 years in 77 community-dwelling individuals (baseline age, 82 ± 4). Regional WMH in SCC, as well as genu and body of corpus callosum, subregions of corona radiata, and superior longitudinal fasciculus were determined using a white matter parcellation atlas. The total WMH volume increased 3.3 ± 3.5 ml/year, mainly through enlargement. Significant WMH increases were observed in all selected regions, particularly within the corona radiata. While at baseline and follow-up we observed correlations between WMH burden and several measures of mobility, longitudinal change correlated only with change in chair rise (CR). SCC-?WMH showed the highest correlation (r =?-0.413, p = 0.0002) and was the best regional predictor of CR decline (OR = 1.5, r(2)?= 0.3). The SCC-?WMH was more than five times larger in the CR-decline group compared to the no-decline group (p = 0.0003). The SCC-?WMH (top quartile) showed a higher sensitivity/specificity for CR decline compared to change in total WMH, 63/88% versus 52/84%, respectively. The findings suggest that accrual of WMHs in posterior areas of the brain supporting inter-hemispheric integration and processing of visual-spatial information is a mechanism contributing to age-related mobility deterioration. PMID:21505765

Moscufo, Nicola; Wolfson, Leslie; Meier, Dominik; Liguori, Maria; Hildenbrand, Peter G; Wakefield, Dorothy; Schmidt, Julia A; Pearlson, Godfrey D; Guttmann, Charles R G

2011-04-20

308

Pervasive microstructural abnormalities in autism: a DTI study  

PubMed Central

Background Recent studies have reported abnormal functional connectivity patterns in the brains of people with autism that may be accompanied by decreases in white matter integrity. Since autism is a developmental disorder, we aim to investigate the nature and location of decreases in white and grey matter integrity in an adolescent sample while accounting for age. Methods We used structural (T1) imaging to study brain volumetrics and diffusion tensor imaging (DTI) to investigate white and grey matter integrity in people with autism. We obtained magnetic resonance images for adolescents aged 12–18 years with high-functioning autism and from matched controls. Fractional anisotropy and mean diffusivity, as well as grey and white matter volumetrics were analyzed. Results There were 17 participants with autism and 25 matched controls included in this study. Participants with autism had lower fractional anisotropy in the left and right superior and inferior longitudinal fasciculus, but this effect was not significant after adjusting for age and intelligence quotient (IQ). The kurtosis of the white matter fractional anisotropy probability distribution was higher in this participant group, with and without adjustment for age and IQ. Most notably, however, the mean diffusivity levels were markedly increased in the autism group throughout the brain, and the mean diffusivity probability distributions of both grey and white matter were shifted toward a higher value, particularly with age and IQ adjustment. No volumetric differences in grey and white matter were found. Limitations We corrected for age and IQ using a linear model. The study was also limited by its sample size, investigated age range and cross-sectional design. Conclusion The findings suggest that autism is characterized by a generalized reduction of white matter integrity that is associated with an increase of interstitial space. The generalized manifestation of the white matter abnormalities provides an important new perspective on autism as a connectivity disorder.

Groen, Wouter B.; Buitelaar, Jan K.; van der Gaag, Rutger J.; Zwiers, Marcel P.

2011-01-01

309

Structural correlates of skilled performance on a motor sequence task  

PubMed Central

The brain regions functionally engaged in motor sequence performance are well-established, but the structural characteristics of these regions and the fiber pathways involved have been less well studied. In addition, relatively few studies have combined multiple magnetic resonance imaging (MRI) and behavioral performance measures in the same sample. Therefore, the current study used diffusion tensor imaging (DTI), probabilistic tractography, and voxel-based morphometry (VBM) to determine the structural correlates of skilled motor performance. Further, we compared these findings with fMRI results in the same sample. We correlated final performance and rate of improvement measures on a temporal motor sequence task (TMST) with skeletonized fractional anisotropy (FA) and whole brain gray matter (GM) volume. Final synchronization performance was negatively correlated with FA in white matter (WM) underlying bilateral sensorimotor cortex—an effect that was mediated by a positive correlation with radial diffusivity. Multi-fiber tractography indicated that this region contained crossing fibers from the corticospinal tract (CST) and superior longitudinal fasciculus (SLF). The identified SLF pathway linked parietal and auditory cortical regions that have been shown to be functionally engaged in this task. Thus, we hypothesize that enhanced synchronization performance on this task may be related to greater fiber integrity of the SLF. Rate of improvement on synchronization was positively correlated with GM volume in cerebellar lobules HVI and V—regions that showed training-related decreases in activity in the same sample. Taken together, our results link individual differences in brain structure and function to motor sequence performance on the same task. Further, our study illustrates the utility of using multiple MR measures and analysis techniques to specify the interpretation of structural findings.

Steele, Christopher J.; Scholz, Jan; Douaud, Gwenaelle; Johansen-Berg, Heidi; Penhune, Virginia B.

2012-01-01

310

White matter abnormalities in Parkinson's disease patients with glucocerebrosidase gene mutations.  

PubMed

Glucocerebrosidase gene mutations represent a genetic risk factor for the development of Parkinson's disease. This study investigated brain alterations in Parkinson's disease patients carrying heterozygous glucocerebrosidase gene mutations using structural and diffusion tensor magnetic resonance imaging. Among 360 Parkinson's disease patients screened for glucocerebrosidase gene mutations, 19 heterozygous mutation carriers (5.3%) were identified. Of these, 15 patients underwent a neuropsychological evaluation and a magnetic resonance imaging scan. Sixteen age- and sex-matched healthy controls and 14 idiopathic Parkinson's disease patients without glucocerebrosidase gene mutations were also studied. Tract-based spatial statistics was used to perform a white matter voxel-wise analysis of diffusion tensor magnetic resonance imaging metrics. Mean fractional anisotropy values were obtained from white matter tracts of interest. Voxel-based morphometry was used to assess gray-matter atrophy. Cognitive deficits were found in 9 mutation carrier patients (60%). Compared with controls, Parkinson's disease patients carrying glucocerebrosidase gene mutations showed decreased fractional anisotropy in the olfactory tracts, corpus callosum, and anterior limb of the internal capsule bilaterally, as well as in the right anterior external capsule, and left cingulum, parahippocampal tract, parietal portion of the superior longitudinal fasciculus, and occipital white matter. Mutation carrier patients also had decreased fractional anisotropy of the majority of white matter tracts compared with Parkinson's disease patients with no mutations. No white matter abnormalities were found in Parkinson's disease patients without glucocerebrosidase gene mutations. No gray matter difference was found between patients and controls. In Parkinson's disease patients, verbal fluency scores correlated with white matter abnormalities. Parkinson's disease patients carrying glucocerebrosidase gene mutations experience a distributed pattern of white matter abnormalities involving the interhemispheric, frontal corticocortical, and parahippocampal tracts. White matter pathology in these patients may have an impact on the clinical manifestations of the disease, including cognitive impairment. PMID:23418083

Agosta, Federica; Kostic, Vladimir S; Davidovic, Kristina; Kresojevi?, Nikola; Sarro, Lidia; Svetel, Marina; Stankovi?, Iva; Comi, Giancarlo; Klein, Christine; Filippi, Massimo

2013-02-15

311

[Cognitive vulnerability to alcohol dependence: Related neuroanatomic endophenotypes.  

PubMed

INTRODUCTION: Executive function impairments and high level of impulsivity may constitute heritable endophenotypes that confer predisposition for alcohol dependence. Brain volume abnormalities have also been reported in young, alcohol-naïve subjects at high risk (HR) for alcohol dependence, and linked to cognitive dysfunction. METHODS: This paper presents a literature review of magnetic resonance imaging (MRI) studies that examined brain volumes in adolescent/young adult HR offspring from families with multiple cases of alcohol dependence compared to low risk controls with no family history of alcohol or drug misuse. In some of these studies, executive functioning and externalizing symptoms were also assessed. RESULTS: In HR subjects, local white matter volume deficits were found in the corpus callosum and in the right orbito-frontal cortex, and lower fractional anisotropy in the left inferior longitudinal fasciculus and in the right optic radiation. Altered fronto-cerebellar connectivity has also been reported. Diminished gray matter volume of the cerebellar cortex was found in HR subjects, in the frontal, cyngulate and para-hippocampal gyri, and also in the amygdala, the thalamus and the cerebellum. These structural abnormalities have been associated with higher impulsivity level and executive function impairments, themselves markers of vulnerability to alcoholism. These premorbid cerebral abnormalities may increase the risk for developing an alcohol use disorder in HR subjects through atypical control processing. CONCLUSION: Brain abnormalities may potentially constitute an abnormal neural network that might underlie the risk towards alcohol dependence. These circuitry abnormalities might contribute to the reward deficiency, as well as impaired response inhibition that predict impulsive spectrum behavior, which are thought to represent the inherited vulnerability to alcohol dependence in HR individuals. PMID:23541231

Seigneurie, A-S; Guérin Langlois, C; Limosin, F

2013-03-26

312

Usefulness of Diffusion Tensor Tractography in Pediatric Epilepsy Surgery  

PubMed Central

Purpose This study was conducted to assess the clinical relevance of diffusion tensor tractography (DTT) in pre- and post-operative evaluations of childhood epilepsy surgery. Materials and Methods Seventy-two patients who received epilepsy surgery between March 2004 and July 2008 were retrospectively analyzed (M : F=40 : 32, ages of 3 months to 24 years, mean age=8.9 years). DTT was performed using a 3.0 T scanner and single-shot spin-echo echo-planar imaging with 32-different diffusion gradient directions. We reviewed the data focusing on the type of surgery, final pathological diagnosis, and how the DTT data were clinically used. Results The most common form of childhood epilepsy surgery was complete resection of an epileptogenic lesion (n=52, 72.2%). The reported etiologies included cortical dysplasia (n=32, 44.4%), hippocampal sclerosis (n=9, 12.5%), brain tumors (n=7, 9.7%), and non-pathologic lesions (n=4, 5.6%) in the final diagnoses. Twenty-one dysplastic cortexes and four brain tumors involved an approximal relationship with the corticospinal tract (n=18), optic radiation (n=2), and arcuate fasciculus (n=5). Additionally, although DTT demonstrated white matter tracts clearly, DTT in the hippocampal sclerosis did not provide any additional information. In cases of callosotomy (n=18, 25%), post-operative DTT was utilized for the evaluation of complete resection in all patients. DTT information was not used in functional hemispherectomy (n=2, 2.8%). Conclusion Preoperatively, DTT was a useful technique in cases of cortical dysplasia and brain tumors, and in cases with callosotomy, postoperatively. DTT should be included among the routine procedures performed in management of epilepsy.

Lee, Mi-Jung; Kim, Heung Dong; Lee, Joon Soo; Kim, Dong-Seok

2013-01-01

313

Quantitative Tract-Specific Measures of Uncinate and Cingulum in Major Depression Using Diffusion Tensor Imaging  

PubMed Central

Previous findings suggested the role of the prefrontal cortex, hippocampus, and cingulate gyrus in major depressive disorders (MDD), but the white matter microstructural abnormalities of the fibers connecting these brain structures are not known. The purpose of this study was to test the hypothesis that white matter abnormalities are present in association fibers of the uncinate fasciculus (UF) and cingulum bundle (CB) among MDD subjects. A total of 21 MDD subjects aged between 30 and 65 years and 21 age-matched healthy controls (HC) were recruited. All subjects were right-handed and without history of diabetes or other cardiac diseases. We extracted quantitative tract-specific measures based on diffusion tensor imaging tractography to examine both diffusivity and geometric properties of the UF and CB. Significantly decreased fractional anisotropy (FA) and increased radial diffusivity of the right UF were observed in MDD patients compared with HC (p<0.05), while their geometric characteristics remained relatively unchanged. Among MDD subjects, depression severity had a significant negative correlation with normalized number of fibers (NNF) in the right UF (r=?0.53, p=0.02). We also found significant age effect (oldR) in both groups in the FA measure of the CB. Our study demonstrates novel findings of white matter microstructural abnormalities of the right UF in MDD. In the MDD group, the severity of depression is associated with reduced NNF in the right UF. These findings have implications for both clinical manifestations of depression as well as its pathophysiology.

Zhang, Aifeng; Leow, Alex; Ajilore, Olusola; Lamar, Melissa; Yang, Shaolin; Joseph, Josh; Medina, Jennifer; Zhan, Liang; Kumar, Anand

2012-01-01

314

Host Brain Regulation of Fetal Locus Coeruleus Neurons Grafted to the Hippocampus in 6-Hydroxydopamine-Treated Rats. An Intracerebral Microdialysis Study.  

PubMed

Release properties of intrahippocampal transplants of noradrenergic neurons were monitored by microdialysis in awake and halothane-anaesthetized rats. Fetal locus coeruleus neurons were implanted as a cell suspension into hippocampi deprived of their innate noradrenalin (NA) innervation by intraventricular 6-hydroxydopamine treatment. Dialysis probes of the loop type were implanted into the dorsal hippocampus 1 - 2 days before each experiment, i.e. 7 - 11 months after grafting. Age-matched intact and lesion-only animals served as controls. Microscopic analysis showed a graft-derived tyrosine hydroxylase immunoreactive, presumably noradrenergic, fibre network throughout the dorsal hippocampal formation, surrounding the probe site. The innervation density varied from sub- to supranormal. The grafts restored baseline NA release in the graft-reinnervated hippocampus to near-normal levels both in awake and halothane-anaesthetized animals. Potassium chloride (100 mM) in the perfusion fluid induced a dramatic increase in NA release that was similar in magnitude in the grafted and intact hippocampi. A NA uptake blocker (desipramine) added to the perfusion fluid at 5 microM induced a similar increase in NA output in the grafted and intact hippocampi, and the output was substantially reduced by tetrodotoxin, added at 1 microM in the presence of uptake blockade. Electrical stimulation of the lateral habenular nucleus (15 Hz, 0.5 mA) in halothane-anaesthetized rats induced a significant increase in NA output both in the intact and grafted hippocampi. This effect was abolished by transection of the fasciculus retroflexus, which carries the efferent projections of the habenular complex. Behavioural activation through handling induced a consistent increase in NA release only in the intact animals, but in a few grafted rats (which also responded to habenular stimulation) the NA output was clearly elevated by handling. Forced immobilization induced a significant increase in NA output both in the intact and grafted hippocampi, but in the grafted ones the response was somewhat smaller and more transient. In the same set of animals, swimming in warm water (25 - 30 degrees C) induced a sharp increase in NA output in the intact animals, whereas only one of the grafted rats responded by increased NA output. The results indicate that the locus coeruleus grafts, despite their ectopic location, can become functionally integrated with the host brain, and that the activity of the transplanted noradrenergic neurons can, under some circumstances, be modulated from the host brain in response to environmental challenges. PMID:12106457

Kalén, Peter; Cenci, M. Angela; Lindvall, Olle; Björklund, Anders

1991-01-01

315

Regional differences in the regulation of dopamine and noradrenaline release in medial frontal cortex, nucleus accumbens and caudate-putamen: a microdialysis study in the rat.  

PubMed

Dopamine (DA) and noradrenaline (NA) extracellular levels have been measured by microdialysis in the medial frontal cortex (MFC), nucleus accumbens (NAc) and caudate-putamen (CP) under baseline conditions in awake and halothane-anaesthetized rats, and after application of three types of stimuli which are likely to activate the brainstem catecholaminergic systems: mild stressors (handling and tail pinch), rewarded behavior (eating palatable food without prior food deprivation) and electrical stimulation of the lateral habenular nucleus. Changes were studied with and without uptake blockade (10 microM nomifensine in the perfusion fluid). The influence of calcium concentration (1.2 or 2.3 mM in the perfusion fluid) on DA and NA overflow was tested in some cases. Handling and tail pinch stimulated both DA and NA overflow in MFC, and enhanced NA overflow in NAc. By contrast, these mildly stressful stimuli had only marginal effects on DA overflow in NAc and no effects on either DA or NA overflow in CP. Eating behavior was accompanied by increased DA and NA overflow in MFC but had no effect in NAc. These regional differences were similar also when the manipulations were applied under uptake blockade, which indicates that the more pronounced changes seen in MFC did not simply reflect a more sparse innervation (i.e. lower density of uptake sites) in the MFC compared to the more densely innervated NAc and CP areas. Stimulation of the lateral habenula induced a 2-3-fold increase in NA overflow in both MFC, NAc and CP but had no consistent effect on DA overflow in any region. The effect on NA release was abolished by a transection of the ipsilateral fasciculus retroflexus (which carries the efferent output of the lateral habenula). The results show that the forebrain DA and NA projections to cortical and striatal targets are differentially regulated during ongoing behavior, that the mesocortical and mesostriatal DA systems respond quite differently to stressful and rewarding stimuli; and that the NA projection to MFC (like the dopaminergic one) is more responsive to stressful and rewarding stimuli than the ones innervating the striatum (NAc and CP). The results support the view that environmental stimuli evoking emotional arousal (whether aversive or non-aversive) are accompanied by increased DA and NA release above all in the MFC and only to a minor extent in limbic and striatal areas. PMID:1393530

Cenci, M A; Kalén, P; Mandel, R J; Björklund, A

1992-05-29

316

Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.  

PubMed

Hereditary spastic paraplegia (HSP) is a syndrome designation describing inherited disorders in which lower extremity weakness and spasticity are the predominant symptoms. There are more than 50 genetic types of HSP. HSP affects individuals of diverse ethnic groups with prevalence estimates ranging from 1.2 to 9.6 per 100,000. Symptoms may begin at any age. Gait impairment that begins after childhood usually worsens very slowly over many years. Gait impairment that begins in infancy and early childhood may not worsen significantly. Postmortem studies consistently identify degeneration of corticospinal tract axons (maximal in the thoracic spinal cord) and degeneration of fasciculus gracilis fibers (maximal in the cervico-medullary region). HSP syndromes thus appear to involve motor-sensory axon degeneration affecting predominantly (but not exclusively) the distal ends of long central nervous system (CNS) axons. In general, proteins encoded by HSP genes have diverse functions including (1) axon transport (e.g. SPG30/KIF1A, SPG10/KIF5A and possibly SPG4/Spastin); (2) endoplasmic reticulum morphology (e.g. SPG3A/Atlastin, SPG4/Spastin, SPG12/reticulon 2, and SPG31/REEP1, all of which interact); (3) mitochondrial function (e.g. SPG13/chaperonin 60/heat-shock protein 60, SPG7/paraplegin; and mitochondrial ATP6); (4) myelin formation (e.g. SPG2/Proteolipid protein and SPG42/Connexin 47); (5) protein folding and ER-stress response (SPG6/NIPA1, SPG8/K1AA0196 (Strumpellin), SGP17/BSCL2 (Seipin), "mutilating sensory neuropathy with spastic paraplegia" owing to CcT5 mutation and presumably SPG18/ERLIN2); (6) corticospinal tract and other neurodevelopment (e.g. SPG1/L1 cell adhesion molecule and SPG22/thyroid transporter MCT8); (7) fatty acid and phospholipid metabolism (e.g. SPG28/DDHD1, SPG35/FA2H, SPG39/NTE, SPG54/DDHD2, and SPG56/CYP2U1); and (8) endosome membrane trafficking and vesicle formation (e.g. SPG47/AP4B1, SPG48/KIAA0415, SPG50/AP4M1, SPG51/AP4E, SPG52/AP4S1, and VSPG53/VPS37A). The availability of animal models (including bovine, murine, zebrafish, Drosophila, and C. elegans) for many types of HSP permits exploration of disease mechanisms and potential treatments. This review highlights emerging concepts of this large group of clinically similar disorders. PMID:23897027

Fink, John K

2013-07-30

317

Prenatal cannabinoid and gene expression for neural adhesion molecule L1 in the fetal rat brain.  

PubMed

The consumption by women of cannabis derivatives during pregnancy and/or lactation affects the development of their offspring because like other psychoactive drugs, cannabinoids, the psychoactive ingredients of marijuana, can cross the placental barrier and be secreted into the maternal milk. Through this way, cannabinoids are able to affect the expression of key genes for neural developmental leading to neurotransmitter and behavioral disturbances. In this present study, we wanted to explore the influence of prenatal cannabinoid exposure on the gene expression of a key protein for brain development, the neural adhesion molecule L1, which plays an important role in processes of cell proliferation and migration, neuritic elongation and guidance, and synaptogenesis. To this end, pregnant rats were daily treated with delta9-tetrahydrocannabinol (delta9-THC) since the 5th day of gestation up to the day before birth (GD21), day at which rats were killed and their pups removed for analysis of L1-mRNA levels in different brain structures. Our results confirmed that the levels of L1 transcripts were significantly increased after prenatal delta9-THC exposure in several regions such as the fimbria, stria terminalis, stria medullaris and corpus callosum, which share the properties of being white matter regions and containing, exclusively during development, an abundant population of cannabinoid CB1 receptors, the major targets for the action of plant-derived cannabinoids. L1-mRNA levels were also increased in grey matter structures such as the septum nuclei and the habenula, but remained unchanged in most of the grey matter structures analyzed (cerebral cortex, basolateral amygdaloid nucleus, hippocampus, thalamic and hypothalamic nuclei, basal ganglia and subventricular zones) and also in a few white matter structures (fornix and fasciculus retroflexus). An important aspect of these observations is that the increase in L1-mRNA levels reached statistical significance only in the case of delta9-THC-exposed males but not in the case of delta9-THC-exposed females where only trends or no effects were detected, this supporting previous evidence on a sexual dimorphism, with greater effects in male fetuses, for the action of cannabinoids in the developing brain. In summary, cannabinoids seem to influence the expression of L1 in specific brain structures during the prenatal period, which, considering the role played by this protein in different events related to neural development, might explain the neurotransmitter and behavioral disturbances reported after prenatal consumption of marijuana. PMID:15068010

Gómez, María; Hernández, Mariluz; Johansson, Björn; de Miguel, Rosario; Ramos, José Antonio; Fernández-Ruiz, Javier

2003-12-30

318

The Prognosis of Allocentric and Egocentric Neglect: Evidence from Clinical Scans  

PubMed Central

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome.

Chechlacz, Magdalena; Rotshtein, Pia; Roberts, Katherine L.; Bickerton, Wai-Ling; Lau, Johnny K. L.; Humphreys, Glyn W.

2012-01-01

319

A case of 'ping-pong' gaze of unknown cause.  

PubMed

A 66 year-old Indian gentleman with a background of type II diabetes, Crohn's disease and previously treated tuberculosis presented with double vision and unsteadiness. He was found to have a right-sided internuclear opthalmoplegia (INO) along with weakness and fasciculations in the lower limbs associated with brisk reflexes and an ataxic gait. An MRI scan of the brain and spinal cord revealed multiple supratentorial and infratentorial lesions. There was a hyperintensity in the right medial longitudinal fasciculus, which was felt to explain the INO. Cord and nerve root changes were also present. A CT angiogram of the brain was unrevealing. A lumbar puncture showed a mildly cellular CSF. CSF protein was 1.24 g/L and CSF glucose was 3.0 mmol/L compared to the paired plasma sample of 10.4 mmol/L. CSF ACE was raised at 1.59 µmol/L. Lactate dehydrogenase was raised at 773IU/L. CSF microbiology, immunology, cytology and flow cytometry were unrevealing. The clinical diagnosis at the time was neurosarcoidosis. The patient was managed with prednisolone and azathioprine. His condition worsened and his Glasgow Coma Scale score dropped requiring admission to the Intensive Care Unit. Whilst on ICU, the patient's eyes began deviating conjugately from one lateral side to the other without any rest period, the cycle lasting around 3 seconds. This was an example of "ping-pong gaze". Ping pong' gaze (PPG) is a term used to define slow conjugate eye deviation from one lateral side to the other with a fixed frequency. The term was coined by Selenick in 1976 after observing the phenomenon in a patient with a cerebellar haemorrhage.(1) PPG has been chiefly observed in unconscious patients with bilateral cerebral impairment. It has, however been described in further cases of cerebellar haemorrhage,(2) tricyclic toxicity(3) and monoamine oxidase inhibitor toxicity.(4) Different pathophysiological mechanisms have been described, most involving the lack of cortical inhibition on the horizontal gaze centres in the brain stem. This lack of input may permit vestibular or other nuclei to act as pacemakers.(5) The majority of cases have been described in patients with persistent vegetative state however it has been demonstrated in awake patients.(2) Unfortunately the patient's condition did not improve and he died. Post-mortem findings from the central nervous system confirmed a diagnosis of intravascular large B-cell lymphoma. In this case the cause of PPG was severe bihemispheric brain injury secondary to intravascular large B-cell lymphoma, a disease which can present with a wide variety of symptoms and often evades diagnosis. PMID:24108884

Bedford, Jonathan

2013-11-01

320

Development of cerebral fiber pathways in cats revealed by diffusion spectrum imaging.  

PubMed

Examination of the three-dimensional axonal pathways in the developing brain is key to understanding the formation of cerebral connectivity. By tracing fiber pathways throughout the entire brain, diffusion tractography provides information that cannot be achieved by conventional anatomical MR imaging or histology. However, standard diffusion tractography (based on diffusion tensor imaging, or DTI) tends to terminate in brain areas with low water diffusivity, indexed by low diffusion fractional anisotropy (FA), which can be caused by crossing fibers as well as fibers with less myelin. For this reason, DTI tractography is not effective for delineating the structural changes that occur in the developing brain, where the process of myelination is incomplete, and where crossing fibers exist in greater numbers than in the adult brain. Unlike DTI, diffusion spectrum imaging (DSI) can define multiple directions of water diffusivity; as such, diffusion tractography based on DSI provides marked flexibility for delineation of fiber tracts in areas where the fiber architecture is complex and multidirectional, even in areas of low FA. In this study, we showed that FA values were lower in the white matter of newborn (postnatal day 0; P0) cat brains than in the white matter of infant (P35) and juvenile (P100) cat brains. These results correlated well with histological myelin stains of the white matter: the newborn kitten brain has much less myelin than that found in cat brains at later stages of development. Using DSI tractography, we successfully identified structural changes in thalamo-cortical and cortico-cortical association tracts in cat brains from one stage of development to another. In newborns, the main body of the thalamo-cortical tract was smooth, and fibers branching from it were almost straight, while the main body became more complex and branching fibers became curved reflecting gyrification in the older cats. Cortico-cortical tracts in the temporal lobe were smooth in newborns, and they formed a sharper angle in the later stages of development. The cingulum bundle and superior longitudinal fasciculus became more visible with time. Within the first month after birth, structural changes occurred in these tracts that coincided with the formation of the gyri. These results show that DSI tractography has the potential for mapping morphological changes in low FA areas associated with growth and development. The technique may also be applicable to the study of other forms of brain plasticity, including future studies in vivo. PMID:19747553

Takahashi, Emi; Dai, Guangping; Wang, Ruopeng; Ohki, Kenichi; Rosen, Glenn D; Galaburda, Albert M; Grant, P Ellen; Wedeen, Van J

2009-09-08

321

Executive deficits, not processing speed relates to abnormalities in distinct prefrontal tracts in amyotrophic lateral sclerosis.  

PubMed

Cognitive impairment in amyotrophic lateral sclerosis is characterized by deficits on tests of executive function; however, the contribution of abnormal processing speed is unknown. Methods are confounded by tasks that depend on motor speed in patients with physical disability. Structural and functional magnetic resonance imaging studies have revealed multi-system cerebral involvement, with evidence of reduced white matter volume and integrity in predominant frontotemporal regions. The current study has two aims. First, to investigate whether cognitive impairments in amyotrophic lateral sclerosis are due to executive dysfunction or slowed processing speed using methodology that accommodates motor disability. This is achieved using a dual-task paradigm and tasks that manipulate stimulus presentation times and do not rely on response motor speed. Second, to identify relationships between specific cognitive impairments and the integrity of distinct white matter tracts. Thirty patients with amyotrophic lateral sclerosis and 30 age- and education-matched control subjects were administered an experimental dual-task procedure that combined a visual inspection time task and digit recall. In addition, measures of executive function (including letter fluency) and processing speed (visual inspection time and rapid serial letter identification) were administered. Integrity of white matter tracts was determined using region of interest analyses of diffusion tensor magnetic resonance imaging data. Patients with amyotrophic lateral sclerosis did not show impairments on tests of processing speed, but executive deficits were revealed once visual inspection time was combined with digit recall (dual-task) and in letter fluency. In addition to the corticospinal tracts, significant differences in fractional anisotropy and mean diffusivity were found between groups in a number of prefrontal and temporal white matter tracts including the anterior cingulate, anterior thalamic radiation, uncinate fasciculus and hippocampal portion of the cingulum bundles. Significant differences also emerged in the anterior corona radiata as well as in white matter underlying the superior, medial and inferior frontal gyri and the temporal gyri. Dual-task performance significantly correlated with fractional anisotropy measures in the middle frontal gyrus white matter and anterior corona radiata. Letter fluency indices significantly correlated with fractional anisotropy measures of the inferior frontal gyrus white matter and corpus callosum in addition to the corticospinal tracts and mean diffusivity measures in the white matter of the superior frontal gyrus. The current study demonstrates that cognitive impairment in amyotrophic lateral sclerosis is not due to generic slowing of processing speed. Moreover, different executive deficits are related to distinct prefrontal tract involvement in amyotrophic lateral sclerosis with dual-task impairment associating with dorsolateral prefrontal dysfunction and letter fluency showing greater dependence on inferolateral prefrontal dysfunction. PMID:24056536

Pettit, Lewis D; Bastin, Mark E; Smith, Colin; Bak, Thomas H; Gillingwater, Thomas H; Abrahams, Sharon

2013-09-20

322

Speech entrainment enables patients with Broca's aphasia to produce fluent speech.  

PubMed

A distinguishing feature of Broca's aphasia is non-fluent halting speech typically involving one to three words per utterance. Yet, despite such profound impairments, some patients can mimic audio-visual speech stimuli enabling them to produce fluent speech in real time. We call this effect 'speech entrainment' and reveal its neural mechanism as well as explore its usefulness as a treatment for speech production in Broca's aphasia. In Experiment 1, 13 patients with Broca's aphasia were tested in three conditions: (i) speech entrainment with audio-visual feedback where they attempted to mimic a speaker whose mouth was seen on an iPod screen; (ii) speech entrainment with audio-only feedback where patients mimicked heard speech; and (iii) spontaneous speech where patients spoke freely about assigned topics. The patients produced a greater variety of words using audio-visual feedback compared with audio-only feedback and spontaneous speech. No difference was found between audio-only feedback and spontaneous speech. In Experiment 2, 10 of the 13 patients included in Experiment 1 and 20 control subjects underwent functional magnetic resonance imaging to determine the neural mechanism that supports speech entrainment. Group results with patients and controls revealed greater bilateral cortical activation for speech produced during speech entrainment compared with spontaneous speech at the junction of the anterior insula and Brodmann area 47, in Brodmann area 37, and unilaterally in the left middle temporal gyrus and the dorsal portion of Broca's area. Probabilistic white matter tracts constructed for these regions in the normal subjects revealed a structural network connected via the corpus callosum and ventral fibres through the extreme capsule. Unilateral areas were connected via the arcuate fasciculus. In Experiment 3, all patients included in Experiment 1 participated in a 6-week treatment phase using speech entrainment to improve speech production. Behavioural and functional magnetic resonance imaging data were collected before and after the treatment phase. Patients were able to produce a greater variety of words with and without speech entrainment at 1 and 6 weeks after training. Treatment-related decrease in cortical activation associated with speech entrainment was found in areas of the left posterior-inferior parietal lobe. We conclude that speech entrainment allows patients with Broca's aphasia to double their speech output compared with spontaneous speech. Neuroimaging results suggest that speech entrainment allows patients to produce fluent speech by providing an external gating mechanism that yokes a ventral language network that encodes conceptual aspects of speech. Preliminary results suggest that training with speech entrainment improves speech production in Broca's aphasia providing a potential therapeutic method for a disorder that has been shown to be particularly resistant to treatment. PMID:23250889

Fridriksson, Julius; Hubbard, H Isabel; Hudspeth, Sarah Grace; Holland, Audrey L; Bonilha, Leonardo; Fromm, Davida; Rorden, Chris

2012-12-01

323

Development of Cerebral Fiber Pathways in Cats revealed by Diffusion Spectrum Imaging  

PubMed Central

Examination of the three-dimensional axonal pathways in the developing brain is key to understanding the formation of cerebral connectivity. By tracing fiber pathways throughout the entire brain, diffusion tractography provides information that cannot be achieved by conventional anatomical MR imaging or histology. However, standard diffusion tractography (based on diffusion tensor imaging, or DTI) tends to terminate in brain areas with low water diffusivity, indexed by low diffusion fractional anisotropy (FA), which can be caused by crossing fibers as well as fibers with less myelin. For this reason, DTI tractography is not effective for delineating the structural changes that occur in the developing brain, where the process of myelination is incomplete, and where crossing fibers exist in greater numbers than in the adult brain. Unlike DTI, diffusion spectrum imaging (DSI) can define multiple directions of water diffusivity; as such, diffusion tractography based on DSI provides marked flexibility for delineation of fiber tracts in areas where the fiber architecture is complex and multidirectional, even in areas of low FA. In this study, we showed that FA values were lower in the white matter of newborn (postnatal day 0; P0) cat brains than in the white matter of infant (P35) and juvenile (P100) cat brains. These results correlated well with histological myelin stains of the white matter: the newborn kitten brain has much less myelin than that found in cat brains at later stages of development. Using DSI tractography, we successfully identified structural changes in thalamo-cortical and cortico-cortical association tracts in cat brains from one stage of development to another. In newborns, the main body of the thalamo-cortical tract was smooth, and fibers branching from it were almost straight, while the main body became more complex and branching fibers became curved reflecting gyrification in the older cats. Cortico-cortical tracts in the temporal lobe were smooth in newborns, and they formed a sharper angle in the later stages of development. The cingulum bundle and superior longitudinal fasciculus became more visible with time. Within the first month after birth, structural changes occurred in these tracts that coincided with the formation of the gyri. These results show that DSI tractography has the potential for mapping morphological changes in low FA areas associated with growth and development. The technique may also be applicable to the study of other forms of brain plasticity, including future studies in vivo.

Takahashi, Emi; Dai, Guangping; Wang, Ruopeng; Ohki, Kenichi; Rosen, Glenn D.; Galaburda, Albert M.; Grant, P. Ellen; Wedeen, Van J.

2009-01-01

324

Alterations in brain structure and functional connectivity in prescription opioid-dependent patients  

PubMed Central

A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, we used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n?=??10); from a larger study on prescription opioid dependent patients (n?=??133)] and matched healthy individuals (n?=??10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. Criteria for patient selection included: (i) no dependence on alcohol or other drugs; (ii) no comorbid psychiatric or neurological disease; and (iii) no medical conditions, including pain. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated with structural and functional changes in brain regions implicated in the regulation of affect and impulse control, as well as in reward and motivational functions. These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure and function.

Upadhyay, Jaymin; Maleki, Nasim; Potter, Jennifer; Elman, Igor; Rudrauf, David; Knudsen, Jaime; Wallin, Diana; Pendse, Gautam; McDonald, Leah; Griffin, Margaret; Anderson, Julie; Nutile, Lauren; Renshaw, Perry; Weiss, Roger; Becerra, Lino

2010-01-01

325

A multimodal imaging study in U.S. veterans of Operations Iraqi and Enduring Freedom with and without major depression after blast-related concussion.  

PubMed

Although the exact number of affected individuals is unknown, it has been estimated that approximately 20% of U.S. veterans of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) have experienced mild traumatic brain injury (mTBI) (i.e., concussion), which is defined as a brief loss or alteration of consciousness from a blow or jolt to the head. Blast exposure is among the most common causes of concussion in OEF-OIF warriors. Although the mechanism is unknown, major depressive disorder (MDD) after head injury is common. The purpose of this study was to use diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to examine the structural and functional neural correlates of MDD in OEF-OIF combat veterans with a self-reported history of blast-related concussion. We hypothesized that subjects in the MDD group (i.e., individuals with a history of blast-related concussion who were experiencing current MDD) relative to individuals in the non-MDD group (i.e., individuals with a history of blast-related concussion but no current or lifetime history of MDD) would show amygdala hyperactivity and disruption of white matter tracts connecting prefrontal and limbic brain regions. To test these hypotheses, 11 MDD and 11 non-MDD individuals underwent DTI and performed a validated emotional face matching task during fMRI. MDD relative to non-MDD individuals showed greater activity during fear matching trials in the amygdala and other emotion processing structures, lower activity during fear matching trials in emotional control structures such as the dorsolateral prefrontal cortex and lower fractional anisotropy (FA) in several white matter tracts including the superior longitudinal fasciculus (SLF). Greater depressive symptom severity correlated negatively with FA in the SLF. These results suggest a biological basis of MDD in OEF-OIF veterans who have experienced blast-related concussion, and may contribute to the development of treatments aimed at improving the clinical care of this unique population of wounded warriors. PMID:20451622

Matthews, Scott C; Strigo, Irina A; Simmons, Alan N; O'Connell, Ryan M; Reinhardt, Lindsay E; Moseley, Suzanne A

2010-05-06

326

Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech.  

PubMed

Apraxia of speech is a disorder of speech motor planning and/or programming that is distinguishable from aphasia and dysarthria. It most commonly results from vascular insults but can occur in degenerative diseases where it has typically been subsumed under aphasia, or it occurs in the context of more widespread neurodegeneration. The aim of this study was to determine whether apraxia of speech can present as an isolated sign of neurodegenerative disease. Between July 2010 and July 2011, 37 subjects with a neurodegenerative speech and language disorder were prospectively recruited and underwent detailed speech and language, neurological, neuropsychological and neuroimaging testing. The neuroimaging battery included 3.0 tesla volumetric head magnetic resonance imaging, [(18)F]-fluorodeoxyglucose and [(11)C] Pittsburg compound B positron emission tomography scanning. Twelve subjects were identified as having apraxia of speech without any signs of aphasia based on a comprehensive battery of language tests; hence, none met criteria for primary progressive aphasia. These subjects with primary progressive apraxia of speech included eight females and four males, with a mean age of onset of 73 years (range: 49-82). There were no specific additional shared patterns of neurological or neuropsychological impairment in the subjects with primary progressive apraxia of speech, but there was individual variability. Some subjects, for example, had mild features of behavioural change, executive dysfunction, limb apraxia or Parkinsonism. Voxel-based morphometry of grey matter revealed focal atrophy of superior lateral premotor cortex and supplementary motor area. Voxel-based morphometry of white matter showed volume loss in these same regions but with extension of loss involving the inferior premotor cortex and body of the corpus callosum. These same areas of white matter loss were observed with diffusion tensor imaging analysis, which also demonstrated reduced fractional anisotropy and increased mean diffusivity of the superior longitudinal fasciculus, particularly the premotor components. Statistical parametric mapping of the [(18)F]-fluorodeoxyglucose positron emission tomography scans revealed focal hypometabolism of superior lateral premotor cortex and supplementary motor area, although there was some variability across subjects noted with CortexID analysis. [(11)C]-Pittsburg compound B positron emission tomography binding was increased in only one of the 12 subjects, although it was unclear whether the increase was actually related to the primary progressive apraxia of speech. A syndrome characterized by progressive pure apraxia of speech clearly exists, with a neuroanatomic correlate of superior lateral premotor and supplementary motor atrophy, making this syndrome distinct from primary progressive aphasia. PMID:22382356

Josephs, Keith A; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Master, Ankit V; Lowe, Val J; Jack, Clifford R; Whitwell, Jennifer L

2012-03-01

327

Multiple origins, migratory paths and molecular profiles of cells populating the avian interpeduncular nucleus.  

PubMed

The interpeduncular nucleus (IP) is a key limbic structure, highly conserved evolutionarily among vertebrates. The IP receives indirect input from limbic areas of the telencephalon, relayed by the habenula via the fasciculus retroflexus. The function of the habenulo-IP complex is poorly understood, although there is evidence that in rodents it modulates behaviors such as learning and memory, avoidance, reward and affective states. The IP has been an important subject of interest for neuroscientists, and there are multiple studies about the adult structure, chemoarchitecture and its connectivity, with complex results, due to the presence of multiple cell types across a variety of subnuclei. However, the ontogenetic origins of these populations have not been examined, and there is some controversy about its location in the midbrain-anterior hindbrain area. To address these issues, we first investigated the anteroposterior (AP) origin of the IP complex by fate-mapping its neuromeric origin in the chick, discovering that the IP develops strictly within isthmus and rhombomere 1. Next, we studied the dorsoventral (DV) positional identity of subpopulations of the IP complex. Our results indicate that there are at least four IP progenitor domains along the DV axis. These specific domains give rise to distinct subtypes of cell populations that target the IP with variable subnuclear specificity. Interestingly, these populations can be characterized by differential expression of the transcription factors Pax7, Nkx6.1, Otp, and Otx2. Each of these subpopulations follows a specific route of migration from its source, and all reach the IP roughly at the same stage. Remarkably, IP progenitor domains were found both in the alar and basal plates. Some IP populations showed rostrocaudal restriction in their origins (isthmus versus anterior or posterior r1 regions). A tentative developmental model of the structure of the avian IP is proposed. The IP emerges as a plurisegmental and developmentally heterogeneous formation that forms ventromedially within the isthmus and r1. These findings are relevant since they help to understand the highly complex chemoarchitecture, hodology and functions of this important brainstem structure. PMID:22019302

Lorente-Cánovas, Beatriz; Marín, Faustino; Corral-San-Miguel, Rubén; Hidalgo-Sánchez, Matías; Ferrán, José Luis; Puelles, Luis; Aroca, Pilar

2011-10-12

328

Leucine-rich repeat-containing G-protein-coupled receptor 8 in the rat brain: Enrichment in thalamic neurons and their efferent projections.  

PubMed

Leucine-rich repeat-containing G-protein-coupled receptor 8 (LGR8; also classified as relaxin family peptide 2 receptor; RXFP2) has been identified as a cognate receptor for the peptide hormone, insulin-like peptide 3 (INSL3) and INSL3-LGR8 signaling plays an essential role in testis descent and germ cell development in human and rodents. Lgr8 mRNA has been detected in human tissues including testis, kidney and brain, but its regional and cellular distribution in these tissues in human or other species is largely unknown. In an initial step to elucidate the physiological function of a putative INSL3-LGR8 system in rat brain, the localization of Lgr8 mRNA was investigated using in situ hybridization histochemistry, revealing a discrete distribution in forebrain, with expression highly enriched in the thalamus. High densities were detected in the parafascicular nucleus (Pf), the dorsolateral, ventrolateral and posterior thalamic nuclei, and in the medial habenula. Lgr8 transcripts were also detected in frontal and motor cortices. The comparative distribution of LGR8 (receptor protein) was examined by autoradiography of [125I]-human INSL3 binding sites, with high densities detected in the thalamus, especially in Pf, and in the entire striatum--the caudate putamen (CPmicro), islands of Calleja, olfactory tubercle, nucleus accumbens--with lower levels in distinct layers of cerebral cortex. Notably, these areas also receive dopaminergic projections. These findings demonstrate the existence of LGR8 in neuronal soma in the thalamus and axons/terminals in thalamic target areas such as the striatum and frontal cortex. LGR8 was also detected throughout the medial habenula-fasciculus retroflexus-interpeduncular nucleus pathway, further indicating that the receptor is transported from mRNA-expressing soma to remote axonal/terminal sites. These findings suggest the existence of a broadly distributed LGR8 signaling system in the rat involved in sensorimotor, limbic and cognitive functions. Further studies are now required to elucidate the precise function of LGR8, under normal and pathological conditions, as importantly, several of the equivalent receptor-positive areas in human brain are part of the pathology of neurodegenerative conditions including Parkinson's disease. PMID:18706979

Sedaghat, K; Shen, P-J; Finkelstein, D I; Henderson, J M; Gundlach, A L

2008-07-25

329

Functional connectivity in the human language system: a cortico-cortical evoked potential study.  

PubMed

A better understanding of the mechanisms involved in human higher cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. Currently no good method for tracking in vivo neuronal connectivity exists. We investigated the inter-areal connections in vivo in the human language system using a new method, which we termed 'cortico-cortical evoked potentials' (CCEPs). Eight patients with epilepsy (age 13-42 years) underwent invasive monitoring with subdural electrodes for epilepsy surgery. Six patients had language dominance on the side of grid implantation and two had bilateral language representation by the intracarotid amobarbital test. Conventional cortical electrical stimulation was performed to identify the anterior and posterior language areas. Single pulse electrical stimuli were delivered to the anterior language (eight patients), posterior language (four patients) or face motor (two patients) area, and CCEPs were obtained by averaging electrocorticograms (ECoGs) recorded from the perisylvian and extrasylvian basal temporal language areas time-locked to the stimulus. The subjects were not asked to perform any tasks during the study. Stimulation at the anterior language area elicited CCEPs in the lateral temporo-parietal area (seven of eight patients) in the middle and posterior part of the superior temporal gyrus, the adjacent part of the middle temporal gyrus and the supramarginal gyrus. CCEPs were recorded in 3-21 electrodes per patient. CCEPs occurred at or around the particular electrodes in the posterior language area which, when stimulated, produced speech arrest. Similar early and late CCEPs were obtained from the basal temporal area by stimulating the anterior language area (three of three patients). In contrast, stimulation of the adjacent face motor area did not elicit CCEPs in language areas but rather in the postcentral gyrus. Stimulation of the posterior language area produced CCEPs in the anterior language (three of four patients) as well as in the basal temporal area (one of two patients). These CCEPs were less well defined. These findings suggest that perisylvian and extrasylvian language areas participate in the language system as components of a network by means of feed-forward and feed-back projections. Different from the classical Wernicke-Geschwind model, the present study revealed a bidirectional connection between Broca's and Wernicke's areas probably through the arcuate fasciculus and/or the cortico-subcortico-cortical pathway. CCEPs were recorded from a larger area than the posterior language area identified by electrical stimulation. This suggests the existence of a rather broad neuronal network surrounding the previously recognized core region of this area. PMID:15269116

Matsumoto, Riki; Nair, Dileep R; LaPresto, Eric; Najm, Imad; Bingaman, William; Shibasaki, Hiroshi; Lüders, Hans O

2004-07-21

330

Lidocaine-induced unilateral internuclear ophthalmoplegia: effects on convergence and conjugate eye movements.  

PubMed

1. To characterize the vergence signal carried by the medial longitudinal fasciculus (MLF), it was subjected to reversible blockade by small injections of 10% lidocaine hydrochloride. The effects of these blockades on both conjugate and vergence eye movements were studied. 2. With this procedure, experimentally induced internuclear ophthalmoplegia (INO) and its effects on conjugate eye movements could be studied acutely, without possible contamination from long-term oculomotor adaptation. In the eye contralateral to the MLF blockade, saccadic and horizontal smooth-pursuit eye movements were normal. Horizontal abducting nystagmus, often seen in patients with INO, was not observed in this eye. 3. As previously reported for INO, profound oculomotor deficits were seen in the eye ipsilateral to the MLF blockade. During maximal blockade, adducting saccades and horizontal smooth-pursuit movements in this eye did not cross the midline. Adducting saccades were reduced in amplitude and peak velocity and showed significantly increased durations. Abducting saccades, which were slightly hypometric, displayed a marked postsaccadic centripetal drift. 4. The eye ipsilateral to the blockade displayed a pronounced, upward, slow drift, whereas the eye contralateral to the blockade showed virtually no drift. Furthermore, although vertical saccades to visual targets remained essentially conjugate, the size of the resetting quick phases in each eye was related to the amplitude of the slow phase movement in that eye. Thus the eye on the affected side displayed large quick phases, whereas the eye on the unaffected side showed only slight movements. On occasion, unilateral downbeating nystagmus was seen. This strongly suggests that the vertical saccade generators for the two eyes can act independently. 5. The effect of MLF blockade on the vergence gain of the eye on the affected side was investigated. As a measure of open-loop vergence gain, the relationship of accommodative convergence to accommodation (AC/A) was measured before, during, and after reversible lidocaine block of the MLF. After taking conjugate deficits into account, the net vergence signal to the eye ipsilateral to the injection was found to increase significantly during the reversible blockade. 6. The most parsimonious explanation for this increased vergence signal is suggested by the accompanying single-unit study. This study showed that abducens internuclear neurons, whose axons course in the MLF, provide medial rectus motoneurons with an appropriate horizontal conjugate eye position signal but an inappropriate vergence signal. Ordinarily, this incorrect vergence signal is overcome by another, more potent, v PMID:2754483

Gamlin, P D; Gnadt, J W; Mays, L E

1989-07-01

331

The organization of monoamine-containing neurons in the brain of the sunfish (Lepomis gibbosus) as revealed by fluorescence microscopy.  

PubMed

The morphological organization of the monoamine-containing neurons in the brain of the sunfish (Lepomis gibbosus) was studied by means of the Falck-Hillarp histofluorescence method. No attempt was made to distinguish between norepinephrine and dopamine, both primary catecholamines (CA) yielding a similar yellow-green fluorescence after paraformaldehyde treatment. In the brain stem of this teleost fish, three groups of CA-containing neuronal somata have been found. First, there is a small collection of CA perikarya located just caudal to the obex of the fourth ventricle. The neurons of this medullo-sinal group give rise to numerous CA fibers many of which ascend within the central portion of the medulla. Intermingled with these CA fibers are some CA cells that constitute the central medullary group. The CA perikarya of this group are scattered between the levels of cranial nerves X and VIII. The tegmentum of the isthmus also contains a small group of very closely packed CA neurons. The large-sized CA cells of the isthmal group are located dorsolateral to the medial longitudinal fasciculus, partly within the periventricular gray. High densities of CA varicosities were also disclosed in various brain stem structures such as the optic tectum, the torus semicircularis and the cerebeller valvula. In addition, numerous serotonin (5-HT)-type neuronal somata were found in the raphe region of the brain stem, particularly at caudal mesencephalic, isthmal and rostral medullary levels. A large number of CA cell bodies were visualized in the sunfish hypothalamus. Most of them form two populations of small, round cells that are located along and partly within the ependymal walls of the posterior and lateral recesses of the third ventricle. These bipolar cells possess one short club-like process protruding into the ventricle and their thin ependymofugal processes contribute to the CA innervation of numerous hypothalamic regions. Large CA neurons apparently without direct CSF contact also occur in the area of nucleus posterior tuberis, at the level of the mesodiencephalic junction. Although the hypothalamic inferior lobes are devoid of CA cell bodies they are heavily innervated by CA axons. The sunfish telencephalon also receives a strikingly massive and complex monoaminergic innervation. Numerous CA fibers which are first observed at the level of the preoptic area, ascend through the central zone of the telencephalon and arborize profusely particularly within the medial zone of area dorsalis telencephali. Other CA fibers, as well as abundant fine 5-HT varicosities were found in the lateral zone of area dorsalis. Although the exact origin of the telencephalic CA afferents in Lepomis is not known, part of it may arise from the isthmal CA cell group which appears similar to the locus coeruleus of reptiles, birds and mammals. PMID:721968

Parent, A; Dube, L; Braford, M R; Northcutt, R G

1978-12-01

332

Myf5 is a novel early axonal marker in the mouse brain and is subjected to post-transcriptional regulation in neurons.  

PubMed

Myf5 is a key basic Helix-Loop-Helix transcription factor capable of converting many non-muscle cells into muscle. Together with MyoD it is essential for initiating the skeletal muscle programme in the embryo. We previously identified unexpected restricted domains of Myf5 transcription in the embryonic mouse brain, first revealed by Myf5-nlacZ(+/)(-) embryos (Tajbakhsh, S. and Buckingham, M. (1995) Development 121, 4077-4083). We have now further characterized these Myf5 expressing neurons. Retrograde labeling with diI, and the use of a transgenic mouse line expressing lacZ under the control of Myf5 regulatory sequences, show that Myf5 transcription provides a novel axonal marker of the medial longitudinal fasciculus (mlf) and the mammillotegmental tract (mtt), the earliest longitudinal tracts to be established in the embryonic mouse brain. Tracts projecting caudally from the developing olfactory system are also labelled. nlacZ and lacZ expression persist in the adult brain, in a few ventral domains such as the mammillary bodies of the hypothalamus and the interpeduncular nucleus, potentially derived from the embryonic structures where the Myf5 gene is transcribed. To investigate the role of Myf5 in the brain, we monitored Myf5 protein accumulation by immunofluorescence and immunoblotting in neurons transcribing the gene. Although Myf5 was detected in muscle myotomal cells, it was absent in neurons. This would account for the lack of myogenic conversion in brain structures and the absence of a neural phenotype in homozygous null mutants. RT-PCR experiments show that the splicing of Myf5 primary transcripts occurs correctly in neurons, suggesting that the lack of Myf5 protein accumulation is due to regulation at the level of mRNA translation or protein stability. In the embryonic neuroepithelium, Myf5 is transcribed in differentiated neurons after the expression of neural basic Helix-Loop-Helix transcription factors. The signalling molecules Wnt1 and Sonic hedgehog, implicated in the activation of Myf5 in myogenic progenitor cells in the somite, are also produced in the viscinity of the Myf5 expression domain in the mesencephalon. We show that cells expressing Wnt1 can activate neuronal Myf5-nlacZ gene expression in dissected head explants isolated from E9.5 embryos. Furthermore, the gene encoding the basic Helix-Loop-Helix transcription factor mSim1 is expressed in adjacent cells in both the somite and the brain, suggesting that signalling molecules necessary for the activation of mSim1 as well as Myf5 are present at these different sites in the embryo. This phenomenon may be widespread and it remains to be seen how many other potentially potent regulatory genes, in addition to Myf5, when activated do not accumulate protein at inappropriate sites in the embryo. PMID:10603349

Daubas, P; Tajbakhsh, S; Hadchouel, J; Primig, M; Buckingham, M

2000-01-01

333

Deficits in vertical and torsional eye movements after uni- and bilateral muscimol inactivation of the interstitial nucleus of Cajal of the alert monkey.  

PubMed

The mesencephalic interstitial nucleus of Cajal (iC) is considered the neural integrator for vertical and torsional eye movements and has also been proposed to be involved in saccade generation. The aim of this study was to elucidate the function of iC in neural integration of different types of eye movements and to distinguish eye movement deficits due to iC impairment from that of the immediately adjacent rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). We addressed the following questions: (1) According to the neural integrator hypothesis, all eye movements including the saccadic system and the vestibulo-ocular reflex (VOR) share a common neural integrator. Do iC lesions impair gaze-holding function for vertical and torsional eye positions and the torsional and vertical VOR gain to a similar degree? (2) What are the dynamic properties of vertical and torsional eye movements deficits after iC lesions, e.g., the specificity of torsional and vertical nystagmus? (3) Is iC involved in saccade generation? We performed 13 uni- and three bilateral iC inactivations by muscimol microinjections in four alert monkeys. Three-dimensional eye movements were studied under head-stationary conditions during vertical and torsional VOR. Under static conditions, unilateral iC injections evoked a shift of Listing's plane to the contralesional side (up to 20 degrees), which increased (ipsilesional ear down) or decreased (ipsilesional ear up) by additional static vestibular stimulation in the roll plane, i.e., ocular counterroll was preserved. The monkeys showed a spontaneous torsional nystagmus with a profound downbeat component. The fast phases of torsional nystagmus always beat toward the lesion side (ipsilesional). Pronounced gaze-holding deficit for torsional and vertical eye positions (neural integrator failure) was reflected by the reduction of time constants of the exponential decay of the slow phase to 330-370 ms. Whereas the vertical oculomotor range was profoundly decreased (up to 50%) and vertical saccades were reduced in amplitude, saccade velocity remained normal and horizontal eye movements were not affected. Bilateral iC injections reduced the shift of Listing's plane caused by unilateral injections, i.e., back toward the plane of zero torsion. Torsional nystagmus reversed its direction and ceased, whereas vertical nystagmus persisted. In contrast to unilateral injection, there was additional upbeating nystagmus. Time constants of the position integrator of the gaze-holding system did not differ between unilateral and bilateral injections. The range of stable vertical eye positions and saccade amplitude was smaller when compared with unilateral injections, but the main sequence remained normal. Dynamic vestibular stimulation after unilateral iC injections had virtually no effect on torsional and vertical VOR gain and phase at the same time when time constants already indicated severe integrator failure. Torsional VOR elicited a constant slow-phase velocity offset up to 30 degrees toward the contralesional side, i.e., in the opposite direction to spontaneous torsional nystagmus. Likewise, vertical VOR showed a velocity offset in an upward direction, i.e., opposite to the spontaneous downbeat nystagmus. Contralesional torsional and upward vertical quick phases were missing or severely reduced in amplitude but showed normal velocity. In contrast, bilateral iC injections reduced the gain of the torsional and vertical VOR by 50% and caused a phase lead of 10-20 degrees (eye compared with head velocity). We propose that the slow-phase velocity offset during torsional and vertical VOR reflects a vestibular imbalance. It therefore appears likely that the vertical and torsional nystagmus after iC lesions is not only caused by a neural integrator failure but also by a vestibular imbalance. Unilateral iC injections have clearly differential effects on the VOR and the gaze-holding function. (ABSTRACT TRUNCATED) PMID:9588778

Helmchen, C; Rambold, H; Fuhry, L; Büttner, U

1998-04-01