Sample records for fronto-occipital fasciculus ifof

  1. The left inferior fronto-occipital fasciculus subserves language semantics: a multilevel lesion study.

    PubMed

    Almairac, Fabien; Herbet, Guillaume; Moritz-Gasser, Sylvie; de Champfleur, Nicolas Menjot; Duffau, Hugues

    2015-07-01

    Consequential works in cognitive neuroscience have led to the formulation of an interactive dual-stream model of language processing: the dorsal stream may process the phonological aspects of language, whereas the ventral stream may process the semantic aspects of language. While it is well-accepted that the dorsal route is subserved by the arcuate fasciculus, the structural connectivity of the semantic ventral stream is a matter of dispute. Here we designed a longitudinal study to gain new insights into this central but controversial question. Thirty-one patients harboring a left diffuse low-grade glioma-a rare neurological condition that infiltrates preferentially white matter associative pathways-were assessed with a prototypical task of language (i.e. verbal fluency) before and after surgery. All were operated under local anesthesia with a cortical and subcortical brain mapping-enabling to identify and preserve eloquent structures for language. We performed voxel-based lesion-symptom (VLSM) analyses on pre- and postoperative behavioral data. Preoperatively, we found a significant relationship between semantic fluency scores and the white matter fibers shaping the ventro-lateral connectivity (P < 0.05 corrected). The statistical map was found to substantially overlap with the spatial position of the inferior fronto-occipital fasciculus (IFOF) (37.7 %). Furthermore, a negative correlation was observed between semantic fluency scores and the infiltration volumes in this fasciculus (r = -0.4, P = 0.029). Postoperatively, VLSM analyses were inconclusive. Taken as a whole and when combined with the literature data, our findings strengthen the view that the IFOF plays an essential role in semantic processing and may subserve the direct ventral pathway of language. PMID:24744151

  2. Decreased white matter integrity in fronto-occipital fasciculus bundles: relation to visual information processing in alcohol-dependent subjects.

    PubMed

    Bagga, Deepika; Sharma, Aakansha; Kumari, Archana; Kaur, Prabhjot; Bhattacharya, Debajyoti; Garg, Mohan Lal; Khushu, Subash; Singh, Namita

    2014-02-01

    Chronic alcohol abuse is characterized by impaired cognitive abilities with a more severe deficit in visual than in verbal functions. Neuropathologically, it is associated with widespread brain structural compromise marked by gray matter shrinkage, ventricular enlargement, and white matter degradation. The present study sought to increase current understanding of the impairment of visual processing abilities in alcohol-dependent subjects, and its correlation with white matter microstructural alterations, using diffusion tensor imaging (DTI). To that end, a DTI study was carried out on 35 alcohol-dependent subjects and 30 healthy male control subjects. Neuropsychological tests were assessed for visual processing skills and deficits were reported as raw dysfunction scores (rDyS). Reduced FA (fractional anisotropy) and increased MD (mean diffusivity) were observed bilaterally in inferior and superior fronto-occipital fasciculus (FOF) fiber bundles. A significant inverse correlation in rDyS and FA values was observed in these fiber tracts whereas a positive correlation of these scores was found with the MD values. Our results suggest that FOF fiber bundles linking the frontal lobe to occipital lobe might be related to visual processing skills. This is the first report of an alteration of the white matter microstructure of FOF fiber bundles that might have functional consequences for visual processing in alcohol-dependent subjects who exhibit no neurological complications. PMID:24388377

  3. Neuropsychological evidence for the functional role of the uncinate fasciculus in semantic control.

    PubMed

    Harvey, Denise Y; Wei, Tao; Ellmore, Timothy M; Hamilton, A Cris; Schnur, Tatiana T

    2013-04-01

    Understanding a word requires mapping sounds to a word-form and then identifying its correct meaning, which in some cases necessitates the recruitment of cognitive control processes to direct the activation of semantic knowledge in a task appropriate manner (i.e., semantic control). Neuroimaging and neuropsychological studies identify a fronto-temporal network important for word comprehension. However, little is known about the connectional architecture subserving controlled retrieval and selection of semantic knowledge during word comprehension. We used diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI) in aphasic individuals with varying degrees of word comprehension deficits to examine the role of three white matter pathways within this network: the uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), and inferior fronto-occipital fasciculus (IFOF). Neuroimaging data from a group of age-matched controls were also collected in order to establish that the patient group had decreased structural and functional connectivity profiles. We obtained behavioral data from aphasic participants on two measures of single word comprehension that involve semantic control, and assessed pathway functional significance by correlating patients' performance with indices of pathway structural integrity and the functional connectivity profiles of regions they connect. Both the structural integrity of the UF and the functional connectivity strength of regions it connects predicted patients' performance. This result suggests the semantic control impairment in word comprehension resulted from poor neural communication between regions the UF connects. Inspections of other subcortical and cortical structures revealed no relationship with patients' performance. We conclude that the UF mediates semantic control during word comprehension by connecting regions specialized for cognitive control with those storing word meanings. These findings also support a relationship between structural and functional connectivity measures, as the rs-fMRI results provide converging evidence with those obtained using DTI. PMID:23395830

  4. White Matter Abnormalities and Cognitive Impairment in Early-Onset Schizophrenia-Spectrum Disorders

    PubMed Central

    Epstein, Katherine A.; Cullen, Kathryn; Mueller, Bryon; Lee, Susanne; Kumra, Sanjiv

    2014-01-01

    OBJECTIVE To characterize white matter abnormalities in adolescents with early onset schizophrenia (EOS) relative to three comparison groups (adolescents at clinical high risk for developing schizophrenia [CHR], adolescents with cannabis use disorder [CUD], and healthy controls [HC]), and to identify neurocognitive correlates of white matter abnormalities in EOS. METHOD We used diffusion tensor imaging and tractography methods to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus in adolescents with EOS (n=55), CHR (n=21), CUD (n=31), and HC (n=55). FA in tracts that were significantly altered in EOS was correlated with neurocognitive performance. RESULTS EOS and CHR groups had significantly lower FA than HC in four tracts: bilateral CST, left ILF, and left IFOF. CUD had lower FA than HC in left IFOF. Lower FA in left IFOF and left ILF predicted worse neurocognitive performance in EOS. CONCLUSIONS This study identified left ILF and left IFOF as possible biomarkers of vulnerability for developing schizophrenia. Lower FA in these tracts may disrupt functioning of ventral visual and language streams, producing domain-specific neurocognitive deficits that interfere with higher order cognitive abilities. PMID:24565363

  5. Association of dorsal inferior frontooccipital fasciculus fibers in the deep parietal lobe with both reading and writing processes: a brain mapping study.

    PubMed

    Motomura, Kazuya; Fujii, Masazumi; Maesawa, Satoshi; Kuramitsu, Shunichiro; Natsume, Atsushi; Wakabayashi, Toshihiko

    2014-07-01

    Alexia and agraphia are disorders common to the left inferior parietal lobule, including the angular and supramarginal gyri. However, it is still unclear how these cortical regions interact with other cortical sites and what the most important white matter tracts are in relation to reading and writing processes. Here, the authors present the case of a patient who underwent an awake craniotomy for a left inferior parietal lobule glioma using direct cortical and subcortical electrostimulation. The use of subcortical stimulation allowed identification of the specific white matter tracts associated with reading and writing. These tracts were found as portions of the dorsal inferior frontooccipital fasciculus (IFOF) fibers in the deep parietal lobe that are responsible for connecting the frontal lobe to the superior parietal lobule. These findings are consistent with previous diffusion tensor imaging tractography and functional MRI studies, which suggest that the IFOF may play a role in the reading and writing processes. This is the first report of transient alexia and agraphia elicited through intraoperative direct subcortical electrostimulation, and the findings support the crucial role of the IFOF in reading and writing. PMID:24655122

  6. Not on speaking terms: hallucinations and structural network disconnectivity in schizophrenia.

    PubMed

    ?ur?i?-Blake, Branislava; Nanetti, Luca; van der Meer, Lisette; Cerliani, Leonardo; Renken, Remco; Pijnenborg, Gerdina H M; Aleman, André

    2015-01-01

    Auditory verbal hallucinations (AVH) in schizophrenia have previously been associated with functional deficiencies in language networks, specifically with functional disconnectivity in fronto-temporal connections in the left hemisphere and in interhemispheric connections between frontal regions. Here, we investigate whether AVH are accompanied by white matter abnormalities in tracts connecting the frontal, parietal and temporal lobes, also engaged during language tasks. We combined diffusion tensor imaging with tract-based spatial statistics and found white matter abnormalities in patients with schizophrenia as compared with healthy controls. The patients showed reduced fractional anisotropy bilaterally: in the anterior thalamic radiation (ATR), body of the corpus callosum (forceps minor), cingulum, temporal part of the superior longitudinal fasciculus (SLF) and a small area in the inferior fronto-occipital fasciculus (IFOF); and in the right hemisphere: in the visual cortex, forceps major, body of the corpus callosum (posterior parts) and inferior parietal cortex. Compared to patients without current hallucinations, patients with hallucinations revealed decreased fractional anisotropy in the left IFOF, uncinate fasciculus, arcuate fasciculus with SLF, corpus callosum (posterior parts-forceps major), cingulate, corticospinal tract and ATR. The severity of hallucinations correlated negatively with white matter integrity in tracts connecting the left frontal lobe with temporal regions (uncinate fasciculus, IFOF, cingulum, arcuate fasciculus anterior and long part and superior long fasciculus frontal part) and in interhemispheric connections (anterior corona radiata). These findings support the hypothesis that hallucinations in schizophrenia are accompanied by a complex pattern of white matter alterations that negatively affect the language, emotion and attention/perception networks. PMID:24185461

  7. Cytotoxic constituents from Podocarpus fasciculus.

    PubMed

    Kuo, Yu-Jen; Hwang, Shy-Yuan; Wu, Ming-Der; Liao, Chia-Ching; Liang, Yu-Han; Kuo, Yao-Haur; Ho, Hsiu-O

    2008-04-01

    A new diterpene, 16-hydroxy communic acid (1), along with thirty one known compounds including five norditerpenes (2-6), twenty two flavonoids containing four biflavonoids (7-10), nine monoflavonoids (11-19) and nine flavanoid glycosides (20-28), as well as four phenolic constituents (29-32) were isolated from the 95% ethanolic extract of Podocarpus fasciculus. The structure of 1 was elucidated using spectral methods. Of these isolates, nagilactone C (2) showed the most significant inhibitory effects against DLD cells (human colon carcinoma) (ED(50)=2.57 microg/ml) and compounds 7, 8, 10, 11, and 12 had moderate cytotoxic activity against human KB (human oral epithelium carcinoma), Hela (human cervical carcinoma), Hepa (human hepatoma), DLD (colon carcinoma), and A-549 (human lung carcinoma) tumor cell lines. Preliminary structure-activity relationship studies of the isolated diterpenoids and biflavonoids are discussed. PMID:18379113

  8. Evaluation of diffusion-tensor imaging-based global search and tractography for tumor surgery close to the language system.

    PubMed

    Richter, Mirco; Zolal, Amir; Ganslandt, Oliver; Buchfelder, Michael; Nimsky, Christopher; Merhof, Dorit

    2013-01-01

    Pre-operative planning and intra-operative guidance in neurosurgery require detailed information about the location of functional areas and their anatomo-functional connectivity. In particular, regarding the language system, post-operative deficits such as aphasia can be avoided. By combining functional magnetic resonance imaging and diffusion tensor imaging, the connectivity between functional areas can be reconstructed by tractography techniques that need to cope with limitations such as limited resolution and low anisotropic diffusion close to functional areas. Tumors pose particular challenges because of edema, displacement effects on brain tissue and infiltration of white matter. Under these conditions, standard fiber tracking methods reconstruct pathways of insufficient quality. Therefore, robust global or probabilistic approaches are required. In this study, two commonly used standard fiber tracking algorithms, streamline propagation and tensor deflection, were compared with a previously published global search, Gibbs tracking and a connection-oriented probabilistic tractography approach. All methods were applied to reconstruct neuronal pathways of the language system of patients undergoing brain tumor surgery, and control subjects. Connections between Broca and Wernicke areas via the arcuate fasciculus (AF) and the inferior fronto-occipital fasciculus (IFOF) were validated by a clinical expert to ensure anatomical feasibility, and compared using distance- and diffusion-based similarity metrics to evaluate their agreement on pathway locations. For both patients and controls, a strong agreement between all methods was observed regarding the location of the AF. In case of the IFOF however, standard fiber tracking and Gibbs tracking predominantly identified the inferior longitudinal fasciculus that plays a secondary role in semantic language processing. In contrast, global search resolved connections in almost every case via the IFOF which could be confirmed by probabilistic fiber tracking. The results show that regarding the language system, our global search is superior to clinically applied conventional fiber tracking strategies with results similar to time-consuming global or probabilistic approaches. PMID:23308093

  9. Evaluation of Diffusion-Tensor Imaging-Based Global Search and Tractography for Tumor Surgery Close to the Language System

    PubMed Central

    Richter, Mirco; Zolal, Amir; Ganslandt, Oliver; Buchfelder, Michael; Nimsky, Christopher; Merhof, Dorit

    2013-01-01

    Pre-operative planning and intra-operative guidance in neurosurgery require detailed information about the location of functional areas and their anatomo-functional connectivity. In particular, regarding the language system, post-operative deficits such as aphasia can be avoided. By combining functional magnetic resonance imaging and diffusion tensor imaging, the connectivity between functional areas can be reconstructed by tractography techniques that need to cope with limitations such as limited resolution and low anisotropic diffusion close to functional areas. Tumors pose particular challenges because of edema, displacement effects on brain tissue and infiltration of white matter. Under these conditions, standard fiber tracking methods reconstruct pathways of insufficient quality. Therefore, robust global or probabilistic approaches are required. In this study, two commonly used standard fiber tracking algorithms, streamline propagation and tensor deflection, were compared with a previously published global search, Gibbs tracking and a connection-oriented probabilistic tractography approach. All methods were applied to reconstruct neuronal pathways of the language system of patients undergoing brain tumor surgery, and control subjects. Connections between Broca and Wernicke areas via the arcuate fasciculus (AF) and the inferior fronto-occipital fasciculus (IFOF) were validated by a clinical expert to ensure anatomical feasibility, and compared using distance- and diffusion-based similarity metrics to evaluate their agreement on pathway locations. For both patients and controls, a strong agreement between all methods was observed regarding the location of the AF. In case of the IFOF however, standard fiber tracking and Gibbs tracking predominantly identified the inferior longitudinal fasciculus that plays a secondary role in semantic language processing. In contrast, global search resolved connections in almost every case via the IFOF which could be confirmed by probabilistic fiber tracking. The results show that regarding the language system, our global search is superior to clinically applied conventional fiber tracking strategies with results similar to time-consuming global or probabilistic approaches. PMID:23308093

  10. Principal eigenvector field segmentation for reproducible diffusion tensor tractography of white matter structures

    Microsoft Academic Search

    Ram K. S. Rathore; Rakesh K. Gupta; Shruti Agarwal; Richa Trivedi; Rajendra P. Tripathi; Rishi Awasthi

    2011-01-01

    The study was aimed to test the feasibility of utilizing an algorithmically determinable stable fiber mass (SFM) map obtained by an unsupervised principal eigenvector field segmentation (PEVFS) for automatic delineation of 18 white matter (WM) tracts: (1) corpus callosum (CC), (2) tapetum (TP), (3) inferior longitudinal fasciculus (ILF), (4) uncinate fasciculus (UNC), (5) inferior fronto-occipital fasciculus (IFO), (6) optic pathways

  11. White matter fractional anisotropy over two time points in early onset schizophrenia and adolescent cannabis use disorder: A naturalistic diffusion tensor imaging study.

    PubMed

    Epstein, Katherine A; Kumra, Sanjiv

    2015-04-30

    Recurrent exposure to cannabis in adolescence increases the risk for later development of psychosis, but there are sparse data regarding the impact of cannabis use on brain structure during adolescence. This pilot study investigated the effect of cannabis use disorder (CUD) upon white matter fractional anisotropy (WM FA) values in non-psychotic treatment-seeking adolescents relative to adolescents with early onset schizophrenia-spectrum disorders (EOSS) and to healthy control (HC) participants. Diffusion tensor imaging (DTI) and tractography methods were used to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus (SLF), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus in adolescents with EOSS (n=34), CUD (n=19) and HC (n=29). Participants received DTI and substance use assessments at baseline and at 18-month follow-up. Using multivariate analysis of variance, a significant main effect of diagnostic group was observed. Post-hoc testing revealed that adolescents with CUD showed an altered change in FA values in the left ILF and in the left IFOF (trend level) compared with HC adolescents. Greater consumption of cannabis during the inter-scan interval predicted a greater decrease in left ILF FA in CUD. These preliminary longitudinal data suggest that heavy cannabis use during adolescence, or some factor associated with cannabis use, is associated with an altered change in WM FA values in a fiber bundle that has been implicated in the pathophysiology of EOSS (i.e., the left ILF). Additional studies are needed to clarify the clinical significance of these findings. PMID:25779033

  12. Involuntary switching into the native language induced by electrocortical stimulation of the superior temporal gyrus: a multimodal mapping study.

    PubMed

    Tomasino, Barbara; Marin, Dario; Canderan, Cinzia; Maieron, Marta; Budai, Riccardo; Fabbro, Franco; Skrap, Miran

    2014-09-01

    We describe involuntary language switching from L2 to L1 evoked by electro-stimulation in the superior temporal gyrus in a 30-year-old right-handed Serbian (L1) speaker who was also a late Italian learner (L2). The patient underwent awake brain surgery. Stimulation of other portions of the exposed cortex did not cause language switching as did not stimulation of the left inferior frontal gyrus, where we evoked a speech arrest. Stimulation effects on language switching were selective, namely, interfered with counting behaviour but not with object naming. The coordinates of the positive site were combined with functional and fibre tracking (DTI) data. Results showed that the language switching site belonged to a significant fMRI cluster in the left superior temporal gyrus/supramarginal gyrus found activated for both L1 and L2, and for both the patient and controls, and did not overlap with the inferior fronto-occipital fasciculus (IFOF), the inferior longitudinal fasciculus (ILF) and the superior longitudinal fasciculus (SLF). This area, also known as Stp, has a role in phonological processing. Language switching phenomenon we observed can be partly explained by transient dysfunction of the feed-forward control mechanism hypothesized by the DIVA (Directions Into Velocities of Articulators) model (Golfinopoulos, E., Tourville, J. A., & Guenther, F. H. (2010). The integration of large-scale neural network modeling and functional brain imaging in speech motor control. PMID:25058058

  13. Abstract--This paper proposes a complete IFoF system architecture derived from simplified IEEE802.15.3c PHY layer

    E-print Network

    Boyer, Edmond

    , the Techim@ges project [1] included in "Media & Network" Cluster. The hardware platform is oriented on a low1 Abstract--This paper proposes a complete IFoF system architecture derived from simplified IEEE802.15.3c PHY layer proposal to successfully ensure near 1 Gbps on the air interface. The system

  14. Individual structural differences in left inferior parietal area are associated with schoolchildrens' arithmetic scores

    PubMed Central

    Li, Yongxin; Hu, Yuzheng; Wang, Yunqi; Weng, Jian; Chen, Feiyan

    2013-01-01

    Arithmetic skill is of critical importance for academic achievement, professional success and everyday life, and childhood is the key period to acquire this skill. Neuroimaging studies have identified that left parietal regions are a key neural substrate for representing arithmetic skill. Although the relationship between functional brain activity in left parietal regions and arithmetic skill has been studied in detail, it remains unclear about the relationship between arithmetic achievement and structural properties in left inferior parietal area in schoolchildren. The current study employed a combination of voxel-based morphometry (VBM) for high-resolution T1-weighted images and fiber tracking on diffusion tensor imaging (DTI) to examine the relationship between structural properties in the inferior parietal area and arithmetic achievement in 10-year-old schoolchildren. VBM of the T1-weighted images revealed that individual differences in arithmetic scores were significantly and positively correlated with the gray matter (GM) volume in the left intraparietal sulcus (IPS). Fiber tracking analysis revealed that the forceps major, left superior longitudinal fasciculus (SLF), bilateral inferior longitudinal fasciculus (ILF) and inferior fronto-occipital fasciculus (IFOF) were the primary pathways connecting the left IPS with other brain areas. Furthermore, the regression analysis of the probabilistic pathways revealed a significant and positive correlation between the fractional anisotropy (FA) values in the left SLF, ILF and bilateral IFOF and arithmetic scores. The brain structure-behavior correlation analyses indicated that the GM volumes in the left IPS and the FA values in the tract pathways connecting left IPS were both related to children's arithmetic achievement. The present findings provide evidence that individual structural differences in the left IPS are associated with arithmetic scores in schoolchildren. PMID:24367320

  15. Dissecting the uncinate fasciculus: disorders, controversies and a hypothesis

    PubMed Central

    Von Der Heide, Rebecca J.; Skipper, Laura M.; Klobusicky, Elizabeth

    2013-01-01

    The uncinate fasciculus is a bidirectional, long-range white matter tract that connects lateral orbitofrontal cortex and Brodmann area 10 with the anterior temporal lobes. Although abnormalities in the uncinate fasciculus have been associated with several psychiatric disorders and previous studies suggest it plays a putative role in episodic memory, language and social emotional processing, its exact function is not well understood. In this review we summarize what is currently known about the anatomy of the uncinate, we review its role in psychiatric and neurological illnesses, and we evaluate evidence related to its putative functions. We propose that an overarching role of the uncinate fasciculus is to allow temporal lobe-based mnemonic associations (e.g. an individual’s name + face + voice) to modify behaviour through interactions with the lateral orbitofrontal cortex, which provides valence-based biasing of decisions. The bidirectionality of the uncinate fasciculus information flow allows orbital frontal cortex-based reward and punishment history to rapidly modulate temporal lobe-based mnemonic representations. According to this view, disruption of the uncinate may cause problems in the expression of memory to guide decisions and in the acquisition of certain types of learning and memory. Moreover, uncinate perturbation should cause problems that extend beyond memory to include social–emotional problems owing to people and objects being stripped of personal value and emotional history and lacking in higher-level motivational value. PMID:23649697

  16. The Role of the Arcuate Fasciculus in Conduction Aphasia

    ERIC Educational Resources Information Center

    Bernal, Byron; Ardila, Alfredo

    2009-01-01

    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…

  17. Diffusion Tensor Anisotropy in Adolescents and Adults

    Microsoft Academic Search

    Jason S. Schneiderman; Monte S. Buchsbaum; M. Mehmet. Haznedar; Erin A. Hazlett; Adam M. Brickman; Lina Shihabuddin; Jesse G. Brand; Yuliya Torosjan; Randall E. Newmark; Cheuk Tang; Jonathan Aronowitz; Reshmi Paul-Odouard; William Byne; Patrick R. Hof

    2007-01-01

    We acquired diffusion tensor images on 33 normal adults aged 22–64 and 15 adolescents aged 14–21. We assessed relative anisotropy in stereotaxically located regions of interest in the internal capsule, corpus callosum, anterior thalamic radiations, frontal anterior fasciculus, fronto-occipital fasciculus, temporal lobe white matter, cingulum bundle, frontal inferior longitudinal fasciculus, frontal superior longitudinal fasciculus, and optic radiations. All of these

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

    PubMed Central

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

    2013-01-01

    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. PMID:23300971

  19. Uncinate fasciculus abnormalities in recent onset schizophrenia and affective psychosis: A diffusion tensor imaging study

    E-print Network

    Uncinate fasciculus abnormalities in recent onset schizophrenia and affective psychosis of illness and specific to schizophrenia. Fifteen schizophrenia subjects and 15 affective psychosis within 4 years of first hospitalization (12 patients with schizophrenia and 12 patients with affective psychosis

  20. Am J Psychiatry 159:5, May 2002 813 Uncinate Fasciculus Findings in Schizophrenia

    E-print Network

    Am J Psychiatry 159:5, May 2002 813 Article Uncinate Fasciculus Findings in Schizophrenia in schizophrenia. Conventional magnetic resonance imaging (MRI) stud- ies, however, have not shown compelling integ- rity. The first three diffusion tensor imag- ing studies in schizophrenia showed lower

  1. Anatomical Properties of the Arcuate Fasciculus Predict Phonological and Reading Skills in Children

    ERIC Educational Resources Information Center

    Yeatman, Jason D.; Dougherty, Robert F.; Rykhlevskaia, Elena; Sherbondy, Anthony J.; Deutsch, Gayle K.; Wandell, Brian A.; Ben-Shachar, Michal

    2011-01-01

    For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual…

  2. Evaluating the Arcuate Fasciculus With Combined Diffusion-Weighted MRI Tractography and Electrocorticography

    PubMed Central

    Brown, Erik C.; Jeong, Jeong-Won; Muzik, Otto; Rothermel, Robert; Matsuzaki, Naoyuki; Juhász, Csaba; Sood, Sandeep; Asano, Eishi

    2014-01-01

    The conventional model of language-related brain structure describing the arcuate fasciculus as a key white matter tract providing a direct connection between Wernicke’s region and Broca’s area has been called into question. Specifically, the inferior precentral gyrus, possessing both primary motor (Brodmann Area [BA] 4) and premotor cortex (BA 6), has been identified as a potential alternative termination. The authors initially localized cortical sites involved in language using measurement of event-related gamma-activity on electrocorticography (ECoG). The authors then determined whether language-related sites of the temporal lobe were connected, via white matter structures, to the inferior frontal gyrus more tightly than to the precentral gyrus. The authors found that language-related sites of the temporal lobe were far more likely to be directly connected to the inferior precentral gyrus through the arcuate fasciculus. Furthermore, tractography was a significant predictor of frontal language-related ECoG findings. Analysis of an interaction between anatomy and tractography in this model revealed tractrography to have the highest predictive value for language-related ECoG findings of the precentral gyrus. This study failed to support the conventional model of language-related brain structure. More feasible models should include the inferior precentral gyrus as a termination of the arcuate fasciculus. The exact functional significance of direct connectivity between temporal language-related sites and the precentral gyrus requires further study. PMID:23982893

  3. Microstructural connectivity of the arcuate fasciculus in adolescents with high-functioning autism.

    PubMed

    Fletcher, P Thomas; Whitaker, Ross T; Tao, Ran; DuBray, Molly B; Froehlich, Alyson; Ravichandran, Caitlin; Alexander, Andrew L; Bigler, Erin D; Lange, Nicholas; Lainhart, Janet E

    2010-07-01

    The arcuate fasciculus is a white matter fiber bundle of great importance in language. In this study, diffusion tensor imaging (DTI) was used to infer white matter integrity in the arcuate fasciculi of a group of subjects with high-functioning autism and a control group matched for age, handedness, IQ, and head size. The arcuate fasciculus for each subject was automatically extracted from the imaging data using a new volumetric DTI segmentation algorithm. The results showed a significant increase in mean diffusivity (MD) in the autism group, due mostly to an increase in the radial diffusivity (RD). A test of the lateralization of DTI measurements showed that both MD and fractional anisotropy (FA) were less lateralized in the autism group. These results suggest that white matter microstructure in the arcuate fasciculus is affected in autism and that the language specialization apparent in the left arcuate of healthy subjects is not as evident in autism, which may be related to poorer language functioning. PMID:20132894

  4. Microstructural connectivity of the arcuate fasciculus in adolescents with high-functioning autism

    PubMed Central

    Fletcher, P. Thomas; Whitaker, Ross T.; Tao, Ran; DuBray, Molly B.; Froehlich, Alyson; Ravichandran, Caitlin; Alexander, Andrew L.; Bigler, Erin D.; Lange, Nicholas; Lainhart, Janet E.

    2010-01-01

    The arcuate fasciculus is a white matter fiber bundle of great importance in language. In this study, diffusion tensor imaging (DTI) was used to infer white matter integrity in the arcuate fasciculi of a group of subjects with high-functioning autism and a control group matched for age, handedness, IQ, and head size. The arcuate fasciculus for each subject was automatically extracted from the imaging data using a new volumetric DTI segmentation algorithm. The results showed a significant increase in mean diffusivity (MD) in the autism group, due mostly to an increase in the radial diffusivity (RD). A test of the lateralization of DTI measurements showed that both MD and fractional anisotropy (FA) were less lateralized in the autism group. These results suggest that white matter microstructure in the arcuate fasciculus is affected in autism and that the language specialization apparent in the left arcuate of healthy subjects is not as evident in autism, which may be related to poorer language functioning. PMID:20132894

  5. 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

    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

    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,…

  6. Alterations in white matter integrity in first-episode, treatment-naive patients with somatization disorder.

    PubMed

    Zhang, Jian; Jiang, Muliang; Yao, Dapeng; Dai, Yi; Long, Liling; Yu, Miaoyu; Liu, Jianrong; Zhang, Zhikun; Xiao, Changqing; Guo, Wenbin

    2015-07-10

    White matter (WM) abnormality in somatization disorder (SD) has not been reported yet. This study was designed to elucidate the alterations in WM integrity in SD. A total of 25 patients with SD and 28 healthy controls were enrolled in the study. WM integrity was analyzed using tract-based spatial statistics. No differences were found between the patients and the controls for fractional anisotropy (FA) values, mean diffusivity (MD), axial diffusivity, and radial diffusivity values at the corrected p<0.05 level. Patients with SD had significantly decreased FA values in the cingulum and inferior fronto-occipital fasciculus, and significantly increased MD values in the anterior thalamic radiation and corticospinal tract compared with the controls at the uncorrected p<0.005 level. Somatization severity was correlated with the FA values of the cingulum and inferior fronto-occipital fasciculus in the patients. The patients exhibit suggestive alterations in WM integrity in the cingulum, inferior fronto-occipital fasciculus, anterior thalamic radiation, and corticospinal tract. PMID:26003450

  7. Left Hemisphere Diffusivity of the Arcuate Fasciculus: Influences of Autism Spectrum Disorder and Language Impairment

    PubMed Central

    Roberts, T.P.L.; Heiken, K.; Zarnow, D.; Dell, J.; Nagae, L.; Blaskey, L.; Solot, C.; Levy, S.E.; Berman, J.I.; Edgar, J.C.

    2014-01-01

    BACKGROUND AND PURPOSE There has been much discussion whether brain abnormalities associated with specific language impairment and autism with language impairment are shared or are disorder specific. Although white matter tract abnormalities are observed in both specific language impairment and autism spectrum disorders, the similarities and differences in the white matter abnormalities in these 2 disorders have not been fully determined. MATERIALS AND METHODS Diffusion tensor imaging diffusion parameters of the arcuate fasciculus were measured in 14 children with specific language impairment as well as in 16 children with autism spectrum disorder with language impairment, 18 with autism spectrum disorder without language impairment, and 25 age-matched typically developing control participants. RESULTS Language impairment and autism spectrum disorder both had (elevating) main effects on mean diffusivity of the left arcuate fasciculus, initially suggesting a shared white matter substrate abnormality. Analysis of axial and radial diffusivity components, however, indicated that autism spectrum disorder and language impairment differentially affect white matter microstructural properties, with a main effect of autism spectrum disorder on axial diffusivity and a main effect of language impairment on radial diffusivity. CONCLUSIONS Although white matter abnormalities appear similar in language impairment and autism spectrum disorder when examining broad white matter measures, a more detailed analysis indicates different mechanisms for the white matter microstructural anomalies associated with language impairment and autism spectrum disorder. PMID:24335547

  8. Psychopathic traits modulate microstructural integrity of right uncinate fasciculus in a community population

    PubMed Central

    Sobhani, Mona; Baker, Laura; Martins, Bradford; Tuvblad, Catherine; Aziz-Zadeh, Lisa

    2015-01-01

    Individuals with psychopathy possess emotional and behavioral abnormalities. Two neural regions, involved in behavioral control and emotion regulation, are often implicated: amygdala and ventromedial prefrontal cortex (VMPFC). Recently, in studies using adult criminal populations, reductions in microstructural integrity of the white matter connections (i.e., uncinate fasciculus (UF)) between these two neural regions have been discovered in criminals with psychopathy, supporting the notion of neural dysfunction in the amygdala–VMPFC circuit. Here, a young adult, community sample is used to assess whether psychopathic traits modulate microstructural integrity of UF, and whether this relationship is dependent upon levels of trait anxiety, which is sometimes used to distinguish subtypes of psychopathy. Results reveal a negative association between psychopathic traits and microstructural integrity of UF, supporting previous findings. However, no moderation of the relationship by trait anxiety was discovered. Findings provide further support for the notion of altered amygdala–VMPFC connectivity in association with higher psychopathic traits.

  9. Bilateral agenesis of arcuate fasciculus demonstrated by fiber tractography in congenital bilateral perisylvian syndrome.

    PubMed

    Kilinc, Ozden; Ekinci, Gazanfer; Demirkol, Ezgi; Agan, Kadriye

    2015-03-01

    Congenital bilateral perisylvian syndrome (CBPS) is a type of cortical developmental abnormality associated with distinctive clinical and imaging features. Clinical spectrum of this syndrome is quite heterogeneous, with different degrees of neurological impairment in affected individuals. High-definition magnetic resonance imaging (MRI) has a great importance in revealing the presence of CBPS, but is limited in elucidating the heterogeneous clinical spectrum. The arcuate fasciculus (AF) is a prominent language tract in the perisylvian region interconnecting Broca and Wernicke areas, and has a high probability of being affected developmentally in CBPS. Herein, we report a case of CBPS with investigation of AF using diffusion tensor imaging (DTI) and fiber tractography in relation to clinical findings. We postulated that proven absence of AF on DTI and fiber tractography would correlate with a severe phenotype of CBPS. PMID:24852949

  10. More is not always better: increased fractional anisotropy of superior longitudinal fasciculus associated with poor visuospatial abilities in Williams syndrome.

    PubMed

    Hoeft, Fumiko; Barnea-Goraly, Naama; Haas, Brian W; Golarai, Golijeh; Ng, Derek; Mills, Debra; Korenberg, Julie; Bellugi, Ursula; Galaburda, Albert; Reiss, Allan L

    2007-10-31

    We used diffusion tensor imaging to examine white matter integrity in the dorsal and ventral streams among individuals with Williams syndrome (WS) compared with two control groups (typically developing and developmentally delayed) and using three separate analysis methods (whole brain, region of interest, and fiber tractography). All analysis methods consistently showed that fractional anisotropy (FA; a measure of microstructural integrity) was higher in the right superior longitudinal fasciculus (SLF) in WS compared with both control groups. There was a significant association with deficits in visuospatial construction and higher FA in WS individuals. Comparable increases in FA across analytic methods were not observed in the left SLF or the bilateral inferior longitudinal fasciculus in WS subjects. Together, these findings suggest a specific role of right SLF abnormality in visuospatial construction deficits in WS. PMID:17978036

  11. Detection of the arcuate fasciculus in congenital amusia depends on the tractography algorithm

    PubMed Central

    Chen, Joyce L.; Kumar, Sukhbinder; Williamson, Victoria J.; Scholz, Jan; Griffiths, Timothy D.; Stewart, Lauren

    2015-01-01

    The advent of diffusion magnetic resonance imaging (MRI) allows researchers to virtually dissect white matter fiber pathways in the brain in vivo. This, for example, allows us to characterize and quantify how fiber tracts differ across populations in health and disease, and change as a function of training. Based on diffusion MRI, prior literature reports the absence of the arcuate fasciculus (AF) in some control individuals and as well in those with congenital amusia. The complete absence of such a major anatomical tract is surprising given the subtle impairments that characterize amusia. Thus, we hypothesize that failure to detect the AF in this population may relate to the tracking algorithm used, and is not necessarily reflective of their phenotype. Diffusion data in control and amusic individuals were analyzed using three different tracking algorithms: deterministic and probabilistic, the latter either modeling two or one fiber populations. Across the three algorithms, we replicate prior findings of a left greater than right AF volume, but do not find group differences or an interaction. We detect the AF in all individuals using the probabilistic 2-fiber model, however, tracking failed in some control and amusic individuals when deterministic tractography was applied. These findings show that the ability to detect the AF in our sample is dependent on the type of tractography algorithm. This raises the question of whether failure to detect the AF in prior studies may be unrelated to the underlying anatomy or phenotype. PMID:25653637

  12. Diffusivity of the uncinate fasciculus in heroin users relates to their levels of anxiety

    PubMed Central

    Wong, N M L; Cheung, S-H; Chan, C C H; Zeng, H; Liu, Y-P; So, K-F; Lee, T M C

    2015-01-01

    Heroin use is closely associated with emotional dysregulation, which may explain its high comorbidity with disorders such as anxiety and depression. However, the understanding of the neurobiological etiology of the association between heroin use and emotional dysregulation is limited. Previous studies have suggested an impact of heroin on diffusivity in white matter involving the emotional regulatory system, but the specificity of this finding remains to be determined. Therefore, this study investigated the association between heroin use and diffusivity of white matter tracts in heroin users and examined whether the tracts were associated with their elevated anxiety and depression levels. A sample of 26 right-handed male abstinent heroin users (25 to 42 years of age) and 32 matched healthy controls (19 to 55 years of age) was recruited for this study. Diffusion tensor imaging data were collected, and their levels of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Our findings indicated that heroin users exhibited higher levels of anxiety and depression, but the heroin use-associated left uncinate fasciculus was only related to their anxiety level, suggesting that association between heroin and anxiety has an incremental organic basis but that for depression could be a threshold issue. This finding improves our understanding of heroin addiction and its comorbid affective disorder and facilitates future therapeutic development. PMID:25918991

  13. Uncinate Fasciculus Abnormalities in Recent Onset Schizophrenia and Affective Psychosis: A Diffusion Tensor Imaging Study

    PubMed Central

    Kawashima, Toshiro; Nakamura, Motoaki; Bouix, Sylvain; Kubicki, Marek; Salisbury, Dean F.; Westin, Carl-Fredrik; McCarley, Robert W.; Shenton, Martha E.

    2009-01-01

    Two of the most frequently investigated regions in diffusion tensor imaging studies in chronic schizophrenia are the uncinate fasciculus (UF) and cingulum bundle (CB). The purpose of the present study was to determine whether UF and CB white matter integrity were altered at the early stage of illness and specific to schizophrenia. Fifteen schizophrenia subjects and 15 affective psychosis within 4 years of first hospitalization (12 patients with schizophrenia and 12 patients with affective psychosis during their first hospitalization), and 15 psychiatrically healthy controls underwent line-scan diffusion tensor imaging. Fractional anisotropy (FA) and mean diffusivity (Dm) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Bilaterally reduced FA, but not Dm, was present in the UF of schizophrenia compared with healthy controls. Affective psychosis was intermediate between schizophrenia subjects and healthy controls, but not significantly different from either. For CB, there was no significant group difference for FA or Dm. These findings suggested that UF, but not CB, white matter integrity is altered at the early stage of illness in schizophrenia although it may not be specific to schizophrenia. The CB abnormalities reported in chronic schizophrenia may develop during the later course of the disease. PMID:19328656

  14. The vertical occipital fasciculus: A century of controversy resolved by in vivo measurements

    PubMed Central

    Yeatman, Jason D.; Weiner, Kevin S.; Pestilli, Franco; Rokem, Ariel; Mezer, Aviv; Wandell, Brian A.

    2014-01-01

    The vertical occipital fasciculus (VOF) is the only major fiber bundle connecting dorsolateral and ventrolateral visual cortex. Only a handful of studies have examined the anatomy of the VOF or its role in cognition in the living human brain. Here, we trace the contentious history of the VOF, beginning with its original discovery in monkey by Wernicke (1881) and in human by Obersteiner (1888), to its disappearance from the literature, and recent reemergence a century later. We introduce an algorithm to identify the VOF in vivo using diffusion-weighted imaging and tractography, and show that the VOF can be found in every hemisphere (n = 74). Quantitative T1 measurements demonstrate that tissue properties, such as myelination, in the VOF differ from neighboring white-matter tracts. The terminations of the VOF are in consistent positions relative to cortical folding patterns in the dorsal and ventral visual streams. Recent findings demonstrate that these same anatomical locations also mark cytoarchitectonic and functional transitions in dorsal and ventral visual cortex. We conclude that the VOF is likely to serve a unique role in the communication of signals between regions on the ventral surface that are important for the perception of visual categories (e.g., words, faces, bodies, etc.) and regions on the dorsal surface involved in the control of eye movements, attention, and motion perception. PMID:25404310

  15. Atypical hemispheric asymmetry in the arcuate fasciculus of completely nonverbal children with autism

    PubMed Central

    Wan, Catherine Y.; Marchina, Sarah; Norton, Andrea; Schlaug, Gottfried

    2015-01-01

    Despite the fact that as many as 25% of the children diagnosed with autism spectrum disorders are nonverbal, surprisingly little research has been conducted on this population. In particular, the mechanisms that underlie their absence of speech remain unknown. Using diffusion tensor imaging, we compared the structure of a language-related white matter tract (the arcuate fasciculus, AF) in five completely nonverbal children with autism to that of typically developing children. We found that, as a group, the nonverbal children did not show the expected left–right AF asymmetry—rather, four of the five nonverbal children actually showed the reversed pattern. It is possible that this unusual pattern of asymmetry may underlie some of the severe language deficits commonly found in autism, particularly in children whose speech fails to develop. Furthermore, novel interventions (such as auditory-motor mapping training) designed to engage brain regions that are connected via the AF may have important clinical potential for facilitating expressive language in nonverbal children with autism. PMID:22524376

  16. Arthroscopic glenohumeral folds and microscopic glenohumeral ligaments: the fasciculus obliquus is the missing link.

    PubMed

    Pouliart, Nicole; Somers, Katia; Gagey, Olivier

    2008-01-01

    This study tested the hypotheses that the folds in the inferior glenohumeral capsule appear at the borders and crossings of the underlying capsular ligaments and that embalming may result in misinterpretation of these folds as ligaments. The inferior capsular structures in 80 unembalmed cadaver shoulders were compared with 24 embalmed shoulders. During arthroscopy and dissection, an anteroinferior fold was more prominently seen in internal rotation and was almost obliterated in external rotation. A posteroinferior fold appeared in external rotation and almost disappeared in internal rotation. During dissection, the anteroinferior fold developed at the border of the anterior band of the inferior glenohumeral ligament (ABIGHL) and where this ligament crossed with the fasciculus obliquus (FO). Several patterns of crossing of the ABIGHL and the FO were seen that determined the folding-unfolding mechanism of the anteroinferior fold and the appearance of possible synovial recesses. The axillary part of the IGHL is formed by the FO on the glenoid side and by the ABIGHL on the humeral side. The posteroinferior fold was determined by the posterior band of the IGHL. The folds in the embalmed specimens did not necessarily correspond with the underlying fibrous structure of the capsule. The folds and recesses observed during arthroscopy indicate the underlying capsular ligaments but are not the ligaments themselves. The IGHL complex is formed by its anterior and posterior bands and also by the FO. Both findings are important during shoulder instability procedures because the ligaments need to be restored to their appropriate anatomy and tension. Because the FO may also be involved, Bankart-type surgery may have to reach far inferiorly. Midsubstance capsular shift procedures also need to incorporate this ligament. PMID:18328738

  17. Effect of clozapine on white matter integrity in patients with schizophrenia: a diffusion tensor imaging study.

    PubMed

    Ozcelik-Eroglu, Elcin; Ertugrul, Aygun; Oguz, Kader Karli; Has, Arzu Ceylan; Karahan, Sevilay; Yazici, Mumin Kazim

    2014-09-30

    Several diffusion tensor imaging (DTI) studies have reported disturbed white matter integrity in various brain regions in patients with schizophrenia, whereas only a few studied the effect of antipsychotics on DTI measures. The aim of this study was to investigate the effect of 12 weeks of clozapine treatment on DTI findings in patients with schizophrenia, and to compare the findings with those in unaffected controls. The study included 16 patients with schizophrenia who were assessed with the Positive and Negative Syndrome Scale, a neurocognitive test battery, and DTI at baseline and 12 weeks after the initiation of clozapine treatment. Eight unaffected controls were assessed once with the neurocognitive test battery and DTI. Voxel-wise analysis of DTI data was performed via tract-based spatial statistics (TBSS). Compared with the control group, the patient group exhibited lower fractional anisotropy (FA) in 16 brain regions, including the bilateral superior longitudinal fasciculi, inferior fronto-occipital fasciculi, superior and inferior parietal lobules, cingulate bundles, cerebellum, middle cerebellar peduncles, and left inferior longitudinal fasciculus, whereas the patients had higher FA in six regions, including the right parahippocampus, left anterior thalamic radiation, and right posterior limb of the internal capsule before clozapine treatment. After 12 weeks of treatment with clozapine, white matter FA was increased in widespread brain regions. In two of the regions where FA had initially been lower in patients compared with controls (left inferior fronto-occipital fasciculus and superior parietal lobule), clozapine appeared to increase FA. An improvement in semantic fluency was correlated with the increase in FA value in the left inferior fronto-occipital fasciculus. An increase in FA following 12 weeks of treatment with clozapine suggests that this treatment alters white matter microstructural integrity in patients with schizophrenia previously treated with typical and/or atypical antipsychotics and, in some locations, reverses a previous deficit. PMID:25012780

  18. Altered integrity of the right arcuate fasciculus as a trait marker of schizophrenia: a sibling study using tractography-based analysis of the whole brain.

    PubMed

    Wu, Chen-Hao; Hwang, Tzung-Jeng; Chen, Yu-Jen; Hsu, Yun-Chin; Lo, Yu-Chun; Liu, Chih-Min; Hwu, Hai-Gwo; Liu, Chen-Chung; Hsieh, Ming H; Chien, Yi Ling; Chen, Chung-Ming; Tseng, Wen-Yih Isaac

    2015-03-01

    Trait markers of schizophrenia aid the dissection of the heterogeneous phenotypes into distinct subtypes and facilitate the genetic underpinning of the disease. The microstructural integrity of the white matter tracts could serve as a trait marker of schizophrenia, and tractography-based analysis (TBA) is the current method of choice. Manual tractography is time-consuming and limits the analysis to preselected fiber tracts. Here, we sought to identify a trait marker of schizophrenia from among 74 fiber tracts across the whole brain using a novel automatic TBA method. Thirty-one patients with schizophrenia, 31 unaffected siblings and 31 healthy controls were recruited to undergo diffusion spectrum magnetic resonance imaging at 3T. Generalized fractional anisotropy (GFA), an index reflecting tract integrity, was computed for each tract and compared among the three groups. Ten tracts were found to exhibit significant differences between the groups with a linear, stepwise order from controls to siblings to patients; they included the right arcuate fasciculus, bilateral fornices, bilateral auditory tracts, left optic radiation, the genu of the corpus callosum, and the corpus callosum to the bilateral dorsolateral prefrontal cortices, bilateral temporal poles, and bilateral hippocampi. Posthoc between-group analyses revealed that the GFA of the right arcuate fasciculus was significantly decreased in both the patients and unaffected siblings compared to the controls. Furthermore, the GFA of the right arcuate fasciculus exhibited a trend toward positive symptom scores. In conclusion, the right arcuate fasciculus may be a candidate trait marker and deserves further study to verify any genetic association. PMID:25366810

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

    PubMed

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

    2011-12-01

    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. PMID:22111962

  20. Excellent recovery of aphasia in a patient with complete injury of the arcuate fasciculus in the dominant hemisphere.

    PubMed

    Kwon, Hyeok Gyu; Jang, Sung Ho

    2011-01-01

    The arcuate fasciculus (AF) is the neural tract that connects Wernicke's area and Broca's area. The main role of the AF is speech repetition; therefore, injury to the AF typically causes conduction aphasia. We report on a patient who showed excellent recovery of aphasia despite complete injury of the AF due to a cerebral infarct. A 54-year-old, right-handed male presented with aphasia and right hemiparesis. Brain MRI showed an infarct in the left centrum semiovale and corona radiata. Diffusion tensor tractography for the AF was reconstructed using DTI-studio software. The Korean-Western Aphasia Battery (K-WAB) was used for measurement of language function. On K-WAB at 1 week after onset, his aphasia type was compatible with global aphasia (aphasia quotient: 12‰, fluency: 5‰, comprehension: 24‰, repetition: 15‰, and naming: 31‰). The patient underwent rehabilitative therapy, including language therapy and medication, which is known to facilitate recovery from aphasia, for a period of 24 months. His aphasia had improved to a nearly normal state at 30 months after onset; aphasia quotient: 93‰ (fluency: 91‰, comprehension: 92‰, repetition: 85‰, and naming: 96‰). The left AF showed a complete disruption on 27-month diffusion tensor tractography. Findings from this study suggest the possibility that aphasia might show good recovery, even in cases of severe injury of the AF. PMID:22207068

  1. Patterns of dysgraphia in primary progressive aphasia compared to post-stroke aphasia.

    PubMed

    Faria, Andreia V; Crinion, Jenny; Tsapkini, Kyrana; Newhart, Melissa; Davis, Cameron; Cooley, Shannon; Mori, Susumu; Hillis, Argye E

    2013-01-01

    We report patterns of dysgraphia in participants with primary progressive aphasia that can be explained by assuming disruption of one or more cognitive processes or representations in the complex process of spelling. These patterns are compared to those described in participants with focal lesions (stroke). Using structural imaging techniques, we found that damage to the left extrasylvian regions, including the uncinate, inferior fronto-occipital fasciculus, and sagittal stratum (including geniculostriate pathway and inferior longitudinal fasciculus), as well as other deep white and grey matter structures, was significantly associated with impairments in access to orthographic word forms and semantics (with reliance on phonology-to-orthography to produce a plausible spelling in the spelling to dictation task). These results contribute not only to our understanding of the patterns of dysgraphia following acquired brain damage but also the neural substrates underlying spelling. PMID:22713396

  2. Patterns of Dysgraphia in Primary Progressive Aphasia Compared to Post-Stroke Aphasia

    PubMed Central

    Faria, Andreia V.; Crinion, Jenny; Tsapkini, Kyrana; Newhart, Melissa; Davis, Cameron; Cooley, Shannon; Mori, Susumu; Hillis, Argye E.

    2013-01-01

    We report patterns of dysgraphia in participants with primary progressive aphasia that can be explained by assuming disruption of one or more cognitive processes or representations in the complex process of spelling. These patterns are compared to those described in participants with focal lesions (stroke). Using structural imaging techniques, we found that damage to the left extrasylvian regions, including the uncinate, inferior fronto-occipital fasciculus, and sagittal stratum (including geniculostriate pathway and inferior longitudinal fasciculus), as well as other deep white and grey matter structures, was significantly associated with impairments in access to orthographic word forms and semantics (with reliance on phonology-to-orthography to produce a plausible spelling in the spelling to dictation task). These results contribute not only to our understanding of the patterns of dysgraphia following acquired brain damage but also the neural substrates underlying spelling. PMID:22713396

  3. The language connectome: new pathways, new concepts.

    PubMed

    Dick, Anthony Steven; Bernal, Byron; Tremblay, Pascale

    2014-10-01

    The field of the neurobiology of language is experiencing a paradigm shift in which the predominant Broca-Wernicke-Geschwind language model is being revised in favor of models that acknowledge that language is processed within a distributed cortical and subcortical system. While it is important to identify the brain regions that are part of this system, it is equally important to establish the anatomical connectivity supporting their functional interactions. The most promising framework moving forward is one in which language is processed via two interacting "streams"--a dorsal and ventral stream--anchored by long association fiber pathways, namely the superior longitudinal fasciculus/arcuate fasciculus, uncinate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and two less well-established pathways, the middle longitudinal fasciculus and extreme capsule. In this article, we review the most up-to-date literature on the anatomical connectivity and function of these pathways. We also review and emphasize the importance of the often overlooked cortico-subcortical connectivity for speech via the "motor stream" and associated fiber systems, including a recently identified cortical association tract, the frontal aslant tract. These pathways anchor the distributed cortical and subcortical systems that implement speech and language in the human brain. PMID:24342910

  4. Failure to Identify the Left Arcuate Fasciculus at Diffusion Tractography Is a Specific Marker of Language Dysfunction in Pediatric Patients with Polymicrogyria

    PubMed Central

    Paldino, Michael J.; Hedges, Kara; Gaab, Nadine; Galaburda, Albert M.; Grant, P. Ellen

    2015-01-01

    Background. Polymicrogyric cortex demonstrates interindividual variation with regard to both extent of dyslamination and functional capacity. Given the relationship between laminar structure and white matter fibers, we sought to define the relationship between polymicrogyria (PMG), intrahemispheric association pathways, and network function. Methods. Each arcuate fasciculus (AF) was categorized as present or absent. Language was characterized by a pediatric neurologist. The presence of dysplastic cortex in the expected anatomic locations of Broca's (BA) and Wernicke's areas (WA) was evaluated by two pediatric neuroradiologists blinded to DTI and language data. Results. 16 PMG patients and 16 age/gender-matched controls were included. All normative controls had an identifiable left AF. 6/7 PMG patients with dysplastic cortex within BA and/or WA had no left AF; PMG patients without involvement of these regions had a lower frequency of absence of the left AF (p < 0.006). All patients without a left AF had some degree of language impairment. PMG patients without a left AF had a significantly greater frequency of language impairment compared to those PMG patients with a left AF (p < 0.003). Conclusion. In patients with PMG (1) the presence of dysplastic cortex within WA and/or BA is associated with absence of the left AF and (2) absence of the left AF is associated with language impairment.

  5. Widespread white matter tract aberrations in youth with familial risk for bipolar disorder.

    PubMed

    Roybal, Donna J; Barnea-Goraly, Naama; Kelley, Ryan; Bararpour, Layla; Howe, Meghan E; Reiss, Allan L; Chang, Kiki D

    2015-05-30

    Few studies have examined multiple measures of white matter (WM) differences in youth with familial risk for bipolar disorder (FR-BD). To investigate WM in the FR-BD group, we used three measures of WM structure and two methods of analysis. We used fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) to analyze diffusion tensor imaging (DTI) findings in 25 youth with familial risk for bipolar disorder, defined as having both a parent with BD and mood dysregulation, and 16 sex-, age-, and IQ-matched healthy controls. We conducted a whole brain voxelwise analysis using tract based spatial statistics (TBSS). Subsequently, we conducted a complementary atlas-based, region-of-interest analysis using Diffeomap to confirm results seen in TBSS. When TBSS was used, significant widespread between-group differences were found showing increased FA, increased AD, and decreased RD in the FR-BD group in the bilateral uncinate fasciculus, cingulum, cingulate, superior fronto-occipital fasciculus (SFOF), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, and corpus callosum. Atlas-based analysis confirmed significant between-group differences, with increased FA and decreased RD in the FR-BD group in the SLF, cingulum, and SFOF. We found significant widespread WM tract aberrations in youth with familial risk for BD using two complementary methods of DTI analysis. PMID:25779034

  6. Tract-based spatial statistics analysis of white matter changes in children with anisometropic amblyopia.

    PubMed

    Li, Qian; Zhai, Liying; Jiang, Qinying; Qin, Wen; Li, Qingji; Yin, Xiaohui; Guo, Mingxia

    2015-06-15

    Amblyopia is a neurological disorder of vision that follows abnormal binocular interaction or visual deprivation during early life. Previous studies have reported multiple functional or structural cortical alterations. Although white matter was also studied, it still cannot be clarified clearly which fasciculus was affected by amblyopia. In the present study, tract-based spatial statistics analysis was applied to diffusion tensor imaging (DTI) to investigate potential diffusion changes of neural tracts in anisometropic amblyopia. Fractional anisotropy (FA) value was calculated and compared between 20 amblyopic children and 18 healthy age-matched controls. In contrast to the controls, significant decreases in FA values were found in right optic radiation (OR), left inferior longitudinal fasciculus/inferior fronto-occipital fasciculus (ILF/IFO) and right superior longitudinal fasciculus (SLF) in the amblyopia. Furthermore, FA values of these identified tracts showed positive correlation with visual acuity. It can be inferred that abnormal visual input not only hinders OR from well developed, but also impairs fasciculi associated with dorsal and ventral visual pathways, which may be responsible for the amblyopic deficiency in object discrimination and stereopsis. Increased FA was detected in right posterior part of corpus callosum (CC) with a medium effect size, which may be due to compensation effect. DTI with subsequent measurement of FA is a useful tool for investigating neuronal tract involvement in amblyopia. PMID:25899779

  7. Lesions of the Fasciculus Retroflexus Alter Footshock-Induced cFos Expression in the Mesopontine Rostromedial Tegmental Area of Rats

    PubMed Central

    Brown, Paul Leon; Shepard, Paul D.

    2013-01-01

    Midbrain dopamine neurons are an essential part of the circuitry underlying motivation and reinforcement. They are activated by rewards or reward-predicting cues and inhibited by reward omission. The lateral habenula (lHb), an epithalamic structure that forms reciprocal connections with midbrain dopamine neurons, shows the opposite response being activated by reward omission or aversive stimuli and inhibited by reward-predicting cues. It has been hypothesized that habenular input to midbrain dopamine neurons is conveyed via a feedforward inhibitory pathway involving the GABAergic mesopontine rostromedial tegmental area. Here, we show that exposing rats to low-intensity footshock (four, 0.5 mA shocks over 20 min) induces cFos expression in the rostromedial tegmental area and that this effect is prevented by lesions of the fasciculus retroflexus, the principal output pathway of the habenula. cFos expression is also observed in the medial portion of the lateral habenula, an area that receives dense DA innervation via the fr and the paraventricular nucleus of the thalamus, a stress sensitive area that also receives dopaminergic input. High-intensity footshock (120, 0.8 mA shocks over 40 min) also elevates cFos expression in the rostromedial tegmental area, medial and lateral aspects of the lateral habenula and the paraventricular thalamus. In contrast to low-intensity footshock, increases in cFos expression within the rostromedial tegmental area are not altered by fr lesions suggesting a role for non-habenular inputs during exposure to highly aversive stimuli. These data confirm the involvement of the lateral habenula in modulating the activity of rostromedial tegmental area neurons in response to mild aversive stimuli and suggest that dopamine input may contribute to footshock- induced activation of cFos expression in the lateral habenula. PMID:23593280

  8. Reconstruction of the arcuate fasciculus for surgical planning in the setting of peritumoral edema using two-tensor unscented Kalman filter tractography

    PubMed Central

    Chen, Zhenrui; Tie, Yanmei; Olubiyi, Olutayo; Rigolo, Laura; Mehrtash, Alireza; Norton, Isaiah; Pasternak, Ofer; Rathi, Yogesh; Golby, Alexandra J.; O'Donnell, Lauren J.

    2015-01-01

    Background Diffusion imaging tractography is increasingly used to trace critical fiber tracts in brain tumor patients to reduce the risk of post-operative neurological deficit. However, the effects of peritumoral edema pose a challenge to conventional tractography using the standard diffusion tensor model. The aim of this study was to present a novel technique using a two-tensor unscented Kalman filter (UKF) algorithm to track the arcuate fasciculus (AF) in brain tumor patients with peritumoral edema. Methods Ten right-handed patients with left-sided brain tumors in the vicinity of language-related cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-Tesla magnetic resonance imaging (MRI) including a diffusion-weighted dataset with 31 directions. Fiber tractography was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform the delineation of the AF. Results from the two different tractography algorithms were compared visually and quantitatively. Results Using single-tensor streamline tractography, the AF appeared disrupted in four patients and contained few fibers in the remaining six patients. Two-tensor UKF tractography delineated an AF that traversed edematous brain areas in all patients. The volume of the AF was significantly larger on two-tensor UKF than on single-tensor streamline tractography (p < 0.01). Conclusions Two-tensor UKF tractography provides the ability to trace a larger volume AF than single-tensor streamline tractography in the setting of peritumoral edema in brain tumor patients.

  9. Neuroanatomical Abnormalities and Cognitive Impairments Are Shared by Adults with Attention-Deficit/Hyperactivity Disorder and Their Unaffected First-Degree Relatives

    PubMed Central

    Pironti, Valentino Antonio; Lai, Meng-Chuan; Müller, Ulrich; Dodds, Chris Martin; Suckling, John; Bullmore, Edward Thomas; Sahakian, Barbara Jacquelyn

    2014-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder, yet the search for genes with a definitive role in its etiology has been elusive. Deconstructing the disorder in its endophenotypic traits, where the variance is thought to be associated with a fewer number of genes, should boost the statistical power of molecular genetic studies and clarify the pathophysiology of ADHD. In this study, we tested for neuroanatomical and cognitive endophenotypes in a group of adults with ADHD, their unaffected first-degree relatives, and typically developing control subjects. Methods Sixty participants, comprising 20 adults with ADHD, 20 unaffected first-degree relatives, and 20 typically developing control subjects matched for age and gender undertook structural magnetic resonance imaging scans. Voxel-based morphometry with DARTEL was performed to obtain regional gray and white matter volumes. General linear analyses of the volumes of brain regions, adjusting for age and total intracranial volume, were used to compare groups. Sustained attention and response inhibition were also investigated as cognitive endophenotypes. Results Neuroanatomical abnormalities in gray matter volume in the right inferior frontal gyrus and white matter volume in the caudal portion of the right inferior fronto-occipital fasciculus were shared between ADHD probands and their unaffected first-degree relatives. In addition, impairments in sustained attention were also found to be shared between ADHD patients and their relatives. Conclusions Cognitive impairments in sustained attention and neuroanatomical abnormalities in the right inferior frontal gyrus and the posterior part of right inferior fronto-occipital fasciculus are putative neurocognitive endophenotypes in adult ADHD. PMID:24199662

  10. Clinical correlations of microstructural changes in progressive supranuclear palsy.

    PubMed

    Tessitore, Alessandro; Giordano, Alfonso; Caiazzo, Giuseppina; Corbo, Daniele; De Micco, Rosa; Russo, Antonio; Liguori, Sara; Cirillo, Mario; Esposito, Fabrizio; Tedeschi, Gioacchino

    2014-10-01

    In patients with progressive supranuclear palsy (PSP), previous reports have shown a severe white matter (WM) damage involving supra and infratentorial regions including cerebellum. In the present study, we investigated potential correlations between WM integrity loss and clinical-cognitive features of patients with PSP. By using magnetic resonance imaging and diffusion tensor imaging with tract based spatial statistic analysis, we analyzed WM volume in 18 patients with PSP and 18 healthy controls (HCs). All patients and HCs underwent a detailed clinical and neuropsychological evaluation. Relative to HCs, patients with PSP showed WM changes encompassing supra and infratentorial areas such as corpus callosum, fornix, midbrain, inferior fronto-occipital fasciculus, anterior thalamic radiation, superior cerebellar peduncle, superior longitudinal fasciculus, uncinate fasciculus, cingulate gyrus, and cortico-spinal tract bilaterally. Among different correlations between motor-cognitive features and WM structural abnormalities, we detected a significant association between fronto-cerebellar WM loss and executive cognitive impairment in patients with PSP. Our findings, therefore, corroborate the hypothesis that cognitive impairment in PSP may result from both "intrinsic" and "extrinsic" frontal lobe dysfunction, likely related to cerebellar disconnection. PMID:24786632

  11. Childhood adversity, depression, age and gender effects on white matter microstructure: a DTI study.

    PubMed

    Ugwu, Izuchukwu D; Amico, Francesco; Carballedo, Angela; Fagan, Andrew J; Frodl, Thomas

    2015-07-01

    Previous diffusion tensor imaging (DTI) studies have shown that various factors can affect white matter (WM) tract diffusivity. The aim of the present study was to investigate the effects of childhood adversity (CA), age and gender on WM diffusivity in tracts that are thought to be involved in emotional regulation in individuals with major depressive disorder (MDD) and healthy controls (HC). DTI was obtained from 46 subjects with MDD and 46 HC subjects. Data were pre-processed and deterministic tractography was applied in the cingulum, uncinate fasciculus (UF), fornix, superior longitudinal fasciculus (SLF) and fronto-occipital fasciculus (FOF). In subjects with a history of CA, fractional anisotropy (FA) was greater in the rostral cingulum (RC) and dorsal cingulum, whereas radial diffusivity (RD) was smaller in the RC when compared with subjects with no history of CA. In the UF, FOF and parahippocampal cingulum, FA was greater in the left hemisphere in the subjects with CA when compared with those without CA. Age affected FA, longitudinal diffusivity and RD in the UF, fornix, FOF and SLF, reflecting axonal and myelin degeneration with increasing age. Depression or gender did not have any effects on the diffusivity measures. Due to the cross-sectional nature of the study, a recall bias for CA and possible effects of medical treatment on diffusivity measures could have played a role. CA and age could increase the likelihood to develop WM microstructural anomalies in the brain affective network. Moreover, subjects with CA could be more vulnerable to FA changes. PMID:24744150

  12. Individual differences in white matter anatomy predict dissociable components of reading skill in adults.

    PubMed

    Welcome, Suzanne E; Joanisse, Marc F

    2014-08-01

    We used diffusion tensor imaging (DTI) to investigate relationships between white matter anatomy and different reading subskills in typical-reading adults. A series of analytic approaches revealed that phonological decoding ability is associated with anatomical markers that do not relate to other reading-related cognitive abilities. Thus, individual differences in phonological decoding might relate to connectivity between a network of cortical regions, while skills like sight word reading might rely less strongly on integration across regions. Specifically, manually-drawn ROIs and probabilistic tractography revealed an association between the volume and integrity of white matter underlying primary auditory cortex and nonword reading ability. In a related finding, more extensive cross-hemispheric connections through the isthmus of the corpus callosum predicted better phonological decoding. Atlas-based white matter ROIs demonstrated that relationships with nonword reading were strongest in the inferior fronto-occipital fasciculus and uncinate fasciculus that connect occipital and anterior temporal cortex with inferior frontal cortex. In contrast, tract volume underlying the left angular gyrus was related to nonverbal IQ. Finally, connectivity underlying functional ROIs that are differentially active during phonological and semantic processing predicted nonword reading and reading comprehension, respectively. Together, these results provide important insights into how white matter anatomy may relate to both typical reading subskills, and perhaps a roadmap for understanding neural connectivity in individuals with reading impairments. PMID:24704456

  13. Emerging structure-function relations in the developing face processing system.

    PubMed

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

    2014-11-01

    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

  14. Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with hepatitis C

    PubMed Central

    Castellon, Steven A.; Singer, Elyse J.; Nagarajan, Rajakumar; Sarma, Manoj K.; Smith, Jason; Thaler, Nicholas S.; Truong, Jonathan Hien; Schonfeld, Daniel; Thomas, M. Albert; Hinkin, Charles H.

    2015-01-01

    Objective: This study examined neurologic abnormalities (as measured by proton magnetic resonance spectroscopy imaging and diffusion tensor imaging), neurocognitive performance, and fatigue among a sample of adults with hepatitis C virus (HCV). We hypothesized that HCV+ individuals would demonstrate structural brain abnormalities and neurocognitive compromise consistent with frontostriatal dysfunction as well as increased fatigue compared to controls. Method: Participants were 76 individuals diagnosed with HCV and 20 controls who underwent a comprehensive neurocognitive evaluation and clinical assessments. A subset of the HCV+ participants (n = 29) and all controls underwent MRI. Results: Individuals diagnosed with chronic HCV infection demonstrated greater fractional anisotropy in the striatum as well as greater mean diffusivity in the fronto-occiptal fasciculus and external capsule compared to HCV? controls. HCV+ participants also demonstrated lower levels of N-acetylaspartate in bilateral parietal white matter and elevations in myo-inosital (mI) in bilateral frontal white matter compared to HCV? controls (all p values < 0.05). HCV+ participants also demonstrated significantly poorer neuropsychological performance, particularly in processing speed and verbal fluency. HCV+ patients reported higher levels of fatigue than controls, and fatigue was significantly correlated with diffusivity in the superior fronto-occipital fasciculus, elevations in mI in frontal white matter, and overall cognitive performance. Conclusions: Our results suggest that HCV-associated neurologic complications disrupt frontostriatal structures, which may result in increased fatigue and poorer cognitive performance, particularly in those cognitive domains regulated by frontostriatal regions. PMID:25610883

  15. Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome.

    PubMed

    Jalbrzikowski, Maria; Villalon-Reina, Julio E; Karlsgodt, Katherine H; Senturk, Damla; Chow, Carolyn; Thompson, Paul M; Bearden, Carrie E

    2014-01-01

    22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk. PMID:25426042

  16. Disconnection Mechanism and Regional Cortical Atrophy Contribute to Impaired Processing of Facial Expressions and Theory of Mind in Multiple Sclerosis: A Structural MRI Study

    PubMed Central

    Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R. G.; Illes, Zsolt

    2013-01-01

    Successful socialization requires the ability of understanding of others’ mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients. PMID:24349280

  17. Multi-modal MRI of mild traumatic brain injury

    PubMed Central

    Narayana, Ponnada A.; Yu, Xintian; Hasan, Khader M.; Wilde, Elisabeth A.; Levin, Harvey S.; Hunter, Jill V.; Miller, Emmy R.; Patel, Vipul Kumar S.; Robertson, Claudia S.; McCarthy, James J.

    2014-01-01

    Multi-modal magnetic resonance imaging (MRI) that included high resolution structural imaging, diffusion tensor imaging (DTI), magnetization transfer ratio (MTR) imaging, and magnetic resonance spectroscopic imaging (MRSI) were performed in mild traumatic brain injury (mTBI) patients with negative computed tomographic scans and in an orthopedic-injured (OI) group without concomitant injury to the brain. The OI group served as a comparison group for mTBI. MRI scans were performed both in the acute phase of injury (~24 h) and at follow-up (~90 days). DTI data was analyzed using tract based spatial statistics (TBSS). Global and regional atrophies were calculated using tensor-based morphometry (TBM). MTR values were calculated using the standard method. MRSI was analyzed using LC Model. At the initial scan, the mean diffusivity (MD) was significantly higher in the mTBI cohort relative to the comparison group in several white matter (WM) regions that included internal capsule, external capsule, superior corona radiata, anterior corona radiata, posterior corona radiata, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal tract in the right hemisphere. TBSS analysis failed to detect significant differences in any DTI measures between the initial and follow-up scans either in the mTBI or OI group. No significant differences were found in MRSI, MTR or morphometry between the mTBI and OI cohorts either at the initial or follow-up scans with or without family wise error (FWE) correction. Our study suggests that a number of WM tracts are affected in mTBI in the acute phase of injury and that these changes disappear by 90 days. This study also suggests that none of the MRI-modalities used in this study, with the exception of DTI, is sensitive in detecting changes in the acute phase of mTBI. PMID:25610770

  18. Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

    PubMed

    Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R G; Illes, Zsolt

    2013-01-01

    Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients. PMID:24349280

  19. The Microstructural Status of the Corpus Callosum Is Associated with the Degree of Motor Function and Neurological Deficit in Stroke Patients

    PubMed Central

    Liang, Fanrong; Huang, Wenhua

    2015-01-01

    Human neuroimaging studies and animal models have suggested that white matter damage from ischemic stroke leads to the functional and structural reorganization of perilesional and remote brain regions. However, the quantitative relationship between the transcallosal tract integrity and clinical motor performance score after stroke remains unexplored. The current study employed a tract-based spatial statistics (TBSS) analysis on diffusion tensor imaging (DTI) to investigate the relationship between white matter diffusivity changes and the clinical scores in stroke patients. Probabilistic fiber tracking was also used to identify structural connectivity patterns in the patients. Thirteen ischemic stroke patients and fifteen healthy control subjects participated in this study. TBSS analyses showed that the corpus callosum (CC) and bilateral corticospinal tracts (CST) in the stroke patients exhibited significantly decreased fractional anisotropy and increased axial and radial diffusivity compared with those of the controls. Correlation analyses revealed that the motor and neurological deficit scores in the stroke patients were associated with the value of diffusivity indices in the CC. Compared with the healthy control group, probabilistic fiber tracking analyses revealed that significant changes in the inter-hemispheric fiber connections between the left and right motor cortex in the stroke patients were primarily located in the genu and body of the CC, left anterior thalamic radiation and inferior fronto-occipital fasciculus, bilateral CST, anterior/superior corona radiate, cingulum and superior longitudinal fasciculus, strongly suggesting that ischemic induces inter-hemispheric network disturbances and disrupts the white matter fibers connecting motor regions. In conclusion, the results of the present study show that DTI-derived measures in the CC can be used to predict the severity of motor skill and neurological deficit in stroke patients. Changes in structural connectivity pattern tracking between the left and right motor areas, particularly in the body of the CC, might reflect functional reorganization and behavioral deficit. PMID:25875333

  20. Altered Structural and Functional Connectivity in Late Preterm Preadolescence: An Anatomic Seed-Based Study of Resting State Networks Related to the Posteromedial and Lateral Parietal Cortex

    PubMed Central

    Degnan, Andrew J.; Wisnowski, Jessica L.; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M.; Corby, Patricia; Schmithorst, Vincent J.; Panigrahy, Ashok

    2015-01-01

    Objective Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth. Methods Thirty-eight preadolescents (ages 9–13; 19 born in the late preterm period (?32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri). Results Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups. Conclusion Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing. PMID:26098888

  1. Anatomo-functional study of the temporo-parieto-occipital region: dissection, tractographic and brain mapping evidence from a neurosurgical perspective.

    PubMed

    De Benedictis, Alessandro; Duffau, Hugues; Paradiso, Beatrice; Grandi, Enrico; Balbi, Sergio; Granieri, Enrico; Colarusso, Enzo; Chioffi, Franco; Marras, Carlo Efisio; Sarubbo, Silvio

    2014-08-01

    The temporo-parieto-occipital (TPO) junction is a complex brain territory heavily involved in several high-level neurological functions, such as language, visuo-spatial recognition, writing, reading, symbol processing, calculation, self-processing, working memory, musical memory, and face and object recognition. Recent studies indicate that this area is covered by a thick network of white matter (WM) connections, which provide efficient and multimodal integration of information between both local and distant cortical nodes. It is important for neurosurgeons to have good knowledge of the three-dimensional subcortical organisation of this highly connected region to minimise post-operative permanent deficits. The aim of this dissection study was to highlight the subcortical functional anatomy from a topographical surgical perspective. Eight human hemispheres (four left, four right) obtained from four human cadavers were dissected according to Klingler's technique. Proceeding latero-medially, the authors describe the anatomical courses of and the relationships between the main pathways crossing the TPO. The results obtained from dissection were first integrated with diffusion tensor imaging reconstructions and subsequently with functional data obtained from three surgical cases, all resection of infiltrating glial tumours using direct electrical mapping in awake patients. The subcortical limits for performing safe lesionectomies within the TPO region are as follows: within the parietal region, the anterior horizontal part of the superior longitudinal fasciculus and, more deeply, the arcuate fasciculus; dorsally, the vertical projective thalamo-cortical fibres. For lesions located within the temporal and occipital lobes, the resection should be tailored according to the orientation of the horizontal associative pathways (the inferior fronto-occipital fascicle, inferior longitudinal fascicle and optic radiation). The relationships between the WM tracts and the ventricle system were also examined. These results indicate that a detailed anatomo-functional awareness of the WM architecture within the TPO area is mandatory when approaching intrinsic brain lesions to optimise surgical results and to minimise post-operative morbidity. PMID:24975421

  2. Distinct loci of lexical and semantic access deficits in aphasia: Evidence from voxel-based lesion-symptom mapping and diffusion tensor imaging.

    PubMed

    Harvey, Denise Y; Schnur, Tatiana T

    2015-06-01

    Naming pictures and matching words to pictures belonging to the same semantic category negatively affects language production and comprehension. By most accounts, semantic interference arises when accessing lexical representations in naming (e.g., Damian, Vigliocco, & Levelt, 2001) and semantic representations in comprehension (e.g., Forde & Humphreys, 1997). Further, damage to the left inferior frontal gyrus (LIFG), a region implicated in cognitive control, results in increasing semantic interference when items repeat across cycles in both language production and comprehension (Jefferies, Baker, Doran, & Lambon Ralph, 2007). This generates the prediction that the LIFG via white matter connections supports resolution of semantic interference arising from different loci (lexical vs semantic) in the temporal lobe. However, it remains unclear whether the cognitive and neural mechanisms that resolve semantic interference are the same across tasks. Thus, we examined which gray matter structures [using whole brain and region of interest (ROI) approaches] and white matter connections (using deterministic tractography) when damaged impact semantic interference and its increase across cycles when repeatedly producing and understanding words in 15 speakers with varying lexical-semantic deficits from left hemisphere stroke. We found that damage to distinct brain regions, the posterior versus anterior temporal lobe, was associated with semantic interference (collapsed across cycles) in naming and comprehension, respectively. Further, those with LIFG damage compared to those without exhibited marginally larger increases in semantic interference across cycles in naming but not comprehension. Lastly, the inferior fronto-occipital fasciculus, connecting the LIFG with posterior temporal lobe, related to semantic interference in naming, whereas the inferior longitudinal fasciculus (ILF), connecting posterior with anterior temporal regions related to semantic interference in comprehension. These neuroanatomical-behavioral findings have implications for models of the lexical-semantic language network by demonstrating that semantic interference in language production and comprehension involves different representations which differentially recruit a cognitive control mechanism for interference resolution. PMID:25880795

  3. Magnetic Resonance Imaging Measures of Brain Structure to Predict Antidepressant Treatment Outcome in Major Depressive Disorder

    PubMed Central

    Korgaonkar, Mayuresh S.; Rekshan, William; Gordon, Evian; Rush, A. John; Williams, Leanne M.; Blasey, Christine; Grieve, Stuart M.

    2014-01-01

    Background Less than 50% of patients with Major Depressive Disorder (MDD) reach symptomatic remission with their initial antidepressant medication (ADM). There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs. Methods 157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER. A score at week 8 of 7 or less on the 17 item Hamilton Rating Scale for Depression defined remission. Receiver Operator Characteristics (ROC) analysis using the first 50% participants was performed to define decision trees of baseline MRI volumetric and connectivity (fractional anisotropy) measures that differentiated non-remitters from remitters with maximal sensitivity and specificity. These decision trees were tested for replication in the remaining participants. Findings Overall, 35% of all participants achieved remission. ROC analyses identified two decision trees that predicted a high probability of non-remission and that were replicated: 1. Left middle frontal volume < 14 · 8 mL & right angular gyrus volume > 6 · 3 mL identified 55% of non-remitters with 85% accuracy; and 2. Fractional anisotropy values in the left cingulum bundle < 0 · 63, right superior fronto-occipital fasciculus < 0 · 54 and right superior longitudinal fasciculus < 0 · 50 identified 15% of the non-remitters with 84% accuracy. All participants who met criteria for both decision trees were correctly identified as non-remitters. Interpretation Pretreatment MRI measures seem to reliably identify a subset of patients who do not remit with a first step medication that includes one of these commonly used medications. Findings are consistent with a neuroanatomical basis for non-remission in depressed patients. Funding Brain Resource Ltd is the sponsor for the iSPOT-D study (NCT00693849).

  4. Abnormalities of cortical thickness, subcortical shapes, and white matter integrity in subcortical vascular cognitive impairment.

    PubMed

    Thong, Jamie Yu Jin; Du, Jia; Ratnarajah, Nagulan; Dong, Yanhong; Soon, Hock Wei; Saini, Monica; Tan, Ming Zhen; Ta, Anh Tuan; Chen, Christopher; Qiu, Anqi

    2014-05-01

    Subcortical vascular cognitive impairment (sVCI) is caused by lacunar infarcts or extensive and/or diffuse lesions in the white matter that may disrupt the white matter circuitry connecting cortical and subcortical regions and result in the degeneration of neurons in these regions. This study used structural magnetic resonance imaging (MRI) and high angular resolution diffusion imaging (HARDI) techniques to examine cortical thickness, subcortical shapes, and white matter integrity in mild vascular cognitive impairment no dementia (VCIND Mild) and moderate-to-severe VCI (MSVCI). Our study found that compared to controls (n = 25), VCIND Mild (n = 25), and MSVCI (n = 30) showed thinner cortex predominantly in the frontal cortex. The cortex in MSVCI was thinner in the parietal and lateral temporal cortices than that in VCIND Mild. Moreover, compared to controls, VCIND Mild and MSVCI showed smaller shapes (i.e., volume reduction) in the thalamus, putamen, and globus pallidus and ventricular enlargement. Finally, compared to controls, VCIND Mild, and MSVCI showed an increased mean diffusivity in the white matter, while decreased generalized fractional anisotropy was only found in the MSVCI subjects. The major axonal bundles involved in the white matter abnormalities were mainly toward the frontal regions, including the internal capsule/corona radiata, uncinate fasciculus, and anterior section of the inferior fronto-occipital fasciculus, and were anatomically connected to the affected cortical and subcortical structures. Our findings suggest that abnormalities in cortical, subcortical, and white matter morphology in sVCI occur in anatomically connected structures, and that abnormalities progress along a similar trajectory from the mild to moderate and severe conditions. PMID:23861356

  5. Joint source based morphometry identifies linked gray and white matter group differences

    PubMed Central

    Xu, Lai; Pearlson, Godfrey; Calhoun, Vince D.

    2009-01-01

    We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray–white matter regions identified in each of the joint sources included: 1) temporal — corpus callosum, 2) occipital/frontal — inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal —superior longitudinal fasciculus and 4) parietal/frontal — thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences. PMID:18992825

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

    PubMed Central

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

    2012-01-01

    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. PMID:22748698

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

    PubMed Central

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

    2013-01-01

    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

  8. Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity

    PubMed Central

    Whalley, Heather C.; Dimitrova, Rali; Sprooten, Emma; Dauvermann, Maria R.; Romaniuk, Liana; Duff, Barbara; Watson, Andrew R.; Moorhead, Bill; Bastin, Mark; Semple, Scott I.; Giles, Stephen; Hall, Jeremy; Thomson, Pippa; Roberts, Neil; Hughes, Zoe A.; Brandon, Nick J.; Dunlop, John; Whitcher, Brandon; Blackwood, Douglas H. R.; McIntosh, Andrew M.; Lawrie, Stephen M.

    2015-01-01

    Objective Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1) is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11) (q42.1;q14.3). Method Within the original pedigree, we examined the effects of the t(1;11) translocation on white matter integrity, measured by fractional anisotropy (FA). This included family members with (n = 7) and without (n = 13) the translocation, along with a clinical control sample of patients with psychosis (n = 34), and a group of healthy controls (n = 33). Results We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity. Conclusions We demonstrate that the t(1;11) translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis. PMID:26102360

  9. White matter disruptions in adolescents exposed to childhood maltreatment and vulnerability to psychopathology.

    PubMed

    Huang, Hao; Gundapuneedi, Tejasvi; Rao, Uma

    2012-11-01

    Childhood maltreatment has been known to produce long-lasting impairments in behavioral, cognitive and social functioning, but their underlying mechanisms are not well-understood. A better understanding of their underlying mechanisms will aid in developing effective preventive interventions. Nineteen adolescent volunteers with no personal history of a psychiatric illness, but who were exposed to maltreatment during childhood, and 13 adolescent volunteers with no personal or family history of a psychiatric disorder (controls) underwent diffusion tensor imaging (DTI) studies. The participants were then followed longitudinally at 6-month intervals for up to 5 years to determine the onset of mood and substance use disorders. The associations among fractional anisotropy (FA) values obtained from the DTI scans at baseline and psychopathology at follow-up were examined. At baseline, adolescents exposed to childhood maltreatment had significantly lower FA values in the left and right superior longitudinal fasciculi, right cingulum bundle projecting to the hippocampus, left inferior fronto-occipital fasciculus, and splenium of the corpus callosum compared with controls. Adolescents who developed major depressive disorder at follow-up had significantly lower FA values in the superior longitudinal fasciculi and the right cingulum-hippocampal projection compared with their counterparts who did not develop the illness. Adolescents who developed substance use disorder during follow-up had significantly lower FA values in the right cingulum-hippocampal projection than their counterparts without the disorder. These preliminary results suggest that white matter disruptions observed in adolescents exposed to childhood maltreatment may be associated with increased vulnerability to psychopathology, specifically depressive and substance use disorders. PMID:22850736

  10. GENETICS OF BRAIN FIBER ARCHITECTURE AND INTELLECTUAL PERFORMANCE

    PubMed Central

    Chiang, Ming-Chang; Barysheva, Marina; Shattuck, David W.; Lee, Agatha D.; Madsen, Sarah; 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.

    2009-01-01

    The paper 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 (DTI) 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 3D 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 (a2 = 0.55, P = 0.04, left; a2 = 0.74, P = 0.006, right), bilateral parietal (a2 = 0.85, P < 0.001, left; a2 = 0.84, P < 0.001, right) and left occipital (a2 = 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

  11. Diffuse alterations in grey and white matter associated with cognitive impairment in Shwachman–Diamond syndrome: Evidence from a multimodal approach

    PubMed Central

    Perobelli, Sandra; Alessandrini, Franco; Zoccatelli, Giada; Nicolis, Elena; Beltramello, Alberto; Assael, Baroukh M.; Cipolli, Marco

    2015-01-01

    Shwachman–Diamond syndrome is a rare recessive genetic disease caused by mutations in SBDS gene, at chromosome 7q11. Phenotypically, the syndrome is characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal dysplasia and variable cognitive impairments. Structural brain abnormalities (smaller head circumference and decreased brain volume) have also been reported. No correlation studies between brain abnormalities and neuropsychological features have yet been performed. In this study we investigate neuroanatomical findings, neurofunctional pathways and cognitive functioning of Shwachman–Diamond syndrome subjects compared with healthy controls. To be eligible for inclusion, participants were required to have known SBDS mutations on both alleles, no history of cranial trauma or any standard contraindication to magnetic resonance imaging. Appropriate tests were used to assess cognitive functions. The static images were acquired on a 3 × 0 T magnetic resonance scanner and blood oxygen level-dependent functional magnetic resonance imaging data were collected both during the execution of the Stroop task and at rest. Diffusion tensor imaging was used to assess brain white matter. The Tract-based Spatial Statistics package and probabilistic tractography were used to characterize white matter pathways. Nine participants (5 males), half of all the subjects aged 9–19 years included in the Italian Shwachman–Diamond Syndrome Registry, were evaluated and compared with nine healthy subjects, matched for sex and age. The patients performed less well than norms and controls on cognitive tasks (p = 0.0002). Overall, cortical thickness was greater in the patients, both in the left (+10%) and in the right (+15%) hemisphere, significantly differently increased in the temporal (left and right, p = 0.04), and right parietal (p = 0.03) lobes and in Brodmann area 44 (p = 0.04) of the right frontal lobe. The greatest increases were observed in the left limbic-anterior cingulate cortex (?43%, p < 0.0004). Only in Broca's area in the left hemisphere did the patients show a thinner cortical thickness than that of controls (p = 0.01). Diffusion tensor imaging showed large, significant difference increases in both fractional anisotropy (+37%, p < 0.0001) and mean diffusivity (+35%, p < 0.005); the Tract-based Spatial Statistics analysis identified six abnormal clusters of white matter fibres in the fronto-callosal, right fronto-external capsulae, left fronto-parietal, right pontine, temporo-mesial and left anterior–medial–temporal regions. Brain areas activated during the Stroop task and those active during the resting state, are different, fewer and smaller in patients and correlate with worse performance (p = 0.002). Cognitive impairment in Shwachman–Diamond syndrome subjects is associated with diffuse brain anomalies in the grey matter (verbal skills with BA44 and BA20 in the right hemisphere; perceptual skills with BA5, 37, 20, 21, 42 in the left hemisphere) and white matter connectivity (verbal skills with alterations in the fronto-occipital fasciculus and with the inferior-longitudinal fasciculus; perceptual skills with the arcuate fasciculus, limbic and ponto-cerebellar fasciculus; memory skills with the arcuate fasciculus; executive functions with the anterior cingulated and arcuate fasciculus). PMID:25844324

  12. Artifact quantification and tractography from 3T MRI after placement of aneurysm clips in subarachnoid hemorrhage patients

    PubMed Central

    2011-01-01

    Background The application of advanced 3T MRI imaging techniques to study recovery after subarachnoid hemorrhage (SAH) is complicated by the presence of image artifacts produced by implanted aneurysm clips. To characterize the effect of these artifacts on image quality, we sought to: 1) quantify extent of image artifact in SAH patients with implanted aneurysm clips across a range of MR sequences typically used in studies of volumetry, blood oxygen level dependent signal change (BOLD-fMRI), and diffusion-weighted imaging (DW-MRI) and 2) to explore the ability to reconstruct white matter pathways in these patients. Methods T1- and T2-weighted structural, BOLD-fMRI, and DW-MRI scans were acquired at 3T in two patients with titanium alloy clips in ACOM and left ACA respectively. Intensity-based planimetric contouring was performed on aligned image volumes to define each artifact. Artifact volumes were quantified by artifact/clip length and artifact/brain volume ratios and analyzed by two-way (scan-by-rater) ANOVAs. Tractography pathways were reconstructed from DW-MRI at varying distances from the artifacts using deterministic methods. Results Artifact volume varied by MR sequence for length (p = 0.007) and volume (p < 0.001) ratios: it was smallest for structural images, larger for DW-MRI acquisitions, and largest on fMRI images. Inter-rater reliability was high (r = 0.9626, p < 0.0001), and reconstruction of white matter connectivity characteristics increased with distance from the artifact border. In both patients, reconstructed white matter pathways of the uncinate fasciculus and inferior fronto-occipital fasciculus were clearly visible within 2 mm of the artifact border. Conclusions Advanced 3T MR can successfully image brain tissue around implanted titanium aneurysm clips at different spatial ranges depending on sequence type. White matter pathways near clip artifacts can be reconstructed and visualized. These findings provide a reference for designing functional and structural neuroimaging studies of recovery in aSAH patients after clip placement. PMID:21970560

  13. Visual-motor deficits relate to altered gray and white matter in young adults born preterm with very low birth weight.

    PubMed

    Sripada, Kam; Løhaugen, Gro C; Eikenes, Live; Bjørlykke, Kjerstin M; Håberg, Asta K; Skranes, Jon; Rimol, Lars M

    2015-04-01

    Individuals born preterm and at very low birth weight (birth weight ? 1500 g) are at an increased risk of perinatal brain injury and neurodevelopmental deficits over the long term. This study examined whether this clinical group has more problems with visual-motor integration, motor coordination, and visual perception compared to term-born controls, and related these findings to cortical surface area and thickness and white matter fractional anisotropy. Forty-seven preterm-born very low birth weight individuals and 56 term-born controls were examined at 18-22 years of age with a combined cognitive, morphometric MRI, and diffusion tensor imaging evaluation in Trondheim, Norway. Visual-motor skills were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration-V (VMI) copying test and its supplemental tests of motor coordination and visual perception. 3D T1-weighted MPRAGE images and diffusion tensor imaging were done at 1.5 T. Cortical reconstruction generated in FreeSurfer and voxelwise maps of fractional anisotropy calculated with Tract-Based Spatial Statistics were used to explore the relationship between MRI findings and cognitive results. Very low birth weight individuals had significantly lower scores on the copying and motor coordination tests compared with controls. In the very low birth weight group, VMI scores showed significant positive relationships with cortical surface area in widespread regions, with reductions of the superior temporal gyrus, insula, and medial occipital lobe in conjunction with the posterior ventral temporal lobe. Visual perception scores also showed positive relationships with cortical thickness in the very low birth weight group, primarily in the lateral occipito-temporo-parietal junction, the superior temporal gyrus, insula, and superior parietal regions. In the very low birth weight group, visual-motor performance correlated positively with fractional anisotropy especially in the corpus callosum, inferior fronto-occipital fasciculus bilaterally, and anterior thalamic radiation bilaterally, driven primarily by an increase in radial diffusivity. VMI scores did not demonstrate a significant relationship to cortical surface area, cortical thickness, or diffusion measures in the control group. Our results indicate that visual-motor integration problems persist into adulthood for very low birth weight individuals, which may be due to structural alterations in several specific gray-white matter networks. Visual-motor deficits appear related to reduced surface area of motor and visual cortices and disturbed connectivity in long association tracts containing visual and motor information. We conjecture that these outcomes may be due to perinatal brain injury or aberrant cortical development secondary to injury or due to very preterm birth. PMID:25592994

  14. Differences in the right inferior longitudinal fasciculus but no general disruption of white matter tracts in

    E-print Network

    Kanwisher, Nancy

    , and worse in the ASD group, with some scans unusable because of head motion artifacts. When we follow is reduced "integrity" of long-range white matter tracts, a claim based primarily on diffusion imaging standard data analysis practices (i.e., without matching head motion between groups), we replicate

  15. Delineation of the Inferior Longitudinal Fasciculus in Subjects with 22q11.2 Deletion Syndrome

    E-print Network

    using tractography. - Subjects: 18 young adult 22q11DS patients were matched on age, gender integrity and myelination in young adults with 22q11DS. BACKGROUND RESULTS CONCLUSIONS REFERENCES MATERIALS11.2 Deletion Syndrome (22q11DS) represents a population at high risk for developing schizophrenia

  16. Diffusion Tensor Imaging of the Superior Longitudinal Fasciculus and Working Memory

    E-print Network

    Poldrack, Russ

    ) in the left and right SLF in 12 young adult patients with recent-onset schizophrenia and 17 matched control-Onset Schizophrenia Katherine H. Karlsgodt, Theo G.M. van Erp, Russell A. Poldrack, Carrie E. Bearden, Keith H-parietal circuitry are thought to be associated with working memory (WM) deficits in patients with schizophrenia

  17. Anatomical Properties of the Arcuate Fasciculus Predict Phonological and Reading Skills in Children

    E-print Network

    Wandell, Brian A.

    that lesions in left posterior inferior frontal cortex (Brocas area) create a deficit in the ability to produce network model of language processing in the brain (Wernicke, 1874). His view of cortical com- putations portrayed the brain as a mosaic of sensory and motor representations, where new functions arise from novel

  18. Bryonora, Praha, 34 (2004) 41 Vzda A. (2003): Lichenes rariores exsiccati. Fasciculus 4950 (numeris 481500). Brno.

    E-print Network

    Kucera, Jan

    2004-01-01

    among Central European species of the aquatic moss Cinclidotus. ­ Cryptogamie Bryologie 24: 147. ­ Journal of Molecular Evolution 55: 595­605. Aldous A. R. (2002): Nitrogen translocation in Sphagnum mosses (2004) Allen B. (ed.) (2002): Moss flora of Central America. Part 2. Encalyptaceae

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

    ERIC Educational Resources Information Center

    Dick, Anthony Steven; Tremblay, Pascale

    2012-01-01

    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…

  20. Mapping the connectivity underlying multimodal (verbal and non-verbal) semantic processing: a brain electrostimulation study.

    PubMed

    Moritz-Gasser, Sylvie; Herbet, Guillaume; Duffau, Hugues

    2013-08-01

    Accessing the meaning of words, objects, people and facts is a human ability, made possible thanks to semantic processing. Although studies concerning its cortical organization are proficient, the subcortical connectivity underlying this semantic network received less attention. We used intraoperative direct electrostimulation, which mimics a transient virtual lesion during brain surgery for glioma in eight awaken patients, to map the anatomical white matter substrate subserving the semantic system. Patients performed a picture naming task and a non-verbal semantic association test during the electrical mapping. Direct electrostimulation of the inferior fronto-occipital fascicle, a poorly known ventral association pathway which runs throughout the brain, induced in all cases semantic disturbances. These transient disorders were highly reproducible, and concerned verbal as well as non-verbal output. Our results highlight for the first time the essential role of the left inferior fronto-occipital fascicle in multimodal (and not only in verbal) semantic processing. On the basis of these original findings, and in the lights of phylogenetic considerations regarding this fascicle, we suggest its possible implication in the monitoring of the human level of consciousness related to semantic memory, namely noetic consciousness. PMID:23778263

  1. Differences in the right inferior longitudinal fasciculus but no general disruption of white matter tracts in children with autism spectrum disorder

    E-print Network

    Koldewyn, Kami

    One of the most widely cited features of the neural phenotype of autism is reduced “integrity” of long-range white matter tracts, a claim based primarily on diffusion imaging studies. However, many prior studies have small ...

  2. White matter diffusion alterations in normal women at risk of Alzheimer's disease.

    PubMed

    Smith, Charles D; Chebrolu, Himachandra; Andersen, Anders H; Powell, David A; Lovell, Mark A; Xiong, Shuling; Gold, Brian T

    2010-07-01

    Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal fasciculi (particularly posteriorly), the splenium of the corpus callosum, subcallosal white matter and the cingulum bundle. These findings demonstrate that specific white matter pathways are altered in normal women at increased risk of AD years before the expected onset of cognitive symptoms. PMID:18801597

  3. 21 CFR 1.231 - How and where do you register?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...into its registration system, along with CD-ROM submissions, as soon as practicable...registration number. (c) Registration by CD-ROM for multiple submissions. If...of this section, you may register by CD-ROM. (1) Registrants submitting...

  4. 78 FR 53675 - Safety Zone; Lake Erie Heritage Foundation, Battle of Lake Erie Reenactment; Lake Erie, Put-in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-30

    ...OF HOMELAND SECURITY Coast Guard...Erie Heritage Foundation, Battle of...FOR FURTHER INFORMATION CONTACT: If...of Homeland Security FR Federal Register...comments or information that may lead...requirements, Security measures, Waterways...Erie Heritage Foundation, Battle...

  5. 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, 2010 CFR

    2010-04-01

    ...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...

  6. 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

    2013-04-01

    ...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...

  7. 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, 2014 CFR

    2014-04-01

    ...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...

  8. 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, 2012 CFR

    2012-04-01

    ...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...

  9. 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, 2011 CFR

    2011-04-01

    ...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...

  10. A computational modelling study of transcranial direct current stimulation montages used in depression.

    PubMed

    Bai, Siwei; Dokos, Socrates; Ho, Kerrie-Anne; Loo, Colleen

    2014-02-15

    Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which involves passing a mild electric current to the brain through electrodes placed on the scalp. Several clinical studies suggest that tDCS may have clinically meaningful efficacy in the treatment of depression. The objective of this study was to simulate and compare the effects of several tDCS montages either used in clinical trials or proposed, for the treatment of depression, in different high-resolution anatomically-accurate head models. Detailed segmented finite element head models of two subjects were presented, and a total of eleven tDCS electrode montages were simulated. Sensitivity analysis on the effects of changing the size of the anode, rotating both electrodes and displacing the anode was also conducted on selected montages. The F3-F8 and F3-F4 montages have been used in clinical trials reporting significant antidepressant effects and both result in relatively high electric fields in dorsolateral prefrontal cortices. Other montages using a fronto-extracephalic or fronto-occipital approach result in greater stimulation of central structures (e.g. anterior cingulate cortex) which may be advantageous in treating depression, but their efficacy has yet to be tested in randomised controlled trials. Results from sensitivity analysis suggest that electrode position and size may be adjusted slightly to accommodate other priorities, such as skin discomfort and damage. PMID:24246487

  11. Structural and effective connectivity reveals potential network-based influences on category-sensitive visual areas

    PubMed Central

    Furl, Nicholas

    2015-01-01

    Visual category perception is thought to depend on brain areas that respond specifically when certain categories are viewed. These category-sensitive areas are often assumed to be “modules” (with some degree of processing autonomy) and to act predominantly on feedforward visual input. This modular view can be complemented by a view that treats brain areas as elements within more complex networks and as influenced by network properties. This network-oriented viewpoint is emerging from studies using either diffusion tensor imaging to map structural connections or effective connectivity analyses to measure how their functional responses influence each other. This literature motivates several hypotheses that predict category-sensitive activity based on network properties. Large, long-range fiber bundles such as inferior fronto-occipital, arcuate and inferior longitudinal fasciculi are associated with behavioral recognition and could play crucial roles in conveying backward influences on visual cortex from anterior temporal and frontal areas. Such backward influences could support top-down functions such as visual search and emotion-based visual modulation. Within visual cortex itself, areas sensitive to different categories appear well-connected (e.g., face areas connect to object- and motion sensitive areas) and their responses can be predicted by backward modulation. Evidence supporting these propositions remains incomplete and underscores the need for better integration of DTI and functional imaging. PMID:25999841

  12. Origin of Emotion Effects on ERP Correlates of Emotional Word Processing: The Emotion Duality Approach

    PubMed Central

    Imbir, Kamil Konrad; Jarymowicz, Maria Teresa; Spustek, Tomasz; Ku?, Rafa?; ?ygierewicz, Jaros?aw

    2015-01-01

    We distinguish two evaluative systems which evoke automatic and reflective emotions. Automatic emotions are direct reactions to stimuli whereas reflective emotions are always based on verbalized (and often abstract) criteria of evaluation. We conducted an electroencephalography (EEG) study in which 25 women were required to read and respond to emotional words which engaged either the automatic or reflective system. Stimulus words were emotional (positive or negative) and neutral. We found an effect of valence on an early response with dipolar fronto-occipital topography; positive words evoked a higher amplitude response than negative words. We also found that topographically specific differences in the amplitude of the late positive complex were related to the system involved in processing. Emotional stimuli engaging the automatic system were associated with significantly higher amplitudes in the left-parietal region; the response to neutral words was similar regardless of the system engaged. A different pattern of effects was observed in the central region, neutral stimuli engaging the reflective system evoked a higher amplitudes response whereas there was no system effect for emotional stimuli. These differences could not be reduced to effects of differences between the arousing properties and concreteness of the words used as stimuli. PMID:25955719

  13. Basal forebrain administration of the somatostatin-analog octreotide does not affect cortical EEG in urethane anaesthetized rats.

    PubMed

    Tóth, Attila; Henter, T; Détári, L

    2012-12-01

    Basal forebrain (BF) plays an important role in the regulation of cortical activation. Somatostatin (SOM) is present both in local neurons as well as in fibers in the BF. In previous studies, SOM axons were found to innervate corticopetal cholinergic cells and SOM was found to presynaptically modulate GABA and glutamate release onto cholinergic neurons in the BF. However, no systematic analysis is available about the EEG effects of SOM or its analog, octreotide (OCTR) injected directly into the BF. In the present experiments, EEG changes were examined following an OCTR injection (0.5 microliter, 500 nmol) into the BF areas containing several choline acetyl transferase-immunoreactive neurons of urethane-anaesthetized rats. Fronto-occipital EEG was recorded on both sides and relative EEG power was calculated in the delta (0-3 Hz), theta (3-9 Hz), alpha (9-16 Hz) and beta (16-48 Hz) frequency bands. OCTR injected to the BF failed to induce significant EEG changes and did not affect tail pinch-evoked cortical activation. Lack of effect may be attributed to the urethane anaesthesia as well as to the possible complex interactions between SOM and BF cholinergic and GABAergic neurons. PMID:23238548

  14. Occipital Cortex of Blind Individuals Is Functionally Coupled with Executive Control Areas of Frontal Cortex.

    PubMed

    Deen, Ben; Saxe, Rebecca; Bedny, Marina

    2015-08-01

    In congenital blindness, the occipital cortex responds to a range of nonvisual inputs, including tactile, auditory, and linguistic stimuli. Are these changes in functional responses to stimuli accompanied by altered interactions with nonvisual functional networks? To answer this question, we introduce a data-driven method that searches across cortex for functional connectivity differences across groups. Replicating prior work, we find increased fronto-occipital functional connectivity in congenitally blind relative to blindfolded sighted participants. We demonstrate that this heightened connectivity extends over most of occipital cortex but is specific to a subset of regions in the inferior, dorsal, and medial frontal lobe. To assess the functional profile of these frontal areas, we used an n-back working memory task and a sentence comprehension task. We find that, among prefrontal areas with overconnectivity to occipital cortex, one left inferior frontal region responds to language over music. By contrast, the majority of these regions responded to working memory load but not language. These results suggest that in blindness occipital cortex interacts more with working memory systems and raise new questions about the function and mechanism of occipital plasticity. PMID:25803598

  15. Changes in whole-brain functional networks and memory performance in aging.

    PubMed

    Sala-Llonch, Roser; Junqué, Carme; Arenaza-Urquijo, Eider M; Vidal-Piñeiro, Dídac; Valls-Pedret, Cinta; Palacios, Eva M; Domènech, Sara; Salvà, Antoni; Bargalló, Nuria; Bartrés-Faz, David

    2014-10-01

    We used resting-functional magnetic resonance imaging data from 98 healthy older adults to analyze how local and global measures of functional brain connectivity are affected by age, and whether they are related to differences in memory performance. Whole-brain networks were created individually by parcellating the brain into 90 cerebral regions and obtaining pairwise connectivity. First, we studied age-associations in interregional connectivity and their relationship with the length of the connections. Aging was associated with less connectivity in the long-range connections of fronto-parietal and fronto-occipital systems and with higher connectivity of the short-range connections within frontal, parietal, and occipital lobes. We also used the graph theory to measure functional integration and segregation. The pattern of the overall age-related correlations presented positive correlations of average minimum path length (r = 0.380, p = 0.008) and of global clustering coefficients (r = 0.454, p < 0.001), leading to less integrated and more segregated global networks. Main correlations in clustering coefficients were located in the frontal and parietal lobes. Higher clustering coefficients of some areas were related to lower performance in verbal and visual memory functions. In conclusion, we found that older participants showed lower connectivity of long-range connections together with higher functional segregation of these same connections, which appeared to indicate a more local clustering of information processing. Higher local clustering in older participants was negatively related to memory performance. PMID:24814675

  16. Prominent periventricular fiber system related to ganglionic eminence and striatum in the human fetal cerebrum.

    PubMed

    Vasung, L; Jovanov-Miloševi?, N; Pletikos, M; Mori, S; Judaš, M; Kostovi?, Ivica

    2011-01-01

    Periventricular pathway (PVP) system of the developing human cerebrum is situated medial to the intermediate zone in the close proximity to proliferative cell compartments. In order to elucidate chemical properties and developing trajectories of the PVP we used DTI in combination with acetylcholinesterase histochemistry, SNAP-25 immunocytochemistry and axonal cytoskeletal markers (SMI312, MAP1b) immunocytochemistry on postmortem paraformaldehyde-fixed brains of 30 human fetuses ranging in age from 10 to 38 postconceptional weeks (PCW), 2 infants (age 1-3 months) and 1 adult brain. The PVP appears in the early fetal period (10-13 PCW) as two defined fibre bundles: the corpus callosum (CC) and the fetal fronto-occipital fascicle (FOF). In the midfetal period (15-18 PCW), all four components of the PVP can be identified: (1) the CC, which at rostral levels forms a voluminous callosal plate; (2) the FOF, with SNAP-25-positive fibers; (3) the fronto-pontine pathway (FPP) which for a short distance runs within the PVP; and (4) the subcallosal fascicle of Muratoff (SFM) which contains cortico-caudate projections. The PVPs are situated medial to the internal capsule at the level of the cortico-striatal junction; they remain prominent during the late fetal and early preterm period (19-28 PCW) and represent a portion of the wider periventricular crossroad of growing associative, callosal and projection pathways. In the perinatal period, the PVPs change their topographical relationships, decrease in size and the FOF looses its SNAP-25-reactivity. In conclusion, the hitherto undescribed PVP of the human fetal cerebrum contains forerunners of adult associative and projection pathways. Its transient chemical properties and relative exuberance suggest that the PVP may exert influence on the development of cortical connectivity (intermediate targeting) and other neurogenetic events such as neuronal proliferation. The PVP's topographical position also indicates that it is a major site of vulnerability in hypoxic-ischaemic perinatal brain injury. PMID:20953626

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

    PubMed Central

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

    2011-01-01

    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. PMID:21890111

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

    SciTech Connect

    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

    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.

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

    PubMed

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

    2011-02-01

    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

  20. Gravity influences top-down signals in visual processing.

    PubMed

    Cheron, Guy; Leroy, Axelle; Palmero-Soler, Ernesto; De Saedeleer, Caty; Bengoetxea, Ana; Cebolla, Ana-Maria; Vidal, Manuel; Dan, Bernard; Berthoz, Alain; McIntyre, Joseph

    2014-01-01

    Visual perception is not only based on incoming visual signals but also on information about a multimodal reference frame that incorporates vestibulo-proprioceptive input and motor signals. In addition, top-down modulation of visual processing has previously been demonstrated during cognitive operations including selective attention and working memory tasks. In the absence of a stable gravitational reference, the updating of salient stimuli becomes crucial for successful visuo-spatial behavior by humans in weightlessness. Here we found that visually-evoked potentials triggered by the image of a tunnel just prior to an impending 3D movement in a virtual navigation task were altered in weightlessness aboard the International Space Station, while those evoked by a classical 2D-checkerboard were not. Specifically, the analysis of event-related spectral perturbations and inter-trial phase coherency of these EEG signals recorded in the frontal and occipital areas showed that phase-locking of theta-alpha oscillations was suppressed in weightlessness, but only for the 3D tunnel image. Moreover, analysis of the phase of the coherency demonstrated the existence on Earth of a directional flux in the EEG signals from the frontal to the occipital areas mediating a top-down modulation during the presentation of the image of the 3D tunnel. In weightlessness, this fronto-occipital, top-down control was transformed into a diverging flux from the central areas toward the frontal and occipital areas. These results demonstrate that gravity-related sensory inputs modulate primary visual areas depending on the affordances of the visual scene. PMID:24400069

  1. Microstructural Correlations of White Matter Tracts in the Human Brain

    PubMed Central

    Wahl, Michael; Li, Yi-Ou; Ng, Joshua; LaHue, Sara C.; Cooper, Shelly R.; Sherr, Elliott H.; Mukherjee, Pratik

    2010-01-01

    The purpose of this study is to investigate whether specific patterns of correlation exist in diffusion tensor imaging (DTI) parameters across white matter tracts in the normal human brain, and whether the relative strengths of these putative microstructural correlations might reflect phylogenetic and functional similarities between tracts. We performed quantitative DTI fiber tracking on 44 healthy adult volunteers to obtain tract-based measures of mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) from four homologous pairs of neocortical association pathways (arcuate fasciculi, inferior fronto-occipital fasciculi, inferior longitudinal fasciculi, and uncinate fasciculi bilaterally), a homologous pair of limbic association pathways (left and right dorsal cingulum bundles), and a homologous pair of cortical-subcortical projection pathways (left and right corticospinal tracts). From the resulting inter-tract correlation matrices, we show that there are statistically significant correlations of DTI parameters between tracts, and that there are statistically significant variations among these inter-tract correlations. Furthermore, we observe that many, but by no means all, of the strongest correlations were between homologous tracts in the left and right hemispheres. Even among homologous pairs of tracts, there were wide variations in the degree of coupling. Finally, we generate a data-driven hierarchical clustering of the fiber pathways based on pairwise FA correlations to demonstrate that the neocortical association pathways tended to group separately from the limbic pathways at trend-level statistical significance, and that the projection pathways of the left and right corticospinal tracts comprise the most distant outgroup with high confidence (p<0.01). Hence, specific patterns of microstructural correlation exist between tracts and may reflect phylogenetic and functional similarities between tracts. The study of these microstructural relationships between white matter pathways might aid research on the genetic basis and on the behavioral effects of axonal connectivity, as well as provide a revealing new perspective with which to investigate neurological and psychiatric disorders. PMID:20206699

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

    PubMed Central

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

    2012-01-01

    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. PMID:22907997

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

    PubMed

    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

    2013-01-01

    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

  4. The Paradoxical Relationship between White Matter, Psychopathology and Cognition in Schizophrenia: A Diffusion Tensor and Proton Spectroscopic Imaging Study.

    PubMed

    Caprihan, Arvind; Jones, Thomas; Chen, Hongji; Lemke, Nicholas; Abbott, Christopher; Qualls, Clifford; Canive, Jose; Gasparovic, Charles; Bustillo, Juan R

    2015-08-01

    White matter disruption has been repeatedly documented in schizophrenia consistent with microstructural disorganization (reduced fractional anisotropy (FA)) and axonal dysfunction (reduced N-acetylaspartate NAAc). However, the clinical significance of these abnormalities is poorly understood. Diffusion tensor and proton spectroscopic imaging where used to assess FA, axial diffusivity and radial diffusivity (RD), and supra-ventricular white matter NAAc, respectively, in 64 schizophrenia and 64 healthy subjects. Schizophrenia patients had reduced FA across several regions, with additional regions where FA correlated positively with positive symptoms severity. These regions included genu, body and splenium of corpus callosum, anterior and superior corona radiata, superior longitudinal and inferior fronto-occipital fasciculi, and internal capsule. The FA/symptoms relationships corresponded with opposite correlations between RD and positive symptoms. The schizophrenia group (SP group) had progressively reduced NAAc with age, and NAAc correlated negatively with positive symptoms. Cognition correlated positively with both FA and NAAc in controls, whereas in the SP group it had a negative correlation with NAAc and no significant relationship with FA. Antipsychotic dose did not account for the results. Correlates of psychosis, cognitive and negative symptoms can be found in white matter. The significant correlations between positive symptoms in schizophrenia and diffusion and NAAc measures suggest decreased axonal density with increased glial cells and higher myelination in this subpopulation. A separate set of abnormal relationships between cognition and FA/RD, as well as with NAAc, converge to suggest that in schizophrenia, white matter microstructure supports the two core illness domains: psychosis and cognitive/negative symptoms. PMID:25786581

  5. Multimodal Magnetic Resonance Imaging Study of Treatment-Naïve Adults with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Chaim, Tiffany M.; Zhang, Tianhao; Zanetti, Marcus V.; da Silva, Maria Aparecida; Louzã, Mário R.; Doshi, Jimit; Serpa, Mauricio H.; Duran, Fabio L. S.; Caetano, Sheila C.; Davatzikos, Christos; Busatto, Geraldo F.

    2014-01-01

    Background Attention-Deficit/Hiperactivity Disorder (ADHD) is a prevalent disorder, but its neuroanatomical circuitry is still relatively understudied, especially in the adult population. The few morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies available to date have found heterogeneous results. This may be at least partly attributable to some well-known technical limitations of the conventional voxel-based methods usually employed to analyze such neuroimaging data. Moreover, there is a great paucity of imaging studies of adult ADHD to date that have excluded patients with history of use of stimulant medication. Methods A newly validated method named optimally-discriminative voxel-based analysis (ODVBA) was applied to multimodal (structural and DTI) MRI data acquired from 22 treatment-naïve ADHD adults and 19 age- and gender-matched healthy controls (HC). Results Regarding DTI data, we found higher fractional anisotropy in ADHD relative to HC encompassing the white matter (WM) of the bilateral superior frontal gyrus, right middle frontal left gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral middle temporal gyrus and right superior temporal gyrus; reductions in trace (a measure of diffusivity) in ADHD relative to HC were also found in fronto-striatal-parieto-occipital circuits, including the right superior frontal gyrus and bilateral middle frontal gyrus, right precentral gyrus, left middle occipital gyrus and bilateral cingulate gyrus, as well as the left body and right splenium of the corpus callosum, right superior corona radiata, and right superior longitudinal and fronto-occipital fasciculi. Volumetric abnormalities in ADHD subjects were found only at a trend level of significance, including reduced gray matter (GM) in the right angular gyrus, and increased GM in the right supplementary motor area and superior frontal gyrus. Conclusions Our results suggest that adult ADHD is associated with neuroanatomical abnormalities mainly affecting the WM microstructure in fronto-parieto-temporal circuits that have been implicated in cognitive, emotional and visuomotor processes. PMID:25310815

  6. Microsurgical anatomy of the inferior limiting insular sulcus and the temporal stem.

    PubMed

    Ribas, Eduardo Carvalhal; Yagmurlu, Kaan; Wen, Hung Tzu; Rhoton, Albert L

    2015-06-01

    OBJECT The purpose of this study was to describe the location of each white matter pathway in the area between the inferior limiting insular sulcus (ILS) and temporal horn that may be crossed in approaches through the temporal stem to the medial temporal lobe. METHODS The fiber tracts in 14 adult cadaveric cerebral hemispheres were examined using the Klingler technique. The fiber dissections were completed in a stepwise manner, identifying each white matter pathway in different planes and describing its position in relation to the anterior end of the ILS. RESULTS The short-association fibers from the extreme capsule, which continue toward the operculae, are the most superficial subcortical layer deep to the ILS. The external capsule fibers are found deeper at an intermediate layer and are formed by the uncinate fasciculus, inferior frontooccipital fasciculus, and claustrocortical fibers in a sequential anteroposterior disposition. The anterior commissure forms the next deeper layer, and the optic radiations in the sublenticular part of the internal capsule represent the deepest layer. The uncinate fasciculus is found deep to the anterior third of the ILS, whereas the inferior frontooccipital fasciculus and optic radiations are found superficial and deep, respectively, at the posterior two-thirds of this length. CONCLUSIONS The authors' findings suggest that in the transsylvian approach, a 6-mm incision beginning just posterior to the limen insula through the ILS will cross the uncinate fasciculus but not the inferior frontooccipital fasciculus or optic radiations, but that longer incisions carry a risk to language and visual functions. PMID:25859806

  7. Plasticity of language pathways in patients with low-grade glioma: A diffusion tensor imaging study?

    PubMed Central

    Zheng, Gang; Chen, Xiaolei; Xu, Bainan; Zhang, Jiashu; Lv, Xueming; Li, Jinjiang; Li, Fangye; Hu, Shen; Zhang, Ting; Li, Ye

    2013-01-01

    Knowledge of the plasticity of language pathways in patients with low-grade glioma is important for neurosurgeons to achieve maximum resection while preserving neurological function. The current study sought to investigate changes in the ventral language pathways in patients with low-grade glioma located in regions likely to affect the dorsal language pathways. The results revealed no significant difference in fractional anisotropy values in the arcuate fasciculus between groups or between hemispheres. However, fractional anisotropy and lateralization index values in the left inferior longitudinal fasciculus and lateralization index values in the left inferior fronto-occpital fasciculus were higher in patients than in healthy subjects. These results indicate plasticity of language pathways in patients with low-grade glioma. The ventral language pathways may perform more functions in patients than in healthy subjects. As such, it is important to protect the ventral language pathways intraoperatively. PMID:25206710

  8. [The features of system organization of the brain activity during different sleep stages and transition states].

    PubMed

    Shepoval'nikov, A N; Tsitseroshin, M N; Gal'perina, E I; Rozhkov, V P; Kruchinina, O V; Za?tseva, L G; Panasevich, E A

    2012-01-01

    Electropoligraphical study of the natural night sleep in 16 adults with the use of correlation, coherent, cluster and factor analysis were used to obtain new data describing the active nature of sleep, which is expressed especially in periods of falling asleep and the transition from one stage to another. It is shown that the process of falling asleep and deeper sleep is accompanied by intense reorganization of cortico-subcortical relations, which is reflected in the dynamics ofcrosscorrelation and coherent estimates of interrelations of biopotentials of the brain. The results of factor analysis of multichannel EEG heterogeneity of the transition process from wakefulness to sleep is manifested in significant changes of I, II and III factors weight during I(B) stage of sleep, which may reflect changes in the degree of contribution of the main integrative brain systems in the reorganization of its integral activity. A considerable increase in the I factor weight (reflecting the generalized modulatory brainstem effect on the cortex), along with a decrease in the balance of factors II and III (associated with organization of fronto-occipital and interhemispheric interactions) clearly indicates a special role of sleep synchronizing influences from the brain stem in the development of this initial stage. Reduction of EEG interhemispheric interrelations in the anterior and inferior frontal areas with the deepening of sleep may be indication of the reorganization of the frontal areas activity associated with the coordinated increasing of inactivation process in the cortex of both hemispheres. Degree of stability of the spatial structure of interregional interactions of different brain cortex areas (according to the analysis of average dispersion of crosscorrelation EEG relations) increases on falling asleep with the onset of stage I(A), but with the transition to the stage I(B) there is a significant increase of instability of values EEG crosscorrelation. With the deepening of sleep the subsequent decrease of the dispersion of EEG crosscorrelations in frontal cortex is revealed. During REM sleep the dispersion levels of inter-regional interactions increases as much as possible, especially for EEG crosscorrelations of posterotemporal and inferiofrontal parts of both hemispheres. PMID:22830239

  9. Wall-Eyed Monocular Internuclear Ophthalmoplegia (WEMINO) with Contraversive Ocular Tilt Reaction

    PubMed Central

    Jeon, Sang Beom; Chung, Sun J.; Ahn, Hyosook; Lee, Jae-Hong; Jung, Jin Man

    2005-01-01

    Wall-eyed monocular internuclear ophthalmoplegia (WEMINO) with contraversive ocular tilt reaction has not been previously reported. A 71-year-old woman suddenly developed blurred vision. Examination revealed left internuclear ophthalmoplegia, left exotropia, right hypotropia, and rightward head tilt. Magnetic resonance imaging showed a tiny infarction at the area of the left medial longitudinal fasciculus in the upper pons. WEMINO with contraversive ocular tilt reaction may be caused by a paramedian pontine tegmental infarction that selectively involves the medial longitudinal fasciculus. PMID:20396478

  10. THE JOURNAL OI' COMPARATIVE NEUROLOGY 233~48-90(1985) Tectoreticular Pathwayis in the Turtle,

    E-print Network

    Sereno, Martin

    1985-01-01

    interstitial nucleus of the medial longitudinal fasciculus and the suprapeduncular nucleus. The main trunks in the uncrossed intermediate pathway also emit collaterals into a midbrain reticular nucleus (profundus (Abrahams and Rose, '75a,b) and from several vestibular nuclei (Maeda et al., '79). Electrical stimulation

  11. Paraphasias in Multilingual Conduction Aphasia: A Single Case Study

    ERIC Educational Resources Information Center

    Hegde, Medha; Bhat, Sapna

    2007-01-01

    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…

  12. Investigating the contribution of ventral-lexical and dorsal-sublexical pathways during reading in bilinguals

    PubMed Central

    Bakhtiari, Reyhaneh; Boliek, Carol; Cummine, Jacqueline

    2014-01-01

    Several studies suggest the existence of ventral-lexical and dorsal-sublexical systems for reading. The relative contribution of these pathways can be manipulated by stimulus type and task demands. However, little is known about how bilinguals use these systems to read in their second language. In this study diffusion tensor imaging (DTI) was used to investigate the relationship between white matter (WM) integrity and reaction time in a group of 12 Chinese–English bilingual and 11 age-matched English monolingual adults. Considering a dual-route model of reading, the following four tracts were isolated in both the left and right hemispheres using a tractography measurement approach. Ventral tracts included the uncinate fasciculus (UF) and the inferior longitudinal fasciculus (ILF). The dorsal tracts of interest were the arcuate fasciculus (AF) and the superior longitudinal fasciculus (SLF). A significant correlation between the reaction time in a reading task and the mean diffusivity (MD) value was observed in the right UF in both bilingual and monolingual groups. Moreover, in the bilingual group we observed significantly more positive relationships between reaction time and MD in the right AF, and bilaterally in the SLF. We concluded that the relative contribution of the dorsal system for reading is greater in bilinguals than monolinguals. Further, these findings implicate a role of the right hemisphere in reading. PMID:25071533

  13. Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging

    Microsoft Academic Search

    Stephen E Rose; Fang Chen; Jonathan B Chalk; Fernando O Zelaya; Wendy E Strugnell; Mark Benson; James Semple; David M Doddrell

    2000-01-01

    A NOVEL MRI METHODdiffusion tensor imaging—was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimer's disease. Relative to normal controls, patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum.

  14. Tracking the Roots of Reading Ability: White Matter Volume and Integrity Correlate with Phonological Awareness in Prereading and Early-Reading Kindergarten Children

    PubMed Central

    Osher, David E.; Beach, Sara D.; Cyr, Abigail B.; Ozernov-Palchik, Ola; Yendiki, Anastasia; Fischl, Bruce; Gaab, Nadine; Gabrieli, John D.E.

    2013-01-01

    Developmental dyslexia, an unexplained difficulty in learning to read, has been associated with alterations in white matter organization as measured by diffusion-weighted imaging. It is unknown, however, whether these differences in structural connectivity are related to the cause of dyslexia or if they are consequences of reading difficulty (e.g., less reading experience or compensatory brain organization). Here, in 40 kindergartners who had received little or no reading instruction, we examined the relation between behavioral predictors of dyslexia and white matter organization in left arcuate fasciculus, inferior longitudinal fasciculus, and the parietal portion of the superior longitudinal fasciculus using probabilistic tractography. Higher composite phonological awareness scores were significantly and positively correlated with the volume of the arcuate fasciculus, but not with other tracts. Two other behavioral predictors of dyslexia, rapid naming and letter knowledge, did not correlate with volumes or diffusion values in these tracts. The volume and fractional anisotropy of the left arcuate showed a particularly strong positive correlation with a phoneme blending test. Whole-brain regressions of behavioral scores with diffusion measures confirmed the unique relation between phonological awareness and the left arcuate. These findings indicate that the left arcuate fasciculus, which connects anterior and posterior language regions of the human brain and which has been previously associated with reading ability in older individuals, is already smaller and has less integrity in kindergartners who are at risk for dyslexia because of poor phonological awareness. These findings suggest a structural basis of behavioral risk for dyslexia that predates reading instruction. PMID:23946384

  15. Drawing connections between white matter and numerical and mathematical cognition: a literature review.

    PubMed

    Matejko, Anna A; Ansari, Daniel

    2015-01-01

    In this review we examine white matter tracts that may support numerical and mathematical abilities and whether abnormalities in these pathways are associated with deficits in numerical and mathematical abilities. Diffusion tensor imaging (DTI) yields indices of white matter integrity and can provide information about the axonal organization of the brain. A growing body of research is using DTI to investigate how individual differences in brain microstructures relate to different numerical and mathematical abilities. Several tracts have been associated with numerical and mathematical abilities such as the superior longitudinal fasciculus, the posterior segment of the corpus callosum, inferior longitudinal fasciculus, corona radiata, and the corticospinal tract. Impairments in mathematics tend to be associated with atypical white matter structures within similar regions, especially in inferior parietal and temporal tracts. This systematic review summarizes and critically examines the current literature on white matter correlates of numerical and mathematical abilities, and provides directions for future research. PMID:25446952

  16. Anatomy is strategy: skilled reading differences associated with structural connectivity differences in the reading network.

    PubMed

    Graves, William W; Binder, Jeffrey R; Desai, Rutvik H; Humphries, Colin; Stengel, Benjamin C; Seidenberg, Mark S

    2014-06-01

    Are there multiple ways to be a skilled reader? To address this longstanding, unresolved question, we hypothesized that individual variability in using semantic information in reading aloud would be associated with neuroanatomical variation in pathways linking semantics and phonology. Left-hemisphere regions of interest for diffusion tensor imaging analysis were defined based on fMRI results, including two regions linked with semantic processing - angular gyrus (AG) and inferior temporal sulcus (ITS) - and two linked with phonological processing - posterior superior temporal gyrus (pSTG) and posterior middle temporal gyrus (pMTG). Effects of imageability (a semantic measure) on response times varied widely among individuals and covaried with the volume of pathways through the ITS and pMTG, and through AG and pSTG, partially overlapping the inferior longitudinal fasciculus and the posterior branch of the arcuate fasciculus. These results suggest strategy differences among skilled readers associated with structural variation in the neural reading network. PMID:24735993

  17. Anatomy is strategy: Skilled reading differences associated with structural connectivity differences in the reading network

    PubMed Central

    Graves, William W.; Binder, Jeffrey R.; Desai, Rutvik H.; Humphries, Colin; Stengel, Benjamin C.; Seidenberg, Mark S.

    2014-01-01

    Are there multiple ways to be a skilled reader? To address this longstanding, unresolved question, we hypothesized that individual variability in using semantic information in reading aloud would be associated with neuroanatomical variation in pathways linking semantics and phonology. Left-hemisphere regions of interest for diffusion tensor imaging analysis were defined based on fMRI results, including two regions linked with semantic processing – angular gyrus (AG) and inferior temporal sulcus (ITS) – and two linked with phonological processing – posterior superior temporal gyrus (pSTG) and posterior middle temporal gyrus (pMTG). Effects of imageability (a semantic measure) on response times varied widely among individuals and covaried with the volume of pathways through the ITS and pMTG, and through AG and pSTG, partially overlapping the inferior longitudinal fasciculus and the posterior branch of the arcuate fasciculus. These results suggest strategy differences among skilled readers associated with structural variation in the neural reading network. PMID:24735993

  18. THE APPEARANCE OF ACETYLCHOLINESTERASE IN THE DORSAL ROOT NEUROBLAST OF THE RABBIT EMBRYO

    PubMed Central

    Tennyson, Virginia M.; Brzin, Miro

    1970-01-01

    In the nine day old embryo, acetylcholinesterase (AChE) is found in the reticulum, i.e. the nuclear envelope, endoplasmic reticulum, and Golgi complex, of a few cells in the neural crest. When the neurite first enters the neural tube, reticulum-bound enzyme is present also in the varicosity of the growth cone of the bipolar neuroblast. At later stages, AChE in the neuroblast has a dual distribution; in addition to the reticulum, activity also appears at the axolemmal surface. The axolemmal activity is found initially on the distal portions of axons in the posterior fasciculus and then progressively appears along the nerve roots in a distal to proximal direction. Very little reticulum-bound enzyme is present within the axon proper. After the 13th day the levels of AChE activity in the posterior fasciculus greatly exceed those in the dorsal root or in the ganglion. Enzymatic activity in the dorsal root equals or exceeds that in the posterior fasciculus by day 16, and both areas are considerably more active than the ganglion. PMID:5459012

  19. White matter disruption at the prodromal stage of Alzheimer's disease: Relationships with hippocampal atrophy and episodic memory performance

    PubMed Central

    Rémy, Florence; Vayssière, Nathalie; Saint-Aubert, Laure; Barbeau, Emmanuel; Pariente, Jérémie

    2015-01-01

    White matter tract alterations have been consistently described in Alzheimer's disease (AD). In particular, limbic fronto-temporal connections, which are critical to episodic memory function, may degenerate early in the course of the disease. However the relation between white matter tract degeneration, hippocampal atrophy and episodic memory impairment at the earliest stages of AD is still unclear. In this magnetic resonance imaging study, white matter integrity and hippocampal volumes were evaluated in patients with amnestic mild cognitive impairment due to AD (Albert et al., 2011) (n = 22) and healthy controls (n = 15). Performance in various episodic memory tasks was also evaluated in each participant. Relative to controls, patients showed a significant reduction of white matter fractional anisotropy (FA) and increase of radial diffusivity (RD) in the bilateral uncinate fasciculus, parahippocampal cingulum and fornix. Within the patient group, significant intra-hemispheric correlations were notably found between hippocampal grey matter volume and FA in the uncinate fasciculus, suggesting a relationship between atrophy and disconnection of the hippocampus. Moreover, episodic recognition scores were related with uncinate fasciculus FA across patients. These results indicate that fronto-hippocampal connectivity is reduced from the earliest pre-demential stages of AD. Disruption of fronto-hippocampal connections may occur progressively, in parallel with hippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory. PMID:25685715

  20. Constrained spherical deconvolution analysis of the limbic network in human, with emphasis on a direct cerebello-limbic pathway

    PubMed Central

    Arrigo, Alessandro; Mormina, Enricomaria; Anastasi, Giuseppe Pio; Gaeta, Michele; Calamuneri, Alessandro; Quartarone, Angelo; De Salvo, Simona; Bruschetta, Daniele; Rizzo, Giuseppina; Trimarchi, Fabio; Milardi, Demetrio

    2014-01-01

    The limbic system is part of an intricate network which is involved in several functions like memory and emotion. Traditionally the role of the cerebellum was considered mainly associated to motion control; however several evidences are raising about a role of the cerebellum in learning skills, emotions control, mnemonic and behavioral processes involving also connections with limbic system. In 15 normal subjects we studied limbic connections by probabilistic Constrained Spherical Deconvolution (CSD) tractography. The main result of our work was to prove for the first time in human brain the existence of a direct cerebello-limbic pathway which was previously hypothesized but never demonstrated. We also extended our analysis to the other limbic connections including cingulate fasciculus, inferior longitudinal fasciculus, uncinated fasciculus, anterior thalamic connections and fornix. Although these pathways have been already described in the tractographic literature we provided reconstruction, quantitative analysis and Fractional Anisotropy (FA) right-left symmetry comparison using probabilistic CSD tractography that is known to provide a potential improvement compared to previously used Diffusion Tensor Imaging (DTI) techniques. The demonstration of the existence of cerebello-limbic pathway could constitute an important step in the knowledge of the anatomic substrate of non-motor cerebellar functions. Finally the CSD statistical data about limbic connections in healthy subjects could be potentially useful in the diagnosis of pathological disorders damaging this system. PMID:25538606

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

    PubMed Central

    Chakravarty, Ambar

    2012-01-01

    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. PMID:22566716

  2. Neural Plasticity After Pre-Linguistic Injury to the Arcuate and Superior Longitudinal Fasciculi

    PubMed Central

    Yeatman, Jason D; Feldman, Heidi M

    2011-01-01

    We describe the case of girl who was born prematurely and diagnosed periventricular leukomalacia, a condition characterized by severe injury to the white matter tracts primarily surrounding the ventricles. At 12 years of age, we obtained diffusion tensor imaging (DTI) data on this child as part of a research protocol. Multiple analyses of DTI data, including tractography, showed that the left and right arcuate and superior longitudinal fasciculi were missing in the child though all other major white matter tracts were present. Standardized psychometric tests at age 12 years revealed that despite early language delays, she had average scores on expressive language, sentence repetition, and reading, functions that have been hypothesized to depend on signals carried by the arcuate fasciculus. We identified intact ventral connections between the temporal and frontal lobes through the extreme capsule fiber system and uncinate fasciculus. Preserved language and reading function after serious injury to the arcuate fasciculus highlights the plasticity of the developing brain after severe white matter injury early in life. PMID:21937035

  3. Outcomes of Diffusion Tensor Tractography-Integrated Stereotactic Radiosurgery

    SciTech Connect

    Koga, Tomoyuki, E-mail: kouga-tky@umin.ac.jp [Department of Neurosurgery, University of Tokyo Hospital, Tokyo (Japan); Maruyama, Keisuke; Kamada, Kyousuke; Ota, Takahiro; Shin, Masahiro [Department of Neurosurgery, University of Tokyo Hospital, Tokyo (Japan); Itoh, Daisuke [Department of Radiology, University of Tokyo Hospital, Tokyo (Japan); Kunii, Naoto [Department of Neurosurgery, University of Tokyo Hospital, Tokyo (Japan); Ino, Kenji; Terahara, Atsuro; Aoki, Shigeki; Masutani, Yoshitaka [Department of Radiology, University of Tokyo Hospital, Tokyo (Japan); Saito, Nobuhito [Department of Neurosurgery, University of Tokyo Hospital, Tokyo (Japan)

    2012-02-01

    Purpose: To analyze the effect of use of tractography of the critical brain white matter fibers created from diffusion tensor magnetic resonance imaging on reduction of morbidity associated with radiosurgery. Methods and Materials: Tractography of the pyramidal tract has been integrated since February 2004 if lesions are adjacent to it, the optic radiation since May 2006, and the arcuate fasciculus since October 2007. By visually confirming the precise location of these fibers, the dose to these fiber tracts was optimized. One hundred forty-four consecutive patients with cerebral arteriovenous malformations who underwent radiosurgery with this technique between February 2004 and December 2009 were analyzed. Results: Tractography was prospectively integrated in 71 of 155 treatments for 144 patients. The pyramidal tract was visualized in 45, the optic radiation in 22, and the arcuate fasciculus in 13 (two tracts in 9). During the follow-up period of 3 to 72 months (median, 23 months) after the procedure, 1 patient showed permanent worsening of pre-existing dysesthesia, and another patient exhibited mild transient hemiparesis 12 months later but fully recovered after oral administration of corticosteroid agents. Two patients had transient speech disturbance before starting integration of the arcuate fasciculus tractography, but no patient thereafter. Conclusion: Integrating tractography helped prevent morbidity of radiosurgery in patients with brain arteriovenous malformations.

  4. Decreased axial diffusivity within language connections: a possible biomarker of schizophrenia risk.

    PubMed

    Kubicki, M; Shenton, M E; Maciejewski, P K; Pelavin, P E; Hawley, K J; Ballinger, T; Swisher, T; Jabbar, G A; Thermenos, H W; Keshavan, M S; Seidman, L J; Delisi, L E

    2013-08-01

    Siblings of patients diagnosed with schizophrenia are at elevated risk for developing this disorder. The nature of such risk associated with brain abnormalities, and whether such abnormalities are similar to those observed in schizophrenia, remain unclear. Deficits in language processing are frequently reported in increased risk populations. Interestingly, white matter pathology involving fronto-temporal language pathways, including arcuate fasciculus (AF), uncinate fasciculus (UF), and inferior occipitofrontal fasciculus (IOFF), are frequently reported in schizophrenia. In this study, high spatial and directional resolution diffusion MRI data was obtained on a 3T magnet from 33 subjects with increased familial risk for developing schizophrenia, and 28 control subjects. Diffusion tractography was performed to measure white matter integrity within AF, UF, and IOFF. To understand these abnormalities, Fractional Anisotropy (FA, a measure of tract integrity) and Trace (a measure of overall diffusion), were combined with more specific measures of axial diffusivity (AX, a putative measure of axonal integrity) and radial diffusivity (RD, a putative measure of myelin integrity). Results revealed a significant decrease in Trace within IOFF, and a significant decrease in AX in all tracts. FA and RD anomalies, frequently reported in schizophrenia, were not observed. Moreover, AX group effect was modulated by age, with increased risk subjects demonstrating a deviation from normal maturation trajectory. Findings suggest that familial risk for schizophrenia may be associated with abnormalities in axonal rather than myelin integrity, and possibly associated with disruptions in normal brain maturation. AX should be considered a possible biomarker of risk for developing schizophrenia. PMID:23800617

  5. Changes to memory structures in children treated for posterior fossa tumors.

    PubMed

    Riggs, Lily; Bouffet, Eric; Laughlin, Suzanne; Laperriere, Normand; Liu, Fang; Skocic, Jovanka; Scantlebury, Nadia; Wang, Frank; Schoenhoff, Nicholas J; Strother, Douglas; Hukin, Juliette; Fryer, Christopher; McConnell, Dina; Mabbott, Donald J

    2014-02-01

    Children treated for medulloblastoma (MB) exhibit long-term impairments in declarative memory, but the pathophysiology underlying this is unclear. Previous studies report declines in global white matter volume, but have failed to link this to declines in memory performance. We examined the effects of treatment on measures of global brain structure (i.e., total white and gray matter volume) and specific memory structures (i.e., hippocampus and uncinate fasciculus). We used volumetric MRI and diffusion tensor imaging in pediatric survivors of MB and one survivor of astrocytoma treated with cranial-spinal radiation (n = 20), and healthy controls (n = 13). Compared to controls, the survivor group exhibited reduced white matter volume, damage to the uncinate fasciculus, and a smaller right hippocampus. Critically, reduced hippocampal volume was not related to differences in brain volume, suggesting that the hippocampus may be especially vulnerable to treatment effects. A subset of the survivors (n = 10) also underwent memory testing using the Children's Memory Scale (CMS). Performance on the general index of the CMS was significantly correlated with measures of hippocampal volume and uncinate fasciculus. The examination of treatment effects on specific brain regions provides a better understanding of long-term cognitive outcome in children with brain tumors, particularly medulloblastoma. PMID:24460980

  6. EXOME SEQUENCING AND DIFFUSION TENSOR IMAGING IN DEVELOPMENTAL DISABILITIES

    PubMed Central

    Sundaram, Senthil K; Huq, AHM M; Hsia, Tammy; Chugani, Harry T

    2013-01-01

    Background We had previously shown that arcuate fasciculus is poorly developed in patients with Intellectual and Developmental Disabilities (IDD) using diffusion tensor imaging (DTI). In the present study, we used exome sequencing to identify the candidate variants in IDD patients with and without DTI abnormalities. Methods Eighteen children with IDD (age: 67±36 months, 9 females) were included in the present study. The DTI was used to determine the integrity of arcuate fasciculus. The next generation sequencing was performed on the Solid 4 platform. A novel, analytical strategy was developed to identify a set of candidate genes of interest. Novel, nonsynonymous variants in the patients were then looked for within this subset of genes and in known IDD genes. Results Seven novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to ultra-conserved genes that are known to cause abnormal brain morphology in mutant mice. Similarly, 3 novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to known IDD genes. Two patients with underdeveloped arcuate fasciculus contained novel, nonsynonymous variants in genes (MID1 and EN2) regulating axon guidance pathway. Conclusions Exome sequencing identified several new the genetic causes of IDD. PMID:24321989

  7. White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease

    PubMed Central

    Adluru, Nagesh; Destiche, Daniel J.; Lu, Sharon Yuan-Fu; Doran, Samuel T.; Birdsill, Alex C.; Melah, Kelsey E.; Okonkwo, Ozioma C.; Alexander, Andrew L.; Dowling, N. Maritza; Johnson, Sterling C.; Sager, Mark A.; Bendlin, Barbara B.

    2014-01-01

    Introduction Little is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype. Methods This study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of interest analysis was performed on fractional anisotropy maps, in addition to mean, radial, and axial diffusivity maps, aligned to a common template space using a diffeomorphic, tensor-based registration method. The analysis focused on brain regions known to be affected in AD including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses assessed the impact of APOE4, parental family history of AD, age, and sex on white matter microstructure in late middle-aged participants (aged 47–76 years). Results Both APOE4 and parental family history were associated with microstructural white matter differences. Participants with parental family history of AD had higher FA in the genu of the corpus callosum and the superior longitudinal fasciculus. We observed an interaction between family history and APOE4, where participants who were family history positive but APOE4 negative had lower axial diffusivity in the uncinate fasciculus, and participants who were both family history positive and APOE4 positive had higher axial diffusivity in this region. We also observed an interaction between APOE4 and age, whereby older participants (=65 years of age) who were APOE4 carriers, had higher MD in the superior longitudinal fasciculus and in the portion of the cingulum bundle running adjacent to the cingulate cortex, compared to non-carriers. Older participants who were APOE4 carriers also showed higher radial diffusivity in the genu compared to non-carriers. Across all participants, age had an effect on FA, MD, and axial and radial diffusivities. Sex differences were observed in FA and radial diffusivity. Conclusion APOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics—both expected and unexpected—may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD. PMID:24936424

  8. Projections of the lateral terminal accessory optic nucleus of the common marmoset (Callithrix jacchus).

    PubMed

    Blanks, R H; Clarke, R J; Lui, F; Giolli, R A; Van Pham, S; Torigoe, Y

    1995-04-17

    The connections of the lateral terminal nucleus (LTN) of the accessory optic system (AOS) of the marmoset monkey were studied with anterograde 3H-amino acid light autoradiography and horseradish peroxidase retrograde labeling techniques. Results show a first and largest LTN projection to the pretectal and AOS nuclei including the ipsilateral nucleus of the optic tract, dorsal terminal nucleus, and interstitial nucleus of the superior fasciculus (posterior fibers); smaller contralateral projections are to the olivary pretectal nucleus, dorsal terminal nucleus, and LTN. A second, major bundle produces moderate-to-heavy labeling in all ipsilateral, accessory oculomotor nuclei (nucleus of posterior commissure, interstitial nucleus of Cajal, nucleus of Darkschewitsch) and nucleus of Bechterew; some of the fibers are distributed above the caudal oculomotor complex within the supraoculomotor periaqueductal gray. A third projection is ipsilateral to the pontine and mesencephalic reticular formations, nucleus reticularis tegmenti pontis and basilar pontine complex (dorsolateral nucleus only), dorsal parts of the medial terminal accessory optic nucleus, ventral tegmental area of Tsai, and rostral interstitial nucleus of the medial longitudinal fasciculus. Lastly, there are two long descending bundles: (1) one travels within the medial longitudinal fasciculus to terminate in the dorsal cap (ipsilateral > contralateral) and medial accessory olive (ipsilateral only) of the inferior olivary complex. (2) The second soon splits, sending axons within the ipsilateral and contralateral brachium conjunctivum and is distributed to the superior and medial vestibular nuclei. The present findings are in general agreement with the documented connections of LTN with brainstem oculomotor centers in other species. In addition, there are unique connections in marmoset monkey that may have developed to serve the more complex oculomotor behavior of nonhuman primates. PMID:7608336

  9. Über die Bahnen der Reizleitung vom Keith-Flackschen Knoten zu den Vorhöfen

    Microsoft Academic Search

    L. Condorelli

    1929-01-01

    Zusammenfassung  1. Die obere Abklemmung bewirkt, indem sie die Reizleitung im oberen sino-aurikul?ren B?ndel unterbricht, entweder ein erniedrigtes\\u000a Potential oder eine Umkehrung der P-Zacke.\\u000a \\u000a 2. Die gleiche ?nderung bedingt die Abklemmung der im Torus Loweri verlaufenden Bahnen.\\u000a \\u000a \\u000a 3. Die Abklemmung des Fasciculus sino-auricularis inferior (untere Abklemmung) bewirkt eine Steigerung des Potentials der\\u000a P-Zacke.\\u000a \\u000a \\u000a \\u000a 4. Die Zweiteilung der P-Zacke entsteht als Folgeerscheinung

  10. Neuronal connections through the posterior commissure in the frog Rana esculenta.

    PubMed

    Lázár, G; Pál, E

    1999-01-01

    The cobalt-labelling technique was used. After iontophoretic injections of cobaltic-lysine complex into the posterior commissure, fibres and neurons were bilaterally labelled in the posterior thalamic nucleus, three other pretectal nuclei, the optic tectum, the nucleus of the medial longitudinal fasciculus, and in the basal optic nucleus. Unilateral cobalt injections into the terminal areas of the posterior commissure in the mesencephalic tegmentum, labelled neurons in the above-mentioned nuclei ipsilaterally, and some cells contralaterally. The connections through the frog's posterior commissure are very similar to those in mammals. PMID:10536869

  11. Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence

    PubMed Central

    Lisiecka, D M; Holt, R; Tait, R; Ford, M; Lai, M-C; Chura, L R; Baron-Cohen, S; Spencer, M D; Suckling, J

    2015-01-01

    During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact with the development of white matter microstructure. This interaction may be present beyond the phenotype of autism in siblings of individuals with ASC, who are 10 to 20 times more likely to develop certain forms of ASC. We use diffusion tensor imaging to examine how white matter microstructure measurements correlate with age in typically developing individuals, and how this correlation differs in n=43 adolescents with ASC and their n=38 siblings. Correlations observed in n=40 typically developing individuals match developmental changes noted in previous longitudinal studies. In comparison, individuals with ASC display weaker negative correlation between age and mean diffusivity in a broad area centred in the right superior longitudinal fasciculus. These differences may be caused either by increased heterogeneity in ASC or by temporal alterations in the group's developmental pattern. Siblings of individuals with ASC also show diminished negative correlation between age and one component of mean diffusivity—second diffusion eigenvalue—in the right superior longitudinal fasciculus. As the observed differences match for location and correlation directionality in our comparison of typically developing individuals to those with ASC and their siblings, we propose that these alterations constitute a part of the endophenotype of autism. PMID:25781228

  12. The regional distribution of myelin oligodendrocyte glycoprotein (MOG) in the developing rat CNS: an in vivo immunohistochemical study.

    PubMed

    Coffey, J C; McDermott, K W

    1997-03-01

    Using an immunohistochemical approach we have characterized the in vivo developmental distribution of myelin oligodendrocyte glycoprotein within the rat CNS. Myelin oligodendrocyte glycoprotein expression emerged in a non-uniform manner during the first 3 postnatal weeks. Although it was absent throughout the CNS of the newborn rat at postnatal day 0(P0), it had appeared in the spinal cord and brainstem by P7. The forebrain and cerebellum remained devoid of immunoreactivity until after P14. Myelin oligodendrocyte glycoprotein emerged at different times within the closely associated fasciculi of the dorsal funiculus. It appeared in the fasciculus cuneatus during the first postnatal week and in the fasciculus gracilis and corticospinal tracts during weeks 2 and 3 respectively. Myelin oligodendrocyte glycoprotein expression developed along a caudo-rostral gradient from spinal cord to forebrain and along an antero-posterior gradient within the CNS in general. The relationship between the onset of myelin oligodendrocyte glycoprotein expression and myelinogenesis was also investigated. In most regions, myelin oligodendrocyte glycoprotein expression lagged behind the initial appearance of myelin basic protein and Luxol Fast Blue-stained myelin by at least 1 week. These observations support the idea that myelin oligodendrocyte glycoprotein is the latest myelin protein to appear in development, only being expressed during the final stages of oligodendrocyte differentiation. Furthermore, the pattern of staggered expression within the dorsal columns indicates that localized, region-specific interactions may comprise a key element in the control of the terminal phases of oligodendrocyte differentiation. PMID:9192283

  13. Developmental synergy between thalamic structure and interhemispheric connectivity in the visual system of preterm infants

    PubMed Central

    Ceschin, Rafael; Wisnowski, Jessica L.; Paquette, Lisa B.; Nelson, Marvin D.; Blüml, Stefan; Panigrahy, Ashok

    2015-01-01

    Thalamic structural co-variation with cortical regions has been demonstrated in preterm infants, but its relationship to cortical function and severity of non-cystic white matter injury (non-cystic WMI) is unclear. The relationship between thalamic morphology and both cortical network synchronization and cortical structural connectivity has not been established. We tested the hypothesis that in preterm neonates, thalamic volume would correlate with primary cortical visual function and microstructural integrity of cortico-cortical visual association pathways. A total of 80 term-equivalent preterm and 44 term-born infants underwent high-resolution structural imaging coupled with visual functional magnetic resonance imaging or diffusion tensor imaging. There was a strong correlation between thalamic volume and primary visual cortical activation in preterms with non-cystic WMI (r = 0.81, p-value = 0.001). Thalamic volume also correlated strongly with interhemispheric cortico-cortical connectivity (splenium) in preterm neonates with a relatively higher severity of non-cystic WMI (p-value < 0.001). In contrast, there was lower correlation between thalamic volume and intrahemispheric cortico-cortical connectivity, including the inferior longitudinal fasciculus and inferior frontal orbital fasciculus. This study shows distinct temporal overlap in the disruption of thalamo-cortical and interhemispheric cortico-cortical connectivity in preterm infants suggesting developmental synergy between thalamic morphology and the emergence of cortical networks in the last trimester.

  14. White matter anisotropy in the ventral language pathway predicts sound-to-word learning success.

    PubMed

    Wong, Francis C K; Chandrasekaran, Bharath; Garibaldi, Kyla; Wong, Patrick C M

    2011-06-15

    According to the dual stream model of auditory language processing, the dorsal stream is responsible for mapping sound to articulation and the ventral stream plays the role of mapping sound to meaning. Most researchers agree that the arcuate fasciculus (AF) is the neuroanatomical correlate of the dorsal steam; however, less is known about what constitutes the ventral one. Nevertheless, two hypotheses exist: one suggests that the segment of the AF that terminates in middle temporal gyrus corresponds to the ventral stream, and the other suggests that it is the extreme capsule that underlies this sound-to-meaning pathway. The goal of this study was to evaluate these two competing hypotheses. We trained participants with a sound-to-word learning paradigm in which they learned to use a foreign phonetic contrast for signaling word meaning. Using diffusion tensor imaging, a brain-imaging tool to investigate white matter connectivity in humans, we found that fractional anisotropy in the left parietal-temporal region positively correlated with the performance in sound-to-word learning. In addition, fiber tracking revealed a ventral pathway, composed of the extreme capsule and the inferior longitudinal fasciculus, that mediated auditory comprehension. Our findings provide converging evidence supporting the importance of the ventral steam, an extreme capsule system, in the frontal-temporal language network. Implications for current models of speech processing are also discussed. PMID:21677162

  15. Eel calcitonin binding site distribution and antinociceptive activity in rats

    SciTech Connect

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

    1986-03-01

    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.

  16. Comparative morphology of the lateral meniscus of the knee in primates.

    PubMed

    Le Minor, J M

    1990-06-01

    The morphology of the lateral meniscus has been studied in a series of 316 non-human primates, representative of 43 genera. The lateral meniscus has a crescentic shape in Prosimii, in Platyrrhinii (New World monkeys) and in Pongo pygmaeus. The lateral meniscus is disc-shaped, with a central foramen, in Catarrhinii (Old World monkeys), in Hylobates, in Gorilla and in Pan Troglodytes. In man, the lateral meniscus has a crescentic shape. Discoid lateral menisci are reported as anomalies in man; their origin has given rise to much discussion, but the comparative data favour a phylogenetic origin. The posterior fasciculus (Wrisberg's ligament) of the posterior menisco-femoral ligament is always present and large in all non-human primates; in man, it may be absent and seems to be a regressive structure. On the other hand, the anterior fasciculus (Humphry's ligament) exists only in man and seems to be a progressive structure. The posterior menisco-tibial attachments are weak or non-existent in non-human primates, but they are well-developed in man. The evolutionary development of these characters can be related to human bipedal locomotion. The lateral meniscus in some Prosimii contains one or two intramensical ossicles (lunulae). These structures are absent or very rare in all other primate groups. In man, intrameniscal ossicles are extremely unusual; their origin, phylogenetic or post-traumatic is controversial, but comparative data favour, at least in some cases, the persistence of an ancestral character. PMID:2123845

  17. Comparative morphology of the lateral meniscus of the knee in primates.

    PubMed Central

    Le Minor, J M

    1990-01-01

    The morphology of the lateral meniscus has been studied in a series of 316 non-human primates, representative of 43 genera. The lateral meniscus has a crescentic shape in Prosimii, in Platyrrhinii (New World monkeys) and in Pongo pygmaeus. The lateral meniscus is disc-shaped, with a central foramen, in Catarrhinii (Old World monkeys), in Hylobates, in Gorilla and in Pan Troglodytes. In man, the lateral meniscus has a crescentic shape. Discoid lateral menisci are reported as anomalies in man; their origin has given rise to much discussion, but the comparative data favour a phylogenetic origin. The posterior fasciculus (Wrisberg's ligament) of the posterior menisco-femoral ligament is always present and large in all non-human primates; in man, it may be absent and seems to be a regressive structure. On the other hand, the anterior fasciculus (Humphry's ligament) exists only in man and seems to be a progressive structure. The posterior menisco-tibial attachments are weak or non-existent in non-human primates, but they are well-developed in man. The evolutionary development of these characters can be related to human bipedal locomotion. The lateral meniscus in some Prosimii contains one or two intramensical ossicles (lunulae). These structures are absent or very rare in all other primate groups. In man, intrameniscal ossicles are extremely unusual; their origin, phylogenetic or post-traumatic is controversial, but comparative data favour, at least in some cases, the persistence of an ancestral character. Images Fig. 1 Fig. 2 PMID:2123845

  18. Improved Fronto-Parietal White Matter Integrity in Overweight Children is Associated with Attendance in an After-School Exercise Program

    PubMed Central

    Krafft, Cynthia E.; Schaeffer, David J.; Schwarz, Nicolette F.; Chi, Lingxi; Weinberger, Abby L.; Pierce, Jordan E.; Rodrigue, Amanda L.; Allison, Jerry D.; Yanasak, Nathan E.; Liu, Tianming; Davis, Catherine L.; McDowell, Jennifer E.

    2014-01-01

    Aerobic fitness is associated with white matter integrity (WMI) in adults as measured by diffusion tensor imaging (DTI). This study examined the effect of an 8-month exercise intervention on WMI in children. Participants were 18 sedentary, overweight (body mass index ? 85th percentile) 8- to 11-year-old children (94% Black), randomly assigned to either an aerobic exercise (n=10) or sedentary attention control group (n=8). Each group was offered an instructor-led after-school program every school day for approximately 8 months. Before and after the program, all subjects participated in DTI scans. Tractography was conducted to isolate the superior longitudinal fasciculus and investigate whether the exercise intervention affected WMI in this region. There was no group by time interaction for WMI in the superior longitudinal fasciculus. There was a group by time by attendance interaction, however, such that higher attendance at the exercise intervention, but not the control intervention, was associated with increased WMI. Heart rate and the total dose of exercise correlated with WMI changes in the exercise group. In the overall sample, increased WMI was associated with improved scores on a measure of attention and improved teacher ratings of executive function. This study indicates that participating in an exercise intervention improves WMI in children as compared to a sedentary after-school program. PMID:24457421

  19. Analyses of Disruption of Cerebral White Matter Integrity in Schizophrenia with MR Diffusion Tensor Fiber Tracking Method

    NASA Astrophysics Data System (ADS)

    Yamamoto, Utako; Kobayashi, Tetsuo; Kito, Shinsuke; Koga, Yoshihiko

    We have analyzed cerebral white matter using magnetic resonance diffusion tensor imaging (MR-DTI) to measure the diffusion anisotropy of water molecules. The goal of this study is the quantitative evaluation of schizophrenia. Diffusion tensor images are acquired for patients with schizophrenia and healthy comparison subjects, group-matched for age, sex, and handedness. Fiber tracking is performed on the superior longitudinal fasciculus for the comparison between the patient and comparison groups. We have analysed and compared the cross-sectional area on the starting coronal plane and the mean and standard deviation of the fractional anisotropy and the apparent diffusion coefficient along fibers in the right and left hemispheres. In the right hemisphere, the cross-sectional areas in patient group are significantly smaller than those in the comparison group. Furthermore, in the comparison group, the cross-sectional areas in the right hemisphere are significantly larger than those in the left hemisphere, whereas there is no significant difference in the patient group. These results suggest that we may evaluate the disruption in white matter integrity in schizophrenic patients quantitatively by comparing the cross-sectional area of the superior longitudinal fasciculus in the right and left hemispheres.

  20. Msx1 disruption leads to diencephalon defects and hydrocephalus.

    PubMed

    Ramos, Casto; Fernández-Llebrez, Pedro; Bach, Antoine; Robert, Benoît; Soriano, Eduardo

    2004-07-01

    We have analyzed the expression of the Msx1 gene in the developing mouse brain and examined the brain phenotype in homozygotes. Msx1 is expressed in every cerebral vesicle throughout development, particularly in neuroepithelia, such as those of the fimbria and the medulla. Timing analysis suggests that Msx1(nLacZ) cells delaminate and migrate radially from these epithelia, mainly at embryonic days 14-16, while immunohistochemistry studies reveal that some of the beta-galactosidase migrating cells are oligodendrocytes or astrocytes. Our results suggest that the Msx1 neuroepithelia of fimbria and medulla may be a source of glial precursors. The Msx1 mutants display severe hydrocephalus at birth, while the subcommissural organ, the habenula, and the posterior commissure fail to develop correctly. No label was detected in the mutant subcommissural organ using a specific antibody against Reissner's fiber. Besides, the fasciculus retroflexus deviates close to the subcommissural organ, while the paraventricular thalamic nucleus shows histological disorganization. Our results implicate the Msx1 gene in the differentiation of the subcommissural organ cells and posterior commissure and that Msx1 protein may play a role in the pathfinding and bundling of the fasciculus retroflexus and in the structural arrangement of the paraventricular thalamic nucleus. PMID:15188430

  1. Neural systems predicting long-term outcome in dyslexia.

    PubMed

    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

    2011-01-01

    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. PMID:21173250

  2. White matter damage in frontotemporal lobar degeneration spectrum.

    PubMed

    Agosta, F; Scola, E; Canu, E; Marcone, A; Magnani, G; Sarro, L; Copetti, M; Caso, F; Cerami, C; Comi, G; Cappa, S F; Falini, A; Filippi, M

    2012-12-01

    White matter (WM) tract damage was assessed in patients with the behavioral variant frontotemporal dementia (bvFTD) and the 3 primary progressive aphasia (PPA) variants and compared with the corresponding brain atrophy patterns. Thirteen bvFTD and 20 PPA patients were studied. Tract-based spatial statistics and voxel-based morphometry were used. Patients with bvFTD showed widespread diffusion tensor magnetic resonance imaging (DT MRI) abnormalities affecting most of the WM bilaterally. In PPA patients, WM damage was more focal and varied across the 3 syndromes: left frontotemporoparietal in nonfluent, left frontotemporal in semantic, and left frontoparietal in logopenic patients. In each syndrome, DT MRI changes extended beyond the topography of gray matter loss. Left uncinate damage was the best predictor of frontotemporal lobar degeneration diagnosis versus controls. DT MRI measures of the anterior corpus callosum and left superior longitudinal fasciculus differentiated bvFTD from nonfluent cases. The best predictors of semantic PPA compared with both bvFTD and nonfluent cases were diffusivity abnormalities of the left uncinate and inferior longitudinal fasciculus. This study provides insights into the similarities and differences of WM damage in bvFTD and PPA variants. DT MRI metrics hold promise to serve as early markers of WM integrity loss that only at a later stage may be detectable by volumetric measures. PMID:21988828

  3. Fronto-temporal white matter connectivity predicts reversal learning errors

    PubMed Central

    Alm, Kylie H.; Rolheiser, Tyler; Mohamed, Feroze B.; Olson, Ingrid R.

    2015-01-01

    Each day, we make hundreds of decisions. In some instances, these decisions are guided by our innate needs; in other instances they are guided by memory. Probabilistic reversal learning tasks exemplify the close relationship between decision making and memory, as subjects are exposed to repeated pairings of a stimulus choice with a reward or punishment outcome. After stimulus–outcome associations have been learned, the associated reward contingencies are reversed, and participants are not immediately aware of this reversal. Individual differences in the tendency to choose the previously rewarded stimulus reveal differences in the tendency to make poorly considered, inflexible choices. Lesion studies have strongly linked reversal learning performance to the functioning of the orbitofrontal cortex, the hippocampus, and in some instances, the amygdala. Here, we asked whether individual differences in the microstructure of the uncinate fasciculus, a white matter tract that connects anterior and medial temporal lobe regions to the orbitofrontal cortex, predict reversal learning performance. Diffusion tensor imaging and behavioral paradigms were used to examine this relationship in 33 healthy young adults. The results of tractography revealed a significant negative relationship between reversal learning performance and uncinate axial diffusivity, but no such relationship was demonstrated in a control tract, the inferior longitudinal fasciculus. Our findings suggest that the uncinate might serve to integrate associations stored in the anterior and medial temporal lobes with expectations about expected value based on feedback history, computed in the orbitofrontal cortex.

  4. Signalling properties of identified deep cerebellar nuclear neurons related to eye and head movements in the alert cat.

    PubMed Central

    Gruart, A; Delgado-García, J M

    1994-01-01

    1. The spike activity of deep cerebellar nuclear neurons was recorded in the alert cat during spontaneous and during vestibularly and visually induced eye movements. 2. Neurons were classified according to their location in the nuclei, their antidromic activation from projection sites, their sensitivity to eye position and velocity during spontaneous eye movements, and their responses to vestibular and optokinetic stimuli. 3. Type I EPV (eye position and velocity) neurons were located mainly in the posterior part of the fastigial nucleus and activated antidromically almost exclusively from the medial longitudinal fasciculus close to the oculomotor complex. These neurons, reported here for the first time, increased their firing rate during saccades and eye fixations towards the contralateral hemifield. Their position sensitivity to eye fixations in the horizontal plane was 5.3 +/- 2.6 spikes s-1 deg-1 (mean +/- S.D.). Eye velocity sensitivity during horizontal saccades was 0.71 +/- 0.52 spikes s-1 deg-1 s-1. Variability of their firing rate during a given eye fixation was higher than that shown by abducens motoneurons. 4. Type I EPV neurons increased their firing rate during ipsilateral head rotations at 0.5 Hz with a mean phase lead over eye position of 95.3 +/- 9.5 deg. They were also activated by contralateral optokinetic stimulation at 30 deg s-1. Their sensitivity to eye position and velocity in the horizontal plane during vestibular and optokinetic stimuli yielded values similar to those obtained for spontaneous eye movements. 5. Type II neurons were located in both fastigial and dentate nuclei and were activated antidromically from the restiform body, the medial longitudinal fasciculus close to the oculomotor complex, the red nucleus and the pontine nuclei. Type II neurons were not related to spontaneous eye movements. These neurons increased their firing rate in response to contralateral head rotation and during ipsilateral optokinetic stimulation, and decreased it with the oppositely directed movements. 6. Saccade-related neurons were located mostly in the fastigial and dentate nuclei. Fastigial neurons were activated antidromically from the medial longitudinal fasciculus, while dentate neurons were activated from the red nucleus. These neurons fired a burst of spikes whose duration was significantly related to saccade duration. Dentate neurons responded during the omni-directional saccades, while some fastigial neurons fired more actively during contralateral saccades. 7. These three types of neuron represent the output channel for oculomotor signals of the posterior vermis and paravermis. It is proposed that type I EPV neurons correspond to a group of premotor neurons directly involved in oculomotor control.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7965834

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

    PubMed

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

    2008-06-01

    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

  6. The impact of depression on Veterans with PTSD and traumatic brain injury: a diffusion tensor imaging study.

    PubMed

    Isaac, Linda; Main, Keith L; Soman, Salil; Gotlib, Ian H; Furst, Ansgar J; Kinoshita, Lisa M; Fairchild, J Kaci; Yesavage, Jerome A; Ashford, J Wesson; Bayley, Peter J; Adamson, Maheen M

    2015-02-01

    A significant proportion of military personnel deployed in support of Operation Enduring Freedom and Operation Iraqi Freedom were exposed to war-zone events associated with traumatic brain injury (TBI), depression (DEP) and posttraumatic stress disorder (PTSD). The co-occurrence of TBI, PTSD and DEP in returning Veterans has recently increased research and clinical interest. This study tested the hypothesis that white matter abnormalities are further impacted by depression. Of particular relevance is the uncinate fasciculus (UF), which is a key fronto-temporal tract involved in mood regulation, and the cingulum; a tract that connects to the hippocampus involved in memory integration. Diffusion tensor imaging (DTI) was performed on 25 patients with a combination of PTSD, TBI and DEP and 20 patients with PTSD and TBI (no DEP). Microstructural changes of white matter were found in the cingulum and UF. Fractional anisotropy (FA) was lower in Veterans with DEP compared to those without DEP. PMID:25559772

  7. Abnormal Vestibular Evoked Myogenic Potentials in Medial Medullary Infarction

    PubMed Central

    Shin, Je-Young; Song, Hyun-Seok; Koo, Ja-Won; Lee, Hak-Seung

    2009-01-01

    Background The medial vestibulospinal tract (MVST), which descends in the medial longitudinal fasciculus (MLF), may mediate the vestibular evoked myogenic potentials (VEMPs) in the contracting sternocleidomastoid muscle. We report herein abnormal VEMPs in a patient with medial medullary infarction (MMI) that appeared to involve the MLF. Case Report A patient with infarction involving the right medial medulla showed decreased p13-n23 amplitude and increased p13/n23 latencies of the VEMPs on the right side. These abnormal VEMPs recorded in an MMI patient support the theory that VEMPs are mediated by the MVST contained within the MLF. Conclusions VEMPs may represent a valuable tool for investigating vestibular dysfunction originating from the saccule, even in patients with central vestibulopathies, which is not readily defined by conventional vestibular function tests. PMID:19587819

  8. A simple method for 3D analysis of immunolabeled axonal tracts in a transparent nervous system.

    PubMed

    Belle, Morgane; Godefroy, David; Dominici, Chloé; Heitz-Marchaland, Céline; Zelina, Pavol; Hellal, Farida; Bradke, Frank; Chédotal, Alain

    2014-11-20

    Clearing techniques have been developed to transparentize mouse brains, thereby preserving 3D structure, but their complexity has limited their use. Here, we show that immunolabeling of axonal tracts followed by optical clearing with solvents (3DISCO) and light-sheet microscopy reveals brain connectivity in mouse embryos and postnatal brains. We show that the Robo3 receptor is selectively expressed by medial habenula axons forming the fasciculus retroflexus (FR) and analyzed the development of this commissural tract in mutants of the Slit/Robo and DCC/Netrin pathways. Netrin-1 and DCC are required to attract FR axons to the midline, but the two mutants exhibit specific and heterogeneous axon guidance defects. Moreover, floor-plate-specific deletion of Slit ligands with a conditional Slit2 allele perturbs not only midline crossing by FR axons but also their anteroposterior distribution. In conclusion, this method represents a unique and powerful imaging tool to study axonal connectivity in mutant mice. PMID:25456121

  9. White matter morphometric changes uniquely predict children's reading acquisition.

    PubMed

    Myers, Chelsea A; Vandermosten, Maaike; Farris, Emily A; Hancock, Roeland; Gimenez, Paul; Black, Jessica M; Casto, Brandi; Drahos, Miroslav; Tumber, Mandeep; Hendren, Robert L; Hulme, Charles; Hoeft, Fumiko

    2014-10-01

    This study examined whether variations in brain development between kindergarten and Grade 3 predicted individual differences in reading ability at Grade 3. Structural MRI measurements indicated that increases in the volume of two left temporo-parietal white matter clusters are unique predictors of reading outcomes above and beyond family history, socioeconomic status, and cognitive and preliteracy measures at baseline. Using diffusion MRI, we identified the left arcuate fasciculus and superior corona radiata as key fibers within the two clusters. Bias-free regression analyses using regions of interest from prior literature revealed that volume changes in temporo-parietal white matter, together with preliteracy measures, predicted 56% of the variance in reading outcomes. Our findings demonstrate the important contribution of developmental differences in areas of left dorsal white matter, often implicated in phonological processing, as a sensitive early biomarker for later reading abilities, and by extension, reading difficulties. PMID:25212581

  10. Mesolimbic Dopamine and Habenulo-Interpeduncular Pathways in Nicotine Withdrawal

    PubMed Central

    Dani, John A.; De Biasi, Mariella

    2013-01-01

    The majority of people who attempt to quit smoking without some assistance relapse within the first couple of weeks, indicating the increased vulnerability during the early withdrawal period. The habenula, which projects via the fasciculus retroflexus to the interpeduncular nucleus, plays an important role in the withdrawal syndrome. Particularly the ?2, ?5, and ?4 subunits of the nicotinic acetylcholine receptor have critical roles in mediating the somatic manifestations of withdrawal. Furthermore, withdrawal from nicotine induces a hypodopaminergic state, but there is a relative increase in the sensitivity to phasic dopamine release that is caused by nicotine. Therefore, acute nicotine re-exposure causes a phasic DA response that more potently reinforces relapse to smoking during the withdrawal period. PMID:23732854

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

    PubMed

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

    2011-09-01

    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

  12. Fronto-Parietal Anatomical Connections Influence the Modulation of Conscious Visual Perception by High-Beta Frontal Oscillatory Activity.

    PubMed

    Quentin, Romain; Chanes, Lorena; Vernet, Marine; Valero-Cabré, Antoni

    2015-08-01

    May white matter connectivity influence rhythmic brain activity underlying visual cognition? We here employed diffusion imaging to reconstruct the fronto-parietal white matter pathways in a group of healthy participants who displayed frequency-specific ameliorations of visual sensitivity during the entrainment of high-beta oscillatory activity by rhythmic transcranial magnetic stimulation over their right frontal eye field. Our analyses reveal a strong tract-specific association between the volume of the first branch of the superior longitudinal fasciculus and improvements of conscious visual detection driven by frontal beta oscillation patterns. These data indicate that the architecture of specific white matter pathways has the ability to influence the distributed effects of rhythmic spatio-temporal activity, and suggest a potentially relevant role for long-range connectivity in the synchronization of oscillatory patterns across fronto-parietal networks subtending the modulation of conscious visual perception. PMID:24554730

  13. Reduced Fractional Anisotropy in the Visual Limbic Pathway of Young Adults Witnessing Domestic Violence in Childhood

    PubMed Central

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

    2011-01-01

    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 yrs) but were not physically or sexually abused were compared to 27 healthy controls (19F/ 8M, 21.9±1.97 yrs) 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 – 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

  14. The relation between structural and functional connectivity depends on age and on task goals

    PubMed Central

    Ford, Jaclyn H.; Kensinger, Elizabeth A.

    2014-01-01

    The last decade has seen an increase in neuroimaging studies examining structural (i.e., structural integrity of white matter tracts) and functional connectivity (e.g., correlations in neural activity throughout the brain). Although structural and functional connectivity changes have often been measured independently, examining the relation between these two measures is critical to understanding the specific function of neural networks and the ways they may differ across tasks and individuals. The current study addressed this question by examining the effect of age (treated as a continuous variable) and emotional valence on the relation between functional and structural connectivity. As prior studies have suggested that prefrontal regions may guide and regulate emotional memory search via functional connections with the amygdala, the current analysis focused on functional connectivity between the left amygdala and the left prefrontal cortex, and structural integrity of the uncinate fasciculus, a white matter tract connecting prefrontal and temporal regions. Participants took part in a scanned retrieval task in which they recalled positive, negative, and neutral images associated with neutral titles. Aging was associated with a significant increase in the relation between measures of structural integrity (specifically, fractional anisotropy, or FA) along the uncinate fasciculus and functional connectivity between the left ventral prefrontal cortex and amygdala during positive event retrieval, but not negative or neutral retrieval. Notably, during negative event retrieval, age was linked to stronger structure-function relations between the amygdala and the dorsal anterior cingulate cortex, such that increased structural integrity predicted stronger negative functional connectivity in older adults only. These findings suggest that young and older adults may utilize a structural pathway to engage different retrieval and regulatory strategies, even when structural integrity along that pathway does not differ. PMID:24904351

  15. Damage to ventral and dorsal language pathways in acute aphasia

    PubMed Central

    Hartwigsen, Gesa; Kellmeyer, Philipp; Glauche, Volkmar; Mader, Irina; Klöppel, Stefan; Suchan, Julia; Karnath, Hans-Otto; Weiller, Cornelius; Saur, Dorothee

    2013-01-01

    Converging evidence from neuroimaging studies and computational modelling suggests an organization of language in a dual dorsal–ventral brain network: a dorsal stream connects temporoparietal with frontal premotor regions through the superior longitudinal and arcuate fasciculus and integrates sensorimotor processing, e.g. in repetition of speech. A ventral stream connects temporal and prefrontal regions via the extreme capsule and mediates meaning, e.g. in auditory comprehension. The aim of our study was to test, in a large sample of 100 aphasic stroke patients, how well acute impairments of repetition and comprehension correlate with lesions of either the dorsal or ventral stream. We combined voxelwise lesion-behaviour mapping with the dorsal and ventral white matter fibre tracts determined by probabilistic fibre tracking in our previous study in healthy subjects. We found that repetition impairments were mainly associated with lesions located in the posterior temporoparietal region with a statistical lesion maximum in the periventricular white matter in projection of the dorsal superior longitudinal and arcuate fasciculus. In contrast, lesions associated with comprehension deficits were found more ventral-anterior in the temporoprefrontal region with a statistical lesion maximum between the insular cortex and the putamen in projection of the ventral extreme capsule. Individual lesion overlap with the dorsal fibre tract showed a significant negative correlation with repetition performance, whereas lesion overlap with the ventral fibre tract revealed a significant negative correlation with comprehension performance. To summarize, our results from patients with acute stroke lesions support the claim that language is organized along two segregated dorsal–ventral streams. Particularly, this is the first lesion study demonstrating that task performance on auditory comprehension measures requires an interaction between temporal and prefrontal brain regions via the ventral extreme capsule pathway. PMID:23378217

  16. Fusing Functional MRI and Diffusion Tensor Imaging Measures of Brain Function and Structure to Predict Working Memory and Processing Speed Performance among Inter-episode Bipolar Patients.

    PubMed

    McKenna, Benjamin S; Theilmann, Rebecca J; Sutherland, Ashley N; Eyler, Lisa T

    2015-05-01

    Evidence for abnormal brain function as measured with diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) and cognitive dysfunction have been observed in inter-episode bipolar disorder (BD) patients. We aimed to create a joint statistical model of white matter integrity and functional response measures in explaining differences in working memory and processing speed among BD patients. Medicated inter-episode BD (n=26; age=45.2±10.1 years) and healthy comparison (HC; n=36; age=46.3±11.5 years) participants completed 51-direction DTI and fMRI while performing a working memory task. Participants also completed a processing speed test. Tract-based spatial statistics identified common white matter tracts where fractional anisotropy was calculated from atlas-defined regions of interest. Brain responses within regions of interest activation clusters were also calculated. Least angle regression was used to fuse fMRI and DTI data to select the best joint neuroimaging predictors of cognitive performance for each group. While there was overlap between groups in which regions were most related to cognitive performance, some relationships differed between groups. For working memory accuracy, BD-specific predictors included bilateral dorsolateral prefrontal cortex from fMRI, splenium of the corpus callosum, left uncinate fasciculus, and bilateral superior longitudinal fasciculi from DTI. For processing speed, the genu and splenium of the corpus callosum and right superior longitudinal fasciculus from DTI were significant predictors of cognitive performance selectively for BD patients. BD patients demonstrated unique brain-cognition relationships compared to HC. These findings are a first step in discovering how interactions of structural and functional brain abnormalities contribute to cognitive impairments in BD. (JINS, 2015, 21, 330-341). PMID:26037664

  17. The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives.

    PubMed

    Cannon, D M; Walshe, M; Dempster, E; Collier, D A; Marshall, N; Bramon, E; Murray, R M; McDonald, C

    2012-01-01

    We investigated the role of variation in putative psychosis genes coding for elements of the white matter system by examining the contribution of genotypic variation in three single-nucleotide polymorphisms (SNPs) neuregulin 1 (NRG1) SNP8NRG221533, myelin oligodendrocytes glycoprotein (MOG) rs2857766 and CNP (rs2070106) and one haplotype HAP(ICE) (deCODE) to white matter volume in patients with psychotic disorder and their unaffected relatives. Structural magnetic resonance imaging and blood samples for genotyping were collected on 189 participants including patients with schizophrenia (SZ) or bipolar I disorder (BDI), unaffected first-degree relatives of these patients and healthy volunteers. The association of genotypic variation with white matter volume was assessed using voxel-based morphometry in SPM5. The NRG1 SNP and the HAP(ICE) haplotype were associated with abnormal white matter volume in the BDI group in the fornix, cingulum and parahippocampal gyrus circuit. In SZ the NRG1 SNP risk allele was associated with lower white matter volume in the uncinate fasciculus (UF), right inferior longitudinal fasciculus and the anterior limb of the internal capsule. Healthy G-homozygotes of the MOG SNP had greater white matter volume in areas of the brainstem and cerebellum; this relationship was absent in those with a psychotic disorder and the unaffected relatives groups. The CNP SNP did not contribute to white matter volume variation in the diagnostic groups studied. Variation in the genes coding for structural and protective components of myelin are implicated in abnormal white matter volume in the emotion circuitry of the cingulum, fornix, parahippocampal gyrus and UF in psychotic disorders. PMID:23032943

  18. Depressive symptoms and white matter dysfunction in retired NFL players with concussion history

    PubMed Central

    Strain, Jeremy; Didehbani, Nyaz; Cullum, C. Munro; Mansinghani, Sethesh; Conover, Heather; Kraut, Michael A.; Womack, Kyle B.

    2013-01-01

    Objective: To determine whether correlates of white matter integrity can provide general as well as specific insight into the chronic effects of head injury coupled with depression symptom expression in professional football players. Method: We studied 26 retired National Football League (NFL) athletes who underwent diffusion tensor imaging (DTI) scanning. Depressive symptom severity was measured using the Beck Depression Inventory II (BDI-II) including affective, cognitive, and somatic subfactor scores (Buckley 3-factor model). Fractional anisotropy (FA) maps were processed using tract-based spatial statistics from FSL. Correlations between FA and BDI-II scores were assessed using both voxel-wise and region of interest (ROI) techniques, with ROIs that corresponded to white matter tracts. Tracts demonstrating significant correlations were further evaluated using a receiver operating characteristic curve that utilized the mean FA to distinguish depressed from nondepressed subjects. Results: Voxel-wise analysis identified widely distributed voxels that negatively correlated with total BDI-II and cognitive and somatic subfactors, with voxels correlating with the affective component (p < 0.05 corrected) localized to frontal regions. Four tract ROIs negatively correlated (p < 0.01) with total BDI-II: forceps minor, right frontal aslant tract, right uncinate fasciculus, and left superior longitudinal fasciculus. FA of the forceps minor differentiated depressed from nondepressed athletes with 100% sensitivity and 95% specificity. Conclusion: Depressive symptoms in retired NFL athletes correlate negatively with FA using either an unbiased voxel-wise or an ROI-based, tract-wise approach. DTI is a promising biomarker for depression in this population. PMID:23709590

  19. White matter pathway supporting phonological encoding in speech production: a multi-modal imaging study of brain damage patients.

    PubMed

    Han, Zaizhu; Ma, Yujun; Gong, Gaolang; Huang, Ruiwang; Song, Luping; Bi, Yanchao

    2014-10-31

    In speech production, an important step before motor programming is the retrieval and encoding of the phonological elements of target words. It has been proposed that phonological encoding is supported by multiple regions in the left frontal, temporal and parietal regions and their underlying white matter, especially the left arcuate fasciculus (AF) or superior longitudinal fasciculus (SLF). It is unclear, however, whether the effects of AF/SLF are indeed related to phonological encoding for output and whether there are other white matter tracts that also contribute to this process. We comprehensively investigated the anatomical connectivity supporting phonological encoding in production by studying the relationship between the integrity of all major white matter tracts across the entire brain and phonological encoding deficits in a group of 69 patients with brain damage. The integrity of each white matter tract was measured both by the percentage of damaged voxels (structural imaging) and the mean fractional anisotropy value (diffusion tensor imaging). The phonological encoding deficits were assessed by various measures in two oral production tasks that involve phonological encoding: the percentage of nonword (phonological) errors in oral picture naming and the accuracy of word reading aloud with word comprehension ability regressed out. We found that the integrity of the left SLF in both the structural and diffusion tensor imaging measures consistently predicted the severity of phonological encoding impairment in the two phonological production tasks. Such effects of the left SLF on phonological production remained significant when a range of potential confounding factors were considered through partial correlation, including total lesion volume, demographic factors, lesions on phonological-relevant grey matter regions, or effects originating from the phonological perception or semantic processes. Our results therefore conclusively demonstrate the central role of the left SLF in phonological encoding in speech production. PMID:25359657

  20. Sex differences in white matter integrity in youths with attention-deficit/hyperactivity disorder: a pilot study

    PubMed Central

    King, Jace B.; Yurgelun-Todd, Deborah; Stoeckel, Amanda; DiMuzio, Jennifer M.; Lopez-Larson, Melissa P.

    2015-01-01

    Widespread disparities in white matter (WM) microstructure and organization have been found in adolescents with attention-deficit/hyperactivity disorder (ADHD); however, little is known about the role sex plays in these differences. The present diffusion tensor imaging (DTI) study performed whole-brain, tract-based, voxel-wise, and region of interest (ROI) analyses to investigate WM microstructure differences between ADHD and healthy control (HC) adolescents to examine the impact of sex on measures of fractional anisotropy (FA). Eighteen adolescents with ADHD and 24 HC were included in this study. All participants received a 64-direction DTI scan on a 3 Tesla Siemens scanner. FSL's TBSS was used to perform whole-brain, tract-based, voxel-wise analyses. Tracts demonstrating significant sex-by-diagnosis interactions were further evaluated using univariate analyses performed on mean FA data that were extracted from ROIs using the Johns Hopkins University WM tractography atlas. TBSS analyses between diagnostic groups revealed significantly increased FA in HC relative to ADHD in the bilateral superior longitudinal fasciculus (SLF), forceps major, left cingulum, and bilateral callosal regions. In addition, both TBSS and separate ROI analyses revealed significant sex-by-diagnosis interactions for the corticospinal tract (CST), inferior longitudinal fasciculus (ILF) and SLF. In the HC group, FA was increased in males relative to females for all analyses. In WM regions demonstrating a significant sex-by-diagnosis, FA was increased in females relative to males in the ADHD group. Our findings suggest that WM microstructure in several major WM tracts differs between males and females with ADHD. These differences in WM microstructure may account for some of the differences in ADHD subtypes and comorbidities seen between the sexes. Additional studies in ADHD, examining sex differences in phenotypic expression, treatment response and brain network trajectories are warranted.

  1. Frontotemporal neural systems supporting semantic processing in Alzheimer's disease.

    PubMed

    Peelle, Jonathan E; Powers, John; Cook, Philip A; Smith, Edward E; Grossman, Murray

    2014-03-01

    We hypothesized that semantic memory for object concepts involves both representations of visual feature knowledge in modality-specific association cortex and heteromodal regions that are important for integrating and organizing this semantic knowledge so that it can be used in a flexible, contextually appropriate manner. We examined this hypothesis in an fMRI study of mild Alzheimer's disease (AD). Participants were presented with pairs of printed words and asked whether the words matched on a given visual-perceptual feature (e.g., guitar, violin: SHAPE). The stimuli probed natural kinds and manufactured objects, and the judgments involved shape or color. We found activation of bilateral ventral temporal cortex and left dorsolateral prefrontal cortex during semantic judgments, with AD patients showing less activation of these regions than healthy seniors. Moreover, AD patients showed less ventral temporal activation than did healthy seniors for manufactured objects, but not for natural kinds. We also used diffusion-weighted MRI of white matter to examine fractional anisotropy (FA). Patients with AD showed significantly reduced FA in the superior longitudinal fasciculus and inferior frontal-occipital fasciculus, which carry projections linking temporal and frontal regions of this semantic network. Our results are consistent with the hypothesis that semantic memory is supported in part by a large-scale neural network involving modality-specific association cortex, heteromodal association cortex, and projections between these regions. The semantic deficit in AD thus arises from gray matter disease that affects the representation of feature knowledge and processing its content, as well as white matter disease that interrupts the integrated functioning of this large-scale network. PMID:24425352

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

    PubMed Central

    Turken, And U.; Dronkers, Nina F.

    2011-01-01

    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. PMID:21347218

  3. White Matter Microstructure Correlates of Narrative Production in Typically Developing Children and Children with High Functioning Autism

    PubMed Central

    Mills, Brian; Lai, Janie; Brown, Timothy T.; Erhart, Matthew; Halgren, Eric; Reilly, Judy; Dale, Anders; Appelbaum, Mark; Moses, Pamela

    2013-01-01

    This study investigated the relationship between white matter microstructure and the development of morphosyntax in a spoken narrative in typically developing children (TD) and in children with high functioning autism (HFA). Autism is characterized by language and communication impairments, yet the relationship between morphosyntactic development in spontaneous discourse contexts and neural development is not well understood in either this population or typical development. Diffusion tensor imaging (DTI) was used to assess multiple parameters of diffusivity as indicators of white matter tract integrity in language-related tracts in children between 6 and 13 years of age. Children were asked to spontaneously tell a story about at time when someone made them sad, mad, or angry. The story was evaluated for morphological accuracy and syntactic complexity. Analysis of the relationship between white matter microstructure and language performance in TD children showed that diffusivity correlated with morphosyntax production in the superior longitudinal fasciculus (SLF), a fiber tract traditionally associated with language. At the anatomical level, the HFA group showed abnormal diffusivity in the right inferior longitudinal fasciculus (ILF) relative to the TD group. Within the HFA group, children with greater white matter integrity in the right ILF displayed greater morphological accuracy during their spoken narrative. Overall, the current study shows an association between white matter structure in a traditional language pathway and narrative performance in TD children. In the autism group, associations were only found in the ILF, suggesting that during real world language use, children with HFA rely less on typical pathways and instead rely on alternative ventral pathways that possibly mediate visual elements of language. PMID:23810972

  4. Sensory-to-motor integration during auditory repetition: a combined fMRI and lesion study

    PubMed Central

    Parker Jones, ‘?iwi; Prejawa, Susan; Hope, Thomas M. H.; Oberhuber, Marion; Seghier, Mohamed L.; Leff, Alex P.; Green, David W.; Price, Cathy J.

    2014-01-01

    The aim of this paper was to investigate the neurological underpinnings of auditory-to-motor translation during auditory repetition of unfamiliar pseudowords. We tested two different hypotheses. First we used functional magnetic resonance imaging in 25 healthy subjects to determine whether a functionally defined area in the left temporo-parietal junction (TPJ), referred to as Sylvian-parietal-temporal region (Spt), reflected the demands on auditory-to-motor integration during the repetition of pseudowords relative to a semantically mediated nonverbal sound-naming task. The experiment also allowed us to test alternative accounts of Spt function, namely that Spt is involved in subvocal articulation or auditory processing that can be driven either bottom-up or top-down. The results did not provide convincing evidence that activation increased in either Spt or any other cortical area when non-semantic auditory inputs were being translated into motor outputs. Instead, the results were most consistent with Spt responding to bottom up or top down auditory processing, independent of the demands on auditory-to-motor integration. Second, we investigated the lesion sites in eight patients who had selective difficulties repeating heard words but with preserved word comprehension, picture naming and verbal fluency (i.e., conduction aphasia). All eight patients had white-matter tract damage in the vicinity of the arcuate fasciculus and only one of the eight patients had additional damage to the Spt region, defined functionally in our fMRI data. Our results are therefore most consistent with the neurological tradition that emphasizes the importance of the arcuate fasciculus in the non-semantic integration of auditory and motor speech processing. PMID:24550807

  5. Influence of the fragile X mental retardation (FMR1) gene on the brain and working memory in men with normal FMR1 alleles.

    PubMed

    Wang, Jun Yi; Hessl, David; Iwahashi, Christine; Cheung, Katherine; Schneider, Andrea; Hagerman, Randi J; Hagerman, Paul J; Rivera, Susan M

    2013-01-15

    The fragile X mental retardation 1 (FMR1) gene plays an important role in the development and maintenance of neuronal circuits that are essential for cognitive functioning. We explored the functional linkage(s) among lymphocytic FMR1 gene expression, brain structure, and working memory in healthy adult males. We acquired T1-weighted and diffusion tensor imaging from 37 males (18-80 years, mean ± SD= 40.7 ± 17.3 years) with normal FMR1 alleles and performed genetic and working memory assessments. Brain measurements were obtained from fiber tracts important for working memory (i.e. the arcuate fasciculus, anterior cingulum bundle, inferior longitudinal fasciculus, and the genu and anterior body of the corpus callosum), individual voxels, and whole brain. Both FMR1 mRNA and protein (FMRP) levels exhibited significant associations with brain measurements, with FMRP correlating positively with gray matter volume and white matter structural organization, and FMR1 mRNA negatively with white matter structural organization. The correlation was widespread, impacting rostral white matter and 2 working-memory fiber tracts for FMRP, and all cerebral white matter areas except the fornix and cerebellar peduncles and all 4 fiber tracts for FMR1 mRNA. In addition, the levels of FMR1 mRNA as well as the fiber tracts demonstrated a significant correlation with working memory performance. While FMR1 mRNA exhibited a negative correlation with working memory, fiber tract structural organization showed a positive correlation. These findings suggest that the FMR1 gene is a genetic factor common for both working memory and brain structure, and has implications for our understanding of the transmission of intelligence and brain structure. PMID:23063447

  6. Altered white matter microstructure in adolescent substance users

    PubMed Central

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

    2009-01-01

    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. Diffusion parameters fractional anisotropy (FA) and mean diffusivity (MD) were subjected to whole-brain voxelwise group comparisons using tract-based spatial statistics (Smith et al., 2006). 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 suggests 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

  7. White matter lesional predictors of chronic visual neglect: a longitudinal study.

    PubMed

    Lunven, Marine; Thiebaut De Schotten, Michel; Bourlon, Clémence; Duret, Christophe; Migliaccio, Raffaella; Rode, Gilles; Bartolomeo, Paolo

    2015-03-01

    Chronic visual neglect prevents brain-damaged patients from returning to an independent and active life. Detecting predictors of persistent neglect as early as possible after the stroke is therefore crucial to plan the relevant interventions. Neglect signs do not only depend on focal brain lesions, but also on dysfunction of large-scale brain networks connected by white matter bundles. We explored the relationship between markers of axonal degeneration occurring after the stroke and visual neglect chronicity. A group of 45 patients with unilateral strokes in the right hemisphere underwent cognitive testing for neglect twice, first at the subacute phase (<3 months after onset) and then at the chronic phase (>1 year). For each patient, magnetic resonance imaging including diffusion sequences was performed at least 4 months after the stroke. After masking each patient's lesion, we used tract-based spatial statistics to obtain a voxel-wise statistical analysis of the fractional anisotropy data. Twenty-seven patients had signs of visual neglect at initial testing. Only 10 of these patients had recovered from neglect at follow-up. When compared with patients without neglect, the group including all subacute neglect patients had decreased fractional anisotropy in the second (II) and third (III) branches of the right superior longitudinal fasciculus, as well as in the splenium of the corpus callosum. The subgroup of chronic patients showed reduced fractional anisotropy in a portion the splenium, the forceps major, which provides interhemispheric communication between regions of the occipital lobe and of the superior parietal lobules. The severity of neglect correlated with fractional anisotropy values in superior longitudinal fasciculus II/III for subacute patients and in its caudal portion for chronic patients. Our results confirm a key role of fronto-parietal disconnection in the emergence and chronic persistence of neglect, and demonstrate an implication of caudal interhemispheric disconnection in chronic neglect. Splenial disconnection may prevent fronto-parietal networks in the left hemisphere from resolving the activity imbalance with their right hemisphere counterparts, thus leading to persistent neglect. PMID:25609686

  8. Relating brain anatomy and cognitive ability using a multivariate multimodal framework.

    PubMed

    Cook, Philip A; McMillan, Corey T; Avants, Brian B; Peelle, Jonathan E; Gee, James C; Grossman, Murray

    2014-10-01

    Linking structural neuroimaging data from multiple modalities to cognitive performance is an important challenge for cognitive neuroscience. In this study we examined the relationship between verbal fluency performance and neuroanatomy in 54 patients with frontotemporal degeneration (FTD) and 15 age-matched controls, all of whom had T1- and diffusion-weighted imaging. Our goal was to incorporate measures of both gray matter (voxel-based cortical thickness) and white matter (fractional anisotropy) into a single statistical model that relates to behavioral performance. We first used eigenanatomy to define data-driven regions of interest (DD-ROIs) for both gray matter and white matter. Eigenanatomy is a multivariate dimensionality reduction approach that identifies spatially smooth, unsigned principal components that explain the maximal amount of variance across subjects. We then used a statistical model selection procedure to see which of these DD-ROIs best modeled performance on verbal fluency tasks hypothesized to rely on distinct components of a large-scale neural network that support language: category fluency requires a semantic-guided search and is hypothesized to rely primarily on temporal cortices that support lexical-semantic representations; letter-guided fluency requires a strategic mental search and is hypothesized to require executive resources to support a more demanding search process, which depends on prefrontal cortex in addition to temporal network components that support lexical representations. We observed that both types of verbal fluency performance are best described by a network that includes a combination of gray matter and white matter. For category fluency, the identified regions included bilateral temporal cortex and a white matter region including left inferior longitudinal fasciculus and frontal-occipital fasciculus. For letter fluency, a left temporal lobe region was also selected, and also regions of frontal cortex. These results are consistent with our hypothesized neuroanatomical models of language processing and its breakdown in FTD. We conclude that clustering the data with eigenanatomy before performing linear regression is a promising tool for multimodal data analysis. PMID:24830834

  9. Tractography reveals diffuse white matter abnormalities in Myotonic Dystrophy Type 1

    PubMed Central

    Wozniak, Jeffrey R.; Mueller, Bryon A.; Lim, Kelvin O.; Hemmy, Laura S.; Day, John W.

    2014-01-01

    Cerebral involvement in Myotonic Dystrophy Type 1 (DM1) is well-established but not well characterized. This study applied new Diffusion Tensor Imaging (DTI) tractography to characterize white matter disturbance in adults with DM1. Forty-five participants with DM1 and 44 control participants had MRIs on a Siemens 3T TIM Trio scanner. Data were processed with TRActs Constrained by UnderLying Anatomy (TRACULA) and 7 tracts were evaluated. Bilateral disturbances in white matter integrity were seen in all tracts in participants with DM1 compared to controls. There were no right-left hemisphere differences. The resulting DTI metrics were correlated with cognitive functioning, particularly working memory and processing speed. Motor speed was not significantly correlated with white matter microstructural integrity and, thus, was not the core explanation for the working memory and processing speed findings. White matter integrity was correlated with important clinical variables including the muscular impairment rating scale (MIRS). CTG repeat length was moderately associated with white matter status in corticospinal tract and cingulum. Sleepiness (Epworth Sleepiness Scale) was moderately associated with white matter status in the superior longitudinal fasciculus and cingulum. Overall, the results add to an emerging literature showing widespread white matter disturbances in both early-onset and adult-onset DM1. Results suggest that further investigation of white matter pathology is warranted in DM1 and that non-invasive measures such as DTI have potentially important clinical value in characterizing the status of individuals with DM1. PMID:24768314

  10. Tractography reveals diffuse white matter abnormalities in Myotonic Dystrophy Type 1.

    PubMed

    Wozniak, Jeffrey R; Mueller, Bryon A; Lim, Kelvin O; Hemmy, Laura S; Day, John W

    2014-06-15

    Cerebral involvement in Myotonic Dystrophy Type 1 (DM1) is well-established but not well characterized. This study applied new Diffusion Tensor Imaging (DTI) tractography to characterize white matter disturbance in adults with DM1. Forty-five participants with DM1 and 44 control participants had MRIs on a Siemens 3T TIM Trio scanner. Data were processed with TRActs Constrained by UnderLying Anatomy (TRACULA) and 7 tracts were evaluated. Bilateral disturbances in white matter integrity were seen in all tracts in participants with DM1 compared to controls. There were no right-left hemisphere differences. The resulting DTI metrics were correlated with cognitive functioning, particularly working memory and processing speed. Motor speed was not significantly correlated with white matter microstructural integrity and, thus, was not the core explanation for the working memory and processing speed findings. White matter integrity was correlated with important clinical variables including the muscular impairment rating scale (MIRS). CTG repeat length was moderately associated with white matter status in corticospinal tract and cingulum. Sleepiness (Epworth Sleepiness Scale) was moderately associated with white matter status in the superior longitudinal fasciculus and cingulum. Overall, the results add to an emerging literature showing widespread white matter disturbances in both early-onset and adult-onset DM1. Results suggest that further investigation of white matter pathology is warranted in DM1 and that non-invasive measures such as DTI have a potentially important clinical value in characterizing the status of individuals with DM1. PMID:24768314

  11. Independent Component Analysis-Based Identification of Covariance Patterns of Microstructural White Matter Damage in Alzheimer’s Disease

    PubMed Central

    Ouyang, Xin; Chen, Kewei; Yao, Li; Wu, Xia; Zhang, Jiacai; Li, Ke; Jin, Zhen; Guo, Xiaojuan

    2015-01-01

    The existing DTI studies have suggested that white matter damage constitutes an important part of the neurodegenerative changes in Alzheimer’s disease (AD). The present study aimed to identify the regional covariance patterns of microstructural white matter changes associated with AD. In this study, we applied a multivariate analysis approach, independent component analysis (ICA), to identify covariance patterns of microstructural white matter damage based on fractional anisotropy (FA) skeletonised images from DTI data in 39 AD patients and 41 healthy controls (HCs) from the Alzheimer’s Disease Neuroimaging Initiative database. The multivariate ICA decomposed the subject-dimension concatenated FA data into a mixing coefficient matrix and a source matrix. Twenty-eight independent components (ICs) were extracted, and a two sample t-test on each column of the corresponding mixing coefficient matrix revealed significant AD/HC differences in ICA weights for 7 ICs. The covariant FA changes primarily involved the bilateral corona radiata, the superior longitudinal fasciculus, the cingulum, the hippocampal commissure, and the corpus callosum in AD patients compared to HCs. Our findings identified covariant white matter damage associated with AD based on DTI in combination with multivariate ICA, potentially expanding our understanding of the neuropathological mechanisms of AD. PMID:25775003

  12. Retinofugal projections in the mouse.

    PubMed

    Morin, Lawrence P; Studholme, Keith M

    2014-11-01

    The laboratory mouse is increasingly a subject for visual system investigation, but there has been no comprehensive evaluation of this species' visual projections. Here, projections were visualized and mapped following intraocular injection of cholera toxin B subunit. Tissue was processed using standard procedures applied to 30 ?m free-floating sections with diaminobenzidine as the chromogen. The mouse retina projects to ~46 brain regions, including 14 not previously described in this species. These include two amygdaloid nuclei, the horizontal limb of the diagonal band, the paraventricular hypothalamic nucleus, several visual thalamic nuclei, the paranigral nucleus, several pretectal nuclei, and the dorsal cortex of the inferior colliculus. Dense retinal patches were also observed in a narrow portion of the ipsilateral intermediate layer of the superior colliculus. The superior fasciculus of the accessory optic tract, which innervates the medial terminal nucleus, was also determined to be a terminal zone throughout its length. The results are compared with previous descriptions of projections from mouse intrinsically photoreceptive retinal ganglion cells, and with data from the hamster, Nile grass rat, and laboratory rat. The retinal projection patterns are similar in all four species, although there are many differences with respect to the details. The specific visual functions of most retinorecipient areas are unknown, but there is substantial convergence of retinal projections onto regions concerned with olfaction and audition. PMID:24889098

  13. Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance.

    PubMed

    Onnink, A Marten H; Zwiers, Marcel P; Hoogman, Martine; Mostert, Jeanette C; Dammers, Janneke; Kan, Cornelis C; Vasquez, Alejandro Arias; Schene, Aart H; Buitelaar, Jan; Franke, Barbara

    2015-12-01

    Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by gray and white matter abnormalities in several brain areas. Considerably less is known about white matter microstructure in adults with ADHD and its relation with clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109 gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). Additionally, we studied the relation of FA and MD values with symptom severity and cognitive performance on tasks measuring working memory, attention, inhibition, and delay discounting. In comparison to controls, participants with ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic radiation. Higher MD and RD were found in overlapping and even more widespread areas in both hemispheres, also encompassing internal and external capsule, sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD were not associated with symptom severity. However, within some white matter clusters that distinguished patients from controls, worse inhibition performance was associated with reduced FA and more impulsive decision making was associated with increased MD. This study shows widespread differences in white matter integrity between adults with persistent ADHD and healthy individuals. Changes in RD suggest aberrant myelination as a pathophysiological factor in persistent ADHD. The microstructural differences in adult ADHD may contribute to poor inhibition and greater impulsivity but appear to be independent of disease severity. PMID:25956761

  14. Mesencephalic cholinergic nuclei in progressive supranuclear palsy.

    PubMed

    Juncos, J L; Hirsch, E C; Malessa, S; Duyckaerts, C; Hersh, L B; Agid, Y

    1991-01-01

    Using an antibody against choline acetyltransferase (ChAT), mesencephalic cholinergic cell nuclei were studied in autopsy material from 3 cases of progressive supranuclear palsy (PSP) and 4 controls. ChAT-immunoreactive neurons were quantified in sections that spanned the rostrocaudal extent of each nucleus. In PSP, there was a significant decrease in the number of neurons with detectable immunoreactivity for ChAT in and adjacent to the central gray substance in the following nuclei: the nucleus of Edinger-Westphal (69%); the rostral interstitial nucleus of the medial longitudinal fasciculus (97%); the interstitial nucleus of Cajal (78%). A cell loss was also evident in a group of neurons found in the deep layers of the superior colliculus (93%). In contrast, the estimated number of ChAT-immunoreactive cell bodies in cranial nerves III and IV, in the mesencephalic reticular formation, and in the parabigeminal nucleus was not different from that of controls. The results are compatible with the notion that, in PSP, there is a regionally selective destruction of cholinergic neurons. PMID:1985290

  15. [Neural representation of human body schema and corporeal self-consciousness].

    PubMed

    Naito, Eiichi; Morita, Tomoyo

    2014-04-01

    The human brain processes every sensation evoked by altered posture and builds up a constantly changing postural model of the body. This is called a body schema, and somatic signals originating from skeletal muscles and joints, i.e. proprioceptive signals, largely contribute its formation. Recent neuroimaging techniques have revealed neuronal substrates for human body schema. A dynamic limb position model seems to be computed in the central motor network (represented by the primary motor cortex). Here, proprioceptive (kinesthetic) signals from muscle spindles are transformed into motor commands, which may underlie somatic perception of limb movement and facilitate its efficient motor control. Somatic signals originating from different body parts are integrated in the course of hierarchical somatosensory processing, and activity in higher-order somatosensory parietal cortices is capable of representing a postural model of the entire body. The left fronto-parietal network associates internal motor representation with external object representation, allowing the embodiment of external objects. In contrast, the right fronto-parietal regions connected by the most inferior branch of superior longitudinal fasciculus fibers seem to have the functions of monitoring bodily states and updating body schema. We hypothesize that activity in these right-sided fronto-parietal regions is deeply involved in corporeal self-consciousness. PMID:24748084

  16. Have You Ever Seen the Impact of Crossing Fiber in DTI?: Demonstration of the Corticospinal Tract Pathway

    PubMed Central

    Lee, Dong-Hoon; Park, Ji Won; Park, Sung-Hee; Hong, Cheolpyo

    2015-01-01

    Objective The identification of the corticospinal tract (CST) pathway with a deterministic fiber tracking approach is limited because of crossing fibers, especially for the hand fibers of the CST due to the crossing superior longitudinal fasciculus (SLF). We examined a patient with congenital bilateral perisylvian syndrome (CBPS) who did not have the SLF, in order to visualize CST hand fibers that were not affected by crossing fibers. Methods A 10-year-old girl without the SLF due to CBPS and three normal healthy subjects participated in this study. We used a deterministic fiber tracking algorithm, and the regions of interest (ROIs) were drawn in the posterior limb of internal capsule (PLIC) and the primary motor cortex. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR) were measured based on the extracted fiber tracts. Results The ADC values were not different between the normal subjects and the patient with CBPS. The FA, RA, and VR values of the normal subjects were similar, but were relatively higher than those of the patient with CBPS. Conclusion Our results clearly show the impact of the crossing fiber for the hand motor fibers of the CST pathway with deterministic tracking algorithms in diffusion tensor tractography. PMID:26135795

  17. Tone-deafness – a new disconnection syndrome?

    PubMed Central

    Loui, Psyche; Alsop, David; Schlaug, Gottfried

    2009-01-01

    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. PMID:19692596

  18. Contemporary model of language organization: an overview for neurosurgeons.

    PubMed

    Chang, Edward F; Raygor, Kunal P; Berger, Mitchel S

    2015-02-01

    Classic models of language organization posited that separate motor and sensory language foci existed in the inferior frontal gyrus (Broca's area) and superior temporal gyrus (Wernicke's area), respectively, and that connections between these sites (arcuate fasciculus) allowed for auditory-motor interaction. These theories have predominated for more than a century, but advances in neuroimaging and stimulation mapping have provided a more detailed description of the functional neuroanatomy of language. New insights have shaped modern network-based models of speech processing composed of parallel and interconnected streams involving both cortical and subcortical areas. Recent models emphasize processing in "dorsal" and "ventral" pathways, mediating phonological and semantic processing, respectively. Phonological processing occurs along a dorsal pathway, from the posterosuperior temporal to the inferior frontal cortices. On the other hand, semantic information is carried in a ventral pathway that runs from the temporal pole to the basal occipitotemporal cortex, with anterior connections. Functional MRI has poor positive predictive value in determining critical language sites and should only be used as an adjunct for preoperative planning. Cortical and subcortical mapping should be used to define functional resection boundaries in eloquent areas and remains the clinical gold standard. In tracing the historical advancements in our understanding of speech processing, the authors hope to not only provide practicing neurosurgeons with additional information that will aid in surgical planning and prevent postoperative morbidity, but also underscore the fact that neurosurgeons are in a unique position to further advance our understanding of the anatomy and functional organization of language. PMID:25423277

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

    PubMed Central

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

    2013-01-01

    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

  20. The association between the 5-HTTLPR and neural correlates of fear conditioning and connectivity.

    PubMed

    Klucken, Tim; Schweckendiek, Jan; Blecker, Carlo; Walter, Bertram; Kuepper, Yvonne; Hennig, Juergen; Stark, Rudolf

    2015-05-01

    Strong evidence links the 5-HTTLPR genotype to the modulation of amygdala reactivity during fear conditioning, which is considered to convey the increased vulnerability for anxiety disorders in s-allele carriers. In addition to amygdala reactivity, the 5-HTTLPR has been shown to be related to alterations in structural and effective connectivity. The aim of this study was to investigate the effects of 5-HTTLPR genotype on amygdala reactivity and effective connectivity during fear conditioning, as well as structural connectivity [as measured by diffusion tensor imaging (DTI)]. To integrate different classification strategies, we used the bi-allelic (s-allele vs l/l-allele group) as well as the tri-allelic (low-functioning vs high-functioning) classification approach. S-allele carriers showed exaggerated amygdala reactivity and elevated amygdala-insula coupling during fear conditioning (CS + > CS-) compared with the l/l-allele group. In addition, DTI analysis showed increased fractional anisotropy values in s-allele carriers within the uncinate fasciculus. Using the tri-allelic classification approach, increased amygdala reactivity and amygdala insula coupling were observed in the low-functioning compared with the high-functioning group. No significant differences between the two groups were found in structural connectivity. The present results add to the current debate on the influence of the 5-HTTLPR on brain functioning. These differences between s-allele and l/l-allele carriers may contribute to altered vulnerability for psychiatric disorders. PMID:25140050

  1. Neuronavigation-guided endoscopic and hodotopic approach to an arachnoid cyst

    PubMed Central

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

    2013-01-01

    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. PMID:24083055

  2. [Enzyme histochemical study of the brain of Chthonerpeton indistinctum (Gymnophiona, Amphibia)].

    PubMed

    Welsch, U; Tan, S H

    1979-01-01

    In the brain of the Caecilian species Chthonerpeton indistinctum the following enzymes have been demonstrated by means of histochemical techniques: acid phosphatase, alpha-naphthylacetate esterase, acetylcholin esterase. Acid phosphatase occurs in the cytoplasm of the neurons in 4 different types of localization. Its activity in the ventral parts of the brain is markedly higher than in the dorsal ones. Of particularly high activity are: the motor neurons in the tegmentum, the nucleus mesencephali trigemini, individual large neurons in the marginal zone of the grey matter of the telencephalon, which seems to be a special character of the Caecilians among the Amphibia. The ependyma exhibits local differences in respect of acid phosphatase activity. alpha-Naphthylacetate esterase marks in particular the secretory neurons of the hypothalamus, the large perikarya of the nucleus mesencephali trigemini and the motor neurons of the tegmentum. In the telencephalon the alpha-naphthylacetate esterase activity corresponds to that of acid phosphatase. Acetylcholin esterase marks--with certain restrictions--cholinergic neurons. These predominate in Chthonerpeton in the caudal parts of the brain. In the telencephalon amygdala, septal area striatum and the mitral cells are of comparatively high activity. The neurosecretory neurons of the hypothalamus are particularly rich in this enzyme. As an anurans the cholinergic fasciculus retroflexus as asymmetric. The tectum opticum is of secondary simplicity and does not exhibit a clearly recognizable stratification. PMID:524986

  3. Detectability of neural tracts and nuclei in the brainstem utilizing 3DAC-PROPELLER.

    PubMed

    Nishikawa, Taro; Okamoto, Kouichirou; Matsuzawa, Hitoshi; Terumitsu, Makoto; Nakada, Tsutomu; Fujii, Yukihiko

    2014-01-01

    Despite clinical importance of identifying exact anatomical location of neural tracts and nuclei in the brainstem, no neuroimaging studies have validated the detectability of these structures. The aim of this study was to assess the detectability of the structures using three-dimensional anisotropy contrast-periodically rotated overlapping parallel lines with enhanced reconstruction (3DAC-PROPELLER) imaging. Forty healthy volunteers (21 males, 19 females; 19-53 years, average 23.4 years) participated in this study. 3DAC-PROPELLER axial images were obtained with a 3T-MR system at four levels of the brainstem: the lower midbrain, upper and lower pons, and medulla oblongata. Three experts independently judged whether five tracts (corticospinal tract, medial lemniscus, medial longitudinal fasciculus, central tegmental and spinothalamic tracts) and 10 nuclei (oculomotor and trochlear nuclei, spinal trigeminal, abducens, facial, vestibular, hypoglossal, prepositus, and solitary nuclei, locus ceruleus, superior and inferior olives) on each side could be identified. In total, 240 assessments were made. The five tracts and eight nuclei were identified in all the corresponding assessments, whereas the locus ceruleus and superior olive could not be identified in 3 (1.3%) and 16 (6.7%) assessments, respectively. 3DAC-PROPELLER seems extremely valuable imaging method for mapping out surgical strategies for brainstem lesions. PMID:23607742

  4. Integrity of medial temporal structures may predict better improvement of spatial neglect with prism adaptation treatment.

    PubMed

    Chen, Peii; Goedert, Kelly M; Shah, Priyanka; Foundas, Anne L; Barrett, A M

    2014-09-01

    Prism adaptation treatment (PAT) is a promising rehabilitative method for functional recovery in persons with spatial neglect. Previous research suggests that PAT improves motor-intentional "aiming" deficits that frequently occur with frontal lesions. To test whether presence of frontal lesions predicted better improvement of spatial neglect after PAT, the current study evaluated neglect-specific improvement in functional activities (assessment with the Catherine Bergego Scale) over time in 21 right-brain-damaged stroke survivors with left-sided spatial neglect. The results demonstrated that neglect patients' functional activities improved after two weeks of PAT and continued improving for four weeks. Such functional improvement did not occur equally in all of the participants: Neglect patients with lesions involving the frontal cortex (n?=?13) experienced significantly better functional improvement than did those without frontal lesions (n?=?8). More importantly, voxel-based lesion-behavior mapping (VLBM) revealed that in comparison to the group of patients without frontal lesions, the frontal-lesioned neglect patients had intact regions in the medial temporal areas, the superior temporal areas, and the inferior longitudinal fasciculus. The medial cortical and subcortical areas in the temporal lobe were especially distinguished in the "frontal lesion" group. The findings suggest that the integrity of medial temporal structures may play an important role in supporting functional improvement after PAT. PMID:22941243

  5. Functional organization of the neural language system: dorsal and ventral pathways are critical for syntax.

    PubMed

    Griffiths, John D; Marslen-Wilson, William D; Stamatakis, Emmanuel A; Tyler, Lorraine K

    2013-01-01

    The core of human language, which differentiates it from the communicative abilities of other species, is the set of combinatorial operations called syntax. For over a century researchers have attempted to understand how this essential function is organized in the brain. Here, we combine behavioral and neuroimaging methods, with left hemisphere-damaged patients and healthy controls, to identify the pathways connecting the brain regions involved in syntactic processing. In a previous functional magnetic resonance imaging study (Tyler LK, Wright P, Randall B, Marslen-Wilson WD, Stamatakis EA. 2010b. Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function? Brain. 133(11):3396-3408.), we established that regions of left inferior frontal cortex and left posterior middle temporal cortex were activated during syntactic processing. These clusters were used here as seeds for probabilistic tractography analyses in patients and controls, allowing us to delineate, and measure the integrity of, the white matter tracts connecting the frontal and temporal regions active for syntax. We found that structural disconnection in either of 2 fiber bundles--the arcuate fasciculus or the extreme capsule fiber system--was associated with syntactic impairment in patients. The results demonstrate the causal role in syntactic analysis of these 2 major left hemisphere fiber bundles--challenging existing views about their role in language functions and providing a new basis for future research in this key area of human cognition. PMID:22275482

  6. Cryptic organisation within an apparently irregular rostrocaudal distribution of interneurons in the embryonic zebrafish spinal cord

    SciTech Connect

    Wells, Simon, E-mail: simon.wells@adelaide.edu.au [Discipline of Genetics, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia 5005 (Australia) [Discipline of Genetics, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia 5005 (Australia); The Special Research Centre for the Molecular Genetics of Development, University of Adelaide, Adelaide, South Australia 5005 (Australia); Conran, John G., E-mail: john.conran@adelaide.edu.au [Ecology and Evolutionary Biology, School of Earth and Environmental Sciences, University of Adelaide, Adelaide, South Australia 5005 (Australia); Tamme, Richard, E-mail: rtamme@ttu.ee [Discipline of Genetics, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia 5005 (Australia)] [Discipline of Genetics, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia 5005 (Australia); Gaudin, Arnaud, E-mail: a.gaudin@uq.edu.au [School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072 (Australia)] [School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072 (Australia); Webb, Jonathan, E-mail: jonathan.webb@worc.ox.ac.uk [Discipline of Genetics, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia 5005 (Australia)] [Discipline of Genetics, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia 5005 (Australia); Lardelli, Michael, E-mail: michael.lardelli@adelaide.edu.au [Discipline of Genetics, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia 5005 (Australia) [Discipline of Genetics, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia 5005 (Australia); The Special Research Centre for the Molecular Genetics of Development, University of Adelaide, Adelaide, South Australia 5005 (Australia)

    2010-11-15

    The molecules and mechanisms involved in patterning the dorsoventral axis of the developing vertebrate spinal cord have been investigated extensively and many are well known. Conversely, knowledge of mechanisms patterning cellular distributions along the rostrocaudal axis is relatively more restricted. Much is known about the rostrocaudal distribution of motoneurons and spinal cord cells derived from neural crest but there is little known about the rostrocaudal patterning of most of the other spinal cord neurons. Here we report data from our analyses of the distribution of dorsal longitudinal ascending (DoLA) interneurons in the developing zebrafish spinal cord. We show that, although apparently distributed irregularly, these cells have cryptic organisation. We present a novel cell-labelling technique that reveals that DoLA interneurons migrate rostrally along the dorsal longitudinal fasciculus of the spinal cord during development. This cell-labelling strategy may be useful for in vivo analysis of factors controlling neuron migration in the central nervous system. Additionally, we show that DoLA interneurons persist in the developing spinal cord for longer than previously reported. These findings illustrate the need to investigate factors and mechanisms that determine 'irregular' patterns of cell distribution, particularly in the central nervous system but also in other tissues of developing embryos.

  7. Neuro-anatomical correlates of a number bisection bias: A neuropsychological voxel-based morphometry study?

    PubMed Central

    Woodbridge, Rachel; Chechlacz, Magdalena; Humphreys, Glyn W.; Demeyere, Nele

    2012-01-01

    The number bisection tasks, whereby participants estimate the midpoint of a given number interval, is frequently used to explore the idea that numbers are spatially represented within the brain across a ‘mental number line’. Some neuropsychological research supports the argument that number bisection is a spatial task, recruiting parietal brain regions, whereas other data suggest that number bisection is dissociable from spatial processing and is instead dependent on working memory in the prefrontal cortices. This study explored the anatomical correlates of deficits in the number bisection task, using voxel-based morphometry in a sample of 25 neuropsychological patients with both left and right hemisphere damage. Interestingly, impairments in number bisection were strongly associated with grey matter lesions in the left hemisphere including both frontal and prefrontal cortices, extending to inferior parietal cortex. Similar prefrontal and frontal grey matter areas were found to be associated with increased leftward deviations (underestimations of the midpoint), whereas no suprathreshold clusters were observed for rightward deviations from the midpoint. Analysis of white matter integrity revealed that lesions in the tracts connecting the parietal and frontal cortices (i.e. the superior longitudinal fasciculus) were highly associated with leftward deviation impairments in number bisection. The data suggest that there is a common parieto-frontal number processing network underlying performances on number bisection, with larger numbers represented on the left side. PMID:24179767

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

    PubMed Central

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

    2012-01-01

    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. PMID:22768035

  9. A possible mechanism for PTSD symptoms in patients with traumatic brain injury: central autonomic network disruption.

    PubMed

    Williamson, John B; Heilman, Kenneth M; Porges, Eric C; Lamb, Damon G; Porges, Stephen W

    2013-01-01

    Patients with traumatic brain injuries (TBI) often develop post traumatic stress disorder (PTSD). This syndrome, defined and diagnosed by psychological and behavioral features, is associated with symptoms such as anxiety and anger with an increase of arousal and vigilance, as well as flashbacks and nightmares. Many of these features and symptoms observed in PTSD may be in part the result of altered autonomic nervous system (ANS) activity in response to psychological and physical challenges. Brain imaging has documented that TBI often induces white matter damage to pathways associated with the anterior limb of the internal capsule and uncinate fasciculus. Since these white matter structures link neocortical networks with subcortical and limbic structures that regulate autonomic control centers, injury to these pathways may induce a loss of inhibitory control of the ANS. In this review, the autonomic features associated with PTSD are discussed in the context of traumatic brain injury. We posit that TBI induced damage to networks that regulate the ANS increase vulnerability to PTSD. The means by which the vulnerability can be measured and tested are also discussed. PMID:24391583

  10. The occipitofrontal fascicle in humans: A quantitative, in vivo, DT-MRI study

    PubMed Central

    Makris, Nikos; Papadimitriou, George M.; Sorg, Scott; Kennedy, David N.; Caviness, Verne S.; Pandya, Deepak N.

    2013-01-01

    Since the existence of the occipitofrontal fascicle (OFF) in humans has remained controversial, we utilized diffusion tensor imaging (DT-MRI)-based segmentation and tractography to investigate its trajectory in vivo in the human. We found that the OFF is distinct from the subcallosal fasciculus or Muratoff’s bundle (MB) and extends from the dorsal and medial parts of the occipital lobe as well as the dorsal, medial and inferior parietal lobules to the dorsal and medial part of the prefrontal and premotor regions. In most of its course, it remains parallel to the corpus callosum, the caudate nucleus and the lateral ventricle. In the coronal plane, the OFF is discerned in the core of the white matter medial to the corona radiata and the superior longitudinal fascicle II (SLF II) and lateral to MB and the corpus callosum. The volumetric measurements of the stem portion of the OFF indicate that the OFF is smaller than the SLF II and the cingulum bundle. Since DT-MRI allows the visualization of OFF fibers leading to the projection areas but not to the origin or termination of these fibers, this has been extrapolated from the experimental data in non-human primates. The OFF may have a role in visual spatial processing along with SLF II. PMID:17681797

  11. Neocortical and hippocampal volume loss in a human ciliopathy: A quantitative MRI study in Bardet-Biedl syndrome.

    PubMed

    Baker, Kate; Northam, Gemma B; Chong, W K; Banks, Tina; Beales, Philip; Baldeweg, Torsten

    2011-01-01

    Cilia are ubiquitous cell surface organelles with diverse roles from embryogenesis to adult life. The neurodevelopmental functions of the cilium are currently under investigation in animal systems, but relevance to human brain development remains uncertain. We present the first systematic investigation of structural neuroanatomy in a ciliopathy-Bardet-Biedl syndrome (BBS). Qualitative and quantitative aspects of brain structure were evaluated via magnetic resonance imaging in 10 patients with BBS (ages 14-28 years). In comparison to age and gender-matched healthy controls, BBS patients had significantly reduced total gray matter (GM) volume but no total white matter (WM) or cerebrospinal fluid volume changes. Voxel-based morphometric analysis indicated regional GM volume loss bilaterally in the anterior temporal lobes and in the medial orbitofrontal cortex, and WM volume loss in the right inferior longitudinal fasciculus. Region-of-interest measurements revealed reduced volume of the hippocampus. Two patients were found to have ventriculomegaly. Global GM reduction and regional volume reductions in the temporal lobe may underlie the learning disabilities and behavioral problems experienced by some patients with BBS. These findings are consistent with previous observations in mouse models of BBS, and further implicate the cilium in neurodevelopmental processes relevant to human cognitive function. PMID:21204204

  12. Channeling of developing rat corticospinal tract axons by myelin-associated neurite growth inhibitors

    SciTech Connect

    Schwab, M.E.; Schnell, L. (Univ. of Zurich (Switzerland))

    1991-03-01

    CNS myelin contains 2 membrane proteins that are potent inhibitors of neurite growth (NI-35 and NI-250). Because myelin formation starts at different times in different regions and tracts of the CNS, this inhibitory property of myelin could serve boundary and guidance functions for late-growing fiber tracts. In the rat, the corticospinal tract (CST) grows into and down the spinal cord during the first 10 postnatal days, in close proximity to the sensory tracts fasciculus cuneatus and gracilis. Immunofluorescence for myelin constituents showed that, in the rostral half of the spinal cord, the myelinating tissue of these ascending tracts surrounds the growing, myelin-free CST in a channellike fashion. Elimination of oligodendrocytes by x-irradiation of the newborn rats, or application of antibody IN-1, which neutralizes the inhibitory substrate property of CNS myelin, resulted in significant anatomical aberration of CST fibers. In particular, the tract was larger in cross-section, and aberrant CST fibers and fascicles intermixed with the neighboring sensory ascending tracts. These results assign an important channeling and guard-rail function to the oligodendrocyte-associated neurite growth inhibitors for the developing CST in the rat spinal cord.

  13. Differential fractional anisotropy abnormalities in adolescents with ADHD or schizophrenia

    PubMed Central

    Davenport, Nicholas D.; Karatekin, Canan; White, Tonya; Lim, Kelvin O.

    2010-01-01

    Schizophrenia and ADHD are associated with similar deficits in working memory, attention, and inhibition. Both disorders also involve abnormalities of white matter integrity, possibly reflecting neural communication disruptions. There are likely some regional white matter abnormalities that underlie the common cognitive impairment, though also some regional abnormalities unique to each disorder. We used diffusion tensor imaging (DTI) to compare white matter integrity, as indicated by fractional anisotropy (FA), in adolescents with schizophrenia (n=15) or ADHD (n=14) and healthy controls (n=26). Schizophrenia patients had uniquely low FA, relative to the other two groups, in bilateral cerebral peduncles, anterior and posterior corpus callosum, right anterior corona radiata, and right superior longitudinal fasciculus. ADHD patients had uniquely high FA in left inferior and right superior frontal regions. Both clinical groups had lower FA than controls in left posterior fornix. The two disorders generally demonstrated distinct patterns of abnormal connectivity suggesting that common cognitive and behavioral deficits derive from distinct sources, though the posterior fornix may be involved in both disorders. Schizophrenia was associated with abnormally low FA in widespread circuitry indicative of general connectivity disruptions, whereas ADHD was associated with abnormally high FA in frontal networks that may indicate impaired branching of fibers. PMID:20153608

  14. The relationship of brain structure to age and executive functioning in adolescent disruptive behavior disorder.

    PubMed

    Hummer, Tom A; Wang, Yang; Kronenberger, William G; Dunn, David W; Mathews, Vincent P

    2015-03-30

    Characterizing brain maturation in adolescents with disruptive behavior disorders (DBDs) may provide insight into the progression of their behavioral deficits. Therefore, this study examined how age and executive functioning were related to structural neural characteristics in DBD. Thirty-three individuals (aged 13-17) with a DBD, along with a matched control sample, completed neuropsychological testing and underwent magnetic resonance imaging (MRI) to measure gray matter volume and microstructural white matter properties. Voxel-based morphometry quantified gray matter volume, and diffusion tensor imaging measured fractional anisotropy (FA) in white matter tracts. In the anterior cingulate, gray matter volume decreased with age in healthy controls but showed no such change in the DBD sample. In the corpus callosum and superior longitudinal fasciculus (SLF), FA increased with age in the control sample significantly more than in the DBD sample. Executive functioning, particularly working memory, was associated with SLF FA bilaterally. However, the relationship of SLF FA to working memory performance was weaker in the DBD sample. These data suggest that youth with DBD have altered brain development compared with typically developing youth. The abnormal maturation of the anterior cingulate and frontoparietal tracts during adolescence may contribute to the persistence of behavioral deficits in teens with a DBD. PMID:25533028

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

    PubMed Central

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

    2011-01-01

    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. PMID:21738785

  16. Language comprehension in young people with severe cerebral palsy in relation to language tracts: a diffusion tensor imaging study.

    PubMed

    Harlaar, Laurike; Pouwels, Petra J; Geytenbeek, Joke; Oostrom, Kim; Barkhof, Frederik; Vermeulen, R Jeroen

    2013-10-01

    Patients with severe cerebral palsy (CP) often have poor speech ability but potentially better language comprehension. The arcuate fasciculus and the extreme capsule are two important language tracts between the Wernicke and Broca areas. Using diffusion tensor imaging, we visualized language tracts and pyramidal tracts in both hemispheres in 10 controls (5 to 18 years) and 5 patients (5 to 23 years) with severe CP. Language comprehension was assessed with a recently designed instrument (the Computer-Based instrument for Low motor Language Testing [C-BiLLT]). The language tracts were visualized in all control children and in four CP patients. In one CP patient without any objective language comprehension skills, no language tract could be visualized. Both language and pyramidal tracts were smaller in patients than in controls. These preliminary data indicate a relation between language tracts and language skills. Further research is necessary to study the value of structural integrity of language tracts in predicting language comprehension in CP patients. PMID:23564318

  17. The Role of Low and High Spatial Frequencies in Exogenous Attention to Biologically Salient Stimuli

    PubMed Central

    Carretié, Luis; Ríos, Marcos; Periáñez, José A.; Kessel, Dominique; Álvarez-Linera, Juan

    2012-01-01

    Exogenous attention can be understood as an adaptive tool that permits the detection and processing of biologically salient events even when the individual is engaged in a resource-consuming task. Indirect data suggest that the spatial frequency of stimulation may be a crucial element in this process. Behavioral and neural data (both functional and structural) were analyzed for 36 participants engaged in a digit categorization task in which distracters were presented. Distracters were biologically salient or anodyne images, and had three spatial frequency formats: intact, low spatial frequencies only, and high spatial frequencies only. Behavior confirmed enhanced exogenous attention to biologically salient distracters. The activity in the right and left intraparietal sulci and the right middle frontal gyrus was associated with this behavioral pattern and was greater in response to salient than to neutral distracters, the three areas presenting strong correlations to each other. Importantly, the enhanced response of this network to biologically salient distracters with respect to neutral distracters relied on low spatial frequencies to a significantly greater extent than on high spatial frequencies. Structural analyses suggested the involvement of internal capsule, superior longitudinal fasciculus and corpus callosum in this network. Results confirm that exogenous attention is preferentially captured by biologically salient information, and suggest that the architecture and function underlying this process are low spatial frequency-biased. PMID:22590649

  18. Body Mass Index Correlates Negatively With White Matter Integrity in The Fornix And Corpus Callosum: A Diffusion Tensor Imaging Study

    PubMed Central

    Xu, Jiansong; Li, Yang; Lin, Haiqun; Sinha, Rajita; Potenza, Marc N.

    2011-01-01

    Overweight or obese body habitus is associated with cognitive deficits, impaired brain function, gray matter atrophy, and white matter (WM) hyperintensities. However, few diffusion tensor imaging (DTI) studies have assessed WM integrity in relation to overweight or obese status. This study assessed relationships between body mass index (BMI) and values of DTI parameters among 51 normal-weight (lean), overweight and obese participants who were otherwise healthy. BMI correlated negatively with fractional anisotropy (FA) and axial eigenvalues (?1) in the body of corpus callosum (CC), positively with mean diffusivity and radial eigenvalues (??) in the fornix and splenium of CC, and positively with ?1 in the right corona radiata (CR) and superior longitudinal fasciculus (SLF). These data indicate that BMI correlates negatively with WM integrity in the fornix and CC. Furthermore, the different patterns of BMI-related differences in DTI parameters at the fornix, body and splenium of the CC, and the right CR and SLF suggest that different biological processes may underlie BMI-related impairments of WM integrity in different brain regions. PMID:22139809

  19. Descending projections to the hindbrain and spinal cord in the paddlefish Polyodon spathula.

    PubMed

    Metzen, Michael G; Chambwa, Mwaka; Wilkens, Lon A; Hofmann, Michael H

    2010-03-01

    In vertebrates, almost all motor neurons innervating skeletal muscles are located in the hindbrain and spinal cord, and all brain centers that control behavior have descending projections into these parts of the central nervous system. With tracer injections into the spinal cord and hindbrain, we have studied cell groups with descending projections in the paddlefish. Spinal cord injections reveal retrogradely labeled cells in all reticular and raphe nuclei, as well as the nucleus of the medial longitudinal fascicle. Additional cell groups with projections to the spinal cord are the nucleus of the fasciculus solitarius, descending trigeminal nucleus, several octavolateral nuclei, the dorsal hypothalamic nucleus, and the pretectum. The only primary sensory fibers with descending projections are trigeminal fibers. Hindbrain injections reveal a number of additional cell groups in di- and mesencephalon. The most prominent source is the mesencephalic tectum. Other descending cells were found in the dorsal posterior thalamic nucleus, ventral thalamus, torus semicircularis, lateral mesencephalic nucleus, and the central gray of the mesencephalon. Our data show that descending spinal projections are comparable to those of other vertebrates and that the tectum is the most important motor control center projecting to the hindbrain. A surprising result was that the dorsal posterior thalamic nucleus also projects to the hindbrain. This nucleus is thought to be a center that relays sensory information to the telencephalon. Further studies are needed to determine the complete set of projections of the dorsal thalamus in paddlefish and other fishes to gain insights into its functional role. PMID:20051233

  20. Projections from the medial agranular cortex to brain stem visuomotor centers in rats.

    PubMed

    Stuesse, S L; Newman, D B

    1990-01-01

    Projections from medial agranular cortex to brain stem in rat were determined by use of the anterograde tracers Phaseolus vulgaris leucoagglutinin, or wheat germ agglutinin conjugated horseradish peroxidase. Axonal trajectories were also followed by means of the Wiitanen modification of the Fink-Heimer degeneration technique. AGm was identified on the basis of its cytoarchitectonics. AGm projected to the anterior pretectal nucleus, the rostral interstitial nucleus of the medial longitudinal fasciculus, the medial accessory oculomotor nucleus of Bechterew, the interstitial nucleus of Cajal, the nucleus of Darkschewitsch, the nucleus cuneiformis and subcuneiformis, intermediate and deep superior collicular layers, the paramedian pontine reticular formation (reticularis pontis oralis and caudalis, and reticularis gigantocellularis), and raphe centralis superior. Differences in connections between rostral and caudal injections were observed: pontine and medullary projections were lighter from the rostral portion of AGm than from the more caudal portions of AGm. The heaviest projections to the anterior pretectal nucleus were from the caudal portion of AGm. The subcortical projections were very similar to those described for the frontal eye field in monkeys, and the majority of them targeted areas thought to be involved in coordination of gaze with head and neck movements. Thus AGm in rats may contain the homologue of the primate frontal eye fields. PMID:1696906

  1. Robust and efficient linear registration of white-matter fascicles in the space of streamlines.

    PubMed

    Garyfallidis, Eleftherios; Ocegueda, Omar; Wassermann, Demian; Descoteaux, Maxime

    2015-08-15

    The neuroscientific community today is very much interested in analyzing specific white matter bundles like the arcuate fasciculus, the corticospinal tract, or the recently discovered Aslant tract to study sex differences, lateralization and many other connectivity applications. For this reason, experts spend time manually segmenting these fascicles and bundles using streamlines obtained from diffusion MRI tractography. However, to date, there are very few computational tools available to register these fascicles directly so that they can be analyzed and their differences quantified across populations. In this paper, we introduce a novel, robust and efficient framework to align bundles of streamlines directly in the space of streamlines. We call this framework Streamline-based Linear Registration. We first show that this method can be used successfully to align individual bundles as well as whole brain streamlines. Additionally, if used as a piecewise linear registration across many bundles, we show that our novel method systematically provides higher overlap (Jaccard indices) than state-of-the-art nonlinear image-based registration in the white matter. We also show how our novel method can be used to create bundle-specific atlases in a straightforward manner and we give an example of a probabilistic atlas construction of the optic radiation. In summary, Streamline-based Linear Registration provides a solid registration framework for creating new methods to study the white matter and perform group-level tractometry analysis. PMID:25987367

  2. Application of Principal Component Analysis to Distinguish Patients with Schizophrenia from Healthy Controls Based on Fractional Anisotropy Measurements

    PubMed Central

    Caprihan, A.; Pearlson, G.D.; Calhoun, V.D.

    2008-01-01

    Principal component analysis (PCA) is often used to reduce the dimension of data before applying more sophisticated data analysis methods such as non-linear classification algorithms or independent component analysis. This practice is based on selecting components corresponding to the largest eigenvalues. If the ultimate goal is separation of data in two groups, then these set of components need not have the most discriminatory power. We measured the distance between two such populations using Mahalanobis distance and chose the eigenvectors to maximize it, a modified PCA method, which we call the discriminant PCA (DPCA). DPCA was applied to diffusion tensor based fractional anisotropy images to distinguish age-matched schizophrenia subjects from healthy controls. The performance of the proposed method was evaluated by the one-leave-out method. We show that for this fractional anisotropy data-set, the classification error with 60 components was close to the minimum error and that the Mahalanobis distance was twice as large with DPCA, than with PCA. Finally, by masking the discriminant function with the white matter tracts of the John Hopkins University atlas, we identified left superior longitudinal fasciculus as the tract which gave the least classification error. In addition, with six optimally chosen tracts the classification error was zero. PMID:18571937

  3. Jerk-waveform see-saw nystagmus due to unilateral meso-diencephalic lesion.

    PubMed

    Halmagyi, G M; Aw, S T; Dehaene, I; Curthoys, I S; Todd, M J

    1994-08-01

    See-saw nystagmus is an uncommon but highly characteristic eye movement disorder comprising intorsion and elevation of one eye, with synchronous extorsion and depression of the other. It generally has a pendular waveform and is due to a midline, extrinsic, suprasellar mass lesion compressing or invading the brainstem bilaterally at the meso-diencephalic junction. This report deals with the clinical and MRI findings in three patients (and binocular three-dimensional quantitative oculographic findings in one patient) with a jerk waveform see-saw nystagmus due in each case to a unilateral meso-diencephalic lesion. In each patient the torsional component of the nystagmus fast phases rotated the upper poles of the eyes toward the side of the lesion. Jerk see-saw nystagmus can be clinically indistinguishable from pendular see-saw nystagmus and from the torsional-vertical nystagmus which occurs with medullary lesions. We propose that jerk see-saw nystagmus is due to unilateral inactivation of the torsional eye-velocity integrator, thought to be in the interstitial nucleus of Cajal, with sparing of the torsional fast-phase generator, thought to be in the adjacent rostral interstitial nucleus of the medial longitudinal fasciculus. PMID:7922466

  4. [Changes of torsional eye movements after lesion of the rostral interstitial nucleus of the MLF (riMLF)--analysis on listing's plane].

    PubMed

    Suzuki, Y

    1995-11-01

    The changes of torsional eye movements after the riMLF (rostral interstitial nucleus of the medial longitudinal fasciculus) lesions with kainic acid have been investigated in three rhesus monkeys. After unilateral lesion, torsional rapid eye movements were lost to ipsi-torsional (extorsion of the ipsilateral eye and intorsion of the contralateral eye) side only, while vertical movements were still possible. All monkeys showed counter-torsional (intorsion of the ipsilateral eye and extorsion of the contralateral eye) shifts and thickening of Listing's plane. These changes of Listing's plane were always less in the dark. After the second contralateral lesions, all torsional and vertical rapid eye movements were permanently lost. Listing's plane moved to the opposite torsional direction beyond zero. On-average, the residual torsional shift in the light was only 17.4% of the shift in the light after the first lesion. Furthermore, the thickness of Listing's plane decreased to the level of the pre-lesion state. These results suggest that burst neurons in the riMLF are essential to generate vertical and/or torsional rapid eye movements and symmetrical activity of them is necessary to keep Listing's plane around zero and to minimize its variability. Yet, after bilateral lesions, Listing's law is still preserved, suggesting its neural implementation in parallel to or downstream of the riMLF. PMID:8582708

  5. A Multimodal Assessment of the Genetic Control over Working Memory

    PubMed Central

    Karlsgodt, KH; Kochunov, P; Winkler, AM; Laird, AR; Almasy, L; Duggirala, R; Olvera, RL; Fox, PT; Blangero, J; Glahn, DC

    2010-01-01

    Working memory performance is significantly influenced by genetic factors. Here, we assessed genetic contributions to both working memory performance and to neuroimaging measures focused on the network of brain regions associated with working memory, using a sample of 467 human participants from extended families. Imaging measures included diffusion tensor imaging (DTI) indices in major white matter tracts thought to be associated with working memory and structural MRI measures of frontal and parietal gray matter density. Analyses directly addressed whether working memory performance and neural structural integrity are influenced by common genetic factors (e.g. pleiotropy). While all cognitive measures, gray matter regions, and white matter tracts assessed were heritable, only performance on a spatial delayed response task and integrity of the superior longitudinal fasciculus (a primary frontoparietal connection) shared genetic factors. As working memory may be a core component of other, higher level processes, such as general intelligence, this finding has implications for the heritability of complex cognitive functions, as well as for our understanding of the transmission of cognitive deficits in mental and neurological disorders. PMID:20554870

  6. White matter fractional anisotropy is inversely related to anxious symptoms in older adults with atherosclerosis

    PubMed Central

    Bijanki, Kelly C. R.; Stillman, Ashley N.; Arndt, Stephan; Magnotta, Vincent A.; Fiedorowicz, Jess G.; Haynes, William G.; Matsui, Joy T.; Johnson, Hans J.; Moser, David J.

    2013-01-01

    Objective Clinical anxiety disorders are associated with white matter hyperintensities and diffusion abnormalities measured using diffusion tensor imaging (DTI). However, it is not known if this association extends into individuals with mild anxious symptoms without formal diagnosis, in those who are older, or in those who have atherosclerosis. The current study explored whether white matter integrity and/or organization significantly associates with anxious symptoms in older adults with and without atherosclerosis. Methods We recruited older adults (ages 55–90); 35 with clinically diagnosed atherosclerotic vascular disease (AVD) and 22 without AVD. Anxious symptoms were measured using the validated Symptom Checklist-90-Revised. Fractional anisotropy (FA), a proxy for white matter organization and health, was measured in the white matter globally, by lobe, and in several smaller regions of interest suggested by the literature. Partial correlations between anxious symptoms and FA were calculated, controlling for significant covariates. Results Participants with and without AVD did not differ in severity of anxious symptom endorsement. There was a unique inverse relationship between white matter health and anxious symptoms in the AVD participants, but not in healthy comparisons. Significant relationships were observed in the superior longitudinal fasciculus (r=?.476, df=32, p=.004), as well as the cingulum bundle, the frontal lobes, and the parietal lobes. Conclusions Anxiety symptoms uniquely correlated with low fractional anisotropy in older adults with atherosclerosis. These findings may have implications for future research on the topic of anxiety in aging and vascular disease and warrant replication. PMID:23348834

  7. Descending projections of the hamster intergeniculate leaflet: relationship to the sleep/arousal and visuomotor systems.

    PubMed

    Morin, Lawrence P; Blanchard, Jane H

    2005-06-27

    The intergeniculate leaflet (IGL), homolog of the primate pregeniculate nucleus, modulates circadian rhythms. However, its extensive anatomical connections suggest that it may regulate other systems, particularly those for visuomotor function and sleep/arousal. Here, descending IGL-efferent pathways are identified with the anterograde tracer, Phaseolus vulgaris leucoagglutinin, with projections to over 50 brain stem nuclei. Projections of the ventral lateral geniculate are similar, but more limited. Many of the nuclei with IGL afferents contribute to circuitry governing visuomotor function. These include the oculomotor, trochlear, anterior pretectal, Edinger-Westphal, and the terminal nuclei; all layers of the superior colliculus, interstitial nucleus of the medial longitudinal fasciculus, supraoculomotor periaqueductal gray, nucleus of the optic tract, the inferior olive, and raphe interpositus. Other target nuclei are known to be involved in the regulation of sleep, including the lateral dorsal and pedunculopontine tegmentum. The dorsal raphe also receives projections from the IGL and may contribute to both sleep/arousal and visuomotor function. However, the locus coeruleus and medial vestibular nucleus, which contribute to sleep and eye movement regulation and which send projections to the IGL, do not receive reciprocal projections from it. The potential involvement of the IGL with the sleep/arousal system is further buttressed by existing evidence showing IGL-efferent projections to the ventrolateral preoptic area, dorsomedial, and medial tuberal hypothalamus. In addition, the great majority of all regions receiving IGL projections also receive input from the orexin/hypocretin system, suggesting that this system contributes not only to the regulation of sleep, but to eye movement control as well. PMID:15880466

  8. [A study of J. A. Kulmus (1689-1745), the author of "Anatomische Tabellen," translated into Japanese as "Kaitai-shinsho"].

    PubMed

    Ishida, Sumio

    2002-03-01

    Genpaku Sugita and Ryotaku Maeno published "Kaita-shinsho (New book of Anatomy)" in 1774 in Edo (Tokyo). The original of this anatomy book was first published by Johann Adam Kulmus (1689-1745) in German in 1722 in Danzig. The third edition of this book (1732) was translated into Dutch and published in 1734 by Dutch surgeon G. Dicten in Leiden. "Kaitai-shinsho" was translated from this Dutch edition. The author visited Gdansk (Danzig) in Poland in 1996, and searched for documents of J. A. Kulmus at archives (Archiwum Panstowowe) and a library (Biblioteka Gdanska PAN). J. A. Kulmus was a professor at the Academy Gymnasium in Danzig which was established in 1558. He was appointed professor on 27th May 1725 and worked until his death. The author obtained "An extract of manuscripts of the late Dr J. A. Kulmus" at Archiwum Panstowowe. It consists of 6 pages manuscripts kept in "Annalen des Danziger Gymnasiums". At first J. A. Kulmus himself wrote this document and then the officer of the gymnasium transcribed it after his death. This document showed the state of the gymnasium during the Kulmus days. Kulmus taught medicine for 8th and 9th year students and natural science for 6th and 7th year students. Also this document showed us the timetable of this gymnasium. The author also found the book titled "Fasciculus Exercitationum Physicarum de variis ac praecipuis rebus ad philosophiam naturaleum," edited by Kulmus in 1729. This book contains 39 articles written by his students. PMID:12148522

  9. An Arbitrary Waveform Wearable Neuro-stimulator System for Neurophysiology Research on Freely Behaving Animals.

    PubMed

    Samani, Mohsen Mosayebi; Mahnam, Amin; Hosseini, Nasrin

    2014-04-01

    Portable wireless neuro-stimulators have been developed to facilitate long-term cognitive and behavioral studies on the central nervous system in freely moving animals. These stimulators can provide precisely controllable input(s) to the nervous system, without distracting the animal attention with cables connected to its body. In this study, a low power backpack neuro-stimulator was developed for animal brain researches that can provides arbitrary stimulus waveforms for the stimulation, while it is small and light weight to be used for small animals including rats. The system consists of a controller that uses an RF link to program and activate a small and light microprocessor-based stimulator. A Howland current source was implemented to produce precise current controlled arbitrary waveform stimulations. The system was optimized for ultra-low power consumption and small size. The stimulator was first tested for its electrical specifications. Then its performance was evaluated in a rat experiment when electrical stimulation of medial longitudinal fasciculus induced circling behavior. The stimulator is capable of delivering programmed stimulations up to ± 2 mA with adjusting steps of 1 ?A, accuracy of 0.7% and compliance of 6 V. The stimulator is 15 mm × 20 mm × 40 mm in size, weights 13.5 g without battery and consumes a total power of only 5.l mW. In the experiment, the rat could easily carry the stimulator and demonstrated the circling behavior for 0.1 ms current pulses of above 400 ?A. The developed system has a competitive size and weight, whereas providing a wide range of operation and the flexibility of generating arbitrary stimulation patterns ideal for long-term experiments in the field of cognitive and neuroscience research. PMID:24761373

  10. An Arbitrary Waveform Wearable Neuro-stimulator System for Neurophysiology Research on Freely Behaving Animals

    PubMed Central

    Samani, Mohsen Mosayebi; Mahnam, Amin; Hosseini, Nasrin

    2014-01-01

    Portable wireless neuro-stimulators have been developed to facilitate long-term cognitive and behavioral studies on the central nervous system in freely moving animals. These stimulators can provide precisely controllable input(s) to the nervous system, without distracting the animal attention with cables connected to its body. In this study, a low power backpack neuro-stimulator was developed for animal brain researches that can provides arbitrary stimulus waveforms for the stimulation, while it is small and light weight to be used for small animals including rats. The system consists of a controller that uses an RF link to program and activate a small and light microprocessor-based stimulator. A Howland current source was implemented to produce precise current controlled arbitrary waveform stimulations. The system was optimized for ultra-low power consumption and small size. The stimulator was first tested for its electrical specifications. Then its performance was evaluated in a rat experiment when electrical stimulation of medial longitudinal fasciculus induced circling behavior. The stimulator is capable of delivering programmed stimulations up to ± 2 mA with adjusting steps of 1 ?A, accuracy of 0.7% and compliance of 6 V. The stimulator is 15 mm × 20 mm × 40 mm in size, weights 13.5 g without battery and consumes a total power of only 5.l mW. In the experiment, the rat could easily carry the stimulator and demonstrated the circling behavior for 0.1 ms current pulses of above 400 ?A. The developed system has a competitive size and weight, whereas providing a wide range of operation and the flexibility of generating arbitrary stimulation patterns ideal for long-term experiments in the field of cognitive and neuroscience research. PMID:24761373

  11. The Role of the Lateral Habenula in Punishment

    PubMed Central

    Jean-Richard Dit Bressel, Philip; McNally, Gavan P.

    2014-01-01

    The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain. The LHb is known to modulate midbrain dopamine (DA) neurons, including inhibition of ventral tegmental area (VTA) neurons via glutamatergic excitation of the GABAergic rostromedial tegmental nucleus (RMTg). A variety of lines of evidence show activity in LHb and the LHb-RMTg pathway is correlated with, and is sufficient to support, punishment learning. However, it is not immediately clear whether LHb is necessary for punishment. Here we used a within-subjects punishment task to assess the role of LHb in the acquisition and expression of punishment as well as in aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of an AMPA receptor antagonist (NBQX) into LHb had no effect on the acquisition or expression of this punishment, or on aversive choice, but did increase locomotion. Infusion of the sodium channel blocker bupivacaine likewise had no effect on expression of punishment. However, infusion of the calcium channel blocker mibefradil did affect expression of punishment by significantly decreasing the latency with which rats responded on the punished lever and significantly increasing unpunished lever-pressing. Taken together, these findings indicate that the LHb plays a limited role in punishment, influencing only latency to respond. This role is linked to calcium channel permeability and not AMPA receptor or sodium channel permeability. PMID:25365401

  12. Thalamic–hippocampal–prefrontal disruption in relapsing–remitting multiple sclerosis

    PubMed Central

    Kern, Kyle C.; Gold, Stefan M.; Lee, Brian; Montag, Michael; Horsfall, Jessica; O'Connor, Mary-Frances; Sicotte, Nancy L.

    2014-01-01

    Background Cortical, thalamic and hippocampal gray matter atrophy in relapsing–remitting MS (RRMS) is associated cognitive deficits. However, the role of interconnecting white matter pathways including the fornix, cingulum, and uncinate fasciculus (UF) is less well studied. Objective To assess MS damage to a hippocampal–thalamic–prefrontal network and the relative contributions of its components to specific cognitive domains. Methods We calculated diffusion tensor fractional anisotropy (FA) in the fornix, cingulum and UF as well as thalamic and hippocampal volumes in 27 RRMS patients and 20 healthy controls. A neuropsychological battery was administered and 4 core tests known to be sensitive to MS changes were used to assess cognitive impairment. To determine the relationships between structure and cognition, all tests were grouped into 4 domains: attention/executive function, processing speed, verbal memory, and spatial memory. Univariate correlations with structural measures and depressive symptoms identified potential contributors to cognitive performance and subsequent linear regression determined their relative effects on performance in each domain. For significant predictors, we also explored the effects of laterality and axial versus radial diffusivity. Results RRMS patients had worse performance on the Symbol Digit Modalities Test, but no significant impairment in the 4 cognitive domains. RRMS had reduced mean FA of all 3 pathways and reduced thalamic and hippocampal volumes compared to controls. In RRMS we found that thalamic volume and BDI predicted attention/executive function, UF FA predicted processing speed, thalamic volume predicted verbal memory, and UF FA and BDI predicted spatial memory. Conclusions Hippocampal–thalamic–prefrontal disruption affects cognitive performance in early RRMS with mild to minimal cognitive impairment, confirming both white and gray matter involvement in MS and demonstrating utility in assessing functional networks to monitor cognition.

  13. Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults

    PubMed Central

    Shollenbarger, Skyler G.; Price, Jenessa; Wieser, Jon; Lisdahl, Krista

    2015-01-01

    Background The heaviest period of cannabis use coincides with ongoing white matter (WM) maturation. Further, cannabis-related changes may be moderated by FAAH genotype (rs324420). We examined the association between cannabis use and FAAH genotype on frontolimbic WM integrity in adolescents and emerging adults. We then tested whether observed WM abnormalities were linked with depressive or apathy symptoms. Methods Participants included 37 cannabis users and 37 healthy controls (33 female; ages 18–25). Multiple regressions examined the independent and interactive effects of variables on WM integrity. Results Regular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls. Marginally reduced WM integrity in the cannabis users was found in the left anterior thalamic radiation (ATR) (FA, p = .08). Cannabis group ? FAAH genotype interaction predicted WM integrity in bilateral ATR (FA, right: p = .05 and left: p = .001) and fMinor (FA, p = .02). In cannabis users, poorer WM integrity was correlated with increased symptoms of depression and apathy in bilateral ATR and UNC. Conclusions Consistent with prior findings, cannabis use was associated with reduced frontolimbic WM integrity. WM integrity was also moderated by FAAH genotype, in that cannabis-using FAAH C/C carriers and A carrying controls had reduced WM integrity compared to control C/C carriers. Observed frontolimbic white matter abnormalities were linked with increased depressive and apathy symptoms in the cannabis users.

  14. Injury to white matter tracts in relapsing–remitting multiple sclerosis: A possible therapeutic window within the first 5 years from onset using diffusion-tensor imaging tract-based spatial statistics

    PubMed Central

    Asaf, Achiron; Evan, Stone; Anat, Achiron

    2015-01-01

    DTI studies in multiple sclerosis (MS) reveal white matter (WM) injury that occurs with disease progression. In the present study we aimed to elucidate the relationship of microstructural WM damage in patients with varying periods of disease duration. DTI scans were acquired from 90 MS patients and 25 healthy controls. Patients were grouped to short (<1 year), moderate (1 up to 6 years) and long (6–10 years) disease duration periods. Statistical analyses of the fractional anisotropy (FA) data were performed using tract-based spatial statistics (TBSS). Whole-brain skeletal FA measurements showed a significant decrease between healthy controls and the short MS disease duration group, as well as between moderate disease duration and long disease duration groups, but failed to show a significant difference between short and moderate disease duration groups. Voxelwise analysis revealed clusters of diffuse FA reductions in 40 WM tracts when comparing healthy controls and MS short disease duration group, with the point of maximal significant difference located in the left inferior longitudinal fasciculus. Comparing short with long disease duration groups, progressive FA reduction was demonstrated across 30 WM tracts, with the point of maximal significant difference migrating to the body of the corpus callosum. A non-linear pattern of WM microstructure disruption occurs in RRMS. Alterations are seen early in the disease course within 1 year from onset, reach a plateau within the next 5 years, and only later additional WM changes are detected. An important period of a possible therapeutic window therefore exists within the early disease stage.

  15. A significant risk factor for poststroke depression: the depression-related subnetwork

    PubMed Central

    Yang, Songran; Hua, Ping; Shang, Xinyuan; Cui, Zaixu; Zhong, Suyu; Gong, Gaolang; Humphreys, Glyn W.

    2015-01-01

    Background Despite being one of the direct causes of depression, whether stroke-induced neuroanatomical deterioration actually plays an important role in the onset of poststroke depression (PSD) is controversial. We assessed the structural basis of PSD, particularly with regard to white matter connectivity. Methods We evaluated lesion index, fractional anisotropy (FA) reduction and brain structural networks and then analyzed whole brain voxel-based lesions and FA maps. To understand brain damage in the context of brain connectivity, we used a graph theoretical approach. We selected nodes whose degree correlated with the Hamilton Rating Scale for Depression score (p < 0.05, false discovery rate–corrected), after controlling for age, sex, years of education, lesion size, Mini Mental State Examination score and National Institutes of Health Stroke Scale score. We used Poisson regression with robust standard errors to assess the contribution of the identified network toward poststroke major depression. Results We included 116 stroke patients in the study. Fourteen patients (12.1%) had diagnoses of major depression and 26 (22.4%) had mild depression. We found that lesions in the right insular cortex, left putamen and right superior longitudinal fasciculus as well as FA reductions in broader areas were all associated with major depression. Seventeen nodes were selected to build the depression-related subnetwork. Decreased local efficiency of the subnetwork was a significant risk factor for poststroke major depression (relative risk 0.84, 95% confidence interval 0.72–0.98, p = 0.027). Limitations The inability of DTI tractography to process fibre crossings may have resulted in inaccurate construction of white matter networks and affected statistical findings. Conclusion The present study provides, to our knowledge, the first graph theoretical analysis of white matter networks linked to poststroke major depression. These findings provide new insights into the neuroanatomical substrates of depression that develops after stroke. PMID:25871495

  16. Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

    PubMed Central

    2013-01-01

    Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use. PMID:24131511

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

    PubMed Central

    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

    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. PMID:22723713

  18. Interhemispheric microstructural connectivity in bitemporal lobe epilepsy with hippocampal sclerosis.

    PubMed

    Miró, Júlia; Gurtubay-Antolin, Ane; Ripollés, Pablo; Sierpowska, Joanna; Juncadella, Montse; Fuentemilla, Lluís; Sánchez, Verónica; Falip, Mercè; Rodríguez-Fornells, Antoni

    2015-06-01

    Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. The most frequent pathologic finding in this condition is hippocampal sclerosis (HS). In addition, in a small proportion (14-23%) of refractory TLE patients, the presence of HS is bilateral. TLE involves grey matter (GM) and white matter (WM) abnormalities in a wide cortico-subcortical network. However, the impact of neuronal loss on specific WM fiber pathways and associated functional systems as well as seizure propagation pathways remains unclear. There is still much controversy regarding the role of the commissures (corpus callosum, hippocampal commissure and anterior commissure) in interhemispheric seizure propagation. This study aimed to investigate the integrity of WM interhemispheric connectivity in a singular sample of patients with TLE and bilateral HS using structural magnetic resonance imaging (MRI). We performed multimodal structural MRI [high resolution T1-weighted and diffusion tensor imaging (DTI)] analyses of seven patients with medically refractory TLE with bilateral HS, fourteen unilateral left TLE patients and fifteen matched healthy individuals. Whole-brain voxel-wise analysis techniques were used. These patients evidenced WM derangement [reduced fractional anisotropy (FA), increased mean diffusivity (MD) or reduced WM volume] in temporal and extratemporal tracks, but also in commissural pathways, compared to the unilateral left TLE patients and the control group. Presence of reduced FA or increased MD in the fornix, cingulum and uncinate fasciculus in addition to reduced WM volume in the fornix was also encountered. Neuropsychological assessment was performed without significant correlations with structural data. The current results support the idea that commissural pathways play a contributory role in interhemispheric TLE seizure propagation in bilateral HS and offer new perspectives about the long-term effects on interhemispheric connectivity associated with seizure propagation patterns in TLE patients. PMID:25955498

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

    PubMed

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

    2013-07-15

    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

  20. Inappropriate rightward saccades after right hemisphere damage: Oculomotor analysis and anatomical correlates.

    PubMed

    Bourgeois, Alexia; Chica, Ana B; Migliaccio, Raffaella; Bayle, Dimitri J; Duret, Christophe; Pradat-Diehl, Pascale; Lunven, Marine; Pouget, Pierre; Bartolomeo, Paolo

    2015-07-01

    Patients with right hemisphere damage and visual neglect have severe problems to orient attention towards left-sided objects, often associated with the tendency to produce inappropriate rightward saccades. In its most severe form, this tendency can assume the compulsive character of a rightward deviation of gaze as soon as the visual scene deploys (so-called "magnetic attraction of gaze"). However, little is known about the exact nature of inappropriate rightward saccades, their relation with impaired conscious perception of left-sided stimuli, and their lesional correlates. To explore these issues, we studied three groups of patients with right brain damage: patients with signs of left visual neglect associated to left homonymous hemianopia, neglect patients without hemianopia, and patients without neglect or hemianopia. Participants searched for a gap missing within a target, presented among distractors. Manual responses for target detection were required, while participants were encouraged to move their eyes during search. Endogenous attention could be summoned to the target location by a central cue. All the three groups of patients produced inappropriate rightward saccades, which could not be completely overcome by the endogenous orienting of attention induced by the cues. Anatomical analysis indicated a specific implication of damage to the right frontal eye field and to a long-range white matter tract, the fronto-parietal superior longitudinal fasciculus. Fronto-parietal networks in the right hemisphere appear thus to be essential to integrate covert and overt orienting of attention, and to thoroughly explore space in order to become aware of the multiple competing objects around us. PMID:25930032

  1. Criteria and Methodology for Identifying Respiratory Denitrifiers

    PubMed Central

    Mahne, I.; Tiedje, J. M.

    1995-01-01

    Respiratory denitrification is not always adequately established when bacteria are characterized. We have tested a simple method that allows one to evaluate whether the two necessary criteria to claim denitrification have been met, namely, that N(inf2) or N(inf2)O is produced from nitrate or nitrite and that this reduction is coupled to a growth yield increase. Microorganisms were cultured in sealed tubes under a helium headspace and in the presence of 0, 2, 4, 7, and 10 mM nitrate or nitrite. After growth had ceased, N(inf2) and N(inf2)O were quantified by gas chromatography and the final protein concentration was measured. Net protein production was linearly related to nitrate concentration for all denitrifiers tested and ranged from 2 to 6 g of protein per mol of electron equivalent reduced. Nitrogen recovery as N(inf2) plus N(inf2)O from nitrate and nitrite transformed exceeded 80% for all denitrifiers. We also suggest that a rate of N gas production of >10 (mu)mol/min/g of protein can be used as an additional characteristic definitive of denitrification since this process produces gas more rapidly than other processes. These characteristics were established after evaluation of a variety of well-characterized respiratory denitrifiers and other N(inf2)O-producing nitrate reducers. Several poorly characterized denitrifiers were also tested and confirmed as respiratory denitrifiers, including Aquaspirillum itersonii, Aquaspirillum fasciculus, Bacillus azotoformans, and Corynebacterium nephridii. These criteria distinguished respiratory denitrifiers from other groups that reduce nitrate or produce N(inf2)O. Furthermore, they correctly identified respiratory denitrification in weak denitrifiers, a group in which the existence of this process may be overlooked. PMID:16534960

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

    PubMed

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

    2012-11-01

    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

  3. Descending projections of the hamster intergeniculate leaflet: relationship to the sleep/arousal and visuomotor systems

    NASA Technical Reports Server (NTRS)

    Morin, Lawrence P.; Blanchard, Jane H.

    2005-01-01

    The intergeniculate leaflet (IGL), homolog of the primate pregeniculate nucleus, modulates circadian rhythms. However, its extensive anatomical connections suggest that it may regulate other systems, particularly those for visuomotor function and sleep/arousal. Here, descending IGL-efferent pathways are identified with the anterograde tracer, Phaseolus vulgaris leucoagglutinin, with projections to over 50 brain stem nuclei. Projections of the ventral lateral geniculate are similar, but more limited. Many of the nuclei with IGL afferents contribute to circuitry governing visuomotor function. These include the oculomotor, trochlear, anterior pretectal, Edinger-Westphal, and the terminal nuclei; all layers of the superior colliculus, interstitial nucleus of the medial longitudinal fasciculus, supraoculomotor periaqueductal gray, nucleus of the optic tract, the inferior olive, and raphe interpositus. Other target nuclei are known to be involved in the regulation of sleep, including the lateral dorsal and pedunculopontine tegmentum. The dorsal raphe also receives projections from the IGL and may contribute to both sleep/arousal and visuomotor function. However, the locus coeruleus and medial vestibular nucleus, which contribute to sleep and eye movement regulation and which send projections to the IGL, do not receive reciprocal projections from it. The potential involvement of the IGL with the sleep/arousal system is further buttressed by existing evidence showing IGL-efferent projections to the ventrolateral preoptic area, dorsomedial, and medial tuberal hypothalamus. In addition, the great majority of all regions receiving IGL projections also receive input from the orexin/hypocretin system, suggesting that this system contributes not only to the regulation of sleep, but to eye movement control as well.

  4. Brain structural abnormalities in patients with major depression with or without generalized anxiety disorder comorbidity.

    PubMed

    Canu, Elisa; Kosti?, Milutin; Agosta, Federica; Munjiza, Ana; Ferraro, Pilar M; Pesic, Danilo; Copetti, Massimiliano; Peljto, Amir; Tosevski, Dusica Lecic; Filippi, Massimo

    2015-05-01

    An overlap frequently occurs between major depression disorder (MDD) and generalized anxiety disorder (GAD). Aim of this study was to assess cortical and white matter (WM) alterations in MDD patients with or without GAD comorbidity. Seventy-one MDD patients and 71 controls were recruited. All subjects underwent T1-weighted and diffusion tensor (DT)/MRI. MRI metrics of cortical thickness and WM integrity were obtained from atlas-based cortical regions and the interhemispheric and major long association WM tracts. Between-group MRI comparisons and multiple regressions with clinical scale scores were performed. Compared to controls, both MDD and MDD-GAD patients showed a cortical thinning of the middle frontal cortex bilaterally, left medial frontal gyrus and frontal pole. Compared to controls and MDD patients, MDD-GAD cases also showed a thinning of the right medial orbitofrontal and fusiform gyri, and left temporal pole and lateral occipital cortices. Compared to controls, MDD patients showed DT MRI abnormalities of the right parahippocampal tract and superior longitudinal fasciculus bilaterally, while no WM alterations were found in MDD-GAD. In all patients, brain abnormalities were related with symptom severity. MDD and MDD-GAD share a common pattern of cortical alterations located in the frontal regions. However, while both the cortex and WM integrity are affected in MDD, only the former is affected in MDD-GAD. These findings support the notion of MDD-GAD as a distinct clinical entity, providing insights into patient vulnerability for specific networks as well as into patient resilience factors reflected by the integrity of other cerebral circuits. PMID:25794861

  5. Diffusion Tensor Imaging of Parkinson’s Disease, Multiple System Atrophy and Progressive Supranuclear Palsy: A Tract-Based Spatial Statistics Study

    PubMed Central

    Worker, Amanda; Blain, Camilla; Jarosz, Jozef; Chaudhuri, K. Ray; Barker, Gareth J.; Williams, Steve C. R.; Brown, Richard G.; Leigh, P. Nigel; Dell’Acqua, Flavio; Simmons, Andrew

    2014-01-01

    Although often clinically indistinguishable in the early stages, Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD. PMID:25405990

  6. Analysis of the contribution of experimental bias, experimental noise, and inter-subject biological variability on the assessment of developmental trajectories in diffusion MRI studies of the brain.

    PubMed

    Sadeghi, Neda; Nayak, Amritha; Walker, Lindsay; Okan Irfanoglu, M; Albert, Paul S; Pierpaoli, Carlo

    2015-04-01

    Metrics derived from the diffusion tensor, such as fractional anisotropy (FA) and mean diffusivity (MD) have been used in many studies of postnatal brain development. A common finding of previous studies is that these tensor-derived measures vary widely even in healthy populations. This variability can be due to inherent inter-individual biological differences as well as experimental noise. Moreover, when comparing different studies, additional variability can be introduced by different acquisition protocols. In this study we examined scans of 61 individuals (aged 4-22 years) from the NIH MRI study of normal brain development. Two scans were collected with different protocols (low and high resolution). Our goal was to separate the contributions of biological variability and experimental noise to the overall measured variance, as well as to assess potential systematic effects related to the use of different protocols. We analyzed FA and MD in seventeen regions of interest. We found that biological variability for both FA and MD varies widely across brain regions; biological variability is highest for FA in the lateral part of the splenium and body of the corpus callosum along with the cingulum and the superior longitudinal fasciculus, and for MD in the optic radiations and the lateral part of the splenium. These regions with high inter-individual biological variability are the most likely candidates for assessing genetic and environmental effects in the developing brain. With respect to protocol-related effects, the lower resolution acquisition resulted in higher MD and lower FA values for the majority of regions compared with the higher resolution protocol. However, the majority of the regions did not show any age-protocol interaction, indicating similar trajectories were obtained irrespective of the protocol used. PMID:25583609

  7. Pioneer midbrain longitudinal axons navigate using a balance of Netrin attraction and Slit repulsion

    PubMed Central

    2014-01-01

    Background Longitudinal axons grow parallel to the embryonic midline to connect distant regions of the central nervous system. Previous studies suggested that repulsive midline signals guide pioneer longitudinal axons by blocking their entry into the floor plate; however, the role of midline attractants, and whether attractant signals may cooperate with repulsive signals, remains unclear. In this study we investigated the navigation of a set of pioneer longitudinal axons, the medial longitudinal fasciculus, in mouse embryos mutant for the Netrin/Deleted in Colorectal Cancer (DCC) attractants, and for Slit repellents, as well as the responses of explanted longitudinal axons in vitro. Results In mutants for Netrin1 chemoattractant or DCC receptor signaling, longitudinal axons shifted away from the ventral midline, suggesting that Netrin1/DCC signals act attractively to pull axons ventrally. Analysis of mutants in the three Slit genes, including Slit1/2/3 triple mutants, suggest that concurrent repulsive Slit/Robo signals push pioneer axons away from the ventral midline. Combinations of mutations between the Netrin and Slit guidance systems provided genetic evidence that the attractive and repulsive signals balance against each other. This balance is demonstrated in vitro using explant culture, finding that the cues can act directly on longitudinal axons. The explants also reveal an unexpected synergy of Netrin1 and Slit2 that promotes outgrowth. Conclusions These results support a mechanism in which longitudinal trajectories are positioned by a push-pull balance between opposing Netrin and Slit signals. Our evidence suggests that longitudinal axons respond directly and simultaneously to both attractants and repellents, and that the combined signals constrain axons to grow longitudinally. PMID:25056828

  8. Maternal Pravastatin Prevents Altered Fetal Brain Development in a Preeclamptic CD-1 Mouse Model

    PubMed Central

    Carver, Alissa R.; Andrikopoulou, Maria; Lei, Jun; Tamayo, Esther; Gamble, Phyllis; Hou, Zhipeng; Zhang, Jiangyang; Mori, Susumu; Saade, George R.; Costantine, Maged M.; Burd, Irina

    2014-01-01

    Objective Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention. Materials and Methods For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra “experimental group”) or water (sFlt-1 “positive control”) until weaning. The mFc group (“negative control”) received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI). MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis. Results Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes. Conclusion Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model. PMID:24963809

  9. Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression

    PubMed Central

    Lyden, H; Espinoza, R T; Pirnia, T; Clark, K; Joshi, S H; Leaver, A M; Woods, R P; Narr, K L

    2014-01-01

    Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5?mm3 voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation. PMID:24713861

  10. Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression.

    PubMed

    Lyden, H; Espinoza, R T; Pirnia, T; Clark, K; Joshi, S H; Leaver, A M; Woods, R P; Narr, K L

    2014-01-01

    Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation. PMID:24713861

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

    SciTech Connect

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

    1991-01-01

    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.

  12. Blocking central pathways in the primate motor system using high-frequency sinusoidal current

    PubMed Central

    Fisher, Karen M.; Jillani, Ngalla E.; Oluoch, George O.

    2014-01-01

    Electrical stimulation with high-frequency (2–10 kHz) sinusoidal currents has previously been shown to produce a transient and complete nerve block in the peripheral nervous system. Modeling and in vitro studies suggest that this is due to a prolonged local depolarization across a broad section of membrane underlying the blocking electrode. Previous work has used cuff electrodes wrapped around the peripheral nerve to deliver the blocking stimulus. We extended this technique to central motor pathways, using a single metal microelectrode to deliver focal sinusoidal currents to the corticospinal tract at the cervical spinal cord in anesthetized adult baboons. The extent of conduction block was assessed by stimulating a second electrode caudal to the blocking site and recording the antidromic field potential over contralateral primary motor cortex. The maximal block achieved was 99.6%, similar to findings of previous work in peripheral fibers, and the optimal frequency for blocking was 2 kHz. Block had a rapid onset, being complete as soon as the transient activation associated with the start of the sinusoidal current was over. High-frequency block was also successfully applied to the pyramidal tract at the medulla, ascending sensory pathways in the dorsal columns, and the descending systems of the medial longitudinal fasciculus. High-frequency sinusoidal stimulation produces transient, reversible lesions in specific target locations and therefore could be a useful alternative to permanent tissue transection in some experimental paradigms. It also could help to control or prevent some of the hyperactivity associated with chronic neurological disorders. PMID:25475345

  13. Declines in inflammation predict greater white matter microstructure in older adults.

    PubMed

    Bettcher, Brianne Magouirk; Yaffe, Kristine; Boudreau, Robert M; Neuhaus, John; Aizenstein, Howard; Ding, Jingzhong; Kritchevsky, Stephen B; Launer, Lenore J; Liu, Yongmei; Satterfield, Suzanne; Rosano, Caterina

    2015-02-01

    Protracted systemic inflammation has been associated with adverse effects on cognition and brain structure and may accelerate neurodegenerative disease processes; however, it is less clear whether changes in inflammation are associated with brain structure. We studied 276 black and white older adults (mean age = 83 years at time of imaging) enrolled in a prospective study of aging. Inflammation (measured with c-reactive protein, CRP) was assessed repeatedly over 6 years (i.e., year 2, 4, 6, and 8). Brain magnetic resonance imaging (MRIs) were obtained at years 10-11 with diffusion tensor imaging; regions of interest included late-myelinating areas vulnerable to aging, including frontal-parietal (superior longitudinal fasciculus [SLF]-dorsal) and temporal (SLF-temporal; uncinate) white matter tracts. Mean CRP values significantly declined (t = -5.54, p < 0.0001) over 6 years, and subject-specific slopes (best linear unbiased predictors of slopes) all showed a decline (mean = -0.57, standard deviation = 0.53) for our participant sample. More than 50% of study participants were still in the moderate to high cardiovascular risk range based on CRP values at year 8. After controlling for demographics, vascular risk factors and MRI white matter hyperintensities, larger decreases in CRP values over time were significantly associated with higher fractional anisotropy in the SLF-dorsal (beta = -0.0052, standard error [SE] = 0.003; 95% confidence interval [CI] = -0.0103 to -0.0025, p = 0.04), SLF-temporal (beta = -0.0109, SE = 0.004; 95% CI = -0.0189 to -0.0029, p = 0.008), and uncinate (beta = -0.0067, SE = 0.003; 95% CI = -0.0132 to -0.0001, p = 0.05) fasciculi. Results suggest that in a prospective cohort of older individuals, faster declines in inflammation over time are related to indicators of white matter health, even after accounting for vascular risk factors. PMID:25554492

  14. Midlife measurements of white matter microstructure predict subsequent regional white matter atrophy in healthy adults

    PubMed Central

    Ly, Martina; Canu, Elisa; Xu, Guofan; Oh, Jennifer; McLaren, Donald G; Dowling, N. Maritza; Alexander, Andrew L; Sager, Mark A; Johnson, Sterling C; Bendlin, Barbara B

    2013-01-01

    Objectives While age-related brain changes are becoming better understood, midlife patterns of change are still in need of characterization, and longitudinal studies are lacking. The aim of this study was to determine if baseline fractional anisotropy (FA), obtained from diffusion tensor imaging (DTI) predicts volume change over a four-year interval. Experimental design Forty-four cognitively healthy middle-age adults underwent baseline DTI and longitudinal T1-weighted magnetic resonance imaging. Tensor Based Morphometry methods were used to evaluate volume change over time. FA values were extracted from regions of interest that included the cingulum, entorhinal white matter, and the genu and splenium of the corpus callosum. Baseline FA was used as a predictor variable, while gray and white matter atrophy rates as indexed by Tensor Based Morphometry were the dependent variables. Principal observations Over a four-year period, participants showed significant contraction of white matter, especially in frontal, temporal, and cerebellar regions (p<0.05, corrected for multiple comparisons). Baseline FA in entorhinal white matter, genu, and splenium, was associated with longitudinal rates of atrophy in regions that included the superior longitudinal fasciculus, anterior corona radiata, temporal stem, and white matter of the inferior temporal gyrus (p<0.001, uncorrected for multiple comparisons). Conclusions Brain change with aging is characterized by extensive shrinkage of white matter. Baseline white matter microstructure as indexed by DTI was associated with some of the observed regional volume loss. The findings suggest that both white matter volume loss and microstructural alterations should be considered more prominently in models of aging and neurodegenerative diseases. PMID:23861348

  15. White Matter Tract Damage in the Behavioral Variant of Frontotemporal and Corticobasal Dementia Syndromes

    PubMed Central

    Tovar-Moll, Fernanda; de Oliveira-Souza, Ricardo; Bramati, Ivanei Edson; Zahn, Roland; Cavanagh, Alyson; Tierney, Michael; Moll, Jorge; Grafman, Jordan

    2014-01-01

    The phenotypes of the behavioral variant of frontotemporal dementia and the corticobasal syndrome present considerable clinical and anatomical overlap. The respective patterns of white matter damage in these syndromes have not been directly contrasted. Beyond cortical involvement, damage to white matter pathways may critically contribute to both common and specific symptoms in both conditions. Here we assessed patients with the behavioral variant of frontotemporal dementia and corticobasal syndrome with whole-brain diffusion tensor imaging to identify the white matter networks underlying these pathologies. Twenty patients with the behavioral variant of frontotemporal dementia, 19 with corticobasal syndrome, and 15 healthy controls were enrolled in the study. Differences in tract integrity between (i) patients and controls, and (ii) patients with the corticobasal syndrome and the behavioral variant of frontotemporal dementia were assessed with whole brain tract-based spatial statistics and analyses of regions of interest. Behavioral variant of frontotemporal dementia and the corticobasal syndrome shared a pattern of bilaterally decreased white matter integrity in the anterior commissure, genu and body of the corpus callosum, corona radiata and in the long intrahemispheric association pathways. Patients with the behavioral variant of frontotemporal dementia showed greater damage to the uncinate fasciculus, genu of corpus callosum and forceps minor. In contrast, corticobasal syndrome patients had greater damage to the midbody of the corpus callosum and perirolandic corona radiata. Whereas several compact white matter pathways were damaged in both the behavioral variant of frontotemporal dementia and corticobasal syndrome, the distribution and degree of white matter damage differed between them. These findings concur with the distinctive clinical manifestations of these conditions and may improve the in vivo neuroanatomical and diagnostic characterization of these disorders. PMID:25054218

  16. Clinical Use of Diffusion Tensor Image-Merged Functional Neuronavigation for Brain Tumor Surgeries: Review of Preoperative, Intraoperative, and Postoperative Data for 123 Cases

    PubMed Central

    Cho, Jin Mo; Kim, Eui Hyun; Kim, Jinna; Lee, Seung Koo; Kim, Sun Ho; Lee, Kyu Sung

    2014-01-01

    Purpose To achieve maximal safe resection during brain tumor surgery, functional image-merged neuronavigation is widely used. We retrospectively reviewed our cases in which diffusion tensor image (DTI)-merged functional neuronavigation was performed during surgery. Materials and Methods Between November 2008 and May 2010, 123 patients underwent surgery utilizing DTI-merged neuronavigation. Anatomical magnetic resonance images (MRI) were obtained preoperatively and fused with DTI of major white matter tracts, such as the corticospinal tract, optic radiation, or arcuate fasciculus. We used this fused image for functional neuronavigation during brain tumor surgery of eloquent areas. We checked the DTI images together with postoperative MRI images and evaluated the integrity of white matter tracts. Results A single white matter tract was inspected in 78 patients, and two or more white matter tracts were checked in 45 patients. Among the 123 patients, a grossly total resection was achieved in 90 patients (73.2%), subtotal resection in 29 patients (23.6%), and partial resection in 4 patients (3.3%). Postoperative neurologic outcomes, compared with preoperative function, included the following: 100 patients (81.3%) displayed improvement of neurologic symptoms or no change, 7 patients (5.7%) experienced postoperative permanent neurologic deterioration (additional or aggravated neurologic symptoms), and 16 patients (13.0%) demonstrated transient worsening. Conclusion DTI-merged functional neuronavigation could be a useful tool in brain tumor surgery for maximal safe resection. However, there are still limitations, including white matter tract shift, during surgery and in DTI itself. Further studies should be conducted to overcome these limitations. PMID:25048489

  17. Carbocyanine Dye Usage in Demarcating Boundaries of the Aged Human Red Nucleus

    PubMed Central

    Onodera, Satoru; Hicks, T. Philip

    2010-01-01

    Background Though the adult human magnocellular Red nucleus (mNr) is essentially vestigial and its boundaries with neighbouring structures have never been well demarcated, human studies in utero have shown a well developed semilunar mNr wrapping around the caudal parvicellular Red nucleus (pNr), similar to what is seen in quadrupeds. In the present study, we have sought to better delineate the morphological determinants of the adult human Red nucleus (ahRn). Methods and Findings Serial sections of ahRn show fine myelinated fibers arising from pNr and turning toward the central tegmental tract. DiI was deposited within a well restricted region of ahRn at the fasciculus retroflexus level and the extent of label determined. Nissl-stained serial sections allowed production of a 3-D mNr model, showing rudimentary, vestigial morphology compared with its well developed infant homologue. DiI within this vestigial mNr region at the level of the oculomotor nerve showed labeled giant/large mNr neurons, coarse fiber bundles at the ventral tegmental decussation and lateral lemniscal label. Conclusions Large amounts of DiI and a long incubation time have proven useful in aged human brain as a marker of long axons and large cell bodies of projecting neurons such as the rubrospinal projection and for clarifying nuclear boundaries of closed nuclei (e.g., the large human pNr). Our 3D model of adult human mNr appeared shrunken in shape and axially rotated compared with the infant mNr, the rotation being a common feature among mammalian mNr. PMID:21203458

  18. Hidden word learning capacity through orthography in aphasia.

    PubMed

    Tuomiranta, Leena M; Càmara, Estela; Froudist Walsh, Seán; Ripollés, Pablo; Saunavaara, Jani P; Parkkola, Riitta; Martin, Nadine; Rodríguez-Fornells, Antoni; Laine, Matti

    2014-01-01

    The ability to learn to use new words is thought to depend on the integrity of the left dorsal temporo-frontal speech processing pathway. We tested this assumption in a chronic aphasic individual (AA) with an extensive left temporal lesion using a new-word learning paradigm. She exhibited severe phonological problems and Magnetic Resonance Imaging (MRI) suggested a complete disconnection of this left-sided white-matter pathway comprising the arcuate fasciculus (AF). Diffusion imaging tractography confirmed the disconnection of the direct segment and the posterior indirect segment of her left AF, essential components of the left dorsal speech processing pathway. Despite her left-hemispheric damage and moderate aphasia, AA learned to name and maintain the novel words in her active vocabulary on par with healthy controls up to 6 months after learning. This exceeds previous demonstrations of word learning ability in aphasia. Interestingly, AA's preserved word learning ability was modality-specific as it was observed exclusively for written words. Functional magnetic resonance imaging (fMRI) revealed that in contrast to normals, AA showed a significantly right-lateralized activation pattern in the temporal and parietal regions when engaged in reading. Moreover, learning of visually presented novel word-picture pairs also activated the right temporal lobe in AA. Both AA and the controls showed increased activation during learning of novel versus familiar word-picture pairs in the hippocampus, an area critical for associative learning. AA's structural and functional imaging results suggest that in a literate person, a right-hemispheric network can provide an effective alternative route for learning of novel active vocabulary. Importantly, AA's previously undetected word learning ability translated directly into therapy, as she could use written input also to successfully re-learn and maintain familiar words that she had lost due to her left hemisphere lesion. PMID:24262200

  19. Diffusion based Abnormality Markers of Pathology: Towards Learned Diagnostic Prediction of ASD

    PubMed Central

    Ingalhalikar, Madhura; Parker, Drew; Bloy, Luke; Roberts, Timothy P.L.; Verma, Ragini

    2011-01-01

    This paper presents a paradigm for generating a quantifiable marker of pathology that supports diagnosis and provides a potential biomarker of neuropsychiatric disorders, such as autism spectrum disorder (ASD). This is achieved by creating high-dimensional nonlinear pattern classifiers using Support Vector Machines (SVM), that learn the underlying pattern of pathology using numerous atlas-based regional features extracted from Diffusion Tensor Imaging (DTI) data. These classifiers, in addition to providing insight into the group separation between patients and controls, are applicable on a single subject basis and have the potential to aid in diagnosis by assigning a probabilistic abnormality score to each subject that quantifies the degree of pathology and can be used in combination with other clinical scores to aid in diagnostic decision. They also produce a ranking of regions that contribute most to the group classification and separation, thereby providing a neurobiological insight into the pathology. As an illustrative application of the general framework for creating diffusion based abnormality classifiers we create classifiers for a dataset consisting of 45 children with autism spectrum disorder (ASD) (mean age 10.5 ± 2.5 yrs) as compared to 30 typically developing (TD) controls ( mean age 10.3 ± 2.5 yrs). Based on the abnormality scores, a distinction between the ASD population and TD controls was achieved with 80% leave one out (LOO) cross-validation accuracy with high significance of p < 0.001, ~84% specificity and ~74% sensitivity. Regions that contributed to this abnormality score involved fractional anisotropy (FA) differences mainly in right occipital regions as well as in left superior longitudinal fasciculus, external and internal capsule while mean diffusivity (MD) discriminates were observed primarily in right occipital gyrus and right temporal white matter. PMID:21609768

  20. Reduced White Matter Integrity in Sibling Pairs Discordant for Bipolar Disorder

    PubMed Central

    Sprooten, Emma; Brumbaugh, Margaret S.; Knowles, Emma E.M.; McKay, D. Reese; Lewis, John; Barrett, Jennifer; Landau, Stefanie; Cyr, Lindsay; Kochunov, Peter; Winkler, Anderson M.; Pearlson, Godfrey D.; Glahn, David C.

    2014-01-01

    Objective Several lines of evidence indicate that white matter integrity is compromised in bipolar disorder, but the nature, extent, and biological causes remain elusive. To determine the extent to which white matter deficits in bipolar disorder are familial, the authors investigated white matter integrity in a large sample of bipolar patients, unaffected siblings, and healthy comparison subjects. Method The authors collected diffusion imaging data for 64 adult bipolar patients, 60 unaffected siblings (including 54 discordant sibling pairs), and 46 demographically matched comparison subjects. Fractional anisotropy was compared between the groups using voxel-wise tract-based spatial statistics and by extracting mean fractional anisotropy from 10 regions of interest. Additionally, intra-class correlation coefficients were calculated between the sibling pairs as an index of familiality. Results Widespread fractional anisotropy reductions in bipolar patients (>40,000 voxels) and more subtle reductions in their siblings, mainly restricted to the corpus callosum, posterior thalamic radiations, and left superior longitudinal fasciculus (>2,000 voxels) were observed. Similarly, region-of-interest analysis revealed significant reductions in most white matter regions in patients. In siblings, fractional anisotropy in the posterior thalamic radiation and the forceps was nominally reduced. Significant between-sibling correlations were found for mean fractional anisotropy across the tract-based spatial statistic skeleton, within significant clusters, and within nearly all regions of interest. Conclusions These findings emphasize the relevance of white matter to neuropathology and familiality of bipolar disorder and encourage further use of white matter integrity markers as endophenotypes in genetic studies. PMID:24185242

  1. Evidence That the Blood Biomarker SNTF Predicts Brain Imaging Changes and Persistent Cognitive Dysfunction in Mild TBI Patients

    PubMed Central

    Siman, Robert; Giovannone, Nicholas; Hanten, Gerri; Wilde, Elisabeth A.; McCauley, Stephen R.; Hunter, Jill V.; Li, Xiaoqi; Levin, Harvey S.; Smith, Douglas H.

    2013-01-01

    Although mild traumatic brain injury (mTBI), or concussion, is not typically associated with abnormalities on computed tomography (CT), it nevertheless causes persistent cognitive dysfunction for many patients. Consequently, new prognostic methods for mTBI are needed to identify at risk cases, especially at an early and potentially treatable stage. Here, we quantified plasma levels of the neurodegeneration biomarker calpain-cleaved ?II-spectrin N-terminal fragment (SNTF) from 38 participants with CT-negative mTBI, orthopedic injury (OI), and normal uninjured controls (UCs) (age range 12–30?years), and compared them with findings from diffusion tensor imaging (DTI) and long-term cognitive assessment. SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI cases and in 3 of 13 OI cases, but in none of the UCs. An elevation in plasma SNTF corresponded with significant differences in fractional anisotropy and the apparent diffusion coefficient in the corpus callosum and uncinate fasciculus measured by DTI. Furthermore, increased plasma SNTF on the day of injury correlated significantly with cognitive impairment that persisted for at least 3?months, both across all study participants and also among the mTBI cases by themselves. The elevation in plasma SNTF in the subset of OI cases, accompanied by corresponding white matter and cognitive abnormalities, raises the possibility of identifying undiagnosed cases of mTBI. These data suggest that the blood level of SNTF on the day of a CT-negative mTBI may identify a subset of patients at risk of white matter damage and persistent disability. SNTF could have prognostic and diagnostic utilities in the assessment and treatment of mTBI. PMID:24302918

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

    PubMed Central

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

    2011-01-01

    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. PMID:20586754

  3. Polygenic risk and white matter integrity in individuals at high risk of mood disorder

    PubMed Central

    Whalley, Heather C; Sprooten, Emma; Hackett, Suzanna; Hall, Lynsey; Blackwood, Douglas H; Glahn, David C; Bastin, Mark; Hall, Jeremy; Lawrie, Stephen M; Sussmann, Jessika E; McIntosh, Andrew M

    2014-01-01

    Background Bipolar disorder (BD) and major depressive disorder (MDD) are highly heritable and genetically overlapping conditions characterised by episodic elevation and/or depression of mood. Both demonstrate abnormalities in white matter integrity, measured using diffusion tensor magnetic resonance imaging (MRI), that are also heritable. However it is unclear how these abnormalities relate to the underlying genetic architecture of each disorder. Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to BD and MDD, where risk is attributed to the summation of many alleles of small effect. Determining the effects of an overall polygenic risk profile score on neuroimaging abnormalities may help to identify proxy measures of genetic susceptibility and thereby inform models of risk prediction. Methods In the current study we determined the extent to which common genetic variation underlying risk to mood disorders (BD and MDD) was related to fractional anisotropy, an index of white matter integrity. This was conducted in unaffected individuals at familial risk of mood disorder (n=70) and comparison subjects (n=62). Polygenic risk scores were calculated separately for BD and MDD based on GWAS data from the Psychiatric Genome Consortia. Results We report that a higher polygenic risk allele load for MDD was significantly associated with decreased white matter integrity across both groups in a large cluster with a peak in the right-sided superior longitudinal fasciculus. Conclusions These findings suggest that the polygenic approach to examining brain imaging data may be a useful means of identifying traits linked to the genetic risk of mood disorders. PMID:23453289

  4. Improving diffusion-weighted imaging of post-mortem human brains: SSFP at 7 T

    PubMed Central

    Foxley, Sean; Jbabdi, Saad; Clare, Stuart; Lam, Wilfred; Ansorge, Olaf; Douaud, Gwenaelle; Miller, Karla

    2014-01-01

    Post-mortem diffusion imaging of whole, human brains has potential to provide data for validation or high-resolution anatomical investigations. Previous work has demonstrated improvements in data acquired with diffusion-weighted steady-state free precession (DW-SSFP) compared with conventional diffusion-weighted spin echo at 3 T. This is due to the ability of DW-SSFP to overcome signal-to-noise and diffusion contrast losses brought about by tissue fixation related decreases in T2 and ADC. In this work, data of four post-mortem human brains were acquired at 3 T and 7 T, using DW-SSFP with similar effective b-values (beff ~ 5150 s/mm2) for inter-field strength comparisons; in addition, DW-SSFP data were acquired at 7 T with higher beff (~ 8550 s/mm2) for intra-field strength comparisons. Results demonstrate that both datasets acquired at 7 T had higher SNR and diffusion contrast than data acquired at 3 T, and data acquired at higher beff had improved diffusion contrast than at lower beff at 7 T. These results translate to improved estimates of secondary fiber orientations leading to higher fidelity tractography results compared with data acquired at 3 T. Specifically, tractography streamlines of cortical projections originating from the corpus callosum, corticospinal tract, and superior longitudinal fasciculus were more successful at crossing the centrum semiovale and projected closer to the cortex. Results suggest that DW-SSFP at 7 T is a preferential method for acquiring diffusion-weighted data of post-mortem human brain, specifically where the primary region of interest involves crossing white matter tracts. PMID:25128709

  5. Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech

    PubMed Central

    Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Senjem, Matthew L.; Master, Ankit V.; Lowe, Val J.; Jack, Clifford R.; Whitwell, Jennifer L.

    2012-01-01

    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, [18F]-fluorodeoxyglucose and [11C] 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 [18F]-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. [11C]-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

  6. Development of Cerebral Fiber Pathways in Cats revealed by Diffusion Spectrum Imaging

    PubMed Central

    Takahashi, Emi; Dai, Guangping; Wang, Ruopeng; Ohki, Kenichi; Rosen, Glenn D.; Galaburda, Albert M.; Grant, P. Ellen; Wedeen, Van J.

    2009-01-01

    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

  7. Development of cerebral fiber pathways in cats revealed by diffusion spectrum imaging.

    PubMed

    Takahashi, Emi; Dai, Guangping; Wang, Ruopeng; Ohki, Kenichi; Rosen, Glenn D; Galaburda, Albert M; Grant, P Ellen; Wedeen, Van J

    2010-01-15

    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

  8. Dissociated repetition deficits in aphasia can reflect flexible interactions between left dorsal and ventral streams and gender-dimorphic architecture of the right dorsal stream

    PubMed Central

    Berthier, Marcelo L.; Froudist Walsh, Seán; Dávila, Guadalupe; Nabrozidis, Alejandro; Juárez y Ruiz de Mier, Rocío; Gutiérrez, Antonio; De-Torres, Irene; Ruiz-Cruces, Rafael; Alfaro, Francisco; García-Casares, Natalia

    2013-01-01

    Assessment of brain-damaged subjects presenting with dissociated repetition deficits after selective injury to either the left dorsal or ventral auditory pathways can provide further insight on their respective roles in verbal repetition. We evaluated repetition performance and its neural correlates using multimodal imaging (anatomical MRI, DTI, fMRI, and18FDG-PET) in a female patient with transcortical motor aphasia (TCMA) and in a male patient with conduction aphasia (CA) who had small contiguous but non-overlapping left perisylvian infarctions. Repetition in the TCMA patient was fully preserved except for a mild impairment in nonwords and digits, whereas the CA patient had impaired repetition of nonwords, digits and word triplet lists. Sentence repetition was impaired, but he repeated novel sentences significantly better than clichés. The TCMA patient had tissue damage and reduced metabolism in the left sensorimotor cortex and insula. DTI showed damage to the left temporo-frontal and parieto-frontal segments of the arcuate fasciculus (AF) and part of the left ventral stream together with well-developed right dorsal and ventral streams, as has been reported in more than one-third of females. The CA patient had tissue damage and reduced metabolic activity in the left temporoparietal cortex with additional metabolic decrements in the left frontal lobe. DTI showed damage to the left temporo-parietal and temporo-frontal segments of the AF, but the ventral stream was spared. The direct segment of the AF in the right hemisphere was also absent with only vestigial remains of the other dorsal subcomponents present, as is often found in males. fMRI during word and nonword repetition revealed bilateral perisylvian activation in the TCMA patient suggesting recruitment of spared segments of the left dorsal stream and right dorsal stream with propagation of signals to temporal lobe structures suggesting a compensatory reallocation of resources via the ventral streams. The CA patient showed a greater activation of these cortical areas than the TCMA patient, but these changes did not result in normal performance. Repetition of word triplet lists activated bilateral perisylvian cortices in both patients, but activation in the CA patient with very poor performance was restricted to small frontal and posterior temporal foci bilaterally. These findings suggest that dissociated repetition deficits in our cases are probably reliant on flexible interactions between left dorsal stream (spared segments, short tracts remains) and left ventral stream and on gender-dimorphic architecture of the right dorsal stream. PMID:24391569

  9. Voxel-based structural magnetic resonance imaging (MRI) study of patients with early onset schizophrenia

    PubMed Central

    Yoshihara, Yujiro; Sugihara, Genichi; Matsumoto, Hideo; Suckling, John; Nishimura, Katsuhiko; Toyoda, Takao; Isoda, Haruo; Tsuchiya, Kenji J; Takebayashi, Kiyokazu; Suzuki, Katsuaki; Sakahara, Harumi; Nakamura, Kazuhiko; Mori, Norio; Takei, Nori

    2008-01-01

    Background Investigation into the whole brain morphology of early onset schizophrenia (EOS) to date has been sparse. We studied the regional brain volumes in EOS patients, and the correlations between regional volume measures and symptom severity. Methods A total of 18 EOS patients (onset under 16 years) and 18 controls matched for age, gender, parental socioeconomic status, and height were examined. Voxel-based morphometric analysis using the Brain Analysis Morphological Mapping (BAMM) software package was employed to explore alterations of the regional grey (GM) and white matter (WM) volumes in EOS patients. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Results EOS patients had significantly reduced GM volume in the left parahippocampal, inferior frontal, and superior temporal gyri, compared with the controls. They also had less WM volume in the left posterior limb of the internal capsule and the left inferior longitudinal fasciculus. The positive symptom score of PANSS (higher values corresponding to more severe symptoms) was negatively related to GM volume in the bilateral posterior cingulate gyrus. The negative symptom score was positively correlated with GM volume in the right thalamus. As for the association with WM volume, the positive symptom score of PANSS was positively related to cerebellar WM (vermis region), and negatively correlated with WM in the brain stem (pons) and in the bilateral cerebellum (hemisphere region). Conclusion Our findings of regional volume alterations of GM and WM in EOS patients coincide with those of previous studies of adult onset schizophrenia patients. However, in brain regions that had no overall structural differences between EOS patients and controls (that is, the bilateral posterior cingulate gyrus, the right thalamus, the cerebellum, and the pons), within-subject analysis of EOS patients alone revealed that there were significant associations of the volume in these areas and the symptom severity. These findings suggest that at an early stage of the illness, especially for those with onset before brain maturation, a wide range of disturbed neural circuits, including these brain regions that show no apparent morphological changes, may contribute to the formation of the symptomatology. PMID:19102744

  10. Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech.

    PubMed

    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

    2012-05-01

    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

  11. Brain microstructural changes and cognitive correlates in patients with pure obsessive compulsive disorder

    PubMed Central

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

    2014-01-01

    Object The aim of this study was to investigate macrostructural and microstructural brain changes in patients with pure obsessive compulsive disorder (OCD) and to examine the relationship between brain structure and neuropsychological deficits. Method 20 patients with OCD underwent a comprehensive neuropsychological battery. A combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis was used to capture gray matter (GM) and white matter changes in OCD patients as compared to pair-matched healthy volunteers. Multiple regression designs explored the relationship between cognition and neuroimaging parameters. Results OCD patients had increased mean diffusivity (MD) in GM nodes of the orbitofronto-striatal loop (left dorsal anterior cingulate [Z = 3.67, P < 0.001] left insula [Z = 3.35 P < 0.001] left thalamus [Z = 3.59, P < 0.001] left parahippocampal gyrus [Z = 3.77 P < 0.001]) and in lateral frontal and posterior associative cortices (right frontal operculum [Z = 3.42 P < 0.001], right temporal lobe [Z = 3.79 P < 0.001] left parietal lobe [Z = 3.91 P < 0.001]). Decreased fractional anisotropy (FA) was detected in intrahemispheric (left superior longitudinal fasciculus [Z = 4.07 P < 0.001]) and interhemispheric (body of corpus callosum [CC, Z = 4.42 P < 0.001]) bundles. Concurrently, the semantic fluency score, a measure of executive control processes, significantly predicted OCD diagnosis (Odds Ratio = 1.37; 95% Confidence Intervals = 1.09–1.73; P = 0.0058), while variation in performance was correlated with increased MD in left temporal (Z = 4.25 P < 0.001) and bilateral parietal regions (left Z = 3.94, right Z = 4.19 P < 0.001), and decreased FA in the right posterior corona radiata (Z = 4.07 P < 0.001) and the left corticospinal tract (Z = 3.95 P < 0.001). Conclusions The reported deficit in executive processes and the underlying microstructural alterations may qualify as behavioral and biological markers of OCD. PMID:24683518

  12. Connections of the corpus cerebelli in the green sunfish and the common goldfish: a comparison of perciform and cypriniform teleosts.

    PubMed

    Wullimann, M F; Northcutt, R G

    1988-01-01

    Examination of the connections of the corpus cerebelli in one perciform (Lepomis cyanellus) and one cypriniform teleost (Carassius auratus) reveal that ipsilateral afferent connections in both species arise from an anterior group of nuclei in the diencephalon and mesencephalon, and a posterior group of nuclei in the rhombencephalon. Some nuclei of the anterior group and all those of the posterior group have in addition a weaker, and the medial octavolateralis nucleus a stronger, contralateral component. The inferior olivary nucleus in both species projects solely contralaterally. Nucleus paracommissuralis, the ventral accessory optic nucleus and nucleus isthmi are minute in Carassius compared to Lepomis. The latter species has in addition a bilateral corpopetal projection (ipsilaterally stronger) from the lateral cuneate nucleus. Efferent fibers in both species reach the contralateral nucleus ruber, oculomotor nucleus, nucleus of the medial longitudinal fasciculus, torus semicircularis, ventromedial and ventrolateral thalamic nuclei, optic tectum and superior and inferior reticular formation. An additional weaker ipsilateral terminal field could be observed in all nuclei except in the ventrolateral and ventromedial thalamic nuclei, the dorsal periventricular pretectal nucleus and the optic tectum. Lepomis in addition has a bilateral terminal field in the ventral accessory optic nucleus (contralaterally stronger). In both species, stronger ipsilateral and weaker contralateral terminal fields were present in the torus longitudinalis and the valvula cerebelli. The two patterns of corpopetal connections in Lepomis and Carassius were used as models for perciforms and cypriniforms in the analysis of the existing information in the literature on teleosts. While most discrepancies in the literature on percomorphs and ostariophysines could be interpreted consistently, the available information on mormyrids revealed a very different pattern of corpopetal organization: presence of additional connections (from a division of the nucleus preglomerulosus) and absence of otherwise well-established corpopetal connections in teleosts. In a second step, a phyletic analysis of teleostean corpopetal organization revealed that while teleosts share with all other vertebrates a group of corpopetal connections from the rhombencephalon, they evolved many new, more anteriorly located afferent inputs to the corpus cerebelli. Furthermore, electroreceptive mormyrids in addition evolved newly at least one corpopetal connection and lost many others. PMID:3233488

  13. Predicting speech fluency and naming abilities in aphasic patients

    PubMed Central

    Wang, Jasmine; Marchina, Sarah; Norton, Andrea C.; Wan, Catherine Y.; Schlaug, Gottfried

    2013-01-01

    There is a need to identify biomarkers that predict degree of chronic speech fluency/language impairment and potential for improvement after stroke. We previously showed that the Arcuate Fasciculus lesion load (AF-LL), a combined variable of lesion site and size, predicted speech fluency in patients with chronic aphasia. In the current study, we compared lesion loads of such a structural map (i.e., AF-LL) with those of a functional map [i.e., the functional gray matter lesion load (fGM-LL)] in their ability to predict speech fluency and naming performance in a large group of patients. The fGM map was constructed from functional brain images acquired during an overt speaking task in a group of healthy elderly controls. The AF map was reconstructed from high-resolution diffusion tensor images also from a group of healthy elderly controls. In addition to these two canonical maps, a combined AF-fGM map was derived from summing fGM and AF maps. Each canonical map was overlaid with individual lesion masks of 50 chronic aphasic patients with varying degrees of impairment in speech production and fluency to calculate a functional and structural lesion load value for each patient, and to regress these values with measures of speech fluency and naming. We found that both AF-LL and fGM-LL independently predicted speech fluency and naming ability; however, AF lesion load explained most of the variance for both measures. The combined AF-fGM lesion load did not have a higher predictability than either AF-LL or fGM-LL alone. Clustering and classification methods confirmed that AF lesion load was best at stratifying patients into severe and non-severe outcome groups with 96% accuracy for speech fluency and 90% accuracy for naming. An AF-LL of greater than 4 cc was the critical threshold that determined poor fluency and naming outcomes, and constitutes the severe outcome group. Thus, surrogate markers of impairments have the potential to predict outcomes and can be used as a stratifier in experimental studies. PMID:24339811

  14. Projections from the red nucleus and surrounding areas to the brainstem and spinal cord in the cat. An HRP and autoradiographical tracing study.

    PubMed

    Holstege, G; Tan, J

    1988-01-01

    HRP injections at the C2, T1 and S1 spinal levels and in the medullary lateral tegmental field revealed that the contralaterally projecting rubro-bulbospinal neurons are located not only in the caudal but also to a certain extent in the rostral red nucleus (RN). These RN projections are somatotopically organized. Neurons projecting to the sacral cord are located in the ventrolateral RN, those projecting to the upper part of the spinal cord lie in the dorsomedial RN and those projecting to the medullary lateral tegmentum were found in the dorsal portions of the RN. These last neurons are smaller than many of the other RN neurons. The HRP results also revealed that the RN does not project to the caudal raphe nuclei. The autoradiographical results confirmed the HRP findings. They further indicated that the contralateral RN projections to the caudal brainstem precerebellar nuclei (nucleus corporis pontobulbaris, lateral reticular nucleus, lateral cuneate nucleus) and the dorsal column nuclei are also somatotopically organized. This was also true for the RN projections to the dorsomedial and intermediate facial subnuclei and the caudal pontine and medullary lateral tegmental field. These areas receive afferents from mainly the dorsal portions of the RN. Regarding the RN projections to the spinal cord, the autoradiographical tracing results revealed somatotopically organized contralateral RN projections to laminae V, VI and VII. Moreover, a small but distinct RN projection to a dorsolaterally located group of motoneurons at the C8-T1 level was demonstrated. Ipsilaterally a minor projection to the cervical and upper thoracic lateral intermediate zone was observed. Finally, strong ipsilateral projections from the rostral mesencephalon to the inferior olive were seen. These projections were derived from various rostral mesencephalic areas, including the nucleus of Darkschewitsch, the nucleus accessorius medialis of Bechterew, the interstitial nucleus of Cajal and the area of the rostral interstitial nucleus of the medial longitudinal fasciculus. In the cat it was difficult to define which of the mesencephalic areas projecting to the inferior olive represented the parvocellular RN. A new subdivision of the RN is proposed based on its projections and not on the size of its cells. In this concept the first group is formed by the RN neurons projecting contralaterally to the caudal brainstem and spinal cord. The second group consists of RN neurons projecting to the inferior olive.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3382519

  15. The bulbocerebellar circumolivary bundle

    PubMed Central

    DE CARO, R.; MUNARI, P. F.; PARENTI, A.

    1998-01-01

    During the course of a systematic study on the human vertebrobasilar arterial system (De Caro et al. 1995), our attention was drawn in one case to a strange morphology of the ventrolateral aspect of one side of the medulla. While initially our impression was that we were facing an actual malformation, review of the structure of the brainstem as described in most standard anatomical texts showed that it could correspond to the circumolivary fasciculus (Williams et al. 1995). The subject was a 63-y-old man who had died from rupture of an atherosclerotic aneurysm of the abdominal aorta. The medical history was negative for neuropsychiatric pathology. Brain examination showed severe atherosclerosis of the cerebral arteries and hypoplasia of the initial segment of the right posterior cerebral artery. A recent infarct was found in the white matter of the right occipital lobe. After removal of the vertebrobasilar arterial system, the right pyramid showed a superficial groove extending from about 2 mm lateral to the foramen caecum obliquely downwards to the right anterolateral sulcus of the medulla, at the level of the superior margin of the inferior root of the hypoglossal nerve (Fig. 1a). Due to this groove, the lateral part of the pyramid formed a ridge that crossed the anterolateral sulcus of the medulla passing between the 2 main roots of the hypoglossal nerve and then continued, below the inferior pole of the olive, over the lateral region of the medulla ending at the level of the posterolateral sulcus (Fig. 1b). The general appearance was that of a small cord forming a loop around the anterior margin and the inferior pole of the olive, with a descending part (8 mm long), a horizontal part (6 mm long) and with a transverse diameter of 3 mm. After formalin fixation, the brainstem was cut in 8 transverse sections. At the level of the medulla the right pyramid appeared larger than the contralateral and the small lateral cord was separated from the main part of the pyramid by a thin whitish transverse stria (Fig. 1c). Macroscopic examination of the cerebellum showed nothing of relevance. PMID:9877303

  16. Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.

    PubMed

    Fink, John K

    2013-09-01

    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