Sample records for abnormal cerebellar morphometry

  1. Abnormal cerebellar morphometry in abstinent adolescent marijuana users

    PubMed Central

    Medina, Krista Lisdahl; Nagel, Bonnie J.; Tapert, Susan F.

    2010-01-01

    Background Functional neuroimaging data from adults have, in general, found frontocerebellar dysfunction associated with acute and chronic marijuana (MJ) use (Loeber & Yurgelun-Todd, 1999). One structural neuroimaging study found reduced cerebellar vermis volume in young adult MJ users with a history of heavy polysubstance use (Aasly et al., 1993). The goal of this study was to characterize cerebellar volume in adolescent chronic MJ users following one month of monitored abstinence. Method Participants were MJ users (n=16) and controls (n=16) aged 16-18 years. Extensive exclusionary criteria included history of psychiatric or neurologic disorders. Drug use history, neuropsychological data, and structural brain scans were collected after 28 days of monitored abstinence. Trained research staff defined cerebellar volumes (including three cerebellar vermis lobes and both cerebellar hemispheres) on high-resolution T1-weighted magnetic resonance images. Results Adolescent MJ users demonstrated significantly larger inferior posterior (lobules VIII-X) vermis volume (p<.009) than controls, above and beyond effects of lifetime alcohol and other drug use, gender, and intracranial volume. Larger vermis volumes were associated with poorer executive functioning (p’s<.05). Conclusions Following one month of abstinence, adolescent MJ users had significantly larger posterior cerebellar vermis volumes than non-using controls. These greater volumes are suggested to be pathological based on linkage to poorer executive functioning. Longitudinal studies are needed to examine typical cerebellar development during adolescence and the influence of marijuana use. PMID:20413277

  2. Cerebellar abnormalities typical of methylmercury poisoning in a fledged saltmarsh sparrow, Ammodramus caudacutus.

    PubMed

    Scoville, Sheila A; Lane, Oksana P

    2013-05-01

    A fledged, 12-15 day-old saltmarsh sparrow, Ammodramus caudacutus, was collected from an accidental kill on Cinder Island, Long Island, NY, USA. The sparrow was assessed for feather mercury levels and the brain analyzed for cerebellar abnormalities by microscopic examination. In humans, fetal Minamata disease is caused by maternal ingestion of mercury. It is characterized by disrupted and disordered cerebellar neuronal migration in the fetus or infant. Results from this sparrow show cerebellar abnormalities typical of Minamata disease. It is the first known avian or mammalian specimen taken from the wild to show the abnormalities typical of the human fetal syndrome.

  3. Cerebellar ataxia: abnormal control of interaction torques across multiple joints.

    PubMed

    Bastian, A J; Martin, T A; Keating, J G; Thach, W T

    1996-07-01

    1. We studied seven subjects with cerebellar lesions and seven control subjects as they made reaching movements in the sagittal plane to a target directly in front of them. Reaches were made under three different conditions: 1) "slow-accurate," 2) "fast-accurate," and 3) "fast as possible." All subjects were videotaped moving in a sagittal plane with markers on the index finger, wrist, elbow, and shoulder. Marker positions were digitized and then used to calculate joint angles. For each of the shoulder, elbow and wrist joints, inverse dynamics equations based on a three-segment limb model were used to estimate the net torque (sum of components) and each of the component torques. The component torques consisted of the torque due to gravity, the dynamic interaction torques induced passively by the movement of the adjacent joint, and the torque produced by the muscles and passive tissue elements (sometimes called "residual" torque). 2. A kinematic analysis of the movement trajectory and the change in joint angles showed that the reaches of subjects with cerebellar lesions were abnormal compared with reaches of control subjects. In both the slow-accurate and fast-accurate conditions the cerebellar subjects made abnormally curved wrist paths; the curvature was greater in the slow-accurate condition. During the slow-accurate condition, cerebellar subjects showed target undershoot and tended to move one joint at a time (decomposition). During the fast-accurate reaches, the cerebellar subjects showed target overshoot. Additionally, in the fast-accurate condition, cerebellar subjects moved the joints at abnormal rates relative to one another, but the movements were less decomposed. Only three subjects were tested in the fast as possible condition; this condition was analyzed only to determine maximal reaching speeds of subjects with cerebellar lesions. Cerebellar subjects moved more slowly than controls in all three conditions. 3. A kinetic analysis of torques generated at

  4. Greater cerebellar gray matter volume in car drivers: an exploratory voxel-based morphometry study

    PubMed Central

    Sakai, Hiroyuki; Ando, Takafumi; Sadato, Norihiro; Uchiyama, Yuji

    2017-01-01

    Previous functional neuroimaging studies have identified multiple brain areas associated with distinct aspects of car driving in simulated traffic environments. Few studies, however, have examined brain morphology associated with everyday car-driving experience in real traffic. Thus, the aim of the current study was to identify gray matter volume differences between drivers and non-drivers. We collected T1-weighted structural brain images from 73 healthy young adults (36 drivers and 37 non-drivers). We performed a whole-brain voxel-based morphometry analysis to examine between-group differences in regional gray matter volume. Compared with non-drivers, drivers showed significantly greater gray matter volume in the left cerebellar hemisphere, which has been associated with cognitive rather than motor functioning. In contrast, we found no brain areas with significantly greater gray matter volume in non-drivers compared with drivers. Our findings indicate that experience with everyday car driving in real traffic is associated with greater gray matter volume in the left cerebellar hemisphere. This brain area may be involved in abilities that are critical for driving a car, but are not commonly or frequently used during other daily activities. PMID:28417971

  5. Greater cerebellar gray matter volume in car drivers: an exploratory voxel-based morphometry study.

    PubMed

    Sakai, Hiroyuki; Ando, Takafumi; Sadato, Norihiro; Uchiyama, Yuji

    2017-04-18

    Previous functional neuroimaging studies have identified multiple brain areas associated with distinct aspects of car driving in simulated traffic environments. Few studies, however, have examined brain morphology associated with everyday car-driving experience in real traffic. Thus, the aim of the current study was to identify gray matter volume differences between drivers and non-drivers. We collected T1-weighted structural brain images from 73 healthy young adults (36 drivers and 37 non-drivers). We performed a whole-brain voxel-based morphometry analysis to examine between-group differences in regional gray matter volume. Compared with non-drivers, drivers showed significantly greater gray matter volume in the left cerebellar hemisphere, which has been associated with cognitive rather than motor functioning. In contrast, we found no brain areas with significantly greater gray matter volume in non-drivers compared with drivers. Our findings indicate that experience with everyday car driving in real traffic is associated with greater gray matter volume in the left cerebellar hemisphere. This brain area may be involved in abilities that are critical for driving a car, but are not commonly or frequently used during other daily activities.

  6. Nicotinic receptor abnormalities in the cerebellar cortex in autism.

    PubMed

    Lee, M; Martin-Ruiz, C; Graham, A; Court, J; Jaros, E; Perry, R; Iversen, P; Bauman, M; Perry, E

    2002-07-01

    Autism is a common developmental disorder associated with structural and inferred neurochemical abnormalities of the brain. Cerebellar abnormalities frequently have been identified, based on neuroimaging or neuropathology. Recently, the cholinergic neurotransmitter system has been implicated on the basis of nicotinic receptor loss in the cerebral cortex. Cerebellar cholinergic activities were therefore investigated in autopsy tissue from a series of autistic individuals. The presynaptic cholinergic enzyme, choline acetyltransferase, together with nicotinic and muscarinic receptor subtypes were compared in the cerebellum from age-matched mentally retarded autistic (eight), normal control (10) and non-autistic mentally retarded individuals (11). The nicotinic receptor binding the agonist epibatidine (the high affinity receptor subtype, consisting primarily of alpha3 and alpha4, together with beta2 receptor subunits) was significantly reduced by 40-50% in the granule cell, Purkinje and molecular layers in the autistic compared with the normal group (P < 0.05). There was an opposite increase (3-fold) in the nicotinic receptor binding alpha-bungarotoxin (to the alpha7 subunit) which reached significance in the granule cell layer (P < 0.05). These receptor changes were paralleled by a significant reduction (P < 0.05) and non-significant increase, respectively, of alpha4 and alpha7 receptor subunit immunoreactivity measured using western blotting. Immunohistochemically loss of alpha(4 )reactivity was apparent from Purkinje and the other cell layers, with increased alpha7 reactivity in the granule cell layer. There were no significant changes in choline acetyltransferase activity, or in muscarinic M1 and M2 receptor subtypes in autism. In the non-autistic mentally retarded group, the only significant abnormality was a reduction in epibatidine binding in the granule cell and Purkinje layers. In two autistic cases examined histologically, Purkinje cell loss was observed in

  7. Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

    PubMed Central

    Baldarçara, Leonardo; Currie, Stuart; Hadjivassiliou, M.; Hoggard, Nigel; Jack, Allison; Jackowski, Andrea P.; Mascalchi, Mario; Parazzini, Cecilia; Reetz, Kathrin; Righini, Andrea; Schulz, Jörg B.; Vella, Alessandra; Webb, Sara Jane; Habas, Christophe

    2016-01-01

    Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine. PMID:25382714

  8. Gestational lead exposure induces developmental abnormalities and up-regulates apoptosis of fetal cerebellar cells in rats.

    PubMed

    Mousa, Alyaa M; Al-Fadhli, Ameera S; Rao, Muddanna S; Kilarkaje, Narayana

    2015-01-01

    Lead (Pb), a known environmental toxicant, adversely affects almost all organ systems. In this study, we investigated the effects of maternal lead exposure on fetal rat cerebellum. Female Sprague-Dawley rats were given lead nitrate in drinking water (0, 0.5, and 1%) for two weeks before conception, and during pregnancy. Fetuses were collected by caesarian section on gestational day 21 and observed for developmental abnormalities. The fetal cerebellar sections from control and 1% lead group were stained with cresyl violet. Immunohistochemical expressions of p53, Bax, Bcl-2, and caspase 3 were quantified by AnalySIS image analyzer (Life Science, Germany). Lead exposure induced developmental abnormalities of eyes, ear, limbs, neck and ventral abdominal wall; however, these abnormalities were commonly seen in the 1% lead-treated group. In addition, lead also caused fetal mortality and reduced body growth in both dose groups and reduced brain weight in the 1% lead-treated group. The fetal cerebella from the 1% lead-treated group showed unorganized cerebellar cortical layers, and degenerative changes in granule and Purkinje cells such as the formation of clumps of Nissl granules. An increase in Bax and caspase 3, and a decrease in Bcl-2 (p < 0.05), but not in p53, showed apoptosis of the neurons. In conclusion, gestational lead exposure in rats induces fetal toxicity and developmental abnormalities. The lead exposure also impairs development of cerebellar layers, induces structural changes, and apoptosis in the fetal cerebellar cortex. These results suggest that lead exposure during gestation is extremely toxic to developing cerebellum in rats.

  9. Cerebellar White Matter Abnormalities following Primary Blast Injury in US Military Personnel

    PubMed Central

    Mac Donald, Christine; Johnson, Ann; Cooper, Dana; Malone, Thomas; Sorrell, James; Shimony, Joshua; Parsons, Matthew; Snyder, Abraham; Raichle, Marcus; Fang, Raymond; Flaherty, Stephen; Russell, Michael; Brody, David L.

    2013-01-01

    Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation. PMID:23409052

  10. Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models

    PubMed Central

    Yokoi, Fumiaki; Dang, Mai T.; Yang, Guang; Li, JinDong; Doroodchi, Atbin; Zhou, Tong; Li, Yuqing

    2011-01-01

    Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ε-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally-inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ε-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ε-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally-inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ε-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ε-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits. PMID:22040906

  11. Possible involvement of rumination in gray matter abnormalities in persistent symptoms of major depression: an exploratory magnetic resonance imaging voxel-based morphometry study.

    PubMed

    Machino, Akihiko; Kunisato, Yoshihiko; Matsumoto, Tomoya; Yoshimura, Shinpei; Ueda, Kazutaka; Yamawaki, Yosuke; Okada, Go; Okamoto, Yasumasa; Yamawaki, Shigeto

    2014-10-01

    A recent meta-analysis of many magnetic resonance imaging (MRI) studies has identified brain regions with gray matter (GM) abnormalities in patients with major depressive disorder (MDD). A few studies addressing GM abnormalities in patients with treatment-resistant depression (TRD) have yielded inconsistent results. Moreover, although TRD patients tend to exhibit ruminative thoughts, it remains unclear whether rumination is related to GM abnormalities in such patients or not. We conducted structural MRI scans and voxel-based morphometry (VBM) to identify GM differences among 29 TRD patients and 29 healthy age-matched and sex-matched controls. A response style questionnaire was used to assess the respective degrees of rumination in TRD patients. Structural correlates of rumination were examined. TRD patients showed several regions with smaller GM volume than in healthy subjects: the left dorsal anterior cingulate cortex (ACC), right ventral ACC, right superior frontal gyrus, right cerebellum (Crus I), and cerebellar vermis. GM volumes in these regions did not correlate to rumination. However, whole-brain analysis revealed that rumination was positively correlated with the GM volume in the right superior temporal gyrus in TRD patients. Structural correlates of rumination were examined only in TRD patients. Our data provide additional evidence supporting the hypothesis that TRD patients show GM abnormalities compared with healthy subjects. Furthermore, this report is the first to describe a study identifying brain regions for which the GM volume is correlated with rumination in TRD patients. These results improve our understanding of the anatomical characteristics of TRD. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models.

    PubMed

    Yokoi, Fumiaki; Dang, Mai T; Yang, Guang; Li, Jindong; Doroodchi, Atbin; Zhou, Tong; Li, Yuqing

    2012-02-01

    Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ɛ-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ɛ-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ɛ-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ɛ-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ɛ-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort.

    PubMed

    Wade, Benjamin S C; Valcour, Victor G; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H; Gutman, Boris A; Thompson, Paul M

    2015-01-01

    Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%.

  14. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    PubMed

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  15. Changes in the cerebellar and cerebro-cerebellar circuit in type 2 diabetes.

    PubMed

    Fang, Peng; An, Jie; Tan, Xin; Zeng, Ling-Li; Shen, Hui; Qiu, Shijun; Hu, Dewen

    2017-04-01

    Currently, 422 million adults suffer from diabetes worldwide, leading to tremendous disabilities and a great burden to families and society. Functional and structural MRIs have demonstrated that patients with type 2 diabetes mellitus (T2DM) exhibit abnormalities in brain regions in the cerebral cortex. However, the changes of cerebellar anatomical connections in diabetic patients remains unclear. In the current study, diffusion tensor imaging deterministic tractography and statistical analysis were employed to investigate abnormal cerebellar anatomical connections in diabetic patients. This is the first study to investigate the altered cerebellar anatomical connectivity in T2DM patients. Decreased anatomical connections were found in the cerebellar and cerebro-cerebellar circuits of T2DM patients, providing valuable new insights into the potential neuro-pathophysiology of diabetes-related motor and cognitive deficits. Copyright © 2017. Published by Elsevier Inc.

  16. Dose-related cerebellar abnormality in rats with prenatal exposure to X-irradiation by magnetic resonance imaging volumetric analysis.

    PubMed

    Sawada, Kazuhiko; Saito, Shigeyoshi; Horiuchi-Hirose, Miwa; Mori, Yuki; Yoshioka, Yoshichika; Murase, Kenya

    2013-09-01

    Cerebellar abnormalities in 4-week-old rats with a single whole body X-irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 were examined by magnetic resonance imaging (MRI) volumetry. A 3D T2 W-MRI anatomical sequence with high-spatial resolution at 11.7-tesla was acquired from the fixed rat heads. By MRI volumetry, whole cerebellar volumes decreased dose-dependently. Multiple linear regression analysis revealed that the cortical volume (standardized β=0.901; P<0.001) was a major explanatory variable for the whole cerebellar volume, whereas both volumes of the white matter and deep cerebellar nuclei also decreased depending on the X-irradiation dose. The present MRI volumetric analysis revealed a dose-related cerebellar cortical hypoplasia by prenatal exposure to X-irradiation on E15. © 2013 The Authors. Congenital Anomalies © 2013 Japanese Teratology Society.

  17. Multivariate Tensor-based Morphometry on Surfaces: Application to Mapping Ventricular Abnormalities in HIV/AIDS

    PubMed Central

    Wang, Yalin; Zhang, Jie; Gutman, Boris; Chan, Tony F.; Becker, James T.; Aizenstein, Howard J.; Lopez, Oscar L.; Tamburo, Robert J.; Toga, Arthur W.; Thompson, Paul M.

    2010-01-01

    Here we developed a new method, called multivariate tensor-based surface morphometry (TBM), and applied it to study lateral ventricular surface differences associated with HIV/AIDS. Using concepts from differential geometry and the theory of differential forms, we created mathematical structures known as holomorphic one-forms, to obtain an efficient and accurate conformal parameterization of the lateral ventricular surfaces in the brain. The new meshing approach also provides a natural way to register anatomical surfaces across subjects, and improves on prior methods as it handles surfaces that branch and join at complex 3D junctions. To analyze anatomical differences, we computed new statistics from the Riemannian surface metrics - these retain multivariate information on local surface geometry. We applied this framework to analyze lateral ventricular surface morphometry in 3D MRI data from 11 subjects with HIV/AIDS and 8 healthy controls. Our method detected a 3D profile of surface abnormalities even in this small sample. Multivariate statistics on the local tensors gave better effect sizes for detecting group differences, relative to other TBM-based methods including analysis of the Jacobian determinant, the largest and smallest eigenvalues of the surface metric, and the pair of eigenvalues of the Jacobian matrix. The resulting analysis pipeline may improve the power of surface-based morphometry studies of the brain. PMID:19900560

  18. Cerebro-cerebellar circuits in autism spectrum disorder.

    PubMed

    D'Mello, Anila M; Stoodley, Catherine J

    2015-01-01

    The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.

  19. Cerebro-cerebellar circuits in autism spectrum disorder

    PubMed Central

    D'Mello, Anila M.; Stoodley, Catherine J.

    2015-01-01

    The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD. PMID:26594140

  20. Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish.

    PubMed

    Aspatwar, Ashok; Tolvanen, Martti E E; Jokitalo, Eija; Parikka, Mataleena; Ortutay, Csaba; Harjula, Sanna-Kaisa E; Rämet, Mika; Vihinen, Mauno; Parkkila, Seppo

    2013-02-01

    Congenital ataxia and mental retardation are mainly caused by variations in the genes that affect brain development. Recent reports have shown that mutations in the CA8 gene are associated with mental retardation and ataxia in humans and ataxia in mice. The gene product, carbonic anhydrase-related protein VIII (CARP VIII), is predominantly present in cerebellar Purkinje cells, where it interacts with the inositol 1,4,5-trisphosphate receptor type 1, a calcium channel. In this study, we investigated the effects of the loss of function of CARP VIII during embryonic development in zebrafish using antisense morpholino oligonucleotides against the CA8 gene. Knockdown of CA8 in zebrafish larvae resulted in a curved body axis, pericardial edema and abnormal movement patterns. Histologic examination revealed gross morphologic defects in the cerebellar region and in the muscle. Electron microscopy studies showed increased neuronal cell death in developing larvae injected with CA8 antisense morpholinos. These data suggest a pivotal role for CARP VIII during embryonic development. Furthermore, suppression of CA8 expression leads to defects in motor and coordination functions, mimicking the ataxic human phenotype. This work reveals an evolutionarily conserved function of CARP VIII in brain development and introduces a novel zebrafish model in which to investigate the mechanisms of CARP VIII-related ataxia and mental retardation in humans.

  1. Feedforward and feedback motor control abnormalities implicate cerebellar dysfunctions in autism spectrum disorder.

    PubMed

    Mosconi, Matthew W; Mohanty, Suman; Greene, Rachel K; Cook, Edwin H; Vaillancourt, David E; Sweeney, John A

    2015-02-04

    Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and among the earliest manifestations of the disorder. They have been studied far less than the social-communication and cognitive deficits that define ASD, but a mechanistic understanding of sensorimotor abnormalities in ASD may provide key insights into the neural underpinnings of the disorder. In this human study, we examined rapid, precision grip force contractions to determine whether feedforward mechanisms supporting initial motor output before sensory feedback can be processed are disrupted in ASD. Sustained force contractions also were examined to determine whether reactive adjustments to ongoing motor behavior based on visual feedback are altered. Sustained force was studied across multiple force levels and visual gains to assess motor and visuomotor mechanisms, respectively. Primary force contractions of individuals with ASD showed greater peak rate of force increases and large transient overshoots. Individuals with ASD also showed increased sustained force variability that scaled with force level and was more severe when visual gain was highly amplified or highly degraded. When sustaining a constant force level, their reactive adjustments were more periodic than controls, and they showed increased reliance on slower feedback mechanisms. Feedforward and feedback mechanism alterations each were associated with more severe social-communication impairments in ASD. These findings implicate anterior cerebellar circuits involved in feedforward motor control and posterior cerebellar circuits involved in transforming visual feedback into precise motor adjustments in ASD. Copyright © 2015 the authors 0270-6474/15/352015-11$15.00/0.

  2. Feedforward and Feedback Motor Control Abnormalities Implicate Cerebellar Dysfunctions in Autism Spectrum Disorder

    PubMed Central

    Mohanty, Suman; Greene, Rachel K.; Cook, Edwin H.; Vaillancourt, David E.; Sweeney, John A.

    2015-01-01

    Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and among the earliest manifestations of the disorder. They have been studied far less than the social-communication and cognitive deficits that define ASD, but a mechanistic understanding of sensorimotor abnormalities in ASD may provide key insights into the neural underpinnings of the disorder. In this human study, we examined rapid, precision grip force contractions to determine whether feedforward mechanisms supporting initial motor output before sensory feedback can be processed are disrupted in ASD. Sustained force contractions also were examined to determine whether reactive adjustments to ongoing motor behavior based on visual feedback are altered. Sustained force was studied across multiple force levels and visual gains to assess motor and visuomotor mechanisms, respectively. Primary force contractions of individuals with ASD showed greater peak rate of force increases and large transient overshoots. Individuals with ASD also showed increased sustained force variability that scaled with force level and was more severe when visual gain was highly amplified or highly degraded. When sustaining a constant force level, their reactive adjustments were more periodic than controls, and they showed increased reliance on slower feedback mechanisms. Feedforward and feedback mechanism alterations each were associated with more severe social-communication impairments in ASD. These findings implicate anterior cerebellar circuits involved in feedforward motor control and posterior cerebellar circuits involved in transforming visual feedback into precise motor adjustments in ASD. PMID:25653359

  3. Bidirectional Causal Connectivity in the Cortico-Limbic-Cerebellar Circuit Related to Structural Alterations in First-Episode, Drug-Naive Somatization Disorder

    PubMed Central

    Li, Ranran; Liu, Feng; Su, Qinji; Zhang, Zhikun; Zhao, Jin; Wang, Ying; Wu, Renrong; Zhao, Jingping; Guo, Wenbin

    2018-01-01

    Background: Anatomical and functional deficits in the cortico-limbic-cerebellar circuit are involved in the neurobiology of somatization disorder (SD). The present study was performed to examine causal connectivity of the cortico-limbic-cerebellar circuit related to structural deficits in first-episode, drug-naive patients with SD at rest. Methods: A total of 25 first-episode, drug-naive patients with SD and 28 healthy controls underwent structural and resting-state functional magnetic resonance imaging. Voxel-based morphometry and Granger causality analysis (GCA) were used to analyze the data. Results: Results showed that patients with SD exhibited decreased gray matter volume (GMV) in the right cerebellum Crus I, and increased GMV in the left anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left angular gyrus. Causal connectivity of the cortico-limbic-cerebellar circuit was partly affected by structural alterations in the patients. Patients with SD showed bidirectional cortico-limbic connectivity abnormalities and bidirectional cortico-cerebellar and limbic-cerebellar connectivity abnormalities. The mean GMV of the right MFG was negatively correlated with the scores of the somatization subscale of the symptom checklist-90 and persistent error response of the Wisconsin Card Sorting Test (WCST) in the patients. A negative correlation was observed between increased driving connectivity from the right MFG to the right fusiform gyrus/cerebellum IV, V and the scores of the Eysenck Personality Questionnaire extraversion subscale. The mean GMV of the left ACC was negatively correlated with the WCST number of errors and persistent error response. Negative correlation was found between the causal effect from the left ACC to the right middle temporal gyrus and the scores of WCST number of categories achieved. Conclusions: Our findings show the partial effects of structural alterations on the cortico-limbic-cerebellar circuit in first-episode, drug

  4. Voxel-based morphometry in creative writers: Gray-matter increase in a prefronto-thalamic-cerebellar network.

    PubMed

    Neumann, Nicola; Domin, Martin; Erhard, Katharina; Lotze, Martin

    2018-05-18

    Continuous practice modulates those features of brain anatomy specifically associated with requirements of the respective training task. The current study aimed to highlight brain structural changes going along with long-term experience in creative writing. To this end, we investigated the gray-matter volume of 23 expert writers with voxel-based morphometry and compared it to 28 matched non-expert controls. Expert writers had higher gray-matter volume in the right superior frontal and middle frontal gyri (BA 9,10) as well as left middle frontal gyrus (BA 9, 10, 46), the bilateral medial dorsal nuclei of the thalamus and left posterior cerebellum. A regression analysis confirmed the association of enhanced gray-matter volume in the right superior frontal gyrus (BA 10) with practice index of writing. In region-of interest based regression analyses, we found associations of gray-matter volume in the right Broca's analogue (BA 44) and right primary visual cortex (BA 17) with creativity ratings of the texts written during scanning, but not with a standardized verbal creativity test. Creative writing thus seems to be strongly connected to a prefronto-thalamic-cerebellar network that supports the continuous generation, organization and revision of ideas that is necessary to write literary texts. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Cerebellar mutism syndrome and its relation to cerebellar cognitive and affective function: Review of the literature

    PubMed Central

    Yildiz, Ozlem; Kabatas, Serdar; Yilmaz, Cem; Altinors, Nur; Agaoglu, Belma

    2010-01-01

    Tumors of the cerebellum and brainstem account for half of all brain tumors in children. The realization that cerebellar lesions produce clinically relevant intellectual disability makes it important to determine whether neuropsychological abnormalities occur in long-term survivors of pediatric cerebellar tumors. Little is known about the neurobehavioral sequale resulting specifically from the resection of these tumors in this population. We therefore reviewed neuropsychological findings associated with postoperative cerebellar mutism syndrome and discuss the further implications for cerebellar cognitive function. PMID:20436742

  6. MRI Evidence of Cerebellar and Extraocular Muscle Atrophy Differently Contributing to Eye Movement Abnormalities in SCA2 and SCA28 Diseases.

    PubMed

    Politi, Letterio Salvatore; Bianchi Marzoli, Stefania; Godi, Claudia; Panzeri, Marta; Ciasca, Paola; Brugnara, Gianluca; Castaldo, Anna; Di Bella, Daniela; Taroni, Franco; Nanetti, Lorenzo; Mariotti, Caterina

    2016-05-01

    Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P < 0.03), and in SCA2 subjects compared with SCA28 (P < 0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P < 0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P < 0.002), and 14% to 36% smaller compared with SCA2 subjects (P < 0.03). Extraocular muscle areas did not differ between SCA2 and controls. Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism.

  7. Directional abnormalities of vestibular and optokinetic responses in cerebellar disease

    NASA Technical Reports Server (NTRS)

    Walker, M. F.; Zee, D. S.; Shelhamer, M. J. (Principal Investigator)

    1999-01-01

    Directional abnormalities of vestibular and optokinetic responses in patients with cerebellar degeneration are reported. Three-axis magnetic search-coil recordings of the eye and head were performed in eight cerebellar patients. Among these patients, examples of directional cross-coupling were found during (1) high-frequency, high-acceleration head thrusts; (2) constant-velocity chair rotations with the head fixed; (3) constant-velocity optokinetic stimulation; and (4) following repetitive head shaking. Cross-coupling during horizontal head thrusts consisted of an inappropriate upward eye-velocity component. In some patients, sustained constant-velocity yaw-axis chair rotations produced a mixed horizontal-torsional nystagmus and/or an increase in the baseline vertical slow-phase velocity. Following horizontal head shaking, some patients showed an increase in the slow-phase velocity of their downbeat nystagmus. These various forms of cross-coupling did not necessarily occur to the same degree in a given patient; this suggests that different mechanisms may be responsible. It is suggested that cross-coupling during head thrusts may reflect a loss of calibration of brainstem connections involved in the direct vestibular pathways, perhaps due to dysfunction of the flocculus. Cross-coupling during constant-velocity rotations and following head shaking may result from a misorientation of the angular eye-velocity vector in the velocity-storage system. Finally, responses to horizontal optokinetic stimulation included an inappropriate torsional component in some patients. This suggests that the underlying organization of horizontal optokinetic tracking is in labyrinthine coordinates. The findings are also consistent with prior animal-lesion studies that have shown a role for the vestibulocerebellum in the control of the direction of the VOR.

  8. Postural Ataxia in Cerebellar Downbeat Nystagmus: Its Relation to Visual, Proprioceptive and Vestibular Signals and Cerebellar Atrophy.

    PubMed

    Helmchen, Christoph; Kirchhoff, Jan-Birger; Göttlich, Martin; Sprenger, Andreas

    2017-01-01

    The cerebellum integrates proprioceptive, vestibular and visual signals for postural control. Cerebellar patients with downbeat nystagmus (DBN) complain of unsteadiness of stance and gait as well as blurred vision and oscillopsia. The aim of this study was to elucidate the differential role of visual input, gaze eccentricity, vestibular and proprioceptive input on the postural stability in a large cohort of cerebellar patients with DBN, in comparison to healthy age-matched control subjects. Oculomotor (nystagmus, smooth pursuit eye movements) and postural (postural sway speed) parameters were recorded and related to each other and volumetric changes of the cerebellum (voxel-based morphometry, SPM). Twenty-seven patients showed larger postural instability in all experimental conditions. Postural sway increased with nystagmus in the eyes closed condition but not with the eyes open. Romberg's ratio remained stable and was not different from healthy controls. Postural sway did not change with gaze position or graviceptive input. It increased with attenuated proprioceptive input and on tandem stance in both groups but Romberg's ratio also did not differ. Cerebellar atrophy (vermal lobule VI, VIII) correlated with the severity of impaired smooth pursuit eye movements of DBN patients. Postural ataxia of cerebellar patients with DBN cannot be explained by impaired visual feedback. Despite oscillopsia visual feedback control on cerebellar postural control seems to be preserved as postural sway was strongest on visual deprivation. The increase in postural ataxia is neither related to modulations of single components characterizing nystagmus nor to deprivation of single sensory (visual, proprioceptive) inputs usually stabilizing stance. Re-weighting of multisensory signals and/or inappropriate cerebellar motor commands might account for this postural ataxia.

  9. Postural Ataxia in Cerebellar Downbeat Nystagmus: Its Relation to Visual, Proprioceptive and Vestibular Signals and Cerebellar Atrophy

    PubMed Central

    Helmchen, Christoph; Kirchhoff, Jan-Birger; Göttlich, Martin; Sprenger, Andreas

    2017-01-01

    Background The cerebellum integrates proprioceptive, vestibular and visual signals for postural control. Cerebellar patients with downbeat nystagmus (DBN) complain of unsteadiness of stance and gait as well as blurred vision and oscillopsia. Objectives The aim of this study was to elucidate the differential role of visual input, gaze eccentricity, vestibular and proprioceptive input on the postural stability in a large cohort of cerebellar patients with DBN, in comparison to healthy age-matched control subjects. Methods Oculomotor (nystagmus, smooth pursuit eye movements) and postural (postural sway speed) parameters were recorded and related to each other and volumetric changes of the cerebellum (voxel-based morphometry, SPM). Results Twenty-seven patients showed larger postural instability in all experimental conditions. Postural sway increased with nystagmus in the eyes closed condition but not with the eyes open. Romberg’s ratio remained stable and was not different from healthy controls. Postural sway did not change with gaze position or graviceptive input. It increased with attenuated proprioceptive input and on tandem stance in both groups but Romberg’s ratio also did not differ. Cerebellar atrophy (vermal lobule VI, VIII) correlated with the severity of impaired smooth pursuit eye movements of DBN patients. Conclusions Postural ataxia of cerebellar patients with DBN cannot be explained by impaired visual feedback. Despite oscillopsia visual feedback control on cerebellar postural control seems to be preserved as postural sway was strongest on visual deprivation. The increase in postural ataxia is neither related to modulations of single components characterizing nystagmus nor to deprivation of single sensory (visual, proprioceptive) inputs usually stabilizing stance. Re-weighting of multisensory signals and/or inappropriate cerebellar motor commands might account for this postural ataxia. PMID:28056109

  10. Cerebellar gray matter and lobular volumes correlate with core autism symptoms

    PubMed Central

    D'Mello, Anila M.; Crocetti, Deana; Mostofsky, Stewart H.; Stoodley, Catherine J.

    2015-01-01

    Neuroanatomical differences in the cerebellum are among the most consistent findings in autism spectrum disorder (ASD), but little is known about the relationship between cerebellar dysfunction and core ASD symptoms. The newly-emerging existence of cerebellar sensorimotor and cognitive subregions provides a new framework for interpreting the functional significance of cerebellar findings in ASD. Here we use two complementary analyses — whole-brain voxel-based morphometry (VBM) and the SUIT cerebellar atlas — to investigate cerebellar regional gray matter (GM) and volumetric lobular measurements in 35 children with ASD and 35 typically-developing (TD) children (mean age 10.4 ± 1.6 years; range 8–13 years). To examine the relationships between cerebellar structure and core ASD symptoms, correlations were calculated between scores on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors. Structural differences and behavioral correlations converged on right cerebellar Crus I/II, a region which shows structural and functional connectivity with fronto-parietal and default mode networks. These results emphasize the importance of the location within the cerebellum to the potential functional impact of structural differences in ASD, and suggest that GM differences in cerebellar right Crus I/II are associated with the core ASD profile. PMID:25844317

  11. Cerebellar mutism--report of four cases.

    PubMed

    Ozimek, A; Richter, S; Hein-Kropp, C; Schoch, B; Gorissen, B; Kaiser, O; Gizewski, E; Ziegler, W; Timmann, D

    2004-08-01

    The aim of the present study was to investigate the manifestations of mutism after surgery in children with cerebellar tumors. Speech impairment following cerebellar mutism in children was investigated based on standardized acoustic speech parameters and perceptual criteria. Mutistic and non-mutistic children after cerebellar surgery as well as orthopedic controls were tested pre-and postoperatively. Speech impairment was compared with the localization of cerebellar lesions (i. e. affected lobules and nuclei). Whereas both control groups showed no abnormalities in speech and behavior, the mutistic group could be divided into children with dysarthria in post mutistic phase and children with mainly behavioral disturbances. In the mutistic children involvement of dentate and fastigial nuclei tended to be more frequent and extended than in the nonmutistic cerebellar children. Cerebellar mutism is a complex phenomenon of at least two types. Dysarthric symptoms during resolution of mutism support the anarthria hypothesis, while mainly behavioral changes suggest an explanation independent from speech motor control.

  12. Cerebellar Hypoplasia and Dysmorphia in Neurofibromatosis Type 1.

    PubMed

    Toelle, Sandra P; Poretti, Andrea; Weber, Peter; Seute, Tatjana; Bromberg, Jacoline E C; Scheer, Ianina; Boltshauser, Eugen

    2015-12-01

    Unidentified bright objects (UBO) and tumors are well-known cerebellar abnormalities in neurofibromatosis type 1 (NF1). Literature reports on malformative cerebellar anomalies in neurofibromatosis type 1 (NF1), however, are scant. We retrospectively studied the clinical and neuroimaging findings of 5 patients with NF1 (4 females, age 6 to 29 years at last follow-up) and cerebellar anomalies. Cerebellar symptoms on neurological examination were mild or even not evident whereas learning disabilities were more or less pronounced in four patients. Two patients had cerebellar hypoplasia (diffusely enlarged cerebellar interfoliar spaces) and three cerebellar dysmorphias involving mainly one cerebellar hemisphere. In NF1, malformative cerebellar anomalies are rare (estimated prevalence of about 1%), but most likely underestimated and easily overlooked, because physicians tend to focus on more prevalent, obvious, and well-known findings such as optic pathway gliomas, other tumors, and UBO. This kind of cerebellar anomaly in NF1 has most likely a malformative origin, but the exact pathogenesis is unknown. The individual clinical significance is difficult to determine. We suggest that cerebellar anomalies should be systematically evaluated in neuroimaging studies of NF1 patients.

  13. Improved segmentation of cerebellar structures in children

    PubMed Central

    Narayanan, Priya Lakshmi; Boonazier, Natalie; Warton, Christopher; Molteno, Christopher D; Joseph, Jesuchristopher; Jacobson, Joseph L; Jacobson, Sandra W; Zöllei, Lilla; Meintjes, Ernesta M

    2016-01-01

    Background Consistent localization of cerebellar cortex in a standard coordinate system is important for functional studies and detection of anatomical alterations in studies of morphometry. To date, no pediatric cerebellar atlas is available. New method The probabilistic Cape Town Pediatric Cerebellar Atlas (CAPCA18) was constructed in the age-appropriate National Institute of Health Pediatric Database asymmetric template space using manual tracings of 16 cerebellar compartments in 18 healthy children (9–13 years) from Cape Town, South Africa. The individual atlases of the training subjects were also used to implement multi atlas label fusion using multi atlas majority voting (MAMV) and multi atlas generative model (MAGM) approaches. Segmentation accuracy in 14 test subjects was compared for each method to ‘gold standard’ manual tracings. Results Spatial overlap between manual tracings and CAPCA18 automated segmentation was 73% or higher for all lobules in both hemispheres, except VIIb and X. Automated segmentation using MAGM yielded the best segmentation accuracy over all lobules (mean Dice Similarity Coefficient 0.76; range 0.55–0.91). Comparison with existing methods In all lobules, spatial overlap of CAPCA18 segmentations with manual tracings was similar or higher than those obtained with SUIT (spatially unbiased infra-tentorial template), providing additional evidence of the benefits of an age appropriate atlas. MAGM segmentation accuracy was comparable to values reported recently by Park et al. (2014) in adults (across all lobules mean DSC = 0.73, range 0.40–0.89). Conclusions CAPCA18 and the associated multi atlases of the training subjects yield improved segmentation of cerebellar structures in children. PMID:26743973

  14. Altered soleus responses to magnetic stimulation in pure cerebellar ataxia.

    PubMed

    Kurokawa-Kuroda, Tomomi; Ogata, Katsuya; Suga, Rie; Goto, Yoshinobu; Taniwaki, Takayuki; Kira, Jun-Ichi; Tobimatsu, Shozo

    2007-06-01

    Transcranial magnetic stimulation (TMS) over the leg motor area elicits a soleus primary response (SPR) and a soleus late response (SLR). We evaluated the influence of the cerebellofugal pathway on the SPR and SLR in patients with 'pure' cerebellar ataxia. SPRs and SLRs were recorded from 11 healthy subjects and 9 patients with 'pure' cerebellar cortical degeneration; 5 with spinocerebellar ataxia type 6 (SCA6), and 4 with late cortical cerebellar ataxia (LCCA). In addition, three patients with localized cerebellar lesions were tested. The SPR latency was significantly longer in patients than in controls, but primary responses in the tibialis anterior muscle were normal. The frequency of abnormal SLR was 38.9% in the supine position and 83.3% in the standing position. Two out of three patients with localized cerebellar lesions also showed abnormal SLR. Altered SPRs in patients may result from a dysfunction of the primary motor cortex caused by crossed cerebello-cerebral diaschisis. In addition, our results suggest that 'pure' cerebellar degeneration involves the mechanism responsible for evoking SLR which is related to the control of posture. SLR can be a useful neurophysiological parameter for evaluating cerebellofugal function.

  15. Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

    PubMed Central

    Wagshal, Dana; Knowlton, Barbara Jean; Cohen, Jessica Rachel; Bookheimer, Susan Yost; Bilder, Robert Martin; Fernandez, Vindia Gisela; Asarnow, Robert Franklin

    2015-01-01

    Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplored is corticostriatal dysfunction. The corticostriatal system plays an important role in skill learning. Our previous studies have demonstrated corticostriatal dysfunction in COS siblings with a profound skill learning deficit and abnormal pattern of brain activation during skill learning. This study investigated whether structural abnormalities measured using volumetric brain morphometry (VBM) were present in siblings of COS patients and whether these were related to deficits in cognitive skill learning. Results revealed smaller GM volume in COS siblings relative to controls in a number of regions, including occipital, parietal, and subcortical regions including the striatum, and greater GM volume relative to controls in several subcortical regions. Volume in the right superior frontal gyrus and cerebellum were related to performance differences between groups on the weather prediction task, a measure of cognitive skill learning. Our results support the idea that corticostriatal and cerebellar impairment in unaffected siblings of COS patients are behaviorally relevant and may reflect genetic risk for schizophrenia. PMID:25541139

  16. Cerebellar Influence on Motor Cortex Plasticity: Behavioral Implications for Parkinson’s Disease

    PubMed Central

    Kishore, Asha; Meunier, Sabine; Popa, Traian

    2014-01-01

    Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration, and normal functioning of these networks. Strong topography-specific connections among the basal ganglia, cerebellum, and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other’s plastic responses and functions. The defective striatal signaling in Parkinson’s disease (PD) could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar, and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD. PMID:24834063

  17. Gaze failure, drifting eye movements, and centripetal nystagmus in cerebellar disease.

    PubMed Central

    Leech, J; Gresty, M; Hess, K; Rudge, P

    1977-01-01

    Three abnormalities of eye movement in man are described which are indicative of cerebellar system disorder, namely, centripetally beating nystagmus, failure to maintain lateral gaze either in darkness or with eye closure, and slow drifting movements of the eyes in the absence of fixation. Similar eye movement signs follow cerebellectomy in the primate and the cat. These abnormalities of eye movement, together with other signs of cerebellar disease, such as rebound alternating, and gaze paretic nystagmus, are explained by the hypothesis that the cerebellum helps to maintain lateral gaze and that brain stem mechanisms which monitor gaze position generate compensatory biases in the absence of normal cerebellar function. PMID:603785

  18. Abnormal cerebellar development and Purkinje cell defects in Lgl1-Pax2 conditional knockout mice.

    PubMed

    Hou, Congzhe; Ding, Lingcui; Zhang, Jian; Jin, Yecheng; Sun, Chen; Li, Zhenzu; Sun, Xiaoyang; Zhang, Tingting; Zhang, Aizhen; Li, Huashun; Gao, Jiangang

    2014-11-01

    Lgl1 was initially identified as a tumour suppressor in flies and is characterised as a key regulator of epithelial polarity and asymmetric cell division. A previous study indicated that More-Cre-mediated Lgl1 knockout mice exhibited significant brain dysplasia and died within 24h after birth. To overcome early neonatal lethality, we generated Lgl1 conditional knockout mice mediated by Pax2-Cre, which is expressed in almost all cells in the cerebellum, and we examined the functions of Lgl1 in the cerebellum. Impaired motor coordination was detected in the mutant mice. Consistent with this abnormal behaviour, homozygous mice possessed a smaller cerebellum with fewer lobes, reduced granule precursor cell (GPC) proliferation, decreased Purkinje cell (PC) quantity and dendritic dysplasia. Loss of Lgl1 in the cerebellum led to hyperproliferation and impaired differentiation of neural progenitors in ventricular zone. Based on the TUNEL assay, we observed increased apoptosis in the cerebellum of mutant mice. We proposed that impaired differentiation and increased apoptosis may contribute to decreased PC quantity. To clarify the effect of Lgl1 on cerebellar granule cells, we used Math1-Cre to specifically delete Lgl1 in granule cells. Interestingly, the Lgl1-Math1 conditional knockout mice exhibited normal proliferation of GPCs and cerebellar development. Thus, we speculated that the reduction in the proliferation of GPCs in Lgl1-Pax2 conditional knockout mice may be secondary to the decreased number of PCs, which secrete the mitogenic factor Sonic hedgehog to regulate GPC proliferation. Taken together, these findings suggest that Lgl1 plays a key role in cerebellar development and folia formation by regulating the development of PCs. Copyright © 2014. Published by Elsevier Inc.

  19. Altered cerebellar feedback projections in Asperger syndrome.

    PubMed

    Catani, Marco; Jones, Derek K; Daly, Eileen; Embiricos, Nitzia; Deeley, Quinton; Pugliese, Luca; Curran, Sarah; Robertson, Dene; Murphy, Declan G M

    2008-07-15

    It has been proposed that the biological basis of autism spectrum disorder includes cerebellar 'disconnection'. However, direct in vivo evidence in support of this is lacking. Here, the microstructural integrity of cerebellar white matter in adults with Asperger syndrome was studied using diffusion tensor magnetic resonance tractography. Fifteen adults with Asperger syndrome and 16 age-IQ-gender-matched healthy controls underwent diffusion tensor magnetic resonance imaging. For each subject, tract-specific measurements of mean diffusivity and fractional anisotropy were made within the inferior, middle, superior cerebellar peduncles and short intracerebellar fibres. No group differences were observed in mean diffusivity. However, people with Asperger syndrome had significantly lower fractional anisotropy in the short intracerebellar fibres (p<0.001) and right superior cerebellar (output) peduncle (p<0.001) compared to controls; but no difference in the input tracts. Severity of social impairment, as measured by the Autistic Diagnostic Interview, was negatively correlated with diffusion anisotropy in the fibres of the left superior cerebellar peduncle. These findings suggest a vulnerability of specific cerebellar neural pathways in people with Asperger syndrome. The localised abnormalities in the main cerebellar outflow pathway may prevent the cerebral cortex from receiving those cerebellar feedback inputs necessary for a successful adaptive social behaviour.

  20. Parvovirus associated cerebellar hypoplasia and hydrocephalus in day-old broiler chickens

    USDA-ARS?s Scientific Manuscript database

    Cerebellar hypoplasia and hydrocephalus were detected in day-old broiler chickens. Brains of chickens evaluated at necropsy appeared to be abnormal; some were disfigured and cerebellae appeared to be smaller than normal. Histopathologic examination of brains revealed cerebellar folia that were sho...

  1. Postoperative cerebellar mutism and autistic spectrum disorder.

    PubMed

    Tasdemiroğlu, Erol; Kaya, Miktat; Yildirim, Can Hakan; Firat, Levent

    2011-06-01

    I read the article "An Inside View of Autism" written by a 44-year-old autistic woman who had a successful international career designing livestock equipment. In this article, she wrote about her life, disease, and experiences as an autistic individual. She stated that "It is interesting that my speech resembled the stressed speech in young children who have had tumors removed from the cerebellum". In this article, we intend to review and extensively document both postoperative cerebellar mutism and autistic spectrum disorder. We reviewed the clinical and neurological findings, etio-pathogenesis, neuroanatomy, mechanisms of development, and similarities between the etio-pathogenesis of both diseases. Cerebellar lesions can produce mutism and dysarthria, symptoms sometimes seen in autistic spectrum disorder. In mammals, cerebellar lesions disturb motivated behavior and reduce social interactions, functions that are disturbed in autistic spectrum disorder and cerebellar mutism. The cerebellum and two regions within the frontal lobes are active in certain language tasks. Language is abnormal in autistic spectrum disorder and cerebellar mutism.

  2. Cerebellar Ataxia, Seizures, Premature Death, and Cardiac Abnormalities in Mice with Targeted Disruption of the Cacna2d2 Gene

    PubMed Central

    Ivanov, Sergey V.; Ward, Jerrold M.; Tessarollo, Lino; McAreavey, Dorothea; Sachdev, Vandana; Fananapazir, Lameh; Banks, Melissa K.; Morris, Nicole; Djurickovic, Draginja; Devor-Henneman, Deborah E.; Wei, Ming-Hui; Alvord, Gregory W.; Gao, Boning; Richardson, James A.; Minna, John D.; Rogawski, Michael A.; Lerman, Michael I.

    2004-01-01

    CACNA2D2 is a putative tumor suppressor gene located in the human chromosome 3p21.3 region that shows frequent allelic imbalances in lung, breast, and other cancers. The α2δ-2 protein encoded by the gene is a regulatory subunit of voltage-dependent calcium channels and is expressed in brain, heart, and other tissues. Here we report that mice homozygous for targeted disruption of the Cacna2d2 gene exhibit growth retardation, reduced life span, ataxic gait with apoptosis of cerebellar granule cells followed by Purkinje cell depletion, enhanced susceptibility to seizures, and cardiac abnormalities. The Cacna2d2tm1NCIF null phenotype has much in common with that of Cacna1a mutants, such as cerebellar neuro-degeneration associated with ataxia, seizures, and premature death. A tendency to bradycardia and limited response of null mutants to isoflurane implicate α2δ-2 in sympathetic regulation of cardiac function. In summary, our findings provide genetic evidence that the α2δ-2 subunit serves in vivo as a component of P/Q-type calcium channels, is indispensable for the central nervous system function, and may be involved in hereditary cerebellar ataxias and epileptic disorders in humans. PMID:15331424

  3. Studying ventricular abnormalities in mild cognitive impairment with hyperbolic Ricci flow and tensor-based morphometry.

    PubMed

    Shi, Jie; Stonnington, Cynthia M; Thompson, Paul M; Chen, Kewei; Gutman, Boris; Reschke, Cole; Baxter, Leslie C; Reiman, Eric M; Caselli, Richard J; Wang, Yalin

    2015-01-01

    Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer's disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. STUDYING VENTRICULAR ABNORMALITIES IN MILD COGNITIVE IMPAIRMENT WITH HYPERBOLIC RICCI FLOW AND TENSOR-BASED MORPHOMETRY

    PubMed Central

    Shi, Jie; Stonnington, Cynthia M.; Thompson, Paul M.; Chen, Kewei; Gutman, Boris; Reschke, Cole; Baxter, Leslie C.; Reiman, Eric M.; Caselli, Richard J.; Wang, Yalin

    2014-01-01

    Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer’s disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD. PMID:25285374

  5. Hypothermia-induced dystonia and abnormal cerebellar activity in a mouse model with a single disease-mutation in the sodium-potassium pump

    PubMed Central

    Isaksen, Toke Jost; Vedovato, Natascia; Vitenzon, Ariel; Gadsby, David C.; Khodakhah, Kamran

    2017-01-01

    Mutations in the neuron-specific α3 isoform of the Na+/K+-ATPase are found in patients suffering from Rapid onset Dystonia Parkinsonism and Alternating Hemiplegia of Childhood, two closely related movement disorders. We show that mice harboring a heterozygous hot spot disease mutation, D801Y (α3+/D801Y), suffer abrupt hypothermia-induced dystonia identified by electromyographic recordings. Single-neuron in vivo recordings in awake α3+/D801Y mice revealed irregular firing of Purkinje cells and their synaptic targets, the deep cerebellar nuclei neurons, which was further exacerbated during dystonia and evolved into abnormal high-frequency burst-like firing. Biophysically, we show that the D-to-Y mutation abolished pump-mediated Na+/K+ exchange, but allowed the pumps to bind Na+ and become phosphorylated. These findings implicate aberrant cerebellar activity in α3 isoform-related dystonia and add to the functional understanding of the scarce and severe mutations in the α3 isoform Na+/K+-ATPase. PMID:28472154

  6. Lissencephaly with brainstem and cerebellar hypoplasia and congenital cataracts.

    PubMed

    Abumansour, Iman S; Wrogemann, Jens; Chudley, Albert E; Chodirker, Bernard N; Salman, Michael S

    2014-06-01

    Classical lissencephaly may be associated with cerebellar hypoplasia and when significant cerebellar abnormalities occur, defects in proteins encoded by TUBA1A, RELN, and very-low-density lipoprotein receptor (VLDLR) genes have been reported. We present a neonate with a severe neurologic phenotype associated with hypotonia, oropharyngeal incoordination that required a gastric tube for feeding, intractable epilepsy, and congenital cataracts. Her brain magnetic resonance imaging (MRI) showed classical lissencephaly, ventriculomegaly, absent corpus callosum, globular and vertical hippocampi, and severe cerebellar and brainstem hypoplasia. She died at 6 weeks of age. No specific molecular diagnosis was made. This likely represents a previously undescribed genetic lissencephaly syndrome. © The Author(s) 2013.

  7. Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome.

    PubMed

    Kumar, Rajesh; Macey, Paul M; Woo, Mary A; Alger, Jeffry R; Harper, Ronald M

    2008-09-01

    Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely axial diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and axial and radial diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphé, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.

  8. Dyslexic Children Show Atypical Cerebellar Activation and Cerebro-Cerebellar Functional Connectivity in Orthographic and Phonological Processing.

    PubMed

    Feng, Xiaoxia; Li, Le; Zhang, Manli; Yang, Xiujie; Tian, Mengyu; Xie, Weiyi; Lu, Yao; Liu, Li; Bélanger, Nathalie N; Meng, Xiangzhi; Ding, Guosheng

    2017-04-01

    Previous neuroimaging studies have found atypical cerebellar activation in individuals with dyslexia in either motor-related tasks or language tasks. However, studies investigating atypical cerebellar activation in individuals with dyslexia have mostly used tasks tapping phonological processing. A question that is yet unanswered is whether the cerebellum in individuals with dyslexia functions properly during orthographic processing of words, as growing evidence shows that the cerebellum is also involved in visual and spatial processing. Here, we investigated cerebellar activation and cerebro-cerebellar functional connectivity during word processing in dyslexic readers and typically developing readers using tasks that tap orthographic and phonological codes. In children with dyslexia, we observed an abnormally higher engagement of the bilateral cerebellum for the orthographic task, which was negatively correlated with literacy measures. The greater the reading impairment was for young dyslexic readers, the stronger the cerebellar activation was. This suggests a compensatory role of the cerebellum in reading for children with dyslexia. In addition, a tendency for higher cerebellar activation in dyslexic readers was found in the phonological task. Moreover, the functional connectivity was stronger for dyslexic readers relative to typically developing readers between the lobule VI of the right cerebellum and the left fusiform gyrus during the orthographic task and between the lobule VI of the left cerebellum and the left supramarginal gyrus during the phonological task. This pattern of results suggests that the cerebellum compensates for reading impairment through the connections with specific brain regions responsible for the ongoing reading task. These findings enhance our understanding of the cerebellum's involvement in reading and reading impairment.

  9. Use of diffusion tensor imaging to identify similarities and differences between cerebellar and Parkinsonism forms of multiple system atrophy.

    PubMed

    Wang, Po-Shan; Wu, Hsiu-Mei; Lin, Ching-Po; Soong, Bing-Wen

    2011-07-01

    We performed diffusion tensor imaging to determine if multiple system atrophy (MSA)-cerebellar (C) and MSA-Parkinsonism (P) show similar changes, as shown in pathological studies. Nineteen patients with MSA-C, 12 patients with MSA-P, 20 patients with Parkinson disease, and 20 healthy controls were evaluated with the use of voxel-based morphometry analysis of diffusion tensor imaging. There was an increase in apparent diffusion coefficient values in the middle cerebellar peduncles and cerebellum and a decrease in fractional anisotropy in the pyramidal tract, middle cerebellar peduncles, and white matter of the cerebellum in patients with MSA-C and MSA-P compared to the controls (P < 0.001). In addition, isotropic diffusion-weighted image values were reduced in the cerebellar cortex and deep cerebellar nuclei in patients with MSA-C and increased in the basal ganglia in patients with MSA-P. These results indicate that despite their disparate clinical manifestations, patients with MSA-C and MSA-P share similar diffusion tensor imaging features in the infratentorial region. Further, the combination of FA, ADC and iDWI images can be used to distinguish between MSA (either form) and Parkinson disease, which has potential therapeutic implications.

  10. Aberrant cerebellar connectivity in bipolar disorder with psychosis.

    PubMed

    Shinn, Ann K; Roh, Youkyung S; Ravichandran, Caitlin T; Baker, Justin T; Öngür, Dost; Cohen, Bruce M

    2017-07-01

    The cerebellum, which modulates affect and cognition in addition to motor functions, may contribute substantially to the pathophysiology of mood and psychotic disorders, such as bipolar disorder. A growing literature points to cerebellar abnormalities in bipolar disorder. However, no studies have investigated the topographic representations of resting state cerebellar networks in bipolar disorder, specifically their functional connectivity to cerebral cortical networks. Using a well-defined cerebral cortical parcellation scheme as functional connectivity seeds, we compared ten cerebellar resting state networks in 49 patients with bipolar disorder and a lifetime history of psychotic features and 55 healthy control participants matched for age, sex, and image signal-to-noise ratio. Patients with psychotic bipolar disorder showed reduced cerebro-cerebellar functional connectivity in somatomotor A, ventral attention, salience, and frontoparietal control A and B networks relative to healthy control participants. These findings were not significantly correlated with current symptoms. Patients with psychotic bipolar disorder showed evidence of cerebro-cerebellar dysconnectivity in selective networks. These disease-related changes were substantial and not explained by medication exposure or substance use. Therefore, they may be mechanistically relevant to the underlying susceptibility to mood dysregulation and psychosis. Cerebellar mechanisms deserve further exploration in psychiatric conditions, and this study's findings may have value in guiding future studies on pathophysiology and treatment of mood and psychotic disorders, in particular.

  11. Cerebellar contribution to locomotor behavior: A neurodevelopmental perspective.

    PubMed

    Sathyanesan, Aaron; Gallo, Vittorio

    2018-04-30

    The developmental trajectory of the formation of cerebellar circuitry has significant implications for locomotor plasticity and adaptive learning at later stages. While there is a wealth of knowledge on the development of locomotor behavior in human infants, children, and adolescents, pre-clinical animal models have fallen behind on the study of the emergence of behavioral motifs in locomotor function across postnatal development. Since cerebellar development is protracted, it is subject to higher risk of genetic or environmental disruption, potentially leading to abnormal behavioral development. This highlights the need for more sophisticated and specific functional analyses of adaptive cerebellar behavior within the context of whole-body locomotion across the entire span of postnatal development. Here we review evidence on cerebellar contribution to adaptive locomotor behavior, highlighting methodologies employed to quantify and categorize behavior at different developmental stages, with the ultimate goal of following the course of early behavioral alterations in neurodevelopmental disorders. Since experimental paradigms used to study cerebellar behavior are lacking in both specificity and applicability to locomotor contexts, we highlight the use of the Erasmus Ladder - an advanced, computerized, fully automated system to quantify adaptive cerebellar learning in conjunction with locomotor function. Finally, we emphasize the need to develop objective, quantitative, behavioral tasks which can track changes in developmental trajectories rather than endpoint measurement at the adult stage of behavior. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Morphometric magnetic resonance imaging and genetic testing in cerebellar abiotrophy in Arabian horses

    PubMed Central

    2013-01-01

    Background Cerebellar abiotrophy (CA) is a rare but significant disease in Arabian horses caused by progressive death of the Purkinje cells resulting in cerebellar ataxia characterized by a typical head tremor, jerky head movements and lack of menace response. The specific role of magnetic resonance imaging (MRI) to support clinical diagnosis has been discussed. However, as yet MR imaging has only been described in one equine CA case. The role of MR morphometry in this regard is currently unknown. Due to the hereditary nature of the disease, genetic testing can support the diagnosis of CA. Therefore, the objective of this study was to perform MR morphometric analysis and genetic testing in four CA-affected Arabian horses and one German Riding Pony with purebred Arabian bloodlines in the third generation. Results CA was diagnosed pathohistologically in the five affected horses (2 months - 3 years) supported by clinical signs, necropsy, and genetic testing which confirmed the TOE1:g.2171G>A SNP genotype A/A in all CA-affected horses. On MR images morphometric analysis of the relative cerebellar size and relative cerebellar cerebrospinal fluid (CSF) space were compared to control images of 15 unaffected horses. It was demonstrated that in MR morphometric analyses, CA affected horses displayed a relatively smaller cerebellum compared to the entire brain mass than control animals (P = 0.0088). The relative cerebellar CSF space was larger in affected horses (P = 0.0017). Using a cut off value of 11.0% for relative cerebellar CSF space, the parameter differentiated between CA-affected horses and controls with a sensitivity of 100% and a specificity of 93.3%. Conclusions In conclusion, morphometric MRI and genetic analysis could be helpful to support the diagnosis of CA in vivo. PMID:23702154

  13. Orthostatic tremor: a cerebellar pathology?

    PubMed Central

    Popa, Traian; García-Lorenzo, Daniel; Valabregue, Romain; Legrand, André-Pierre; Apartis, Emmanuelle; Marais, Lea; Degos, Bertrand; Hubsch, Cecile; Fernández-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Lehéricy, Stéphane; Meunier, Sabine; Vidailhet, Marie

    2016-01-01

    Abstract See Muthuraman et al. (doi:10.1093/aww164) for a scientific commentary on this article. Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects. PMID:27329770

  14. Delayed rotation of the cerebellar vermis: a pitfall in early second-trimester fetal magnetic resonance imaging.

    PubMed

    Pinto, J; Paladini, D; Severino, M; Morana, G; Pais, R; Martinetti, C; Rossi, A

    2016-07-01

    We describe two cases in which delayed rotation of the cerebellar vermis simulated a Dandy-Walker malformation (DWM) on early second-trimester magnetic resonance imaging (MRI). Two pregnant women with suspected fetal posterior fossa anomaly on ultrasound examination underwent fetal MRI at 21 (Case 1) and 19 (Case 2) weeks' gestation. In both cases, upward rotation of the cerebellar vermis was noted; on midsagittal imaging, the brainstem-vermis angle was 28° and 43°, respectively, while cerebellar morphometry showed a reduced vermian anteroposterior diameter compared to reference data. The posterior fossa appeared to be mildly enlarged, while all other findings were normal. Follow-up MRI at 28 + 3 weeks' gestation (Case 1) and at 1 postnatal year (Case 2) showed completely normal findings. Both children had normal psychomotor development and neurological examinations at 1 year of age. Incomplete rotation of the cerebellar vermis can be a physiological finding on early second-trimester fetal MRI examination and can simulate DWM or other forms of cerebellar hypoplasia. Embryologically, delayed permeabilization of Blake's pouch could account for the delayed vermian rotation. Follow-up imaging at a later gestational age is crucial to ensure that this condition is not over-reported and to avoid the potential risk of unnecessary pregnancy interruption. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  15. Aberrant cerebellar connectivity in motor and association networks in schizophrenia

    PubMed Central

    Shinn, Ann K.; Baker, Justin T.; Lewandowski, Kathryn E.; Öngür, Dost; Cohen, Bruce M.

    2015-01-01

    Schizophrenia is a devastating illness characterized by disturbances in multiple domains. The cerebellum is involved in both motor and non-motor functions, and the “cognitive dysmetria” and “dysmetria of thought” models propose that abnormalities of the cerebellum may contribute to schizophrenia signs and symptoms. The cerebellum and cerebral cortex are reciprocally connected via a modular, closed-loop network architecture, but few schizophrenia neuroimaging studies have taken into account the topographical and functional heterogeneity of the cerebellum. In this study, using a previously defined 17-network cerebral cortical parcellation system as the basis for our functional connectivity seeds, we systematically investigated connectivity abnormalities within the cerebellum of 44 schizophrenia patients and 28 healthy control participants. We found selective alterations in cerebro-cerebellar functional connectivity. Specifically, schizophrenia patients showed decreased cerebro-cerebellar functional connectivity in higher level association networks (ventral attention, salience, control, and default mode networks) relative to healthy control participants. Schizophrenia patients also showed increased cerebro-cerebellar connectivity in somatomotor and default mode networks, with the latter showing no overlap with the regions found to be hypoconnected within the same default mode network. Finally, we found evidence to suggest that somatomotor and default mode networks may be inappropriately linked in schizophrenia. The relationship of these dysconnectivities to schizophrenia symptoms, such as neurological soft signs and altered sense of agency, is discussed. We conclude that the cerebellum ought to be considered for analysis in all future studies of network abnormalities in SZ, and further suggest the cerebellum as a potential target for further elucidation, and possibly treatment, of the underlying mechanisms and network abnormalities producing symptoms of

  16. High Incidence of Progressive Postnatal Cerebellar Enlargement in Costello Syndrome: Brain Overgrowth Associated with HRAS Mutations as the Likely Cause of Structural Brain and Spinal Cord Abnormalities

    PubMed Central

    Gripp, Karen W.; Hopkins, Elisabeth; Doyle, Daniel; Dobyns, William B.

    2010-01-01

    Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. In a systematic review we found absolute or relative macrocephaly (100%), ventriculomegaly (50%), and other abnormalities on brain and spinal cord imaging studies in 27/28 individuals. Posterior fossa crowding with cerebellar tonsillar herniation (CBTH) was noted in 27/28 (96%), and in 10/17 (59%) with serial studies posterior fossa crowding progressed. Sequelae of posterior fossa crowding and CBTH included hydrocephalus requiring shunt or ventriculostomy (25%), Chiari 1 malformation (32%) and syrinx formation (25%). Our data reveal macrocephaly with progressive frontal bossing and CBTH, documenting an ongoing process rather than a static congenital anomaly. Comparison of images obtained in young infants to subsequent studies demonstrated postnatal development of posterior fossa crowding. This process of evolving megalencephaly and cerebellar enlargement is in keeping with mouse model data, delineating abnormal genesis of neurons and glia, resulting in an increased number of astrocytes and enlarged brain volume. In Costello syndrome and macrocephaly-capillary malformation syndrome disproportionate brain growth is the main factor resulting in postnatal CBTH and Chiari 1 malformation. PMID:20425820

  17. Anterior cingulate cortex and cerebellar hemisphere neurometabolite changes in depression treatment: A 1H magnetic resonance spectroscopy study.

    PubMed

    Chen, Li-Ping; Dai, Hai-Yang; Dai, Zhuo-Zhi; Xu, Chong-Tao; Wu, Ren-Hua

    2014-05-01

    We utilized single-voxel 1H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder (MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and cerebellar hemisphere before and after antidepressant treatment. Fifteen adult MDD patients and 15 age- and sex-matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment. At baseline, N-acetyl aspartate (NAA), total glutamine plus glutamate (Glx) and myo-inositol (MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls (P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline. Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  18. Orthostatic tremor: a cerebellar pathology?

    PubMed

    Gallea, Cécile; Popa, Traian; García-Lorenzo, Daniel; Valabregue, Romain; Legrand, André-Pierre; Apartis, Emmanuelle; Marais, Lea; Degos, Bertrand; Hubsch, Cecile; Fernández-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Lehéricy, Stéphane; Meunier, Sabine; Vidailhet, Marie

    2016-08-01

    SEE MUTHURAMAN ET AL DOI101093/AWW164 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Lobular patterns of cerebellar resting-state connectivity in adults with Autism Spectrum Disorder.

    PubMed

    Olivito, Giusy; Lupo, Michela; Laghi, Fiorenzo; Clausi, Silvia; Baiocco, Roberto; Cercignani, Mara; Bozzali, Marco; Leggio, Maria

    2018-03-01

    Autism spectrum disorder is a neurodevelopmental disorder characterized by core deficits in social functioning. Core autistics traits refer to poor social and imagination skills, poor attention-switching/strong focus of attention, exceptional attention to detail, as expressed by the autism-spectrum quotient. Over the years, the importance of the cerebellum in the aetiology of autism spectrum disorder has been acknowledged. Neuroimaging studies have provided a strong support to this view, showing both structural and functional connectivity alterations to affect the cerebellum in autism spectrum disorder. According to the underconnectivity theory, disrupted connectivity within cerebello-cerebral networks has been specifically implicated in the aetiology of autism spectrum disorder. However, inconsistent results have been generated across studies. In this study, an integrated approach has been used in a selected population of adults with autism spectrum disorder to analyse both cerebellar morphometry and functional connectivity. In individuals with autism spectrum disorder, a decreased cerebellar grey matter volume affected the right Crus II, a region showing extensive connections with cerebral areas related to social functions. This grey matter reduction correlates with the degree of autistic traits as measured by autism-spectrum quotient. Interestingly, altered functional connectivity was found between the reduced cerebellar Crus II and contralateral cerebral regions, such as frontal and temporal areas. Overall, the present data suggest that adults with autism spectrum disorder present with specific cerebellar structural alterations that may affect functional connectivity within cerebello-cerebral modules relevant to social processing and account for core autistics traits. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Bilateral cerebellar activation in unilaterally challenged essential tremor.

    PubMed

    Broersma, Marja; van der Stouwe, Anna M M; Buijink, Arthur W G; de Jong, Bauke M; Groot, Paul F C; Speelman, Johannes D; Tijssen, Marina A J; van Rootselaar, Anne-Fleur; Maurits, Natasha M

    2016-01-01

    Essential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous research into the pathophysiology of ET suggested underlying cerebellar abnormalities. In this study, we added electromyography as an index of tremor intensity to functional Magnetic Resonance Imaging (EMG-fMRI) to study a group of ET patients selected according to strict criteria to achieve maximal homogeneity. With this approach we expected to improve upon the localization of the bilateral cerebellar abnormalities found in earlier fMRI studies. We included 21 propranolol sensitive patients, who were not using other tremor medication, with a definite diagnosis of ET defined by the Tremor Investigation Group. Simultaneous EMG-fMRI recordings were performed while patients were off tremor medication. Patients performed unilateral right hand and arm extension, inducing tremor, alternated with relaxation (rest). Twenty-one healthy, age- and sex-matched participants mimicked tremor during right arm extension. EMG power variability at the individual tremor frequency as a measure of tremor intensity variability was used as a regressor, mathematically independent of the block regressor, in the general linear model used for fMRI analysis, to find specific tremor-related activations. Block-related activations were found in the classical upper-limb motor network, both for ET patients and healthy participants in motor, premotor and supplementary motor areas. In ET patients, we found tremor-related activations bilaterally in the cerebellum: in left lobules V, VI, VIIb and IX and in right lobules V, VI, VIIIa and b, and in the brainstem. In healthy controls we found simulated tremor-related activations in right cerebellar lobule V. Our results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII.

  1. Neurofilament protein levels: quantitative analysis in essential tremor cerebellar cortex.

    PubMed

    Louis, Elan D; Ma, Karen; Babij, Rachel; Cortés, Etty; Liem, Ronald K; Vonsattel, Jean-Paul G; Faust, Phyllis L

    2012-06-14

    Essential tremor (ET) is among the most prevalent neurological diseases. A substantial increase in the number of Purkinje cell axonal swellings (torpedoes) has been identified in ET brains. We recently demonstrated that torpedoes in ET contain an over-accumulation of disorganized neurofilament (NF) proteins. This now raises the question whether NF protein composition and/or phosphorylation state in cerebellar tissue might differ between ET cases and controls. We used a Western blot analysis to compare the levels and phosphorylation state of NF proteins and α-internexin in cerebellar tissue from 47 ET cases versus 26 controls (2:1 ratio). Cases and controls did not differ with respect to the cerebellar levels of NF-light (NF-L), NF-medium (NF-M), NF-heavy (NF-H), or α-internexin. However, SMI-31 levels (i.e., phosphorylated NF-H) and SMI-32 levels (i.e., non-phosphorylated NF-H) were significantly higher in ET cases than controls (1.28±0.47 vs. 1.06±0.32, p=0.02; and 1.38±0.75 vs. 1.00±0.42, p=0.006). Whether the abnormal phosphorylation state that we observed is a cause of defective axonal transport and/or function of NFs in ET is not known. NF abnormalities have been demonstrated in several neurodegenerative diseases. Regardless of whether these protein aggregates are the cause or consequence of these diseases, NF abnormalities have been shown to be an important factor in the cellular disruption observed in several neurodegenerative diseases. Therefore, further analyses of these NF abnormalities and their mechanisms are important to enhance our understanding of disease pathogenesis in ET. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome.

    PubMed

    Whittaker, Danielle E; Kasah, Sahrunizam; Donovan, Alex P A; Ellegood, Jacob; Riegman, Kimberley L H; Volk, Holger A; McGonnell, Imelda; Lerch, Jason P; Basson, M Albert

    2017-12-01

    Mutations in the gene encoding the ATP dependent chromatin-remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital-urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio-temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay. © 2017 The Authors. American Journal of Medical Genetics Part C Published by Wiley Periodicals, Inc.

  3. Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

    PubMed Central

    Whittaker, Danielle E.; Kasah, Sahrunizam; Donovan, Alex P. A.; Ellegood, Jacob; Riegman, Kimberley L. H.; Volk, Holger A.; McGonnell, Imelda; Lerch, Jason P.

    2017-01-01

    Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay. PMID:29168327

  4. Gray matter abnormalities associated with fibromyalgia: A meta-analysis of voxel-based morphometric studies.

    PubMed

    Shi, HaiCun; Yuan, CongHu; Dai, ZhenYu; Ma, HaiRong; Sheng, LiQin

    2016-12-01

    Studies employing voxel-based morphometry (VBM) have reported inconsistent findings on the association of gray matter (GM) abnormalities with fibromyalgia. The aim of the present study is to identify the most prominent and replicable GM areas that involved in fibromyalgia. A systematic search of the PubMed database from January 2000 to September 2015 was performed to identify eligible whole-brain VBM studies. Comprehensive meta-analyses to investigate regional GM abnormalities in fibromyalgia were conducted with the Seed-based d Mapping software package. Seven studies, reporting nine comparisons and including a grand total of 180 fibromyalgia patients and 126 healthy controls, were included in the meta-analyses. In fibromyalgia patients compared with healthy controls, regional GM decreases were consistently found in the bilateral anterior cingulate/paracingulate cortex/medial prefrontal cortex, the bilateral posterior cingulate/paracingulate cortex, the left parahippocampal gyrus/fusiform cortex, and the right parahippocampal gyrus/hippocampus. Regional GM increases were consistently found in the left cerebellum. Meta-regression demonstrated that age was correlated with GM anomalies in fibromyalgia patients. The current meta-analysis identified a characteristic pattern of GM alterations within the medial pain system, default mode network, and cerebro-cerebellar circuits, which further supports the concept that fibromyalgia is a symptom complex involving brain areas beyond those implicated in chronic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Brain Morphometry using MRI in Schizophrenia Patients

    NASA Astrophysics Data System (ADS)

    Abanshina, I.; Pirogov, Yu.; Kupriyanov, D.; Orlova, V.

    2010-01-01

    Schizophrenia has been the focus of intense neuroimaging research. Although its fundamental pathobiology remains elusive, neuroimaging studies provide evidence of abnormalities of cerebral structure and function in patients with schizophrenia. We used morphometry as a quantitative method for estimation of volume of brain structures. Seventy eight right-handed subjects aged 18-45 years were exposed to MRI-examination. Patients were divided into 3 groups: patients with schizophrenia, their relatives and healthy controls. The volumes of interested structures (caudate nucleus, putamen, ventricles, frontal and temporal lobe) were measured using T2-weighted MR-images. Correlations between structural differences and functional deficit were evaluated.

  6. "Acquired" Dandy-Walker malformation and cerebellar hemorrhage: Usefulness of serial MRI.

    PubMed

    Pichiecchio, Anna; Decio, Alice; Di Perri, Carol; Parazzini, Cecilia; Rossi, Andrea; Signorini, Sabrina

    2016-01-01

    Neuroimaging plays a fundamental role in the diagnosis of Dandy Walker malformation (DWM), a posterior fossa anomaly that is usually associated with genetic abnormalities, but may rarely be ascribed to acquired causes. Here, we report the clinical history and neuroimaging studies of a child with a complex cardiac malformation, developmental delay, and oculomotor anomalies whose neuroimaging findings were consistent with an acquired form of DWM. Fetal MRI at gestational weeks 27 and 31 showed cerebellar and vermis hypoplasia and fourth ventricle enlargement, together with hemosiderin deposits on the cerebellar hemispheric surface, but without significant vermian rotation. Postnatal MRIs at 5 days and 13 months revealed progressive counter-clockwise rotation of the hypoplastic cerebellar vermis with cystic dilation of the fourth ventricle, eventually leading to a full-blown DWM. This case strengthens the opinion that DWM is a heterogeneous condition, and may support the hypothesis that acquired meningeal abnormalities in the form of cortico-pial hemosiderosis may play a role in the development of DWM. This case also demonstrates that serial neuroimaging plays a key role in the correct diagnosis of posterior fossa malformations, whose prognosis is difficult to establish on second trimester fetal MRI and requires longer clinical follow-up. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  7. Friedreich and dominant ataxias: quantitative differences in cerebellar dysfunction measurements.

    PubMed

    Tanguy Melac, Audrey; Mariotti, Caterina; Filipovic Pierucci, Antoine; Giunti, Paola; Arpa, Javier; Boesch, Sylvia; Klopstock, Thomas; Müller Vom Hagen, Jennifer; Klockgether, Thomas; Bürk, Katrin; Schulz, Jörg B; Reetz, Kathrin; Pandolfo, Massimo; Durr, Alexandra; Tezenas du Montcel, Sophie

    2018-06-01

    Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction. We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively. There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated. ClinicalTrials.gov: NCT02069509. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Postural sway and regional cerebellar volume in adults with attention-deficit/hyperactivity disorder

    PubMed Central

    Hove, Michael J.; Zeffiro, Thomas A.; Biederman, Joseph; Li, Zhi; Schmahmann, Jeremy; Valera, Eve M.

    2015-01-01

    Objective Motor abnormalities, including impaired balance and increased postural sway, are commonly reported in children with ADHD, but have yet to be investigated in adults with ADHD. Furthermore, although these abnormalities are thought to stem from cerebellar deficits, evidence for an association between the cerebellum and these motor deficits has yet to be provided for either adults or children with ADHD. Method In this study, we measured postural sway in adults with ADHD and controls, examining the relationship between sway and regional cerebellar gray matter volume. Thirty-two ADHD and 28 control participants completed various standing-posture tasks on a Wii balance board. Results Postural sway was significantly higher for the ADHD group compared to the healthy controls. Higher sway was positively associated with regional gray matter volume in the right posterior cerebellum (lobule VIII/IX). Conclusion These findings show that sway abnormalities commonly reported in children with ADHD are also present in adults, and for the first time show a relationship between postural control atypicalities and the cerebellum in this group. Our findings extend the literature on motor abnormalities in ADHD and contribute to our knowledge of their neural substrate. PMID:26106567

  9. Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation During Hypertension.

    PubMed

    Figueira, Leticia; Israel, Anita

    2017-02-01

    Adrenomedullin (AM) and its receptors components, calcitonin-receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP1, RAMP2, and RAMP3) are expressed in cerebellum. Cerebellar AM, AM binding sites and receptor components are altered during hypertension, suggesting a role for cerebellar AM in blood pressure regulation. Thus, we assessed the effect of valsartan, on AM and its receptor components expression in the cerebellar vermis of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Additionally, we evaluated AM action on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, and thiobarbituric acid reactive substances (TBARS) production in cerebellar vermis. Animals were treated with valsartan or vehicle for 11 days. Rats were sacrificed by decapitation; cerebellar vermis was dissected; and AM, CRLR, RAMP1, RAMP2, and RAMP3 expression was quantified by Western blot analysis. CAT, SOD, and GPx activity was determined spectrophotometrically and blood pressure by non-invasive plethysmography. We demonstrate that AM and RAMP2 expression was lower in cerebellum of SHR rats, while CRLR, RAMP1, and RAMP3 expression was higher than those of WKY rats. AM reduced cerebellar CAT, SOD, GPx activities, and TBARS production in WKY rats, but not in SHR rats. Valsartan reduced blood pressure and reversed the altered expression of AM and its receptors components, as well the loss of AM capacity to reduce antioxidant enzyme activity and TBARS production in SHR rats. These findings demonstrate that valsartan is able to reverse the dysregulation of cerebellar adrenomedullinergic system; and they suggest that altered AM system in the cerebellum could represent the primary abnormality leading to hypertension.

  10. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.

    PubMed

    McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

    2013-01-09

    Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.

  11. Altered Cerebellar Organization and Function in Monoamine Oxidase A Hypomorphic Mice

    PubMed Central

    Alzghoul, Loai; Bortolato, Marco; Delis, Foteini; Thanos, Panayotis K.; Darling, Ryan D.; Godar, Sean C; Zhang, Junlin; Grant, Samuel; Wang, Gene-Jack; Simpson, Kimberly L.; Chen, Kevin; Volkow, Nora D.; Lin, Rick C.S.; Shih, Jean C.

    2012-01-01

    Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO-ANeo), featuring elevated monoamine levels, social deficits and perseverative behaviors as well as morphological changes in the basolateral amygdala and orbitofrontal cortex. Here we showed that MAO-ANeo mice displayed deficits in motor control, manifested as subtle disturbances in gait, motor coordination, and balance. Furthermore, magnetic resonance imaging of the cerebellum revealed morphological changes and a moderate reduction in the cerebellar size of MAO- ANeo mice compared to wild type (WT) mice. Histological and immunohistochemical analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje cell count and their dendritic density in MAO- ANeo mice compared to WT. Our current findings suggest that congenitally low MAO-A activity leads to abnormal development of the cerebellum. PMID:22971542

  12. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice.

    PubMed

    Tsai, Peter T; Hull, Court; Chu, YunXiang; Greene-Colozzi, Emily; Sadowski, Abbey R; Leech, Jarrett M; Steinberg, Jason; Crawley, Jacqueline N; Regehr, Wade G; Sahin, Mustafa

    2012-08-30

    Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders, but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showing cerebellar Purkinje cell (PC) loss, and isolated cerebellar injury has been associated with a higher incidence of ASDs. However, the extent of cerebellar contribution to the pathogenesis of ASDs remains unclear. Tuberous sclerosis complex (TSC) is a genetic disorder with high rates of comorbid ASDs that result from mutation of either TSC1 or TSC2, whose protein products dimerize and negatively regulate mammalian target of rapamycin (mTOR) signalling. TSC is an intriguing model to investigate the cerebellar contribution to the underlying pathogenesis of ASDs, as recent studies in TSC patients demonstrate cerebellar pathology and correlate cerebellar pathology with increased ASD symptomatology. Functional imaging also shows that TSC patients with ASDs display hypermetabolism in deep cerebellar structures, compared to TSC patients without ASDs. However, the roles of Tsc1 and the sequelae of Tsc1 dysfunction in the cerebellum have not been investigated so far. Here we show that both heterozygous and homozygous loss of Tsc1 in mouse cerebellar PCs results in autistic-like behaviours, including abnormal social interaction, repetitive behaviour and vocalizations, in addition to decreased PC excitability. Treatment of mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioural deficits. These findings demonstrate new roles for Tsc1 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.

  13. Grey matter abnormalities in untreated hyperthyroidism: a voxel-based morphometry study using the DARTEL approach.

    PubMed

    Zhang, Wei; Song, Lingheng; Yin, Xuntao; Zhang, Jiuquan; Liu, Chen; Wang, Jian; Zhou, Daiquan; Chen, Bing; Lii, Haitao

    2014-01-01

    Hyperthyroidism is frequently associated with pronounced neuropsychiatric symptoms such as impulsiveness, irritability, poor concentration, and memory impairments. Functional neuroimaging has revealed changes in cerebral metabolism in hyperthyroidism, but regional changes in cortical morphology associated with specific neurological deficits have not been studied so far. To investigate the pathophysiology underlying hyperthyroid-associated neural dysfunction, we compared grey matter volume (GMV) between adult hyperthyroid patients and matched healthy controls using voxel-based morphometry (VBM). High resolution 3D T1-weighted images were acquired by 3T MRI from 51 hyperthyroid patients and 51 controls. VBM analysis was performed using SPM8. Correlations between regional GMV and both serum free thyroid hormone (TH) concentrations and disease duration were assessed by multiple regression analysis. Compared to controls, GM volumes in the bilateral hippocampus, parahippocampal gyrus, calcarine, lingual gyrus, and left temporal pole were lower and bilateral supplementary motor area GMV higher in hyperthyroid patients. Serum free triiodothyronine (FT3) concentration was negatively correlated with the normalized regional volume (NRV) of the left parahippocampal gyrus and serum free thyroxine (FT4) concentration negatively correlated with the NRV of the left hippocampus and right parahippocampal gyrus. Disease duration was negatively correlated with the NRV of the left hippocampus, bilateral parahippocampal gyrus, and left temporal pole. Hyperthyroid patients exhibited reduced GMV in regions associated with memory, attention, emotion, vision, and motor planning. Negative correlations between GMV and both free TH and disease duration suggest that chronic TH elevation induces abnormalities in the adult cortex. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Cerebellar contribution to motor and cognitive performance in multiple sclerosis: An MRI sub-regional volumetric analysis.

    PubMed

    D'Ambrosio, Alessandro; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo; Rocca, Maria A

    2017-08-01

    To investigate the role of cerebellar sub-regions on motor and cognitive performance in multiple sclerosis (MS) patients. Whole and sub-regional cerebellar volumes, brain volumes, T2 hyperintense lesion volumes (LV), and motor performance scores were obtained from 95 relapse-onset MS patients and 32 healthy controls (HC). MS patients also underwent an evaluation of working memory and processing speed functions. Cerebellar anterior and posterior lobes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12). Multivariate linear regression models assessed the relationship between magnetic resonance imaging (MRI) measures and motor/cognitive scores. Compared to HC, only secondary progressive multiple sclerosis (SPMS) patients had lower cerebellar volumes (total and posterior cerebellum). In MS patients, lower anterior cerebellar volume and brain T2 LV predicted worse motor performance, whereas lower posterior cerebellar volume and brain T2 LV predicted poor cognitive performance. Global measures of brain volume and infratentorial T2 LV were not selected by the final multivariate models. Cerebellar volumetric abnormalities are likely to play an important contribution to explain motor and cognitive performance in MS patients. Consistently with functional mapping studies, cerebellar posterior-inferior volume accounted for variance in cognitive measures, whereas anterior cerebellar volume accounted for variance in motor performance, supporting the assessment of cerebellar damage at sub-regional level.

  15. Structure–function relationships in the developing cerebellum: evidence from early-life cerebellar injury and neurodevelopmental disorders

    PubMed Central

    Stoodley, Catherine J.; Limperopoulos, Catherine

    2016-01-01

    SUMMARY The increasing appreciation of the role of the cerebellum in motor and non-motor functions is crucial to understanding the outcomes of acquired cerebellar injury and developmental lesions in high-risk fetal and neonatal populations, children with cerebellar damage (e.g. posterior fossa tumors), and neurodevelopmental disorders (e.g. autism). We review available data regarding the relationship between the topography of cerebellar injury or abnormality and functional outcomes. We report emerging structure–function relationships with specific symptoms: cerebellar regions that interconnect with sensorimotor cortices are associated with motor impairments when damaged; disruption to posterolateral cerebellar regions that form circuits with association cortices impact long-term cognitive outcomes; and midline posterior vermal damage is associated with behavioral dysregulation and an autism-like phenotype. We also explore the impact of age and the potential role for critical periods on cerebellar structure and child function. These findings suggest that the cerebellum plays a critical role in motor, cognitive, and social–behavioral development, possibly via modulatory effects on the developing cerebral cortex. PMID:27184461

  16. [Cerebellar cognitive affective syndrome secondary to a cerebellar tumour].

    PubMed

    Domínguez-Carral, J; Carreras-Sáez, I; García-Peñas, J J; Fournier-Del Castillo, C; Villalobos-Reales, J

    2015-01-01

    Cerebellar cognitive affective syndrome is characterized by disturbances of executive function, impaired spatial cognition, linguistic difficulties, and personality change. The case of an 11 year old boy is presented, with behavior problems, learning difficulties and social interaction problems. In the physical examination he had poor visual contact, immature behavior, reduced expressive language and global motor disability with gait dyspraxia, with no defined cerebellar motor signs. In the neuropsychological evaluation he has a full scale overall intellectual quotient of 84, with signs of cerebellar cognitive affective syndrome. A tumour affecting inferior cerebellar vermis was observed in the magnetic resonance imaging, which had not significantly grown during 5 years of follow up. The cerebellum participates in controlling cognitive and affective functions. Cerebellar pathology must be considered in the differential diagnosis of children with cognitive or learning disorder with associated behavioral and emotional components. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  17. Voxel-based morphometry of auditory and speech-related cortex in stutterers.

    PubMed

    Beal, Deryk S; Gracco, Vincent L; Lafaille, Sophie J; De Nil, Luc F

    2007-08-06

    Stutterers demonstrate unique functional neural activation patterns during speech production, including reduced auditory activation, relative to nonstutterers. The extent to which these functional differences are accompanied by abnormal morphology of the brain in stutterers is unclear. This study examined the neuroanatomical differences in speech-related cortex between stutterers and nonstutterers using voxel-based morphometry. Results revealed significant differences in localized grey matter and white matter densities of left and right hemisphere regions involved in auditory processing and speech production.

  18. Abnormal Eye Movements in Creutzfeldt-Jakob Disease

    NASA Technical Reports Server (NTRS)

    Grant, Michael P.; Cohen, Mark; Petersen, Robert B.; Halmagyi, G. Michael; McDougall, Alan; Tusa, Ronald J.; Leigh, R. John

    1993-01-01

    We report 3 patients with autopsy-proven Creutzfeldt-Jakob disease who, early in their course, developed abnormal eye movements that included periodic alternating nystagmus and slow vertical saccades. These findings suggested involvement of the cerebellar nodulus and uvula, and the brainstem reticular formation, respectively. Cerebellar ataxia was also an early manifestation and, in one patient, a frontal lobe brain biopsy was normal at a time when ocular motor and cerebellar signs were conspicuous. As the disease progressed, all saccades and quick phases of nystagmus were lost, but periodic alternating gaze deviation persisted. At autopsy, 2 of the 3 patients had pronounced involvement of the cerebellum, especially of the midline structures. Creutzfeldt-Jakob disease should be considered in patients with subacute progressive neurological disease when cognitive changes are overshadowed by ocular motor findings or ataxia.

  19. The Cerebellar Dysplasia of Chiari II Malformation as Revealed by Eye Movements

    PubMed Central

    Salman, Michael S.; Dennis, Maureen; Sharpe, James A.

    2011-01-01

    Introduction Chiari type II malformation (CII) is a developmental deformity of the hindbrain. We have previously reported that many patients with CII have impaired smooth pursuit, while few make inaccurate saccades or have an abnormal vestibulo-ocular reflex. In contrast, saccadic adaptation and visual fixation are normal. In this report, we correlate results from several eye movement studies with neuroimaging in CII. We present a model for structural changes within the cerebellum in CII. Methods Saccades, smooth pursuit, the vestibulo-ocular reflex, and visual fixation were recorded in 21 patients with CII, aged 8–19 years and 39 age-matched controls, using an infrared eye tracker. Qualitative and quantitative MRI data were correlated with eye movements in 19 CII patients and 28 controls. Results Nine patients with CII had abnormal eye movements. Smooth pursuit gain was subnormal in eight, saccadic accuracy abnormal in four, and vestibulo-ocular reflex gain abnormal in three. None had fixation instability. Patients with CII had a significantly smaller cerebellar volume than controls, and those with normal eye motion had an expanded midsagittal vermis compared to controls. However, patients with abnormal eye movements had a smaller (non-expanded) midsagittal vermis area, posterior fossa area and medial cerebellar volumes than CII patients with normal eye movements. Conclusions The deformity of CII affects the structure and function of the cerebellum selectively and differently in those with abnormal eye movements. We propose that the vermis can expand when compressed within a small posterior fossa in some CII patients, thus sparing its ocular motor functions. PMID:19960749

  20. COMPARISON OF REAL-TIME MICROVASCULAR ABNORMALITIES IN PEDIATRIC AND ADULT SICKLE CELL ANEMIA PATIENTS

    PubMed Central

    Cheung, Anthony T.W.; Miller, Joshua W.; Craig, Sarah M.; To, Patricia L.; Lin, Xin; Samarron, Sandra L.; Chen, Peter C.Y.; Zwerdling, Theodore; Wun, Ted; Li, Chin-Shang; Green, Ralph

    2010-01-01

    The conjunctival microcirculation in 14 pediatric and 8 adult sickle cell anemia (SCA) patients was studied using computer-assisted intravital microscopy. The bulbar conjunctiva in SCA patients in both age groups exhibited a blanched/avascular appearance characterized by decreased vascularity. SCA patients from both age groups had many of the same abnormal morphometric {vessel diameter, vessel distribution, morphometry (shape), tortuosity, arteriole:venule (A:V) ratio, and hemosiderin deposits} and dynamic {vessel sludging/sludged flow, boxcar blood (trickled) flow and abnormal flow velocity} abnormalities. A severity index (SI) was computed to quantify the degree of vasculopathy for comparison between groups. The severity of vasculopathy differed significantly between the pediatric and adult patients (SI: 4.2 ± 1.8 vs 6.6 ± 2.4; p=0.028), indicative of a lesser degree of overall severity in the pediatric patients. Specific abnormalities that were less prominent in the pediatric patients included abnormal vessel morphometry and tortuosity. Sludged flow, abnormal vessel distribution, abnormal A:V ratio, and boxcar flow, appeared in high prevalence in both age groups. The results indicate that SCA microvascular abnormalities develop in childhood and the severity of vasculopathy likely progresses with age. Intervention and effective treatment/management modalities should target pediatric patients to ameliorate, slow down or prevent progressive microvascular deterioration. PMID:20872552

  1. White matter volume loss in amyotrophic lateral sclerosis: A meta-analysis of voxel-based morphometry studies.

    PubMed

    Chen, Guangxiang; Zhou, Baiwan; Zhu, Hongyan; Kuang, Weihong; Bi, Feng; Ai, Hua; Gu, Zhongwei; Huang, Xiaoqi; Lui, Su; Gong, Qiyong

    2018-04-20

    Structural neuroimaging studies of white matter (WM) volume in amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) have yielded inconsistent findings. This study aimed to perform a quantitative voxel-based meta-analysis using effect-size signed differential mapping (ES-SDM) to establish a statistical consensus between published studies for WM volume alterations in ALS. The pooled meta-analysis revealed significant WM volume losses in the bilateral supplementary motor areas (SMAs), bilateral precentral gyri (PGs), left middle cerebellar peduncle and right cerebellum in patients with ALS, involving the corticospinal tract (CST), interhemispheric fibers, subcortical arcuate fibers, projection fibers to the striatum and cortico-ponto-cerebellar tract. The meta-regression showed that the ALS functional rating scale-revised (ALSFRS-R) was positively correlated with decreased WM volume in the bilateral SMAs, whereas illness duration was negatively correlated with WM volume reduction in the right SMA. This study provides a thorough profile of WM volume loss in ALS and robust evidence that ALS is a multisystem neurodegenerative disease that involves a variety of subcortical WM tracts extending beyond motor cortex involvement. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry.

    PubMed

    Gogtay, Nitin; Lu, Allen; Leow, Alex D; Klunder, Andrea D; Lee, Agatha D; Chavez, Alex; Greenstein, Deanna; Giedd, Jay N; Toga, Arthur W; Rapoport, Judith L; Thompson, Paul M

    2008-10-14

    Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.

  3. Brain volumetric abnormalities in patients with anorexia and bulimia nervosa: a voxel-based morphometry study.

    PubMed

    Amianto, Federico; Caroppo, Paola; D'Agata, Federico; Spalatro, Angela; Lavagnino, Luca; Caglio, Marcella; Righi, Dorico; Bergui, Mauro; Abbate-Daga, Giovanni; Rigardetto, Roberto; Mortara, Paolo; Fassino, Secondo

    2013-09-30

    Recent studies focussing on neuroimaging features of eating disorders have observed that anorexia nervosa (AN) is characterized by significant grey matter (GM) atrophy in many brain regions, especially in the cerebellum and anterior cingulate cortex. To date, no studies have found GM atrophy in bulimia nervosa (BN) or have directly compared patients with AN and BN. We used voxel-based morphometry (VBM) to characterize brain abnormalities in AN and BN patients, comparing them with each other and with a control group, and correlating brain volume with clinical features. We recruited 17 AN, 13 BN and 14 healthy controls. All subjects underwent high-resolution magnetic resonance imaging (MRI) with a T1-weighted 3D image. VBM analysis was carried out with the FSL-VBM 4.1 tool. We found no global atrophy, but regional GM reduction in AN with respect to controls and BN in the cerebellum, fusiform area, supplementary motor area, and occipital cortex, and in the caudate in BN compared to AN and controls. Both groups of patients had a volumetric increase bilaterally in somatosensory regions with respect to controls, in areas that are typically involved in the sensory-motor integration of body stimuli and in mental representation of the body image. Our VBM study documented, for the first time in BN patients, the presence of volumetric alterations and replicated previous findings in AN patients. We evidenced morphological differences between AN and BN, demonstrating in the latter atrophy of the caudate nucleus, a region involved in reward mechanisms and processes of self-regulation, perhaps involved in the genesis of the binge-eating behaviors of this disorder. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation.

    PubMed

    Romaniello, Romina; Arrigoni, Filippo; Panzeri, Elena; Poretti, Andrea; Micalizzi, Alessia; Citterio, Andrea; Bedeschi, Maria Francesca; Berardinelli, Angela; Cusmai, Raffaella; D'Arrigo, Stefano; Ferraris, Alessandro; Hackenberg, Annette; Kuechler, Alma; Mancardi, Margherita; Nuovo, Sara; Oehl-Jaschkowitz, Barbara; Rossi, Andrea; Signorini, Sabrina; Tüttelmann, Frank; Wahl, Dagmar; Hehr, Ute; Boltshauser, Eugen; Bassi, Maria Teresa; Valente, Enza Maria; Borgatti, Renato

    2017-12-01

    To determine the neuroimaging pattern of cerebellar dysplasia (CD) and other posterior fossa morphological anomalies associated with mutations in tubulin genes and to perform clinical and genetic correlations. Twenty-eight patients harbouring 23 heterozygous pathogenic variants (ten novel) in tubulin genes TUBA1A (n = 10), TUBB2B (n = 8) or TUBB3 (n = 5) were studied by a brain MRI scan performed either on a 1.5 T (n = 10) or 3 T (n = 18) MR scanner with focus on the posterior fossa. Cerebellar anomalies were detected in 24/28 patients (86%). CD was recognised in 19/28 (68%) including cortical cerebellar dysplasia (CCD) in 18/28, either involving only the cerebellar hemispheres (12/28) or associated with vermis dysplasia (6/28). CCD was located only in the right hemisphere in 13/18 (72%), including four TUBB2B-, four TUBB3- and five TUBA1A-mutated patients, while in the other five TUBA1A cases it was located only in the left hemisphere or in both hemispheres. The postero-superior region of the cerebellar hemispheres was most frequently affected. The cerebellar involvement in tubulinopathies shows specific features that may be labelled as 'tubulin-related CD'. This pattern is unique and differs from other genetic causes of cerebellar dysplasia. • Cortical cerebellar dysplasia without cysts is suggestive of tubulin-related disorder. • Cerebellar dysplasia in tubulinopathies shows specific features labelled as 'tubulin-related CD'. • Focal and unilateral involvement of cerebellar hemispheres has important implications for counselling.

  5. Hypersomnia due to injury of the ventral ascending reticular activating system following cerebellar herniation: A case report.

    PubMed

    Jang, Sung Ho; Chang, Chul Hoon; Jung, Young Jin; Kwon, Hyeok Gyu

    2017-01-01

    We report on a patient with hypersomnia who showed injury of the lower ascending reticular activating system (ARAS) following cerebellar herniation due to a cerebellar infarct, detected on diffusion tensor tractography (DTT). A 53-year-old male patient was diagnosed as a left cerebellar infarct, and underwent decompressive suboccipital craniectomy due to brain edema at 2 days after the onset of a cerebellar infarct. Three weeks after onset when the patient started rehabilitation, he showed hypersomnia without impairment of consciousness; he fell asleep most of daytime without external stimulation and showed an abnormal score on the Epworth Sleepiness Scale: 15 (full score: 24, cut off for hypersomnia: 10). On 3-week DTT, narrowing of the upper portion of the lower ventral ARAS between the pontine reticular formation and the hypothalamus was observed on both sides. In addition, partial tearing was observed in the middle portion of the right lower ventral ARAS. In conclusion, we found injury of the lower ventral ARAS in a patient with hypersomnia following cerebellar herniation due to a cerebellar infarct.

  6. Magnetic resonance imaging findings in patients presenting with (sub)acute cerebellar ataxia.

    PubMed

    Schneider, Tanja; Thomalla, Götz; Goebell, Einar; Piotrowski, Anna; Yousem, David Mark

    2015-06-01

    Acute or subacute cerebellar inflammation is mainly caused by postinfectious, toxic, neoplastic, vascular, or idiopathic processes and can result in cerebellar ataxia. Previous magnetic resonance (MR) studies in single patients who developed acute or subacute ataxia showed varying imaging features. Eighteen patients presenting with acute and subacute onset of ataxia were included in this study. Cases of chronic-progressive/hereditary and noncerebellar causes (ischemia, multiple sclerosis lesions, metastasis, bleedings) were excluded. MR imaging findings were then matched with the clinical history of the patient. An underlying etiology for ataxic symptoms were found in 14/18 patients (postinfectious/infectious, paraneoplastic, autoimmune, drug-induced). In two of five patients without MR imaging findings and three of eight patients with minimal imaging features (cerebellar atrophy, slight signal alterations, and small areas of restricted diffusion), adverse clinical outcomes were documented. Of the five patients with prominent MR findings (cerebellar swelling, contrast enhancement, or broad signal abnormalities), two were lost to follow-up and two showed long-term sequelae. No correlation was found between the presence of initial MRI findings in subacute or acute ataxia patients and their long-term clinical outcome. MR imaging was more flagrantly positive in cases due to encephalitis.

  7. Cerebellar infarction in the territory of the medial branch of the superior cerebellar artery.

    PubMed

    Sohn, Sung-Il; Lee, Hyung; Lee, Seong-Ryong; Baloh, Robert W

    2006-01-10

    The authors studied 14 patients with an isolated cerebellar infarct in the territory of the medial branch of the superior cerebellar artery (MSCA). The most common clinical finding was severe gait ataxia with sudden falling (n = 9) or severe veering (n = 2). Cerebellar dysarthria was found in 8 patients. Eight patients had a mild unilateral limb ataxia. These findings emphasize that MSCA territory cerebellar infarction presented with the prominent gait ataxia and cerebellar dysarthria.

  8. Atypical Activations of Fronto-Cerebellar Regions During Forethought in Parents of Children With ADHD.

    PubMed

    Rapin, Lucile; Poissant, Hélène; Mendrek, Adrianna

    2017-10-01

    Although several studies suggest heritability of ADHD, only a few investigations of possible associations between people at risk and neural abnormalities in ADHD exist. In this study, we tested whether parents of children with ADHD would show atypical patterns of cerebral activations during forethought, a feature of working memory. Using Functional Magnetic Resonance Imaging (fMRI), we compared 12 parents of children with ADHD and 9 parents of control children during a forethought task. Parents of children with ADHD exhibited significantly increased neural activations in the posterior lobes of the cerebellum and in the left inferior frontal gyrus, relative to parents of control children. These findings are consistent with previous reports in children and suggest the fronto-cerebellar circuit's abnormalities during forethought in parents of children with ADHD. Future studies of people at risk of ADHD are needed to fully understand the extent of the fronto-cerebellar heritability.

  9. 3D PATTERN OF BRAIN ABNORMALITIES IN FRAGILE X SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

    PubMed Central

    Lee, Agatha D.; Leow, Alex D.; Lu, Allen; Reiss, Allan L.; Hall, Scott; Chiang, Ming-Chang; Toga, Arthur W.; Thompson, Paul M.

    2007-01-01

    Fragile X syndrome (FraX), a genetic neurodevelopmental disorder, results in impaired cognition with particular deficits in executive function and visuo-spatial skills. Here we report the first detailed 3D maps of the effects of the Fragile X mutation on brain structure, using tensor-based morphometry. TBM visualizes structural brain deficits automatically, without time-consuming specification of regions-of-interest. We compared 36 subjects with FraX (age: 14.66+/−1.58SD, 18 females/18 males), and 33 age-matched healthy controls (age: 14.67+/−2.2SD, 17 females/16 males), using high-dimensional elastic image registration. All 69 subjects' 3D T1-weighted brain MRIs were spatially deformed to match a high-resolution single-subject average MRI scan in ICBM space, whose geometry was optimized to produce a minimal deformation target. Maps of the local Jacobian determinant (expansion factor) were computed from the deformation fields. Statistical maps showed increased caudate (10% higher; p=0.001) and lateral ventricle volumes (19% higher; p=0.003), and trend-level parietal and temporal white matter excesses (10% higher locally; p=0.04). In affected females, volume abnormalities correlated with reduction in systemically measured levels of the fragile X mental retardation protein (FMRP; Spearman's r<−0.5 locally). Decreased FMRP correlated with ventricular expansion (p=0.042; permutation test), and anterior cingulate tissue reductions (p=0.0026; permutation test) supporting theories that FMRP is required for normal dendritic pruning in fronto-striatal-limbic pathways. No sex differences were found; findings were confirmed using traditional volumetric measures in regions of interest. Deficit patterns were replicated using Lie group statistics optimized for tensor-valued data. Investigation of how these anomalies emerge over time will accelerate our understanding of FraX and its treatment. PMID:17161622

  10. Insights into cerebellar development and medulloblastoma.

    PubMed

    Bihannic, Laure; Ayrault, Olivier

    2016-01-01

    Cerebellar development is an extensive process that begins during early embryonic stages and persists more than one year after birth in human. Therefore, the cerebellum is susceptible to acquire various developmental abnormalities leading to numerous diseases such as medulloblastoma, the most common pediatric malignant brain tumor. One third of the patients with medulloblastoma are incurable and survivors have a poor quality of life due to the aggressiveness of the broad-spectrum treatments. Within the past few years, it has been highlighted that medulloblastoma is a heterogeneous disease that is divided in four molecular subgroups. This recent advance in the field, combined with the development of associated preclinical models for each subgroup, should enable, in the future, the discovery and use of targeted therapy in clinical treatments for each subtype of medulloblastoma. In this review, we first aim to show how deregulation of cerebellar development can lead to medulloblastoma formation and then to present the advances in the molecular subgrouping of medulloblastoma and the associated preclinical models. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  11. Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules.

    PubMed

    Balsters, J H; Cussans, E; Diedrichsen, J; Phillips, K A; Preuss, T M; Rilling, J K; Ramnani, N

    2010-02-01

    It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  12. Neurological signs in 23 dogs with suspected rostral cerebellar ischaemic stroke.

    PubMed

    Thomsen, Barbara; Garosi, Laurent; Skerritt, Geoff; Rusbridge, Clare; Sparrow, Tim; Berendt, Mette; Gredal, Hanne

    2016-06-07

    In dogs with ischaemic stroke, a very common site of infarction is the cerebellum. The aim of this study was to characterise neurological signs in relation to infarct topography in dogs with suspected cerebellar ischaemic stroke and to report short-term outcome confined to the hospitalisation period. A retrospective multicentre study of dogs with suspected cerebellar ischaemic stroke examined from 2010-2015 at five veterinary referral hospitals was performed. Findings from clinical, neurological, and paraclinical investigations including magnetic resonance imaging were assessed. Twenty-three dogs, 13 females and 10 males with a median age of 8 years and 8 months, were included in the study. The Cavalier King Charles Spaniel (n = 9) was a commonly represented breed. All ischaemic strokes were located to the vascular territory of the rostral cerebellar artery including four extensive and 19 limited occlusions. The most prominent neurological deficits were gait abnormalities (ataxia with hypermetria n = 11, ataxia without hypermetria n = 4, non-ambulatory n = 6), head tilt (n = 13), nystagmus (n = 8), decreased menace response (n = 7), postural reaction deficits (n = 7), and proprioceptive deficits (n = 5). Neurological signs appeared irrespective of the infarct being classified as extensive or limited. All dogs survived and were discharged within 1-10 days of hospitalisation. Dogs affected by rostral cerebellar ischaemic stroke typically present with a collection of neurological deficits characterised by ataxia, head tilt, and nystagmus irrespective of the specific cerebellar infarct topography. In dogs with peracute to acute onset of these neurological deficits, cerebellar ischaemic stroke should be considered an important differential diagnosis, and neuroimaging investigations are indicated. Although dogs are often severely compromised at presentation, short-term prognosis is excellent and rapid clinical improvement may be observed within the

  13. Neonatal Brain Abnormalities and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

    PubMed Central

    Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

    2014-01-01

    Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function. PMID:23805915

  14. Questioning the cerebellar doctrine.

    PubMed

    Galliano, Elisa; De Zeeuw, Chris I

    2014-01-01

    The basic principles of cerebellar function were originally described by Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can be considered to be the classic cerebellar doctrine. In their concepts, the main cerebellar function is to control motor behavior, Purkinje cells are the only cortical neuron receiving and integrating inputs from climbing fiber and mossy-parallel fiber pathways, and plastic modification at the parallel fiber synapses onto Purkinje cells constitutes the substrate of motor learning. Yet, because of recent technical advances and new angles of investigation, all pillars of the cerebellar doctrine now face regular re-examination. In this review, after summarizing the classic concepts and recent disputes, we attempt to synthesize an integrated view and propose a revisited version of the cerebellar doctrine. © 2014 Elsevier B.V. All rights reserved.

  15. Effect of Experimental Thyrotoxicosis on Brain Gray Matter: A Voxel-Based Morphometry Study.

    PubMed

    Göbel, Anna; Heldmann, Marcus; Göttlich, Martin; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F

    2015-09-01

    Hyper-as well hypothyroidism have an effect on behavior and brain function. Moreover, during development thyroid hormones influence brain structure. This study aimed to demonstrate an effect of experimentally induced hyperthyroidism on brain gray matter in healthy adult humans. High-resolution 3D T1-weighted images were acquired in 29 healthy young subjects prior to as well as after receiving 250 µg of T4 per day for 8 weeks. Voxel-based morphometry analysis was performed using Statistical Parametric Mapping 8 (SPM8). Laboratory testing confirmed the induction of hyperthyroidism. In the hyperthyroid condition, gray matter volumes were increased in the right posterior cerebellum (lobule VI) and decreased in the bilateral visual cortex and anterior cerebellum (lobules I-IV) compared to the euthyroid condition. Our study provides evidence that short periods of hyperthyroidism induce distinct alterations in brain structures of cerebellar regions that have been associated with sensorimotor functions as well as working memory in the literature.

  16. Cerebellar Development and Disease

    PubMed Central

    Gleeson, Joseph G.

    2008-01-01

    Recent Advances The molecular control of cell type specification within the developing cerebellum as well as the genetic causes of the most common human developmental cerebellar disorders have long remained mysterious. Recent genetic lineage and loss-of-function data from mice have revealed unique and non-overlapping anatomical origins for GABAergic neurons from ventricular zone precursors and glutamatergic cell from rhombic lip precursors, mirroring distinct origins for these neurotransmitter-specific cell types in the cerebral cortex. Mouse studies elucidating the role of Ptf1a as a cerebellar ventricular zone GABerigic fate switch were actually preceded by the recognition that PTF1A mutations in humans cause cerebellar agenesis, a birth defect of the human cerebellum. Indeed, several genes for congenital human cerebellar malformations have recently been identified, including genes causing Joubert syndrome, Dandy-Walker malformation and Ponto-cerebellar hypoplasia. These studies have pointed to surprisingly complex roles for transcriptional regulation, mitochondrial function and neuronal cilia in patterning, homeostasis and cell proliferation during cerebellar development. Together mouse and human studies are synergistically advancing our understanding of the developmental mechanisms that generate the uniquely complex mature cerebellum. PMID:18513948

  17. Altered fronto-cerebellar connectivity in alcohol-naïve youth with a family history of alcoholism

    PubMed Central

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

    2011-01-01

    Fronto-cerebellar connections are thought to be involved in higher-order cognitive functioning. It is suspected that damage to this network may contribute to cognitive deficits in chronic alcoholics. However, it remains to be elucidated if fronto-cerebellar circuitry is altered in high-risk individuals even prior to alcohol use onset. The current study used functional connectivity MRI (fcMRI) to examine fronto-cerebellar circuitry in 13 alcohol-naïve, at-risk youth with a family history of alcoholism (FH+) and 14 age-matched controls. In addition, we examined how white matter microstructure, as evidenced by fractional anisotropy (FA) related to fcMRI. FH+ youth showed significantly reduced functional connectivity between bilateral anterior prefrontal cortices and contralateral cerebellar seed regions compared to controls. We found that this reduction in connectivity significantly correlated with reduced FA in the anterior limb of the internal capsule and the superior longitudinal fasciculus. Taken together, our findings reflect associated aberrant functional and structural connectivity in substance-naïve FH+ adolescents, perhaps suggesting an identifiable neurophenotypic precursor to substance use. Given the role of frontal and cerebellar brain regions in subserving executive functioning, the presence of premorbid abnormalities in fronto-cerebellar circuitry may heighten the risk for developing an alcohol use disorder in FH+ youth through atypical control processing. PMID:20970506

  18. A voxel-based morphometry (VBM) analysis of regional grey and white matter volume abnormalities within the speech production network of children who stutter.

    PubMed

    Beal, Deryk S; Gracco, Vincent L; Brettschneider, Jane; Kroll, Robert M; De Nil, Luc F

    2013-09-01

    It is well documented that neuroanatomical differences exist between adults who stutter and their fluently speaking peers. Specifically, adults who stutter have been found to have more grey matter volume (GMV) in speech relevant regions including inferior frontal gyrus, insula and superior temporal gyrus (Beal et al., 2007; Song et al., 2007). Despite stuttering having its onset in childhood only one study has investigated the neuroanatomical differences between children who do and do not stutter. Chang et al. (2008) reported children who stutter had less GMV in the bilateral inferior frontal gyri and middle temporal gyrus relative to fluently speaking children. Thus it appears that children who stutter present with unique neuroanatomical abnormalities as compared to those of adults who stutter. In order to better understand the neuroanatomical correlates of stuttering earlier in its development, near the time of onset, we used voxel-based morphometry to examine volumetric differences between 11 children who stutter and 11 fluent children. Children who stutter had less GMV in the bilateral inferior frontal gyri and left putamen but more GMV in right Rolandic operculum and superior temporal gyrus relative to fluent children. Children who stutter also had less white matter volume bilaterally in the forceps minor of the corpus callosum. We discuss our findings of widespread anatomic abnormalities throughout the cortical network for speech motor control within the context of the speech motor skill limitations identified in people who stutter (Namasivayam and van Lieshout, 2008; Smits-Bandstra et al., 2006). Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Early Disruption of Extracellular Pleiotrophin Distribution Alters Cerebellar Neuronal Circuit Development and Function.

    PubMed

    Hamza, M M; Rey, S A; Hilber, P; Arabo, A; Collin, T; Vaudry, D; Burel, D

    2016-10-01

    The cerebellum is a structure of the central nervous system involved in balance, motor coordination, and voluntary movements. The elementary circuit implicated in the control of locomotion involves Purkinje cells, which receive excitatory inputs from parallel and climbing fibers, and are regulated by cerebellar interneurons. In mice as in human, the cerebellar cortex completes its development mainly after birth with the migration, differentiation, and synaptogenesis of granule cells. These cellular events are under the control of numerous extracellular matrix molecules including pleiotrophin (PTN). This cytokine has been shown to regulate the morphogenesis of Purkinje cells ex vivo and in vivo via its receptor PTPζ. Since Purkinje cells are the unique output of the cerebellar cortex, we explored the consequences of their PTN-induced atrophy on the function of the cerebellar neuronal circuit in mice. Behavioral experiments revealed that, despite a normal overall development, PTN-treated mice present a delay in the maturation of their flexion reflex. Moreover, patch clamp recording of Purkinje cells revealed a significant increase in the frequency of spontaneous excitatory postsynaptic currents in PTN-treated mice, associated with a decrease of climbing fiber innervations and an abnormal perisomatic localization of the parallel fiber contacts. At adulthood, PTN-treated mice exhibit coordination impairment on the rotarod test associated with an alteration of the synchronization gait. Altogether these histological, electrophysiological, and behavior data reveal that an early ECM disruption of PTN composition induces short- and long-term defaults in the establishment of proper functional cerebellar circuit.

  20. Cerebro-Cerebellar Functional Connectivity is Associated with Cerebellar Excitation-Inhibition Balance in Autism Spectrum Disorder.

    PubMed

    Hegarty, John P; Weber, Dylan J; Cirstea, Carmen M; Beversdorf, David Q

    2018-05-23

    Atypical functional connectivity (FC) and an imbalance of excitation-to-inhibition (E/I) have been previously reported in cerebro-cerebellar circuits in autism spectrum disorder (ASD). The current investigation used resting state fMRI and proton magnetic resonance spectroscopy ( 1 H-MRS) to examine the relationships between E/I (glutamate + glutamine/GABA) and FC of the dorsolateral prefrontal cortex and posterolateral cerebellar hemisphere from 14 adolescents/adults with ASD and 12 age/sex/IQ-matched controls. In this pilot sample, cerebro-cerebellar FC was positively associated with cerebellar E/I and listening comprehension abilities in individuals with ASD but not controls. Additionally, a subgroup of individuals with ASD and low FC (n = 5) exhibited reduced E/I and impaired listening comprehension. Thus, altered functional coherence of cerebro-cerebellar circuits in ASD may be related with a cerebellar E/I imbalance.

  1. Surface-based brain morphometry and diffusion tensor imaging in schizoaffective disorder.

    PubMed

    Landin-Romero, Ramón; Canales-Rodríguez, Erick J; Kumfor, Fiona; Moreno-Alcázar, Ana; Madre, Mercè; Maristany, Teresa; Pomarol-Clotet, Edith; Amann, Benedikt L

    2017-01-01

    The profile of grey matter abnormalities and related white-matter pathology in schizoaffective disorder has only been studied to a limited extent. The aim of this study was to identify grey- and white-matter abnormalities in patients with schizoaffective disorder using complementary structural imaging techniques. Forty-five patients meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria and Research Diagnostic Criteria for schizoaffective disorder and 45 matched healthy controls underwent structural-T1 and diffusion magnetic resonance imaging to enable surface-based brain morphometry and diffusion tensor imaging analyses. Analyses were conducted to determine group differences in cortical volume, cortical thickness and surface area, as well as in fractional anisotropy and mean diffusivity. At a threshold of p = 0.05 corrected, all measures revealed significant differences between patients and controls at the group level. Spatial overlap of abnormalities was observed across the various structural neuroimaging measures. In grey matter, patients with schizoaffective disorder showed abnormalities in the frontal and temporal lobes, striatum, fusiform, cuneus, precuneus, lingual and limbic regions. White-matter abnormalities were identified in tracts connecting these areas, including the corpus callosum, superior and inferior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus and cingulum bundle. The spatial overlap of abnormalities across the different imaging techniques suggests widespread and consistent brain pathology in schizoaffective disorder. The abnormalities were mainly detected in areas that have commonly been reported to be abnormal in schizophrenia, and to some extent in bipolar disorder, which may explain the clinical and aetiological overlap in these disorders.

  2. Volumetric abnormalities of the brain in a rat model of recurrent headache.

    PubMed

    Jia, Zhihua; Tang, Wenjing; Zhao, Dengfa; Hu, Guanqun; Li, Ruisheng; Yu, Shengyuan

    2018-01-01

    Voxel-based morphometry is used to detect structural brain changes in patients with migraine. However, the relevance of migraine and structural changes is not clear. This study investigated structural brain abnormalities based on voxel-based morphometry using a rat model of recurrent headache. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious male rats. Rats were subgrouped according to the frequency and duration of the inflammatory soup infusion. Tactile sensory testing was conducted prior to infusion of the inflammatory soup or saline. The periorbital tactile thresholds in the high-frequency inflammatory soup stimulation group declined persistently from day 5. Increased white matter volume was observed in the rats three weeks after inflammatory soup stimulation, brainstem in the in the low-frequency inflammatory soup-infusion group and cortex in the high-frequency inflammatory soup-infusion group. After six weeks' stimulation, rats showed gray matter volume changes. The brain structural abnormalities recovered after the stimulation was stopped in the low-frequency inflammatory soup-infused rats and persisted even after the high-frequency inflammatory soup stimulus stopped. The changes of voxel-based morphometry in migraineurs may be the result of recurrent headache. Cognition, memory, and learning may play an important role in the chronification of migraines. Reducing migraine attacks has the promise of preventing chronicity of migraine.

  3. Structural and Functional Magnetic Resonance Imaging of the Cerebellum: Considerations for Assessing Cerebellar Ataxias.

    PubMed

    Deistung, Andreas; Stefanescu, Maria R; Ernst, Thomas M; Schlamann, Marc; Ladd, Mark E; Reichenbach, Jürgen R; Timmann, Dagmar

    2016-02-01

    Magnetic resonance imaging (MRI) of the brain is of high interest for diagnosing and understanding degenerative ataxias. Here, we present state-of-the-art MRI methods to characterize structural alterations of the cerebellum and introduce initial experiments to show abnormalities in the cerebellar nuclei. Clinically, T1-weighted MR images are used to assess atrophy of the cerebellar cortex, the brainstem, and the spinal cord, whereas T2-weighted and PD-weighted images are typically employed to depict potential white matter lesions that may be associated with certain types of ataxias. More recently, attention has also focused on the characterization of the cerebellar nuclei, which are discernible on spatially highly resolved iron-sensitive MR images due to their relatively high iron content, including T2 (*)-weighted images, susceptibility-weighted images (SWI), effective transverse relaxation rate (R2 (*)) maps, and quantitative susceptibility maps (QSM). Among these iron-sensitive techniques, QSM reveals the best contrast between cerebellar nuclei and their surroundings. In particular, the gyrification of the dentate nuclei is prominently depicted, even at the clinically widely available field strength of 3 T. The linear relationship between magnetic susceptibility and local iron content allows for determination of iron deposition in cerebellar nuclei non-invasively. The increased signal-to-noise ratio of ultrahigh-field MRI (B0 ≥ 7 T) and advances in spatial normalization methods enable functional MRI (fMRI) at the level of the cerebellar cortex and cerebellar nuclei. Data from initial fMRI studies are presented in three common forms of hereditary ataxias (Friedreich's ataxia, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6). Characteristic changes in the fMRI signal are discussed in the light of histopathological data and current knowledge of the underlying physiology of the fMRI signal in the cerebellum.

  4. Cerebellar microfolia and other abnormalities of neuronal growth, migration, and lamination in the Pit1dw-J homozygote mutant mouse

    NASA Technical Reports Server (NTRS)

    Sekiguchi, M.; Abe, H.; Moriya, M.; Tanaka, O.; Nowakowski, R. S.

    1998-01-01

    The Snell dwarf mouse (Pit1dw-J homozygote) has a mutation in the Pit1 gene that prevents the normal formation of the anterior pituitary. In neonates and adults there is almost complete absence of growth hormone (GH), prolactin (PRL), thyroxin (T4), and thyroid-stimulating hormone (TSH). Since these hormones have been suggested to play a role in normal development of the central nervous system (CNS), we have investigated the effects of the Pit1dw-J mutation on the cerebellum and hippocampal formation. In the cerebellum, there were abnormalities of both foliation and lamination. The major foliation anomalies were 1) changes in the relative size of specific folia and also the proportional sizes of the anterior vs posterior cerebellum; and 2) the presence of between one and three microfolia per half cerebellum. The microfolia were all in the medial portion of the hemisphere in the caudal part of the cerebellum. Each microfolium was just rostral to a normal fissure and interposed between the fissure and a normal gyrus. Lamination abnormalities included an increase in the number of single ectopic granule cells in the molecular layer in both cerebellar vermis (86%) and hemisphere (40%) in comparison with the wild-type mouse. In the hippocampus of the Pit1dw-J homozygote mouse, the number of pyramidal cells was decreased, although the width of the pyramidal cell layer throughout areas CA1-CA3 appeared to be normal, but less densely populated than in the wild-type mouse. Moreover, the number of granule cells that form the granule cell layer was decreased from the wild-type mouse and some ectopic granule cells (occurring both as single cells and as small clusters) were observed in the innermost portion of the molecular layer. The abnormalities observed in the Pit1dw-J homozygote mouse seem to be caused by both direct and indirect effects of the deficiency of TSH (or T4), PRL, or GH rather than by a direct effect of the deletion of Pit1.

  5. What is the impact of child abuse on gray matter abnormalities in individuals with major depressive disorder: a case control study.

    PubMed

    Ahn, Sung Jun; Kyeong, Sunghyon; Suh, Sang Hyun; Kim, Jae-Jin; Chung, Tae-Sub; Seok, Jeong-Ho

    2016-11-14

    Patients with major depressive disorder (MDD) present heterogeneous clinical symptoms, and childhood abuse is associated with deepening of psychopathology. The aim of this study was to identify structural brain abnormalities in MDD and to assess further differences in gray matter density (GMD) associated with childhood abuse in MDD. Differences in regional GMD between 34 MDD patients and 26 healthy controls were assessed using magnetic resonance imaging and optimized voxel-based morphometry. Within the MDD group, further comparisons were performed focusing on the experience of maltreatment during childhood (23 MDD with child abuse vs 11 MDD without child abuse). Compared with healthy controls, the MDD patient group showed decreased GMD in the bilateral orbitofrontal cortices, right superior frontal gyrus, right posterior cingulate gyrus, bilateral middle occipital gyri, and left cuneus. In addition, the patient group showed increased GMD in bilateral postcentral gyri, parieto-occipital cortices, putamina, thalami, and hippocampi, and left cerebellar declive and tuber of vermis. Within the MDD patient group, the subgroup with abuse showed a tendency of decreased GMD in right orbitofrontal cortex, but showed increased GMD in the left postcentral gyrus compared to the subgroup without abuse. Our findings suggest a complicated dysfunction of networks between cortical-subcortical circuits in MDD. In addition, increased GMD in postcentral gyrus and a possible reduction of GMD in the orbitofrontal cortex of MDD patients with abuse subgroup may be associated with abnormalities of body perception and emotional dysregulation.

  6. Cerebro-cerebellar resting state functional connectivity in children and adolescents with autism spectrum disorder

    PubMed Central

    Khan, Amanda J.; Nair, Aarti; Keown, Christopher L.; Datko, Michael C.; Lincoln, Alan J.; Müller, Ralph-Axel

    2017-01-01

    Background The cerebellum plays important roles in both sensorimotor and supramodal cognitive functions. Cellular, volumetric, and functional abnormalities of the cerebellum have been found in autism spectrum disorders (ASD), but no comprehensive investigation of cerebro-cerebellar connectivity in ASD is available. Methods We used resting-state functional connectivity MRI in 56 children and adolescents (28 ASD, 28 typically developing [TD]) aged 8–17 years. Partial and total correlation analyses were performed for unilateral regions of interest (ROIs), distinguished in two broad domains as sensorimotor (premotor/primary motor, somatosensory, superior temporal, occipital) and supramodal (prefrontal, posterior parietal, and inferior and middle temporal). Results There were three main findings: (i) Total correlation analyses showed predominant cerebro-cerebellar functional overconnectivity in the ASD group; (ii) partial correlation analyses that emphasized domain-specificity (sensorimotor vs. supramodal) indicated a pattern of robustly increased connectivity in the ASD group (compared to the TD group) for sensorimotor ROIs, but predominantly reduced connectivity for supramodal ROIs; (iii) this atypical pattern of connectivity was supported by significantly increased non-canonical connections (between sensorimotor cerebral and supramodal cerebellar ROIs, and vice versa) in the ASD group. Conclusions Our findings indicate that sensorimotor intrinsic functional connectivity is atypically increased in ASD, at the expense of connectivity supporting cerebellar participation in supramodal cognition. PMID:25959247

  7. Altered Functional Connectivity of Cognitive-Related Cerebellar Subregions in Alzheimer’s Disease

    PubMed Central

    Zheng, Weimin; Liu, Xingyun; Song, Haiqing; Li, Kuncheng; Wang, Zhiqun

    2017-01-01

    Alzheimer’s disease (AD) is the most common cause of dementia. Previous studies have found disrupted resting state functional connectivities (rsFCs) in various brain networks in the AD patients. However, few studies have focused on the rsFCs of the cerebellum and its sub-regions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (rs-fMRI) data including 32 AD patients and 38 healthy controls (HCs). We selected two cognitive-related subregions of the cerebellum as seed region and mapped the whole-brain rsFCs for each subregion. We identified several distinct rsFC patterns of the two cognitive-related cerebellar subregions: default-mode network (DMN), frontoparietal network (FPN), visual network (VN) and sensorimotor network (SMN). Compared with the controls, the AD patients showed disrupted rsFCs in several different networks (DMN, VN and SMN), predicting the impairment of the functional integration in the cerebellum. Notably, these abnormal rsFCs of the two cerebellar subregions were closely associated with cognitive performance. Collectively, we demonstrated the distinct rsFCs patterns of cerebellar sub-regions with various functional networks, which were differentially impaired in the AD patients. PMID:28559843

  8. Cerebellar abiotrophy in a miniature schnauzer.

    PubMed

    Berry, Michelle L; Blas-Machado, Uriel

    2003-08-01

    A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

  9. Brain growth rate abnormalities visualized in adolescents with autism.

    PubMed

    Hua, Xue; Thompson, Paul M; Leow, Alex D; Madsen, Sarah K; Caplan, Rochelle; Alger, Jeffry R; O'Neill, Joseph; Joshi, Kishori; Smalley, Susan L; Toga, Arthur W; Levitt, Jennifer G

    2013-02-01

    Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. Copyright © 2011 Wiley Periodicals, Inc.

  10. Using tensor-based morphometry to detect structural brain abnormalities in rats with adolescent intermittent alcohol exposure

    NASA Astrophysics Data System (ADS)

    Paniagua, Beatriz; Ehlers, Cindy; Crews, Fulton; Budin, Francois; Larson, Garrett; Styner, Martin; Oguz, Ipek

    2011-03-01

    Understanding the effects of adolescent binge drinking that persist into adulthood is a crucial public health issue. Adolescent intermittent ethanol exposure (AIE) is an animal model that can be used to investigate these effects in rodents. In this work, we investigate the application of a particular image analysis technique, tensor-based morphometry, for detecting anatomical differences between AIE and control rats using Diffusion Tensor Imaging (DTI). Deformation field analysis is a popular method for detecting volumetric changes analyzing Jacobian determinants calculated on deformation fields. Recent studies showed that computing deformation field metrics on the full deformation tensor, often referred to as tensor-based morphometry (TBM), increases the sensitivity to anatomical differences. In this paper we conduct a comprehensive TBM study for precisely locating differences between control and AIE rats. Using a DTI RARE sequence designed for minimal geometric distortion, 12-directional images were acquired postmortem for control and AIE rats (n=9). After preprocessing, average images for the two groups were constructed using an unbiased atlas building approach. We non-rigidly register the two atlases using Large Deformation Diffeomorphic Metric Mapping, and analyze the resulting deformation field using TBM. In particular, we evaluate the tensor determinant, geodesic anisotropy, and deformation direction vector (DDV) on the deformation field to detect structural differences. This yields data on the local amount of growth, shrinkage and the directionality of deformation between the groups. We show that TBM can thus be used to measure group morphological differences between rat populations, demonstrating the potential of the proposed framework.

  11. Resting-state cerebellar-cerebral networks are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings.

    PubMed

    Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xiao, Changqing; Zhao, Jingping

    2015-11-26

    Dysconnectivity hypothesis posits that schizophrenia is a disorder with dysconnectivity of the cortico-cerebellar-thalamic-cortical circuit (CCTCC). However, it remains unclear to the changes of the cerebral connectivity with the cerebellum in schizophrenia patients and unaffected siblings. Forty-nine patients with first-episode, drug-naive schizophrenia patients, 46 unaffected siblings of schizophrenia patients and 46 healthy controls participated in the study. Seed-based resting-state functional connectivity approach was employed to analyze the data. Compared with the controls, the patients and the siblings share increased default-mode network (DMN) seed - right Crus II connectivity. The patients have decreased right dorsal attention network (DAN) seed - bilateral cerebellum 4,5 connectivity relative to the controls. By contrast, the siblings exhibit increased FC between the right DAN seed and the right cerebellum 6 and right cerebellum 4,5 compared to the controls. No other abnormal connectivities (executive control network and salience network) are observed in the patients/siblings relative to the controls. There are no correlations between abnormal cerebellar-cerebral connectivities and clinical variables. Cerebellar-cerebral connectivity of brain networks within the cerebellum are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings. Increased DMN connectivity with the cerebellum may serve as potential endophenotype for schizophrenia.

  12. Resting-state cerebellar-cerebral networks are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings

    PubMed Central

    Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xiao, Changqing; Zhao, Jingping

    2015-01-01

    Dysconnectivity hypothesis posits that schizophrenia is a disorder with dysconnectivity of the cortico-cerebellar-thalamic-cortical circuit (CCTCC). However, it remains unclear to the changes of the cerebral connectivity with the cerebellum in schizophrenia patients and unaffected siblings. Forty-nine patients with first-episode, drug-naive schizophrenia patients, 46 unaffected siblings of schizophrenia patients and 46 healthy controls participated in the study. Seed-based resting-state functional connectivity approach was employed to analyze the data. Compared with the controls, the patients and the siblings share increased default-mode network (DMN) seed – right Crus II connectivity. The patients have decreased right dorsal attention network (DAN) seed – bilateral cerebellum 4,5 connectivity relative to the controls. By contrast, the siblings exhibit increased FC between the right DAN seed and the right cerebellum 6 and right cerebellum 4,5 compared to the controls. No other abnormal connectivities (executive control network and salience network) are observed in the patients/siblings relative to the controls. There are no correlations between abnormal cerebellar-cerebral connectivities and clinical variables. Cerebellar-cerebral connectivity of brain networks within the cerebellum are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings. Increased DMN connectivity with the cerebellum may serve as potential endophenotype for schizophrenia. PMID:26608842

  13. Cerebellar abiotrophy in a miniature schnauzer

    PubMed Central

    Berry, Michelle L.; Blas-Machado, Uriel

    2003-01-01

    A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer. PMID:13677598

  14. Functional recovery after cerebellar damage is related to GAP-43-mediated reactive responses of pre-cerebellar and deep cerebellar nuclei.

    PubMed

    Burello, Lorena; De Bartolo, Paola; Gelfo, Francesca; Foti, Francesca; Angelucci, Francesco; Petrosini, Laura

    2012-01-01

    Since brain injuries in adulthood are a leading cause of long-term disabilities, the development of rehabilitative strategies able to impact on functional outcomes requires detailing adaptive neurobiological responses. Functional recovery following brain insult is mainly ascribed to brain neuroplastic properties although the close linkage between neuronal plasticity and functional recovery is not yet fully clarified. The present study analyzed the reactive responses of pre-cerebellar (inferior olive, lateral reticular nucleus and pontine nuclei) and deep cerebellar nuclei after a hemicerebellectomy, considering the great plastic potential of the cerebellar system in physiological and pathological conditions. The time course of the plastic reorganization following cerebellar lesion was investigated by monitoring the Growth Associated Protein-43 (GAP-43) immunoreactivity. The time course of recovery from cerebellar symptoms was also assessed to parallel behavioral and neurobiological parameters. A key role of GAP-43 in neuronal reactive responses was evidenced. Neurons that underwent an axotomy as consequence of the right hemicerebellectomy (neurons of left inferior olive, right lateral reticular nucleus and left pontine nuclei) exhibited enhanced GAP-43 immunoreactivity and cell death. As for the not-axotomized neurons, we found enhanced GAP-43 immunoreactivity only in right pontine nuclei projecting to the spared (left) hemicerebellum. GAP-43 levels augmented also in the three deep cerebellar nuclei of the spared hemicerebellum, indicating the ponto-cerebellar circuit as crucially involved in functional recovery. Interestingly, each nucleus showed a distinct time course in GAP-43 immunoreactivity. GAP-43 levels peaked during the first post-operative week in the fastigial and interposed nuclei and after one month in the dentate nucleus. These results suggest that the earlier plastic events of the fastigial and interposed nuclei were driving compensation of the

  15. A Cerebellar Framework for Predictive Coding and Homeostatic Regulation in Depressive Disorder.

    PubMed

    Schutter, Dennis J L G

    2016-02-01

    Depressive disorder is associated with abnormalities in the processing of reward and punishment signals and disturbances in homeostatic regulation. These abnormalities are proposed to impair error minimization routines for reducing uncertainty. Several lines of research point towards a role of the cerebellum in reward- and punishment-related predictive coding and homeostatic regulatory function in depressive disorder. Available functional and anatomical evidence suggests that in addition to the cortico-limbic networks, the cerebellum is part of the dysfunctional brain circuit in depressive disorder as well. It is proposed that impaired cerebellar function contributes to abnormalities in predictive coding and homeostatic dysregulation in depressive disorder. Further research on the role of the cerebellum in depressive disorder may further extend our knowledge on the functional and neural mechanisms of depressive disorder and development of novel antidepressant treatments strategies targeting the cerebellum.

  16. Phenotypic outcomes in Mouse and Human Foxc1 dependent Dandy-Walker cerebellar malformation suggest shared mechanisms.

    PubMed

    Haldipur, Parthiv; Dang, Derek; Aldinger, Kimberly A; Janson, Olivia K; Guimiot, Fabien; Adle-Biasette, Homa; Dobyns, William B; Siebert, Joseph R; Russo, Rosa; Millen, Kathleen J

    2017-01-16

    FOXC1 loss contributes to Dandy-Walker malformation (DWM), a common human cerebellar malformation. Previously, we found that complete Foxc1 loss leads to aberrations in proliferation, neuronal differentiation and migration in the embryonic mouse cerebellum (Haldipur et al., 2014). We now demonstrate that hypomorphic Foxc1 mutant mice have granule and Purkinje cell abnormalities causing subsequent disruptions in postnatal cerebellar foliation and lamination. Particularly striking is the presence of a partially formed posterior lobule which echoes the posterior vermis DW 'tail sign' observed in human imaging studies. Lineage tracing experiments in Foxc1 mutant mouse cerebella indicate that aberrant migration of granule cell progenitors destined to form the posterior-most lobule causes this unique phenotype. Analyses of rare human del chr 6p25 fetal cerebella demonstrate extensive phenotypic overlap with our Foxc1 mutant mouse models, validating our DWM models and demonstrating that many key mechanisms controlling cerebellar development are likely conserved between mouse and human.

  17. The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration

    PubMed Central

    Elsen, Gina E.; Choi, Louis Y.; Prince, Victoria E.; Ho, Robert K.

    2009-01-01

    During development, Met signaling regulates a range of cellular processes including growth, differentiation, survival and migration. The Met gene encodes a tyrosine kinase receptor, which is activated by Hgf (hepatocyte growth factor) ligand. Altered regulation of human MET expression has been implicated in autism. In mouse, Met signaling has been shown to regulate cerebellum development. Since abnormalities in cerebellar structure have been reported in some autistic patients, we have used the zebrafish to address the role of Met signaling during cerebellar development and thus further our understanding of the molecular basis of autism. We find that zebrafish met is expressed in the cerebellar primordium, later localizing to the ventricular zone (VZ), with the hgf1 and hgf2 ligand genes expressed in surrounding tissues. Morpholino knockdown of either Met or its Hgf ligands leads to a significant reduction in the size of the cerebellum, primarily as a consequence of reduced proliferation. Met signaling knockdown disrupts specification of VZ-derived cell types, and also reduces granule cell numbers, due to an early effect on cerebellar proliferation and/or as an indirect consequence of loss of signals from VZ-derived cells later in development. These patterning defects preclude analysis of cerebellar neuronal migration, but we have found that Met signaling is necessary for migration of hindbrain facial motor neurons. In summary, we have described roles for Met signaling in coordinating growth and cell type specification within the developing cerebellum, and in migration of hindbrain neurons. These functions may underlie the correlation between altered MET regulation and Autism Spectrum Disorders. PMID:19732764

  18. Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia.

    PubMed

    Iskusnykh, Igor Y; Buddington, Randal K; Chizhikov, Victor V

    2018-08-01

    Preterm birth is a leading cause of long-term motor and cognitive deficits. Clinical studies suggest that some of these deficits result from disruption of cerebellar development, but the mechanisms that mediate cerebellar abnormalities in preterm infants are largely unknown. Furthermore, it remains unclear whether preterm birth and precocious exposure to the ex-utero environment directly disrupt cerebellar development or indirectly by increasing the probability of cerebellar injury, including that resulting from clinical interventions and protocols associated with the care of preterm infants. In this study, we analyzed the cerebellum of preterm pigs delivered via c-section at 91% term and raised for 10 days, until term-equivalent age. The pigs did not receive any treatments known or suspected to affect cerebellar development and had no evidence of brain damage. Term pigs sacrificed at birth were used as controls. Immunohistochemical analysis revealed that preterm birth did not affect either size or numbers of Purkinje cells or molecular layer interneurons at term-equivalent age. The number of granule cell precursors and Bergmann glial fibers, however, were reduced in preterm pigs. Preterm pigs had reduced proliferation but not differentiation of granule cells. qRT-PCR analysis of laser capture microdissected external granule cell layer showed that preterm pigs had a reduced expression of Ccnd1 (Cyclin D1), Ccnb1 (Cyclin B1), granule cell master regulatory transcription factor Atoh1, and signaling molecule Jag1. In vitro rescue experiments identified Jag1 as a central granule cell gene affected by preterm birth. Thus, preterm birth and precocious exposure to the ex-utero environment disrupt cerebellum by modulating expression of key cerebellar developmental genes, predominantly affecting development of granule precursors and Bergmann glia. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Autosomal recessive cerebellar ataxias

    PubMed Central

    Palau, Francesc; Espinós, Carmen

    2006-01-01

    Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia. PMID:17112370

  20. Disruptive changes of cerebellar functional connectivity with the default mode network in schizophrenia.

    PubMed

    Wang, Lubin; Zou, Feng; Shao, Yongcong; Ye, Enmao; Jin, Xiao; Tan, Shuwen; Hu, Dewen; Yang, Zheng

    2014-12-01

    The default mode network (DMN) plays an important role in the physiopathology of schizophrenia. Previous studies have suggested that the cerebellum participates in higher-order cognitive networks such as the DMN. However, the specific contribution of the cerebellum to the DMN abnormalities in schizophrenia has yet to be established. In this study, we investigated cerebellar functional connectivity differences between 60 patients with schizophrenia and 60 healthy controls from a public resting-state fMRI database. Seed-based correlation analysis was performed by using seeds from the left Crus I, right Crus I and Lobule IX, which have previously been identified as being involved in the DMN. Our results revealed that, compared with the healthy controls, the patients showed significantly reduced cerebellar functional connectivity with the thalamus and several frontal regions including the middle frontal gyrus, anterior cingulate cortex, and supplementary motor area. Moreover, the positive correlations between the strength of frontocerebellar and thalamocerebellar functional connectivity observed in the healthy subjects were diminished in the patients. Our findings implicate disruptive changes of the fronto-thalamo-cerebellar circuit in schizophrenia, which may provide further evidence for the "cognitive dysmetria" concept of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Cerebellar liponeurocytoma with extracranial extension: case report.

    PubMed

    Ben Nsir, A; Ben Said, I; Hammami, N; Sebai, R; Jemel, H

    2014-01-01

    Cerebellar liponeurocytoma is a newly recognized, rare clinicopathological entity commonly described in the cerebellar hemispheres or the vermis. We present a rare case of cerebellar liponeurocytoma arising from the left cerebellar amygdala with extracranial extension. Such a condition has never been previously reported. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Cerebellar and Brainstem Malformations.

    PubMed

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-08-01

    The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Pronounced within-individual plasticity in sperm morphometry across social environments.

    PubMed

    Immler, Simone; Pryke, Sarah R; Birkhead, Tim R; Griffith, Simon C

    2010-06-01

    Sperm morphometry (i.e., size and shape) and function are important determinants of male reproductive success and are thought to be under stabilizing selection. However, recent studies suggest that sperm morphometry can be a phenotypically plastic trait, which can be adjusted to varying conditions. We tested whether different behavioral strategies in aggression between aggressive red and nonaggressive black males of the color polymorphic Gouldian finch (Erythrura gouldiae) can influence sperm morphometry. We show pronounced within-individual phenotypic plasticity in sperm morphometry of male Gouldian finches in three different social environments. Both red and black males placed in intermediate to high competitive environments (high frequency of red males) increased the relative length of their sperm midpiece. By contrast, red males placed in low to intermediate competitive environments (higher frequency of black males) increased the length of the sperm flagellum. Significant changes in stress and sex steroid hormone levels (in response to the competitive environment) appear to influence sperm traits in red but not in black males, suggesting that changes in hormonal levels are not solely responsible for the observed changes in sperm morphometry. These findings imply that males can adjust sperm morphometry across social environments.

  4. Mitotic events in cerebellar granule progenitor cells that expand cerebellar surface area are critical for normal cerebellar cortical lamination in mice.

    PubMed

    Chang, Joshua C; Leung, Mark; Gokozan, Hamza Numan; Gygli, Patrick Edwin; Catacutan, Fay Patsy; Czeisler, Catherine; Otero, José Javier

    2015-03-01

    Late embryonic and postnatal cerebellar folial surface area expansion promotes cerebellar cortical cytoarchitectural lamination. We developed a streamlined sampling scheme to generate unbiased estimates of murine cerebellar surface area and volume using stereologic principles. We demonstrate that, during the proliferative phase of the external granular layer (EGL) and folial surface area expansion, EGL thickness does not change and thus is a topological proxy for progenitor self-renewal. The topological constraints indicate that, during proliferative phases, migration out of the EGL is balanced by self-renewal. Progenitor self-renewal must, therefore, include mitotic events yielding 2 cells in the same layer to increase surface area (β events) and mitotic events yielding 2 cells, with 1 cell in a superficial layer and 1 cell in a deeper layer (α events). As the cerebellum grows, therefore, β events lie upstream of α events. Using a mathematical model constrained by the measurements of volume and surface area, we could quantify intermitotic times for β events on a per-cell basis in postnatal mouse cerebellum. Furthermore, we found that loss of CCNA2, which decreases EGL proliferation and secondarily induces cerebellar cortical dyslamination, shows preserved α-type events. Thus, CCNA2-null cerebellar granule progenitor cells are capable of self-renewal of the EGL stem cell niche; this is concordant with prior findings of extensive apoptosis in CCNA2-null mice. Similar methodologies may provide another layer of depth to the interpretation of results from stereologic studies.

  5. Effect of edaravone on acute brainstem-cerebellar infarction with vertigo and sudden hearing loss.

    PubMed

    Inoue, Yuta; Yabe, Takao; Okada, Kazunari; Nakamura, Yuka

    2014-06-01

    We report 2 cases with acute brainstem and brainstem-cerebellar infarction showed improvement of their signs and symptoms after administration of edaravone. Case 1, a 74-year-old woman who experienced sudden vertigo, also had dysarthria and left hemiplegia. Magnetic resonance imaging (MRI) showed an abnormal region in the right ventrolateral medulla oblongata. The patient's vertigo and hemiplegia improved completely after treatment. Case 2, a 50-year-old man who experienced sudden vertigo and sensorineural hearing loss (SNHL), developed dysarthria after admission. MRI revealed acute infarction in the right cerebellar hemisphere. Magnetic resonance angiography revealed dissection of the basilar artery and occlusion of the right anterior inferior cerebellar artery. The patient's vertigo and hearing remarkably improved. We have described 2 patients whose early symptoms were vertigo and sudden SNHL, but who were later shown to have ischemic lesions of the central nervous system. Edaravone is neuroprotective drug with free radical-scavenging actions. Free radicals in the ear are responsible for ischemic damage. Edaravone, a free radical scavenger, may be useful in the treatment of vertigo and SNHL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Upper body kinematics in patients with cerebellar ataxia.

    PubMed

    Conte, Carmela; Pierelli, Francesco; Casali, Carlo; Ranavolo, Alberto; Draicchio, Francesco; Martino, Giovanni; Harfoush, Mahmoud; Padua, Luca; Coppola, Gianluca; Sandrini, Giorgio; Serrao, Mariano

    2014-12-01

    Although abnormal oscillations of the trunk are a common clinical feature in patients with cerebellar ataxia, the kinematic behaviour of the upper body in ataxic patients has yet to be investigated in quantitative studies. In this study, an optoelectronic motion analysis system was used to measure the ranges of motion (ROMs) of the head and trunk segments in the sagittal, frontal and yaw planes in 16 patients with degenerative cerebellar ataxia during gait at self-selected speed. The data obtained were compared with those collected in a gender-, age- and gait speed-matched sample of healthy subjects and correlated with gait variables (time-distance means and coefficients of variation) and clinical variables (disease onset, duration and severity). The results showed significantly larger head and/or trunk ROMs in ataxic patients compared with controls in all three spatial planes, and significant correlations between trunk ROMs and disease duration and severity (in sagittal and frontal planes) and time-distance parameters (in the yaw plane), and between both head and trunk ROMs and swing phase duration variability (in the sagittal plane). Furthermore, the ataxic patients showed a flexed posture of both the head and the trunk during walking. In conclusion, our study revealed abnormal motor behaviour of the upper body in ataxic patients, mainly resulting in a flexed posture and larger oscillations of the head and trunk. The results of the correlation analyses suggest that the longer and more severe the disease, the larger the upper body oscillations and that large trunk oscillations may explain some aspects of gait variability. These results suggest the need of specific rehabilitation treatments or the use of elastic orthoses that may be particularly useful to reduce trunk oscillations and improve dynamic stability.

  7. Multiple developmental programs are altered by loss of Zic1 and Zic4 to cause Dandy-Walker malformation cerebellar pathogenesis

    PubMed Central

    Blank, Marissa C.; Grinberg, Inessa; Aryee, Emmanuel; Laliberte, Christine; Chizhikov, Victor V.; Henkelman, R. Mark; Millen, Kathleen J.

    2011-01-01

    Heterozygous deletions encompassing the ZIC1;ZIC4 locus have been identified in a subset of individuals with the common cerebellar birth defect Dandy-Walker malformation (DWM). Deletion of Zic1 and Zic4 in mice produces both cerebellar size and foliation defects similar to human DWM, confirming a requirement for these genes in cerebellar development and providing a model to delineate the developmental basis of this clinically important congenital malformation. Here, we show that reduced cerebellar size in Zic1 and Zic4 mutants results from decreased postnatal granule cell progenitor proliferation. Through genetic and molecular analyses, we show that Zic1 and Zic4 have Shh-dependent function promoting proliferation of granule cell progenitors. Expression of the Shh-downstream genes Ptch1, Gli1 and Mycn was downregulated in Zic1/4 mutants, although Shh production and Purkinje cell gene expression were normal. Reduction of Shh dose on the Zic1+/−;Zic4+/− background also resulted in cerebellar size reductions and gene expression changes comparable with those observed in Zic1−/−;Zic4−/− mice. Zic1 and Zic4 are additionally required to pattern anterior vermis foliation. Zic mutant folial patterning abnormalities correlated with disrupted cerebellar anlage gene expression and Purkinje cell topography during late embryonic stages; however, this phenotype was Shh independent. In Zic1+/−;Zic4+/−;Shh+/−, we observed normal cerebellar anlage patterning and foliation. Furthermore, cerebellar patterning was normal in both Gli2-cko and Smo-cko mutant mice, where all Shh function was removed from the developing cerebellum. Thus, our data demonstrate that Zic1 and Zic4 have both Shh-dependent and -independent roles during cerebellar development and that multiple developmental disruptions underlie Zic1/4-related DWM. PMID:21307096

  8. Cerebellar Hematoma Location: Implications for the Underlying Microangiopathy.

    PubMed

    Pasi, Marco; Marini, Sandro; Morotti, Andrea; Boulouis, Gregoire; Xiong, Li; Charidimou, Andreas; Ayres, Alison M; Lee, Myung Joo; Biffi, Alessandro; Goldstein, Joshua N; Rosand, Jonathan; Gurol, M Edip; Greenberg, Steven M; Viswanathan, Anand

    2018-01-01

    Spontaneous cerebellar intracerebral hemorrhage (ICH) has been reported to be mainly associated with vascular changes secondary to hypertension. However, a subgroup of cerebellar ICH seems related to vascular amyloid deposition (cerebral amyloid angiopathy). We sought to determine whether location of hematoma in the cerebellum (deep and superficial regions) was suggestive of a particular hemorrhage-prone small-vessel disease pathology (cerebral amyloid angiopathy or hypertensive vasculopathy). Consecutive patients with cerebellar ICH from a single tertiary care medical center were recruited. Based on data from pathological reports, patients were divided according to the location of the primary cerebellar hematoma (deep versus superficial). Location of cerebral microbleeds (CMBs; strictly lobar, strictly deep, and mixed CMB) was evaluated on magnetic resonance imaging. One-hundred and eight patients (84%) had a deep cerebellar hematoma, and 20 (16%) a superficial cerebellar hematoma. Hypertension was more prevalent in deep than in patients with superficial cerebellar ICH (89% versus 65%, respectively; P <0.05). Among patients who underwent magnetic resonance imaging, those with superficial cerebellar ICH had higher prevalence of strictly lobar CMB (43%) and lower prevalence of strictly deep or mixed CMB (0%) compared with those with deep superficial cerebellar ICH (6%, 17%, and 38%, respectively). In a multivariable model, presence of strictly lobar CMB was associated with superficial cerebellar ICH (odds ratio, 3.8; 95% confidence interval, 1.5-8.5; P =0.004). Our study showed that superficial cerebellar ICH is related to the presence of strictly lobar CMB-a pathologically proven marker of cerebral amyloid angiopathy. Cerebellar hematoma location may thus help to identify those patients likely to have cerebral amyloid angiopathy pathology. © 2017 American Heart Association, Inc.

  9. LKB1 Regulates Cerebellar Development by Controlling Sonic Hedgehog-mediated Granule Cell Precursor Proliferation and Granule Cell Migration.

    PubMed

    Men, Yuqin; Zhang, Aizhen; Li, Haixiang; Jin, Yecheng; Sun, Xiaoyang; Li, Huashun; Gao, Jiangang

    2015-11-09

    The Liver Kinase B1 (LKB1) gene plays crucial roles in cell differentiation, proliferation and the establishment of cell polarity. We created LKB1 conditional knockout mice (LKB1(Atoh1) CKO) to investigate the function of LKB1 in cerebellar development. The LKB1(Atoh1) CKO mice displayed motor dysfunction. In the LKB1(Atoh1) CKO cerebellum, the overall structure had a larger volume and more lobules. LKB1 inactivation led to an increased proliferation of granule cell precursors (GCPs), aberrant granule cell migration and overproduction of unipolar brush cells. To investigate the mechanism underlying the abnormal foliation, we examined sonic hedgehog signalling (Shh) by testing its transcriptional mediators, the Gli proteins, which regulate the GCPs proliferation and cerebellar foliation during cerebellar development. The expression levels of Gli genes were significantly increased in the mutant cerebellum. In vitro assays showed that the proliferation of cultured GCPs from mutant cerebellum significantly increased, whereas the proliferation of mutant GCPs significantly decreased in the presence of a Shh inhibitor GDC-0049. Thus, LKB1 deficiency in the LKB1(Atoh1) CKO mice enhanced Shh signalling, leading to the excessive GCP proliferation and the formation of extra lobules. We proposed that LKB1 regulates cerebellar development by controlling GCPs proliferation through Shh signalling during cerebellar development.

  10. LKB1 Regulates Cerebellar Development by Controlling Sonic Hedgehog-mediated Granule Cell Precursor Proliferation and Granule Cell Migration

    PubMed Central

    Men, Yuqin; Zhang, Aizhen; Li, Haixiang; Jin, Yecheng; Sun, Xiaoyang; Li, Huashun; Gao, Jiangang

    2015-01-01

    The Liver Kinase B1 (LKB1) gene plays crucial roles in cell differentiation, proliferation and the establishment of cell polarity. We created LKB1 conditional knockout mice (LKB1Atoh1 CKO) to investigate the function of LKB1 in cerebellar development. The LKB1Atoh1 CKO mice displayed motor dysfunction. In the LKB1Atoh1 CKO cerebellum, the overall structure had a larger volume and morelobules. LKB1 inactivationled to an increased proliferation of granule cell precursors (GCPs), aberrant granule cell migration and overproduction of unipolar brush cells. To investigate the mechanism underlying the abnormal foliation, we examined sonic hedgehog signalling (Shh) by testing its transcriptional mediators, the Gli proteins, which regulate the GCPs proliferation and cerebellar foliation during cerebellar development. The expression levels of Gli genes were significantly increased in the mutant cerebellum. In vitro assays showed that the proliferation of cultured GCPs from mutant cerebellum significantly increased, whereas the proliferation of mutant GCPs significantly decreased in the presence of a Shh inhibitor GDC-0049. Thus, LKB1 deficiency in the LKB1Atoh1 CKO mice enhanced Shh signalling, leading to the excessive GCP proliferation and the formation of extra lobules. We proposed that LKB1 regulates cerebellar development by controlling GCPs proliferation through Shh signalling during cerebellar development. PMID:26549569

  11. Eyeblink Conditioning Deficits Indicate Timing and Cerebellar Abnormalities in Schizophrenia

    ERIC Educational Resources Information Center

    Brown, S.M.; Kieffaber, P.D.; Carroll, C.A.; Vohs, J.L.; Tracy, J.A.; Shekhar, A.; O'Donnell, B.F.; Steinmetz, J.E.; Hetrick, W.P.

    2005-01-01

    Accumulating evidence indicates that individuals with schizophrenia manifest abnormalities in structures (cerebellum and basal ganglia) and neurotransmitter systems (dopamine) linked to internal-timing processes. A single-cue tone delay eyeblink conditioning paradigm comprised of 100 learning and 50 extinction trials was used to examine cerebellar…

  12. The Cerebellar-Cerebral Microstructure Is Disrupted at Multiple Sites in Very Preterm Infants with Cerebellar Haemorrhage.

    PubMed

    Neubauer, Vera; Djurdjevic, Tanja; Griesmaier, Elke; Biermayr, Marlene; Gizewski, Elke Ruth; Kiechl-Kohlendorfer, Ursula

    2018-01-01

    Recent advances in magnetic resonance imaging (MRI) techniques have prompted reconsideration of the anatomical correlates of adverse outcomes in preterm infants. The importance of the contribution made by the cerebellum is now increasingly appreciated. The effect of cerebellar haemorrhage (CBH) on the microstructure of the cerebellar-cerebral circuit is largely unexplored. To investigate the effect of CBH on the microstructure of cerebellar-cerebral connections in preterm infants aged <32 gestational weeks. Infants underwent diffusion tensor MRI at term-equivalent age. MRI was evaluated for CBH and additional supratentorial brain injury using a validated scoring system. Region of interest-based measures of brain microstructure (fractional anisotropy [FA] and apparent diffusion coefficient) were quantified in 5 vulnerable regions (the centrum semiovale, posterior limb of the internal capsule, corpus callosum, and superior and middle cerebellar peduncles). Group differences between infants with CBH and infants without CBH were assessed. There were 267 infants included in the study. Infants with CBH (isolated and combined) had significantly lower FA values in all regions investigated. Infants with isolated CBH showed lower FA in the middle and superior cerebellar peduncles and in the posterior limb of the internal capsule. This study provides evidence that CBH causes alterations in localised and remote WM pathways in the developing brain. The disruption of the cerebellar-cerebral microstructure at multiple sites adds further support for the concept of developmental diaschisis, which is propagated as an explanation for the consequences of early cerebellar injury on cognitive and affective domains. © 2017 S. Karger AG, Basel.

  13. Phenotypic outcomes in Mouse and Human Foxc1 dependent Dandy-Walker cerebellar malformation suggest shared mechanisms

    PubMed Central

    Haldipur, Parthiv; Dang, Derek; Aldinger, Kimberly A; Janson, Olivia K; Guimiot, Fabien; Adle-Biasette, Homa; Dobyns, William B; Siebert, Joseph R; Russo, Rosa; Millen, Kathleen J

    2017-01-01

    FOXC1 loss contributes to Dandy-Walker malformation (DWM), a common human cerebellar malformation. Previously, we found that complete Foxc1 loss leads to aberrations in proliferation, neuronal differentiation and migration in the embryonic mouse cerebellum (Haldipur et al., 2014). We now demonstrate that hypomorphic Foxc1 mutant mice have granule and Purkinje cell abnormalities causing subsequent disruptions in postnatal cerebellar foliation and lamination. Particularly striking is the presence of a partially formed posterior lobule which echoes the posterior vermis DW 'tail sign' observed in human imaging studies. Lineage tracing experiments in Foxc1 mutant mouse cerebella indicate that aberrant migration of granule cell progenitors destined to form the posterior-most lobule causes this unique phenotype. Analyses of rare human del chr 6p25 fetal cerebella demonstrate extensive phenotypic overlap with our Foxc1 mutant mouse models, validating our DWM models and demonstrating that many key mechanisms controlling cerebellar development are likely conserved between mouse and human. DOI: http://dx.doi.org/10.7554/eLife.20898.001 PMID:28092268

  14. Time course of changes in sperm morphometry and semen variables during testosterone-induced suppression of human spermatogenesis.

    PubMed

    Garrett, C; Liu, D Y; McLachlan, R I; Baker, H W G

    2005-11-01

    Quantification of changes in semen may give insight into the testosterone (T)-induced disruption of spermatogenesis in man. A model analogous to flushing of sperm from the genital tract after vasectomy was used to quantify the time course of semen changes in subjects participating in male contraceptive trials using 800 mg T-implant (n = 25) or 200 mg weekly intramuscular injection (IM-T; n = 33). A modified exponential decay model allowed for delayed onset and incomplete disruption to spermatogenesis. Semen variables measured weekly during a 91-day period after initial treatment were fitted to the model. Sperm concentration, total count, motility and morphometry exhibited similar average decay rates (5 day half-life). The mean delay to onset of decline in concentration was 15 (IM-T) and 18 (T-implant) days. The significantly longer (P < 0.005) delays deduced for the commencement of fall in normal morphology (41 days), normal morphometry (40 days) and sperm viability (43 and 55 days), and the change of morphometry to smaller more compact sperm heads are consistent with sperm being progressively cleared from the genital tract rather than continued shedding of immature or abnormal sperm by the seminiferous epithelium. A significant negative relationship was found between lag time and baseline sperm concentration, consistent with longer sperm-epididymal transit times associated with lower daily production rates.

  15. Diagnostic yield of a routine magnetic resonance imaging in tinnitus and clinical relevance of the anterior inferior cerebellar artery loops.

    PubMed

    Hoekstra, Carlijn E L; Prijs, Vera F; van Zanten, Gijsbert A

    2015-02-01

    To assess the diagnostic yield of a routine magnetic resonance imaging (MRI) scan in patients with (unilateral) chronic tinnitus, to define the frequency of incidental findings, and to assess the clinical relevance of potentially found anterior inferior cerebellar artery (AICA) loops. Retrospective cohort study. Tertiary Tinnitus Care Group at the University Medical Center Utrecht. Three hundred twenty-one patients with chronic tinnitus. Routine diagnostic magnetic resonance imaging (MRI) and diagnostic auditory brainstem responses (ABR) when an AICA loop was found. Relationship between abnormalities on MRI and tinnitus. In 138 patients (45%), an abnormality on the MRI scan was described. In only 7 patients (2.2%), the abnormality probably related to the patient's tinnitus. Results were not significantly better in patients with unilateral tinnitus (abnormalities in 3.2%). Incidental findings, not related to the tinnitus, were found in 41% of the patients. In 70 patients (23%), an AICA loop was found in the internal auditory canal. No significant relationships were found between the presence of an AICA loop and the side of the tinnitus, abnormalities on the ABR or complaints specific to nerve compression syndrome. A routine MRI is of little or no value in patients with tinnitus with persistent complaints. Anterior inferior cerebellar artery loops are often encountered on an MRI scan but rarely relate to the tinnitus and should thus be considered incidental findings. It is advised to only perform an MRI when on clinical grounds a specific etiology with tinnitus as the symptom seems probable.

  16. Relationship between structural abnormalities in the cerebellum and dementia, posttraumatic stress disorder and bipolar disorder.

    PubMed

    Baldaçara, Leonardo; Borgio, João Guilherme Fiorani; Araújo, Célia; Nery-Fernandes, Fabiana; Lacerda, Acioly Luiz Taveres; Moraes, Walter André Dos Santos; Montaño, Maria Beatriz Marcondes Macedo; Rocha, Marlos; Quarantini, Lucas C; Schoedl, Aline; Pupo, Mariana; Mello, Marcelo F; Andreoli, Sergio B; Miranda-Scippa, Angela; Ramos, Luiz Roberto; Mari, Jair J; Bressan, Rodrigo Affonseca; Jackowski, Andrea Parolin

    2012-01-01

    New evidence suggests that the cerebellum has structural and functional abnormalities in psychiatric disorders. In this research, the goal was to measure the volume of the cerebellum and its subregions in individuals with psychiatric disorders and to relate these findings to their symptoms. Patients with different degrees of cognitive impairment (Epidemiology of the Elderly - UNIFESP) and patients with post-traumatic stress disorder (PTSD) from population studies were analyzed. Also, patients with bipolar disorder from an outpatient clinic (Center for the Study of Mood and Anxiety Disorders, Universidade Federal da Bahia) were recruited for this study. All subjects underwent a 1.5T structural magnetic resonance scan. Volumetric measures and symptom measurements, by psychometric scales, were performed and compared between patients and controls. The cerebellum volume was reduced in patients with cognitive impairment without dementia and with dementia, in patients with PTSD, and in patients with bipolar disorder compared to controls. In dementia and PTSD, the left cerebellar hemisphere and vermis volume were reduced. In bipolar disorder, volumes of both hemispheres and the vermis were reduced. In the first two studies, these cerebellar volumetric reductions correlated with symptoms of the disease. The exact nature of cerebellar involvement in mental processes is still not fully understood. However, abnormalities in cerebellar structure and its functions have been reported in some of these diseases. Future studies with larger samples are needed to clarify these findings and investigate whether they are important for treatment and prognosis.

  17. Cerebellar learning mechanisms

    PubMed Central

    Freeman, John H.

    2014-01-01

    The mechanisms underlying cerebellar learning are reviewed with an emphasis on old arguments and new perspectives on eyeblink conditioning. Eyeblink conditioning has been used for decades a model system for elucidating cerebellar learning mechanisms. The standard model of the mechanisms underlying eyeblink conditioning is that there two synaptic plasticity processes within the cerebellum that are necessary for acquisition of the conditioned response: 1) long-term depression (LTD) at parallel fiber-Purkinje cell synapses and 2) long-term potentiation (LTP) at mossy fiber-interpositus nucleus synapses. Additional Purkinje cell plasticity mechanisms may also contribute to eyeblink conditioning including LTP, excitability, and entrainment of deep nucleus activity. Recent analyses of the sensory input pathways necessary for eyeblink conditioning indicate that the cerebellum regulates its inputs to facilitate learning and maintain plasticity. Cerebellar learning during eyeblink conditioning is therefore a dynamic interactive process which maximizes responding to significant stimuli and suppresses responding to irrelevant or redundant stimuli. PMID:25289586

  18. Cerebro-cerebellar Resting-State Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder.

    PubMed

    Khan, Amanda J; Nair, Aarti; Keown, Christopher L; Datko, Michael C; Lincoln, Alan J; Müller, Ralph-Axel

    2015-11-01

    The cerebellum plays important roles in sensori-motor and supramodal cognitive functions. Cellular, volumetric, and functional abnormalities of the cerebellum have been found in autism spectrum disorders (ASD), but no comprehensive investigation of cerebro-cerebellar connectivity in ASD is available. We used resting-state functional connectivity magnetic resonance imaging in 56 children and adolescents (28 subjects with ASD, 28 typically developing subjects) 8-17 years old. Partial and total correlation analyses were performed for unilateral regions of interest (ROIs), distinguished in two broad domains as sensori-motor (premotor/primary motor, somatosensory, superior temporal, and occipital) and supramodal (prefrontal, posterior parietal, and inferior and middle temporal). There were three main findings: 1) Total correlation analyses showed predominant cerebro-cerebellar functional overconnectivity in the ASD group; 2) partial correlation analyses that emphasized domain specificity (sensori-motor vs. supramodal) indicated a pattern of robustly increased connectivity in the ASD group (compared with the typically developing group) for sensori-motor ROIs but predominantly reduced connectivity for supramodal ROIs; and 3) this atypical pattern of connectivity was supported by significantly increased noncanonical connections (between sensori-motor cerebral and supramodal cerebellar ROIs and vice versa) in the ASD group. Our findings indicate that sensori-motor intrinsic functional connectivity is atypically increased in ASD, at the expense of connectivity supporting cerebellar participation in supramodal cognition. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Viewing the Personality Traits Through a Cerebellar Lens: a Focus on the Constructs of Novelty Seeking, Harm Avoidance, and Alexithymia.

    PubMed

    Petrosini, Laura; Cutuli, Debora; Picerni, Eleonora; Laricchiuta, Daniela

    2017-02-01

    The variance in the range of personality trait expression appears to be linked to structural variance in specific brain regions. In evidencing associations between personality factors and neurobiological measures, it seems evident that the cerebellum has not been up to now thought as having a key role in personality. This paper will review the most recent structural and functional neuroimaging literature that engages the cerebellum in personality traits, as novelty seeking and harm avoidance, and it will discuss the findings in the context of contemporary theories of affective and cognitive cerebellar function. By using region of interest (ROI)- and voxel-based approaches, we recently evidenced that the cerebellar volumes correlate positively with novelty seeking scores and negatively with harm avoidance scores. Subjects who search for new situations as a novelty seeker does (and a harm avoiding does not do) show a different engagement of their cerebellar circuitries in order to rapidly adapt to changing environments. The emerging model of cerebellar functionality may explain how the cerebellar abilities in planning, controlling, and putting into action the behavior are associated to normal or abnormal personality constructs. In this framework, it is worth reporting that increased cerebellar volumes are even associated with high scores in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. On such a basis, it seems necessary to go over the traditional cortico-centric view of personality constructs and to address the function of the cerebellar system in sustaining aspects of motivational network that characterizes the different temperamental traits.

  20. A toolbox to visually explore cerebellar shape changes in cerebellar disease and dysfunction.

    PubMed

    Abulnaga, S Mazdak; Yang, Zhen; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M; Onyike, Chiadi U; Ying, Sarah H; Prince, Jerry L

    2016-02-27

    The cerebellum plays an important role in motor control and is also involved in cognitive processes. Cerebellar function is specialized by location, although the exact topographic functional relationship is not fully understood. The spinocerebellar ataxias are a group of neurodegenerative diseases that cause regional atrophy in the cerebellum, yielding distinct motor and cognitive problems. The ability to study the region-specific atrophy patterns can provide insight into the problem of relating cerebellar function to location. In an effort to study these structural change patterns, we developed a toolbox in MATLAB to provide researchers a unique way to visually explore the correlation between cerebellar lobule shape changes and function loss, with a rich set of visualization and analysis modules. In this paper, we outline the functions and highlight the utility of the toolbox. The toolbox takes as input landmark shape representations of subjects' cerebellar substructures. A principal component analysis is used for dimension reduction. Following this, a linear discriminant analysis and a regression analysis can be performed to find the discriminant direction associated with a specific disease type, or the regression line of a specific functional measure can be generated. The characteristic structural change pattern of a disease type or of a functional score is visualized by sampling points on the discriminant or regression line. The sampled points are used to reconstruct synthetic cerebellar lobule shapes. We showed a few case studies highlighting the utility of the toolbox and we compare the analysis results with the literature.

  1. A toolbox to visually explore cerebellar shape changes in cerebellar disease and dysfunction

    NASA Astrophysics Data System (ADS)

    Abulnaga, S. Mazdak; Yang, Zhen; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi U.; Ying, Sarah H.; Prince, Jerry L.

    2016-03-01

    The cerebellum plays an important role in motor control and is also involved in cognitive processes. Cerebellar function is specialized by location, although the exact topographic functional relationship is not fully understood. The spinocerebellar ataxias are a group of neurodegenerative diseases that cause regional atrophy in the cerebellum, yielding distinct motor and cognitive problems. The ability to study the region-specific atrophy patterns can provide insight into the problem of relating cerebellar function to location. In an effort to study these structural change patterns, we developed a toolbox in MATLAB to provide researchers a unique way to visually explore the correlation between cerebellar lobule shape changes and function loss, with a rich set of visualization and analysis modules. In this paper, we outline the functions and highlight the utility of the toolbox. The toolbox takes as input landmark shape representations of subjects' cerebellar substructures. A principal component analysis is used for dimension reduction. Following this, a linear discriminant analysis and a regression analysis can be performed to find the discriminant direction associated with a specific disease type, or the regression line of a specific functional measure can be generated. The characteristic structural change pattern of a disease type or of a functional score is visualized by sampling points on the discriminant or regression line. The sampled points are used to reconstruct synthetic cerebellar lobule shapes. We showed a few case studies highlighting the utility of the toolbox and we compare the analysis results with the literature.

  2. A probabilistic atlas of the cerebellar white matter.

    PubMed

    van Baarsen, K M; Kleinnijenhuis, M; Jbabdi, S; Sotiropoulos, S N; Grotenhuis, J A; van Cappellen van Walsum, A M

    2016-01-01

    Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. [Cerebellar atrophy in Minamata disease: comparison with spino-cerebellar degeneration on MR images].

    PubMed

    Ikeda, O; Okajima, T; Korogi, Y; Kitajima, M; Uchino, M; Takahasi, M

    1997-02-01

    We evaluated atrophic patterns of the cerebellar vermis in seven patients with Minamata disease (MD) and nine patients with spino-cerebellar degeneration (SCD) on MR images. Twenty-five control subjects were also examined. The cerebellar vermis was divided into superior, middle, and inferior parts by the primary fissure and the prepyramidal fissure on the median sagittal T1-weighted MR image. The length and area of each part were measured. In the patients with SCD, there were no significant differences in the degree of atrophy among the three parts. However, MR images of the patients with MD showed more severe atrophy in the middle and inferior parts than in the superior part. Atrophy of the superior part was less frequently observed in MD patients.

  4. Thyroid hormone and cerebellar development.

    PubMed

    Anderson, Grant W

    2008-01-01

    Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit in the developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.

  5. WDR73 missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in a consanguineous family.

    PubMed

    Jiang, Chen; Gai, Nan; Zou, Yongyi; Zheng, Yu; Ma, Ruiyu; Wei, Xianda; Liang, Desheng; Wu, Lingqian

    2017-01-01

    Galloway-Mowat syndrome (GMS) is a very rare autosomal-recessive disorder characterized by nephrotic syndrome associated with microcephaly, and various central nervous system abnormalities, mostly cerebral hypoplasia or cerebellar atrophy, intellectual disability and neural-migration defects. WDR73 is the only gene known to cause GMS, and has never been implicated in other disease. Here we present a Chinese consanguineous family with infantile onset intellectual disability and cerebellar hypoplasia but no microcephaly. Whole exome sequencing identified a WDR73 p.W371G missense mutation. The mutation is confirmed to be segregated in this family by Sanger sequencing according to a recessive inheritance pattern. It is predicted to be deleterious by multiple algorithms and affect highly conserved site. Structural modeling revealed conformational differences between the wild type protein and the p.W371G protein. Real-time PCR and Western blotting revealed altered mRNA and protein levels in mutated samples. Our study indicates the novel WDR73 p.W371G missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in recessive mode of inheritance. Our findings imply that microcephaly is a variable phenotype in WDR73-related disease, suggest WDR73 to be a candidate gene of severe intellectual disability and cerebellar hypoplasia, and expand the molecular spectrum of WDR73-related disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Cerebellar contributions to spatial memory.

    PubMed

    Tomlinson, Simon P; Davis, Nick J; Morgan, Helen M; Bracewell, R Martyn

    2014-08-22

    There is mounting evidence for a role for the cerebellum in working memory (WM). The majority of relevant studies has examined verbal WM and has suggested specialisation of the right cerebellar hemisphere for language processing. Our study used theta burst stimulation (TBS) to examine whether there is a converse cerebellar hemispheric specialisation for spatial WM. We conducted two experiments to examine spatial WM performance before and after TBS to mid-hemispheric and lateral locations in the posterior cerebellum. Participants were required to recall the order of presentation of targets on a screen or the targets' order of presentation and their locations. We observed impaired recollection of target order after TBS to the mid left cerebellar hemisphere and reduced response speed after TBS to the left lateral cerebellum. We suggest that these results give evidence of the contributions of the left cerebellar cortex to the encoding and retrieval of spatial information. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Distributed Cerebellar Motor Learning: A Spike-Timing-Dependent Plasticity Model

    PubMed Central

    Luque, Niceto R.; Garrido, Jesús A.; Naveros, Francisco; Carrillo, Richard R.; D'Angelo, Egidio; Ros, Eduardo

    2016-01-01

    Deep cerebellar nuclei neurons receive both inhibitory (GABAergic) synaptic currents from Purkinje cells (within the cerebellar cortex) and excitatory (glutamatergic) synaptic currents from mossy fibers. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP) located at different cerebellar sites (parallel fibers to Purkinje cells, mossy fibers to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells) in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibers to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP) and inhibitory (i-STDP) mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibers to Purkinje cells synapses and then transferred to mossy fibers to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation toward optimizing its working range). PMID:26973504

  8. Decreased cerebellar-cerebral connectivity contributes to complex task performance

    PubMed Central

    Knops, André

    2016-01-01

    The cerebellum's role in nonmotor processes is now well accepted, but cerebellar interaction with cerebral targets is not well understood. Complex cognitive tasks activate cerebellar, parietal, and frontal regions, but the effective connectivity between these regions has never been tested. To this end, we used psycho-physiological interactions (PPI) analysis to test connectivity changes of cerebellar and parietal seed regions in complex (2-digit by 1-digit multiplication, e.g., 12 × 3) vs. simple (1-digit by 1-digit multiplication, e.g., 4 × 3) task conditions (“complex − simple”). For cerebellar seed regions (lobule VI, hemisphere and vermis), we found significantly decreased cerebellar-parietal, cerebellar-cingulate, and cerebellar-frontal connectivity in complex multiplication. For parietal seed regions (PFcm, PFop, PFm) we found significantly increased parietal-parietal and parietal-frontal connectivity in complex multiplication. These results suggest that decreased cerebellar-cerebral connectivity contributes to complex task performance. Interestingly, BOLD activity contrasts revealed partially overlapping parietal areas of increased BOLD activity but decreased cerebellar-parietal PPI connectivity. PMID:27334957

  9. [Voxel-Based Morphometry in Medicated-naive Boys with Attention-deficit/hyperactivity Disorder(ADHD)].

    PubMed

    Liu, Qi; Chen, Lizhou; Li, Fei; Chen, Ying; Guo, Lanting; Gong, Qiyong; Huang, Xiaoqi

    2016-06-01

    Attention-deficit/hyperactivity disorder(ADHD)is one of the most common neuro-developmental disorders occurring in childhood,characterized by symptoms of age-inappropriate inattention,hyperactivity/impulsivity,and the prevalence is higher in boys.Although gray matter volume deficits have been frequently reported for ADHD children via structural magnetic resonance imaging,few of them had specifically focused on male patients.The present study aimed to explore the alterations of gray matter volumes in medicated-naive boys with ADHD via a relatively new voxel-based morphometry technique.According to the criteria of DSM-IV-TR,43medicated-naive ADHD boys and 44age-matched healthy boys were recruited.The magnetic resonance image(MRI)scan was performed via a 3T MRI system with three-dimensional(3D)spoiled gradient recalled echo(SPGR)sequence.Voxel-based morphometry with diffeomorphic anatomical registration through exponentiated lie algebra in SPM8 was used to preprocess the3DT1-weighted images.To identify gray matter volume differences between the ADHD and the controls,voxelbased analysis of whole brain gray matter volumes between two groups were done via two sample t-test in SPM8 with age as covariate,threshold at P<0.001.Finally,compared to the controls,significantly reduced gray matter volumes were identified in the right orbitofrontal cortex(peak coordinates[-2,52,-25],t=4.01),and bilateral hippocampus(Left:peak coordinates[14,0,-18],t=3.61;Right:peak coordinates[-14,15,-28],t=3.64)of ADHD boys.Our results demonstrated obvious reduction of whole brain gray matter volumes in right orbitofrontal cortex and bilateral hippocampus in boys with ADHD.This suggests that the abnormalities of prefrontal-hippocampus circuit may be the underlying cause of the cognitive dysfunction and abnormal behavioral inhibition in medicatednaive boys with ADHD.

  10. Brain Morphometry on Congenital Hand Deformities based on Teichmüller Space Theory.

    PubMed

    Peng, Hao; Wang, Xu; Duan, Ye; Frey, Scott H; Gu, Xianfeng

    2015-01-01

    Congenital Hand Deformities (CHD) are usually occurred between fourth and eighth week after the embryo is formed. Failure of the transformation from arm bud cells to upper limb can lead to an abnormal appearing/functioning upper extremity which is presented at birth. Some causes are linked to genetics while others are affected by the environment, and the rest have remained unknown. CHD patients develop prehension through the use of their hands, which affect the brain as time passes. In recent years, CHD have gain increasing attention and researches have been conducted on CHD, both surgically and psychologically. However, the impacts of CHD on brain structure are not well-understood so far. Here, we propose a novel approach to apply Teichmüller space theory and conformal welding method to study brain morphometry in CHD patients. Conformal welding signature reflects the geometric relations among different functional areas on the cortex surface, which is intrinsic to the Riemannian metric, invariant under conformal deformation, and encodes complete information of the functional area boundaries. The computational algorithm is based on discrete surface Ricci flow, which has theoretic guarantees for the existence and uniqueness of the solutions. In practice, discrete Ricci flow is equivalent to a convex optimization problem, therefore has high numerically stability. In this paper, we compute the signatures of contours on general 3D surfaces with surface Ricci flow method, which encodes both global and local surface contour information. Then we evaluated the signatures of pre-central and post-central gyrus on healthy control and CHD subjects for analyzing brain cortical morphometry. Preliminary experimental results from 3D MRI data of CHD/control data demonstrate the effectiveness of our method. The statistical comparison between left and right brain gives us a better understanding on brain morphometry of subjects with Congenital Hand Deformities, in particular, missing

  11. Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich's ataxia.

    PubMed

    Rezende, Thiago J R; Silva, Cynthia B; Yassuda, Clarissa L; Campos, Brunno M; D'Abreu, Anelyssa; Cendes, Fernando; Lopes-Cendes, Iscia; França, Marcondes C

    2016-01-01

    Spinal cord and peripheral nerves are classically known to be damaged in Friedreich's ataxia, but the extent of cerebral involvement in the disease and its progression over time are not yet characterized. The aim of this study was to evaluate longitudinally cerebral damage in Friedreich's ataxia. We enrolled 31 patients and 40 controls, which were evaluated at baseline and after 1 and 2 years. To assess gray matter, we employed voxel-based morphometry and cortical thickness measurements. White matter was evaluated using diffusion tensor imaging. Statistical analyses were both cross-sectional and longitudinal (corrected for multiple comparisons). Group comparison between patients and controls revealed widespread macrostructural differences at baseline: gray matter atrophy in the dentate nuclei, brainstem, and precentral gyri; and white matter atrophy in the cerebellum and superior cerebellar peduncles, brainstem, and periventricular areas. We did not identify any longitudinal volumetric change over time. There were extensive microstructural alterations, including superior cerebellar peduncles, corpus callosum, and pyramidal tracts. Longitudinal analyses identified progressive microstructural abnormalities at the corpus callosum, pyramidal tracts, and superior cerebellar peduncles after 1 year of follow-up. Patients with Friedreich's ataxia present more widespread gray and white matter damage than previously reported, including not only infratentorial areas, but also supratentorial structures. Furthermore, patients with Friedreich's ataxia have progressive microstructural abnormalities amenable to detection in a short-term follow-up. © 2015 International Parkinson and Movement Disorder Society.

  12. Voxel-based morphometry study of the insular cortex in bipolar depression.

    PubMed

    Tang, Li-Rong; Liu, Chun-Hong; Jing, Bin; Ma, Xin; Li, Hai-Yun; Zhang, Yu; Li, Feng; Wang, Yu-Ping; Yang, Zhi; Wang, Chuan-Yue

    2014-11-30

    Bipolar depression (BD) is a common psychiatric illness characterized by deficits in emotional and cognitive processing. Abnormalities in the subregions of the insula are common findings in neuroanatomical studies of patients with bipolar disorder. However, the specific relationships between morphometric changes in specific insular subregions and the pathogenesis of BD are not clear. In this study, structural magnetic resonance imaging (MRI) was used to investigate gray matter volume abnormalities in the insular subregion in 27 patients with BD and in 27 age and sex-matched controls. Using DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) for voxel-based morphometry (VBM), we examined changes in regional gray matter volumes of the insula in patients with BD. As compared with healthy controls, the BD patients showed decreased gray matter volumes in the right posterior insula and left ventral anterior insula and increased gray matter volumes in the left dorsal anterior insula. Consistent with the emerging theory of insular interference as a contributor to emotional-cognitive dysregulation, the current findings suggest that the insular cortex may be involved in the neural substrates of BD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Dystonia and Cerebellar Degeneration in the Leaner Mouse Mutant

    PubMed Central

    Raike, Robert S.; Hess, Ellen J.; Jinnah, H.A.

    2015-01-01

    Cerebellar degeneration is traditionally associated with ataxia. Yet, there are examples of both ataxia and dystonia occurring in individuals with cerebellar degeneration. There is also substantial evidence suggesting that cerebellar dysfunction alone may cause dystonia. The types of cerebellar defects that may cause ataxia, dystonia, or both have not been delineated. In the current study, we explored the relationship between cerebellar degeneration and dystonia using the leaner mouse mutant. Leaner mice have severe dystonia that is associated with dysfunctional and degenerating cerebellar Purkinje cells. Whereas the density of Purkinje cells was not significantly reduced in 4 week-old leaner mice, approximately 50% of the neurons were lost by 34 weeks of age. On the other hand, the dystonia and associated functional disability became significantly less severe during this same interval. In other words, dystonia improved as Purkinje cells were lost, suggesting that dysfunctional Purkinje cells, rather than Purkinje cell loss, contribute to the dystonia. These results provide evidence that distorted cerebellar function may cause dystonia and support the concept that different types of cerebellar defects can have different functional consequences. PMID:25791619

  14. lakemorpho: Calculating lake morphometry metrics in R.

    PubMed

    Hollister, Jeffrey; Stachelek, Joseph

    2017-01-01

    Metrics describing the shape and size of lakes, known as lake morphometry metrics, are important for any limnological study. In cases where a lake has long been the subject of study these data are often already collected and are openly available. Many other lakes have these data collected, but access is challenging as it is often stored on individual computers (or worse, in filing cabinets) and is available only to the primary investigators. The vast majority of lakes fall into a third category in which the data are not available. This makes broad scale modelling of lake ecology a challenge as some of the key information about in-lake processes are unavailable. While this valuable in situ information may be difficult to obtain, several national datasets exist that may be used to model and estimate lake morphometry. In particular, digital elevation models and hydrography have been shown to be predictive of several lake morphometry metrics. The R package lakemorpho has been developed to utilize these data and estimate the following morphometry metrics: surface area, shoreline length, major axis length, minor axis length, major and minor axis length ratio, shoreline development, maximum depth, mean depth, volume, maximum lake length, mean lake width, maximum lake width, and fetch. In this software tool article we describe the motivation behind developing lakemorpho , discuss the implementation in R, and describe the use of lakemorpho with an example of a typical use case.

  15. Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity

    PubMed Central

    Shaikh, Aasef G.; Hong, Simon; Liao, Ke; Tian, Jing; Solomon, David; Zee, David S.; Leigh, R. John

    2010-01-01

    The inferior olivary nuclei clearly play a role in creating oculopalatal tremor, but the exact mechanism is unknown. Oculopalatal tremor develops some time after a lesion in the brain that interrupts inhibition of the inferior olive by the deep cerebellar nuclei. Over time the inferior olive gradually becomes hypertrophic and its neurons enlarge developing abnormal soma-somatic gap junctions. However, results from several experimental studies have confounded the issue because they seem inconsistent with a role for the inferior olive in oculopalatal tremor, or because they ascribe the tremor to other brain areas. Here we look at 3D binocular eye movements in 15 oculopalatal tremor patients and compare their behaviour to the output of our recent mathematical model of oculopalatal tremor. This model has two mechanisms that interact to create oculopalatal tremor: an oscillator in the inferior olive and a modulator in the cerebellum. Here we show that this dual mechanism model can reproduce the basic features of oculopalatal tremor and plausibly refute the confounding experimental results. Oscillations in all patients and simulations were aperiodic, with a complicated frequency spectrum showing dominant components from 1 to 3 Hz. The model’s synchronized inferior olive output was too small to induce noticeable ocular oscillations, requiring amplification by the cerebellar cortex. Simulations show that reducing the influence of the cerebellar cortex on the oculomotor pathway reduces the amplitude of ocular tremor, makes it more periodic and pulse-like, but leaves its frequency unchanged. Reducing the coupling among cells in the inferior olive decreases the oscillation’s amplitude until they stop (at ∼20% of full coupling strength), but does not change their frequency. The dual-mechanism model accounts for many of the properties of oculopalatal tremor. Simulations suggest that drug therapies designed to reduce electrotonic coupling within the inferior olive or

  16. Origin, lineage and function of cerebellar glia.

    PubMed

    Buffo, Annalisa; Rossi, Ferdinando

    2013-10-01

    The glial cells of the cerebellum, and particularly astrocytes and oligodendrocytes, are characterized by a remarkable phenotypic variety, in which highly peculiar morphological features are associated with specific functional features, unique among the glial cells of the entire CNS. Here, we provide a critical report about the present knowledge of the development of cerebellar glia, including lineage relationships between cerebellar neurons, astrocytes and oligodendrocytes, the origins and the genesis of the repertoire of glial types, and the processes underlying their acquisition of mature morphological and functional traits. In parallel, we describe and discuss some fundamental roles played by specific categories of glial cells during cerebellar development. In particular, we propose that Bergmann glia exerts a crucial scaffolding activity that, together with the organizing function of Purkinje cells, is necessary to achieve the normal pattern of foliation and layering of the cerebellar cortex. Moreover, we discuss some of the functional tasks of cerebellar astrocytes and oligodendrocytes that are distinctive of cerebellar glia throughout the CNS. Notably, we report about the regulation of synaptic signalling in the molecular and granular layer mediated by Bergmann glia and parenchymal astrocytes, and the functional interaction between oligodendrocyte precursor cells and neurons. On the whole, this review provides an extensive overview of the available literature and some novel insights about the origin and differentiation of the variety of cerebellar glial cells and their function in the developing and mature cerebellum. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Decreased number and increased volume with mitochondrial enlargement of cerebellar synaptic terminals in a mouse model of chronic demyelination.

    PubMed

    Nguyen, Huy Bang; Sui, Yang; Thai, Truc Quynh; Ikenaka, Kazuhiro; Oda, Toshiyuki; Ohno, Nobuhiko

    2018-05-23

    Impaired nerve conduction, axonal degeneration, and synaptic alterations contribute to neurological disabilities in inflammatory demyelinating diseases. Cerebellar dysfunction is associated with demyelinating disorders, but the alterations of axon terminals in cerebellar gray matter during chronic demyelination are still unclear. We analyzed the morphological and ultrastructural changes of climbing fiber terminals in a mouse model of hereditary chronic demyelination. Three-dimensional ultrastructural analyses using serial block-face scanning electron microscopy and immunostaining for synaptic markers were performed in a demyelination mouse model caused by extra copies of myelin gene (PLP4e). At 1 month old, many myelinated axons were observed in PLP4e and wild-type mice, but demyelinated axons and axons with abnormally thin myelin were prominent in PLP4e mice at 5 months old. The density of climbing fiber terminals was significantly reduced in PLP4e mice at 5 months old. Reconstruction of climbing fiber terminals revealed that PLP4e climbing fibers had increased varicosity volume and enlarged mitochondria in the varicosities at 5-month-old mice. These results suggest that chronic demyelination is associated with alterations and loss of climbing fiber terminals in the cerebellar cortex, and that synaptic changes may contribute to cerebellar phenotypes observed in hereditary demyelinating disorders.

  18. Synchrony and neural coding in cerebellar circuits

    PubMed Central

    Person, Abigail L.; Raman, Indira M.

    2012-01-01

    The cerebellum regulates complex movements and is also implicated in cognitive tasks, and cerebellar dysfunction is consequently associated not only with movement disorders, but also with conditions like autism and dyslexia. How information is encoded by specific cerebellar firing patterns remains debated, however. A central question is how the cerebellar cortex transmits its integrated output to the cerebellar nuclei via GABAergic synapses from Purkinje neurons. Possible answers come from accumulating evidence that subsets of Purkinje cells synchronize their firing during behaviors that require the cerebellum. Consistent with models predicting that coherent activity of inhibitory networks has the capacity to dictate firing patterns of target neurons, recent experimental work supports the idea that inhibitory synchrony may regulate the response of cerebellar nuclear cells to Purkinje inputs, owing to the interplay between unusually fast inhibitory synaptic responses and high rates of intrinsic activity. Data from multiple laboratories lead to a working hypothesis that synchronous inhibitory input from Purkinje cells can set the timing and rate of action potentials produced by cerebellar nuclear cells, thereby relaying information out of the cerebellum. If so, then changing spatiotemporal patterns of Purkinje activity would allow different subsets of inhibitory neurons to control cerebellar output at different times. Here we explore the evidence for and against the idea that a synchrony code defines, at least in part, the input–output function between the cerebellar cortex and nuclei. We consider the literature on the existence of simple spike synchrony, convergence of Purkinje neurons onto nuclear neurons, and intrinsic properties of nuclear neurons that contribute to responses to inhibition. Finally, we discuss factors that may disrupt or modulate a synchrony code and describe the potential contributions of inhibitory synchrony to other motor circuits. PMID

  19. Cerebellar contribution to mental rotation: a cTBS study.

    PubMed

    Picazio, Silvia; Oliveri, Massimiliano; Koch, Giacomo; Caltagirone, Carlo; Petrosini, Laura

    2013-12-01

    A cerebellar role in spatial information processing has been advanced even in the absence of physical manipulation, as occurring in mental rotation. The present study was aimed at investigating the specific involvement of left and right cerebellar hemispheres in two tasks of mental rotation. We used continuous theta burst stimulation to downregulate cerebellar hemisphere excitability in healthy adult subjects performing two mental rotation tasks: an Embodied Mental Rotation (EMR) task, entailing an egocentric strategy, and an Abstract Mental Rotation (AMR) task entailing an allocentric strategy. Following downregulation of left cerebellar hemisphere, reaction times were slower in comparison to sham stimulation in both EMR and AMR tasks. Conversely, identical reaction times were obtained in both tasks following right cerebellar hemisphere and sham stimulations. No effect of cerebellar stimulation side was found on response accuracy. The present findings document a specialization of the left cerebellar hemisphere in mental rotation regardless of the kind of stimulus to be rotated.

  20. New Evidence of Cerebellar and Brainstem Hypoplasia in Autistic Infants, Children and Adolescents: The MR Imaging Study by Hashimoto and Colleagues.

    ERIC Educational Resources Information Center

    Courchesne, Eric

    1995-01-01

    In a study by Toshiaki Hashimoto and colleagues (EC 611 142), 10 infants with developmental delay, poor eye contact, and poor facial expression underwent magnetic resonance brain imaging and were later diagnosed with autism. This offered direct evidence of abnormality of the cerebellar vermis and the brainstem at the beginning stages of behavioral…

  1. Humor and laughter in patients with cerebellar degeneration.

    PubMed

    Frank, B; Propson, B; Göricke, S; Jacobi, H; Wild, B; Timmann, D

    2012-06-01

    Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation.

  2. Modulation of p53 and met expression by Krüppel-like factor 8 regulates zebrafish cerebellar development.

    PubMed

    Tsai, Ming-Yuan; Lu, Yu-Fen; Liu, Yu-Hsiu; Lien, Huang-Wei; Huang, Chang-Jen; Wu, Jen-Leih; Hwang, Sheng-Ping L

    2015-09-01

    Krüppel-like factor 8 (Klf8) is a zinc-finger transcription factor implicated in cell proliferation, and cancer cell survival and invasion; however, little is known about its role in normal embryonic development. Here, we show that Klf8 is required for normal cerebellar development in zebrafish embryos. Morpholino knockdown of klf8 resulted in abnormal cerebellar primordium morphology and the induction of p53 in the brain region at 24 hours post-fertilization (hpf). Both p53-dependent reduction of cell proliferation and augmentation of apoptosis were observed in the cerebellar anlage of 24 hpf-klf8 morphants. In klf8 morphants, expression of ptf1a in the ventricular zone was decreased from 48 to 72 hpf; on the other hand, expression of atohla in the upper rhombic lip was unaffected. Consistent with this finding, Purkinje cell development was perturbed and granule cell number was reduced in 72 hpf-klf8 morphants; co-injection of p53 MO(sp) or klf8 mRNA substantially rescued development of cerebellar Purkinje cells in klf8 morphants. Hepatocyte growth factor/Met signaling is known to regulate cerebellar development in zebrafish and mouse. We observed decreased met expression in the tectum and rhombomere 1 of 24 hpf-klf8 morphants, which was largely rescued by co-injection with klf8 mRNA. Moreover, co-injection of met mRNA substantially rescued formation of Purkinje cells in klf8 morphants at 72 hpf. Together, these results demonstrate that Klf8 modulates expression of p53 and met to maintain ptf1a-expressing neuronal progenitors, which are required for the appropriate development of cerebellar Purkinje and granule cells in zebrafish embryos. © 2014 Wiley Periodicals, Inc.

  3. Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

    PubMed

    Lamont, Matthew G; Weber, John T

    2015-06-01

    The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Exploring the effects of acid mine drainage on diatom teratology using geometric morphometry.

    PubMed

    Olenici, Adriana; Blanco, Saúl; Borrego-Ramos, María; Momeu, Laura; Baciu, Călin

    2017-10-01

    Metal pollution of aquatic habitats is a major and persistent environmental problem. Acid mine drainage (AMD) affects lotic systems in numerous and interactive ways. In the present work, a mining area (Roșia Montană) was chosen as study site, and we focused on two aims: (i) to find the set of environmental predictors leading to the appearance of the abnormal diatom individuals in the study area and (ii) to assess the relationship between the degree of valve outline deformation and AMD-derived pollution. In this context, morphological differences between populations of Achnanthidium minutissimum and A. macrocephalum, including normal and abnormal individuals, were evidenced by means of valve shape analysis. Geometric morphometry managed to capture and discriminate normal and abnormal individuals. Multivariate analyses (NMDS, PLS) separated the four populations of the two species mentioned and revealed the main physico-chemical parameters that influenced valve deformation in this context, namely conductivity, Zn, and Cu. ANOSIM test evidenced the presence of statistically significant differences between normal and abnormal individuals within both chosen Achnanthidium taxa. In order to determine the relative contribution of each of the measured physico-chemical parameters in the observed valve outline deformations, a PLS was conducted, confirming the results of the NMDS. The presence of deformed individuals in the study area can be attributed to the fact that the diatom communities were strongly affected by AMD released from old mining works and waste rock deposits.

  5. Patterns of magnetic resonance imaging abnormalities in symptomatic patients with Krabbe disease correspond to phenotype.

    PubMed

    Abdelhalim, Ahmed N; Alberico, Ronald A; Barczykowski, Amy L; Duffner, Patricia K

    2014-02-01

    Initial magnetic resonance imaging studies of individuals with Krabbe disease were analyzed to determine whether the pattern of abnormalities corresponded to the phenotype. This was a retrospective, nonblinded study. Families/patients diagnosed with Krabbe disease submitted medical records and magnetic resonance imaging discs for central review. Institutional review board approval/informed consents were obtained. Sixty-four magnetic resonance imaging scans were reviewed by two neuroradiologists and a child neurologist according to phenotype: early infantile (onset 0-6 months) = 39 patients; late infantile (onset 7-12 months) = 10 patients; later onset (onset 13 months-10 years) = 11 patients; adolescent (onset 11-20 years) = one patient; and adult (21 years or greater) = three patients. Local interpretations were compared with central review. Magnetic resonance imaging abnormalities differed among phenotypes. Early infantile patients had a predominance of increased intensity in the dentate/cerebellar white matter as well as changes in the deep cerebral white matter. Later onset patients did not demonstrate involvement in the dentate/cerebellar white matter but had extensive involvement of the deep cerebral white matter, parieto-occipital region, and posterior corpus callosum. Late infantile patients exhibited a mixed pattern; 40% had dentate/cerebellar white matter involvement while all had involvement of the deep cerebral white matter. Adolescent/adult patients demonstrated isolated corticospinal tract involvement. Local and central reviews primarily differed in interpretation of the early infantile phenotype. Analysis of magnetic resonance imaging in a large cohort of symptomatic patients with Krabbe disease demonstrated imaging abnormalities correspond to specific phenotypes. Knowledge of these patterns along with typical clinical signs/symptoms should promote earlier diagnosis and facilitate treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Feature-based Morphometry

    PubMed Central

    Toews, Matthew; Wells, William M.; Collins, Louis; Arbel, Tal

    2013-01-01

    This paper presents feature-based morphometry (FBM), a new, fully data-driven technique for identifying group-related differences in volumetric imagery. In contrast to most morphometry methods which assume one-to-one correspondence between all subjects, FBM models images as a collage of distinct, localized image features which may not be present in all subjects. FBM thus explicitly accounts for the case where the same anatomical tissue cannot be reliably identified in all subjects due to disease or anatomical variability. A probabilistic model describes features in terms of their appearance, geometry, and relationship to sub-groups of a population, and is automatically learned from a set of subject images and group labels. Features identified indicate group-related anatomical structure that can potentially be used as disease biomarkers or as a basis for computer-aided diagnosis. Scale-invariant image features are used, which reflect generic, salient patterns in the image. Experiments validate FBM clinically in the analysis of normal (NC) and Alzheimer’s (AD) brain images using the freely available OASIS database. FBM automatically identifies known structural differences between NC and AD subjects in a fully data-driven fashion, and obtains an equal error classification rate of 0.78 on new subjects. PMID:20426102

  7. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor.

    PubMed

    Buijink, A W G; Broersma, M; van der Stouwe, A M M; van Wingen, G A; Groot, P F C; Speelman, J D; Maurits, N M; van Rootselaar, A F

    2015-04-01

    Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar output in essential tremor during rhythmic finger tapping employing functional MRI. Thirty-one propranolol-sensitive essential tremor patients with upper limb tremor and 29 healthy controls were measured. T2*-weighted EPI sequences were acquired. The task consisted of alternating rest and finger tapping blocks. A whole-brain and region-of-interest analysis was performed, the latter focusing on the cerebellar cortex, dentate nucleus and inferior olive nucleus. Activations were also related to tremor severity. In patients, dentate activation correlated positively with tremor severity as measured by the tremor rating scale part A. Patients had reduced activation in widespread cerebellar cortical regions, and additionally in the inferior olive nucleus, and parietal and frontal cortex, compared to controls. The increase in dentate activation with tremor severity supports involvement of the dentate nucleus in essential tremor. Cortical and cerebellar changes during a motor timing task in essential tremor might point to widespread changes in cerebellar output in essential tremor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Local and long-range circuit elements for cerebellar function.

    PubMed

    Xiao, Le; Scheiffele, Peter

    2018-02-01

    The view of cerebellar functions has been extended from controlling sensorimotor processes to processing 'contextual' information and generating predictions for a diverse range of behaviors. These functions rely on the computation of the local cerebellar microcircuits and long-range connectivity that relays cerebellar output to various brain areas. In this review, we discuss recent work on two of the circuit elements, which are thought to be fundamental for a wide range of non-sensorimotor behaviors: The role for cerebellar granule cells in multimodal integration in the cerebellar cortex and the long-range connectivity between the deep cerebellar nuclei and the basal ganglia. Lastly, we discuss how studies on synapses and circuits of the cerebellum in rodent models of autism-spectrum disorders might contribute to our understanding of the pathophysiology of this class of neurodevelopmental disorders. Copyright © 2017. Published by Elsevier Ltd.

  9. Voltage-gated calcium channel autoimmune cerebellar degeneration

    PubMed Central

    McKasson, Marilyn; Clawson, Susan A.; Hill, Kenneth E.; Wood, Blair; Carlson, Noel; Bromberg, Mark; Greenlee, John E.

    2016-01-01

    Objectives: To describe response to treatment in a patient with autoantibodies against voltage-gated calcium channels (VGCCs) who presented with autoimmune cerebellar degeneration and subsequently developed Lambert-Eaton myasthenic syndrome (LEMS), and to study the effect of the patient's autoantibodies on Purkinje cells in rat cerebellar slice cultures. Methods: Case report and study of rat cerebellar slice cultures incubated with patient VGCC autoantibodies. Results: A 53-year-old man developed progressive incoordination with ataxic speech. Laboratory evaluation revealed VGCC autoantibodies without other antineuronal autoantibodies. Whole-body PET scans 6 and 12 months after presentation detected no malignancy. The patient improved significantly with IV immunoglobulin G (IgG), prednisone, and mycophenolate mofetil, but worsened after IV IgG was halted secondary to aseptic meningitis. He subsequently developed weakness with electrodiagnostic evidence of LEMS. The patient's IgG bound to Purkinje cells in rat cerebellar slice cultures, followed by neuronal death. Reactivity of the patient's autoantibodies with VGCCs was confirmed by blocking studies with defined VGCC antibodies. Conclusions: Autoimmune cerebellar degeneration associated with VGCC autoantibodies may precede onset of LEMS and may improve with immunosuppressive treatment. Binding of anti-VGCC antibodies to Purkinje cells in cerebellar slice cultures may be followed by cell death. Patients with anti-VGCC autoantibodies may be at risk of irreversible neurologic injury over time, and treatment should be initiated early. PMID:27088118

  10. Acute bilateral cerebellar infarction in the territory of the medial branches of posterior inferior cerebellar arteries.

    PubMed

    Gurer, G; Sahin, G; Cekirge, S; Tan, E; Saribas, O

    2001-10-01

    The most frequent type of cerebellar infarcts involved the posterior inferior cerebellar artery (PICA) and superior cerebellar artery territories but bilateral involvement of lateral or medial branches of PICA is extremely rare. In this report, we present a 55-year-old male who admitted to hospital with vomiting, nausea and dizziness. On examination left-sided hemiparesia and ataxic gait were detected. Infarct on bilateral medial branch of PICA artery territories was found out with cranial magnetic resonance imaging (MRI) technique and 99% stenosis of the left vertebral artery was found out with digital subtraction arteriography. The patient was put on heparin treatment. After 3 weeks, his complaints and symptoms had disappeared except for mild gait ataxia.

  11. Comparison between magnetic resonance imaging and fetopathology in the evaluation of fetal posterior fossa non-cystic abnormalities.

    PubMed

    Tilea, B; Delezoide, A L; Khung-Savatovski, S; Guimiot, F; Vuillard, E; Oury, J F; Garel, C

    2007-06-01

    To compare magnetic resonance imaging (MRI) and fetopathological findings in the evaluation of non-cystic fetal posterior fossa anomalies and to describe associated abnormalities. This was a prospective study from 2000 to 2005 of fetuses identified on ultrasound as having sonographic suspicion of posterior fossa malformation. All underwent a thorough MRI examination of the fetal brain, after which we classified each fetus as presenting one of the following pathologies: vermian hypoplasia or agenesis, cerebellar and/or brain stem hypoplasia, destructive or dysplastic lesions. All of the pregnancies were then terminated, after which the whole fetus underwent fetopathological examination. We compared the findings from MRI and fetopathological examinations and recorded the associated cerebral and extracerebral abnormalities. Twenty-five fetuses were included. MRI was performed at a mean gestational age of 31 weeks, and fetopathological examination at 33 weeks. In 12 cases we observed vermian hypoplasia, six had partial vermian agenesis, 11 had cerebellar hemisphere hypoplasia, seven had brain stem hypoplasia, four had destructive lesions and six had dysplastic lesions. The two techniques were similar in their performance with respect to the detection of vermian agenesis, brain stem hypoplasia and destructive lesions. There were four false-positive results of MRI for vermian hypoplasia and a poor agreement regarding cerebellar hemisphere hypoplasia. No dysplastic lesions were diagnosed by MRI. None of the posterior fossa malformations was isolated and many cerebral and extracerebral abnormalities were found. A systematic analysis of the posterior fossa in fetal MRI makes it possible to diagnose accurately most posterior fossa malformations. These malformations never occurred in isolation in our study.

  12. Acute Cerebellar Ataxia Induced by Nivolumab

    PubMed Central

    Kawamura, Reina; Nagata, Eiichiro; Mukai, Masako; Ohnuki, Yoichi; Matsuzaki, Tomohiko; Ohiwa, Kana; Nakagawa, Tomoki; Kohno, Mitsutomo; Masuda, Ryota; Iwazaki, Masayuki; Takizawa, Shunya

    2017-01-01

    A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment. PMID:29249765

  13. Acute cerebellar ataxia and infectious mononucleosis.

    PubMed Central

    Wadhwa, N. K.; Ghose, R. R.

    1983-01-01

    A 28-year-old man, who presented with acute cerebellar ataxia, was found to have haematological features of infectious mononucleosis. There was serological evidence of recent infection with Epstein-Barr virus. It is speculated that cerebellar dysfunction results from virus-induced inflammatory changes within the central nervous system. PMID:6312442

  14. Cerebellar Plasticity and Motor Learning Deficits in a Copy Number Variation Mouse Model of Autism

    PubMed Central

    Piochon, Claire; Kloth, Alexander D; Grasselli, Giorgio; Titley, Heather K; Nakayama, Hisako; Hashimoto, Kouichi; Wan, Vivian; Simmons, Dana H; Eissa, Tahra; Nakatani, Jin; Cherskov, Adriana; Miyazaki, Taisuke; Watanabe, Masahiko; Takumi, Toru; Kano, Masanobu; Wang, Samuel S-H; Hansel, Christian

    2014-01-01

    A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behavior and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behavior deficits. We find that in patDp/+ mice delay eyeblink conditioning—a form of cerebellum-dependent motor learning—is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fiber-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibers—a model for activity-dependent synaptic pruning—is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism. PMID:25418414

  15. A Novel and Multivalent Role of Pax6 in Cerebellar Development

    PubMed Central

    Yeung, Joanna; Ha, Thomas J.; Swanson, Douglas J.

    2016-01-01

    Pax6 is a prominent gene in brain development. The deletion of Pax6 results in devastated development of eye, olfactory bulb, and cortex. However, it has been reported that the Pax6-null Sey cerebellum only has minor defects involving granule cells despite Pax6 being expressed throughout cerebellar development. The present work has uncovered a requirement of Pax6 in the development of all rhombic lip (RL) lineages. A significant downregulation of Tbr1 and Tbr2 expression is found in the Sey cerebellum, these are cell-specific markers of cerebellar nuclear (CN) neurons and unipolar brush cells (UBCs), respectively. The examination of Tbr1 and Lmx1a immunolabeling and Nissl staining confirmed the loss of CN neurons from the Sey cerebellum. CN neuron progenitors are produced in the mutant but there is an enhanced death of these neurons as shown by increased presence of caspase-3-positive cells. These data indicate that Pax6 regulates the survival of CN neuron progenitors. Furthermore, the analysis of experimental mouse chimeras suggests a cell-extrinsic role of Pax6 in CN neuron survival. For UBCs, using Tbr2 immunolabeling, these cells are significantly reduced in the Sey cerebellum. The loss of UBCs in the mutant is due partly to cell death in the RL and also to the reduced production of progenitors from the RL. These results demonstrate a critical role for Pax6 in regulating the generation and survival of UBCs. This and previous work from our laboratory demonstrate a seminal role of Pax6 in the development of all cerebellar glutamatergic neurons. SIGNIFICANCE STATEMENT Pax6 is a key molecule in development. Pax6 is best known as the master control gene in eye development with mutations causing aniridia in humans. Pax6 also plays important developmental roles in the cortex and olfactory bulb. During cerebellar development, Pax6 is robustly expressed in the germinal zone of all glutamatergic neurons [cerebellar nuclear (CN) neurons, granule cells, and unipolar brush

  16. New MR imaging assessment tool to define brain abnormalities in very preterm infants at term.

    PubMed

    Kidokoro, H; Neil, J J; Inder, T E

    2013-01-01

    WM injury is the dominant form of injury in preterm infants. However, other cerebral structures, including the deep gray matter and the cerebellum, can also be affected by injury and/or impaired growth. Current MR imaging injury assessment scales are subjective and are challenging to apply. Thus, we developed a new assessment tool and applied it to MR imaging studies obtained from very preterm infants at term age. MR imaging scans from 97 very preterm infants (< 30 weeks' gestation) and 22 healthy term-born infants were evaluated retrospectively. The severity of brain injury (defined by signal abnormalities) and impaired brain growth (defined with biometrics) was scored in the WM, cortical gray matter, deep gray matter, and cerebellum. Perinatal variables for clinical risks were collected. In very preterm infants, brain injury was observed in the WM (n=23), deep GM (n=5), and cerebellum (n=23). Combining measures of injury and impaired growth showed moderate to severe abnormalities most commonly in the WM (n=38) and cerebellum (n=32) but still notable in the cortical gray matter (n=16) and deep gray matter (n=11). WM signal abnormalities were associated with a reduced deep gray matter area but not with cerebellar abnormality. Intraventricular and/or parenchymal hemorrhage was associated with cerebellar signal abnormality and volume reduction. Multiple clinical risk factors, including prolonged intubation, prolonged parenteral nutrition, postnatal corticosteroid use, and postnatal sepsis, were associated with increased global abnormality on MR imaging. Very preterm infants demonstrate a high prevalence of injury and growth impairment in both the WM and gray matter. This MR imaging scoring system provides a more comprehensive and objective classification of the nature and extent of abnormalities than existing measures.

  17. Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

    PubMed Central

    Passot, Jean-Baptiste; Sheynikhovich, Denis; Duvelle, Éléonore; Arleo, Angelo

    2012-01-01

    Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation. PMID:22485133

  18. Acute cerebellar ataxia

    MedlinePlus

    ... swelling (inflammation) of the cerebellum (such as from multiple sclerosis). Cerebellar ataxia caused by a recent viral infection may not need treatment. Outlook (Prognosis) People whose condition was caused by ...

  19. [Gray matter abnormalities in developmental stuttering determined with voxel-based morphometry].

    PubMed

    Song, Lu-ping; Peng, Dan-ling; Jin, Zhen; Yao, Li; Ning, Ning; Guo, Xiao-juan; Zhang, Tong

    2007-11-06

    To investigate the differences of regional grey matter volume between adults with persistent developmental stuttering and fluent speaking adults, and to determine whether stutterers have anomalous anatomy of speech-relevant brain areas that possibly affect speech fluency. High-resolution magnetic resonance imaging (MRI) scanning was performed on 10 adults with developmental stuttering, aged 26 (21 - 35) with the onset age of 4 (3 - 7) and 12 age, sex, hand preference, and education-matched controls. The customized brain templates were created in order to improve spatial normalization and segmentation. Then automated preprocessing of MRI data was conducted using an optimized version of VBM, a fully automated unbiased and objective whole-brain MRI analysis technique. VBM analysis revealed that compared with the controls, the stuttering adults had significant clusters of locally gray matter volume increased in the superior temporal, middle temporal, precentral and postcentral gyrus, and inferior parietal lobule of the bilateral hemisphere (P < 0.001), the numbers of increased gray matter volume in the right and left hemispheres were 60,247 and 48,782 voxels respectively. The, Grey matter decrease was shown with an overall decreased gray matter volume of 32 394 voxels, mainly in the bilateral cerebella posterior lobe and dorsal part of medulla, especially inferior semi-lunar lobule, followed by cerebellar tonsil and bilateral medulla in comparison with the controls (P < 0.001). The reduction of the regional gray matter volume of bilateral cerebella and medulla is related to the neural mechanism of the controlling disorder of speech production and may be the essential cause of stuttering. Some areas with increased gray matter volume in temporal lobe, parietal lobe, and frontal lobe, may be the result of long term functional compensation for the cerebella and medulla function deficiency.

  20. Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates.

    PubMed

    Eluvathingal, Thomas J; Behen, Michael E; Chugani, Harry T; Janisse, James; Bernardi, Bruno; Chakraborty, Pulak; Juhasz, Csaba; Muzik, Otto; Chugani, Diane C

    2006-10-01

    We assessed the structural and functional imaging features of cerebellar lesions and their neurobehavioral correlates in a large cohort of patients with tuberous sclerosis complex. A consecutive series of 78 patients with tuberous sclerosis complex underwent magnetic resonance imaging (MRI) and positron emission tomography (PET) studies with [(18)F]fluorodeoxyglucose (FDG) and alpha-[(11)C]methyl-l-tryptophan (AMT) as part of their evaluation for epilepsy surgery. Neurobehavioral assessment included the Gilliam Autism Rating Scales (GARS) and the Vineland Adaptive Behavior Scales (VABS). Twenty-one patients (27%) had cerebellar lesions (10 boys; mean age 9 +/- 8 years; 9 had right-sided, 10 had left-sided, and 2 had bilateral cerebellar lesions). The lesions showed decreased glucose metabolism (0.79 +/- 0.10) and increased (1.04 +/- 0.10) AMT uptake compared with the normal (nonlesional) cerebellar cortex. Comparisons between patients with (n = 20) and without (n = 57) a cerebellar lesion on neurobehavioral functioning, controlling for the number and location of cortical tubers, revealed that the cerebellar lesion group had higher overall autistic symptomatology. Within-group analyses of the cerebellar lesion group revealed that children with right-sided cerebellar lesions had higher social isolation and communicative and developmental disturbance compared with children with left-sided cerebellar lesions. The side of the cerebellar lesion was not related to adaptive behavior functioning. These findings provide additional empiric support for a role of the cerebellum in autistic symptomatology. Further investigation of the potential role of the right cerebellum in autism, particularly with regard to the dentatothalamofrontal circuit, is warranted.

  1. Autosomal-recessive congenital cerebellar ataxia is caused by mutations in metabotropic glutamate receptor 1.

    PubMed

    Guergueltcheva, Velina; Azmanov, Dimitar N; Angelicheva, Dora; Smith, Katherine R; Chamova, Teodora; Florez, Laura; Bynevelt, Michael; Nguyen, Thai; Cherninkova, Sylvia; Bojinova, Veneta; Kaprelyan, Ara; Angelova, Lyudmila; Morar, Bharti; Chandler, David; Kaneva, Radka; Bahlo, Melanie; Tournev, Ivailo; Kalaydjieva, Luba

    2012-09-07

    Autosomal-recessive congenital cerebellar ataxia was identified in Roma patients originating from a small subisolate with a known strong founder effect. Patients presented with global developmental delay, moderate to severe stance and gait ataxia, dysarthria, mild dysdiadochokinesia, dysmetria and tremors, intellectual deficit, and mild pyramidal signs. Brain imaging revealed progressive generalized cerebellar atrophy, and inferior vermian hypoplasia and/or a constitutionally small brain were observed in some patients. Exome sequencing, used for linkage analysis on extracted SNP genotypes and for mutation detection, identified two novel (i.e., not found in any database) variants located 7 bp apart within a unique 6q24 linkage region. Both mutations cosegregated with the disease in five affected families, in which all ten patients were homozygous. The mutated gene, GRM1, encodes metabotropic glutamate receptor mGluR1, which is highly expressed in cerebellar Purkinje cells and plays an important role in cerebellar development and synaptic plasticity. The two mutations affect a gene region critical for alternative splicing and the generation of receptor isoforms; they are a 3 bp exon 8 deletion and an intron 8 splicing mutation (c.2652_2654del and c.2660+2T>G, respectively [RefSeq accession number NM_000838.3]). The functional impact of the deletion is unclear and is overshadowed by the splicing defect. Although ataxia lymphoblastoid cell lines expressed GRM1 at levels comparable to those of control cells, the aberrant transcripts skipped exon 8 or ended in intron 8 and encoded various species of nonfunctional receptors either lacking the transmembrane domain and containing abnormal intracellular tails or completely missing the tail. The study implicates mGluR1 in human hereditary ataxia. It also illustrates the potential of the Roma founder populations for mutation identification by exome sequencing. Copyright © 2012 The American Society of Human Genetics. Published

  2. Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia

    PubMed Central

    Fyfe, John C.; Al-Tamimi, Raba' A.; Castellani, Rudy J.; Rosenstein, Diana; Goldowitz, Daniel; Henthorn, Paula S.

    2010-01-01

    Neuroaxonal dystrophy in brainstem, spinal cord tracts, and spinal nerves accompanied by cerebellar hypoplasia was observed in a colony of laboratory dogs. Fetal akinesia was documented by ultrasonographic examination. At birth, affected puppies exhibited stereotypical positioning of limbs, scoliosis, arthrogryposis, pulmonary hypoplasia, and respiratory failure. Regional hypoplasia in the central nervous system was apparent grossly, most strikingly as underdeveloped cerebellum and spinal cord. Histopathologic abnormalities included swollen axons and spheroids in brainstem and spinal cord tracts; reduced cerebellar foliation, patchy loss of Purkinje cells, multifocal thinning of the external granular cell layer, and loss of neurons in the deep cerebellar nuclei; spheroids and loss of myelinated axons in spinal roots and peripheral nerves; increased myocyte apoptosis in skeletal muscle; and fibrofatty connective tissue proliferation around joints. Breeding studies demonstrated that the canine disorder is a fully penetrant, simple autosomal recessive trait. The disorder demonstrated a type and distribution of lesions homologous to that of human infantile neuroaxonal dystrophy (INAD), most commonly caused by mutations of PLA2G6, but alleles of informative markers flanking the canine PLA2G6 locus did not associate with the canine disorder. Thus, fetal-onset neuroaxonal dystrophy in dogs, a species with well-developed genome mapping resources, provides a unique opportunity for additional disease gene discovery and understanding of this pathology. PMID:20653033

  3. Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1.

    PubMed

    Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S; Anthony, Todd E; Wang, Chenran; Li, Yi E; Guan, Jun-Lin; Murphy, Geoffrey G; Zhu, Yuan

    2014-12-23

    Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities.

  4. Merosin-deficient congenital muscular dystrophy with mental retardation and cerebellar cysts, unlinked to the LAMA2, FCMD, MEB and CMD1B loci, in three Tunisian patients.

    PubMed

    Triki, Chahnez; Louhichi, Nacim; Méziou, Mériam; Choyakh, Fakher; Kéchaou, Mohamed Salah; Jlidi, Rachid; Mhiri, Chokri; Fakhfakh, Faiza; Ayadi, Hamadi

    2003-01-01

    We report three Tunisian patients affected by congenital muscular dystrophy with mental retardation and cerebellar cysts on cranial magnetic resonance imaging. The clinical features were characterized by hypotonia at birth, joint contractures associated with severe psychomotor retardation, absence of speech, inability to walk in three patients, but calf hypertrophy was noted only in two patients. Brain magnetic resonance imaging showed several cerebellar cysts and vermis hypoplasia in all of the patients. Abnormality of the white matter was present in two patients. The pattern of gyration was normal in all cases. Serum creatine kinase was elevated in all three cases and their muscle biopsy showed dystrophic changes compatible with congenital muscular dystrophy. The immunohistochemical analysis of the skeletal muscle revealed partial merosin deficiency, more pronounced for the N-terminal antibody. Linkage analysis excluded congenital muscular dystrophy loci on chromosomes 6q22, 9q31, 1p32 and 1q42. These patients constituted a particular form of congenital muscular dystrophy with a combination of severe motor delay, mental retardation, partial merosin deficiency and cerebellar cysts. Two patients showed white matter abnormalities on magnetic resonance imaging and hypertrophy of the calves. These cases, in addition to those reported previously, confirmed the large phenotypic variability in the group of secondary merosin deficiency congenital muscular dystrophy.

  5. Factors associated with the misdiagnosis of cerebellar infarction.

    PubMed

    Masuda, Yoko; Tei, Hideaki; Shimizu, Satoru; Uchiyama, Shinichiro

    2013-10-01

    Cerebellar infarction is easily misdiagnosed or underdiagnosed. In this study, we investigated factors leading to misdiagnosis of cerebellar infarction in patients with acute ischemic stroke. Data on neurological and radiological findings from 114 consecutive patients with acute cerebellar infarction were analyzed. We investigated factors associated with misdiagnosis from the data on clinical findings. Thirty-two (28%) patients were misdiagnosed on admission. Misdiagnosis was significantly more frequent in patients below 60 years of age and in patients with vertebral artery dissection, and significantly less frequent in patients with dysarthria. It tended to be more frequent in patients with the medial branch of posterior inferior cerebellar artery territory infarction, and infrequent in patients with the medial branch of the superior cerebellar artery territory infarction. Thirty out of 32 (94%) misdiagnosed patients were seen by physicians that were not neurologists at the first visit. Twenty-four of 32 (75%) misdiagnosed patients were screened only by brain CT. However, patients were not checked by brain MRI or follow-up CT until their conditions worsened. Patients below 60 years of age and patients with vertebral artery dissection are more likely to have a cerebellar infarction misdiagnosed by physicians other than neurologists. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  6. A dynamical system view of cerebellar function

    NASA Astrophysics Data System (ADS)

    Keeler, James D.

    1990-06-01

    First some previous theories of cerebellar function are reviewed, and deficiencies in how they map onto the neurophysiological structure are pointed out. I hypothesize that the cerebellar cortex builds an internal model, or prediction, of the dynamics of the animal. A class of algorithms for doing prediction based on local reconstruction of attractors are described, and it is shown how this class maps very well onto the structure of the cerebellar cortex. I hypothesize that the climbing fibers multiplex between different trajectories corresponding to different modes of operation. Then the vestibulo-ocular reflex is examined, and experiments to test the proposed model are suggested. The purpose of the presentation here is twofold: (1) To enlighten physiologists to the mathematics of a class of prediction algorithms that map well onto cerebellar architecture. (2) To enlighten dynamical system theorists to the physiological and anatomical details of the cerebellum.

  7. Potential mechanisms of cerebellar hypoplasia in prematurity.

    PubMed

    Tam, Emily W Y

    2013-09-01

    The cerebellum undergoes dramatic growth and maturation over the neonatal period after preterm birth and is thus particularly sensitive to impaired development due to various clinical factors. Impairments in growth can occur independent of cerebellar parenchymal damage, such as from local hemorrhage, resulting from reduced expression of sonic hedgehog signaling to trigger the appropriate expansion of the granule precursor cells. The primary risk factors for impaired cerebellar development include postnatal glucocorticoid exposure, which has direct effects on the sonic hedgehog pathway, and supratentorial brain injury, including intraventricular hemorrhage and white matter injury, which may result in crossed cerebellar diaschisis and local toxic effects of blood products on the external granular layer. Other cardiorespiratory and nutritional factors may also exist. Impaired cerebellar development is associated with adverse outcomes in motor and cognitive development. New approaches to care to counteract these risk factors may help improve long-term outcome after preterm birth.

  8. Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas.

    PubMed

    Palesi, Fulvia; De Rinaldis, Andrea; Castellazzi, Gloria; Calamante, Fernando; Muhlert, Nils; Chard, Declan; Tournier, J Donald; Magenes, Giovanni; D'Angelo, Egidio; Gandini Wheeler-Kingshott, Claudia A M

    2017-10-09

    Cerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI-based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated.

  9. Superior and anterior inferior cerebellar arteries and their relationship with cerebello-pontine angle cranial nerves revisited in the light of cranial cephalometric indexes: a cadaveric study.

    PubMed

    Habibi, Zohreh; Meybodi, Ali Tayebi; Maleki, Farid; Tabatabai, Seyed

    2011-01-01

    The aim was to clarify the anatomical features of the superior and anterior inferior cerebellar arteries in relation to the trigeminal nerve and acoustic-facial complex and to the bony structures of the skull in a sample of male Iranian cadavers. Bilateral dissections, calvariectomy, and brain evacuation were performed on 31 adult human fresh brains and skull bases to assess the neurovascular associations, and skull base morphometry. Equations were defined to estimate posterior fossa volume and the relationships between bony and neurovascular elements. Eight SCAs were duplicated from origin. There were 9 cases of SCA-trigeminal contacts, which were at the root entry zone in 7. Mean distance from the origin of AICA to the vertebrobasilar junction was 11.80 mm, while 79% of AICAs originated from the lower half of the BA. This was significantly associated with "posterior fossa funneling" and "basilar narrowing" indexes. In most cases AICA crossed the acoustic-facial complex and coursed between neural bundles (48.3%). The AICA reached or entered the internal acoustic canal in 22.6% of cases and was medial to porous in 77.4%. We documented anatomical variations of the superior and anterior inferior cerebellar arteries along with some cephalometric equations with relevant neurovascular anatomy in Iranian cadavers.

  10. Detection of whole-brain abnormalities in temporal lobe epilepsy using tensor-based morphometry with DARTEL

    NASA Astrophysics Data System (ADS)

    Li, Wenjing; He, Huiguang; Lu, Jingjing; Lv, Bin; Li, Meng; Jin, Zhengyu

    2009-10-01

    Tensor-based morphometry (TBM) is an automated technique for detecting the anatomical differences between populations by examining the gradients of the deformation fields used to nonlinearly warp MR images. The purpose of this study was to investigate the whole-brain volume changes between the patients with unilateral temporal lobe epilepsy (TLE) and the controls using TBM with DARTEL, which could achieve more accurate inter-subject registration of brain images. T1-weighted images were acquired from 21 left-TLE patients, 21 right-TLE patients and 21 healthy controls, which were matched in age and gender. The determinants of the gradient of deformation fields at voxel level were obtained to quantify the expansion or contraction for individual images relative to the template, and then logarithmical transformation was applied on it. A whole brain analysis was performed using general lineal model (GLM), and the multiple comparison was corrected by false discovery rate (FDR) with p<0.05. For left-TLE patients, significant volume reductions were found in hippocampus, cingulate gyrus, precentral gyrus, right temporal lobe and cerebellum. These results potentially support the utility of TBM with DARTEL to study the structural changes between groups.

  11. Paraneoplastic cerebellar ataxia and the paraneoplastic syndromes

    PubMed Central

    Afzal, Sadaf; Recio, Maria

    2015-01-01

    Paraneoplastic cerebellar ataxia, also known as paraneoplastic cerebellar degeneration, is one of the wide array of paraneoplastic neurological syndromes in which neurological symptoms are indirectly caused by an underlying malignancy, most commonly gynecological, breast, or lung cancer or Hodgkin's lymphoma. We describe a patient with severe cerebellar dysfunction attributed to a paraneoplastic neurological syndrome. The case highlights the need to look for paraneoplastic syndromes—both to discover malignancies early, at a treatable stage, and, as in our case, to address very distressing symptoms for the patient's relief even if the malignancy is not curable. PMID:25829659

  12. Modality specificity in the cerebro-cerebellar neurocircuitry during working memory.

    PubMed

    Ng, H B Tommy; Kao, K-L Cathy; Chan, Y C; Chew, Effie; Chuang, K H; Chen, S H Annabel

    2016-05-15

    Previous studies have suggested cerebro-cerebellar circuitry in working memory. The present fMRI study aims to distinguish differential cerebro-cerebellar activation patterns in verbal and visual working memory, and employs a quantitative analysis to deterimine lateralization of the activation patterns observed. Consistent with Chen and Desmond (2005a,b) predictions, verbal working memory activated a cerebro-cerebellar circuitry that comprised left-lateralized language-related brain regions including the inferior frontal and posterior parietal areas, and subcortically, right-lateralized superior (lobule VI) and inferior cerebellar (lobule VIIIA/VIIB) areas. In contrast, a distributed network of bilateral inferior frontal and inferior temporal areas, and bilateral superior (lobule VI) and inferior (lobule VIIB) cerebellar areas, was recruited during visual working memory. Results of the study verified that a distinct cross cerebro-cerebellar circuitry underlies verbal working memory. However, a neural circuitry involving specialized brain areas in bilateral neocortical and bilateral cerebellar hemispheres subserving visual working memory is observed. Findings are discussed in the light of current models of working memory and data from related neuroimaging studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. A New Mouse Allele of Glutamate Receptor Delta 2 with Cerebellar Atrophy and Progressive Ataxia

    PubMed Central

    Miyoshi, Yuka; Yoshioka, Yoshichika; Suzuki, Kinuko; Miyazaki, Taisuke; Koura, Minako; Saigoh, Kazumasa; Kajimura, Naoko; Monobe, Yoko; Kusunoki, Susumu; Matsuda, Junichiro; Watanabe, Masahiko; Hayasaka, Naoto

    2014-01-01

    Spinocerebellar degenerations (SCDs) are a large class of sporadic or hereditary neurodegenerative disorders characterized by progressive motion defects and degenerative changes in the cerebellum and other parts of the CNS. Here we report the identification and establishment from a C57BL/6J mouse colony of a novel mouse line developing spontaneous progressive ataxia, which we refer to as ts3. Frequency of the phenotypic expression was consistent with an autosomal recessive Mendelian trait of inheritance, suggesting that a single gene mutation is responsible for the ataxic phenotype of this line. The onset of ataxia was observed at about three weeks of age, which slowly progressed until the hind limbs became entirely paralyzed in many cases. Micro-MRI study revealed significant cerebellar atrophy in all the ataxic mice, although individual variations were observed. Detailed histological analyses demonstrated significant atrophy of the anterior folia with reduced granule cells (GC) and abnormal morphology of cerebellar Purkinje cells (PC). Study by ultra-high voltage electron microscopy (UHVEM) further indicated aberrant morphology of PC dendrites and their spines, suggesting both morphological and functional abnormalities of the PC in the mutants. Immunohistochemical studies also revealed defects in parallel fiber (PF)–PC synapse formation and abnormal distal extension of climbing fibers (CF). Based on the phenotypic similarities of the ts3 mutant with other known ataxic mutants, we performed immunohistological analyses and found that expression levels of two genes and their products, glutamate receptor delta2 (grid2) and its ligand, cerebellin1 (Cbln1), are significantly reduced or undetectable. Finally, we sequenced the candidate genes and detected a large deletion in the coding region of the grid2 gene. Our present study suggests that ts3 is a new allele of the grid2 gene, which causes similar but different phenotypes as compared to other grid2 mutants. PMID

  14. Abnormal Structure–Function Relationship in Spasmodic Dysphonia

    PubMed Central

    Ludlow, Christy L.

    2012-01-01

    Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure–function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level–dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD. PMID:21666131

  15. EFFECTS OF LINDANE AND LINURON ON CALCIUM METABOLISM, MORPHOMETRY, AND THE KIDNEY

    EPA Science Inventory

    The effects of lindane and linuron on calcium metabolism, bone morphometry and the kidney. xperiments were performed to investigate the effects of lindane and linuron on calcium metabolism, femur morphometry and nephrotoxicity. ong-Evans hooded rats were dosed daily for 10 weeks ...

  16. Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome

    PubMed Central

    Bodranghien, Florian; Bastian, Amy; Casali, Carlo; Hallett, Mark; Louis, Elan D.; Mariën, Peter; Nowak, Dennis A.; Schmahmann, Jeremy D.; Serrao, Mariano; Steiner, Katharina Marie; Strupp, Michael; Tilikete, Caroline; Timmann, Dagmar; van Dun, Kim

    2017-01-01

    The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann’s syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor

  17. Aryl Hydrocarbon Receptor (AhR) Deletion in Cerebellar Granule Neuron Precursors Impairs Neurogenesis

    PubMed Central

    Dever, Daniel P.; Adham, Zachariah O.; Thompson, Bryan; Genestine, Matthieu; Cherry, Jonathan; Olschowka, John A.; DiCicco-Bloom, Emanuel; Opanashuk, Lisa A.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated member of the basic-helix-loop-helix (bHLH)/PER-ARNT-SIM(PAS) transcription factor superfamily that also mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence suggests that AhR influences the development of many tissues, including the central nervous system. Our previous studies suggest that sustained AhR activation by TCDD and/or AhR deletion disrupts cerebellar granule neuron precursor (GNP) development. In the current study, to determine whether endogenous AhR controls GNP development in a cell autonomous manner, we created a GNP-specific AhR deletion mouse, AhRfx/fx/Math1CRE/+ (AhR CKO). Selective AhR deletion in GNPs produced abnormalities in proliferation and differentiation. Specifically, fewer GNPs were engaged in S-phase, as demonstrated by ~25% reductions in thymidine (in vitro) and BrdU (in vivo) incorporation. Furthermore, total granule neuron numbers in the IGL at PND21 and PND60 were diminished in AhR CKO mice compared to controls. On the other hand, differentiation was enhanced, including ~40% increase in neurite outgrowth and 50% increase in GABARα6 receptor expression in deletion mutants. Our results suggest that AhR activity plays a role in regulating granule neuron number and differentiation, possibly by coordinating this GNP developmental transition. These studies provide novel insights for understanding the normal roles of AhR signaling during cerebellar granule cell neurogenesis, and may have important implications for the effects of environmental factors in cerebellar dysgenesis. PMID:26243376

  18. Network-targeted cerebellar transcranial magnetic stimulation improves attentional control

    PubMed Central

    Esterman, Michael; Thai, Michelle; Okabe, Hidefusa; DeGutis, Joseph; Saad, Elyana; Laganiere, Simon E.; Halko, Mark A.

    2018-01-01

    Developing non-invasive brain stimulation interventions to improve attentional control is extremely relevant to a variety of neurologic and psychiatric populations, yet few studies have identified reliable biomarkers that can be readily modified to improve attentional control. One potential biomarker of attention is functional connectivity in the core cortical network supporting attention - the dorsal attention network (DAN). We used a network-targeted cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance cortical functional connectivity in the DAN. Specifically, in healthy young adults we administered intermittent theta burst TMS (iTBS) to the midline cerebellar node of the DAN and, as a control, the right cerebellar node of the default mode network (DMN). These cerebellar targets were localized using individual resting-state fMRI scans. Participants completed assessments of both sustained (gradual onset continuous performance task, gradCPT) and transient attentional control (attentional blink) immediately before and after stimulation, in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation, participants had significantly fewer attentional lapses (lower commission error rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not affect gradCPT performance. Further, in the DAN condition, individuals with worse baseline gradCPT performance showed the greatest enhancement in gradCPT performance. These results suggest that temporarily increasing functional connectivity in the DAN via network-targeted cerebellar stimulation can enhance sustained attention, particularly in those with poor baseline performance. With regard to transient attention, TMS stimulation improved attentional blink performance across both stimulation sites, suggesting increasing functional connectivity in both networks can enhance this aspect of attention. These findings have important implications for intervention applications

  19. Neurodevelopmental Malformations of the Cerebellar Vermis in Genetically Engineered Rats.

    PubMed

    Ramos, Raddy L; Van Dine, Sarah E; Gilbert, Mary E; Leheste, Joerg R; Torres, German

    2015-12-01

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformations are almost exclusively found along the primary fissure and are indicative of deficits of neuronal migration during cerebellar development. In the present report, we test the prediction that genetically engineered rats on Sprague-Dawley or Long-Evans backgrounds will also exhibit the same cerebellar malformations. Consistent with our hypothesis, we found that three different transgenic lines on two different backgrounds had cerebellar malformations. Heterotopia in transgenic rats had identical cytoarchitecture as that observed in wild-type rats including altered morphology of Bergmann glia. In light of the possibility that heterotopia could affect results from behavioral studies, these data suggest that histological analyses be performed in studies of cerebellar function or development when using genetically engineered rats on these backgrounds in order to have more careful interpretation of experimental findings.

  20. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation

    PubMed Central

    Aldinger, Kimberly A; Lehmann, Ordan J; Hudgins, Louanne; Chizhikov, Victor V; Bassuk, Alexander G; Ades, Lesley C; Krantz, Ian D; Dobyns, William B; Millen, Kathleen J

    2010-01-01

    Dandy-Walker malformation (DWM), the most common human cerebellar malformation, has only one characterized associated locus1,2. Here we characterize a second DWM-linked locus on 6p25.3, showing that deletions or duplications encompassing FOXC1 are associated with cerebellar and posterior fossa malformations including cerebellar vermis hypoplasia (CVH), mega-cisterna magna (MCM) and DWM. Foxc1-null mice have embryonic abnormalities of the rhombic lip due to loss of mesenchyme-secreted signaling molecules with subsequent loss of Atoh1 expression in vermis. Foxc1 homozygous hypomorphs have CVH with medial fusion and foliation defects. Human FOXC1 heterozygous mutations are known to affect eye development, causing a spectrum of glaucoma-associated anomalies (Axenfeld-Rieger syndrome, ARS; MIM no. 601631). We report the first brain imaging data from humans with FOXC1 mutations and show that these individuals also have CVH. We conclude that alteration of FOXC1 function alone causes CVH and contributes to MCM and DWM. Our results highlight a previously unrecognized role for mesenchyme-neuroepithelium interactions in the mid-hindbrain during early embryogenesis. PMID:19668217

  1. Recent Advances in Cerebellar Ischemic Stroke Syndromes Causing Vertigo and Hearing Loss.

    PubMed

    Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

    2016-12-01

    Cerebellar ischemic stroke is one of the common causes of vascular vertigo. It usually accompanies other neurological symptoms or signs, but a small infarct in the cerebellum can present with vertigo without other localizing symptoms. Approximately 11 % of the patients with isolated cerebellar infarction simulated acute peripheral vestibulopathy, and most patients had an infarct in the territory of the medial branch of the posterior inferior cerebellar artery (PICA). A head impulse test can differentiate acute isolated vertigo associated with PICA territory cerebellar infarction from more benign disorders involving the inner ear. Acute hearing loss (AHL) of a vascular cause is mostly associated with cerebellar infarction in the territory of the anterior inferior cerebellar artery (AICA), but PICA territory cerebellar infarction rarely causes AHL. To date, at least eight subgroups of AICA territory infarction have been identified according to the pattern of neurotological presentations, among which the most common pattern of audiovestibular dysfunction is the combined loss of auditory and vestibular functions. Sometimes acute isolated audiovestibular loss can be the initial symptom of impending posterior circulation ischemic stroke (particularly within the territory of the AICA). Audiovestibular loss from cerebellar infarction has a good long-term outcome than previously thought. Approximately half of patients with superior cerebellar artery territory (SCA) cerebellar infarction experienced true vertigo, suggesting that the vertigo and nystagmus in the SCA territory cerebellar infarctions are more common than previously thought. In this article, recent findings on clinical features of vertigo and hearing loss from cerebellar ischemic stroke syndrome are summarized.

  2. Learning of Sensory Sequences in Cerebellar Patients

    ERIC Educational Resources Information Center

    Frings, Markus; Boenisch, Raoul; Gerwig, Marcus; Diener, Hans-Christoph; Timmann, Dagmar

    2004-01-01

    A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for…

  3. The Cerebellar Mutism Syndrome and Its Relation to Cerebellar Cognitive Function and the Cerebellar Cognitive Affective Disorder

    ERIC Educational Resources Information Center

    Wells, Elizabeth M.; Walsh, Karin S.; Khademian, Zarir P.; Keating, Robert F.; Packer, Roger J.

    2008-01-01

    The postoperative cerebellar mutism syndrome (CMS), consisting of diminished speech output, hypotonia, ataxia, and emotional lability, occurs after surgery in up to 25% of patients with medulloblastoma and occasionally after removal of other posterior fossa tumors. Although the mutism is transient, speech rarely normalizes and the syndrome is…

  4. Microvascular anatomy of the cerebellar parafloccular perforating space.

    PubMed

    Sosa, Pablo; Dujovny, Manuel; Onyekachi, Ibe; Sockwell, Noressia; Cremaschi, Fabián; Savastano, Luis E

    2016-02-01

    The cerebellopontine angle is a common site for tumor growth and vascular pathologies requiring surgical manipulations that jeopardize cranial nerve integrity and cerebellar and brainstem perfusion. To date, a detailed study of vessels perforating the cisternal surface of the middle cerebellar peduncle-namely, the paraflocculus or parafloccular perforating space-has yet to be published. In this report, the perforating vessels of the anterior inferior cerebellar artery (AICA) in the parafloccular space, or on the cisternal surface of the middle cerebellar peduncle, are described to elucidate their relevance pertaining to microsurgery and the different pathologies that occur at the cerebellopontine angle. Fourteen cadaveric cerebellopontine cisterns (CPCs) were studied. Anatomical dissections and analysis of the perforating arteries of the AICA and posterior inferior cerebellar artery at the parafloccular space were recorded using direct visualization by surgical microscope, optical histology, and scanning electron microscope. A comprehensive review of the English-language and Spanish-language literature was also performed, and findings related to anatomy, histology, physiology, neurology, neuroradiology, microsurgery, and endovascular surgery pertaining to the cerebellar flocculus or parafloccular spaces are summarized. A total of 298 perforating arteries were found in the dissected specimens, with a minimum of 15 to a maximum of 26 vessels per parafloccular perforating space. The average outer diameter of the cisternal portion of the perforating arteries was 0.11 ± 0.042 mm (mean ± SD) and the average length was 2.84 ± 1.2 mm. Detailed schematics and the surgical anatomy of the perforating vessels at the CPC and their clinical relevance are reported. The parafloccular space is a key entry point for many perforating vessels toward the middle cerebellar peduncle and lateral brainstem, and it must be respected and protected during surgical approaches to the

  5. Vertigo in brainstem and cerebellar strokes.

    PubMed

    Choi, Kwang-Dong; Lee, Hyung; Kim, Ji-Soo

    2013-02-01

    The aim of this study is to review the recent findings on the prevalence, clinical features, and diagnosis of vertigo from brainstem and cerebellar strokes. Patients with isolated vertigo are at higher risk for stroke than the general population. Strokes involving the brainstem and cerebellum may manifest as acute vestibular syndrome, and acute isolated audiovestibular loss may herald impending infarction in the territory of the anterior inferior cerebellar artery. Appropriate bedside evaluation is superior to MRI for detecting central vestibular syndromes. Recording of vestibular-evoked myogenic potentials is useful for evaluation of the central otolithic pathways in brainstem and cerebellar strokes. Accurate identification of isolated vascular vertigo is very important since misdiagnosis of acute stroke may result in significant morbidity and mortality, whereas overdiagnosis of vascular vertigo would lead to unnecessary costly work-ups and medication.

  6. Past, Present and Future Therapeutics for Cerebellar Ataxias

    PubMed Central

    Marmolino, D; Manto, M

    2010-01-01

    Cerebellar ataxias are a group of disabling neurological disorders. Patients exhibit a cerebellar syndrome and can also present with extra-cerebellar deficits, namely pigmentary retinopathy, extrapyramidal movement disorders, pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioural symptoms), and peripheral neuropathy. Recently, deficits in cognitive operations have been unraveled. Cerebellar ataxias are heterogeneous both at the phenotypic and genotypic point of view. Therapeutical trials performed during these last 4 decades have failed in most cases, in particular because drugs were not targeting a deleterious pathway, but were given to counteract putative defects in neurotransmission. The identification of the causative mutations of many hereditary ataxias, the development of relevant animal models and the recent identifications of the molecular mechanisms underlying ataxias are impacting on the development of new drugs. We provide an overview of the pharmacological treatments currently used in the clinical practice and we discuss the drugs under development. PMID:20808545

  7. Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1

    PubMed Central

    Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S; Anthony, Todd E; Wang, Chenran; Li, Yi E; Guan, Jun-Lin; Murphy, Geoffrey G; Zhu, Yuan

    2014-01-01

    Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities. DOI: http://dx.doi.org/10.7554/eLife.05151.001 PMID:25535838

  8. Morphometric brain abnormalities in boys with conduct disorder.

    PubMed

    Huebner, Thomas; Vloet, Timo D; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R; Herpertz, Sabine C; Herpertz-Dahlmann, Beate

    2008-05-01

    Children with the early-onset type of conduct disorder (CD) are at high risk for developing an antisocial personality disorder. Although there have been several neuroimaging studies on morphometric differences in adults with antisocial personality disorder, little is known about structural brain aberrations in boys with CD. Magnetic resonance imaging and voxel-based morphometry were used to assess abnormalities in gray matter volumes in 23 boys ages 12 to 17 years with CD (17 comorbid for attention-deficit/hyperactivity disorder) in comparison with age- and IQ-matched controls. Compared with healthy controls, mean gray matter volume was 6% smaller in the clinical group. Compared with controls, reduced gray matter volumes were found in the left orbitofrontal region and bilaterally in the temporal lobes, including the amygdala and hippocampus on the left side in the CD group. Regression analyses in the clinical group indicated an inverse association of hyperactive/impulsive symptoms and widespread gray matter abnormalities in the frontoparietal and temporal cortices. By contrast, CD symptoms correlated primarily with gray matter reductions in limbic brain structures. The data suggest that boys with CD and comorbid attention-deficit/hyperactivity disorder show brain abnormalities in frontolimbic areas that resemble structural brain deficits, which are typically observed in adults with antisocial behavior.

  9. The study of Lake Urmia desiccation: morphometry impress

    NASA Astrophysics Data System (ADS)

    Moradi, Ayoub; Rasouli, Ali Akbar; Roostaei, Shahram

    2017-04-01

    Located in northwestern Iran, the hypersaline Lake Urmia has started a serious uninterrupted desiccation since 1995. The lake has lost about eight meters of water level and about 75% of water surface area during past 20 years. In particular, the lake water volume decrement has been accelerated in recent years. The importance of the Lake Urmia for human life in northwestern Iran, and its destructive effects on a vast region if totally dry up, demands comprehensive studies of the lake level fluctuations mechanism. According to literature review, the water volume of the lake behaves sometimes differently from the water storage of the whole basin. Our time series analysis using Land Data Assimilation Systems also confirms those differences within last decades. In other hand, many studies addressed the lake desiccation to climatic changes and/or anthropogenic influences such as excessive dam constructions in the watershed during last decades. As water leaves the lake only through evaporation, the fluctuation of evaporation has a distinctive role in the lake level variations. Dramatic decreament in the lake extent indicates of a special morphometry. The lake's morphometry has made it vulnerable to temperature and salinity changes. It strongly controls the lake's water heat capacity and water density. And, it therefore controls the rate of evaporation from water surface. We study the role of lake's morphometry on the lake desiccation. Although, the global climatic change is known as the primary reason for current droughts in the Middle East generally, our preliminary results show that the lake's morphometry is the main cause for the accelerating of water volume lost in Lake Urmia. In particular, after 2007, lake's water temperature and density show significant variations. Water heat capacity and evaporation rate are consistent with information of lake's hypsometry.

  10. Effects of accuracy constraints on reach-to-grasp movements in cerebellar patients.

    PubMed

    Rand, M K; Shimansky, Y; Stelmach, G E; Bracha, V; Bloedel, J R

    2000-11-01

    Reach-to-grasp movements of patients with pathology restricted to the cerebellum were compared with those of normal controls. Two types of paradigms with different accuracy constraints were used to examine whether cerebellar impairment disrupts the stereotypic relationship between arm transport and grip aperture and whether the variability of this relationship is altered when greater accuracy is required. The movements were made to either a vertical dowel or to a cross bar of a small cross. All subjects were asked to reach for either target at a fast but comfortable speed, grasp the object between the index finger and thumb, and lift it a short distance off the table. In terms of the relationship between arm transport and grip aperture, the control subjects showed a high consistency in grip aperture and wrist velocity profiles from trial to trial for movements to both the dowel and the cross. The relationship between the maximum velocity of the wrist and the time at which grip aperture was maximal during the reach was highly consistent throughout the experiment. In contrast, the time of maximum grip aperture and maximum wrist velocity of the cerebellar patients was quite variable from trial to trial, and the relationship of these measurements also varied considerably. These abnormalities were present regardless of the accuracy requirement. In addition, the cerebellar patients required a significantly longer time to grasp and lift the objects than the control subjects. Furthermore, the patients exhibited a greater grip aperture during reach than the controls. These data indicate that the cerebellum contributes substantially to the coordination of movements required to perform reach-to-grasp movements. Specifically, the cerebellum is critical for executing this behavior with a consistent, well-timed relationship between the transport and grasp components. This contribution is apparent even when accuracy demands are minimal.

  11. Improving cerebellar segmentation with statistical fusion

    NASA Astrophysics Data System (ADS)

    Plassard, Andrew J.; Yang, Zhen; Prince, Jerry L.; Claassen, Daniel O.; Landman, Bennett A.

    2016-03-01

    The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multiatlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non- Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution.

  12. Anticoagulation therapy is harmful to large-sized cerebellar infarction.

    PubMed

    Zhang, She-Qing; Wang, Wei; Ma, Xiao-Long; Xia, Yu-Ye; Liu, Ai-Jun

    2014-09-01

    Anticoagulants are commonly used to treat ischemic stroke. Its impact on cerebellar infarction has not been fully understood. In the clinical study, we reviewed a consecutive series of patients with large-sized cerebellar infarction (diameter > 3 cm, n = 30) treated with or without anticoagulation. In animal study, cerebellar infarction operation was performed in 12 Cynomolgus monkeys. Then the animals were administrated with low molecular weight heparin (LMWH) or vehicle for 14 days. Six patients died during the following treatment. All the subjects that died received anticoagulation therapy, while nobody in the survival group received such a therapy. Compared with sham-operated animals, all monkeys with cerebellar infarction have obvious neurological deficits. The number and size of the Purkinje cells in the cerebellar area were also reduced. Two animals in the LMWH group (33%) died, while all animals in the vehicle control group survived. Compared with the vehicle group, the neurological score in the LMWH group was significantly increased (P < 0.05). The water content in the cerebella was also significantly higher (P < 0.05). Edema, hemorrhage, and subarachnoid hemorrhage occurred in the cerebella as well as brainstem of all the LMWH treated animals. These results indicated the harmful effects of anticoagulation therapy on large-sized cerebellar infarction. © 2014 John Wiley & Sons Ltd.

  13. Cerebellar blood flow in methylmercury poisoning (Minamata disease).

    PubMed

    Itoh, K; Korogi, Y; Tomiguchi, S; Takahashi, M; Okajima, T; Sato, H

    2001-04-01

    We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part.

  14. Tracking the development of agrammatic aphasia: A tensor-based morphometry study.

    PubMed

    Whitwell, Jennifer L; Duffy, Joseph R; Machulda, Mary M; Clark, Heather M; Strand, Edythe A; Senjem, Matthew L; Gunter, Jeffrey L; Spychalla, Anthony J; Petersen, Ronald C; Jack, Clifford R; Josephs, Keith A

    2017-05-01

    Agrammatic aphasia can be observed in neurodegenerative disorders and has been traditionally linked with damage to Broca's area, although there have been disagreements concerning whether damage to Broca's area is necessary or sufficient for the development of agrammatism. We aimed to investigate the neuroanatomical correlates of the emergence of agrammatic aphasia utilizing a unique cohort of patients with primary progressive apraxia of speech (PPAOS) that did not have agrammatism at baseline but developed agrammatic aphasia over time. Twenty PPAOS patients were recruited and underwent detailed speech/language assessments and 3T MRI at two visits, approximately two years apart. None of the patients showed evidence of agrammatism in writing or speech at baseline. Eight patients developed aphasia at follow-up (progressors) and 12 did not (non-progressors). Tensor-based morphometry utilizing symmetric normalization (SyN) was used to assess patterns of grey matter atrophy and voxel-based morphometry was used to assess patterns of grey matter loss at baseline. The progressors were younger at onset and more likely to show distorted sound substitutions or additions compared to non-progressors. Both groups showed change over time in premotor and motor cortices, posterior frontal lobe, basal ganglia, thalamus and midbrain, but the progressors showed greater rates of atrophy in left pars triangularis, thalamus and putamen compared to non-progressors. The progressors also showed greater grey matter loss in pars triangularis and putamen at baseline. This cohort provided a unique opportunity to assess the anatomical changes that accompany the development of agrammatic aphasia. The results suggest that damage to a network of regions including Broca's area, thalamus and basal ganglia are responsible for the development of agrammatic aphasia in PPAOS. Clinical and neuroimaging abnormalities were also present before the onset of agrammatism that could help improve prognosis in

  15. Mechanisms of human cerebellar dysmetria: experimental evidence and current conceptual bases

    PubMed Central

    Manto, Mario

    2009-01-01

    The human cerebellum contains more neurons than any other region in the brain and is a major actor in motor control. Cerebellar circuitry is unique by its stereotyped architecture and its modular organization. Understanding the motor codes underlying the organization of limb movement and the rules of signal processing applied by the cerebellar circuits remains a major challenge for the forthcoming decades. One of the cardinal deficits observed in cerebellar patients is dysmetria, designating the inability to perform accurate movements. Patients overshoot (hypermetria) or undershoot (hypometria) the aimed target during voluntary goal-directed tasks. The mechanisms of cerebellar dysmetria are reviewed, with an emphasis on the roles of cerebellar pathways in controlling fundamental aspects of movement control such as anticipation, timing of motor commands, sensorimotor synchronization, maintenance of sensorimotor associations and tuning of the magnitudes of muscle activities. An overview of recent advances in our understanding of the contribution of cerebellar circuitry in the elaboration and shaping of motor commands is provided, with a discussion on the relevant anatomy, the results of the neurophysiological studies, and the computational models which have been proposed to approach cerebellar function. PMID:19364396

  16. Mindboggling morphometry of human brains

    PubMed Central

    Bao, Forrest S.; Giard, Joachim; Stavsky, Eliezer; Lee, Noah; Rossa, Brian; Reuter, Martin; Chaibub Neto, Elias

    2017-01-01

    Mindboggle (http://mindboggle.info) is an open source brain morphometry platform that takes in preprocessed T1-weighted MRI data and outputs volume, surface, and tabular data containing label, feature, and shape information for further analysis. In this article, we document the software and demonstrate its use in studies of shape variation in healthy and diseased humans. The number of different shape measures and the size of the populations make this the largest and most detailed shape analysis of human brains ever conducted. Brain image morphometry shows great potential for providing much-needed biological markers for diagnosing, tracking, and predicting progression of mental health disorders. Very few software algorithms provide more than measures of volume and cortical thickness, while more subtle shape measures may provide more sensitive and specific biomarkers. Mindboggle computes a variety of (primarily surface-based) shapes: area, volume, thickness, curvature, depth, Laplace-Beltrami spectra, Zernike moments, etc. We evaluate Mindboggle’s algorithms using the largest set of manually labeled, publicly available brain images in the world and compare them against state-of-the-art algorithms where they exist. All data, code, and results of these evaluations are publicly available. PMID:28231282

  17. Inhibition of the amygdala central nucleus by stimulation of cerebellar output in rats: a putative mechanism for extinction of the conditioned fear response.

    PubMed

    Magal, Ari; Mintz, Matti

    2014-11-01

    The amygdala and the cerebellum serve two distinctively different functions. The amygdala plays a role in the expression of emotional information, whereas the cerebellum is involved in the timing of discrete motor responses. Interaction between these two systems is the basis of the two-stage theory of learning, according to which an encounter with a challenging event triggers fast classical conditioning of fear-conditioned responses in the amygdala and slow conditioning of motor-conditioned responses in the cerebellum. A third stage was hypothesised when an apparent interaction between amygdala and cerebellar associative plasticity was observed: an adaptive rate of cerebellum-dependent motor-conditioned responses was associated with a decrease in amygdala-dependent fear-conditioned responses, and was interpreted as extinction of amygdala-related fear-conditioned responses by the cerebellar output. To explore this hypothesis, we mimicked some components of classical eyeblink conditioning in anesthetised rats by applying an aversive periorbital pulse as an unconditioned stimulus and a train of pulses to the cerebellar output nuclei as a cerebellar neuronal-conditioned response. The central amygdala multiple unit response to the periorbital pulse was measured with or without a preceding train to the cerebellar output nuclei. The results showed that activation of the cerebellar output nuclei prior to periorbital stimulation produced diverse patterns of inhibition of the amygdala response to the periorbital aversive stimulus, depending upon the nucleus stimulated, the laterality of the nucleus stimulated, and the stimulus interval used. These results provide a putative extinction mechanism of learned fear behavior, and could have implications for the treatment of pathologies involving abnormal fear responses by using motor training as therapy. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Maternal Postsecondary Education Associated With Improved Cerebellar Growth After Preterm Birth.

    PubMed

    Stiver, Mikaela L; Kamino, Daphne; Guo, Ting; Thompson, Angela; Duerden, Emma G; Taylor, Margot J; Tam, Emily W Y

    2015-10-01

    The preterm cerebellum is vulnerable to impaired development impacting long-term outcome. Preterm newborns (<32 weeks) underwent serial magnetic resonance imaging (MRI) scans. The association between parental education and cerebellar volume at each time point was assessed, adjusting for age at scan. In 26 infants, cerebellar volumes at term (P = .001), but not birth (P = .4), were associated with 2-year volumes. For 1 cm(3) smaller cerebellar volume (4% total volume) at term, the cerebellum was 3.18 cm(3) smaller (3% total volume) by 2 years. Maternal postsecondary education was not associated with cerebellar volume at term (P = .16). Maternal postsecondary education was a significant confounder in the relationship between term and 2-year cerebellar volumes (P = .016), with higher education associated with improved volumes by 2 years. Although preterm birth has been found to be associated with smaller cerebellar volumes at term, maternal postsecondary education is associated with improved growth detectable by 2 years. © The Author(s) 2015.

  19. Differentiating Cerebellar Impact on Thalamic Nuclei.

    PubMed

    Gornati, Simona V; Schäfer, Carmen B; Eelkman Rooda, Oscar H J; Nigg, Alex L; De Zeeuw, Chris I; Hoebeek, Freek E

    2018-05-29

    The cerebellum plays a role in coordination of movements and non-motor functions. Cerebellar nuclei (CN) axons connect to various parts of the thalamo-cortical network, but detailed information on the characteristics of cerebello-thalamic connections is lacking. Here, we assessed the cerebellar input to the ventrolateral (VL), ventromedial (VM), and centrolateral (CL) thalamus. Confocal and electron microscopy showed an increased density and size of CN axon terminals in VL compared to VM or CL. Electrophysiological recordings in vitro revealed that optogenetic CN stimulation resulted in enhanced charge transfer and action potential firing in VL neurons compared to VM or CL neurons, despite that the paired-pulse ratio was not significantly different. Together, these findings indicate that the impact of CN input onto neurons of different thalamic nuclei varies substantially, which highlights the possibility that cerebellar output differentially controls various parts of the thalamo-cortical network. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Recovery of biological motion perception and network plasticity after cerebellar tumor removal.

    PubMed

    Sokolov, Arseny A; Erb, Michael; Grodd, Wolfgang; Tatagiba, Marcos S; Frackowiak, Richard S J; Pavlova, Marina A

    2014-10-01

    Visual perception of body motion is vital for everyday activities such as social interaction, motor learning or car driving. Tumors to the left lateral cerebellum impair visual perception of body motion. However, compensatory potential after cerebellar damage and underlying neural mechanisms remain unknown. In the present study, visual sensitivity to point-light body motion was psychophysically assessed in patient SL with dysplastic gangliocytoma (Lhermitte-Duclos disease) to the left cerebellum before and after neurosurgery, and in a group of healthy matched controls. Brain activity during processing of body motion was assessed by functional magnetic resonance imaging (MRI). Alterations in underlying cerebro-cerebellar circuitry were studied by psychophysiological interaction (PPI) analysis. Visual sensitivity to body motion in patient SL before neurosurgery was substantially lower than in controls, with significant improvement after neurosurgery. Functional MRI in patient SL revealed a similar pattern of cerebellar activation during biological motion processing as in healthy participants, but located more medially, in the left cerebellar lobules III and IX. As in normalcy, PPI analysis showed cerebellar communication with a region in the superior temporal sulcus, but located more anteriorly. The findings demonstrate a potential for recovery of visual body motion processing after cerebellar damage, likely mediated by topographic shifts within the corresponding cerebro-cerebellar circuitry induced by cerebellar reorganization. The outcome is of importance for further understanding of cerebellar plasticity and neural circuits underpinning visual social cognition.

  1. Postnatal Migration of Cerebellar Interneurons

    PubMed Central

    Galas, Ludovic; Bénard, Magalie; Lebon, Alexis; Komuro, Yutaro; Schapman, Damien; Vaudry, Hubert; Vaudry, David; Komuro, Hitoshi

    2017-01-01

    Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders. PMID:28587295

  2. Cerebellar abiotrophy in a family of Border Collie dogs.

    PubMed

    Sandy, J R; Slocombe, R E; Mitten, R W; Jedwab, D

    2002-11-01

    Cerebellar abiotrophies have a nonsex-linked, autosomal, recessively inherited basis in a number of species, and lesions typically reflect profound and progressive loss of Purkinje cells. In this report, an unusual form of abiotrophy is described for two sibling Border Collies. Extensive loss of the cerebellar granular cell layer was present with relative sparing of Purkinje cells of two female pups. The biochemical basis for this form of cerebellar abiotrophy is unknown, but the lack of disease in other siblings supports an autosomal recessive mode of inheritance.

  3. Blood harmane is correlated with cerebellar metabolism in essential tremor: a pilot study.

    PubMed

    Louis, Elan D; Zheng, Wei; Mao, Xiangling; Shungu, Dikoma C

    2007-08-07

    On proton magnetic resonance spectroscopic imaging ((1)H MRSI), there is a decrease in cerebellar N-acetylaspartate/total creatine (NAA/tCr) in essential tremor (ET), signifying cerebellar neuronal dysfunction or degeneration. Harmane, which is present in the human diet, is a potent tremor-producing neurotoxin. Blood harmane concentrations seem to be elevated in ET. To assess in patients with ET whether blood harmane concentration is correlated with cerebellar NAA/tCR, a neuroimaging measure of neuronal dysfunction or degeneration. Twelve patients with ET underwent (1)H MRSI. The major neuroanatomic structure of interest was the cerebellar cortex. Secondary regions were the central cerebellar white matter, cerebellar vermis, thalamus, and basal ganglia. Blood concentrations of harmane and another neurotoxin, lead, were also assessed. Mean +/- SD cerebellar NAA/tCR was 1.52 +/- 0.41. In a linear regression model that adjusted for age and gender, log blood harmane concentration was a predictor of cerebellar NAA/tCR (beta = -0.41, p = 0.009); every 1 g(-10)/mL unit increase in log blood harmane concentration was associated with a 0.41 unit decrease in cerebellar NAA/tCR. The association between blood harmane concentration and brain NAA/tCR only occurred in the cerebellar cortex; it was not observed in secondary brain regions of interest. Furthermore, the association was specific to harmane and not another neurotoxin, lead. This study provides additional support for the emerging link between harmane, a neurotoxin, and ET. Further studies are warranted to address whether cerebellar harmane concentrations are associated with cerebellar pathology in postmortem studies of the ET brain.

  4. Remote cerebellar hemorrhage following supratentorial craniotomy.

    PubMed

    Huang, Chih-Yuan; Lee, Po-Hsuan; Lin, Sheng-Hsiang; Chuang, Ming-Tsung; Sun, Yuan-Ting; Hung, Yu-Chang; Lee, E-Jian

    2012-06-01

    Cerebellar hemorrhage remote from the site of surgery may complicate neurosurgical procedure. The exact pathophysiology of this type of hemorrhage is poorly understood. We retrospectively compared 16 patients who had remote cerebellar hemorrhage (RCH) with a case-matched control cohort, to determine the significance of perisurgical and surgical factors that may predispose patients to such bleeding events. From 1 June 2005 to 31 December 2008, postoperative routine head computed tomographic (CT) scan was performed in our institution and 16 patients with RCH after supratentorial neurosurgical procedure were identified. The medical charts of these 16 cases and a control cohort of 64 patients were recorded. All parameters were analyzed with regards to various variables. The incidence RCH after supratentorial craniotomy increased after postoperative computed tomographic scan. The mechanism of cerebellar hemorrhage in this series of patients is most likely multifactorial. Several variables showed a significant association with the occurrence of RCH. Multivariate analysis indicated that the following two factors independently correlated with occurrence of RCH: (1) postoperative epidural drainage amount; and (2) history of previous cerebrovascular accident (CVA) with cerebral atrophy. All cases with RCH underwent medical treatment and no neurological sequelae associated with RCH. Postoperative epidural drainage amount and history of previous CVA with cerebral atrophy can reliably predict the occurrence of cerebellar hemorrhage after supratentorial craniotomy. One of the most important strategies to minimize hazardous complications is to be aware of these potential risk factors and to take action to prevent them.

  5. An evaluation of volume-based morphometry for prediction of mild cognitive impairment and Alzheimer's disease

    PubMed Central

    Schmitter, Daniel; Roche, Alexis; Maréchal, Bénédicte; Ribes, Delphine; Abdulkadir, Ahmed; Bach-Cuadra, Meritxell; Daducci, Alessandro; Granziera, Cristina; Klöppel, Stefan; Maeder, Philippe; Meuli, Reto; Krueger, Gunnar

    2014-01-01

    Voxel-based morphometry from conventional T1-weighted images has proved effective to quantify Alzheimer's disease (AD) related brain atrophy and to enable fairly accurate automated classification of AD patients, mild cognitive impaired patients (MCI) and elderly controls. Little is known, however, about the classification power of volume-based morphometry, where features of interest consist of a few brain structure volumes (e.g. hippocampi, lobes, ventricles) as opposed to hundreds of thousands of voxel-wise gray matter concentrations. In this work, we experimentally evaluate two distinct volume-based morphometry algorithms (FreeSurfer and an in-house algorithm called MorphoBox) for automatic disease classification on a standardized data set from the Alzheimer's Disease Neuroimaging Initiative. Results indicate that both algorithms achieve classification accuracy comparable to the conventional whole-brain voxel-based morphometry pipeline using SPM for AD vs elderly controls and MCI vs controls, and higher accuracy for classification of AD vs MCI and early vs late AD converters, thereby demonstrating the potential of volume-based morphometry to assist diagnosis of mild cognitive impairment and Alzheimer's disease. PMID:25429357

  6. Heat stroke induced cerebellar dysfunction: A “forgotten syndrome”

    PubMed Central

    Kosgallana, Athula D; Mallik, Shreyashee; Patel, Vishal; Beran, Roy G

    2013-01-01

    We report a case of heat stroke induced acute cerebellar dysfunction, a rare neurological disease characterized by gross cerebellar dysfunction with no acute radiographic changes, in a 61 years old ship captain presenting with slurred speech and gait ataxia. A systematic review of the literature on heat stroke induced cerebellar dysfunction was performed, with a focus on investigations, treatment and outcomes. After review of the literature and detailed patient investigation it was concluded that this patient suffered heat stroke at a temperature less than that quoted in the literature. PMID:24340279

  7. Diffusion tensor imaging of the human cerebellar pathways and their interplay with cerebral macrostructure

    PubMed Central

    Keser, Zafer; Hasan, Khader M.; Mwangi, Benson I.; Kamali, Arash; Ucisik-Keser, Fehime Eymen; Riascos, Roy F.; Yozbatiran, Nuray; Francisco, Gerard E.; Narayana, Ponnada A.

    2015-01-01

    Cerebellar white matter (WM) connections to the central nervous system are classified functionally into the Spinocerebellar (SC), vestibulocerebellar (VC), and cerebrocerebellar subdivisions. The SC pathways project from spinal cord to cerebellum, whereas the VC pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC) pathways being of cortical origin and the dentate-rubro-thalamo-cortical (DRTC) pathway being of cerebellar origin. In this study we systematically quantified the whole cerebellar system connections using diffusion tensor magnetic resonance imaging (DT-MRI). Ten right-handed healthy subjects (7 males and 3 females, age range 20–51 years) were studied. DT-MRI data were acquired with a voxel size = 2 mm × 2 mm × 2 mm at a 3.0 Tesla clinical MRI scanner. The DT-MRI data were prepared and analyzed using anatomically-guided deterministic tractography methods to reconstruct the SC, DRTC, fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC) and occipito-ponto-cerebellar (OPC). The DTI-attributes or the cerebellar tracts along with their cortical representation (Brodmann areas) were presented in standard Montréal Neurological Institute space. All cerebellar tract volumes were quantified and correlated with volumes of cerebral cortical, subcortical gray matter (GM), cerebral WM and cerebellar GM, and cerebellar WM. On our healthy cohort, the ratio of total cerebellar GM-to-WM was ~3.29 ± 0.24, whereas the ratio of cerebral GM-to-WM was approximately 1.10 ± 0.11. The sum of all cerebellar tract volumes is ~25.8 ± 7.3 mL, or a percentage of 1.6 ± 0.45 of the total intracranial volume (ICV). PMID:25904851

  8. Defective cerebellar control of cortical plasticity in writer’s cramp

    PubMed Central

    Hubsch, Cecile; Roze, Emmanuel; Popa, Traian; Russo, Margherita; Balachandran, Ammu; Pradeep, Salini; Mueller, Florian; Brochard, Vanessa; Quartarone, Angelo; Degos, Bertrand; Vidailhet, Marie; Kishore, Asha

    2013-01-01

    A large body of evidence points to a role of basal ganglia dysfunction in the pathophysiology of dystonia, but recent studies indicate that cerebellar dysfunction may also be involved. The cerebellum influences sensorimotor adaptation by modulating sensorimotor plasticity of the primary motor cortex. Motor cortex sensorimotor plasticity is maladaptive in patients with writer’s cramp. Here we examined whether putative cerebellar dysfunction in dystonia is linked to these patients’ maladaptive plasticity. To that end we compared the performances of patients and healthy control subjects in a reaching task involving a visuomotor conflict generated by imposing a random deviation (−40° to 40°) on the direction of movement of the mouse/cursor. Such a task is known to involve the cerebellum. We also compared, between patients and healthy control subjects, how the cerebellum modulates the extent and duration of an ongoing sensorimotor plasticity in the motor cortex. The cerebellar cortex was excited or inhibited by means of repeated transcranial magnetic stimulation before artificial sensorimotor plasticity was induced in the motor cortex by paired associative stimulation. Patients with writer’s cramp were slower than the healthy control subjects to reach the target and, after having repeatedly adapted their trajectories to the deviations, they were less efficient than the healthy control subjects to perform reaching movement without imposed deviation. It was interpreted as impaired washing-out abilities. In healthy subjects, cerebellar cortex excitation prevented the paired associative stimulation to induce a sensorimotor plasticity in the primary motor cortex, whereas cerebellar cortex inhibition led the paired associative stimulation to be more efficient in inducing the plasticity. In patients with writer’s cramp, cerebellar cortex excitation and inhibition were both ineffective in modulating sensorimotor plasticity. In patients with writer’s cramp, but not

  9. Cerebro-cerebellar interactions underlying temporal information processing.

    PubMed

    Aso, Kenji; Hanakawa, Takashi; Aso, Toshihiko; Fukuyama, Hidenao

    2010-12-01

    The neural basis of temporal information processing remains unclear, but it is proposed that the cerebellum plays an important role through its internal clock or feed-forward computation functions. In this study, fMRI was used to investigate the brain networks engaged in perceptual and motor aspects of subsecond temporal processing without accompanying coprocessing of spatial information. Direct comparison between perceptual and motor aspects of time processing was made with a categorical-design analysis. The right lateral cerebellum (lobule VI) was active during a time discrimination task, whereas the left cerebellar lobule VI was activated during a timed movement generation task. These findings were consistent with the idea that the cerebellum contributed to subsecond time processing in both perceptual and motor aspects. The feed-forward computational theory of the cerebellum predicted increased cerebro-cerebellar interactions during time information processing. In fact, a psychophysiological interaction analysis identified the supplementary motor and dorsal premotor areas, which had a significant functional connectivity with the right cerebellar region during a time discrimination task and with the left lateral cerebellum during a timed movement generation task. The involvement of cerebro-cerebellar interactions may provide supportive evidence that temporal information processing relies on the simulation of timing information through feed-forward computation in the cerebellum.

  10. Visuomotor learning in cerebellar patients.

    PubMed

    Timmann, D; Shimansky, Y; Larson, P S; Wunderlich, D A; Stelmach, G E; Bloedel, J R

    1996-11-01

    The aim of the present study was to demonstrate that patients with pathology affecting substantial regions of the cerebellum can improve their performance in a series of two-dimensional tracing tasks, thus supporting the view that this type of motor behavior can be acquired even when the integrity of this structure is compromised. Eight patients with chronic, isolated cerebellar lesions and eight age- and sex-matched healthy controls were tested. Three patients had mild, five had moderate upper limb ataxia. The experiment was divided into two parts. In the first, subjects traced an irregularly shaped outline over 20 consecutive trials ('Trace 1' task). Next, subjects were asked to redraw the object without any underlying template as a guide ('Memory 1' task). In the second part of the study, subjects were asked to trace a different, irregularly shaped outline over 20 consecutive trials ('Trace 2' task). Next, they were required to redraw it by memory with its axis rotated 90 degrees ('Memory 2' task). In each of the memory tasks the template was placed over the drawn image after each trial and shown to the subjects. The error of performance was determined by calculating three different measurements, each focused on different aspects of the task. Based on these measurements, the cerebellar patients showed improvement in both memory tasks. In the 'Memory 1' task the calculated error decreased significantly for the patients with mild ataxia. In the 'Memory 2' task all cerebellar patients improved their performance substantially enough to reduce significantly the magnitude of all three error measurements. The experiments demonstrate that patients with cerebellar lesions are capable of improving substantially their performance of a complex motor task involving the recall of memorized shapes and the visuomotor control of a tracing movement.

  11. Subacute sclerosing panencephalitis presenting as acute cerebellar ataxia and brain stem hyperintensities.

    PubMed

    Saini, Arushi Gahlot; Sankhyan, Naveen; Padmanabh, Hansashree; Sahu, Jitendra Kumar; Vyas, Sameer; Singhi, Pratibha

    2016-05-01

    Subacute sclerosing panencephalitis is a devastating neurodegenerative disease with a characteristic clinical course. Atypical presentations may be seen in 10% of the cases. To describe the atypical clinical and radiological features of SSPE in a child form endemic country. A 5-year-old boy presented with acute-onset cerebellar ataxia without associated encephalopathy, focal motor deficits, seizures or cognitive decline. He had varicella-like illness with vesicular, itchy truncal rash erupting one month prior to the onset of these symptoms. He underwent detailed neurological assessment, relevant laboratory and radiological investigations. Neuroimaging revealed peculiar brain stem lesions involving the pons and cerebellum suggestive of demyelination. With a presumptive diagnosis of clinically isolated syndrome of demyelination, he was administered pulse methylprednisolone (30 mg/kg/day for 5 days). Four weeks later he developed myoclonic jerks. Electroencephalogram showed characteristic periodic complexes time-locked with myoclonus. CSF and serum anti-measles antibody titres were elevated (1:625). Our report highlights that subacute sclerosing panencephalitis can present atypically as isolated acute cerebellar ataxia and peculiar involvement of longitudinal and sparing of transverse pontine fibres. The predominant brainstem abnormalities in the clinical setting may mimick acute demyelinating syndrome. Hence, it is important to recognize these features of subacute sclerosing panencephalitis in children, especially in the endemic countries. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  12. Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition

    PubMed Central

    D'Angelo, Egidio; Casali, Stefano

    2013-01-01

    Following the fundamental recognition of its involvement in sensory-motor coordination and learning, the cerebellum is now also believed to take part in the processing of cognition and emotion. This hypothesis is recurrent in numerous papers reporting anatomical and functional observations, and it requires an explanation. We argue that a similar circuit structure in all cerebellar areas may carry out various operations using a common computational scheme. On the basis of a broad review of anatomical data, it is conceivable that the different roles of the cerebellum lie in the specific connectivity of the cerebellar modules, with motor, cognitive, and emotional functions (at least partially) segregated into different cerebro-cerebellar loops. We here develop a conceptual and operational framework based on multiple interconnected levels (a meta-levels hypothesis): from cellular/molecular to network mechanisms leading to generation of computational primitives, thence to high-level cognitive/emotional processing, and finally to the sphere of mental function and dysfunction. The main concept explored is that of intimate interplay between timing and learning (reminiscent of the “timing and learning machine” capabilities long attributed to the cerebellum), which reverberates from cellular to circuit mechanisms. Subsequently, integration within large-scale brain loops could generate the disparate cognitive/emotional and mental functions in which the cerebellum has been implicated. We propose, therefore, that the cerebellum operates as a general-purpose co-processor, whose effects depend on the specific brain centers to which individual modules are connected. Abnormal functioning in these loops could eventually contribute to the pathogenesis of major brain pathologies including not just ataxia but also dyslexia, autism, schizophrenia, and depression. PMID:23335884

  13. Differential Effects of Intraventricular Hemorrhage and White Matter Injury on Preterm Cerebellar Growth

    PubMed Central

    Tam, Emily W.Y.; Miller, Steven P.; Studholme, Colin; Chau, Vann; Glidden, David; Poskitt, Kenneth J.; Ferriero, Donna M.; Barkovich, A. James

    2010-01-01

    Objective To hypothesize that detailed examination of early cerebellar volumes over time would distinguish differences in cerebellar growth associated with intraventricular hemorrhage (IVH) and white matter injury (WMI) in preterm infants. Study design Preterm newborns at the University of California San Francisco (n=57) and the University of British Columbia (n=115) were studied using serial MRI scans near birth and again at near term-equivalent age. Interactive semi-automated tools were used to determine volumes of the cerebellar hemispheres. Results Adjusting for supratentorial brain injury, cerebellar hemorrhage, and study site, cerebellar volume increased 1.7cm3/week postmenstrual age (95% CI 1.6–1.7, P<0.001). More severe supratentorial IVH was associated with slower growth of cerebellar volumes (P<0.001). Volumes by 40 weeks were 1.4 cm3 lower in premature infants with grade 1–2 IVH and 5.4 cm3 lower with grade 3–4 IVH. The same magnitude of decrease was found between ipsilateral and contralateral IVH. No association was found with severity of WMI (P=0.3). Conclusions Early effects of decreased cerebellar volume associated with supratentorial IVH in either hemisphere may be a result of concurrent cerebellar injury or direct effects of subarachnoid blood on cerebellar development. PMID:20961562

  14. In and out of the loop: external and internal modulation of the olivo-cerebellar loop

    PubMed Central

    Libster, Avraham M.; Yarom, Yosef

    2013-01-01

    Cerebellar anatomy is known for its crystal like structure, where neurons and connections are precisely and repeatedly organized with minor variations across the Cerebellar Cortex. The olivo-cerebellar loop, denoting the connections between the Cerebellar cortex, Inferior Olive and Cerebellar Nuclei (CN), is also modularly organized to form what is known as the cerebellar module. In contrast to the relatively organized and static anatomy, the cerebellum is innervated by a wide variety of neuromodulator carrying axons that are heterogeneously distributed along the olivo-cerebellar loop, providing heterogeneity to the static structure. In this manuscript we review modulatory processes in the olivo-cerebellar loop. We start by discussing the relationship between neuromodulators and the animal behavioral states. This is followed with an overview of the cerebellar neuromodulatory signals and a short discussion of why and when the cerebellar activity should be modulated. We then devote a section for three types of neurons where we briefly review its properties and propose possible neuromodulation scenarios. PMID:23626524

  15. Late Onset of Cerebellar Abiotrophy in a Boxer Dog

    PubMed Central

    Gumber, Sanjeev; Cho, Doo-Youn; Morgan, Timothy W.

    2010-01-01

    Cerebellar abiotrophy is a degenerative disorder of the central nervous system and has been reported in humans and animals. This case report documents clinical, histopathological, and immunohistochemical findings of cerebellar abiotrophy in an adult Boxer dog. A 3.5-year-old, female, tan Boxer dog presented with a six-week history of left-sided head tilt. Neurological examination and additional diagnostics during her three subsequent visits over 4.5 months revealed worsening of neurological signs including marked head pressing, severe proprioceptive deficits in all the four limbs, loss of menace response and palpebral reflex in the left eye, and a gradual seizure lasting one hour at her last visit. Based on the immunohistochemical staining for glial fibrillary acidic protein and histopathological examination of cerebellum, cerebellar cortical abiotrophy was diagnosed. This is the first reported case of cerebellar abiotrophy in a Boxer dog to our knowledge. PMID:21151662

  16. Cerebellar theta-burst stimulation selectively enhances lexical associative priming.

    PubMed

    Argyropoulos, Giorgos P

    2011-09-01

    Recent research in cerebellar cognitive and linguistic functions makes plausible the idea that the cerebellum is involved in processing temporally contiguous linguistic input. In order to assess this hypothesis, a simple lexical decision task was constructed to study whether the effect of transcranial magnetic stimulation on two different cerebellar sites would have a selective impact on associative as opposed to semantic priming. This is the first experiment applying transcranial magnetic stimulation of the cerebellum to a linguistic task. The results show a selective drop in lexical decision accuracy after stimulation of a medial cerebellar site in the first session of participation. Most importantly, they also demonstrate a selective increase of associative priming sizes after stimulation of the same site that cannot be attributed to changes in sensorimotor performance or in accuracy rates. The finding is discussed within the context of domain-general associative cerebellar computations.

  17. Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred

    PubMed Central

    Gulsuner, Suleyman; Tekinay, Ayse Begum; Doerschner, Katja; Boyaci, Huseyin; Bilguvar, Kaya; Unal, Hilal; Ors, Aslihan; Onat, O. Emre; Atalar, Ergin; Basak, A. Nazli; Topaloglu, Haluk; Kansu, Tulay; Tan, Meliha; Tan, Uner; Gunel, Murat; Ozcelik, Tayfun

    2011-01-01

    The biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1–13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans. PMID:21885617

  18. Homolateral ataxia and crural paresis: a crossed cerebral-cerebellar diaschisis.

    PubMed Central

    Giroud, M; Creisson, E; Fayolle, H; Gras, P; Vion, P; Brunotte, F; Dumas, R

    1994-01-01

    A patient developed weakness of the right leg and homolateral ataxia of the arm, caused by a subcortical infarct in the area supplied by the anterior cerebral artery in the left paracentral region, demonstrated by CT and MRI. Cerebral blood flow studied by technetium-labelled hexamethyl-propylene-amine oxime using single photon emission computed tomography showed decreased blood flow in the left lateral frontal cortex and in the right cerebellar hemisphere ("crossed cerebral-cerebellar diaschisis"). The homolateral ataxia of the arm may be caused by decreased function of the right cerebellar hemisphere, because of a lesion of the corticopontine-cerebellar tracts, whereas crural hemiparesis is caused by a lesion of the upper part of the corona radiata. Images PMID:8126511

  19. Co-localisation of abnormal brain structure and function in specific language impairment

    PubMed Central

    Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

  20. Cerebellar malformations alter regional cerebral development.

    PubMed

    Bolduc, Marie-Eve; Du Plessis, Adre J; Evans, Alan; Guizard, Nicolas; Zhang, Xun; Robertson, Richard L; Limperopoulos, Catherine

    2011-12-01

    The aim of this study was to compare total and regional cerebral volumes in children with isolated cerebellar malformations (CBMs) with those in typically developing children, and to examine the extent to which cerebellar volumetric reductions are associated with total and regional cerebral volumes. This is a case-control study of children diagnosed with isolated CBMs. Each child was matched on age and sex to two typically developing children. Using advanced three-dimensional volumetric magnetic resonance imaging, the cerebrum was segmented into tissue classes and partitioned into eight regions. Analysis of variance was used to compare cerebral volumes between children with CBMs and control children, and linear regressions to examine the impact of cerebellar volume reduction on cerebral volumes. Magnetic resonance imaging was performed at a mean age of 27 months in 20 children (10 males, 10 females) with CBMs and 40 typically developing children. Children with CBMs showed significantly smaller deep grey matter nuclei (p < 0.001), subgenual white matter (p = 0.03), midtemporal white matter (p = 0.02), and inferior occipital grey matter (p = 0.03) volumes than typically developing children. Greater cerebellar volumetric reduction in children with CBMs was associated with decreased total cerebral volume and deep grey matter nuclei (p = 0.02), subgenual white/grey matter (p = 0.001), midtemporal white (p = 0.02) and grey matter (p = 0.01), and parieto-occipital grey matter (p = 0.004). CBMs are associated with impaired regional cerebral growth, suggesting deactivation of principal cerebello-cerebral pathways. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

  1. Primary Cerebellar Gliosarcoma with Extracranial Metastases: An Orphan Differential Diagnosis.

    PubMed

    Ben Nsir, Atef; Thai, Quoc-Anh; Kassar, Alia Zhani; Ben Said, Imed; Jemel, Hafedh

    2015-12-01

    Gliosarcomas are rare, malignant primary brain tumors, most commonly located in the temporal lobe, that contain both glial and mesenchymal elements. Gliosarcomas located within the cerebellum are exceedingly rare. The previously unreported finding of a cerebellar gliosarcoma concurrently with an extracranial metastasis to the lungs is discussed here. A 57-year-old man presented with a 3-month history of chest pain, weight loss, headaches, and vomiting. Physical examination revealed a left cerebellar dysfunction, and the radiological work-up revealed a 6 × 6-cm right apical pulmonary tumor and a 4 × 3.5 × 3.8-cm peripherally enhancing left cerebellar mass. On the basis of a smoking history in the setting of a lung lesion and cerebellar mass, the presumptive diagnosis was primary lung cancer with metastasis to the cerebellum. Gross total resection of a firm pseudo-encapsulated cerebellar mass was performed. The microscopic features and the immunohistochemical profile confirmed the diagnosis of Gliosarcoma. The thoracic lesion was removed subsequently, and pathology confirmed it as an extracranial metastasis from the cerebellar gliosarcoma. Adjuvant radiation and chemotherapy were then administered. No clinical or radiographic evidence of recurrence was observed during one year of follow-up monitoring. To the best of our knowledge, a primary infratentorial gliosarcoma with extracranial metastases has not been previously described. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Cerebellar Volume in Children With Attention-Deficit Hyperactivity Disorder (ADHD).

    PubMed

    Wyciszkiewicz, Aleksandra; Pawlak, Mikolaj A; Krawiec, Krzysztof

    2017-02-01

    Attention Deficit Hyperactivity Disorder (ADHD) is associated with altered cerebellar volume and cerebellum is associated with cognitive performance. However there are mixed results regarding the cerebellar volume in young patients with ADHD. To clarify the size and direction of this effect, we conducted the analysis on the large public database of brain images. The aim of this study was to confirm that cerebellar volume in ADHD is smaller than in control subjects in currently the largest publicly available cohort of ADHD subjects.We applied cross-sectional case control study design by comparing 286 ADHD patients (61 female) with age and gender matched control subjects. Volumetric measurements of cerebellum were obtained using automated segmentation with FreeSurfer 5.1. Statistical analysis was performed in R-CRAN statistical environment. Patients with ADHD had significantly smaller total cerebellar volumes (134.5±17.11cm 3 vs.138.90±15.32 cm 3 ). The effect was present in both females and males (males 136.9±14.37 cm 3 vs. 141.20±14.75 cm 3 ; females 125.7±12.34 cm 3 vs. 131.20±15.03 cm 3 ). Age was positively and significantly associated with the cerebellar volumes. These results indicate either delayed or disrupted cerebellar development possibly contributing to ADHD pathophysiology.

  3. Cerebellar stroke presenting with isolated dizziness: Brain MRI in 136 patients.

    PubMed

    Perloff, Michael D; Patel, Nimesh S; Kase, Carlos S; Oza, Anuja U; Voetsch, Barbara; Romero, Jose R

    2017-11-01

    To evaluate occurrence of cerebellar stroke in Emergency Department (ED) presentations of isolated dizziness (dizziness with a normal exam and negative neurological review of systems). A 5-year retrospective study of ED patients presenting with a chief complaint of "dizziness or vertigo", without other symptoms or signs in narrative history or on exam to suggest a central nervous system lesion, and work-up included a brain MRI within 48h. Patients with symptoms commonly peripheral in etiology (nystagmus, tinnitus, gait instability, etc.) were included in the study. Patient demographics, stroke risk factors, and gait assessments were recorded. One hundred and thirty-six patients, who had a brain MRI for isolated dizziness, were included. There was a low correlation of gait assessment between ED physician and Neurologist (49 patients, Spearman's correlation r 2 =0.17). Based on MRI DWI sequence, 3.7% (5/136 patients) had acute cerebellar strokes, limited to or including, the medial posterior inferior cerebellar artery vascular territory. In the 5 cerebellar stroke patients, mean age, body mass index (BMI), hemoglobin A1c, gender distribution, and prevalence of hypertension were similar to the non-cerebellar stroke patient group. Mean LDL/HDL ratio was 3.63±0.80 and smoking prevalence was 80% in the cerebellar stroke group compared to 2.43±0.79 and 22% (respectively, p values<0.01) in the non-cerebellar stroke group. Though there was preselection bias for stroke risk factors, our study suggests an important proportion of cerebellar stroke among ED patients with isolated dizziness, considering how common this complaint is. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. lakemorpho: Calculating lake morphometry metrics in R

    EPA Science Inventory

    Metrics describing the shape and size of lakes, known as lake morphometry metrics, are important for any limnological study. In cases where a lake has long been the subject of study these data are often already collected and are openly available. Many other lakes have these data ...

  5. Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm.

    PubMed

    Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

    2014-01-01

    Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

  6. [Voxel-Based Morphometry in Autism Spectrum Disorder].

    PubMed

    Yamasue, Hidenori

    2017-05-01

    Autism spectrum disorder shows deficits in social communication and interaction including nonverbal communicative behaviors (e.g., eye contact, gestures, voice prosody, and facial expressions) and restricted and repetitive behaviors as its core symptoms. These core symptoms are emerged as an atypical behavioral development in toddlers with the disorder. Atypical neural development is considered to be a neural underpinning of such behaviorally atypical development. A number of studies using voxel-based morphometry have already been conducted to compare regional brain volumes between individuals with autism spectrum disorder and those with typical development. Furthermore, more than ten papers employing meta-analyses of the comparisons using voxel based morphometry between individuals with autism spectrum disorder and those with typical development have already been published. The current review paper adds some brief discussions about potential factors contributing to the inconsistency observed in the previous findings such as difficulty in controlling the confounding effects of different developmental phases among study participants.

  7. Disentangling diatom species complexes: does morphometry suffice?

    PubMed Central

    Borrego-Ramos, María; Olenici, Adriana

    2017-01-01

    Accurate taxonomic resolution in light microscopy analyses of microalgae is essential to achieve high quality, comparable results in both floristic analyses and biomonitoring studies. A number of closely related diatom taxa have been detected to date co-occurring within benthic diatom assemblages, sharing many morphological, morphometrical and ecological characteristics. In this contribution, we analysed the hypothesis that, where a large sample size (number of individuals) is available, common morphometrical parameters (valve length, width and stria density) are sufficient to achieve a correct identification to the species level. We focused on some common diatom taxa belonging to the genus Gomphonema. More than 400 valves and frustules were photographed in valve view and measured using Fiji software. Several statistical tools (mixture and discriminant analysis, k-means clustering, classification trees, etc.) were explored to test whether mere morphometry, independently of other valve features, leads to correct identifications, when compared to identifications made by experts. In view of the results obtained, morphometry-based determination in diatom taxonomy is discouraged. PMID:29250472

  8. Abnormal regional cerebral blood flow in childhood autism.

    PubMed

    Ohnishi, T; Matsuda, H; Hashimoto, T; Kunihiro, T; Nishikawa, M; Uema, T; Sasaki, M

    2000-09-01

    Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

  9. Structural Basis of Cerebellar Microcircuits in the Rat

    PubMed Central

    Cerminara, Nadia L.; Aoki, Hanako; Loft, Michaela; Apps, Richard

    2013-01-01

    The topography of the cerebellar cortex is described by at least three different maps, with the basic units of each map termed “microzones,” “patches,” and “bands.” These are defined, respectively, by different patterns of climbing fiber input, mossy fiber input, and Purkinje cell (PC) phenotype. Based on embryological development, the “one-map” hypothesis proposes that the basic units of each map align in the adult animal and the aim of the present study was to test this possibility. In barbiturate anesthetized adult rats, nanoinjections of bidirectional tracer (Retrobeads and biotinylated dextran amine) were made into somatotopically identified regions within the hindlimb C1 zone in copula pyramidis. Injection sites were mapped relative to PC bands defined by the molecular marker zebrin II and were correlated with the pattern of retrograde cell labeling within the inferior olive and in the basilar pontine nuclei to determine connectivity of microzones and patches, respectively, and also with the distributions of biotinylated dextran amine-labeled PC terminals in the cerebellar nuclei. Zebrin bands were found to be related to both climbing fiber and mossy fiber inputs and also to cortical representation of different parts of the ipsilateral hindpaw, indicating a precise spatial organization within cerebellar microcircuitry. This precise connectivity extends to PC terminal fields in the cerebellar nuclei and olivonuclear projections. These findings strongly support the one-map hypothesis and suggest that, at the microcircuit level of resolution, the cerebellar cortex has a common plan of spatial organization for major inputs, outputs, and PC phenotype. PMID:24133249

  10. Increased cerebellar PET glucose metabolism corresponds to ataxia in Wernicke-Korsakoff syndrome.

    PubMed

    Fellgiebel, Andreas; Siessmeier, Thomas; Winterer, Georg; Lüddens, Hartmut; Mann, Klaus; Schmidt, Lutz G; Bartenstein, Peter

    2004-01-01

    To investigate a possible relationship between cerebellar glucose metabolism and recovery from ataxia in the first months of acute Wernicke-Korsakoff syndrome. Two cases of alcoholic Wernicke-Korsakoff syndrome were followed up with the clinical status and cerebral glucose metabolism over a 4- and 9-month period. Initially both patients showed severe ataxia and elevated cerebellar glucose metabolism that decreased corresponding to the restitution of stance and gait. Increased cerebellar glucose metabolism at the onset of the illness may reflect the reorganization process of disturbed motor skills and may indicate cerebellar plasticity.

  11. CT morphometry of adult thoracic intervertebral discs.

    PubMed

    Fletcher, Justin G R; Stringer, Mark D; Briggs, Christopher A; Davies, Tilman M; Woodley, Stephanie J

    2015-10-01

    Despite being commonly affected by degenerative disorders, there are few data on normal thoracic intervertebral disc dimensions. A morphometric analysis of adult thoracic intervertebral discs was, therefore, undertaken. Archival computed tomography scans of 128 recently deceased individuals (70 males, 58 females, 20-79 years) with no known spinal pathology were analysed to determine thoracic disc morphometry and variations with disc level, sex and age. Reliability was assessed by intraclass correlation coefficients (ICCs). Anterior and posterior intervertebral disc heights and axial dimensions were significantly greater in men (anterior disc height 4.0±1.4 vs 3.6±1.3 mm; posterior disc height 3.6±0.90 vs 3.4±0.93 mm; p<0.01). Disc heights and axial dimensions at T4-5 were similar or smaller than at T2-3, but thereafter increased caudally (mean anterior disc height T4-5 and T10-11, 2.7±0.7 and 5.4±1.2 mm, respectively, in men; 2.6±0.8 and 5.1±1.3 mm, respectively, in women; p<0.05). Except at T2-3, anterior disc height decreased with advancing age and anteroposterior and transverse disc dimensions increased; posterior and middle disc heights and indices of disc shape showed no consistent statistically significant changes. Most parameters showed substantial to almost perfect agreement for intra- and inter-rater reliability. Thoracic disc morphometry varies significantly and consistently with disc level, sex and age. This study provides unique reference data on adult thoracic intervertebral disc morphometry, which may be useful when interpreting pathological changes and for future biomechanical and functional studies.

  12. Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

    EPA Science Inventory

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

  13. Cerebellar contribution to feedforward control of locomotion.

    PubMed

    Pisotta, Iolanda; Molinari, Marco

    2014-01-01

    The cerebellum is an important contributor to feedforward control mechanisms of the central nervous system, and sequencing-the process that allows spatial and temporal relationships between events to be recognized-has been implicated as the fundamental cerebellar mode of operation. By adopting such a mode and because cerebellar activity patterns are sensitive to a variety of sensorimotor-related tasks, the cerebellum is believed to support motor and cognitive functions that are encoded in the frontal and parietal lobes of the cerebral cortex. In this model, the cerebellum is hypothesized to make predictions about the consequences of a motor or cognitive command that originates from the cortex to prepare the entire system to cope with ongoing changes. In this framework, cerebellar predictive mechanisms for locomotion are addressed, focusing on sensorial and motoric sequencing. The hypothesis that sequence recognition is the mechanism by which the cerebellum functions in gait control is presented and discussed.

  14. Cerebellar contribution to feedforward control of locomotion

    PubMed Central

    Pisotta, Iolanda; Molinari, Marco

    2014-01-01

    The cerebellum is an important contributor to feedforward control mechanisms of the central nervous system, and sequencing—the process that allows spatial and temporal relationships between events to be recognized—has been implicated as the fundamental cerebellar mode of operation. By adopting such a mode and because cerebellar activity patterns are sensitive to a variety of sensorimotor-related tasks, the cerebellum is believed to support motor and cognitive functions that are encoded in the frontal and parietal lobes of the cerebral cortex. In this model, the cerebellum is hypothesized to make predictions about the consequences of a motor or cognitive command that originates from the cortex to prepare the entire system to cope with ongoing changes. In this framework, cerebellar predictive mechanisms for locomotion are addressed, focusing on sensorial and motoric sequencing. The hypothesis that sequence recognition is the mechanism by which the cerebellum functions in gait control is presented and discussed. PMID:25009490

  15. Gaze holding deficits discriminate early from late onset cerebellar degeneration.

    PubMed

    Tarnutzer, Alexander A; Weber, K P; Schuknecht, B; Straumann, D; Marti, S; Bertolini, G

    2015-08-01

    The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocity-to-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle = ±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities ≥20°. Pure scaling was most frequently observed (n = 10/18), followed by pure shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing patients were significantly (p = 0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early- from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined.

  16. Dissociation of functional and anatomical brain abnormalities in unaffected siblings of schizophrenia patients.

    PubMed

    Guo, Wenbin; Song, Yan; Liu, Feng; Zhang, Zhikun; Zhang, Jian; Yu, Miaoyu; Liu, Jianrong; Xiao, Changqing; Liu, Guiying; Zhao, Jingping

    2015-05-01

    Schizophrenia patients and their unaffected siblings share similar brain functional and structural abnormalities. However, no study is engaged to investigate whether and how functional abnormalities are related to structural abnormalities in unaffected siblings. This study was undertaken to examine the association between functional and anatomical abnormalities in unaffected siblings. Forty-six unaffected siblings of schizophrenia patients and 46 age-, sex-, and education-matched healthy controls underwent structural and resting-state functional magnetic resonance imaging scanning. Voxel-based morphometry (VBM), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were utilized to analyze imaging data. The VBM analysis showed gray matter volume decreases in the fronto-temporal regions (the left middle temporal gyrus and right inferior frontal gyrus, orbital part) and increases in basal ganglia system (the left putamen). Functional abnormalities measured by ALFF and fALFF mainly involved in the fronto-limbic-sensorimotor circuit (decreased ALFF in bilateral middle frontal gyrus and the right middle cingulate gyrus, and decreased fALFF in the right inferior frontal gyrus, orbital part; and increased ALFF in the left fusiform gyrus and left lingual gyrus, and increased fALFF in bilateral calcarine cortex). No significant correlation was found between functional and anatomical abnormalities in the sibling group. A dissociation pattern of brain regions with functional and anatomical abnormalities is observed in unaffected siblings. Our findings suggest that brain functional and anatomical abnormalities might be present independently in unaffected siblings of schizophrenia patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Subarachnoid Hemorrhage Because of Distal Superior Cerebellar Artery Dissection in Neurofibromatosis Type 1.

    PubMed

    Takeshima, Yuki; Ohmori, Yuki; Nakagawa, Takashi; Kaku, Yasuyuki; Kuratsu, Jun-Ichi; Yano, Shigetoshi

    2017-09-01

    Neurofibromatosis type 1 (NF1) is a rare disease with an incidence of 1 in every 3000 births. Numerous studies have focused on the main function of NF1 as a tumor suppressor, whereas few have examined the cerebrovascular abnormalities observed in patients with NF1. It is worth noting that intracranial aneurysms are uncommon in this condition. We report a case of NF1 with a dissection of the distal segment of the superior cerebellar artery. A 36-year-old woman presented with a distal superior cerebellar artery (SCA) dissection causing subarachnoid hemorrhage. Subsequently, because of the rich collateral blood flow distal to the dissection, N-butyl cyanoacrylate (NBCA) glue embolization was unsuccessful. Therefore, direct trapping of the artery was necessary. The patient was discharged after an uneventful postoperative period, and has remained without complications. In the treatment of subarachnoid hemorrhage because of a distal SCA dissection in patients with NF1, NBCA glue embolization may be a safer option than microsurgery or coil embolization, in the acute phase, considering the possible vulnerability of the vessel wall, accessibility, morphology of the lesions, and the risk of developing unpredictable infarcts in the case of parent artery occlusion. However, regular reevaluation of the blood flow is necessary to monitor recurrence, given the rich collateral circulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Incidence and anatomy of gaze-evoked nystagmus in patients with cerebellar lesions.

    PubMed

    Baier, Bernhard; Dieterich, Marianne

    2011-01-25

    Disorders of gaze-holding--organized by a neural network located in the brainstem or the cerebellum--may lead to nystagmus. Based on previous animal studies it was concluded that one key player of the cerebellar part of this gaze-holding neural network is the flocculus. Up to now, in humans there are no systematic studies in patients with cerebellar lesions examining one of the most common forms of nystagmus: gaze-evoked nystagmus (GEN). The aim of our present study was to clarify which cerebellar structures are involved in the generation of GEN. Twenty-one patients with acute unilateral cerebellar stroke were analyzed by means of modern MRI-based voxel-wise lesion-behavior mapping. Our data indicate that cerebellar structures such as the vermal pyramid, the uvula, and the tonsil, but also parts of the biventer lobule and the inferior semilunar lobule, were affected in horizontal GEN. It seems that these structures are part of a gaze-holding neural integrator control system. Furthermore, GEN might present a diagnostic sign pointing toward ipsilesionally located lesions of midline and lower cerebellar structures.

  19. Ultastructural analysis on acetylcholinesterase localization in the cerebellar cortex of teleosts.

    PubMed

    Contestabile, A; Villani, L; Ciani, F

    1977-12-28

    The histochemical localization of acetylcholinesterase (AChE) was studied by electron microscopy in the cerebellar cortex of the goldfish and the catfish. The patterns of enzyme distribution show noticeable differences in the two teleost species at the level of the corresponding cerebellar structures. Among the most distinctive features is the prevailing intracellular localization of enzyme activity in the goldfish and the prevailing extracellular localization in the catfish in the molecular layer and, to a lesser extent, the granular layer. Only quantitative differences in the ability to synthesize AChE can be recorded among the different cerebellar neurons in the two species, since all these neurons exhibit different amounts of enzyme activity linked to their cytoplasmic structures. Comparing the results obtained with those of previous histochemical, experimental and developmental researches, the hypothesis seems well founded that the embryonic pool of cerebellar neurons is made up of AChE-synthesizing nruroblasts which, during development, loss or maintain to a different the mechanisms for AChE synthesis. In addition the light and electron microscope histochemistry reveals at different levels of resolution that the final pattern of AChE distribution in the cerebellar cortex is the sum of different degress of AChE synthesis by cerebellar neurons and different degrees of enzyme release in extracellular spaces.

  20. Neural correlates of abnormal sensory discrimination in laryngeal dystonia.

    PubMed

    Termsarasab, Pichet; Ramdhani, Ritesh A; Battistella, Giovanni; Rubien-Thomas, Estee; Choy, Melissa; Farwell, Ian M; Velickovic, Miodrag; Blitzer, Andrew; Frucht, Steven J; Reilly, Richard B; Hutchinson, Michael; Ozelius, Laurie J; Simonyan, Kristina

    2016-01-01

    Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder.

  1. Morphological and functional abnormalities of salience network in the early-stage of paranoid schizophrenia.

    PubMed

    Pu, Weidan; Li, Li; Zhang, Huiran; Ouyang, Xuan; Liu, Haihong; Zhao, Jingping; Li, Lingjiang; Xue, Zhimin; Xu, Ke; Tang, Haibo; Shan, Baoci; Liu, Zhening; Wang, Fei

    2012-10-01

    A salience network (SN), mainly composed of the anterior insula (AI) and anterior cingulate cortex (ACC), has been suggested to play an important role in salience attribution which has been proposed as central to the pathology of paranoid schizophrenia. The role of this SN in the pathophysiology of paranoid schizophrenia, however, still remains unclear. In the present study, voxel-based morphometry and resting-state functional connectivity analyses were combined to identify morphological and functional abnormalities in the proposed SN in the early-stage of paranoid schizophrenia (ESPS). Voxel-based morphometry and resting-state functional connectivity analyses were applied to 90 ESPS patients and 90 age- and sex-matched healthy controls (HC). Correlation analyses were performed to examine the relationships between various clinical variables and both gray matter morphology and functional connectivity within the SN in ESPS. Compared to the HC group, the ESPS group showed significantly reduced gray matter volume (GMV) in both bilateral AI and ACC. Moreover, significantly reduced functional connectivity within the SN sub-networks was identified in the ESPS group. These convergent morphological and functional deficits in SN were significantly associated with hallucinations. Additionally, illness duration correlated with reduced GMV in the left AI in ESPS. In conclusion, these findings provide convergent evidence for the morphological and functional abnormalities of the SN in ESPS. Moreover, the association of illness duration with the reduced GMV in the left AI suggests that the SN and the AI, in particular, may manifest progressive morphological changes that are especially important in the emergence of ESPS. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Cerebellar Abiotrophy Across Domestic Species.

    PubMed

    Scott, Erica Yuki; Woolard, Kevin Douglas; Finno, Carrie J; Murray, James D

    2018-06-01

    Cerebellar abiotrophy (CA) is a neurodegenerative disorder affecting the cerebellum and occurs in multiple species. Although CA is well researched in humans and mice, domestic species such as the dog, cat, sheep, cow, and horse receive little recognition. This may be due to few studies addressing the mechanism of CA in these species. However, valuable information can still be extracted from these cases. A review of the clinicohistologic phenotype of CA in these species and determining the various etiologies of CA may aid in determining conserved and required pathways necessary for proper cerebellar development and function. This review outlines research approaches of studies of CA in domestic species, compared to the approaches used in mice, with the objective of comparing CA in domestic species while identifying areas for further research efforts.

  3. Co-localisation of abnormal brain structure and function in specific language impairment.

    PubMed

    Badcock, Nicholas A; Bishop, Dorothy V M; Hardiman, Mervyn J; Barry, Johanna G; Watkins, Kate E

    2012-03-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Comparative Minicolumnar Morphometry of Three Distinguished Scientists

    ERIC Educational Resources Information Center

    Casanova, Manuel F.; Switala, Andrew E.; Trippe, Juan; Fitzgerald, Michael

    2007-01-01

    It has been suggested that the cell minicolumn is the smallest module capable of information processing within the brain. In this case series, photomicrographs of six regions of interests (Brodmann areas 4, 9, 17, 21, 22, and 40) were analyzed by computerized image analysis for minicolumnar morphometry in the brains of three distinguished…

  5. Magnetic resonance imaging and brainstem auditory evoked responses in the diagnosis of cerebellar cortical degeneration in american staffordshire terriers.

    PubMed

    Kwiatkowska, Miłosława; Pomianowski, Andrzej; Adamiak, Zbigniew; Bocheńska, Aneta

    2013-03-01

    The aim of the study was to determine the diagnostic usefulness of magnetic resonance imaging (MRI) and brainstem auditory evoked responses (BAER) in dogs suspected of having cerebellar cortical degeneration (CCD). In the years 2009-2011, six dogs with suspected CCD were examined. Both MRI and BAER examinations revealed abnormalities in all dogs (100%). By MRI, T2-weighted midsagittal images revealed an increased amount of cerebrospinal fluid (CSF) surrounding the cerebellum within the sulci of the folia in all dogs (100%). In 4 out of the 6 dogs (66.66%), cerebellar hypoplasia was more visible in the region of the dorsal cerebellar lobules. In 5 out of the 6 dogs (83.33%), the fourth ventricle was enlarged. In our studies, the brain to cerebellum ratio evaluated on the midsagittal image was 11.93%, in comparison to 14.9% in normal dogs. By BAER examination, the amplitude of the first and second waves was diminished and III-V interlatency was prolonged in 5 out of the 6 dogs (83.33%). In one out of the 6 dogs (16.67%), only the III-V interlatency was prolonged. In one dog (16.67%), somato-nervous deafness in the left ear was detected, whereas in the right ear the III-V interlatency was prolonged. MRI of the cerebellum is a reliable method for the antemortem diagnosis of CCD in American Staffordshire terriers, as is BAER examination. BAER is an objective diagnostic tool, which - along with other diagnostic modalities - can be helpful in the assessment, management and follow-up of dogs with cerebellar abiotrophy. It proved to be useful in determining the severity of neurological lesions in comparison to MRI findings, as well as in assessing the prognosis.

  6. Prediction of vascular abnormalities on CT angiography in patients with acute headache.

    PubMed

    Alons, Imanda M E; Goudsmit, Ben F J; Jellema, Korné; van Walderveen, Marianne A A; Wermer, Marieke J H; Algra, Ale

    2018-05-09

    Patients with acute headache increasingly undergo CT-angiography (CTA) to evaluate underlying vascular causes. The aim of this study is to determine clinical and non-contrast CT (NCCT) criteria to select patients who might benefit from CTA. We retrospectively included patients with acute headache who presented to the emergency department of an academic medical center and large regional teaching hospital and underwent NCCT and CTA. We identified factors that increased the probability of finding a vascular abnormality on CTA, performed multivariable regression analyses and determined discrimination with the c-statistic. A total of 384 patients underwent NCCT and CTA due to acute headache. NCCT was abnormal in 194 patients. Among these, we found abnormalities in 116 cases of which 99 aneurysms. In the remaining 190 with normal NCCT we found abnormalities in 12 cases; four unruptured aneurysms, three cerebral venous thrombosis', two reversible cerebral vasoconstriction syndromes, two cervical arterial dissections and one cerebellar infarction. In multivariable analysis abnormal NCCT, lowered consciousness and presentation within 6 hr of headache onset were independently associated with abnormal CTA. The c-statistic of abnormal NCCT alone was 0.80 (95% CI: 0.75-0.80), that also including the other two variables was 0.84 (95% CI: 0.80-0.88). If NCCT was normal no other factors could help identify patients at risk for abnormalities. In patients with acute headache abnormal NCCT is the strongest predictor of a vascular abnormality on CTA. If NCCT is normal no other predictors increase the probability of finding an abnormality on CTA and diagnostic yield is low. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

  7. Patterns of Gray Matter Abnormalities in Schizophrenia Based on an International Mega-analysis.

    PubMed

    Gupta, Cota Navin; Calhoun, Vince D; Rachakonda, Srinivas; Chen, Jiayu; Patel, Veena; Liu, Jingyu; Segall, Judith; Franke, Barbara; Zwiers, Marcel P; Arias-Vasquez, Alejandro; Buitelaar, Jan; Fisher, Simon E; Fernandez, Guillen; van Erp, Theo G M; Potkin, Steven; Ford, Judith; Mathalon, Daniel; McEwen, Sarah; Lee, Hyo Jong; Mueller, Bryon A; Greve, Douglas N; Andreassen, Ole; Agartz, Ingrid; Gollub, Randy L; Sponheim, Scott R; Ehrlich, Stefan; Wang, Lei; Pearlson, Godfrey; Glahn, David C; Sprooten, Emma; Mayer, Andrew R; Stephen, Julia; Jung, Rex E; Canive, Jose; Bustillo, Juan; Turner, Jessica A

    2015-09-01

    Analyses of gray matter concentration (GMC) deficits in patients with schizophrenia (Sz) have identified robust changes throughout the cortex. We assessed the relationships between diagnosis, overall symptom severity, and patterns of gray matter in the largest aggregated structural imaging dataset to date. We performed both source-based morphometry (SBM) and voxel-based morphometry (VBM) analyses on GMC images from 784 Sz and 936 controls (Ct) across 23 scanning sites in Europe and the United States. After correcting for age, gender, site, and diagnosis by site interactions, SBM analyses showed 9 patterns of diagnostic differences. They comprised separate cortical, subcortical, and cerebellar regions. Seven patterns showed greater GMC in Ct than Sz, while 2 (brainstem and cerebellum) showed greater GMC for Sz. The greatest GMC deficit was in a single pattern comprising regions in the superior temporal gyrus, inferior frontal gyrus, and medial frontal cortex, which replicated over analyses of data subsets. VBM analyses identified overall cortical GMC loss and one small cluster of increased GMC in Sz, which overlapped with the SBM brainstem component. We found no significant association between the component loadings and symptom severity in either analysis. This mega-analysis confirms that the commonly found GMC loss in Sz in the anterior temporal lobe, insula, and medial frontal lobe form a single, consistent spatial pattern even in such a diverse dataset. The separation of GMC loss into robust, repeatable spatial patterns across multiple datasets paves the way for the application of these methods to identify subtle genetic and clinical cohort effects. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit.

    PubMed

    Mapelli, Lisa; Pagani, Martina; Garrido, Jesus A; D'Angelo, Egidio

    2015-01-01

    The way long-term potentiation (LTP) and depression (LTD) are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network, in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei) and correspondingly regulate the function of their three main neurons: granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN) cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  9. Brain abnormalities in high-risk violent offenders and their association with psychopathic traits and criminal recidivism.

    PubMed

    Leutgeb, V; Leitner, M; Wabnegger, A; Klug, D; Scharmüller, W; Zussner, T; Schienle, A

    2015-11-12

    Measures of psychopathy have been proved to be valuable for risk assessment in violent criminals. However, the neuronal basis of psychopathy and its contribution to the prediction of criminal recidivism is still poorly understood. We compared structural imaging data from 40 male high-risk violent offenders and 37 non-delinquent healthy controls via voxel-based morphometry. Psychopathic traits and risk of violence recidivism were correlated with gray matter volume (GMV) of regions of interest previously shown relevant for criminal behavior. Relative to controls, criminals showed less GMV in the prefrontal cortex (PFC) and more GMV in cerebellar regions and basal ganglia structures. Within criminals, we found a negative correlation between prefrontal GMV and psychopathy. Additionally, there was a positive correlation between cerebellar GMV and psychopathy as well as risk of recidivism for violence. Moreover, GMVs of the basal ganglia and supplementary motor area (SMA) were positively correlated with anti-sociality. GMV of the amygdala was negatively correlated with dynamic risk for violence recidivism. In contrast, GMV of (para)limbic areas (orbitofrontal cortex, insula) was positively correlated with anti-sociality and risk of violence recidivism. The current investigation revealed that in violent offenders deviations in GMV of the PFC as well as areas involved in the motor component of impulse control (cerebellum, basal ganglia, SMA) are differentially related to psychopathic traits and the risk of violence recidivism. The results might be valuable for improving existing risk assessment tools. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Motion perception without Nystagmus--a novel manifestation of cerebellar stroke.

    PubMed

    Shaikh, Aasef G

    2014-01-01

    The motion perception and the vestibulo-ocular reflex (VOR) each serve distinct functions. The VOR keeps the gaze steady on the target of interest, whereas vestibular perception serves a number of tasks, including awareness of self-motion and orientation in space. VOR and motion perception might abide the same neurophysiological principles, but their distinct anatomical correlates were proposed. In patients with cerebellar stroke in distribution of medial division of posterior inferior cerebellar artery, we asked whether specific location of the focal lesion in vestibulocerebellum could cause impaired perception of motion but normal eye movements. Thirteen patients were studied, 5 consistently perceived spinning of surrounding environment (vertigo), but the eye movements were normal. This group was called "disease model." Remaining 8 patients were also symptomatic for vertigo, but they had spontaneous nystagmus. The latter group was called "disease control." Magnetic resonance imaging in both groups consistently revealed focal cerebellar infarct affecting posterior cerebellar vermis (lobule IX). In the "disease model" group, only part of lobule IX was affected. In the disease control group, however, complete lobule IX was involved. This study discovered a novel presentation of cerebellar stroke where only motion perception was affected, but there was an absence of objective neurologic signs. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics

    PubMed Central

    Sommer, Wieland H; Bollwein, Christine; Thierfelder, Kolja M; Baumann, Alena; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Plate, Annika; Straube, Andreas

    2015-01-01

    We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis. PMID:26661242

  12. Diagnosis and initial management of cerebellar infarction.

    PubMed

    Edlow, Jonathan A; Newman-Toker, David E; Savitz, Sean I

    2008-10-01

    Cerebellar infarction is an important cause of stroke that often presents with common and non-specific symptoms such as dizziness, nausea and vomiting, unsteady gait, and headache. Accurate diagnosis frequently relies on careful attention to patients' coordination, gait, and eye movements--components of the neurological physical examination that are sometimes omitted or abridged if cerebellar stroke is not specifically being considered. The differential diagnosis is broad, and includes many common and benign causes. Furthermore, early-stage posterior fossa ischaemia is rarely seen with brain CT--the most commonly available initial imaging test that is used for stroke. Insufficient examination and imaging can result in misdiagnosis. However, early correct diagnosis is crucial to help prevent treatable but potentially fatal complications, such as brainstem compression and obstructive hydrocephalus. The identification and treatment of the underlying vascular lesions at an early stage can also prevent subsequent occurrences of stroke and improve patients' outcomes. Here, we review the clinical presentation of cerebellar infarction, from diagnosis and misdiagnosis to patients' monitoring, treatment, and potential complications.

  13. Implied functional crossed cerebello-cerebral diaschisis and interhemispheric compensation during hand grasping more than 20 years after unilateral cerebellar injury in early childhood.

    PubMed

    Nakahachi, Takayuki; Ishii, Ryouhei; Canuet, Leonides; Iwase, Masao

    2015-01-01

    Crossed cerebello-cerebral diaschisis (CCCD) conventionally refers to decreased resting cerebral activity caused by injury to the contralateral cerebellum. We investigated whether functional activation of a contralesional cerebral cortical region controlling a specific task is reduced during task performance in a patient with a unilateral cerebellar lesion. We also examined functional compensation by the corresponding ipsilesional cerebral cortex. It was hypothesized that dysfunction of the primary sensorimotor cortex (SM1) contralateral to the cerebellar lesion would be detected together with a compensatory increase in neural activity of the ipsilesional SM1. To test these possibilities, we conducted non-invasive functional neuroimaging techniques for bilateral SM1 during hand grasping, a task known to activate predominantly the SM1 contralateral to the grasping hand. Activity in SM1 during hand grasping was measured electrophysiologically by magnetoencephalography and hemodynamically by near-infrared spectroscopy in an adult with mild right hemiataxia associated with a large injury of the right cerebellum due to resection of a tumor in early childhood. During left hand grasping, increased neural activity was detected predominantly in the right SM1, the typical developmental pattern. In contrast, neural activity increased in the bilateral SM1 with slight right-side dominance during right (ataxic) hand grasping. This study reported a case that implied functional CCCD and compensatory neural activity in the SM1 during performance of a simple hand motor task in an adult with unilateral cerebellar injury and mild hemiataxia 24 years prior to the study without rehabilitative interventions. This suggests that unilateral cerebellar injuries in early childhood may result in persistent functional abnormalities in the cerebrum into adulthood. Therapeutic treatments that target functional CCCD and interhemispheric compensation might be effective for treating ataxia due to

  14. Inverse Stochastic Resonance in Cerebellar Purkinje Cells

    PubMed Central

    Häusser, Michael; Gutkin, Boris S.; Roth, Arnd

    2016-01-01

    Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR). While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing. PMID:27541958

  15. Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics.

    PubMed

    Sommer, Wieland H; Bollwein, Christine; Thierfelder, Kolja M; Baumann, Alena; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Plate, Annika; Straube, Andreas; von Baumgarten, Louisa

    2016-04-01

    We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis. © The Author(s) 2015.

  16. Delayed reverberation through time windows as a key to cerebellar function.

    PubMed

    Kistler, W M; Leo van Hemmen, J

    1999-11-01

    We present a functional model of the cerebellum comprising cerebellar cortex, inferior olive, deep cerebellar nuclei, and brain stem nuclei. The discerning feature of the model being time coding, we consistently describe the system in terms of postsynaptic potentials, synchronous action potentials, and propagation delays. We show by means of detailed single-neuron modeling that (i) Golgi cells can fulfill a gating task in that they form short and well-defined time windows within which granule cells can reach firing threshold, thus organizing neuronal activity in discrete 'time slices', and that (ii) rebound firing in cerebellar nuclei cells is a robust mechanism leading to a delayed reverberation of Purkinje cell activity through cerebellar-reticular projections back to the cerebellar cortex. Computer simulations of the whole cerebellar network consisting of several thousand neurons reveal that reverberation in conjunction with long-term plasticity at the parallel fiber-Purkinje cell synapses enables the system to learn, store, and recall spatio-temporal patterns of neuronal activity. Climbing fiber spikes act both as a synchronization and as a teacher signal, not as an error signal. They are due to intrinsic oscillatory properties of inferior olivary neurons and to delayed reverberation within the network. In addition to clear experimental predictions the present theory sheds new light on a number of experimental observation such as the synchronicity of climbing fiber spikes and provides a novel explanation of how the cerebellum solves timing tasks on a time scale of several hundreds of milliseconds.

  17. Neuroimaging Evidence of Cerebellar Involvement in Premenstrual Dysphoric Disorder

    PubMed Central

    Rapkin, Andrea J.; Berman, Steven M.; Mandelkern, Mark A.; Silverman, Daniel H. S.; Morgan, Melinda; London, Edythe D.

    2010-01-01

    Background Premenstrual dysphoric disorder (PMDD) is a debilitating cyclic disorder that is characterized by affective symptoms, including irritability, depression, and anxiety which arise in the luteal phase of the menstrual cycle and resolve soon after the onset of menses. Despite a prevalence of up to 8% in women of reproductive age, few studies have investigated the brain mechanisms that underlie this disorder. Methods We used positron emission tomography with [18F] fluorodeoxyglucose and self-report questionnaires to assess cerebral glucose metabolism and mood in 12 women with PMDD and 12 healthy comparison subjects in the follicular and late luteal phases of the menstrual cycle. The primary biological endpoint was incorporated regional cerebral radioactivity (scaled to the global mean) as an index of glucose metabolism. Relationships between regional brain activity and mood ratings were assessed. Blood samples were taken before each session for assay of plasma estradiol and progesterone concentrations. Results There were no group differences in hormone levels in either the follicular or late luteal phase, but the groups differed in the effect of menstrual phase on cerebellar activity. Women with PMDD, but not comparison subjects, showed an increase in cerebellar activity (particularly in the right cerebellar vermis) from the follicular phase to the late luteal phase (p = 0.003). In the PMDD group, this increase in cerebellar activity was correlated with worsening of mood (p = 0.018). Conclusions These findings suggest that the midline cerebellar nuclei, which have been implicated in other mood disorders, also contribute to negative mood in PMDD. PMID:21092938

  18. Cerebellar damage diminishes long-latency responses to multijoint perturbations

    PubMed Central

    Trautman, Paxson; Rasquinha, Russell J.; Bhanpuri, Nasir H.; Scott, Stephen H.; Bastian, Amy J.

    2013-01-01

    Damage to the cerebellum can cause significant problems in the coordination of voluntary arm movements. One prominent idea is that incoordination stems from an inability to predictively account for the complex mechanical interactions between the arm's several joints. Motivated by growing evidence that corrective feedback control shares important capabilities and neural substrates with feedforward control, we asked whether cerebellar damage impacts feedback stabilization of the multijoint arm appropriate for the arm's intersegmental dynamics. Specifically, we tested whether cerebellar dysfunction impacts the ability of posterior deltoid to incorporate elbow motion in its long-latency response (R2 = 45–75 ms and R3 = 75–100 ms after perturbation) to an unexpected torque perturbation. Healthy and cerebellar-damaged subjects were exposed to a selected pattern of shoulder-elbow displacements to probe the response pattern from this shoulder extensor muscle. The healthy elderly subjects expressed a long-latency response linked to both shoulder and elbow motion, including an increase/decrease in shoulder extensor activity with elbow flexion/extension. Critically, cerebellar-damaged subjects displayed the normal pattern of activity in the R3 period indicating an intact ability to rapidly integrate multijoint motion appropriate to the arm's intersegmental dynamics. However, cerebellar-damaged subjects had a lower magnitude of activity that was specific to the long-latency period (both R2 and R3) and a slightly delayed onset of multijoint sensitivity. Taken together, our results suggest that the basic motor pattern of the long-latency response is housed outside the cerebellum and is scaled by processes within the cerebellum. PMID:23390311

  19. Laterality and the evolution of the prefronto-cerebellar system in anthropoids.

    PubMed

    Smaers, Jeroen B; Steele, James; Case, Charleen R; Amunts, Katrin

    2013-06-01

    There is extensive evidence for an early vertebrate origin of lateralized motor behavior and of related asymmetries in underlying brain systems. We investigate human lateralized motor functioning in a broad comparative context of evolutionary neural reorganization. We quantify evolutionary trends in the fronto-cerebellar system (involved in motor learning) across 46 million years of divergent primate evolution by comparing rates of evolution of prefrontal cortex, frontal motor cortex, and posterior cerebellar hemispheres along individual branches of the primate tree of life. We provide a detailed evolutionary model of the neuroanatomical changes leading to modern human lateralized motor functioning, demonstrating an increased role for the fronto-cerebellar system in the apes dating to their evolutionary divergence from the monkeys (∼30 million years ago (Mya)), and a subsequent shift toward an increased role for prefrontal cortex over frontal motor cortex in the fronto-cerebellar system in the Homo-Pan ancestral lineage (∼10 Mya) and in the human ancestral lineage (∼6 Mya). We discuss these results in the context of cortico-cerebellar functions and their likely role in the evolution of human tool use and speech. © 2013 New York Academy of Sciences.

  20. [Cerebellar infarction in vascular teritorry of arteria cerebelli superior].

    PubMed

    Savić, Dejan; Savić, Ljiljana

    2010-01-01

    Cerebellar vascular diseases are focal cerebrovascular diseases in posterior circulation--vertebrobasilar system. The cerebellum is supplied by three main arteries arising from the vertebrobasilar system: arteria cerebelli inferior posterior, arteria cerebelli inferior anterior and arteria cerebelli superior. Cerebelar infarctions are rare but unpredictable disorders. The aim of this study was determination of main risk factors, clinical presentation and prognosis of the cerebellar infarctions in distal vascular teritorry of the arteria cerebelli superior. We evaluated 60 patients hospitalized after acute cerebellar infarction among other hospitalized patients in five year period. In 18 patients computerized tomography demonstrated infarction in distal vascular teritorry of the arteria cerebelli superior. All patients underwent clinical and other diagnostic investigations (computerized tomography, electrocardyography and standard blood tests) and were questioned by phone after finishing hospital treatment. Cerebellar infarcts in distal vascular teritorry of arteria cerebell superior was 30% of all cerebellar infarcts. The most frequent risk factor was hypertension (66.7%). Symptomatology and clinical signs were heterogenous but the most frequent were instability (77.8%), vertigo (72.2%) and vomiting (55.6%) followed by ataxia of the limbs (77.8%) and the body (61.1%), nystagmus (55.6%) and disarthria (33.3%) in clinical presentation. All patients had good recovery in hospital and one year afterwards. Infarctions in distribution of arteria cerebelli superior are rare and have multiple risk factors and various clinical features in majority of other studies as in this one. Mass effects are present in several studies but none in this one which reflects contraversions present in other published investigations. Cerebellar infarctions in vascular teritorry of arteria cerebelli superior have multiple risk factors, mostly heterogenous clinical presentations with

  1. Cerebellar Purkinje Cells Generate Highly Correlated Spontaneous Slow-Rate Fluctuations.

    PubMed

    Cao, Ying; Liu, Yu; Jaeger, Dieter; Heck, Detlef H

    2017-01-01

    Cerebellar Purkinje cells (PC) fire action potentials at high, sustained rates. Changes in spike rate that last a few tens of milliseconds encode sensory and behavioral events. Here we investigated spontaneous fluctuations of PC simple spike rate at a slow time scale of the order of 1 s. Simultaneous recordings from pairs of PCs that were aligned either along the sagittal or transversal axis of the cerebellar cortex revealed that simple spike rate fluctuations at the 1 s time scale were highly correlated. Each pair of PCs had either a predominantly positive or negative slow-rate correlation, with negative correlations observed only in PC pairs aligned along the transversal axis. Slow-rate correlations were independent of faster rate changes that were correlated with fluid licking behavior. Simultaneous recordings from PCs and cerebellar nuclear (CN) neurons showed that slow-rate fluctuations in PC and CN activity were also highly correlated, but their correlations continually alternated between periods of positive and negative correlation. The functional significance of this new aspect of cerebellar spike activity remains to be determined. Correlated slow-rate fluctuations seem too slow to be involved in the real-time control of ongoing behavior. However, slow-rate fluctuations of PCs converging on the same CN neuron are likely to modulate the excitability of the CN neuron, thus introduce a possible slow modulation of cerebellar output activity.

  2. Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.

    PubMed

    Mittleman, Guy; Goldowitz, Daniel; Heck, Detlef H; Blaha, Charles D

    2008-07-01

    Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 muA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked prefrontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders.

  3. Cerebellar Modulation of Frontal Cortex Dopamine Efflux in Mice: Relevance to Autism and Schizophrenia

    PubMed Central

    MITTLEMAN, GUY; GOLDOWITZ, DANIEL; HECK, DETLEF H.; BLAHA, CHARLES D.

    2013-01-01

    Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 μA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked pre-frontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders. PMID:18435424

  4. Cadherins in cerebellar development: translation of embryonic patterning into mature functional compartmentalization.

    PubMed

    Redies, Christoph; Neudert, Franziska; Lin, Juntang

    2011-09-01

    Cadherins are cell adhesion molecules with multiple morphogenic functions in brain development, for example, in neuroblast migration and aggregation, axon navigation, neural circuit formation, and synaptogenesis. More than 100 members of the cadherin superfamily are expressed in the developing and mature brain. Most of the cadherins investigated, in particular classic cadherins and δ-protocadherins, are expressed in the cerebellum. For several cadherin subtypes, expression begins at early embryonic stages and persists until mature stages of cerebellar development. At intermediate stages, distinct Purkinje cell clusters exhibit unique rostrocaudal and mediolateral expression profiles for each cadherin. In the chicken, mouse, and other species, the Purkinje cell clusters are separated by intervening raphes of migrating granule cells. This pattern of Purkinje cell clusters/raphes is, at least in part, continuous with the parasagittal striping pattern that is apparent in the mature cerebellar cortex, for example, for zebrin II/aldolase C. Moreover, subregions of the deep cerebellar nuclei, vestibular nuclei and the olivary complex also express cadherins differentially. Neuroanatomical evidence suggests that the nuclear subregions and cortical domains that express the same cadherin subtype are connected to each other, to form neural subcircuits of the cerebellar system. Cadherins thus provide a molecular code that specifies not only embryonic structures but also functional cerebellar compartmentalization. By following the implementation of this code, it can be revealed how mature functional architecture emerges from embryonic patterning during cerebellar development. Dysfunction of some cadherins is associated with psychiatric diseases and developmental impairments and may also affect cerebellar function.

  5. The organization of plasticity in the cerebellar cortex: from synapses to control.

    PubMed

    D'Angelo, Egidio

    2014-01-01

    The cerebellum is thought to play a critical role in procedural learning, but the relationship between this function and the underlying cellular and synaptic mechanisms remains largely speculative. At present, at least nine forms of long-term synaptic and nonsynaptic plasticity (some of which are bidirectional) have been reported in the cerebellar cortex and deep cerebellar nuclei. These include long-term potentiation (LTP) and long-term depression at the mossy fiber-granule cell synapse, at the synapses formed by parallel fibers, climbing fibers, and molecular layer interneurons on Purkinje cells, and at the synapses formed by mossy fibers and Purkinje cells on deep cerebellar nuclear cells, as well as LTP of intrinsic excitability in granule cells, Purkinje cells, and deep cerebellar nuclear cells. It is suggested that the complex properties of cerebellar learning would emerge from the distribution of plasticity in the network and from its dynamic remodeling during the different phases of learning. Intrinsic and extrinsic factors may hold the key to explain how the different forms of plasticity cooperate to select specific transmission channels and to regulate the signal-to-noise ratio through the cerebellar cortex. These factors include regulation of neuronal excitation by local inhibitory networks, engagement of specific molecular mechanisms by spike bursts and theta-frequency oscillations, and gating by external neuromodulators. Therefore, a new and more complex view of cerebellar plasticity is emerging with respect to that predicted by the original "Motor Learning Theory," opening issues that will require experimental and computational testing. © 2014 Elsevier B.V. All rights reserved.

  6. Progressive Non-familial Adult onset Cerebellar Degeneration: An Unusual Occurrence with Hashimoto's Thyroiditis.

    PubMed

    Rao, Raghavendra S; Sheshadri, Shubha; Bhattacharjee, Dipanjan; Patil, Navin; Rao, Karthik

    2018-03-13

    Progressive non-familial adult onset cerebellar degeneration has been rarely associated with hypothyroidism and is known to be reversible after therapy. We report a case of cerebellar atrophy in a 31 year old female whose detailed evaluation had revealed sub-clinical hypothyroidism secondary to autoimmune thyroiditis with a very high anti-TPO (anti-thyroid peroxidase) antibody levels. MRI (Magnetic Resonanace Imaging) of brain showed diffuse bilateral cerebellar atrophy. She was treated with thyroid hormone supplementation and after one year of follow up, cerebellar signs had disappeared completely with significant reduction in anti-TPO antibody levels. Imaging of the brain post one year of follow-up revealed normal cerebellum. Hence, we opine that thyroid dysfunction should always be kept in mind while evaluating patients presenting with acute onset cerebellar ataxia as it can be easily reversed with thyroid hormone replacement therapy.

  7. Distinct Critical Cerebellar Subregions for Components of Verbal Working Memory

    ERIC Educational Resources Information Center

    Cooper, Freya E.; Grube, Manon; Von Kriegstein, Katharina; Kumar, Sukhbinder; English, Philip; Kelly, Thomas P.; Chinnery, Patrick F.; Griffiths, Timothy D.

    2012-01-01

    A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between…

  8. The Cerebellum and Language: Evidence from Patients with Cerebellar Degeneration

    ERIC Educational Resources Information Center

    Stoodley, Catherine J.; Schmahmann, Jeremy D.

    2009-01-01

    Clinical and imaging studies suggest that the cerebellum is involved in language tasks, but the extent to which slowed language production in cerebellar patients contributes to their poor performance on these tasks is not clear. We explored this relationship in 18 patients with cerebellar degeneration and 16 healthy controls who completed measures…

  9. [Cerebellar, pulmonary and cutaneous localizations of juvenile xanthogranuloma].

    PubMed

    Cauro, F; Houtteville, J P; Mesnil, J L; Guarnieri, J

    2002-03-01

    Juvenile xanthogranuloma is one of the most common non-langerhan cell histiocytoses in children. Usually cutaneous, there are disseminated forms. However, neurological localizations remain exceptional. We report the case of a cerebellar localization, associated with cutaneous and pulmonary lesions in a 13-month old child. Surgical treatment of the cerebellar lesion was associated with vinblastin chemotherapy, that led to total regression of the cutaneous and pulmonary lesions, neurological stabilization, without recurrence on the control IRM, after a period of 7 years. This is the second reported case of histologically documented cerebellar juvenile xanthogranuloma. In the event of cutaneous juvenile xanthogranuloma, the neurological examination must be attentive and supplemented, in case of any suspicion, by medical imaging. We believe that surgical treatment of neurological juvenile xanthogranuloma is necessary, in the event of symptomatic lesions and accessible to surgery. No consensus has been reached on subsequent treatments (radiotherapy, chemotherapy) and must be discussed according to the clinical profile and data in the literature.

  10. Recurrent cerebellar architecture solves the motor-error problem.

    PubMed Central

    Porrill, John; Dean, Paul; Stone, James V.

    2004-01-01

    Current views of cerebellar function have been heavily influenced by the models of Marr and Albus, who suggested that the climbing fibre input to the cerebellum acts as a teaching signal for motor learning. It is commonly assumed that this teaching signal must be motor error (the difference between actual and correct motor command), but this approach requires complex neural structures to estimate unobservable motor error from its observed sensory consequences. We have proposed elsewhere a recurrent decorrelation control architecture in which Marr-Albus models learn without requiring motor error. Here, we prove convergence for this architecture and demonstrate important advantages for the modular control of systems with multiple degrees of freedom. These results are illustrated by modelling adaptive plant compensation for the three-dimensional vestibular ocular reflex. This provides a functional role for recurrent cerebellar connectivity, which may be a generic anatomical feature of projections between regions of cerebral and cerebellar cortex. PMID:15255096

  11. Marijuana alters the human cerebellar clock.

    PubMed

    O'Leary, Daniel S; Block, Robert I; Turner, Beth M; Koeppel, Julie; Magnotta, Vincent A; Ponto, Laura Boles; Watkins, G Leonard; Hichwa, Richard D; Andreasen, Nancy C

    2003-06-11

    The effects of marijuana on brain perfusion and internal timing were assessed using [15O] water PET in occasional and chronic users. Twelve volunteers who smoked marijuana recreationally about once weekly, and 12 volunteers who smoked daily for a number of years performed a self-paced counting task during PET imaging, before and after smoking marijuana and placebo cigarettes. Smoking marijuana increased rCBF in the ventral forebrain and cerebellar cortex in both groups, but resulted in significantly less frontal lobe activation in chronic users. Counting rate increased after smoking marijuana in both groups, as did a behavioral measure of self-paced tapping, and both increases correlated with rCBF in the cerebellum. Smoking marijuana appears to accelerate a cerebellar clock altering self-paced behaviors.

  12. Isolated rhomboencephalosynapsis - a rare cerebellar anomaly.

    PubMed

    Paprocka, Justyna; Jamroz, Ewa; Scieszka, Ewa; Kluczewska, Ewa

    2012-01-01

    Rhomboencephalosynapsis (RES, RS) is a unique entity usually recognized in infancy based on neuroimaging. Cerebellar fusion and absence of cerebellar vermis is often associated with supratentorial findings. Since now there are about 50 cases described worldwide, with approximately 36 patients diagnosed by MRI. The authors present the first in Poland case of this uncommon malformation and review the literature. The authors describe a 28-month-old-girl with microcephaly and proper psychomotor development. The family history was unrelevant. Based on MRI the congenital malformation of posterior fossa-rhombencephalosynapsis was confirmed Presented patient is a typical example of MRI usefulness especially in patients with RES. RES symptoms are mild and that is why the diagnosis is usually made only in adulthood.

  13. Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.

    PubMed

    van Rooij, Daan; Anagnostou, Evdokia; Arango, Celso; Auzias, Guillaume; Behrmann, Marlene; Busatto, Geraldo F; Calderoni, Sara; Daly, Eileen; Deruelle, Christine; Di Martino, Adriana; Dinstein, Ilan; Duran, Fabio Luis Souza; Durston, Sarah; Ecker, Christine; Fair, Damien; Fedor, Jennifer; Fitzgerald, Jackie; Freitag, Christine M; Gallagher, Louise; Gori, Ilaria; Haar, Shlomi; Hoekstra, Liesbeth; Jahanshad, Neda; Jalbrzikowski, Maria; Janssen, Joost; Lerch, Jason; Luna, Beatriz; Martinho, Mauricio Moller; McGrath, Jane; Muratori, Filippo; Murphy, Clodagh M; Murphy, Declan G M; O'Hearn, Kirsten; Oranje, Bob; Parellada, Mara; Retico, Alessandra; Rosa, Pedro; Rubia, Katya; Shook, Devon; Taylor, Margot; Thompson, Paul M; Tosetti, Michela; Wallace, Gregory L; Zhou, Fengfeng; Buitelaar, Jan K

    2018-04-01

    Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different

  14. Functional and Structural Correlates of Motor Speed in the Cerebellar Anterior Lobe

    PubMed Central

    Wenzel, Uwe; Taubert, Marco; Ragert, Patrick; Krug, Jürgen; Villringer, Arno

    2014-01-01

    In athletics, motor performance is determined by different abilities such as technique, endurance, strength and speed. Based on animal studies, motor speed is thought to be encoded in the basal ganglia, sensorimotor cortex and the cerebellum. The question arises whether there is a unique structural feature in the human brain, which allows “power athletes” to perform a simple foot movement significantly faster than “endurance athletes”. We acquired structural and functional brain imaging data from 32 track-and-field athletes. The study comprised of 16 “power athletes” requiring high speed foot movements (sprinters, jumpers, throwers) and 16 endurance athletes (distance runners) which in contrast do not require as high speed foot movements. Functional magnetic resonance imaging (fMRI) was used to identify speed specific regions of interest in the brain during fast and slow foot movements. Anatomical MRI scans were performed to assess structural grey matter volume differences between athletes groups (voxel based morphometry). We tested maximum movement velocity of plantarflexion (PF-Vmax) and acquired electromyographical activity of the lateral and medial gastrocnemius muscle. Behaviourally, a significant difference between the two groups of athletes was noted in PF-Vmax and fMRI indicates that fast plantarflexions are accompanied by increased activity in the cerebellar anterior lobe. The same region indicates increased grey matter volume for the power athletes compared to the endurance counterparts. Our results suggest that speed-specific neuro-functional and -structural differences exist between power and endurance athletes in the peripheral and central nervous system. PMID:24800742

  15. Cerebellar ataxia and epilepsy with anti-GAD antibodies: treatment with IVIG and plasmapheresis

    PubMed Central

    Georgieva, Zoya; Parton, Matthew

    2014-01-01

    Glutamic acid decarboxylase autoantibody (GAD-65) catalyses glutamate conversion into γ-aminobutyric acid (GABA) in the central nervous system and in the pancreatic β cells. Antibodies targeting GAD-65 are of uncertain pathogenic significance and occur in stiff person syndrome, cerebellar ataxia, epilepsy, limbic encephalitis and combinations thereof and diabetes mellitus. A 45-year-old man with a cerebellar gait ataxia, dysmetria, nystagmus and mild cerebellar dysarthria was diagnosed with insulin-dependent diabetes mellitus a year after the onset of neurological symptoms. He also developed complex and tonic-clonic seizures, resistant to anticonvulsant medication and deteriorated cognitively. Blood and cerebrospinal fluid serology, and imaging supported the diagnosis of GAD-65 cerebellar ataxia and epilepsy. He was treated with intravenous immunoglobulin and subsequently plasmapheresis. We report the outcome of 3 years of treatment, which resulted in the improvement of cerebellar signs (particularly gait), with some ultimate decline of efficacy. PMID:24419643

  16. Altered Associations between Pain Symptoms and Brain Morphometry in the Pain Matrix of HIV-Seropositive Individuals.

    PubMed

    Castillo, Deborrah; Ernst, Thomas; Cunningham, Eric; Chang, Linda

    2018-03-01

    Pain remains highly prevalent in HIV-seropositive (HIV+) patients despite their well-suppressed viremia with combined antiretroviral therapy. Investigating brain abnormalities within the pain matrix, and in relation to pain symptoms, in HIV+ participants may provide objective biomarkers and insights regarding their pain symptoms. We used Patient-Reported Outcome Measurement Information System (PROMIS®) pain questionnaire to evaluate pain symptoms (pain intensity, pain interference and pain behavior), and structural MRI to assess brain morphometry using FreeSurfer (cortical area, cortical thickness and subcortical volumes were evaluated in 12 regions within the pain matrix). Compared to seronegative (SN) controls, HIV+ participants had smaller surface areas in prefrontal pars triangularis (right: p = 0.04, left: p = 0.007) and right anterior cingulate cortex (p = 0.03) and smaller subcortical regions (thalamus: p ≤ 0.003 bilaterally; right putamen: p = 0.01), as well as higher pain scores (pain intensity-p = 0.005; pain interference-p = 0.008; pain-behavior-p = 0.04). Furthermore, higher pain scores were associated with larger cortical areas, thinner cortices and larger subcortical volumes in HIV+ participants; but smaller cortical areas, thicker cortices and smaller subcortical volumes in SN controls (interaction-p = 0.009 to p = 0.04). These group differences in the pain-associated brain abnormalities suggest that HIV+ individuals have abnormal pain responses. Since these abnormal pain-associated brain regions belong to the affective component of the pain matrix, affective symptoms may influence pain perception in HIV+ patients and should be treated along with their physical pain symptoms. Lastly, associations of lower pain scores with better physical or mental health scores, regardless of HIV-serostatus (p < 0.001), suggest adequate pain treatment would lead to better quality of life in all participants.

  17. Early Cerebellar Network Shifting in Spinocerebellar Ataxia Type 6

    PubMed Central

    Falcon, M.I.; Gomez, C.M.; Chen, E.E.; Shereen, A.; Solodkin, A.

    2016-01-01

    Spinocerebellar ataxia 6 (SCA6), an autosomal dominant degenerative disease, is characterized by diplopia, gait ataxia, and incoordination due to severe progressive degeneration of Purkinje cells in the vestibulo- and spinocerebellum. Ocular motor deficits are common, including difficulty fixating on moving objects, nystagmus and disruption of smooth pursuit movements. In presymptomatic SCA6, there are alterations in saccades and smooth-pursuit movements. We sought to assess functional and structural changes in cerebellar connectivity associated with a visual task, hypothesizing that gradual changes would parallel disease progression. We acquired functional magnetic resonance imaging and diffusion tensor imaging data during a passive smooth-pursuit task in 14 SCA6 patients, representing a range of disease duration and severity, and performed a cross-sectional comparison of cerebellar networks compared with healthy controls. We identified a shift in activation from vermis in presymptomatic individuals to lateral cerebellum in moderate-to-severe cases. Concomitantly, effective connectivity between regions of cerebral cortex and cerebellum was at its highest in moderate cases, and disappeared in severe cases. Finally, we noted structural differences in the cerebral and cerebellar peduncles. These unique results, spanning both functional and structural domains, highlight widespread changes in SCA6 and compensatory mechanisms associated with cerebellar physiology that could be utilized in developing new therapies. PMID:26209844

  18. Essential tremor, the cerebellum, and motor timing: towards integrating them into one complex entity.

    PubMed

    Bareš, Martin; Husárová, Ivica; Lungu, Ovidiu V

    2012-01-01

    Essential tremor (ET) is the most common movement disorder in humans. It is characterized by a postural and kinetic tremor most commonly affecting the forearms and hands. Isolated head tremor has been found in 1-10% of patients, suggesting that ET may be a composite of several phenotypes. The exact pathophysiology of ET is still unknown. ET has been repeatedly shown as a disorder of mild cerebellar degeneration, particularly in postmortem studies. Clinical observations, electrophysiological, volumetric and functional imaging studies all reinforce the fact that the cerebellum is involved in the generation of ET. However, crucial debate exists as to whether ET is a neurodegenerative disease. Data suggesting that it is neurodegenerative include postmortem findings of pathological abnormalities in the brainstem and cerebellum, white matter changes on diffusion tensor imaging, and clinical studies demonstrating an association with cognitive and gait changes. There is also conflicting evidence against ET as a neurodegenerative disease: the improvement of gait abnormalities with ethanol administration, lack of gray matter volume loss on voxel-based morphometry, failure to confirm the prominent presence of Lewy bodies in the locus ceruleus, and other pathological findings. To clarify this issue, future research is needed to describe the mechanism of cellular changes in the ET brain and to understand the order in which they occur. The cerebellum has been shown to be involved in the timing of movement and sensation, acting as an internal timing system that provides the temporal representation of salient events spanning hundreds of milliseconds. It has been reported that cerebellar timing function is altered in patients with ET, showing an increased variability of rhythmic hand movements as well as diminished performance during predictive motor timing task. Based on current knowledge and observations, we argue that ET is essentially linked with cerebellar degeneration, or at

  19. Cerebellar Output in Zebrafish: An Analysis of Spatial Patterns and Topography in Eurydendroid Cell Projections

    PubMed Central

    Heap, Lucy A.; Goh, Chi Ching; Kassahn, Karin S.; Scott, Ethan K.

    2013-01-01

    The cerebellum is a brain region responsible for motor coordination and for refining motor programs. While a great deal is known about the structure and connectivity of the mammalian cerebellum, fundamental questions regarding its function in behavior remain unanswered. Recently, the zebrafish has emerged as a useful model organism for cerebellar studies, owing in part to the similarity in cerebellar circuits between zebrafish and mammals. While the cell types composing their cerebellar cortical circuits are generally conserved with mammals, zebrafish lack deep cerebellar nuclei, and instead a majority of cerebellar output comes from a single type of neuron: the eurydendroid cell. To describe spatial patterns of cerebellar output in zebrafish, we have used genetic techniques to label and trace eurydendroid cells individually and en masse. We have found that cerebellar output targets the thalamus and optic tectum, and have confirmed the presence of pre-synaptic terminals from eurydendroid cells in these structures using a synaptically targeted GFP. By observing individual eurydendroid cells, we have shown that different medial-lateral regions of the cerebellum have eurydendroid cells projecting to different targets. Finally, we found topographic organization in the connectivity between the cerebellum and the optic tectum, where more medial eurydendroid cells project to the rostral tectum while lateral cells project to the caudal tectum. These findings indicate that there is spatial logic underpinning cerebellar output in zebrafish with likely implications for cerebellar function. PMID:23554587

  20. Gravity-dependent nystagmus and inner-ear dysfunction suggest anterior and posterior inferior cerebellar artery infarct.

    PubMed

    Shaikh, Aasef G; Miller, Benjamin R; Sundararajan, Sophia; Katirji, Bashar

    2014-04-01

    Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Early childhood obesity is associated with compromised cerebellar development.

    PubMed

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p < .0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

  2. Brain Growth Rate Abnormalities Visualized in Adolescents with Autism

    PubMed Central

    Hua, Xue; Thompson, Paul M.; Leow, Alex D.; Madsen, Sarah K.; Caplan, Rochelle; Alger, Jeffry R.; O’Neill, Joseph; Joshi, Kishori; Smalley, Susan L.; Toga, Arthur W.; Levitt, Jennifer G.

    2014-01-01

    Autism spectrum disorder (ASD) is a heterogeneous disorder of brain development with wide-ranging cognitive deficits. Typically diagnosed before age 3, ASD is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared to those of typically developing children and adolescents. Using tensor-based morphometry (TBM), we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and 7 typically developing boys (mean age/inter-scan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole-brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (p = 0.03, corrected), especially in the parietal (p = 0.008), temporal (p = 0.03) and occipital lobes (p =0.02). We also visualized abnormal overgrowth in autism in some gray matter structures, such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. TBM revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. PMID:22021093

  3. Chromosomal aneuploidies and copy number variations in posterior fossa abnormalities diagnosed by prenatal ultrasonography.

    PubMed

    Lei, Ting; Feng, Jie-Ling; Xie, Ying-Jun; Xie, Hong-Ning; Zheng, Ju; Lin, Mei-Fang

    2017-11-01

    To explore the genetic aetiology of fetal posterior fossa abnormalities (PFAs). This study involved cases of PFAs that were identified by prenatal ultrasonographic screening and confirmed postnatally between January 2012 and January 2016. Conventional cytogenetic analyses and chromosomal microarray analysis were performed, and chromosomal aneuploidies and copy number variations (CNVs) were identified. Among 74 cases included in this study, 8 were of Blake's pouch cyst; 7, Dandy-Walker malformation; 11, vermian hypoplasia; 32, enlarged cisterna magna; and 16, cerebellar hypoplasia. The rates of nonbenign chromosomal aberrations (including chromosomal aneuploidies, pathogenic CNVs, and variants of unknown significance) were 2/8 (25.0%), 2/7 (28.5%), 8/11 (72.7%), 7/32 (21.9%), and 6/16 (37.5%), respectively. Cases were also classified as isolated PFAs (30/74), PFAs with other central nervous system (CNS) abnormalities (13/74), or PFAs with extra-CNS structural abnormalities (31/74). No fetuses with isolated PFAs or PFAs accompanied by other CNS abnormalities exhibited chromosomal aneuploidies or pathogenic CNVs. The rate of pathogenic chromosomal aberrations in the remaining fetuses was 17/31 (22.9%). The combined use of chromosomal microarray analysis and karyotype analysis might assist the prenatal diagnosis and management of PFAs, with extra-CNS structural abnormalities being detected by ultrasonography. © 2017 John Wiley & Sons, Ltd.

  4. Incidence of Dysarthria in Children with Cerebellar Tumors: A Prospective Study

    ERIC Educational Resources Information Center

    Richter, S.; Schoch, B.; Ozimek, A.; Gorissen, B.; Hein-Kropp, C.; Kaiser, O.; Hovel, M.; Wieland, R.; Gizewski, E.; Timmann, D.

    2005-01-01

    The present study investigated dysarthric symptoms in children with cerebellar tumors. Ten children with cerebellar tumors and 10 orthopedic control children were tested prior and one week after surgery. Clinical dysarthric symptoms were quantified in spontaneous speech. Syllable durations were analyzed in syllable repetition and sentence…

  5. Cytological Evaluation of Thyroid Lesions by Nuclear Morphology and Nuclear Morphometry.

    PubMed

    Yashaswini, R; Suresh, T N; Sagayaraj, A

    2017-01-01

    Fine needle aspiration (FNA) of the thyroid gland is an effective diagnostic method. The Bethesda system for reporting thyroid cytopathology classifies them into six categories and gives implied risk for malignancy and management protocol in each category. Though the system gives specific criteria, diagnostic dilemma still exists. Using nuclear morphometry, we can quantify the number of parameters, such as those related to nuclear size and shape. The evaluation of nuclear morphometry is not well established in thyroid cytology. To classify thyroid lesions on fine needle aspiration cytology (FNAC) using Bethesda system and to evaluate the significance of nuclear parameters in improving the prediction of thyroid malignancy. In the present study, 120 FNAC cases of thyroid lesions with histological diagnosis were included. Computerized nuclear morphometry was done on 81 cases which had confirmed cytohistological correlation, using Aperio computer software. One hundred nuclei from each case were outlined and eight nuclear parameters were analyzed. In the present study, thyroid lesions were common in female with M: F ratio of 1:5 and most commonly in 40-60 yrs. Under Bethesda system, 73 (60.83%) were category II; 14 (11.6%) were category III, 3 (2.5%) were category IV, 8 (6.6%) were category V, and 22 (18.3%) were category VI, which were malignant on histopathological correlation. Sensitivity, specificity, and diagnostic accuracy of Bethesda reporting system are 62.5, 84.38, and 74.16%, respectively. Minimal nuclear diameter, maximal nuclear diameter, nuclear perimeter, and nuclear area were higher in malignant group compared to nonneoplastic and benign group. The Bethesda system is a useful standardized system of reporting thyroid cytopathology. It gives implied risk of malignancy. Nuclear morphometry by computerized image analysis can be utilized as an additional diagnostic tool.

  6. Developmental Injury to the Cerebellar Cortex Following Hydroxyurea Treatment in Early Postnatal Life: An Immunohistochemical and Electron Microscopic Study.

    PubMed

    Martí, Joaquín; Molina, Vanesa; Santa-Cruz, M C; Hervás, José P

    2017-02-01

    Postnatal development of the cerebellar cortex was studied in rats administered with a single dose (2 mg/g) of the cytotoxic agent hydroxyurea (HU) on postnatal day (P) 9 and collected at appropriate times ranging from 6 h to 45 days. Quantification of several parameters such as the density of pyknotic, mitotic, BrdU-positive, and vimentin-stained cells revealed that HU compromises the survival of the external granular layer (EGL) cells. Moreover, vimentin immunocytochemistry revealed overexpression and thicker immunoreactive glial processes in HU-treated rats. On the other hand, we also show that HU leads to the activation of apoptotic cellular events, resulting in a substantial number of dying EGL cells, as revealed by TUNEL staining and at the electron microscope level. Additionally, we quantified several features of the cerebellar cortex of rats exposed to HU in early postnatal life and collected in adulthood. Data analysis indicated that the analyzed parameters were less pronounced in rats administered with this agent. Moreover, we observed several alterations in the cerebellar cortex cytoarchitecture of rats injected with HU. Anomalies included ectopic placement of Purkinje cells and abnormities in the dendritic arbor of these macroneurons. Ectopic granule cells were also found in the molecular layer. These findings provide a clue for investigating the mechanisms of HU-induced toxicity during the development of the central nervous system. Our results also suggest that it is essential to avoid underestimating the adverse effects of this hydroxylated analog of urea when administered during early postnatal life.

  7. Changes in cerebro-cerebellar interaction during response inhibition after performance improvement.

    PubMed

    Hirose, Satoshi; Jimura, Koji; Kunimatsu, Akira; Abe, Osamu; Ohtomo, Kuni; Miyashita, Yasushi; Konishi, Seiki

    2014-10-01

    It has been demonstrated that motor learning is supported by the cerebellum and the cerebro-cerebellar interaction. Response inhibition involves motor responses and the higher-order inhibition that controls the motor responses. In this functional MRI study, we measured the cerebro-cerebellar interaction during response inhibition in two separate days of task performance, and detected the changes in the interaction following performance improvement. Behaviorally, performance improved in the second day, compared to the first day. The psycho-physiological interaction (PPI) analysis revealed the interaction decrease from the right inferior frontal cortex (rIFC) to the cerebellum (lobule VII or VI). It was also revealed that the interaction increased from the same cerebellar region to the primary motor area. These results suggest the involvement of the cerebellum in response inhibition, and raise the possibility that the performance improvement was supported by the changes in the cerebro-cerebellar interaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Restoring Cognitive Functions Using Non-Invasive Brain Stimulation Techniques in Patients with Cerebellar Disorders

    PubMed Central

    Pope, Paul A.; Miall, R. Chris

    2014-01-01

    Numerous studies have highlighted the possibility of modulating the excitability of cerebro–cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral–lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato–rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro–cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided toward neuro-enhancement in certain patient populations, using what is commonly termed “non-invasive brain stimulation” as a cognitive rehabilitation tool to modulate cerebro–cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo

  9. Long term clinical and neurophysiological effects of cerebellar transcranial direct current stimulation in patients with neurodegenerative ataxia.

    PubMed

    Benussi, Alberto; Dell'Era, Valentina; Cotelli, Maria Sofia; Turla, Marinella; Casali, Carlo; Padovani, Alessandro; Borroni, Barbara

    Neurodegenerative cerebellar ataxias represent a group of disabling disorders for which we currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. The present study investigated whether a two-weeks' treatment with cerebellar anodal tDCS could improve symptoms in patients with neurodegenerative cerebellar ataxia and could modulate cerebello-motor connectivity, at short and long term. We performed a double-blind, randomized, sham controlled trial with cerebellar tDCS (5 days/week for 2 weeks) in twenty patients with ataxia. Each patient underwent a clinical evaluation pre- and post-anodal tDCS or sham stimulation. A follow-up evaluation was performed at one and three months. Cerebello-motor connectivity was evaluated using transcranial magnetic stimulation (TMS) at baseline and at follow-up. Patients who underwent anodal tDCS showed a significant improvement in all performance scores (scale for the assessment and rating of ataxia, international cooperative ataxia rating scale, 9-hole peg test, 8-m walking time) and in cerebellar brain inhibition compared to patients who underwent sham stimulation. A two-weeks' treatment with anodal cerebellar tDCS improves symptoms in patients with ataxia and restores physiological cerebellar brain inhibition pathways. Cerebellar tDCS might represent a promising future therapeutic and rehabilitative approach in patients with neurodegenerative ataxia. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Childhood cerebellar ataxia.

    PubMed

    Fogel, Brent L

    2012-09-01

    Childhood presentations of ataxia, an impairment of balance and coordination caused by damage to or dysfunction of the cerebellum, can often be challenging to diagnose. Presentations tend to be clinically heterogeneous, but key considerations may vary based on the child's age at onset, the course of illness, and subtle differences in phenotype. Systematic investigation is recommended for efficient diagnosis. In this review, we outline common etiologies and describe a comprehensive approach to the evaluation of both acquired and genetic cerebellar ataxia in children.

  11. Surgical and clinical aspects of cerebellar pilomyxoid-spectrum astrocytomas in children.

    PubMed

    El Beltagy, Mohamed A; Atteya, Mostafa M E; El-Haddad, Alaa; Awad, Madiha; Taha, Hala; Kamal, Mohamed; El Naga, Sherif Abou

    2014-06-01

    Cerebellar pilomyxoid astrocytomas (PMAs) and intermediate pilomyxoid astrocytomas (IPAs) are collectively called "pilomyxoid-spectrum astrocytomas (PMSAs)." Cerebellar PMSAs are thought to behave more aggressively than pilocytic astrocytomas (PAs). Our objective is to compare PMSAs to PAs in terms of surgical and clinical profiles. This retrospective study included 66 cases (35 males and 31 females) with cerebellar astrocytomas treated between July 2007 and December 2012 at Children's Cancer Hospital Egypt (CCHE 57357) with a mean age of 7 (±1.5) years. Cases were divided into three subgroups as follows: 44 PAs, 10 IPAs, and 12 PMAs. Comparison between all groups was focusing on brain stem invasion, intrinsic necrotic cavitation, extent of resection, recurrence, leptomeningeal dissemination (LD), metastases, need for CSF diversion, and cerebellar mutism (CM). Cerebellar PMAs and IPAs separately and collectively had higher incidence of brain stem invasion, intrinsic necrotic cavitation, tumor recurrence, and LD when compared to PAs (P < 0.001). Gross total resection was 13.6 % in PMSAs versus 90.9 % in PAs (P < 0.001). PMAs had a higher incidence of tumor recurrence than IPAs (66.7 versus 20 %, P < 0.001). Incidence of recurrence in PAs was 9.1 % in partially resected cases. Mean interval to recurrence was 9 (±1.5) months in PMSAs and 42 (±2) months in PAs. Cerebellar PMSAs express an aggressive clinical behavior and impose more operative challenges than PAs. These tumors may represent a clinical spectrum-at its benign end lies PA, while PMA lies at the aggressive end, with IPA lying just behind. Such concepts could be used to guide management in the future.

  12. Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization

    PubMed Central

    Mankiw, Catherine; Park, Min Tae M.; Reardon, P.K.; Fish, Ari M.; Clasen, Liv S.; Greenstein, Deanna; Blumenthal, Jonathan D.; Lerch, Jason P.; Chakravarty, M. Mallar

    2017-01-01

    The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences—including their spatial distribution, potential biological determinants, and independence from brain volume variation—lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male–female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size. SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the

  13. Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization.

    PubMed

    Mankiw, Catherine; Park, Min Tae M; Reardon, P K; Fish, Ari M; Clasen, Liv S; Greenstein, Deanna; Giedd, Jay N; Blumenthal, Jonathan D; Lerch, Jason P; Chakravarty, M Mallar; Raznahan, Armin

    2017-05-24

    The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences-including their spatial distribution, potential biological determinants, and independence from brain volume variation-lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male-female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size. SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human

  14. Comparative neuronal morphology of the cerebellar cortex in afrotherians, carnivores, cetartiodactyls, and primates

    PubMed Central

    Jacobs, Bob; Johnson, Nicholas L.; Wahl, Devin; Schall, Matthew; Maseko, Busisiwe C.; Lewandowski, Albert; Raghanti, Mary A.; Wicinski, Bridget; Butti, Camilla; Hopkins, William D.; Bertelsen, Mads F.; Walsh, Timothy; Roberts, John R.; Reep, Roger L.; Hof, Patrick R.; Sherwood, Chet C.; Manger, Paul R.

    2014-01-01

    Although the basic morphological characteristics of neurons in the cerebellar cortex have been documented in several species, virtually nothing is known about the quantitative morphological characteristics of these neurons across different taxa. To that end, the present study investigated cerebellar neuronal morphology among eight different, large-brained mammalian species comprising a broad phylogenetic range: afrotherians (African elephant, Florida manatee), carnivores (Siberian tiger, clouded leopard), cetartiodactyls (humpback whale, giraffe) and primates (human, common chimpanzee). Specifically, several neuron types (e.g., stellate, basket, Lugaro, Golgi, and granule neurons; N = 317) of the cerebellar cortex were stained with a modified rapid Golgi technique and quantified on a computer-assisted microscopy system. There was a 64-fold variation in brain mass across species in our sample (from clouded leopard to the elephant) and a 103-fold variation in cerebellar volume. Most dendritic measures tended to increase with cerebellar volume. The cerebellar cortex in these species exhibited the trilaminate pattern common to all mammals. Morphologically, neuron types in the cerebellar cortex were generally consistent with those described in primates (Fox et al., 1967) and rodents (Palay and Chan-Palay, 1974), although there was substantial quantitative variation across species. In particular, Lugaro neurons in the elephant appeared to be disproportionately larger than those in other species. To explore potential quantitative differences in dendritic measures across species, MARSplines analyses were used to evaluate whether species could be differentiated from each other based on dendritic characteristics alone. Results of these analyses indicated that there were significant differences among all species in dendritic measures. PMID:24795574

  15. Effects of cerebellar neuromodulation in movement disorders: A systematic review.

    PubMed

    França, Carina; de Andrade, Daniel Ciampi; Teixeira, Manoel Jacobsen; Galhardoni, Ricardo; Silva, Valquiria; Barbosa, Egberto Reis; Cury, Rubens Gisbert

    The cerebellum is involved in the pathophysiology of many movement disorders and its importance in the field of neuromodulation is growing. To review the current evidence for cerebellar modulation in movement disorders and its safety profile. Eligible studies were identified after a systematic literature review of the effects of cerebellar modulation in cerebellar ataxia, Parkinson's disease (PD), essential tremor (ET), dystonia and progressive supranuclear palsy (PSP). Neuromodulation techniques included transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS). The changes in motor scores and the incidence of adverse events after the stimulation were reviewed. Thirty-four studies were included in the systematic review, comprising 431 patients. The evaluation after stimulation ranged from immediately after to 12 months after. Neuromodulation techniques improved cerebellar ataxia due to vascular or degenerative etiologies (TMS, tDCS and DBS), dyskinesias in PD patients (TMS), gross upper limb movement in PD patients (tDCS), tremor in ET (TMS and tDCS), cervical dystonia (TMS and tDCS) and dysarthria in PSP patients (TMS). All the neuromodulation techniques were safe, since only three studies reported the existence of side effects (slight headache after TMS, local skin erythema after tDCS and infectious complication after DBS). Eleven studies did not mention if adverse events occurred. Cerebellar modulation can improve specific symptoms in some movement disorders and is a safe and well-tolerated procedure. Further studies are needed to lay the groundwork for new researches in this promising target. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Gait ataxia in humans: vestibular and cerebellar control of dynamic stability.

    PubMed

    Schniepp, Roman; Möhwald, Ken; Wuehr, Max

    2017-10-01

    During human locomotion, vestibular feedback control is fundamental for maintaining dynamic stability and adapting the gait pattern to external circumstances. Within the supraspinal locomotor network, the cerebellum represents the key site for the integration of vestibular feedback information. The cerebellum is further important for the fine-tuning and coordination of limb movements during walking. The aim of this review article is to highlight the shared structural and functional sensorimotor principles in vestibular and cerebellar locomotion control. Vestibular feedback for the maintenance of dynamic stability is integrated into the locomotor pattern via midline, caudal cerebellar structures (vermis, flocculonodular lobe). Hemispheric regions of the cerebellum facilitate feed-forward control of multi-joint coordination and higher locomotor functions. Characteristic features of the gait disorder in patients with vestibular deficits or cerebellar ataxia are increased levels of spatiotemporal gait variability in the fore-aft and the medio-lateral gait dimension. In the fore-aft dimension, pathologic increases of gait fluctuations critically depend on the locomotion speed and predominantly manifest during slow walking velocities. This feature is associated with an increased risk of falls in both patients with vestibular hypofunction as well as patients with cerebellar ataxia. Pharmacological approaches for the treatment of vestibular or cerebellar gait ataxia are currently not available. However, new promising options are currently tested in randomized, controlled trials (fampridine/FACEG; acetyl-DL-leucine/ALCAT).

  17. Systemic inflammation combined with neonatal cerebellar haemorrhage aggravates long-term structural and functional outcomes in a mouse model.

    PubMed

    Tremblay, Sophie; Pai, Alex; Richter, Lindsay; Vafaei, Rod; Potluri, Praneetha; Ellegood, Jacob; Lerch, Jason P; Goldowitz, Daniel

    2017-11-01

    Despite the increased recognition of cerebellar injury in survivors of preterm birth, the neurodevelopmental consequences of isolated cerebellar injury have been largely unexplored and our current understanding of the functional deficits requires further attention in order to translate knowledge to best practices. Preterm infants are exposed to multiple stressors during their postnatal development including perinatal cerebellar haemorrhage (CBH) and postnatal infection, two major risk factors for neurodevelopmental impairments. We developed a translational mouse model of CBH and/or inflammation to measure the short- and long-term outcomes in cerebellar structure and function. Mice exposed to early combined insults of CBH and early inflammatory state (EIS) have a delay in grasping acquisition, neonatal motor deficits and deficient long-term memory. CBH combined with late inflammatory state (LIS) does not induce neonatal motor problems but leads to poor fine motor function and long-term memory deficits at adulthood. Early combined insults result in poor cerebellar growth from postnatal day 15 until adulthood shown by MRI, which are reflected in diminished volumes of cerebellar structures. There are also decreases in volumes of gray matter and hippocampus. Cerebellar microgliosis appears 24h after the combined insults and persists until postnatal day 15 in the cerebellar molecular layer and cerebellar nuclei in association with a disrupted patterning of myelin deposition, a delay of oligodendrocyte maturation and reduced white matter cerebellar volume. Together, these findings reveal poor outcomes in developing brains exposed to combined cerebellar perinatal insults in association with cerebellar hypoplasia, persistence of microgliosis and alterations of cerebellar white matter maturation and growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Neurochemical abnormalities in brains of renal failure patients treated by repeated hemodialysis.

    PubMed

    Perry, T L; Yong, V W; Kish, S J; Ito, M; Foulks, J G; Godolphin, W J; Sweeney, V P

    1985-10-01

    We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean gamma-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being greater than 40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25-35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.

  19. Cerebellar interaction with the acoustic reflex.

    PubMed

    Jastreboff, P J

    1981-01-01

    The involvement of the cerebellar vermis in the acoustic reflex was analyzed in 12 cats, decerebrated or in pentobarbital anesthesia. Anatomical data suggested the existence of a connection of lobules VIII with the ventral cochlear nucleus. Single cell recording and evoked potential techniques demonstrated the existence of the acoustic projection to lobulus VIII. Electrical stimulation of this area changed the tension of the middle ear muscle and caused evoked potential responses in the caudal part of the ventral cochlear nucleus. Electrical stimulation of the motor nucleus of the facial nerve evoked a slow wave in the recording taken from the surrounding of the cochlear round window. A hypothesis is proposed which postulates the involvement of the acoustic reflex in space localization of acoustic stimuli and the action of cerebellar vermis in order to assure the stability and plasticity of the acoustic reflex arc.

  20. Childhood Cerebellar Ataxia

    PubMed Central

    Fogel, Brent L.

    2012-01-01

    Childhood presentations of ataxia, an impairment of balance and coordination caused by damage to or dysfunction of the cerebellum, can often be challenging to diagnose. Presentations tend to be clinically heterogeneous but key considerations may vary based on the child's age at onset, the course of illness, and subtle differences in phenotype. Systematic investigation is recommended for efficient diagnosis. In this review, we outline common etiologies and describe a comprehensive approach to the evaluation of both acquired and genetic cerebellar ataxia in children. PMID:22764177

  1. [Metronidazole-induced reversible cerebellar lesions and peripheral neuropathy].

    PubMed

    Toumi, S; Hammouda, M; Essid, A; Medimagh, L; Slamia, L Ben; Laouani-Kechrid, C

    2009-12-01

    Metronidazole is a widely prescribed treatment for amoebic and anaerobic germ infections. Its neurologic toxicity is rare but can be serious. We report the case of a 27-year-old male patient, treated with metronidazole for a cerebral abscess. He presented with a cerebellar syndrome and peripheral neuropathy at a cumulative metronidazole dose of 60g. The MRI aspect of the cerebellar lesions in addition to their reversibility after treatment cessation led to the diagnosis of metronidazole induced neurologic toxicity. The occurrence of neurologic disorders in patients treated with metronidazole must suggest drug toxicity and lead to cessation of treatment.

  2. Surgical approach to posterior inferior cerebellar artery aneurysms.

    PubMed

    La Pira, Biagia; Sturiale, Carmelo Lucio; Della Pepa, Giuseppe Maria; Albanese, Alessio

    2018-02-01

    The far-lateral is a standardised approach to clip aneurysms of the posterior inferior cerebellar artery (PICA). Different variants can be adopted to manage aneurysms that differ in morphology, topography, ruptured status, cerebellar swelling and surgeon preference. We distinguished five paradigmatic approaches aimed to manage aneurysms that are: proximal unruptured; proximal ruptured requiring posterior fossa decompression (PFD); proximal ruptured not requiring PFD; distal unruptured; distal ruptured. Preoperative planning in the setting of PICA aneurysm surgery is of paramount importance to perform an effective and safe procedure, to ensure an adequate PFD and optimal proximal control before aneurysm manipulation.

  3. Diffusion tensor imaging and voxel based morphometry study in amyotrophic lateral sclerosis: relationships with motor disability

    PubMed Central

    Thivard, Lionel; Pradat, Pierre‐François; Lehéricy, Stéphane; Lacomblez, Lucette; Dormont, Didier; Chiras, Jacques; Benali, Habib; Meininger, Vincent

    2007-01-01

    The aim of this study was to investigate the extent of cortical and subcortical lesions in amyotrophic lateral sclerosis (ALS) using, in combination, voxel based diffusion tensor imaging (DTI) and voxel based morphometry (VBM). We included 15 patients with definite or probable ALS and 25 healthy volunteers. Patients were assessed using the revised ALS Functional Rating Scale (ALSFRS‐R). In patients, reduced fractional anisotropy was found in bilateral corticospinal tracts, the left insula/ventrolateral premotor cortex, the right parietal cortex and the thalamus, which correlated with the ALSFRS‐R. Increased mean diffusivity (MD) was found bilaterally in the motor cortex, the ventrolateral premotor cortex/insula, the hippocampal formations and the right superior temporal gyrus, which did not correlate with the ALSFRS‐R. VBM analysis showed no changes in white matter but widespread volume decreases in grey matter in several regions exhibiting MD abnormalities. In ALS patients, our results show that subcortical lesions extend beyond the corticospinal tract and are clinically relevant. PMID:17635981

  4. Diffusion tensor imaging and voxel based morphometry study in amyotrophic lateral sclerosis: relationships with motor disability.

    PubMed

    Thivard, Lionel; Pradat, Pierre-François; Lehéricy, Stéphane; Lacomblez, Lucette; Dormont, Didier; Chiras, Jacques; Benali, Habib; Meininger, Vincent

    2007-08-01

    The aim of this study was to investigate the extent of cortical and subcortical lesions in amyotrophic lateral sclerosis (ALS) using, in combination, voxel based diffusion tensor imaging (DTI) and voxel based morphometry (VBM). We included 15 patients with definite or probable ALS and 25 healthy volunteers. Patients were assessed using the revised ALS Functional Rating Scale (ALSFRS-R). In patients, reduced fractional anisotropy was found in bilateral corticospinal tracts, the left insula/ventrolateral premotor cortex, the right parietal cortex and the thalamus, which correlated with the ALSFRS-R. Increased mean diffusivity (MD) was found bilaterally in the motor cortex, the ventrolateral premotor cortex/insula, the hippocampal formations and the right superior temporal gyrus, which did not correlate with the ALSFRS-R. VBM analysis showed no changes in white matter but widespread volume decreases in grey matter in several regions exhibiting MD abnormalities. In ALS patients, our results show that subcortical lesions extend beyond the corticospinal tract and are clinically relevant.

  5. Whole-brain voxel-based morphometry in Kallmann syndrome associated with mirror movements.

    PubMed

    Koenigkam-Santos, M; Santos, A C; Borduqui, T; Versiani, B R; Hallak, J E C; Crippa, J A S; Castro, M

    2008-10-01

    There are 2 main hypotheses concerning the cause of mirror movements (MM) in Kallmann syndrome (KS): abnormal development of the primary motor system, involving the ipsilateral corticospinal tract; and lack of contralateral motor cortex inhibitory mechanisms, mainly through the corpus callosum. The purpose of our study was to determine white and gray matter volume changes in a KS population by using optimized voxel-based morphometry (VBM) and to investigate the relationship between the abnormalities and the presence of MM, addressing the 2 mentioned hypotheses. T1-weighted volumetric images from 21 patients with KS and 16 matched control subjects were analyzed with optimized VBM. Images were segmented and spatially normalized, and these deformation parameters were then applied to the original images before the second segmentation. Patients were divided into groups with and without MM, and a t test statistic was then applied on a voxel-by-voxel basis between the groups and controls to evaluate significant differences. When considering our hypothesis a priori, we found that 2 areas of increased gray matter volume, in the left primary motor and sensorimotor cortex, were demonstrated only in patients with MM, when compared with healthy controls. Regarding white matter alterations, no areas of altered volume involving the corpus callosum or the projection of the corticospinal tract were demonstrated. The VBM study did not show significant white matter changes in patients with KS but showed gray matter alterations in keeping with a hypertrophic response to a deficient pyramidal decussation in patients with MM. In addition, gray matter alterations were observed in patients without MM, which can represent more complex mechanisms determining the presence or absence of this symptom.

  6. Inositol Hexakisphosphate Kinase-3 Regulates the Morphology and Synapse Formation of Cerebellar Purkinje Cells via Spectrin/Adducin

    PubMed Central

    Fu, Chenglai; Xu, Jing; Li, Ruo-Jing; Crawford, Joshua A.; Khan, A. Basit; Ma, Ting Martin; Cha, Jiyoung Y.; Snowman, Adele M.; Pletnikov, Mikhail V.

    2015-01-01

    The inositol hexakisphosphate kinases (IP6Ks) are the principal enzymes that generate inositol pyrophosphates. There are three IP6Ks (IP6K1, 2, and 3). Functions of IP6K1 and IP6K2 have been substantially delineated, but little is known of IP6K3's role in normal physiology, especially in the brain. To elucidate functions of IP6K3, we generated mice with targeted deletion of IP6K3. We demonstrate that IP6K3 is highly concentrated in the brain in cerebellar Purkinje cells. IP6K3 physiologically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are perturbed in IP6K3-null mutants. Consequently, IP6K3 knock-out cerebella manifest abnormalities in Purkinje cell structure and synapse number, and the mutant mice display deficits in motor learning and coordination. Thus, IP6K3 is a major determinant of cytoskeletal disposition and function of cerebellar Purkinje cells. SIGNIFICANCE STATEMENT We identified and cloned a family of three inositol hexakisphosphate kinases (IP6Ks) that generate the inositol pyrophosphates, most notably 5-diphosphoinositol pentakisphosphate (IP7). Of these, IP6K3 has been least characterized. In the present study we generated IP6K3 knock-out mice and show that IP6K3 is highly expressed in cerebellar Purkinje cells. IP6K3-deleted mice display defects of motor learning and coordination. IP6K3-null mice manifest aberrations of Purkinje cells with a diminished number of synapses. IP6K3 interacts with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mice may mediate phenotypic features of the mutant mice. These findings afford molecular/cytoskeletal mechanisms by which the inositol polyphosphate system impacts brain function. PMID:26245967

  7. A Multiple-Plasticity Spiking Neural Network Embedded in a Closed-Loop Control System to Model Cerebellar Pathologies.

    PubMed

    Geminiani, Alice; Casellato, Claudia; Antonietti, Alberto; D'Angelo, Egidio; Pedrocchi, Alessandra

    2018-06-01

    The cerebellum plays a crucial role in sensorimotor control and cerebellar disorders compromise adaptation and learning of motor responses. However, the link between alterations at network level and cerebellar dysfunction is still unclear. In principle, this understanding would benefit of the development of an artificial system embedding the salient neuronal and plastic properties of the cerebellum and operating in closed-loop. To this aim, we have exploited a realistic spiking computational model of the cerebellum to analyze the network correlates of cerebellar impairment. The model was modified to reproduce three different damages of the cerebellar cortex: (i) a loss of the main output neurons (Purkinje Cells), (ii) a lesion to the main cerebellar afferents (Mossy Fibers), and (iii) a damage to a major mechanism of synaptic plasticity (Long Term Depression). The modified network models were challenged with an Eye-Blink Classical Conditioning test, a standard learning paradigm used to evaluate cerebellar impairment, in which the outcome was compared to reference results obtained in human or animal experiments. In all cases, the model reproduced the partial and delayed conditioning typical of the pathologies, indicating that an intact cerebellar cortex functionality is required to accelerate learning by transferring acquired information to the cerebellar nuclei. Interestingly, depending on the type of lesion, the redistribution of synaptic plasticity and response timing varied greatly generating specific adaptation patterns. Thus, not only the present work extends the generalization capabilities of the cerebellar spiking model to pathological cases, but also predicts how changes at the neuronal level are distributed across the network, making it usable to infer cerebellar circuit alterations occurring in cerebellar pathologies.

  8. Hydranencephaly and cerebellar hypoplasia in two kittens attributed to intrauterine parvovirus infection.

    PubMed

    Sharp, N J; Davis, B J; Guy, J S; Cullen, J M; Steingold, S F; Kornegay, J N

    1999-07-01

    Six weeks after vaccination with modified live feline parvovirus vaccine, a cat gave birth to five kittens, three of which died soon afterwards. The remaining two kittens (A and B) survived, but at 8 weeks of age were unable to walk and showed abnormal behaviour, with lack of menace and oculovestibular responses, and severe dysmetria. These signs suggested multifocal disease associated with the cerebrum and cerebellum. Magnetic resonance imaging demonstrated severe bilateral (kitten A) or unilateral (kitten B) hydrocephalus or hydranencephaly, combined with cerebellar agenesis (kitten A) or severe hypoplasia (kitten B). Hydranencephaly was confirmed histopathologically in both kittens. Parvovirus was isolated from the kidney of one kitten. Parvoviral DNA was amplified by the polymerase chain reaction (PCR) from paraffin wax-embedded brain of both kittens. The severe malformations observed in these kittens presumably resulted from an in-utero parvovirus infection, possibly due to vaccination, that occurred late in the first, or early in the second, trimester of pregnancy. Copyright 1999 W.B. Saunders Company Ltd.

  9. Humor, laughter, and the cerebellum: insights from patients with acute cerebellar stroke.

    PubMed

    Frank, B; Andrzejewski, K; Göricke, S; Wondzinski, E; Siebler, M; Wild, B; Timmann, D

    2013-12-01

    Extent of cerebellar involvement in cognition and emotion is still a topic of ongoing research. In particular, the cerebellar role in humor processing and control of laughter is not well known. A hypermetric dysregulation of affective behavior has been assumed in cerebellar damage. Thus, we aimed at investigating humor comprehension and appreciation as well as the expression of laughter in 21 patients in the acute or subacute state after stroke restricted to the cerebellum, and in the same number of matched healthy control subjects. Patients with acute and subacute cerebellar damage showed preserved comprehension and appreciation of humor using a validated humor test evaluating comprehension, funniness and aversiveness of cartoons ("3WD Humor Test"). Additionally, there was no difference when compared to healthy controls in the number and intensity of facial reactions and laughter while observing jokes, humorous cartoons, or video sketches measured by the Facial Action Coding System. However, as depression scores were significantly increased in patients with cerebellar stroke, a concealing effect of accompanying depression cannot be excluded. Current findings add to descriptions in the literature that cognitive or affective disorders in patients with lesions restricted to the cerebellum, even in the acute state after damage, are frequently mild and might only be present in more sensitive or specific tests.

  10. Enhancing the Temporal Complexity of Distributed Brain Networks with Patterned Cerebellar Stimulation

    PubMed Central

    Farzan, Faranak; Pascual-Leone, Alvaro; Schmahmann, Jeremy D.; Halko, Mark

    2016-01-01

    Growing evidence suggests that sensory, motor, cognitive and affective processes map onto specific, distributed neural networks. Cerebellar subregions are part of these networks, but how the cerebellum is involved in this wide range of brain functions remains poorly understood. It is postulated that the cerebellum contributes a basic role in brain functions, helping to shape the complexity of brain temporal dynamics. We therefore hypothesized that stimulating cerebellar nodes integrated in different networks should have the same impact on the temporal complexity of cortical signals. In healthy humans, we applied intermittent theta burst stimulation (iTBS) to the vermis lobule VII or right lateral cerebellar Crus I/II, subregions that prominently couple to the dorsal-attention/fronto-parietal and default-mode networks, respectively. Cerebellar iTBS increased the complexity of brain signals across multiple time scales in a network-specific manner identified through electroencephalography (EEG). We also demonstrated a region-specific shift in power of cortical oscillations towards higher frequencies consistent with the natural frequencies of targeted cortical areas. Our findings provide a novel mechanism and evidence by which the cerebellum contributes to multiple brain functions: specific cerebellar subregions control the temporal dynamics of the networks they are engaged in. PMID:27009405

  11. GABAergic neurons in cerebellar interposed nucleus modulate cellular and humoral immunity via hypothalamic and sympathetic pathways.

    PubMed

    Lu, Jian-Hua; Wang, Xiao-Qin; Huang, Yan; Qiu, Yi-Hua; Peng, Yu-Ping

    2015-06-15

    Our previous work has shown that cerebellar interposed nucleus (IN) modulates immune function. Herein, we reveal mechanism underlying the immunomodulation. Treatment of bilateral cerebellar IN of rats with 3-mercaptopropionic acid (3-MP), a glutamic acid decarboxylase antagonist that reduces γ-aminobutyric acid (GABA) synthesis, enhanced cellular and humoral immune responses to bovine serum albumin, whereas injection of vigabatrin, a GABA-transaminase inhibitor that inhibits GABA degradation, in bilateral cerebellar IN attenuated the immune responses. The 3-MP or vigabatrin administrations in the cerebellar IN decreased or increased hypothalamic GABA content and lymphoid tissues' norepinephrine content, respectively, but did not alter adrenocortical or thyroid hormone levels in serum. In addition, a direct GABAergic projection from cerebellar IN to hypothalamus was found. These findings suggest that GABAergic neurons in cerebellar IN regulate immune system via hypothalamic and sympathetic pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Quantification and Comparison of Anti-Fibrotic Therapies by Polarized SRM and SHG-Based Morphometry in Rat UUO Model

    PubMed Central

    Weldon, Steve M.; Matera, Damian; Lee, ChungWein; Yang, Haichun; Fryer, Ryan M.; Fogo, Agnes B.; Reinhart, Glenn A.

    2016-01-01

    Renal interstitial fibrosis (IF) is an important pathologic manifestation of disease progression in a variety of chronic kidney diseases (CKD). However, the quantitative and reproducible analysis of IF remains a challenge, especially in experimental animal models of progressive IF. In this study, we compare traditional polarized Sirius Red morphometry (SRM) to novel Second Harmonic Generation (SHG)-based morphometry of unstained tissues for quantitative analysis of IF in the rat 5 day unilateral ureteral obstruction (UUO) model. To validate the specificity of SHG for detecting fibrillar collagen components in IF, co-localization studies for collagens type I, III, and IV were performed using IHC. In addition, we examined the correlation, dynamic range, sensitivity, and ability of polarized SRM and SHG-based morphometry to detect an anti-fibrotic effect of three different treatment regimens. Comparisons were made across three separate studies in which animals were treated with three mechanistically distinct pharmacologic agents: enalapril (ENA, 15, 30, 60 mg/kg), mycophenolate mofetil (MMF, 2, 20 mg/kg) or the connective tissue growth factor (CTGF) neutralizing antibody, EX75606 (1, 3, 10 mg/kg). Our results demonstrate a strong co-localization of the SHG signal with fibrillar collagens I and III but not non-fibrillar collagen IV. Quantitative IF, calculated as percent cortical area of fibrosis, demonstrated similar response profile for both polarized SRM and SHG-based morphometry. The two methodologies exhibited a strong correlation across all three pharmacology studies (r2 = 0.89–0.96). However, compared with polarized SRM, SHG-based morphometry delivered a greater dynamic range and absolute magnitude of reduction of IF after treatment. In summary, we demonstrate that SHG-based morphometry in unstained kidney tissues is comparable to polarized SRM for quantitation of fibrillar collagens, but with an enhanced sensitivity to detect treatment-induced reductions in

  13. Beta-gamma burst stimulations of the inferior olive induce high-frequency oscillations in the deep cerebellar nuclei.

    PubMed

    Cheron, Julian; Cheron, Guy

    2018-02-20

    The cerebellum displays various sorts of rhythmic activities covering both low- and high-frequency oscillations. These cerebellar high-frequency oscillations were observed in the cerebellar cortex. Here, we hypothesised that not only is the cerebellar cortex a generator of high-frequency oscillations but also that the deep cerebellar nuclei may also play a similar role. Thus, we analysed local field potentials and single-unit activities in the deep cerebellar nuclei before, during and after electric stimulation in the inferior olive of awake mice. A high-frequency oscillation of 350 Hz triggered by the stimulation of the inferior olive, within the beta-gamma range, was observed in the deep cerebellar nuclei. The amplitude and frequency of the oscillation were independent of the frequency of stimulation. This oscillation emerged during the period of stimulation and persisted after the end of the stimulation. The oscillation coincided with the inhibition of deep cerebellar neurons. As the inhibition of the deep cerebellar nuclei is related to inhibitory inputs from Purkinje cells, we speculate that the oscillation represents the unmasking of the synchronous activation of another subtype of deep cerebellar neuronal subtype, devoid of GABA receptors and under the direct control of the climbing fibres from the inferior olive. Still, the mechanism sustaining this oscillation remains to be deciphered. Our study sheds new light on the role of the olivo-cerebellar loop as the final output control of the intercerebellar circuitry. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Surface-based atlases of cerebellar cortex in the human, macaque, and mouse.

    PubMed

    Van Essen, David C

    2002-12-01

    This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

  15. Surface-based atlases of cerebellar cortex in the human, macaque, and mouse

    NASA Technical Reports Server (NTRS)

    Van Essen, David C.

    2002-01-01

    This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

  16. Correlation Between Cerebellar Retraction and Hearing Loss After Microvascular Decompression for Hemifacial Spasm: A Prospective Study.

    PubMed

    Li, Ning; Zhao, Wei-Guo; Pu, Chun-Hua; Yang, Wen-Lei

    2017-06-01

    This study prospectively investigated the relationship between cerebellar retraction factors measured on preoperative magnetic resonance and the development of postoperative hearing loss and evaluated their potential role in predicting the possibility of hearing loss after microvascular decompression (MVD) for hemifacial spasm (HFS). The study included 110 patients clinically diagnosed with primary HFS who underwent MVD in our department. The cerebellar retraction factors were quantitatively measured on preoperative magnetic resonance. Associations of cerebellar retraction and other risk factors with postoperative hearing loss were analyzed. Eleven patients (10%) developed nonserviceable hearing loss after MVD. Compared with the group without hearing loss, the cerebellar retraction distance and depth of the group with hearing loss were significantly greater (P < 0.05). Multivariate logistic regression analysis showed that greater cerebellar retraction depth was significantly associated with the higher incidence of postoperative hearing loss (P < 0.05). The results in this study strongly suggested the correlation between the cerebellar retraction depth and the possibility of hearing loss after MVD for HFS. In addition, cerebellar retraction depth could be considered as a useful tool to predict the risk of post-MVD hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A multicohort, longitudinal study of cerebellar development in attention deficit hyperactivity disorder.

    PubMed

    Shaw, Philip; Ishii-Takahashi, Ayaka; Park, Min Tae; Devenyi, Gabriel A; Zibman, Chava; Kasparek, Steven; Sudre, Gustavo; Mangalmurti, Aman; Hoogman, Martine; Tiemeier, Henning; von Polier, Georg; Shook, Devon; Muetzel, Ryan; Chakravarty, M Mallar; Konrad, Kerstin; Durston, Sarah; White, Tonya

    2018-04-25

    The cerebellum supports many cognitive functions disrupted in attention deficit hyperactivity disorder (ADHD). Prior neuroanatomic studies have been often limited by small sample sizes, inconsistent findings, and a reliance on cross-sectional data, limiting inferences about cerebellar development. Here, we conduct a multicohort study using longitudinal data, to characterize cerebellar development. Growth trajectories of the cerebellar vermis, hemispheres and white matter were estimated using piecewise linear regression from 1,656 youth; of whom 63% had longitudinal data, totaling 2,914 scans. Four cohorts participated, all contained childhood data (age 4-12 years); two had adolescent data (12-25 years). Growth parameters were combined using random-effects meta-analysis. Diagnostic differences in growth were confined to the corpus medullare (cerebellar white matter). Here, the ADHD group showed slower growth in early childhood compared to the typically developing group (left corpus medullare z = 2.49, p = .01; right z = 2.03, p = .04). This reversed in late childhood, with faster growth in ADHD in the left corpus medullare (z = 2.06, p = .04). Findings held when gender, intelligence, comorbidity, and psychostimulant medication were considered. Across four independent cohorts, containing predominately longitudinal data, we found diagnostic differences in the growth of cerebellar white matter. In ADHD, slower white matter growth in early childhood was followed by faster growth in late childhood. The findings are consistent with the concept of ADHD as a disorder of the brain's structural connections, formed partly by developing cortico-cerebellar white matter tracts. © 2018 Association for Child and Adolescent Mental Health.

  18. Modality specific cerebro-cerebellar activations in verbal working memory: an fMRI study.

    PubMed

    Kirschen, Matthew P; Chen, S H Annabel; Desmond, John E

    2010-01-01

    Verbal working memory (VWM) engages frontal and temporal/parietal circuits subserving the phonological loop, as well as, superior and inferior cerebellar regions which have projections from these neocortical areas. Different cerebro-cerebellar circuits may be engaged for integrating aurally- and visually-presented information for VWM. The present fMRI study investigated load (2, 4, or 6 letters) and modality (auditory and visual) dependent cerebro-cerebellar VWM activation using a Sternberg task. FMRI revealed modality-independent activations in left frontal (BA 6/9/44), insular, cingulate (BA 32), and bilateral inferior parietal/supramarginal (BA 40) regions, as well as in bilateral superior (HVI) and right inferior (HVIII) cerebellar regions. Visual presentation evoked prominent activations in right superior (HVI/CrusI) cerebellum, bilateral occipital (BA19) and left parietal (BA7/40) cortex while auditory presentation showed robust activations predominantly in bilateral temporal regions (BA21/22). In the cerebellum, we noted a visual to auditory emphasis of function progressing from superior to inferior and from lateral to medial regions. These results extend our previous findings of fMRI activation in cerebro-cerebellar networks during VWM, and demonstrate both modality dependent commonalities and differences in activations with increasing memory load.

  19. Specific cerebellar activation during Braille reading in blind subjects.

    PubMed

    Gizewski, Elke R; Timmann, Dagmar; Forsting, Michael

    2004-07-01

    The traditional view that the cerebellum is involved only in the control of movements has been changed recently. It has been suggested that the human cerebellum is involved in cognition and language. Likewise, besides cortical activity in sensorimotor and visual areas, an increased global activation of the cerebellum has been revealed during Braille reading in blind subjects. Our purpose was to investigate whether there is cerebellar activation during Braille reading by blind subjects other than sensorimotor activation related to finger movements. Early blind and normal sighted subjects were studied with functional magnetic resonance imaging (fMRI) during Braille reading, tactile discrimination of nonsense dots, dots forming symbols, and finger tapping. The experiments were done in block design. Echo planar imaging sequences were carried out on a 1.5-T MR scanner. All blind individuals reading Braille showed robust activation of the posterior and lateral aspects of cerebellar hemispheral lobules Crus I bilaterally but more predominately on the right side. Additionally, activation was present in the medial cerebellum within lobules IV, V, and VIIIA, predominantly on the right. Discriminating nonsense dots did not reveal any activation of Crus I, but did reveal activation within the medial part of lobules IV, V, and VIIIA, predominately on the right. Analysis of sighted subjects during reading of printed text revealed activation of the posterolateral cerebellar hemisphere in Crus I bilaterally, predominantly on the right. Tactile analysis of dots representing symbols revealed an activation in lobules IV and VIII and in right Crus II but not in Crus I. In conclusion, parts of cerebellar activation during Braille reading in blind subjects (i.e., within lobules IV, V, and VIII) overlap with the known hand representation within the cerebellum and are likely related to the sensorimotor part of the task. Cerebellar activation during Braille reading within bilateral Crus I

  20. Automated MRI Cerebellar Size Measurements Using Active Appearance Modeling

    PubMed Central

    Price, Mathew; Cardenas, Valerie A.; Fein, George

    2014-01-01

    Although the human cerebellum has been increasingly identified as an important hub that shows potential for helping in the diagnosis of a large spectrum of disorders, such as alcoholism, autism, and fetal alcohol spectrum disorder, the high costs associated with manual segmentation, and low availability of reliable automated cerebellar segmentation tools, has resulted in a limited focus on cerebellar measurement in human neuroimaging studies. We present here the CATK (Cerebellar Analysis Toolkit), which is based on the Bayesian framework implemented in FMRIB’s FIRST. This approach involves training Active Appearance Models (AAM) using hand-delineated examples. CATK can currently delineate the cerebellar hemispheres and three vermal groups (lobules I–V, VI–VII, and VIII–X). Linear registration with the low-resolution MNI152 template is used to provide initial alignment, and Point Distribution Models (PDM) are parameterized using stellar sampling. The Bayesian approach models the relationship between shape and texture through computation of conditionals in the training set. Our method varies from the FIRST framework in that initial fitting is driven by 1D intensity profile matching, and the conditional likelihood function is subsequently used to refine fitting. The method was developed using T1-weighted images from 63 subjects that were imaged and manually labeled: 43 subjects were scanned once and were used for training models, and 20 subjects were imaged twice (with manual labeling applied to both runs) and used to assess reliability and validity. Intraclass correlation analysis shows that CATK is highly reliable (average test-retest ICCs of 0.96), and offers excellent agreement with the gold standard (average validity ICC of 0.87 against manual labels). Comparisons against an alternative atlas-based approach, SUIT (Spatially Unbiased Infratentorial Template), that registers images with a high-resolution template of the cerebellum, show that our AAM

  1. DNA fragmentation and sperm head morphometry in cat epididymal spermatozoa.

    PubMed

    Vernocchi, Valentina; Morselli, Maria Giorgia; Lange Consiglio, Anna; Faustini, Massimo; Luvoni, Gaia Cecilia

    2014-10-15

    Sperm DNA fragmentation is an important parameter to assess sperm quality and can be a putative fertility predictor. Because the sperm head consists almost entirely of DNA, subtle differences in sperm head morphometry might be related to DNA status. Several techniques are available to analyze sperm DNA fragmentation, but they are labor-intensive and require expensive instrumentations. Recently, a kit (Sperm-Halomax) based on the sperm chromatin dispersion test and developed for spermatozoa of different species, but not for cat spermatozoa, became commercially available. The first aim of the present study was to verify the suitability of Sperm-Halomax assay, specifically developed for canine semen, for the evaluation of DNA fragmentation of epididymal cat spermatozoa. For this purpose, DNA fragmentation indexes (DFIs) obtained with Sperm-Halomax and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) were compared. The second aim was to investigate whether a correlation between DNA status, sperm head morphology, and morphometry assessed by computer-assisted semen analysis exists in cat epididymal spermatozoa. No differences were observed in DFIs obtained with Sperm-Halomax and TUNEL. This result indicates that Sperm-Halomax assay provides a reliable evaluation of DNA fragmentation of epididymal feline spermatozoa. The DFI seems to be independent from all the measured variables of sperm head morphology and morphometry. Thus, the evaluation of the DNA status of spermatozoa could effectively contribute to the completion of the standard analysis of fresh or frozen semen used in assisted reproductive technologies. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Bilaterally Abnormal Head Impulse Tests Indicate a Large Cerebellopontine Angle Tumor.

    PubMed

    Kim, Hyo Jung; Park, Seong Ho; Kim, Ji Soo; Koo, Ja Won; Kim, Chae Yong; Kim, Young Hoon; Han, Jung Ho

    2016-01-01

    Tumors involving the cerebellopontine angle (CPA) pose a diagnostic challenge due to their diverse manifestations. Head impulse tests (HITs) have been used to evaluate vestibular function, but few studies have explored the head impulse gain of the vestibulo-ocular reflex (VOR) in patients with a vestibular schwannoma. This study tested whether the head impulse gain of the VOR is an indicator of the size of a unilateral CPA tumor. Twenty-eight patients (21 women; age=64±12 years, mean±SD) with a unilateral CPA tumor underwent a recording of the HITs using a magnetic search coil technique. Patients were classified into non-compressing (T1-T3) and compressing (T4) groups according to the Hannover classification. Most (23/28, 82%) of the patients showed abnormal HITs for the semicircular canals on the lesion side. The bilateral abnormality in HITs was more common in the compressing group than the non-compressing group (80% vs. 8%, Pearson's chi-square test: p<0.001). The tumor size was inversely correlated with the head impulse gain of the VOR in either direction. Bilaterally abnormal HITs indicate that a patient has a large unilateral CPA tumor. The abnormal HITs in the contralesional direction may be explained either by adaptation or by compression and resultant dysfunction of the cerebellar and brainstem structures. The serial evaluation of HITs may provide information on tumor growth, and thereby reduce the number of costly brain scans required when following up patients with CPA tumors.

  3. Mutant ataxin1 disrupts cerebellar development in spinocerebellar ataxia type 1.

    PubMed

    Edamakanti, Chandrakanth Reddy; Do, Jeehaeh; Didonna, Alessandro; Martina, Marco; Opal, Puneet

    2018-06-01

    Spinocerebellar ataxia type 1 (SCA1) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the protein ATXN1, which is involved in transcriptional regulation. Although symptoms appear relatively late in life, primarily from cerebellar dysfunction, pathogenesis begins early, with transcriptional changes detectable as early as a week after birth in SCA1-knockin mice. Given the importance of this postnatal period for cerebellar development, we asked whether this region might be developmentally altered by mutant ATXN1. We found that expanded ATXN1 stimulates the proliferation of postnatal cerebellar stem cells in SCA1 mice. These hyperproliferating stem cells tended to differentiate into GABAergic inhibitory interneurons rather than astrocytes; this significantly increased the GABAergic inhibitory interneuron synaptic connections, disrupting cerebellar Purkinje cell function in a non-cell autonomous manner. We confirmed the increased basket cell-Purkinje cell connectivity in human SCA1 patients. Mutant ATXN1 thus alters the neural circuitry of the developing cerebellum, setting the stage for the later vulnerability of Purkinje cells to SCA1. We propose that other late-onset degenerative diseases may also be rooted in subtle developmental derailments.

  4. Stars and Stripes in the Cerebellar Cortex: A Voltage Sensitive Dye Study

    PubMed Central

    Rokni, Dan; Llinas, Rodolfo; Yarom, Yosef

    2007-01-01

    The lattice-like structure of the cerebellar cortex and its anatomical organization in two perpendicular axes provided the foundations for many theories of cerebellar function. However, the functional organization does not always match the anatomical organization. Thus direct measurement of the functional organization is central to our understanding of cerebellar processing. Here we use voltage sensitive dye imaging in the isolated cerebellar preparation to characterize the spatio-temporal organization of the climbing and mossy fiber (MF) inputs to the cerebellar cortex. Spatial and temporal parameters were used to develop reliable criteria to distinguish climbing fiber (CF) responses from MF responses. CF activation excited postsynaptic neurons along a parasagittal cortical band. These responses were composed of slow (∼25 ms), monophasic depolarizing signals. Neither the duration nor the spatial distribution of CF responses were affected by inhibition. Activation of MF generated responses that were organized in radial patches, and were composed of a fast (∼5 ms) depolarizing phase followed by a prolonged (∼100 ms) negative wave. Application of a GABAA blocker eliminated the hyperpolarizing phase and prolonged the depolarizing phase, but did not affect the spatial distribution of the response, thus suggesting that it is not the inhibitory system that is responsible for the inability of the MF input to generate beams of activity that propagate along the parallel fiber system. PMID:18958242

  5. Adaptive robotic control driven by a versatile spiking cerebellar network.

    PubMed

    Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A; Carrillo, Richard R; Luque, Niceto R; Ros, Eduardo; Pedrocchi, Alessandra; D'Angelo, Egidio

    2014-01-01

    The cerebellum is involved in a large number of different neural processes, especially in associative learning and in fine motor control. To develop a comprehensive theory of sensorimotor learning and control, it is crucial to determine the neural basis of coding and plasticity embedded into the cerebellar neural circuit and how they are translated into behavioral outcomes in learning paradigms. Learning has to be inferred from the interaction of an embodied system with its real environment, and the same cerebellar principles derived from cell physiology have to be able to drive a variety of tasks of different nature, calling for complex timing and movement patterns. We have coupled a realistic cerebellar spiking neural network (SNN) with a real robot and challenged it in multiple diverse sensorimotor tasks. Encoding and decoding strategies based on neuronal firing rates were applied. Adaptive motor control protocols with acquisition and extinction phases have been designed and tested, including an associative Pavlovian task (Eye blinking classical conditioning), a vestibulo-ocular task and a perturbed arm reaching task operating in closed-loop. The SNN processed in real-time mossy fiber inputs as arbitrary contextual signals, irrespective of whether they conveyed a tone, a vestibular stimulus or the position of a limb. A bidirectional long-term plasticity rule implemented at parallel fibers-Purkinje cell synapses modulated the output activity in the deep cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain of the motor responses by tuning its output discharge. It succeeded in reproducing how human biological systems acquire, extinguish and express knowledge of a noisy and changing world. By varying stimuli and perturbations patterns, real-time control robustness and generalizability were validated. The implicit spiking dynamics of the cerebellar model fulfill timing, prediction and learning functions.

  6. Segregated Fronto-Cerebellar Circuits Revealed by Intrinsic Functional Connectivity

    PubMed Central

    Buckner, Randy L.

    2009-01-01

    Multiple, segregated fronto-cerebellar circuits have been characterized in nonhuman primates using transneuronal tracing techniques including those that target prefrontal areas. Here, we used functional connectivity MRI (fcMRI) in humans (n = 40) to identify 4 topographically distinct fronto-cerebellar circuits that target 1) motor cortex, 2) dorsolateral prefrontal cortex, 3) medial prefrontal cortex, and 4) anterior prefrontal cortex. All 4 circuits were replicated and dissociated in an independent data set (n = 40). Direct comparison of right- and left-seeded frontal regions revealed contralateral lateralization in the cerebellum for each of the segregated circuits. The presence of circuits that involve prefrontal regions confirms that the cerebellum participates in networks important to cognition including a specific fronto-cerebellar circuit that interacts with the default network. Overall, the extent of the cerebellum associated with prefrontal cortex included a large portion of the posterior hemispheres consistent with a prominent role of the cerebellum in nonmotor functions. We conclude by providing a provisional map of the topography of the cerebellum based on functional correlations with the frontal cortex. PMID:19592571

  7. Neuromagnetic Cerebellar Activity Entrains to the Kinematics of Executed Finger Movements.

    PubMed

    Marty, Brice; Wens, V; Bourguignon, M; Naeije, G; Goldman, S; Jousmäki, V; De Tiège, X

    2018-05-03

    This magnetoencephalography (MEG) study aims at characterizing the coupling between cerebellar activity and the kinematics of repetitive self-paced finger movements. Neuromagnetic signals were recorded in 11 right-handed healthy adults while they performed repetitive flexion-extensions of right-hand fingers at three different movement rates: slow (~ 1 Hz), medium (~ 2 Hz), and fast (~ 3 Hz). Right index finger acceleration was monitored with an accelerometer. Coherence analysis was used to index the coupling between right index finger acceleration and neuromagnetic signals. Dynamic imaging of coherent sources was used to locate coherent sources. Coupling directionality between primary sensorimotor (SM1), cerebellar, and accelerometer signals was assessed with renormalized partial directed coherence. Permutation-based statistics coupled with maximum statistic over the entire brain volume or restricted to the cerebellum were used. At all movement rates, maximum coherence peaked at SM1 cortex contralateral to finger movements at movement frequency (F0) and its first harmonic (F1). Significant (statistics restricted to the cerebellum) coherence consistently peaked at the right posterior lobe of the cerebellum at F0 with no influence of movement rate. Coupling between Acc and cerebellar signals was significantly stronger in the afferent than in the efferent direction with no effective contribution of cortico-cerebellar or cerebello-cortical pathways. This study demonstrates the existence of significant coupling between finger movement kinematics and neuromagnetic activity at the posterior cerebellar lobe ipsilateral to finger movement at F0. This coupling is mainly driven by spinocerebellar, presumably proprioceptive, afferences.

  8. Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia.

    PubMed

    van der Velde, Jorien; Gromann, Paula M; Swart, Marte; de Haan, Lieuwe; Wiersma, Durk; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André

    2015-05-01

    Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.

  9. Tensor-based morphometry of cannabis use on brain structure in individuals at elevated genetic risk of schizophrenia.

    PubMed

    Welch, K A; Moorhead, T W; McIntosh, A M; Owens, D G C; Johnstone, E C; Lawrie, S M

    2013-10-01

    Schizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis. Magnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n=23) and not exposed to cannabis (n=32) in the intervening period was compared using tensor-based morphometry (TBM). Cannabis exposure was associated with significantly greater loss of right anterior hippocampal (pcorrected=0.029, t=3.88) and left superior frontal lobe GM (pcorrected=0.026, t=4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval. Using an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

  10. Purkinje Cell Activity in the Cerebellar Anterior Lobe after Rabbit Eyeblink Conditioning

    ERIC Educational Resources Information Center

    Green, John T.; Steinmetz, Joseph E.

    2005-01-01

    The cerebellar anterior lobe may play a critical role in the execution and proper timing of learned responses. The current study was designed to monitor Purkinje cell activity in the rabbit cerebellar anterior lobe after eyeblink conditioning, and to assess whether Purkinje cells in recording locations may project to the interpositus nucleus.…

  11. The Cerebellar Deficit Hypothesis and Dyslexic Tendencies in a Non-Clinical Sample

    ERIC Educational Resources Information Center

    Brookes, Rebecca L.; Stirling, John

    2005-01-01

    In order to assess the relationship between cerebellar deficits and dyslexic tendencies in a non-clinical sample, 27 primary school children aged 8-9 completed a cerebellar soft signs battery and were additionally assessed for reading age, sequential memory, picture arrangement and knowledge of common sequences. An average measure of the soft…

  12. Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

    PubMed Central

    Alston, Robert; Wright, Neville B; Chandler, Kate; Bonney, Denise; Wynn, Robert F; Will, Andrew M; Punekar, Maqsood; Loughran, Sean; Kilday, John-Paul; Schindler, Detlev; Patel, Leena; Meyer, Stefan

    2015-01-01

    Objective: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. Methods: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. Results: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). Conclusion: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. Advances in knowledge: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality. PMID:26369989

  13. Increased Cerebellar Functional Connectivity With the Default-Mode Network in Unaffected Siblings of Schizophrenia Patients at Rest

    PubMed Central

    Guo, Wenbin; Liu, Feng; Zhang, Zhikun; Liu, Guiying; Liu, Jianrong; Yu, Liuyu; Xiao, Changqing; Zhao, Jingping

    2015-01-01

    The default-mode network (DMN) is vital in the neurobiology of schizophrenia, and the cerebellum participates in the high-order cognitive network such as the DMN. However, the specific contribution of the cerebellum to the DMN abnormalities remains unclear in unaffected siblings of schizophrenia patients. Forty-six unaffected siblings of schizophrenia patients and 46 healthy controls were recruited for a resting-state scan. The images were analyzed using the functional connectivity (FC) method. The siblings showed significantly increased FCs between the left Crus I and the left superior medial prefrontal cortex (MPFC), as well as between the lobule IX and the bilateral MPFC (orbital part) and right superior MPFC compared with the controls. No significantly decreased FC was observed in the siblings relative to the controls. The analyses were replicated in 49 first-episode, drug-naive patients with schizophrenia, and the results showed that the siblings and the patients shared increased FCs between the left Crus I and the left superior MPFC, as well as between the lobule IX and the left MPFC (orbital part) compared with the controls. These findings suggest that increased cerebellar-DMN connectivities emerge earlier than illness onset, which highlight the contribution of the cerebellum to the DMN alterations in unaffected siblings. The shared increased cerebellar-DMN connectivities between the patients and the siblings may be used as candidate endophenotypes for schizophrenia. PMID:25956897

  14. The Contribution of Brainstem and Cerebellar Pathways to Auditory Recognition

    PubMed Central

    McLachlan, Neil M.; Wilson, Sarah J.

    2017-01-01

    The cerebellum has been known to play an important role in motor functions for many years. More recently its role has been expanded to include a range of cognitive and sensory-motor processes, and substantial neuroimaging and clinical evidence now points to cerebellar involvement in most auditory processing tasks. In particular, an increase in the size of the cerebellum over recent human evolution has been attributed in part to the development of speech. Despite this, the auditory cognition literature has largely overlooked afferent auditory connections to the cerebellum that have been implicated in acoustically conditioned reflexes in animals, and could subserve speech and other auditory processing in humans. This review expands our understanding of auditory processing by incorporating cerebellar pathways into the anatomy and functions of the human auditory system. We reason that plasticity in the cerebellar pathways underpins implicit learning of spectrotemporal information necessary for sound and speech recognition. Once learnt, this information automatically recognizes incoming auditory signals and predicts likely subsequent information based on previous experience. Since sound recognition processes involving the brainstem and cerebellum initiate early in auditory processing, learnt information stored in cerebellar memory templates could then support a range of auditory processing functions such as streaming, habituation, the integration of auditory feature information such as pitch, and the recognition of vocal communications. PMID:28373850

  15. Genetics Home Reference: lissencephaly with cerebellar hypoplasia

    MedlinePlus

    ... on PubMed or Free article on PubMed Central Ross ME, Swanson K, Dobyns WB. Lissencephaly with cerebellar ... AA, Abdel-Salam G, Koeller HB, Ilkin Y, Ross ME, Dobyns WB, Gleeson JG. Identification of a ...

  16. Evidence for distinct cognitive deficits after focal cerebellar lesions.

    PubMed

    Gottwald, B; Wilde, B; Mihajlovic, Z; Mehdorn, H M

    2004-11-01

    Anatomical evidence and lesion studies, as well as functional magnetic resonance imaging (fMRI) studies, indicate that the cerebellum contributes to higher cognitive functions. Cerebellar posterior lateral regions seem to be relevant for cognition, while vermal lesions seem to be associated with changes in affect. However, the results remain controversial. Deficits of patients are sometimes still attributed to motor impairment. We present data from a detailed neuropsychological examination of 21 patients with cerebellar lesions due to tumour or haematoma, and 21 controls matched for age, sex, and years of education. Patients showed deficits in executive function, and in attentional processes such as working memory and divided attention. Further analysis revealed that patients with right-sided lesions were in general more impaired than those with left-sided lesions. Those hypotheses that suggest that lesions of the right cerebellar hemisphere lead to verbal deficits, while those of the left lead to non-verbal deficits, have in part been confirmed. The generally greater impairment of those patients with a right-sided lesion has been interpreted as resulting from the connection of the right cerebellum to the left cerebral hemisphere, which is dominant for language functions and crucial for right hand movements. Motor impairment was correlated with less than half of the cognitive measures, with no stronger tendency for correlation with cognitive tests that require motor responses discernible. The results are discussed on the basis of an assumption that the cerebellum has a predicting and preparing function, indicating that cerebellar lesions lead to a "dysmetria of thought."

  17. Relationships between regional cerebellar volume and sensorimotor and cognitive function in young and older adults

    PubMed Central

    Bernard, Jessica A.; Seidler, Rachael D.

    2013-01-01

    The cerebellum has been implicated in both sensorimotor and cognitive function, but is known to undergo volumetric declines with advanced age. Individual differences in regional cerebellar volume may therefore provide insight into performance variability across the lifespan, as has been shown with other brain structures and behaviors. Here, we investigated whether there are regional age differences in cerebellar volume in young and older adults, and whether these volumes explain, in part, individual differences in sensorimotor and cognitive task performance. We found that older adults had smaller cerebellar volume than young adults; specifically, lobules in the anterior cerebellum were more impacted by age. Multiple regression analyses for both age groups revealed associations between sensorimotor task performance in several domains (balance, choice reaction time, and timing) and regional cerebellar volume. There were also relationships with working memory, but none with measures of general cognitive or executive function. Follow-up analyses revealed several differential relationships with age between regional volume and sensorimotor performance. These relationships were predominantly selective to cerebellar regions that have been implicated in cognitive functions. Therefore, it may be the cognitive aspects of sensorimotor task performance that are best explained by individual differences in regional cerebellar volumes. In sum, our results demonstrate the importance of regional cerebellar volume with respect to both sensorimotor and cognitive performance, and we provide additional insight into the role of the cerebellum in age-related performance declines. PMID:23625382

  18. Modulation of error-sensitivity during a prism adaptation task in people with cerebellar degeneration

    PubMed Central

    Shadmehr, Reza; Ohminami, Shinya; Tsutsumi, Ryosuke; Shirota, Yuichiro; Shimizu, Takahiro; Tanaka, Nobuyuki; Terao, Yasuo; Tsuji, Shoji; Ugawa, Yoshikazu; Uchimura, Motoaki; Inoue, Masato; Kitazawa, Shigeru

    2015-01-01

    Cerebellar damage can profoundly impair human motor adaptation. For example, if reaching movements are perturbed abruptly, cerebellar damage impairs the ability to learn from the perturbation-induced errors. Interestingly, if the perturbation is imposed gradually over many trials, people with cerebellar damage may exhibit improved adaptation. However, this result is controversial, since the differential effects of gradual vs. abrupt protocols have not been observed in all studies. To examine this question, we recruited patients with pure cerebellar ataxia due to cerebellar cortical atrophy (n = 13) and asked them to reach to a target while viewing the scene through wedge prisms. The prisms were computer controlled, making it possible to impose the full perturbation abruptly in one trial, or build up the perturbation gradually over many trials. To control visual feedback, we employed shutter glasses that removed visual feedback during the reach, allowing us to measure trial-by-trial learning from error (termed error-sensitivity), and trial-by-trial decay of motor memory (termed forgetting). We found that the patients benefited significantly from the gradual protocol, improving their performance with respect to the abrupt protocol by exhibiting smaller errors during the exposure block, and producing larger aftereffects during the postexposure block. Trial-by-trial analysis suggested that this improvement was due to increased error-sensitivity in the gradual protocol. Therefore, cerebellar patients exhibited an improved ability to learn from error if they experienced those errors gradually. This improvement coincided with increased error-sensitivity and was present in both groups of subjects, suggesting that control of error-sensitivity may be spared despite cerebellar damage. PMID:26311179

  19. Cerebellar contribution to spatial event processing: involvement in procedural and working memory components.

    PubMed

    Mandolesi, L; Leggio, M G; Graziano, A; Neri, P; Petrosini, L

    2001-12-01

    Spatial function is one of the cognitive functions altered in the presence of cerebellar lesions. We investigated the cerebellar contribution to the acquisition of spatial procedural and working memory components by means of a radial maze. To establish whether a cerebellar lesion would cause a deficit in solving the radial maze, a first experiment was carried out by using a full-baited maze procedure in different experimental groups, with or without cerebellar lesion and with or without pretraining. Non-pretrained hemicerebellectomized (HCbed) animals exhibited impaired performances in all (motor, spatial and procedural) task aspects. Pre-trained HCbed animals performed similarly to control animals in the task aspects linked to the processing of spatial and procedural factors. To distinguish procedural from working memory components, a forced-choice paradigm of the radial maze was used in the second experiment. Non-pretrained HCbed rats continued to make a lot of errors and show severe perseverative tendencies, already observed in the first experiment, supporting a specific cerebellar role in acquiring new behaviours and in modifying them in relation to the context. Interestingly, hindered from putting the acquired explorative patterns into action and compelled to use only working memory abilities, the pretrained HCbed group exhibited a dramatic worsening of performance. In conclusion, the present findings demonstrate that cerebellar damage induces a specific behaviour in radial maze tasks, characterized by an inflexible use of the procedures (if indeed any procedure was acquired before the lesion) and by a severe impairment in working memory processes.

  20. Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry.

    PubMed

    Katuwal, Gajendra J; Baum, Stefi A; Cahill, Nathan D; Michael, Andrew M

    2016-01-01

    Low success (<60%) in autism spectrum disorder (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7-8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4-5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13-18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD.

  1. Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry

    PubMed Central

    Baum, Stefi A.; Cahill, Nathan D.; Michael, Andrew M.

    2016-01-01

    Low success (<60%) in autism spectrum disorder (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7–8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4–5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13–18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD. PMID:27065101

  2. A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar Dysgenesis.

    PubMed

    Olson, Heather E; Jean-Marçais, Nolwenn; Yang, Edward; Heron, Delphine; Tatton-Brown, Katrina; van der Zwaag, Paul A; Bijlsma, Emilia K; Krock, Bryan L; Backer, E; Kamsteeg, Erik-Jan; Sinnema, Margje; Reijnders, Margot R F; Bearden, David; Begtrup, Amber; Telegrafi, Aida; Lunsing, Roelineke J; Burglen, Lydie; Lesca, Gaetan; Cho, Megan T; Smith, Lacey A; Sheidley, Beth R; Moufawad El Achkar, Christelle; Pearl, Phillip L; Poduri, Annapurna; Skraban, Cara M; Tarpinian, Jennifer; Nesbitt, Addie I; Fransen van de Putte, Dietje E; Ruivenkamp, Claudia A L; Rump, Patrick; Chatron, Nicolas; Sabatier, Isabelle; De Bellescize, Julitta; Guibaud, Laurent; Sweetser, David A; Waxler, Jessica L; Wierenga, Klaas J; Donadieu, Jean; Narayanan, Vinodh; Ramsey, Keri M; Nava, Caroline; Rivière, Jean-Baptiste; Vitobello, Antonio; Tran Mau-Them, Frédéric; Philippe, Christophe; Bruel, Ange-Line; Duffourd, Yannis; Thomas, Laurel; Lelieveld, Stefan H; Schuurs-Hoeijmakers, Janneke; Brunner, Han G; Keren, Boris; Thevenon, Julien; Faivre, Laurence; Thomas, Gary; Thauvin-Robinet, Christel

    2018-05-03

    Developmental and epileptic encephalopathies (DEEs) represent a large clinical and genetic heterogeneous group of neurodevelopmental diseases. The identification of pathogenic genetic variants in DEEs remains crucial for deciphering this complex group and for accurately caring for affected individuals (clinical diagnosis, genetic counseling, impacting medical, precision therapy, clinical trials, etc.). Whole-exome sequencing and intensive data sharing identified a recurrent de novo PACS2 heterozygous missense variant in 14 unrelated individuals. Their phenotype was characterized by epilepsy, global developmental delay with or without autism, common cerebellar dysgenesis, and facial dysmorphism. Mixed focal and generalized epilepsy occurred in the neonatal period, controlled with difficulty in the first year, but many improved in early childhood. PACS2 is an important PACS1 paralog and encodes a multifunctional sorting protein involved in nuclear gene expression and pathway traffic regulation. Both proteins harbor cargo(furin)-binding regions (FBRs) that bind cargo proteins, sorting adaptors, and cellular kinase. Compared to the defined PACS1 recurrent variant series, individuals with PACS2 variant have more consistently neonatal/early-infantile-onset epilepsy that can be challenging to control. Cerebellar abnormalities may be similar but PACS2 individuals exhibit a pattern of clear dysgenesis ranging from mild to severe. Functional studies demonstrated that the PACS2 recurrent variant reduces the ability of the predicted autoregulatory domain to modulate the interaction between the PACS2 FBR and client proteins, which may disturb cellular function. These findings support the causality of this recurrent de novo PACS2 heterozygous missense in DEEs with facial dysmorphim and cerebellar dysgenesis. Copyright © 2018 American Society of Human Genetics. All rights reserved.

  3. Consensus Paper: Pathological Role of the Cerebellum in Autism

    PubMed Central

    Fatemi, S. Hossein; Aldinger, Kimberly A.; Ashwood, Paul; Bauman, Margaret L.; Blaha, Charles D.; Blatt, Gene J.; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R.; Dickson, Price E.; Estes, Annette M.; Goldowitz, Dan; Heck, Detlef H.; Kemper, Thomas L.; King, Bryan H.; Martin, Loren A.; Millen, Kathleen J.; Mittleman, Guy; Mosconi, Matthew W.; Persico, Antonio M.; Sweeney, John A.; Webb, Sara J.; Welsh, John P.

    2013-01-01

    There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation. PMID:22370873

  4. Consensus paper: pathological role of the cerebellum in autism.

    PubMed

    Fatemi, S Hossein; Aldinger, Kimberly A; Ashwood, Paul; Bauman, Margaret L; Blaha, Charles D; Blatt, Gene J; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R; Dickson, Price E; Estes, Annette M; Goldowitz, Dan; Heck, Detlef H; Kemper, Thomas L; King, Bryan H; Martin, Loren A; Millen, Kathleen J; Mittleman, Guy; Mosconi, Matthew W; Persico, Antonio M; Sweeney, John A; Webb, Sara J; Welsh, John P

    2012-09-01

    There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin-related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism, and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia, and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation.

  5. Disrupted functional connectivity of cerebellar default network areas in attention-deficit/hyperactivity disorder.

    PubMed

    Kucyi, Aaron; Hove, Michael J; Biederman, Joseph; Van Dijk, Koene R A; Valera, Eve M

    2015-09-01

    Attention-deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain-network interactions. The default mode network (DMN), implicated in ADHD-linked behaviors including mind-wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within-network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age-, IQ-, and sex-matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole-brain between-group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between-group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of cerebro-cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD. © 2015 Wiley Periodicals, Inc.

  6. Disrupted functional connectivity of cerebellar default network areas in attention-deficit/hyperactivity disorder

    PubMed Central

    Kucyi, Aaron; Hove, Michael J.; Biederman, Joseph; Van Dijk, Koene R.A.; Valera, Eve M.

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain-network interactions. The default mode network (DMN), implicated in ADHD-linked behaviors including mind-wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within-network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age-, IQ-, and sex-matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole-brain between-group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between-group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of the cerebro-cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD. PMID:26109476

  7. Cerebellar theta burst stimulation modulates short latency afferent inhibition in Alzheimer's disease patients

    PubMed Central

    Di Lorenzo, Francesco; Martorana, Alessandro; Ponzo, Viviana; Bonnì, Sonia; D'Angelo, Egidio; Caltagirone, Carlo; Koch, Giacomo

    2013-01-01

    The dysfunction of cholinergic neurons is a typical hallmark in Alzheimer's disease (AD). Previous findings demonstrated that high density of cholinergic receptors is found in the thalamus and the cerebellum compared with the cerebral cortex and the hippocampus. We aimed at investigating whether activation of the cerebello-thalamo-cortical pathway by means of cerebellar theta burst stimulation (TBS) could modulate central cholinergic functions evaluated in vivo by using the neurophysiological determination of Short-Latency Afferent Inhibition (SLAI). We tested the SLAI circuit before and after administration of cerebellar continuous TBS (cTBS) in 12 AD patients and in 12 healthy age-matched control subjects (HS). We also investigated potential changes of intracortical circuits of the contralateral primary motor cortex (M1) by assessing short intracortical inhibition (SICI) and intracortical facilitation (ICF). SLAI was decreased in AD patients compared to HS. Cerebellar cTBS partially restored SLAI in AD patients at later inter-stimulus intervals (ISIs), but did not modify SLAI in HS. SICI and ICF did not differ in the two groups and were not modulated by cerebellar cTBS. These results demonstrate that cerebellar magnetic stimulation is likely to affect mechanisms of cortical cholinergic activity, suggesting that the cerebellum may have a direct influence on the cholinergic dysfunction in AD. PMID:23423358

  8. Modality Specific Cerebro-Cerebellar Activations in Verbal Working Memory: An fMRI Study

    PubMed Central

    Kirschen, Matthew P.; Chen, S. H. Annabel; Desmond, John E.

    2010-01-01

    Verbal working memory (VWM) engages frontal and temporal/parietal circuits subserving the phonological loop, as well as, superior and inferior cerebellar regions which have projections from these neocortical areas. Different cerebro-cerebellar circuits may be engaged for integrating aurally- and visually-presented information for VWM. The present fMRI study investigated load (2, 4, or 6 letters) and modality (auditory and visual) dependent cerebro-cerebellar VWM activation using a Sternberg task. FMRI revealed modality-independent activations in left frontal (BA 6/9/44), insular, cingulate (BA 32), and bilateral inferior parietal/supramarginal (BA 40) regions, as well as in bilateral superior (HVI) and right inferior (HVIII) cerebellar regions. Visual presentation evoked prominent activations in right superior (HVI/CrusI) cerebellum, bilateral occipital (BA19) and left parietal (BA7/40) cortex while auditory presentation showed robust activations predominately in bilateral temporal regions (BA21/22). In the cerebellum, we noted a visual to auditory emphasis of function progressing from superior to inferior and from lateral to medial regions. These results extend our previous findings of fMRI activation in cerebro-cerebellar networks during VWM, and demonstrate both modality dependent commonalities and differences in activations with increasing memory load. PMID:20714061

  9. Cortico-Cerebellar Structural Connectivity Is Related to Residual Motor Output in Chronic Stroke.

    PubMed

    Schulz, Robert; Frey, Benedikt M; Koch, Philipp; Zimerman, Maximo; Bönstrup, Marlene; Feldheim, Jan; Timmermann, Jan E; Schön, Gerhard; Cheng, Bastian; Thomalla, Götz; Gerloff, Christian; Hummel, Friedhelm C

    2017-01-01

    Functional imaging studies have argued that interactions between cortical motor areas and the cerebellum are relevant for motor output and recovery processes after stroke. However, the impact of the underlying structural connections is poorly understood. To investigate this, diffusion-weighted brain imaging was conducted in 26 well-characterized chronic stroke patients (aged 63 ± 1.9 years, 18 males) with supratentorial ischemic lesions and 26 healthy participants. Probabilistic tractography was used to reconstruct reciprocal cortico-cerebellar tracts and to relate their microstructural integrity to residual motor functioning applying linear regression modeling. The main finding was a significant association between cortico-cerebellar structural connectivity and residual motor function, independent from the level of damage to the cortico-spinal tract. Specifically, white matter integrity of the cerebellar outflow tract, the dentato-thalamo-cortical tract, was positively related to both general motor output and fine motor skills. Additionally, the integrity of the descending cortico-ponto-cerebellar tract contributed to rather fine motor skills. A comparable structure-function relationship was not evident in the controls. The present study provides first tract-related structural data demonstrating a critical importance of distinct cortico-cerebellar connections for motor output after stroke. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning.

    PubMed

    Gao, Zhenyu; Proietti-Onori, Martina; Lin, Zhanmin; Ten Brinke, Michiel M; Boele, Henk-Jan; Potters, Jan-Willem; Ruigrok, Tom J H; Hoebeek, Freek E; De Zeeuw, Chris I

    2016-02-03

    Closed-loop circuitries between cortical and subcortical regions can facilitate precision of output patterns, but the role of such networks in the cerebellum remains to be elucidated. Here, we characterize the role of internal feedback from the cerebellar nuclei to the cerebellar cortex in classical eyeblink conditioning. We find that excitatory output neurons in the interposed nucleus provide efference-copy signals via mossy fibers to the cerebellar cortical zones that belong to the same module, triggering monosynaptic responses in granule and Golgi cells and indirectly inhibiting Purkinje cells. Upon conditioning, the local density of nucleocortical mossy fiber terminals significantly increases. Optogenetic activation and inhibition of nucleocortical fibers in conditioned animals increases and decreases the amplitude of learned eyeblink responses, respectively. Our data show that the excitatory nucleocortical closed-loop circuitry of the cerebellum relays a corollary discharge of premotor signals and suggests an amplifying role of this circuitry in controlling associative motor learning. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

    PubMed

    Gilmer, Jesse I; Person, Abigail L

    2017-12-13

    Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs

  12. Monogenean anchor morphometry: systematic value, phylogenetic signal, and evolution

    PubMed Central

    Soo, Oi Yoon Michelle; Tan, Wooi Boon; Lim, Lee Hong Susan

    2016-01-01

    Background. Anchors are one of the important attachment appendages for monogenean parasites. Common descent and evolutionary processes have left their mark on anchor morphometry, in the form of patterns of shape and size variation useful for systematic and evolutionary studies. When combined with morphological and molecular data, analysis of anchor morphometry can potentially answer a wide range of biological questions. Materials and Methods. We used data from anchor morphometry, body size and morphology of 13 Ligophorus (Monogenea: Ancyrocephalidae) species infecting two marine mugilid (Teleostei: Mugilidae) fish hosts: Moolgarda buchanani (Bleeker) and Liza subviridis (Valenciennes) from Malaysia. Anchor shape and size data (n = 530) were generated using methods of geometric morphometrics. We used 28S rRNA, 18S rRNA, and ITS1 sequence data to infer a maximum likelihood phylogeny. We discriminated species using principal component and cluster analysis of shape data. Adams’s Kmult was used to detect phylogenetic signal in anchor shape. Phylogeny-correlated size and shape changes were investigated using continuous character mapping and directional statistics, respectively. We assessed morphological constraints in anchor morphometry using phylogenetic regression of anchor shape against body size and anchor size. Anchor morphological integration was studied using partial least squares method. The association between copulatory organ morphology and anchor shape and size in phylomorphospace was used to test the Rohde-Hobbs hypothesis. We created monogeneaGM, a new R package that integrates analyses of monogenean anchor geometric morphometric data with morphological and phylogenetic data. Results. We discriminated 12 of the 13 Ligophorus species using anchor shape data. Significant phylogenetic signal was detected in anchor shape. Thus, we discovered new morphological characters based on anchor shaft shape, the length between the inner root point and the outer root

  13. Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia.

    PubMed

    Main, Stacey L; Kulesza, Randy J

    2017-01-06

    Autism spectrum disorder (ASD) is a developmental brain disorder characterized by restricted and repetitive patterns of behavior, social and communication defects, and is commonly associated with difficulties with motor coordination. The etiology of ASD, while mostly idiopathic, has been linked to hereditary factors and teratogens, such as valproic acid (VPA). VPA is used clinically to treat epilepsy, mood disorders, and in the prevention of migraines. The use of VPA during pregnancy significantly increases the risk of ASD in the offspring. Neuropathological studies show decreased cerebellar function in patients with ASD, resulting in gait, balance and coordination impairments. Herein, we have exposed pregnant rats to a repeated oral dose of VPA on embryonic days 10 and 12 and performed a detailed investigation of the structure and function of the cerebellar vermis. We found that throughout all ten lobules of the cerebellar vermis, Purkinje cells were significantly smaller and expression of the calcium binding protein calbindin (CB) was significantly reduced. We also found that dendritic arbors of Purkinje cells were shorter and less complex. Additionally, animals exposed to a repeated dose of VPA performed significantly worse in a number of motor tasks, including beam walking and the rotarod. These results suggest that repeated embryonic exposure to VPA induces significant cerebellar dysfunction and is an effective animal model to study the cerebellar alterations in ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Cellular and genetic regulation of the development of the cerebellar system.

    PubMed

    Sotelo, Constantino

    2004-04-01

    Recent advances in molecular biology have drastically changed our vision on the development of the nervous system, the cerebellum in particular. After a classical descriptive period, we are now in a modern mechanistic epoch as we begin to answer crucial questions in our quest to understand the mechanisms underlying the emergence of brain complexity. This review begins with an analysis of the role of the "isthmic organizer" in the induction and specification of the cerebellar territory and progresses through cerebellar development to the formation of cerebellar maps. It gathers information about the control of the proliferation of granule cell precursors by Purkinje cells and the role of Shh/Gli-patched signaling. The migratory routes for cerebellar and precerebellar neurons, together with the long-range and short-range cues guiding gliophilic and, particularly, neurophilic migrations, are also discussed. Because these cues are similar to those involved in axon guidance, both processes are under the same molecular constraints. Finally, using primarily the olivocerebellar projection as a model, the cellular and molecular mechanisms involved in the formation of cerebellar maps are discussed. During embryonic development, Purkinje cells in the cerebellum and neurons in the inferior olive follow a simultaneous, but independent, process of intrinsic parcellation, giving rise to subsets of biochemically different cortical compartments. The occurrence of positional information shared between olivary axons and their postsynaptic targets, the Purkinje cells, provides a molecular code for the formation of coarse-grained maps. Activity-dependent mechanisms are required for the transition from crude to fine-grained maps. This important refinement, which confers ultimate specificity to the maps, is under the regulation of parallel fiber-Purkinje cell synaptic activity.

  15. Modelling the electric field and the current density generated by cerebellar transcranial DC stimulation in humans.

    PubMed

    Parazzini, Marta; Rossi, Elena; Ferrucci, Roberta; Liorni, Ilaria; Priori, Alberto; Ravazzani, Paolo

    2014-03-01

    Transcranial Direct Current Stimulation (tDCS) over the cerebellum (or cerebellar tDCS) modulates working memory, changes cerebello-brain interaction, and affects locomotion in humans. Also, the use of tDCS has been proposed for the treatment of disorders characterized by cerebellar dysfunction. Nonetheless, the electric field (E) and current density (J) spatial distributions generated by cerebellar tDCS are unknown. This work aimed to estimate E and J distributions during cerebellar tDCS. Computational electromagnetics techniques were applied in three human realistic models of different ages and gender. The stronger E and J occurred mainly in the cerebellar cortex, with some spread (up to 4%) toward the occipital cortex. Also, changes by ±1cm in the position of the active electrode resulted in a small effect (up to 4%) in the E and J spatial distribution in the cerebellum. Finally, the E and J spreads to the brainstem and the heart were negligible, thus further supporting the safety of this technique. Despite inter-individual differences, our modeling study confirms that the cerebellum is the structure mainly involved by cerebellar tDCS. Modeling approach reveals that during cerebellar tDCS the current spread to other structures outside the cerebellum is unlike to produce functional effects. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Metronome Cueing of Walking Reduces Gait Variability after a Cerebellar Stroke.

    PubMed

    Wright, Rachel L; Bevins, Joseph W; Pratt, David; Sackley, Catherine M; Wing, Alan M

    2016-01-01

    Cerebellar stroke typically results in increased variability during walking. Previous research has suggested that auditory cueing reduces excessive variability in conditions such as Parkinson's disease and post-stroke hemiparesis. The aim of this case report was to investigate whether the use of a metronome cue during walking could reduce excessive variability in gait parameters after a cerebellar stroke. An elderly female with a history of cerebellar stroke and recurrent falling undertook three standard gait trials and three gait trials with an auditory metronome. A Vicon system was used to collect 3-D marker trajectory data. The coefficient of variation was calculated for temporal and spatial gait parameters. SDs of the joint angles were calculated and used to give a measure of joint kinematic variability. Step time, stance time, and double support time variability were reduced with metronome cueing. Variability in the sagittal hip, knee, and ankle angles were reduced to normal values when walking to the metronome. In summary, metronome cueing resulted in a decrease in variability for step, stance, and double support times and joint kinematics. Further research is needed to establish whether a metronome may be useful in gait rehabilitation after cerebellar stroke and whether this leads to a decreased risk of falling.

  17. Metronome Cueing of Walking Reduces Gait Variability after a Cerebellar Stroke

    PubMed Central

    Wright, Rachel L.; Bevins, Joseph W.; Pratt, David; Sackley, Catherine M.; Wing, Alan M.

    2016-01-01

    Cerebellar stroke typically results in increased variability during walking. Previous research has suggested that auditory cueing reduces excessive variability in conditions such as Parkinson’s disease and post-stroke hemiparesis. The aim of this case report was to investigate whether the use of a metronome cue during walking could reduce excessive variability in gait parameters after a cerebellar stroke. An elderly female with a history of cerebellar stroke and recurrent falling undertook three standard gait trials and three gait trials with an auditory metronome. A Vicon system was used to collect 3-D marker trajectory data. The coefficient of variation was calculated for temporal and spatial gait parameters. SDs of the joint angles were calculated and used to give a measure of joint kinematic variability. Step time, stance time, and double support time variability were reduced with metronome cueing. Variability in the sagittal hip, knee, and ankle angles were reduced to normal values when walking to the metronome. In summary, metronome cueing resulted in a decrease in variability for step, stance, and double support times and joint kinematics. Further research is needed to establish whether a metronome may be useful in gait rehabilitation after cerebellar stroke and whether this leads to a decreased risk of falling. PMID:27313563

  18. Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue.

    PubMed

    D'Angelo, Egidio; Antonietti, Alberto; Casali, Stefano; Casellato, Claudia; Garrido, Jesus A; Luque, Niceto Rafael; Mapelli, Lisa; Masoli, Stefano; Pedrocchi, Alessandra; Prestori, Francesca; Rizza, Martina Francesca; Ros, Eduardo

    2016-01-01

    The cerebellar microcircuit has been the work bench for theoretical and computational modeling since the beginning of neuroscientific research. The regular neural architecture of the cerebellum inspired different solutions to the long-standing issue of how its circuitry could control motor learning and coordination. Originally, the cerebellar network was modeled using a statistical-topological approach that was later extended by considering the geometrical organization of local microcircuits. However, with the advancement in anatomical and physiological investigations, new discoveries have revealed an unexpected richness of connections, neuronal dynamics and plasticity, calling for a change in modeling strategies, so as to include the multitude of elementary aspects of the network into an integrated and easily updatable computational framework. Recently, biophysically accurate "realistic" models using a bottom-up strategy accounted for both detailed connectivity and neuronal non-linear membrane dynamics. In this perspective review, we will consider the state of the art and discuss how these initial efforts could be further improved. Moreover, we will consider how embodied neurorobotic models including spiking cerebellar networks could help explaining the role and interplay of distributed forms of plasticity. We envisage that realistic modeling, combined with closed-loop simulations, will help to capture the essence of cerebellar computations and could eventually be applied to neurological diseases and neurorobotic control systems.

  19. Investigating the neuroanatomical substrate of pathological laughing and crying in amyotrophic lateral sclerosis with multimodal neuroimaging techniques.

    PubMed

    Christidi, Foteini; Karavasilis, Efstratios; Ferentinos, Panagiotis; Xirou, Sophia; Velonakis, Georgios; Rentzos, Michalis; Zouvelou, Vasiliki; Zalonis, Ioannis; Efstathopoulos, Efstathios; Kelekis, Nikolaos; Evdokimidis, Ioannis

    2018-02-01

    Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS). We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms. In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold). PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.

  20. Reference range of fetal transverse cerebellar diameter between 18 and 24 weeks of pregnancy in a Brazilian population.

    PubMed

    Araujo Júnior, Edward; Martins, Wellington P; Nardozza, Luciano Marcondes Machado; Pires, Claudio Rodrigues; Filho, Sebastião Marques Zanforlin

    2015-02-01

    To determine a reference range of fetal transverse cerebellar diameter in Brazilian population. This was a retrospective cross-sectional study with 3772 normal singleton pregnancies between 18 and 24 weeks of pregnancy. The transverse cerebellar diameter was measured on the axial plane of the fetal head at the level of the lateral ventricles, including the thalamus, cavum septum pellucidum, and third ventricle. To assess the correlation between transverse cerebellar diameter and gestational age, polynomial equations were calculated, with adjustments by the determination coefficient (R2). The mean of fetal transverse cerebellar diameter ranged from 18.49 ± 1.24 mm at 18 weeks to 25.86 ± 1.66 mm at 24 weeks of pregnancy. We observed a good correlation between transverse cerebellar diameter and gestational age, which was best represented by a linear equation: transverse cerebellar diameter: -6.21 + 1.307*gestational age (R2 = 0.707). We determined a reference range of fetal transverse cerebellar diameter for the second trimester of pregnancy in Brazilian population. © The Author(s) 2014.

  1. A comparison between pre- and posthibernation morphometry, hematology, and blood chemistry in viperid snakes.

    PubMed

    Dutton, Christopher J; Taylor, Peter

    2003-03-01

    Snakes from temperate climates are often made to hibernate in zoos to stimulate reproduction. Unfortunately, deaths have occurred during and after hibernation. This study evaluated the health status, pre- and posthibernation, of 31 adult viperid snakes. It included morphometric measurements, hematology, and blood chemistry. No differences were seen in body weights and weight to length ratios between pre- and posthibernation examinations, suggesting that the overall condition of the snakes did not change. No differences were seen in hematologic and blood chemistry parameters, except that bile acids (3alpha-hydroxybile acids) decreased, the implications of which are unknown. Three individuals had markedly high plasma uric acid levels posthibernation; of these, two individuals died from extensive visceral gout and one recovered with fluid therapy. Viperid snakes should be clinically healthy, well hydrated, and in good body condition when they are put into hibernation. They should be maintained in an environment with sufficient humidity and should have access to water. Blood samples should be collected on arousal for measuring plasma uric acid levels. Changes in morphometry, hematology, and blood chemistry appear to be abnormal and should be investigated thoroughly.

  2. Cerebellar haematomas caused by angiomas in children1

    PubMed Central

    Erenberg, G.; Rubin, R.; Shulman, K.

    1972-01-01

    Spontaneous cerebellar haematomas in previously well children are most often caused by haemorrhage from small angiomas. Eight such cases in children 12 years of age or younger have been reported previously. Their clinical course was usually not as acute as the course most commonly seen in adults, and four of the children survived after evacuation of the haematoma. Two additional cases are presented. Both children were admitted in a comatose state, but survived after surgical intervention. Cerebellar haematomas in children seem to have a better prognosis than in adults and should be considered in the evaluation of children with subarachnoid haemorrhage or the rapid onset of coma. Even if admitted in extremis, recovery is possible after prompt diagnosis and surgical evacuation of the haematoma. PMID:5035308

  3. Hippocampal and cerebellar atrophy in patients with Cushing's disease.

    PubMed

    Burkhardt, Till; Lüdecke, Daniel; Spies, Lothar; Wittmann, Linus; Westphal, Manfred; Flitsch, Jörg

    2015-11-01

    OBJECT Cushing's disease (CD) may cause atrophy of different regions of the human brain, mostly affecting the hippocampus and the cerebellum. This study evaluates the use of 3-T MRI of newly diagnosed patients with CD to detect atrophic degeneration with voxel-based volumetry. METHODS Subjects with newly diagnosed, untreated CD were included and underwent 3-T MRI. Images were analyzed using a voxelwise statistical test to detect reduction of brain parenchyma. In addition, an atlas-based volumetric study for regions likely to be affected by CD was performed. RESULTS Nineteen patients with a mean disease duration of 24 months were included. Tumor markers included adrenocorticotropic hormone (median 17.5 pmol/L), cortisol (949.4 nmol/L), and dehydroepiandrosterone sulfate (5.4 μmol/L). The following values are expressed as the mean ± SD. The voxelwise statistical test revealed clusters of significantly reduced gray matter in the hippocampus and cerebellum, with volumes of 2.90 ± 0.26 ml (right hippocampus), 2.89 ± 0.28 ml (left hippocampus), 41.95 ± 4.67 ml (right cerebellar hemisphere), and 42.11 ± 4.59 ml (left cerebellar hemisphere). Healthy control volunteers showed volumes of 3.22 ± 0.25 ml for the right hippocampus, 3.23 ± 0.25 ml for the left hippocampus, 50.87 ± 4.23 ml for the right cerebellar hemisphere, and 50.42 ± 3.97 ml for the left cerebellar hemisphere. CONCLUSIONS Patients with untreated CD show significant reduction of gray matter in the cerebellum and hippocampus. These changes can be analyzed and objectified with the quantitative voxel-based method described in this study.

  4. Nothing can be coincidence: synaptic inhibition and plasticity in the cerebellar nuclei

    PubMed Central

    Pugh, Jason R.; Raman, Indira M.

    2009-01-01

    Many cerebellar neurons fire spontaneously, generating 10–100 action potentials per second even without synaptic input. This high basal activity correlates with information-coding mechanisms that differ from those of cells that are quiescent until excited synaptically. For example, in the deep cerebellar nuclei, Hebbian patterns of coincident synaptic excitation and postsynaptic firing fail to induce long-term increases in the strength of excitatory inputs. Instead, excitatory synaptic currents are potentiated by combinations of inhibition and excitation that resemble the activity of Purkinje and mossy fiber afferents that is predicted to occur during cerebellar associative learning tasks. Such results indicate that circuits with intrinsically active neurons have rules for information transfer and storage that distinguish them from other brain regions. PMID:19178955

  5. Failure of Fixation Suppression of Spontaneous Nystagmus in Cerebellar Infarction: Frequency, Pattern, and a Possible Structure.

    PubMed

    Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

    2016-04-01

    To investigate the frequency and pattern of failure of the fixation suppression (FFS) of spontaneous nystagmus (SN) in unilateral cerebellar infarction, and to identify the structure responsible for FFS, 29 patients with acute, mainly unilateral, isolated cerebellar infarction who had SN with a predominantly horizontal component were enrolled in this study. The ocular fixation index (OFI) was defined as the mean slow phase velocity (SPV) of the horizontal component of SN with fixation divided by the mean SPV of the horizontal component of SN without fixation. The OFI from age- and sex-matched patients with vestibular neuritis was calculated and used as the control data. The FFS of SN was only found in less than half (41 %, 12/29) of the patients. Approximately 65 % (n = 7) of the patients with isolated anterior inferior cerebellar artery territory cerebellar infarction showed FFS, whereas only a quarter (n = 3) of the patients with isolated posterior inferior cerebellar artery (PICA) territory cerebellar infarction showed FFS. The proportion of gaze-evoked nystagmus (6/12 [50 %] vs. 2/17 [12 %], p = 0.04) and deficient gain of ipsilesional pursuit (10/12 [83 %] vs. 6/17 [35 %], p = 0.05) was more frequent in the FFS group than in the group without FFS. Lesion subtraction analysis in isolated PICA territory cerebellar infarction revealed that the nodulus was commonly damaged in patients with FFS, compared to that of patients without FFS. Our study shows that FFS of SN due to acute cerebellar infarction is less common than previously thought and the nodulus may be an important structure for the suppression of SN in humans.

  6. Absence of gender effect on children with attention-deficit/hyperactivity disorder as assessed by optimized voxel-based morphometry.

    PubMed

    Yang, Pinchen; Wang, Pei-Ning; Chuang, Kai-Hsiang; Jong, Yuh-Jyh; Chao, Tzu-Cheng; Wu, Ming-Ting

    2008-12-30

    Brain abnormalities, as determined by structural magnetic resonance imaging (MRI), have been reported in patients with attention-deficit hyperactivity disorder (ADHD); however, female subjects have been underrepresented in previous reports. In this study, we used optimized voxel-based morphometry to compare the total and regional gray matter volumes between groups of 7- to 17-year-old ADHD and healthy children (total 114 subjects). Fifty-seven children with ADHD (n=57, 35 males and 22 females) and healthy children (n=57) received MRI scans. Segmented brain MRI images were normalized into standardized stereotactic space, modulated to allow volumetric analysis, smoothed and compared at the voxel level with statistical parametric mapping. Global volumetric comparisons between groups revealed that the total brain volumes of ADHD children were smaller than those of the control children. As for the regional brain analysis, the brain volumes of ADHD children were found to be bilaterally smaller in the following regions as compared with normal control values: the caudate nucleus and the cerebellum. There were two clusters of regional decrease in the female brain, left posterior cingulum and right precuneus, as compared with the male brain. Brain regions showing the interaction effect of diagnosis and gender were negligible. These results were consistent with the hypothesized dysfunctional systems in ADHD, and they also suggested that neuroanatomical abnormalities in ADHD were not influenced by gender.

  7. Abnormalities in substance P neurokinin-1 receptor binding in key brainstem nuclei in sudden infant death syndrome related to prematurity and sex.

    PubMed

    Bright, Fiona M; Vink, Robert; Byard, Roger W; Duncan, Jhodie R; Krous, Henry F; Paterson, David S

    2017-01-01

    Sudden infant death syndrome (SIDS) involves failure of arousal to potentially life threatening events, including hypoxia, during sleep. While neuronal dysfunction and abnormalities in neurotransmitter systems within the medulla oblongata have been implicated, the specific pathways associated with autonomic and cardiorespiratory failure are unknown. The neuropeptide substance P (SP) and its tachykinin neurokinin-1 receptor (NK1R) have been shown to play an integral role in the modulation of homeostatic function in the medulla, including regulation of respiratory rhythm generation, integration of cardiovascular control, and modulation of the baroreceptor reflex and mediation of the chemoreceptor reflex in response to hypoxia. Abnormalities in SP neurotransmission may therefore result in autonomic dysfunction during sleep and contribute to SIDS deaths. [125I] Bolton Hunter SP autoradiography was used to map the distribution and density of the SP, NK1R to 13 specific nuclei intimately related to cardiorespiratory function and autonomic control in the human infant medulla of 55 SIDS and 21 control (non-SIDS) infants. Compared to controls, SIDS cases exhibited a differential, abnormal developmental profile of the SP/NK1R system in the medulla. Furthermore the study revealed significantly decreased NK1R binding within key medullary nuclei in SIDS cases, principally in the nucleus tractus solitarii (NTS) and all three subdivisions of the inferior portion of the olivo-cerebellar complex; the principal inferior olivary complex (PIO), medial accessory olive (MAO) and dorsal accessory olive (DAO). Altered NK1R binding was significantly influenced by prematurity and male sex, which may explain the increased risk of SIDS in premature and male infants. Abnormal NK1R binding in these medullary nuclei may contribute to the defective interaction of critical medullary mechanisms with cerebellar sites, resulting in an inability of a SIDS infant to illicit appropriate respiratory and

  8. Abnormalities in substance P neurokinin-1 receptor binding in key brainstem nuclei in sudden infant death syndrome related to prematurity and sex

    PubMed Central

    Vink, Robert; Byard, Roger W.; Duncan, Jhodie R.; Krous, Henry F.; Paterson, David S.

    2017-01-01

    Sudden infant death syndrome (SIDS) involves failure of arousal to potentially life threatening events, including hypoxia, during sleep. While neuronal dysfunction and abnormalities in neurotransmitter systems within the medulla oblongata have been implicated, the specific pathways associated with autonomic and cardiorespiratory failure are unknown. The neuropeptide substance P (SP) and its tachykinin neurokinin-1 receptor (NK1R) have been shown to play an integral role in the modulation of homeostatic function in the medulla, including regulation of respiratory rhythm generation, integration of cardiovascular control, and modulation of the baroreceptor reflex and mediation of the chemoreceptor reflex in response to hypoxia. Abnormalities in SP neurotransmission may therefore result in autonomic dysfunction during sleep and contribute to SIDS deaths. [125I] Bolton Hunter SP autoradiography was used to map the distribution and density of the SP, NK1R to 13 specific nuclei intimately related to cardiorespiratory function and autonomic control in the human infant medulla of 55 SIDS and 21 control (non-SIDS) infants. Compared to controls, SIDS cases exhibited a differential, abnormal developmental profile of the SP/NK1R system in the medulla. Furthermore the study revealed significantly decreased NK1R binding within key medullary nuclei in SIDS cases, principally in the nucleus tractus solitarii (NTS) and all three subdivisions of the inferior portion of the olivo-cerebellar complex; the principal inferior olivary complex (PIO), medial accessory olive (MAO) and dorsal accessory olive (DAO). Altered NK1R binding was significantly influenced by prematurity and male sex, which may explain the increased risk of SIDS in premature and male infants. Abnormal NK1R binding in these medullary nuclei may contribute to the defective interaction of critical medullary mechanisms with cerebellar sites, resulting in an inability of a SIDS infant to illicit appropriate respiratory and

  9. Differential effects of age and sex on the cerebellar hemispheres and the vermis: a prospective MR study.

    PubMed

    Raz, N; Dupuis, J H; Briggs, S D; McGavran, C; Acker, J D

    1998-01-01

    The purpose of this study was to determine the effects of age and sex on the size of the cerebellar hemispheres, the cerebellar vermis, and the pons in healthy adults. We estimated the volumes of the cerebellar hemispheres (excluding the vermis and the peduncles), the cross-sectional area of the vermis, and the cross-sectional area of the ventral pons from MR images obtained in 146 healthy volunteers, 18 to 77 years old. We found a mild but significant age-related reduction in the volume of the cerebellar hemispheres and in the total area of the cerebellar vermis; however, the analysis of age trends in the vermian lobules revealed differential age-related declines. The areas of lobules VI and VII and of the posterior vermian lobules (VIII-X) declined significantly with age, whereas the anterior vermis (I-V) showed no significant age-related shrinkage. The volume of the cerebellar hemispheres (especially the right) and the area of the anterior vermis were greater in men, even after adjustment for height. Neither age nor sex affected the area of the ventral pons. Normal aging of the cerebellum is associated with selective regional shrinkage. The cerebellar hemispheres and the area of the anterior vermis may be larger in men than in women regardless of differences in body size.

  10. The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression

    PubMed Central

    Whittaker, Danielle E.; Riegman, Kimberley L.H.; Kasah, Sahrunizam; Mohan, Conor; Yu, Tian; Sala, Blanca Pijuan; Hebaishi, Husam; Caruso, Angela; Marques, Ana Claudia; Michetti, Caterina; Smachetti, María Eugenia Sanz; Shah, Apar; Sabbioni, Mara; Kulhanci, Omer; Tee, Wee-Wei; Reinberg, Danny; Scattoni, Maria Luisa; McGonnell, Imelda; Wardle, Fiona C.; Fernandes, Cathy

    2017-01-01

    The mechanisms underlying the neurodevelopmental deficits associated with CHARGE syndrome, which include cerebellar hypoplasia, developmental delay, coordination problems, and autistic features, have not been identified. CHARGE syndrome has been associated with mutations in the gene encoding the ATP-dependent chromatin remodeler CHD7. CHD7 is expressed in neural stem and progenitor cells, but its role in neurogenesis during brain development remains unknown. Here we have shown that deletion of Chd7 from cerebellar granule cell progenitors (GCps) results in reduced GCp proliferation, cerebellar hypoplasia, developmental delay, and motor deficits in mice. Genome-wide expression profiling revealed downregulated expression of the gene encoding the glycoprotein reelin (Reln) in Chd7-deficient GCps. Recessive RELN mutations have been associated with severe cerebellar hypoplasia in humans. We found molecular and genetic evidence that reductions in Reln expression contribute to GCp proliferative defects and cerebellar hypoplasia in GCp-specific Chd7 mouse mutants. Finally, we showed that CHD7 is necessary for maintaining an open, accessible chromatin state at the Reln locus. Taken together, this study shows that Reln gene expression is regulated by chromatin remodeling, identifies CHD7 as a previously unrecognized upstream regulator of Reln, and provides direct in vivo evidence that a mammalian CHD protein can control brain development by modulating chromatin accessibility in neuronal progenitors. PMID:28165338

  11. Statistical characteristics of climbing fiber spikes necessary for efficient cerebellar learning.

    PubMed

    Kuroda, S; Yamamoto, K; Miyamoto, H; Doya, K; Kawat, M

    2001-03-01

    Mean firing rates (MFRs), with analogue values, have thus far been used as information carriers of neurons in most brain theories of learning. However, the neurons transmit the signal by spikes, which are discrete events. The climbing fibers (CFs), which are known to be essential for cerebellar motor learning, fire at the ultra-low firing rates (around 1 Hz), and it is not yet understood theoretically how high-frequency information can be conveyed and how learning of smooth and fast movements can be achieved. Here we address whether cerebellar learning can be achieved by CF spikes instead of conventional MFR in an eye movement task, such as the ocular following response (OFR), and an arm movement task. There are two major afferents into cerebellar Purkinje cells: parallel fiber (PF) and CF, and the synaptic weights between PFs and Purkinje cells have been shown to be modulated by the stimulation of both types of fiber. The modulation of the synaptic weights is regulated by the cerebellar synaptic plasticity. In this study we simulated cerebellar learning using CF signals as spikes instead of conventional MFR. To generate the spikes we used the following four spike generation models: (1) a Poisson model in which the spike interval probability follows a Poisson distribution, (2) a gamma model in which the spike interval probability follows the gamma distribution, (3) a max model in which a spike is generated when a synaptic input reaches maximum, and (4) a threshold model in which a spike is generated when the input crosses a certain small threshold. We found that, in an OFR task with a constant visual velocity, learning was successful with stochastic models, such as Poisson and gamma models, but not in the deterministic models, such as max and threshold models. In an OFR with a stepwise velocity change and an arm movement task, learning could be achieved only in the Poisson model. In addition, for efficient cerebellar learning, the distribution of CF spike

  12. Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations.

    PubMed

    Rocca, Maria A; Bianchi-Marzoli, Stefania; Messina, Roberta; Cascavilla, Maria Lucia; Zeviani, Massimo; Lamperti, Costanza; Milesi, Jacopo; Carta, Arturo; Cammarata, Gabriella; Leocani, Letizia; Lamantea, Eleonora; Bandello, Francesco; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

    2015-05-01

    Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

  13. A Meta-analysis of Cerebellar Contributions to Higher Cognition from PET and fMRI studies

    PubMed Central

    Keren-Happuch, E; Chen, Shen-Hsing Annabel; Ho, Moon-Ho Ringo; Desmond, John E.

    2013-01-01

    A growing interest in cerebellar function and its involvement in higher cognition have prompted much research in recent years. Cerebellar presence in a wide range of cognitive functions examined within an increasing body of neuroimaging literature has been observed. We applied a meta-analytic approach, which employed the activation likelihood estimate method, to consolidate results of cerebellar involvement accumulated in different cognitive tasks of interest and systematically identified similarities among the studies. The current analysis included 88 neuroimaging studies demonstrating cerebellar activations in higher cognitive domains involving emotion, executive function, language, music, timing and working memory. While largely consistent with a prior meta-analysis by Stoodley and Schmahmann (2009), our results extended their findings to include music and timing domains to provide further insights into cerebellar involvement and elucidate its role in higher cognition. In addition, we conducted inter- and intra-domain comparisons for the cognitive domains of emotion, language and working memory. We also considered task differences within the domain of verbal working memory by conducting a comparison of the Sternberg with the n-back task, as well as an analysis of the differential components within the Sternberg task. Results showed a consistent cerebellar presence in the timing domain, providing evidence for a role in time keeping. Unique clusters identified within the domain further refine the topographic organization of the cerebellum. PMID:23125108

  14. Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists

    PubMed Central

    Priori, Alberto; Ciocca, Matteo; Parazzini, Marta; Vergari, Maurizio; Ferrucci, Roberta

    2014-01-01

    Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists. PMID:24907311

  15. The coevolution of play and the cortico-cerebellar system in primates.

    PubMed

    Kerney, Max; Smaers, Jeroen B; Schoenemann, P Thomas; Dunn, Jacob C

    2017-10-01

    Primates are some of the most playful animals in the natural world, yet the reason for this remains unclear. One hypothesis posits that primates are so playful because playful activity functions to help develop the sophisticated cognitive and behavioural abilities that they are also renowned for. If this hypothesis were true, then play might be expected to have coevolved with the neural substrates underlying these abilities in primates. Here, we tested this prediction by conducting phylogenetic comparative analyses to determine whether play has coevolved with the cortico-cerebellar system, a neural system known to be involved in complex cognition and the production of complex behaviour. We used phylogenetic generalised least squares analyses to compare the relative volume of the largest constituent parts of the primate cortico-cerebellar system (prefrontal cortex, non-prefrontal heteromodal cortical association areas, and posterior cerebellar hemispheres) to the mean percentage of time budget spent in play by a sample of primate species. Using a second categorical data set on play, we also used phylogenetic analysis of covariance to test for significant differences in the volume of the components of the cortico-cerebellar system among primate species exhibiting one of three different levels of adult-adult social play. Our results suggest that, in general, a positive association exists between the amount of play exhibited and the relative size of the main components of the cortico-cerebellar system in our sample of primate species. Although the explanatory power of this study is limited by the correlational nature of its analyses and by the quantity and quality of the data currently available, this finding nevertheless lends support to the hypothesis that play functions to aid the development of cognitive and behavioural abilities in primates.

  16. Relationship between ultrasound estimated fetal gestational age and cerebellar appearance in healthy pregnant Nigerian women.

    PubMed

    Adeyekun, Ademola A; Orji, Michael O

    2015-01-01

    Fetal biometry by ultrasound provides reliable and important information about fetal growth and wellbeing. Evaluation of the fetal posterior fossa is useful in the assessment of neural tube-defects. Studies on normal ultrasound fetal cerebellar appearance and diameter across gestational age (GA) are scanty in the Nigerian medical literature. This study was carried out to study normal fetal cerebellar appearance and diameter at various GAs among healthy pregnant Nigerian Africans. This was a prospective study of 450 healthy singleton pregnant women between 13 and 42 weeks gestation. A curvilinear probe with a 3.5 MHz transducer of a SonoAce X6 (Medison Inc., Korea 2010) scanner was used to assess fetal transcerebellar diameter (TCD) and appearance. GA was also determined using fetal biometric parameters such as the biparietal diameter, femur length, and abdominal circumference. Fetal cerebellar appearance was correlated against GA. The cerebellar appearance was graded into: Grade I: 164 fetuses (36.4%), Grade II; 102 fetuses (22.7%) and Grade III: 184 fetuses (40.9%). Mean GA and TCD was 21 weeks and 21.2 mm for Grade I; 28 weeks and 32.6 mm for Grade II; and 35 weeks and 47.1 mm for Grade III. There was significance difference among the cerebellar grades at the GA groups and transverse cerebellar diameter (P < 0.000). There is a gradual and steady change in ultrasonographic appearance of the fetal cerebellar and diameter appearance with advancing gestation. The changes ranged from anechoic, "pair of eye glass" appearance at second trimester to relatively echogenic, "dumb-bell" appearance at early third trimester, and solid, "fan-shape" in late third trimester.

  17. Cerebellar neuronal loss in amyotrophic lateral sclerosis cases with ATXN2 intermediate repeat expansions.

    PubMed

    Tan, Rachel H; Kril, Jillian J; McGinley, Ciara; Hassani, Mohammad; Masuda-Suzukake, Masami; Hasegawa, Masato; Mito, Remika; Kiernan, Matthew C; Halliday, Glenda M

    2016-02-01

    Despite evidence suggesting that the cerebellum may be targeted in amyotrophic lateral sclerosis (ALS), particularly in cases with repeat expansions in the ATXN2 and C9ORF72 genes, the integrity of cerebellar neurons has yet to be examined. The present study undertakes a histopathological analysis to assess the impact of these repeat expansions on cerebellar neurons and determine whether similar cerebellar pathology occurs in sporadic disease. Purkinje and granule cells were quantified in the vermis and lateral cerebellar hemispheres of ALS cases with repeat expansions in the ATXN2 and C9ORF72 genes, sporadic disease, and sporadic progressive muscular atrophy with only lower motor neuron degeneration. ALS cases with intermediate repeat expansions in the ATXN2 gene demonstrate a significant loss in Purkinje cells in the cerebellar vermis only. Despite ALS cases with expansions in the C9ORF72 gene having the highest burden of inclusion pathology, no neuronal loss was observed in this group. Neuronal numbers were also unchanged in sporadic ALS and sporadic PMA cases. The present study has established a selective loss of Purkinje cells in the cerebellar vermis of ALS cases with intermediate repeat expansions in the ATXN2 gene, suggesting a divergent pathogenic mechanism independent of upper and lower motor neuron degeneration in ALS. We discuss these findings in the context of large repeat expansions in ATXN2 and spinocerebellar ataxia type 2, providing evidence that intermediate repeats in ATXN2 cause significant, albeit less substantial, spinocerebellar damage compared with longer repeats in ATXN2. © 2016 American Neurological Association.

  18. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted cerebellar stimulator. 882.5820 Section 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820 Implanted...

  19. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted cerebellar stimulator. 882.5820 Section 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820 Implanted...

  20. Cerebellar-M1 Connectivity Changes Associated with Motor Learning Are Somatotopic Specific.

    PubMed

    Spampinato, Danny A; Block, Hannah J; Celnik, Pablo A

    2017-03-01

    One of the functions of the cerebellum in motor learning is to predict and account for systematic changes to the body or environment. This form of adaptive learning is mediated by plastic changes occurring within the cerebellar cortex. The strength of cerebellar-to-cerebral pathways for a given muscle may reflect aspects of cerebellum-dependent motor adaptation. These connections with motor cortex (M1) can be estimated as cerebellar inhibition (CBI): a conditioning pulse of transcranial magnetic stimulation delivered to the cerebellum before a test pulse over motor cortex. Previously, we have demonstrated that changes in CBI for a given muscle representation correlate with learning a motor adaptation task with the involved limb. However, the specificity of these effects is unknown. Here, we investigated whether CBI changes in humans are somatotopy specific and how they relate to motor adaptation. We found that learning a visuomotor rotation task with the right hand changed CBI, not only for the involved first dorsal interosseous of the right hand, but also for an uninvolved right leg muscle, the tibialis anterior, likely related to inter-effector transfer of learning. In two follow-up experiments, we investigated whether the preparation of a simple hand or leg movement would produce a somatotopy-specific modulation of CBI. We found that CBI changes only for the effector involved in the movement. These results indicate that learning-related changes in cerebellar-M1 connectivity reflect a somatotopy-specific interaction. Modulation of this pathway is also present in the context of interlimb transfer of learning. SIGNIFICANCE STATEMENT Connectivity between the cerebellum and motor cortex is a critical pathway for the integrity of everyday movements and understanding the somatotopic specificity of this pathway in the context of motor learning is critical to advancing the efficacy of neurorehabilitation. We found that adaptive learning with the hand affects cerebellar

  1. The Changeable Nervous System: Studies On Neuroplasticity In Cerebellar Cultures

    PubMed Central

    Seil, Fredrick J.

    2014-01-01

    Circuit reorganization after injury was studied in a cerebellar culture model. When cerebellar cultures derived from newborn mice were exposed at explantation to a preparation of cytosine arabinoside that destroyed granule cells and oligodendrocytes and compromised astrocytes, Purkinje cells surviving in greater than usual numbers were unensheathed by astrocytic processes and received twice the control number of inhibitory axosomatic synapses. Purkinje cell axon collaterals sprouted and many of their terminals formed heterotypical synapses with other Purkinje cell dendritic spines. The resulting circuit reorganization preserved inhibition in the cerebellar cortex. Following this reorganization, replacement of the missing granule cells and glia was followed by a restitution of the normal circuitry. Most of these developmental and reconstructive changes were not dependent on neuronal activity, the major exception being inhibitory synaptogenesis. The full complement of inhibitory synapses did not develop in the absence of neuronal activity, which could be mitigated by application of exogenous TrkB receptor ligands. Inhibitory synaptogenesis could also be promoted by activity-induced release of endogenous TrkB receptor ligands or by antibody activation of the TrkB receptor. PMID:24933693

  2. Cerebellar Tests Differentiate between Groups of Poor Readers with and without IQ Discrepancy.

    ERIC Educational Resources Information Center

    Fawcett, Angela J.; Nicolson, Roderick I.; Maclagan, Fiona

    2001-01-01

    Tests of phonological, speed, motor and cerebellar tasks were given to 36 students with learning disabilities, 29 of whom were classified as non-discrepant (IQ<90) and 7 as discrepant, (IQ at least 90 and dyslexic). On the cerebellar tests of postural stability and muscle tone, the non-discrepant group performed significantly better than the…

  3. Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

    PubMed Central

    D’Angelo, Egidio; Antonietti, Alberto; Casali, Stefano; Casellato, Claudia; Garrido, Jesus A.; Luque, Niceto Rafael; Mapelli, Lisa; Masoli, Stefano; Pedrocchi, Alessandra; Prestori, Francesca; Rizza, Martina Francesca; Ros, Eduardo

    2016-01-01

    The cerebellar microcircuit has been the work bench for theoretical and computational modeling since the beginning of neuroscientific research. The regular neural architecture of the cerebellum inspired different solutions to the long-standing issue of how its circuitry could control motor learning and coordination. Originally, the cerebellar network was modeled using a statistical-topological approach that was later extended by considering the geometrical organization of local microcircuits. However, with the advancement in anatomical and physiological investigations, new discoveries have revealed an unexpected richness of connections, neuronal dynamics and plasticity, calling for a change in modeling strategies, so as to include the multitude of elementary aspects of the network into an integrated and easily updatable computational framework. Recently, biophysically accurate “realistic” models using a bottom-up strategy accounted for both detailed connectivity and neuronal non-linear membrane dynamics. In this perspective review, we will consider the state of the art and discuss how these initial efforts could be further improved. Moreover, we will consider how embodied neurorobotic models including spiking cerebellar networks could help explaining the role and interplay of distributed forms of plasticity. We envisage that realistic modeling, combined with closed-loop simulations, will help to capture the essence of cerebellar computations and could eventually be applied to neurological diseases and neurorobotic control systems. PMID:27458345

  4. Cerebellar damage impairs the self-rating of regret feeling in a gambling task

    PubMed Central

    Clausi, Silvia; Coricelli, Giorgio; Pisotta, Iolanda; Pavone, Enea Francesco; Lauriola, Marco; Molinari, Marco; Leggio, Maria

    2015-01-01

    Anatomical, clinical, and neuroimaging evidence implicates the cerebellum in processing emotions and feelings. Moreover recent studies showed a cerebellar involvement in pathologies such as autism, schizophrenia and alexithymia, in which emotional processing have been found altered. However, cerebellar function in the modulation of emotional responses remains debated. In this study, emotions that are involved directly in decision-making were examined in 15 patients (six males; age range 17–60 years) affected by cerebellar damage and 15 well matched healthy controls. We used a gambling task, in which subjects’ choices and evaluation of outcomes with regard to their anticipated and actual emotional impact were analyzed. Emotions, such as regret and relief, were elicited, based on the outcome of the unselected gamble. Interestingly, despite their ability to avoid regret in subsequent choices, patients affected by cerebellar lesions were significantly impaired in evaluating the feeling of regret subjectively. These results demonstrate that the cerebellum is involved in conscious recognizing of negative feelings caused by the sense of self-responsibility for an incorrect decision. PMID:25999829

  5. Intrauterine Growth Restriction Affects Cerebellar Granule Cells in the Developing Guinea Pig Brain.

    PubMed

    Tolcos, Mary; McDougall, Annie; Shields, Amy; Chung, Yoonyoung; O'Dowd, Rachael; Turnley, Ann; Wallace, Megan; Rees, Sandra

    2018-01-01

    Intrauterine growth restriction (IUGR) can lead to adverse neurodevelopmental sequelae in postnatal life. However, the effects of IUGR on the cerebellum are still to be fully elucidated. A major determinant of growth and development of the cerebellum is proliferation and subsequent migration of cerebellar granule cells. Our objective was to determine whether IUGR, induced by chronic placental insufficiency (CPI) in guinea pigs, results in abnormal cerebellar development due to deficits suggestive of impaired granule cell proliferation and/or migration. CPI was induced by unilateral ligation of the uterine artery at mid-gestation, producing growth-restricted (GR) foetuses at 52 and 60 days of gestation (dg), and neonates at 1 week postnatal age (term approx. 67 dg). Controls were from sham-operated animals. In GR foetuses compared with controls at 52 dg, the external granular layer (EGL) width and internal granular layer (IGL) area were similar. In GR foetuses compared with controls at 60 dg: (a) the EGL width was greater (p < 0.005); (b) the IGL area was smaller (p < 0.005); (c) the density of Ki67-negative (postmitotic) granule cells in the EGL was greater (p < 0.01); (d) the somal area of Purkinje cells was reduced (p < 0.005), and (e) the linear density of Bergmann glia was similar. The EGL width in GR foetuses at 60 dg was comparable to that of 52 dg control and GR foetuses. The pattern of p27-immunoreactivity in the EGL was the inverse of Ki67-immunoreactivity at both foetal ages; there was no difference between control and GR foetuses at either age in the width of p27-immunoreactivity, or in the percentage of the EGL width that it occupied. In the molecular layer of GR neonates compared with controls there was an increase in the areal density of granule cells (p < 0.05) and in the percentage of migrating to total number of granule cells (p < 0.01) at 1 week but not at 60 dg (p > 0.05). Thus, we found no specific evidence that IUGR affects granule cell

  6. Reorganization of the cerebro-cerebellar network of language production in patients with congenital left-hemispheric brain lesions.

    PubMed

    Lidzba, K; Wilke, M; Staudt, M; Krägeloh-Mann, I; Grodd, W

    2008-09-01

    Patients with congenital lesions of the left cerebral hemisphere may reorganize language functions into the right hemisphere. In these patients, language production is represented homotopically to the left-hemispheric language areas. We studied cerebellar activation in five patients with congenital lesions of the left cerebral hemisphere to assess if the language network is reorganized completely in these patients, i.e. including also cerebellar language functions. As compared to a group of controls matched for age, sex, and verbal IQ, the patients recruited an area not in the right but in the left cerebellar hemisphere. The extent of laterality of the cerebellar activation correlated significantly with the laterality of the frontal activation. We suggest that the developing brain reacts to early focal lesions in the left hemisphere with a mirror-image organization of the entire cerebro-cerebellar network engaged in speech production.

  7. Abnormal development of sensory-motor, visual temporal and parahippocampal cortex in children with learning disabilities and borderline intellectual functioning

    PubMed Central

    Baglio, Francesca; Cabinio, Monia; Ricci, Cristian; Baglio, Gisella; Lipari, Susanna; Griffanti, Ludovica; Preti, Maria G.; Nemni, Raffaello; Clerici, Mario; Zanette, Michela; Blasi, Valeria

    2014-01-01

    Borderline intellectual functioning (BIF) is a condition characterized by an intelligence quotient (IQ) between 70 and 85. BIF children present with cognitive, motor, social, and adaptive limitations that result in learning disabilities and are more likely to develop psychiatric disorders later in life. The aim of this study was to investigate brain morphometry and its relation to IQ level in BIF children. Thirteen children with BIF and 14 age- and sex-matched typically developing (TD) children were enrolled. All children underwent a full IQ assessment (WISC-III scale) and a magnetic resonance (MR) examination including conventional sequences to assess brain structural abnormalities and high resolution 3D images for voxel-based morphometry analysis. To investigate to what extent the group influenced gray matter (GM) volumes, both univariate and multivariate generalized linear model analysis of variance were used, and the varimax factor analysis was used to explore variable correlations and clusters among subjects. Results showed that BIF children, compared to controls have increased regional GM volume in bilateral sensorimotor and right posterior temporal cortices and decreased GM volume in the right parahippocampal gyrus. GM volumes were highly correlated with IQ indices. The present work is a case study of a group of BIF children showing that BIF is associated with abnormal cortical development in brain areas that have a pivotal role in motor, learning, and behavioral processes. Our findings, although allowing for little generalization to the general population, contribute to the very limited knowledge in this field. Future longitudinal MR studies will be useful in verifying whether cortical features can be modified over time even in association with rehabilitative intervention. PMID:25360097

  8. Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

    PubMed Central

    van der Velde, Jorien; Gromann, Paula M.; Swart, Marte; de Haan, Lieuwe; Wiersma, Durk; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André

    2015-01-01

    Background Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. Methods We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. Results We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. Limitations The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. Conclusion These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia. PMID:25768029

  9. Morphometry of boar sperm head and flagellum in semen backflow after insemination.

    PubMed

    García-Vázquez, Francisco Alberto; Hernández-Caravaca, Iván; Yánez-Quintana, Wellington; Matás, Carmen; Soriano-Úbeda, Cristina; Izquierdo-Rico, María José

    2015-09-01

    Once deposited in the female reproductive system, sperm begin their competition and undergo a selection to reach the site of fertilization. Little is known about the special characteristics of sperm that reach the oviduct and are able to fertilize, with even less information on the role of sperm dimension and shape in transport and fertilization. Here, we examine whether sperm morphometry could be involved in their journey within the uterus. For this purpose, sperm head dimension (length, width, area, and perimeter) and shape (shape factor, ellipticity, elongation, and regularity), and flagellum length were analyzed in the backflow at different times after insemination (0-15, 16-30, and 31-60 minutes). Sperm morphometry in the backflow was also analyzed taking into account the site of semen deposition (cervical vs. intrauterine). Finally, flagellum length was measured at the uterotubal junction. Sperm analyzed in the backflow were small (head and flagellum) with different head shapes compared with sperm observed in the dose before insemination. The site of deposition influenced head morphometry and tail size both being smaller in the backflow after cervical insemination compared with intrauterine insemination. Mean tail length of sperm collected in the backflow was smaller than that in the insemination dose and at the uterotubal junction. Overall, our results suggest that sperm size may be involved in sperm transport either because of environment or through sperm selection and competence on their way to encounter the female gamete. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Morphometry and mixing regime of a tropical lake: Lake Nova (Southeastern Brazil).

    PubMed

    Gonçalves, Monica A; Garcia, Fábio C; Barroso, Gilberto F

    2016-09-01

    Lake Nova (15.5 km2) is the second largest lake in the Lower Doce River Valley (Southeastern Brazil). A better understanding of ecosystem structure and functioning requires knowledge about lake morphometry, given that lake basin form influences water column stratification. The present study aims to contribute to the understanding of relationship between morphometry and mixing patterns of deep tropical lakes in Brazil. Water column profiles of temperature and dissolved oxygen were taken on four sampling sites along the lake major axis during 2011, 2012 and 2013. The bathymetric survey was carried out in July 2011, along 131.7 km of hydrographic tracks yield 51,692 depth points. Morphometric features of lake size and form factors describe the relative deep subrectangular elongated basin with maximum length of 15.7 km, shoreline development index 5.0, volume of 0.23 km3, volume development of 1.3, and maximum, mean and relative depths of 33.9 m, 14.7 m and 0.7 %, respectively. The deep basin induces a monomictic pattern, with thermal stratification during the wet/warm season associated with anoxic bottom waters (1/3 of lake volume), and mixing during dry and cool season. Based on in situ measurements of tributary river discharges, theoretical retention time (RT) has been estimated in 13.4 years. The morphometry of Lake Nova promote long water RT and the warm monomictic mixing pattern, which is in accordance to the deep tropical lakes in Brazil.

  11. High-Frequency Network Oscillations in Cerebellar Cortex

    PubMed Central

    Middleton, Steven J.; Racca, Claudia; Cunningham, Mark O.; Traub, Roger D.; Monyer, Hannah; Knöpfel, Thomas; Schofield, Ian S.; Jenkins, Alistair; Whittington, Miles A.

    2016-01-01

    SUMMARY Both cerebellum and neocortex receive input from the somatosensory system. Interaction between these regions has been proposed to underpin the correct selection and execution of motor commands, but it is not clear how such interactions occur. In neocortex, inputs give rise to population rhythms, providing a spatiotemporal coding strategy for inputs and consequent outputs. Here, we show that similar patterns of rhythm generation occur in cerebellum during nicotinic receptor subtype activation. Both gamma oscillations (30–80 Hz) and very fast oscillations (VFOs, 80–160 Hz) were generated by intrinsic cerebellar cortical circuitry in the absence of functional glutamatergic connections. As in neocortex, gamma rhythms were dependent on GABAA receptor-mediated inhibition, whereas VFOs required only nonsynaptically connected intercellular networks. The ability of cerebellar cortex to generate population rhythms within the same frequency bands as neocortex suggests that they act as a common spatiotemporal code within which corticocerebellar dialog may occur. PMID:18549787

  12. The incidence and nature of cerebellar findings in schizophrenia: a quantitative review of fMRI literature.

    PubMed

    Lungu, Ovidiu; Barakat, Marc; Laventure, Samuel; Debas, Karen; Proulx, Sébastien; Luck, David; Stip, Emmanuel

    2013-07-01

    Clinical evidence and structural neuroimaging studies linked cerebellar deficits to cognitive-related symptoms in schizophrenia. Yet, in functional neuroimaging literature to date, the role of the cerebellum in schizophrenia was not explored in a systematic fashion. Here, we reviewed 234 functional magnetic resonance imaging studies indexed by PubMed and published in 1997-2010 that had at least one group of schizophrenia patients, used blood oxygenation level dependent contrast and the general linear model to assess neuronal activity. We quantified presence/absence of cerebellar findings and the frequency of hypo- and hyperactivations (ie, less or more activity in patients relative to healthy controls). We used peaks of activations reported in these studies to build a topographical representation of group differences on a cerebellar map. Cerebellar activity was reported in patients in 41.02% of the articles, with more than 80% of these dedicated to cognitive, emotional, and executive processes in schizophrenia. Almost two-thirds of group comparisons resulted in cerebellar hypoactivation, with a frequency that presented an inverted U shape across different age categories. The majority of the hypoactivation foci were located in the medial portion of the anterior lobe and the lateral hemispheres (lobules IV-V) of the cerebellum. Even though most experimental manipulations did not target explicitly the cerebellum's functions in schizophrenia, the cerebellar findings are frequent and cerebellar hypoactivations predominant. Therefore, although the cerebellum seems to play an important functional role in schizophrenia, the lack of reporting and interpretation of these data may hamper the full understanding of the disorder.

  13. GENETIC INFLUENCE OF APOE4 GENOTYPE ON HIPPOCAMPAL MORPHOMETRY - AN N=725 SURFACE-BASED ADNI STUDY

    PubMed Central

    Shi, Jie; Leporé, Natasha; Gutman, Boris A.; Thompson, Paul M.; Baxter, Leslie C.; Caselli, Richard L.; Wang, Yalin

    2014-01-01

    The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer’s disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 non-carriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database – the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High-order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling’s T2 test, we found significant morphological deformation in APOE e4 carriers relative to non-carriers in the entire cohort as well as in the non-demented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. PMID:24453132

  14. Critical role of cerebellar fastigial nucleus in programming sequences of saccades

    PubMed Central

    King, Susan A.; Schneider, Rosalyn M.; Serra, Alessandro; Leigh, R. John

    2011-01-01

    The cerebellum plays an important role in programming accurate saccades. Cerebellar lesions affecting the ocular motor region of the fastigial nucleus (FOR) cause saccadic hypermetria; however, if a second target is presented before a saccade can be initiated (double-step paradigm), saccade hypermetria may be decreased. We tested the hypothesis that the cerebellum, especially FOR, plays a pivotal role in programming sequences of saccades. We studied patients with saccadic hypermetria due either to genetic cerebellar ataxia or surgical lesions affecting FOR and confirmed that the gain of initial saccades made to double-step stimuli was reduced compared with the gain of saccades to single target jumps. Based on measurements of the intersaccadic interval, we found that the ability to perform parallel processing of saccades was reduced or absent in all of our patients with cerebellar disease. Our results support the crucial role of the cerebellum, especially FOR, in programming sequences of saccades. PMID:21950988

  15. Critical role of cerebellar fastigial nucleus in programming sequences of saccades.

    PubMed

    King, Susan A; Schneider, Rosalyn M; Serra, Alessandro; Leigh, R John

    2011-09-01

    The cerebellum plays an important role in programming accurate saccades. Cerebellar lesions affecting the ocular motor region of the fastigial nucleus (FOR) cause saccadic hypermetria; however, if a second target is presented before a saccade can be initiated (double-step paradigm), saccade hypermetria may be decreased. We tested the hypothesis that the cerebellum, especially FOR, plays a pivotal role in programming sequences of saccades. We studied patients with saccadic hypermetria because of either genetic cerebellar ataxia or surgical lesions affecting FOR and confirmed that the gain of initial saccades made to double-step stimuli was reduced compared with the gain of saccades to single target jumps. Based on measurements of the intersaccadic interval, we found that the ability to perform parallel processing of saccades was reduced or absent in all of our patients with cerebellar disease. Our results support the crucial role of the cerebellum, especially FOR, in programming sequences of saccades. © 2011 New York Academy of Sciences.

  16. Volumetric Analysis of Cerebral Peduncles and Cerebellar Hemispheres for Predicting Hemiparesis After Hemispherectomy.

    PubMed

    Mullin, Jeffrey P; Soni, Pranay; Lee, Sungho; Jehi, Lara; Naduvil Valappi, Ahsan Moosa; Bingaman, William; Gonzalez-Martinez, Jorge

    2016-09-01

    In some cases of refractory epilepsy, hemispherectomy is the final invasive treatment option. However, predictors of postoperative hemiparesis in these patients have not been widely studied. To investigate how the volumetric analysis of cerebral peduncles and cerebellar hemispheres in patients who have undergone hemispherectomy may determine prognostic implications for postoperative hemiparesis. Twenty-two patients who underwent hemispherectomy at our institution were retrospectively included. Using iPlan/BrainLAB (BrainLAB, Feldkirchen, Germany) imaging software and a semiautomatic voxel-based segmentation method, we calculated the preoperative cerebral peduncle and cerebellar hemisphere volumes. Cerebral peduncle and cerebellar hemisphere ratios were compared between patients with worsened or unchanged/better hemiparesis postoperatively. The ratios of ipsilateral/contralateral cerebral peduncles (0.570 vs 0.828; P = .02) and contralateral/ipsilateral cerebellar hemispheres (0.885 vs 1.031; P = .009) were significantly lower in patients who had unchanged/improved hemiparesis postoperatively compared with patients who had worsened hemiparesis. Relative risk of worsening hemiparesis was significantly higher in patients with a cerebral peduncle ratio < 0.7 (relative risk, 4.3; P = .03) or a cerebellar ratio < 1.0 (relative risk, 6.4; P = .006). Although patients who undergo hemispherectomy are heterogeneous, we report a method of predicting postoperative hemiparesis using only standard volumetric magnetic resonance imaging. This information could be used in preoperative discussions with patients and families to help better understand that chance of retaining baseline motor function. CST, corticospinal tractfMRI, functional magnetic resonance imagingTMS, transcranial magnetic stimulation.

  17. Cerebellar involvement in essential tremor with and without resting tremor: A Diffusion Tensor Imaging study.

    PubMed

    Novellino, Fabiana; Nicoletti, Giuseppe; Cherubini, Andrea; Caligiuri, Maria Eugenia; Nisticò, Rita; Salsone, Maria; Morelli, Maurizio; Arabia, Gennarina; Cavalli, Salvatore Maria; Vaccaro, Maria Grazia; Chiriaco, Carmelina; Quattrone, Aldo

    2016-06-01

    Essential Tremor with resting tremor (rET) is a debated and poorly understood clinical phenotype. Converging evidences show that neurodegeneration of the cerebellum underlies the pathophysiology of ET, but it is not known if cerebellar changes also occurs in patients with rET. The aim of our study was to evaluate cerebellar microstructure in patients with ET with- (rET) and without resting tremor (ETwr) in comparison to healthy controls by MR Diffusion Tensor Imaging (DTI). We studied 67 patients with ET (rET: 29 and ETwr: 38) and 39 age-matched healthy controls (HC). DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) of white and grey matter (WM, GM) in the entire cerebellum and in right and left cerebellar hemispheres. MD was significantly higher in the cerebellar GM of ET total group (10.39 ± 0.87) in comparison with HC (9.90 ± 0.71) (p = 0.0027). Interestingly, MD was significantly different when ETwr (10.48 ± 0.77) were compared with HC (p = 0.0017), whereas a trend toward significance were found between rET (10.29 ± 0.99) and HC (p = 0.067). No differences among groups were found in MD of cerebellar WM and in FA values neither in the WM nor in the GM. Our results demonstrate the presence of microstructural changes in the cerebellum of patients with ET. It is noteworthy that rET showed intermediate values compared to HC and ETwr, suggesting that rET shares part of the pathophysiological mechanisms of ETwr, but cerebellar involvement seems do not fully account for rET. In addition to the cerebellar loops, other networks may play a role in rET pathophysiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Quantitative evaluation of the fetal cerebellar vermis using the median view on three-dimensional ultrasound.

    PubMed

    Zhao, Dan; Liu, Wei; Cai, Ailu; Li, Jingyu; Chen, Lizhu; Wang, Bing

    2013-02-01

    The purpose of this study was to investigate the effectiveness for quantitative evaluation of cerebellar vermis using three-dimensional (3D) ultrasound and to establish a nomogram for Chinese fetal vermis measurements during gestation. Sonographic examinations were performed in normal fetuses and in cases suspected of the diagnosis of vermian rotation. 3D median planes were obtained with both OMNIVIEW and tomographic ultrasound imaging. Measurements of the cerebellar vermis were highly correlated between two-dimensional and 3D median planes. The diameter of the cerebellar vermis follows growth approximately predicted by the quadratic regression equation. The normal vermis was almost parallel to the brain stem, with the average angle degree to be <2° in normal fetuses. The average angle degree of the 9 cases of vermian rotation was >5°. Three-dimensional median planes are obtained more easily than two-dimensional ones, and allow accurate measurements of the cerebellar vermis. The 3D approach may enable rapid assessment of fetal cerebral anatomy in standard examination. Measurements of cerebellar vermis may provide a quantitative index for prenatal diagnosis of posterior fossa malformations. © 2012 John Wiley & Sons, Ltd.

  19. Cerebellar Modulation of Cortically Evoked Complex Movements in Rats.

    PubMed

    Viaro, Riccardo; Bonazzi, Laura; Maggiolini, Emma; Franchi, Gianfranco

    2017-07-01

    Intracortical microstimulation (ICMS) delivered to the motor cortex (M1) via long- or short-train duration (long- or short-duration ICMS) can evoke coordinated complex movements or muscle twitches, respectively. The role of subcortical cerebellar input in M1 output, in terms of long- and short-duration ICMS-evoked movement and motor skill performance, was evaluated in rats with bilateral lesion of the deep cerebellar nuclei. After the lesion, distal forelimb movements were seldom observed, and almost 30% of proximal forelimb movements failed to match criteria defining the movement class observed under control conditions. The classifiable movements could be evoked in different cortical regions with respect to control and many kinematic variables were strongly affected. Furthermore, movement endpoints within the rat's workspace shrunk closer to the body, while performance in the reaching/grasping task worsened. Surprisingly, neither the threshold current values for evoking movements nor the overall size of forelimb movement representation changed with respect to controls in either long- or short-duration ICMS. We therefore conclude that cerebellar input via the motor thalamus is crucial for expressing the basic functional features of the motor cortex. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Su, Xin; Guan, Wuqiang; Yu, Yong-Chun

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1{sup +} or nestin{sup +} stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU{sup +} cells in adult mouse cerebellum, and their quantity and density decreasesmore » significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU{sup +} cells, very few are mash1{sup +} or nestin{sup +} stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1{sup +} microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition.« less

  1. A Cerebellar Tremor in a Patient with Human Immunodeficiency Virus-1 Associated with Progressive Multifocal Leukoencephalopathy

    PubMed Central

    Kim, Hee-Jin; Lee, Jae-Jung; Lee, Phil Hyu

    2009-01-01

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by JC virus infection in oligodendrocytes, especially in patients with acquired immunodeficiency syndrome (AIDS). Movement disorders associated with PML are very rare. Here, we report a case of PML in an AIDS patient who presented with a cerebellar tremor, caused by lesions in the cerebellar outflow tract. A cerebellar tremor can be a rare clinical manifestation in patients with PML. PMID:24868366

  2. Main inherited neurodegenerative cerebellar ataxias, how to recognize them using magnetic resonance imaging?

    PubMed

    Heidelberg, Damien; Ronsin, Solene; Bonneville, Fabrice; Hannoun, Salem; Tilikete, Caroline; Cotton, François

    2018-06-16

    Ataxia is a neurodegenerative disease resulting from brainstem, cerebellar, and/or spinocerebellar tract impairments. Symptom onset could vary widely from childhood to late-adulthood. Autosomal cerebellar ataxias are considered as one of the most complex groups in neurogenetics. In addition to their genetic heterogeneity, there is an important phenotypic variability in the expression of cerebellar impairment, complicating the genetic mutation research. A pattern recognition approach using brain magnetic resonance imaging measures of atrophy, hyperintensities and iron-induced hypointensity of the dentate nuclei could be therefore helpful in guiding genetic research. This review will discuss a pattern recognition approach that, associated with the age at disease onset, and clinical manifestations, may help neuroradiologists differentiate the most frequent profiles of ataxia. Copyright © 2018. Published by Elsevier Masson SAS.

  3. Quantitative study of the correlation between cerebellar retraction factors and hearing loss following microvascular decompression for hemifacial spasm.

    PubMed

    Li, Ning; Zhao, Wei-Guo; Pu, Chun-Hua; Yang, Wen-Lei

    2018-01-01

    This prospective study quantitatively measured the cerebellar retraction factors, including retraction distance, depth and duration, and evaluated their potential relationship to the development of hearing loss after microvascular decompression (MVD) for hemifacial spasm (HFS). One hundred ten patients with primary HFS who underwent MVD in our department were included into this study. The cerebellar retraction factors were quantitatively measured on preoperative MR and timed during MVD. Associations of cerebellar retraction and other factors to postoperative hearing loss were analyzed. Eleven (10%) patients developed hearing loss after MVD. Compared with the group without hearing loss, the cerebellar retraction distance, depth and duration of the group with hearing loss were significantly greater (p < 0.05). Multivariate regression analysis showed that greater cerebellar retraction depth and longer retraction duration were significantly associated with a higher incidence of postoperative hearing impairment (p < 0.05). This study strongly suggested a correlation between the cerebellar retraction factors, especially retraction depth and duration, and possibility of hearing loss following MVD for HFS.

  4. Consensus Paper: Roles of the Cerebellum in Motor Control—The Diversity of Ideas on Cerebellar Involvement in Movement

    PubMed Central

    Bower, James M.; Conforto, Adriana Bastos; Delgado-García, José M.; da Guarda, Suzete Nascimento Farias; Gerwig, Marcus; Habas, Christophe; Hagura, Nobuhiro; Ivry, Richard B.; Mariën, Peter; Molinari, Marco; Naito, Eiichi; Nowak, Dennis A.; Ben Taib, Nordeyn Oulad; Pelisson, Denis; Tesche, Claudia D.; Tilikete, Caroline; Timmann, Dagmar

    2015-01-01

    Considerable progress has been made in developing models of cerebellar function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this consensus paper, we discuss the literature on the role of the cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-cerebellar interaction in visuokinesthetic perception of hand movement, functional neuroimaging studies, and magnetoencephalographic mapping of cortico-cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address cerebellar function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure. PMID:22161499

  5. What’s special about task in dystonia? A voxel-based morphometry and diffusion weighted imaging study

    PubMed Central

    Ramdhani, Ritesh A.; Kumar, Veena; Velickovic, Miodrag; Frucht, Steven J.; Tagliati, Michele; Simonyan, Kristina

    2014-01-01

    Background Numerous brain imaging studies have demonstrated structural changes in the basal ganglia, thalamus, sensorimotor cortex and cerebellum across different forms of primary dystonia. However, our understanding of brain abnormalities contributing to the clinically well-described phenomenon of task-specificity in dystonia remained limited. Methods We used high-resolution MRI with voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics of fractional anisotropy to examine gray and white matter organization in two task-specific dystonia forms, writer’s cramp and laryngeal dystonia, and two non-task-specific dystonia forms, cervical dystonia and blepharospasm. Results A direct comparison between the both dystonia forms revealed that characteristic gray matter volumetric changes in task-specific dystonia involve the brain regions responsible for sensorimotor control during writing and speaking, such as primary somatosensory cortex, middle frontal gyrus, superior/inferior temporal gyrus, middle/posterior cingulate cortex, occipital cortex as well as the striatum and cerebellum (lobules VI-VIIa). These gray matter changes were accompanied by white matter abnormalities in the premotor cortex, middle/inferior frontal gyrus, genu of the corpus callosum, anterior limb/genu of the internal capsule, and putamen. Conversely, gray matter volumetric changes in non-task-specific group were limited to the left cerebellum (lobule VIIa) only, while white matter alterations were found to underlie the primary sensorimotor cortex, inferior parietal lobule and middle cingulate gyrus. Conclusion Distinct microstructural patterns in task-specific and non-task-specific dystonias may represent neuroimaging markers and provide evidence that these two dystonia subclasses likely follow divergent pathophysiological mechanisms precipitated by different triggers. PMID:24925463

  6. Regional grey matter volume abnormalities in bulimia nervosa and binge-eating disorder.

    PubMed

    Schäfer, Axel; Vaitl, Dieter; Schienle, Anne

    2010-04-01

    This study investigated whether bulimia nervosa (BN) and binge-eating disorder (BED) are associated with structural brain abnormalities. Both disorders share the main symptom binge-eating, but are considered differential diagnoses. We attempted to identify alterations in grey matter volume (GMV) that are present in both psychopathologies as well as disorder-specific GMV characteristics. Such information can help to improve neurobiological models of eating disorders and their classification. A total of 50 participants (patients suffering from BN (purge type), BED, and normal-weight controls) underwent structural MRI scanning. GMV for specific brain regions involved in food/reinforcement processing was analyzed by means of voxel-based morphometry. Both patient groups were characterized by greater volumes of the medial orbitofrontal cortex (OFC) compared to healthy controls. In BN patients, who had increased ventral striatum volumes, body mass index and purging severity were correlated with striatal grey matter volume. Altogether, our data implicate a crucial role of the medial OFC in the studied eating disorders. The structural abnormality might be associated with dysfunctions in food reward processing and/or self-regulation. The bulimia-specific volume enlargement of the ventral striatum is discussed in the framework of negative reinforcement through purging and associated weight regulation. Copyright 2009 Elsevier Inc. All rights reserved.

  7. Structural and functional brain changes in early- and mid-stage primary open-angle glaucoma using voxel-based morphometry and functional magnetic resonance imaging.

    PubMed

    Jiang, Ming-Ming; Zhou, Qing; Liu, Xiao-Yong; Shi, Chang-Zheng; Chen, Jian; Huang, Xiang-He

    2017-03-01

    To investigate structural and functional brain changes in patients with primary open-angle glaucoma (POAG) by using voxel-based morphometry based on diffeomorphic anatomical registration through exponentiated Lie algebra (VBM-DARTEL) and blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI), respectively.Thirteen patients diagnosed with POAG and 13 age- and sex-matched healthy controls were enrolled in the study. For each participant, high-resolution structural brain imaging and blood flow imaging were acquired on a 3.0-Tesla magnetic resonance imaging (MRI) scanner. Structural and functional changes between the POAG and control groups were analyzed. An analysis was carried out to identify correlations between structural and functional changes acquired in the previous analysis and the retinal nerve fiber layer (RNFL).Patients in the POAG group showed a significant (P < 0.001) volume increase in the midbrain, left brainstem, frontal gyrus, cerebellar vermis, left inferior parietal lobule, caudate nucleus, thalamus, precuneus, and Brodmann areas 7, 18, and 46. Moreover, significant (P < 0.001) BOLD signal changes were observed in the right supramarginal gyrus, frontal gyrus, superior frontal gyrus, left inferior parietal lobule, left cuneus, and left midcingulate area; many of these regions had high correlations with the RNFL.Patients with POAG undergo widespread and complex changes in cortical brain structure and blood flow. (ClinicalTrials.gov number: NCT02570867).

  8. Effective reinforcement learning following cerebellar damage requires a balance between exploration and motor noise

    PubMed Central

    Therrien, Amanda S.; Wolpert, Daniel M.

    2016-01-01

    Abstract See Miall and Galea (doi: 10.1093/awv343 ) for a scientific commentary on this article. Reinforcement and error-based processes are essential for motor learning, with the cerebellum thought to be required only for the error-based mechanism. Here we examined learning and retention of a reaching skill under both processes. Control subjects learned similarly from reinforcement and error-based feedback, but showed much better retention under reinforcement. To apply reinforcement to cerebellar patients, we developed a closed-loop reinforcement schedule in which task difficulty was controlled based on recent performance. This schedule produced substantial learning in cerebellar patients and controls. Cerebellar patients varied in their learning under reinforcement but fully retained what was learned. In contrast, they showed complete lack of retention in error-based learning. We developed a mechanistic model of the reinforcement task and found that learning depended on a balance between exploration variability and motor noise. While the cerebellar and control groups had similar exploration variability, the patients had greater motor noise and hence learned less. Our results suggest that cerebellar damage indirectly impairs reinforcement learning by increasing motor noise, but does not interfere with the reinforcement mechanism itself. Therefore, reinforcement can be used to learn and retain novel skills, but optimal reinforcement learning requires a balance between exploration variability and motor noise. PMID:26626368

  9. Effective reinforcement learning following cerebellar damage requires a balance between exploration and motor noise.

    PubMed

    Therrien, Amanda S; Wolpert, Daniel M; Bastian, Amy J

    2016-01-01

    Reinforcement and error-based processes are essential for motor learning, with the cerebellum thought to be required only for the error-based mechanism. Here we examined learning and retention of a reaching skill under both processes. Control subjects learned similarly from reinforcement and error-based feedback, but showed much better retention under reinforcement. To apply reinforcement to cerebellar patients, we developed a closed-loop reinforcement schedule in which task difficulty was controlled based on recent performance. This schedule produced substantial learning in cerebellar patients and controls. Cerebellar patients varied in their learning under reinforcement but fully retained what was learned. In contrast, they showed complete lack of retention in error-based learning. We developed a mechanistic model of the reinforcement task and found that learning depended on a balance between exploration variability and motor noise. While the cerebellar and control groups had similar exploration variability, the patients had greater motor noise and hence learned less. Our results suggest that cerebellar damage indirectly impairs reinforcement learning by increasing motor noise, but does not interfere with the reinforcement mechanism itself. Therefore, reinforcement can be used to learn and retain novel skills, but optimal reinforcement learning requires a balance between exploration variability and motor noise. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  10. Diffusion Tensor Tractography of the Cerebellar Peduncles in Prematurely Born 7-Year-Old Children.

    PubMed

    Shany, Eilon; Inder, Terrie E; Goshen, Sharon; Lee, Iris; Neil, Jeffrey J; Smyser, Christopher D; Doyle, Lex W; Anderson, Peter J; Shimony, Joshua S

    2017-04-01

    The objective of this study was to correlate neurodevelopmental outcome of preterm-born children and their perinatal clinical and imaging characteristics with diffusion magnetic resonance imaging (MRI) measures of the three cerebellar peduncles at age 7. Included in this prospective longitudinal study were 140 preterm-born children (<30 weeks gestation) who underwent neurodevelopmental assessment (IQ, motor, language, working memory) and diffusion-weighted imaging (DWI) at age 7 years. White matter tracts in the superior, middle, and inferior cerebellar peduncles were delineated using regions of interest drawn on T2-weighted images and fractional anisotropy (FA) maps. Diffusion measures (mean diffusivity (MD) and FA) and tract volumes were calculated. Linear regression was used to assess relationships with outcome. The severity of white matter injury in the neonatal period was associated with lower FA in the right superior cerebellar peduncle (SCP) and lower tract volumes of both SCPs and middle cerebellar peduncles (MCPs). In the MCP, higher IQ was associated with lower MD in the whole group and higher FA in right-handed children. In the SCP, lower motor scores were associated with higher MD and higher language scores were associated with higher FA. These associations remained significant in multivariable models. This study adds to the body of literature detailing the importance of cerebellar involvement in cognitive function related to reciprocal connections with supratentorial structures.

  11. Motor Deficits and Cerebellar Atrophy in Elovl5 Knock Out Mice.

    PubMed

    Hoxha, Eriola; Gabriele, Rebecca M C; Balbo, Ilaria; Ravera, Francesco; Masante, Linda; Zambelli, Vanessa; Albergo, Cristian; Mitro, Nico; Caruso, Donatella; Di Gregorio, Eleonora; Brusco, Alfredo; Borroni, Barbara; Tempia, Filippo

    2017-01-01

    Spino-Cerebellar-Ataxia type 38 (SCA38) is caused by missense mutations in the very long chain fatty acid elongase 5 gene, ELOVL5 . The main clinical findings in this disease are ataxia, hyposmia and cerebellar atrophy. Mice in which Elovl5 has been knocked out represent a model of the loss of function hypothesis of SCA38. In agreement with this hypothesis, Elovl5 knock out mice reproduced the main symptoms of patients, motor deficits at the beam balance test and hyposmia. The cerebellar cortex of Elovl5 knock out mice showed a reduction of thickness of the molecular layer, already detectable at 6 months of age, confirmed at 12 and 18 months. The total perimeter length of the Purkinje cell (PC) layer was also reduced in Elovl5 knock out mice. Since Elovl5 transcripts are expressed by PCs, whose dendrites are a major component of the molecular layer, we hypothesized that an alteration of their dendrites might be responsible for the reduced thickness of this layer. Reconstruction of the dendritic tree of biocytin-filled PCs, followed by Sholl analysis, showed that the distribution of distal dendrites was significantly reduced in Elovl5 knock out mice. Dendritic spine density was conserved. These results suggest that Elovl5 knock out mice recapitulate SCA38 symptoms and that their cerebellar atrophy is due, at least in part, to a reduced extension of PC dendritic arborization.

  12. Oculomotor evidence for neocortical systems but not cerebellar dysfunction in autism

    PubMed Central

    Minshew, Nancy J.; Luna, Beatriz; Sweeney, John A.

    2010-01-01

    Objective To investigate the functional integrity of cerebellar and frontal system in autism using oculomotor paradigms. Background Cerebellar and neocortical systems models of autism have been proposed. Courchesne and colleagues have argued that cognitive deficits such as shifting attention disturbances result from dysfunction of vermal lobules VI and VII. Such a vermal deficit should be associated with dysmetric saccadic eye movements because of the major role these areas play in guiding the motor precision of saccades. In contrast, neocortical models of autism predict intact saccade metrics, but impairments on tasks requiring the higher cognitive control of saccades. Methods A total of 26 rigorously diagnosed nonmentally retarded autistic subjects and 26 matched healthy control subjects were assessed with a visually guided saccade task and two volitional saccade tasks, the oculomotor delayed-response task and the antisaccade task. Results Metrics and dynamic of the visually guided saccades were normal in autistic subjects, documenting the absence of disturbances in cerebellar vermal lobules VI and VII and in automatic shifts of visual attention. Deficits were demonstrated on both volitional saccade tasks, indicating dysfunction in the circuitry of prefrontal cortex and its connections with the parietal cortex, and associated cognitive impairments in spatial working memory and in the ability to voluntarily suppress context-inappropriate responses. Conclusions These findings demonstrate intrinsic neocortical, not cerebellar, dysfunction in autism, and parallel deficits in higher order cognitive mechanisms and not in elementary attentional and sensorimotor systems in autism. PMID:10102406

  13. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia

    PubMed Central

    Boczonadi, Veronika; Müller, Juliane S.; Pyle, Angela; Munkley, Jennifer; Dor, Talya; Quartararo, Jade; Ferrero, Ileana; Karcagi, Veronika; Giunta, Michele; Polvikoski, Tuomo; Birchall, Daniel; Princzinger, Agota; Cinnamon, Yuval; Lützkendorf, Susanne; Piko, Henriett; Reza, Mojgan; Florez, Laura; Santibanez-Koref, Mauro; Griffin, Helen; Schuelke, Markus; Elpeleg, Orly; Kalaydjieva, Luba; Lochmüller, Hanns; Elliott, David J.; Chinnery, Patrick F.; Edvardson, Shimon; Horvath, Rita

    2014-01-01

    The exosome is a multi-protein complex, required for the degradation of AU-rich element (ARE) containing messenger RNAs (mRNAs). EXOSC8 is an essential protein of the exosome core, as its depletion causes a severe growth defect in yeast. Here we show that homozygous missense mutations in EXOSC8 cause progressive and lethal neurological disease in 22 infants from three independent pedigrees. Affected individuals have cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system or spinal motor neuron disease. Experimental downregulation of EXOSC8 in human oligodendroglia cells and in zebrafish induce a specific increase in ARE mRNAs encoding myelin proteins, showing that the imbalanced supply of myelin proteins causes the disruption of myelin, and explaining the clinical presentation. These findings show the central role of the exosomal pathway in neurodegenerative disease. PMID:24989451

  14. Cerebellar asymmetry and its relation to cerebral asymmetry estimated by intrinsic functional connectivity

    PubMed Central

    Wang, Danhong; Buckner, Randy L.

    2013-01-01

    Asymmetry of the human cerebellum was investigated using intrinsic functional connectivity. Regions of functional asymmetry within the cerebellum were identified during resting-state functional MRI (n = 500 subjects) and replicated in an independent cohort (n = 500 subjects). The most strongly right lateralized cerebellar regions fell within the posterior lobe, including crus I and crus II, in regions estimated to link to the cerebral association cortex. The most strongly left lateralized cerebellar regions were located in lobules VI and VIII in regions linked to distinct cerebral association networks. Comparison of cerebellar asymmetry with independently estimated cerebral asymmetry revealed that the lateralized regions of the cerebellum belong to the same networks that are strongly lateralized in the cerebrum. The degree of functional asymmetry of the cerebellum across individuals was significantly correlated with cerebral asymmetry and varied with handedness. In addition, cerebellar asymmetry estimated at rest predicted cerebral lateralization during an active language task. These results demonstrate that functional lateralization is likely a unitary feature of large-scale cerebrocerebellar networks, consistent with the hypothesis that the cerebellum possesses a roughly homotopic map of the cerebral cortex including the prominent asymmetries of the association cortex. PMID:23076113

  15. Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder

    PubMed Central

    Rogers, Tiffany D.; Dickson, Price E.; McKimm, Eric; Heck, Detlef H.; Goldowitz, Dan; Blaha, Charles D.; Mittleman, Guy

    2013-01-01

    Imaging, clinical and pre-clinical studies have provided ample evidence for a cerebellar involvement in cognitive brain function including cognitive brain disorders, such as autism and schizophrenia. We previously reported that cerebellar activity modulates dopamine release in the mouse medial prefrontal cortex (mPFC) via two distinct pathways: (1) cerebellum to mPFC via dopaminergic projections from the ventral tegmental area [VTA] and (2) cerebellum to mPFC via glutamatergic projections from the mediodorsal and ventrolateral thalamus (ThN md and vl). The present study compared functional adaptations of cerebello-cortical circuitry following developmental cerebellar pathology in a mouse model of developmental loss of Purkinje cells (Lurcher) and a mouse model of fragile X syndrome (Fmr1 KO mice). Fixed potential amperometry was used to measure mPFC dopamine release in response to cerebellar electrical stimulation. Mutant mice of both strains showed an attenuation in cerebellar-evoked mPFC dopamine release compared to respective wildtype mice. This was accompanied by a functional reorganization of the VTA and thalamic pathways mediating cerebellar modulation of mPFC dopamine release. Inactivation of the VTA pathway by intra-VTA lidocaine or kynurenate infusions decreased dopamine release by 50% in wildtype and 20-30% in mutant mice of both strains. Intra-ThN vl infusions of either drug decreased dopamine release by 15% in wildtype and 40% in mutant mice of both strains, while dopamine release remained relatively unchanged following intra-ThN md drug infusions. These results indicate a shift in strength towards the thalamic vl projection, away from the VTA. Thus, cerebellar neuropathologies associated with autism spectrum disorders may cause a reduction in cerebellar modulation of mPFC dopamine release that is related to a reorganization of the mediating neuronal pathways. PMID:23436049

  16. Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder.

    PubMed

    Rogers, Tiffany D; Dickson, Price E; McKimm, Eric; Heck, Detlef H; Goldowitz, Dan; Blaha, Charles D; Mittleman, Guy

    2013-08-01

    Imaging, clinical, and pre-clinical studies have provided ample evidence for a cerebellar involvement in cognitive brain function including cognitive brain disorders, such as autism and schizophrenia. We previously reported that cerebellar activity modulates dopamine release in the mouse medial prefrontal cortex (mPFC) via two distinct pathways: (1) cerebellum to mPFC via dopaminergic projections from the ventral tegmental area (VTA) and (2) cerebellum to mPFC via glutamatergic projections from the mediodorsal and ventrolateral thalamus (ThN md and vl). The present study compared functional adaptations of cerebello-cortical circuitry following developmental cerebellar pathology in a mouse model of developmental loss of Purkinje cells (Lurcher) and a mouse model of fragile X syndrome (Fmr1 KO mice). Fixed potential amperometry was used to measure mPFC dopamine release in response to cerebellar electrical stimulation. Mutant mice of both strains showed an attenuation in cerebellar-evoked mPFC dopamine release compared to respective wildtype mice. This was accompanied by a functional reorganization of the VTA and thalamic pathways mediating cerebellar modulation of mPFC dopamine release. Inactivation of the VTA pathway by intra-VTA lidocaine or kynurenate infusions decreased dopamine release by 50 % in wildtype and 20-30 % in mutant mice of both strains. Intra-ThN vl infusions of either drug decreased dopamine release by 15 % in wildtype and 40 % in mutant mice of both strains, while dopamine release remained relatively unchanged following intra-ThN md drug infusions. These results indicate a shift in strength towards the thalamic vl projection, away from the VTA. Thus, cerebellar neuropathologies associated with autism spectrum disorders may cause a reduction in cerebellar modulation of mPFC dopamine release that is related to a reorganization of the mediating neuronal pathways.

  17. [Type I Chiari malformation associated with cerebellar atrophy. Case report].

    PubMed

    Moscote-Salazar, Luis Rafael; Calderón-Miranda, Willem Guillermo; Alvis-Miranda, Hernando Raphael; Lee-Aguirre, Ángel; Alcalá-Cerra, Gabriel

    2017-01-01

    Chiari malformation is characterized by caudal displacement of the cerebellar tonsils that penetrate into the spinal canal through the foramen magnum, achieving reach the atlas or axis. trunk and any drop of the fourth ventricle is observed. Typically is seen in young adults. In some cases scoliosis and Syringomyelic cavities may occur. The authors present (as far as they know) the first case in the literature with long term follow-up, of a caucasian woman with an unusual form of cerebellar atrophy and Chiari Type I malformation, suffering from weakness in his upper and lower extremities with rapidly progression. The patient was successfully treated with suboccipital decompression and C1 laminectomy.

  18. Distinct white matter abnormalities in different idiopathic generalized epilepsy syndromes.

    PubMed

    Liu, Min; Concha, Luis; Beaulieu, Christian; Gross, Donald W

    2011-12-01

    By definition idiopathic generalized epilepsy (IGE) is not associated with structural abnormalities on conventional magnetic resonance imaging (MRI). However, recent quantitative studies suggest white and gray matter alterations in IGE. The purpose of this study was to investigate whether there are white and/or gray matter structural differences between controls and two subsets of IGE, namely juvenile myoclonic epilepsy (JME) and IGE with generalized tonic-clonic seizures only (IGE-GTC). We assessed white matter integrity and gray matter volume using diffusion tensor tractography-based analysis of fractional anisotropy and voxel-based morphometry, respectively, in 25 patients with IGE, all of whom had experienced generalized tonic-clonic convulsions. Specifically, 15 patients with JME and 10 patients with IGE-GTC were compared to two groups of similarly matched controls separately. Correlations between total lifetime generalized tonic-clonic seizures and fractional anisotropy were investigated for both groups. Tractography revealed lower fractional anisotropy in specific tracts including the crus of the fornix, body of corpus callosum, uncinate fasciculi, superior longitudinal fasciculi, anterior limb of internal capsule, and corticospinal tracts in JME with respect to controls, whereas there were no fractional anisotropy differences in IGE-GTC. No correlation was found between fractional anisotropy and total lifetime generalized tonic-clonic seizures for either JME or IGE-GTC. Although false discovery rate-corrected voxel-based morphometry (VBM) showed no gray matter volume differences between patient and control groups, spatial extent cluster-corrected VBM analysis suggested a trend of gray matter volume reduction in frontal and central regions in both patient groups, more lateral in JME and more medial in IGE-GTC. The findings support the idea that the clinical syndromes of JME and IGE-GTC have unique anatomic substrates. The fact that the primary clinical

  19. Cerebellar learning properties are modulated by the CRF receptor in granular cells.

    PubMed

    Ezra-Nevo, Gili; Prestori, Francesca; Locatelli, Francesca; Soda, Teresa; Ten Brinke, Michiel M; Engel, Mareen; Boele, Henk-Jan; Botta, Laura; Leshkowitz, Dena; Ramot, Assaf; Tsoory, Michael; Biton, Inbal E; Deussing, Jan; D'Angelo, Egidio; De Zeeuw, Chris I; Chen, Alon

    2018-06-22

    Corticotropin-releasing factor (CRF) and its type 1 receptor (CRFR 1 ) play an important role in the responses to stressful challenges. Despite the well-established expression of CRFR 1 in granular cells (GrCs), its role in procedural motor performance and memory formation remains elusive. To investigate the role of CRFR 1 expression in cerebellar GrCs, we used a mouse model depleted of CRFR 1 in these cells. We detected changes in the cellular learning mechanisms in GrCs depleted of CRFR 1 in that they showed changes in intrinsic excitability and long-term synaptic plasticity. Moreover, male mice depleted of CRFR 1 specifically in GrCs showed accelerated Pavlovian associative eye-blink conditioning, but no differences in baseline motor performance, locomotion or fear and anxiety-related behaviors. Last, we analyzed cerebella transcriptome of KO and control mice and detected prominent alterations in the expression of calcium signaling pathways components. Our findings shed light on the interplay between stress-related central mechanisms and cerebellar motor conditioning, highlighting the role of the CRF system in regulating particular forms of cerebellar learning. SIGNIFICANCE STATEMENT Although it is known that CRFR 1 is highly expressed in the cerebellum, little attention has been given to its role in cerebellar functions in the behaving animal. Moreover, most of the attention was directed to the effect of CRF on Purkinje cells at the cellular level, and to this date, almost no data exist on the role of this stress-related receptor in other cerebellar structures. Here, we explored the behavioral and cellular effect of GrCs specific ablation of CRFR 1 We found a profound effect on learning, both at the cellular and behavioral levels, without affecting baseline motor skills. Copyright © 2018 the authors.

  20. Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia

    PubMed Central

    Fogel, Brent L.; Lee, Hane; Deignan, Joshua L.; Strom, Samuel P.; Kantarci, Sibel; Wang, Xizhe; Quintero-Rivera, Fabiola; Vilain, Eric; Grody, Wayne W.; Perlman, Susan; Geschwind, Daniel H.; Nelson, Stanley F.

    2015-01-01

    IMPORTANCE Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. OBJECTIVE To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTS We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. MAIN OUTCOMES AND MEASURES Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. RESULTS We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND RELEVANCE This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia

  1. An agonist–antagonist cerebellar nuclear system controlling eyelid kinematics during motor learning

    PubMed Central

    Sánchez-Campusano, Raudel; Gruart, Agnès; Fernández-Mas, Rodrigo; Delgado-García, José M.

    2012-01-01

    The presence of two antagonistic groups of deep cerebellar nuclei neurons has been reported as necessary for a proper dynamic control of learned motor responses. Most models of cerebellar function seem to ignore the biomechanical need for a double activation–deactivation system controlling eyelid kinematics, since most of them accept that, for closing the eyelid, only the activation of the orbicularis oculi (OO) muscle (via the red nucleus to the facial motor nucleus) is necessary, without a simultaneous deactivation of levator palpebrae motoneurons (via unknown pathways projecting to the perioculomotor area). We have analyzed the kinetic neural commands of two antagonistic types of cerebellar posterior interpositus neuron (IPn) (types A and B), the electromyographic (EMG) activity of the OO muscle, and eyelid kinematic variables in alert behaving cats during classical eyeblink conditioning, using a delay paradigm. We addressed the hypothesis that the interpositus nucleus can be considered an agonist–antagonist system controlling eyelid kinematics during motor learning. To carry out a comparative study of the kinetic–kinematic relationships, we applied timing and dispersion pattern analyses. We concluded that, in accordance with a dominant role of cerebellar circuits for the facilitation of flexor responses, type A neurons fire during active eyelid downward displacements—i.e., during the active contraction of the OO muscle. In contrast, type B neurons present a high tonic rate when the eyelids are wide open, and stop firing during any active downward displacement of the upper eyelid. From a functional point of view, it could be suggested that type B neurons play a facilitative role for the antagonistic action of the levator palpebrae muscle. From an anatomical point of view, the possibility that cerebellar nuclear type B neurons project to the perioculomotor area—i.e., more or less directly onto levator palpebrae motoneurons—is highly appealing. PMID

  2. Structural graph-based morphometry: A multiscale searchlight framework based on sulcal pits.

    PubMed

    Takerkart, Sylvain; Auzias, Guillaume; Brun, Lucile; Coulon, Olivier

    2017-01-01

    Studying the topography of the cortex has proved valuable in order to characterize populations of subjects. In particular, the recent interest towards the deepest parts of the cortical sulci - the so-called sulcal pits - has opened new avenues in that regard. In this paper, we introduce the first fully automatic brain morphometry method based on the study of the spatial organization of sulcal pits - Structural Graph-Based Morphometry (SGBM). Our framework uses attributed graphs to model local patterns of sulcal pits, and further relies on three original contributions. First, a graph kernel is defined to provide a new similarity measure between pit-graphs, with few parameters that can be efficiently estimated from the data. Secondly, we present the first searchlight scheme dedicated to brain morphometry, yielding dense information maps covering the full cortical surface. Finally, a multi-scale inference strategy is designed to jointly analyze the searchlight information maps obtained at different spatial scales. We demonstrate the effectiveness of our framework by studying gender differences and cortical asymmetries: we show that SGBM can both localize informative regions and estimate their spatial scales, while providing results which are consistent with the literature. Thanks to the modular design of our kernel and the vast array of available kernel methods, SGBM can easily be extended to include a more detailed description of the sulcal patterns and solve different statistical problems. Therefore, we suggest that our SGBM framework should be useful for both reaching a better understanding of the normal brain and defining imaging biomarkers in clinical settings. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Discovery of Transcription Factors Novel to Mouse Cerebellar Granule Cell Development Through Laser-Capture Microdissection.

    PubMed

    Zhang, Peter G Y; Yeung, Joanna; Gupta, Ishita; Ramirez, Miguel; Ha, Thomas; Swanson, Douglas J; Nagao-Sato, Sayaka; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Daub, Carsten O; Arner, Erik; de Hoon, Michiel; Carninci, Piero; Forrest, Alistair R R; Hayashizaki, Yoshihide; Goldowitz, Dan

    2018-06-01

    Laser-capture microdissection was used to isolate external germinal layer tissue from three developmental periods of mouse cerebellar development: embryonic days 13, 15, and 18. The cerebellar granule cell-enriched mRNA library was generated with next-generation sequencing using the Helicos technology. Our objective was to discover transcriptional regulators that could be important for the development of cerebellar granule cells-the most numerous neuron in the central nervous system. Through differential expression analysis, we have identified 82 differentially expressed transcription factors (TFs) from a total of 1311 differentially expressed genes. In addition, with TF-binding sequence analysis, we have identified 46 TF candidates that could be key regulators responsible for the variation in the granule cell transcriptome between developmental stages. Altogether, we identified 125 potential TFs (82 from differential expression analysis, 46 from motif analysis with 3 overlaps in the two sets). From this gene set, 37 TFs are considered novel due to the lack of previous knowledge about their roles in cerebellar development. The results from transcriptome-wide analyses were validated with existing online databases, qRT-PCR, and in situ hybridization. This study provides an initial insight into the TFs of cerebellar granule cells that might be important for development and provide valuable information for further functional studies on these transcriptional regulators.

  4. Vergence Deficits in Patients with Cerebellar Lesions

    ERIC Educational Resources Information Center

    Sander, T.; Sprenger, A.; Neumann, G.; Machner, B.; Gottschalk, S.; Rambold, H.; Helmchen, C.

    2009-01-01

    The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Recent animal data suggest an additional role of the cerebellum for the control of binocular alignment and disconjugate, i.e. vergence eye movements. The latter is separated into two different components: fast vergence (to step targets) and slow vergence…

  5. Cerebellar dentate nuclei lesions reduce motivation in appetitive operant conditioning and open field exploration.

    PubMed

    Bauer, David J; Kerr, Abigail L; Swain, Rodney A

    2011-02-01

    Recently identified pathways from the dentate nuclei of the cerebellum to the rostral cerebral cortex via the thalamus suggest a cerebellar role in frontal and prefrontal non-motor functioning. Disturbance of cerebellar morphology and connectivity, particularly involving these cerebellothalamocortical (CTC) projections, has been implicated in motivational and cognitive deficits. The current study explored the effects of CTC disruption on motivation in male Long Evans rats. The results of two experiments demonstrate that electrolytic lesions of the cerebellar dentate nuclei lower breaking points on an operant conditioning progressive ratio schedule and decrease open field exploration compared to sham controls. Changes occurred in the absence of motor impairment, assessed via lever pressing frequency and rotarod performance. Similar elevated plus maze performances between lesioned and sham animals indicated that anxiety did not influence task performance. Our results demonstrate hedonic and purposive motivational reduction and suggest a CTC role in global motivational processes. These implications are discussed in terms of psychiatric disorders such as schizophrenia and autism, in which cerebellar damage and motivational deficits often present concomitantly. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Distributed cerebellar plasticity implements generalized multiple-scale memory components in real-robot sensorimotor tasks.

    PubMed

    Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A; Ferrigno, Giancarlo; D'Angelo, Egidio; Pedrocchi, Alessandra

    2015-01-01

    The cerebellum plays a crucial role in motor learning and it acts as a predictive controller. Modeling it and embedding it into sensorimotor tasks allows us to create functional links between plasticity mechanisms, neural circuits and behavioral learning. Moreover, if applied to real-time control of a neurorobot, the cerebellar model has to deal with a real noisy and changing environment, thus showing its robustness and effectiveness in learning. A biologically inspired cerebellar model with distributed plasticity, both at cortical and nuclear sites, has been used. Two cerebellum-mediated paradigms have been designed: an associative Pavlovian task and a vestibulo-ocular reflex, with multiple sessions of acquisition and extinction and with different stimuli and perturbation patterns. The cerebellar controller succeeded to generate conditioned responses and finely tuned eye movement compensation, thus reproducing human-like behaviors. Through a productive plasticity transfer from cortical to nuclear sites, the distributed cerebellar controller showed in both tasks the capability to optimize learning on multiple time-scales, to store motor memory and to effectively adapt to dynamic ranges of stimuli.

  7. Cognitive training with action-related verbs induces neural plasticity in the action representation system as assessed by gray matter brain morphometry.

    PubMed

    Ghio, Marta; Locatelli, Matteo; Tettamanti, Andrea; Perani, Daniela; Gatti, Roberto; Tettamanti, Marco

    2018-06-01

    Embodied cognition theories of semantic memory still face the need for multiple sources of converging evidence in support of the involvement of sensory-motor systems in action-related knowledge. Previous studies showed that training manual actions improves semantic processing of verbs referring to the trained actions. The present work aimed to provide complementary evidence by measuring the brain plasticity effects of a cognitive training requiring sustained lexical-semantic processing of action-related verbs. We included two groups of participants, namely the Proximal Group (PG) and the Distal Group (DG), which underwent a 3-week training with verbs referring to actions involving the proximal and the distal upper limb musculature, respectively. Before and after training, we measured gray matter voxel brain morphometry based on T1 structural magnetic resonance imaging. By means of this 2 (Group: PG, DG) × 2 (Time: pre-, post-training) factorial design, we tested whether sustained cognitive experience with specific action-related verbs induces congruent brain plasticity modifications in target regions of interest pertaining to the action representation system. We found significant post- versus pre-training gray matter volume increases, specifically for PG in the left dorsal precentral gyrus, and for DG in the right cerebellar lobule VIIa. These preliminary results suggest that a cognitive training can induce structural plasticity modifications in brain regions specifically coding for the distal and proximal motor actions the trained verbs refer to. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia.

    PubMed

    Schiffer, Boris; Peschel, Thomas; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Krueger, Tillmann H C

    2007-11-01

    Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders.

  9. Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder.

    PubMed

    Noordermeer, Siri D S; Luman, Marjolein; Greven, Corina U; Veroude, Kim; Faraone, Stephen V; Hartman, Catharina A; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan K; Heslenfeld, Dirk J; Oosterlaan, Jaap

    2017-11-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. The aim of this study was to investigate the effect of comorbid ODD on cerebral volume and cortical thickness in ADHD. Three groups, 16 ± 3.5 years of age (mean ± SD; range 7-29 years), were studied on volumetric and cortical thickness characteristics using structural magnetic resonance imaging (surface-based morphometry): ADHD+ODD (n = 67), ADHD-only (n = 243), and control subjects (n = 233). Analyses included the moderators age, gender, IQ, and scan site. ADHD+ODD and ADHD-only showed volumetric reductions in total gray matter and (mainly) frontal brain areas. Stepwise volumetric reductions (ADHD+ODD < ADHD-only < control subjects) were found for mainly frontal regions, and ADHD+ODD was uniquely associated with reductions in several structures (e.g., the precuneus). In general, findings remained significant after accounting for ADHD symptom severity. There were no group differences in cortical thickness. Exploratory voxelwise analyses showed no group differences. ADHD+ODD and ADHD-only were associated with volumetric reductions in brain areas crucial for attention, (working) memory, and decision-making. Volumetric reductions of frontal lobes were largest in the ADHD+ODD group, possibly underlying observed larger impairments in neurocognitive functions. Previously reported striatal abnormalities in ADHD may be caused by comorbid conduct disorder rather than ODD. Copyright © 2017 Society of Biological Psychiatry

  10. Morphological and Biochemical Features of Cerebellar Cortex After Exposure to Zinc Oxide Nanoparticles: Possible Protective Role of Curcumin.

    PubMed

    Amer, Mona G; Karam, Rehab A

    2018-03-25

    Zinc oxide nanoparticles (ZnONPs) are widely used in the last decades. Therefore, investigation of its neurotoxic effect is important. This work aimed to investigate the potential adverse effects of ZnONPs on rat's cerebellar cortex and the possible neuroprotective role of curcumin (Cur). Forty male albino rats were randomly divided into four equal groups. Two groups were injected with ZnONPs and one group was previously received Cur before ZnONPs. At the end of the experiment, cerebellar tissue samples were prepared for histological, morphometric, immunohistochemical study, and tissue levels of oxidative stress markers and cytokine analysis. cerebellar damage is clearly visible with ZnONPs. Degeneration, loss, disorganization of cerebellar neurons was observed. Histopathological degeneration of Purkinje and granular cells together with loss of Nissl substance, astrocyte gliosis, and affection of cerebellar blood brain barrier were detected. Moreover, an apoptotic marker (caspase-3) was significantly expressed in Purkinje and granular layers together with elevated gene expression of P53 and COX-2 in cerebellar tissue of ZnONPs intoxicated group. Astrocyte gliosis and inflammatory markers IL-1, IL-6, and TNF-α were expressed significantly in ZnONPs intoxicated cerebellum. These changes were associated with evidence of cerebellar oxidative stress. Strikingly, treatment with Cur together with ZnONPs recorded morphological improvement, with increased number of Purkinje cells and decreased caspase +ve cells. These findings were confirmed by morphometric and statistical analysis. Cur ameliorates the deterious effect of ZnONPs on the cerebellar cortex through its antioxidant, antiapoptotic, and anti-inflammatory efficacies. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  11. Inpatient rehabilitation performance of patients with paraneoplastic cerebellar degeneration.

    PubMed

    Fu, Jack B; Raj, Vishwa S; Asher, Arash; Lee, Jay; Guo, Ying; Konzen, Benedict S; Bruera, Eduardo

    2014-12-01

    To evaluate the functional improvement of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Retrospective review. Referral-based hospitals. Cancer rehabilitation inpatients (N=7) admitted to 3 different cancer centers with a diagnosis of paraneoplastic cerebellar degeneration. Medical records were retrospectively analyzed for demographic, laboratory, medical, and functional data. FIM. All 7 patients were white women (median age, 62y). Primary cancers included ovarian carcinoma (n=2), small cell lung cancer (n=2), uterine carcinoma (n=2), and invasive ductal breast carcinoma (n=1). Mean admission total FIM score was 61±23.97. Mean discharge total FIM score was 73.6±29.35. The mean change in total FIM score was 12.6 (P=.0018). The mean length of rehabilitation stay was 17.1 days. The mean total FIM efficiency was .73. Of the 7 patients, 5 (71%) were discharged home, 1 (14%) was discharged to a nursing home, and 1 (14%) was transferred to the primary acute care service. To our knowledge, this is the first study to demonstrate the functional performance of a group of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Despite the poor neurologic prognosis associated with this syndrome, these patients made significant functional improvements in inpatient rehabilitation. When appropriate, inpatient rehabilitation should be considered. Further studies with larger sample sizes are needed. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  12. Inpatient Rehabilitation Performance of Patients with Paraneoplastic Cerebellar Degeneration

    PubMed Central

    Fu, Jack B.; Raj, Vishwa S.; Asher, Arash; Lee, Jay; Guo, Ying; Konzen, Benedict S.; Bruera, Eduardo

    2014-01-01

    Objective To evaluate the functional improvement of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Design Retrospective Review Setting Three tertiary referral based hospitals. Interventions Medical records were retrospectively analyzed for demographic, laboratory, medical and functional data. Main Outcome Measure Functional Independence Measure (FIM) Participants Cancer rehabilitation inpatients admitted to three different cancer centers with a diagnosis of paraneoplastic cerebellar degeneration (n=7). Results All 7 patients were white females. Median age was 62. Primary cancers included ovarian carcinoma (2), small cell lung cancer (2), uterine carcinoma (2), and invasive ductal breast carcinoma. Mean admission total FIM score was 61.0 (SD=23.97). Mean discharge total FIM score was 73.6 (SD=29.35). The mean change in total FIM score was 12.6 (p=.0018). The mean length of rehabilitation stay was 17.1 days. The mean total FIM efficiency was 0.73. 5/7 (71%) patients were discharged home. 1/7 (14%) was discharged to a nursing home. 1/7 (14%) transferred to the primary acute care service. Conclusions This is the first study to demonstrate the functional performance of a group of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Despite the poor neurologic prognosis associated with this syndrome, these patients made significant functional improvements on inpatient rehabilitation. When appropriate, inpatient rehabilitation should be considered. Further studies with larger sample sizes are needed. PMID:25051460

  13. Convergence of pontine and proprioceptive streams onto multimodal cerebellar granule cells

    PubMed Central

    Huang, Cheng-Chiu; Sugino, Ken; Shima, Yasuyuki; Guo, Caiying; Bai, Suxia; Mensh, Brett D; Nelson, Sacha B; Hantman, Adam W

    2013-01-01

    Cerebellar granule cells constitute the majority of neurons in the brain and are the primary conveyors of sensory and motor-related mossy fiber information to Purkinje cells. The functional capability of the cerebellum hinges on whether individual granule cells receive mossy fiber inputs from multiple precerebellar nuclei or are instead unimodal; this distinction is unresolved. Using cell-type-specific projection mapping with synaptic resolution, we observed the convergence of separate sensory (upper body proprioceptive) and basilar pontine pathways onto individual granule cells and mapped this convergence across cerebellar cortex. These findings inform the long-standing debate about the multimodality of mammalian granule cells and substantiate their associative capacity predicted in the Marr-Albus theory of cerebellar function. We also provide evidence that the convergent basilar pontine pathways carry corollary discharges from upper body motor cortical areas. Such merging of related corollary and sensory streams is a critical component of circuit models of predictive motor control. DOI: http://dx.doi.org/10.7554/eLife.00400.001 PMID:23467508

  14. Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG).

    PubMed

    de Diego, Víctor; Martínez-Monseny, Antonio F; Muchart, Jordi; Cuadras, Daniel; Montero, Raquel; Artuch, Rafael; Pérez-Cerdá, Celia; Pérez, Belén; Pérez-Dueñas, Belén; Poretti, Andrea; Serrano, Mercedes

    2017-09-01

    We aim to delineate the progression of cerebellar atrophy (the primary neuroimaging finding) in children with phosphomannomutase-deficiency (PMM2-CDG) by analyzing longitudinal MRI studies and performing cerebellar volumetric analysis and a 2D cerebellar measurement. Statistical analysis was used to compare MRI measurements [midsagittal vermis relative diameter (MVRD) and volume] of children with PMM2-CDG and sex- and age-matched controls, and to determine the rate of progression of cerebellar atrophy at different ages. Fifty MRI studies of 33 PMM2-CDG patients were used for 2D evaluation, and 19 MRI studies were available for volumetric analysis. Results from a linear regression model showed that patients have a significantly lower MVRD and cerebellar volume compared to controls (p < 0.001 and p < 0.001 respectively). There was a significant negative correlation between age and MVRD for patients (p = 0.014). The rate of cerebellar atrophy measured by the loss of MVRD and cerebellar volume per year was higher at early ages (r = -0.578, p = 0.012 and r = -0.323, p = 0.48 respectively), particularly in patients under 11 years (p = 0.004). There was a significant positive correlation between MVRD and cerebellar volume in PMM2-CDG patients (r = 0.669, p = 0.001). Our study quantifies a progression of cerebellar atrophy in PMM2-CDG patients, particularly during the first decade of life, and suggests a simple and reliable measure, the MVRD, to monitor cerebellar atrophy. Quantitative measurement of MVRD and cerebellar volume are essential for correlation with phenotype and outcome, natural follow-up, and monitoring in view of potential therapies in children with PMM2-CDG.

  15. Auditory-perceptual speech analysis in children with cerebellar tumours: a long-term follow-up study.

    PubMed

    De Smet, Hyo Jung; Catsman-Berrevoets, Coriene; Aarsen, Femke; Verhoeven, Jo; Mariën, Peter; Paquier, Philippe F

    2012-09-01

    Mutism and Subsequent Dysarthria (MSD) and the Posterior Fossa Syndrome (PFS) have become well-recognized clinical entities which may develop after resection of cerebellar tumours. However, speech characteristics following a period of mutism have not been documented in much detail. This study carried out a perceptual speech analysis in 24 children and adolescents (of whom 12 became mute in the immediate postoperative phase) 1-12.2 years after cerebellar tumour resection. The most prominent speech deficits in this study were distorted vowels, slow rate, voice tremor, and monopitch. Factors influencing long-term speech disturbances are presence or absence of postoperative PFS, the localisation of the surgical lesion and the type of adjuvant treatment. Long-term speech deficits may be present up to 12 years post-surgery. The speech deficits found in children and adolescents with cerebellar lesions following cerebellar tumour surgery do not necessarily resemble adult speech characteristics of ataxic dysarthria. Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  16. Neurotoxicological effects of nicotine on the embryonic development of cerebellar cortex of chick embryo during various stages of incubation.

    PubMed

    El-Beltagy, Abd El-Fattah B M; Abou-El-Naga, Amoura M; Sabry, Dalia M

    2015-10-01

    Long-acting nicotine is known to exert pathological effects on almost all tissues including the cerebellar cortex. The present work was designed to elucidate the effect of nicotine on the development of cerebellar cortex of chick embryo during incubation period. The fertilized eggs of hen (Gallus gallus domesticus) were injected into the air space by a single dose of long acting nicotine (1.6 mg/kg/egg) at the 4th day of incubation. The embryos were taken out of the eggs on days 8, 12 and 16 of incubation. The cerebellum of the control and treated embryos at above ages were processed for histopathological examination. The TEM were examined at 16th day of incubation. The results of the present study revealed that, exposure to long-acting nicotine markedly influence the histogenesis of cerebellar cortex of chick embryo during the incubation period. At 8th day of incubation, nicotine delayed the differentiation of the cerebellar analge; especially the external granular layer (EGL) and inner cortical layer (ICL). Furthermore, at 12th day of incubation, the cerebellar foliation was irregular and the Purkinje cells not recognized. By 16th day of incubation, the cerebellar foliations were irregular with interrupted cerebellar cortex and irregular arrangement of Purkinje cells. Immunohistochemical analysis for antibody P53 protein revealed that the cerebellar cortex in all stages of nicotine treated groups possessed a moderate to weak reaction for P53 protein however; this reaction was markedly stronger in the cerebellar cortex of control groups. Moreover, the flow cytometric analysis confirmed that the percentage of apoptosis in control group was significantly higher compared with that of nicotine treated group. At the TEM level, the cerebellar Purkinje cells of 16th day of treated groups showed multiple subcellular alterations in compared with those of the corresponding control group. Such changes represented by appearing of vacuolated mitochondria, cisternal

  17. LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bian, Xuting; Zhong, Hongyu; Li, Fen

    Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the externalmore » granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.« less

  18. A test of the cerebellar hypothesis of dyslexia in adequate and inadequate responders to reading intervention.

    PubMed

    Barth, Amy E; Denton, Carolyn A; Stuebing, Karla K; Fletcher, Jack M; Cirino, Paul T; Francis, David J; Vaughn, Sharon

    2010-05-01

    The cerebellar hypothesis of dyslexia posits that cerebellar deficits are associated with reading disabilities and may explain why some individuals with reading disabilities fail to respond to reading interventions. We tested these hypotheses in a sample of children who participated in a grade 1 reading intervention study (n = 174) and a group of typically achieving children (n = 62). At posttest, children were classified as adequately responding to the intervention (n = 82), inadequately responding with decoding and fluency deficits (n = 36), or inadequately responding with only fluency deficits (n = 56). Based on the Bead Threading and Postural Stability subtests from the Dyslexia Screening Test-Junior, we found little evidence that assessments of cerebellar functions were associated with academic performance or responder status. In addition, we did not find evidence supporting the hypothesis that cerebellar deficits are more prominent for poor readers with "specific" reading disabilities (i.e., with discrepancies relative to IQ) than for poor readers with reading scores consistent with IQ. In contrast, measures of phonological awareness, rapid naming, and vocabulary were strongly associated with responder status and academic outcomes. These results add to accumulating evidence that fails to associate cerebellar functions with reading difficulties.

  19. Behavior modification after inactivation of cerebellar dentate nuclei.

    PubMed

    Peterson, Todd C; Villatoro, Lee; Arneson, Tom; Ahuja, Brittany; Voss, Stephanie; Swain, Rodney A

    2012-08-01

    Effort-based decision making occurs when subjects are given a choice between a reward available at a high response cost and a reward available at a low response cost and is altered in individuals with disorders such as autism or particular patterns of brain injury. The current study explored the relationship between effort-based decision making and reinforcement characteristics in the T maze. This was done using both normal animals and animals with bilateral inactivation of the cerebellar dentate nuclei. Rats chose between alternatives in which one arm contained high-density reinforcement (HR) and the other arm contained low-density reinforcement (LR). During training, the HR arm was obstructed and the point at which the animal no longer worked for reinforcement (breaking point) was determined. The cerebellar dentate nuclei were then transiently inactivated and once again breaking points were assessed. The results indicated that inactivation of the dentate nucleus disrupted effort-based decision making. Additionally, altering both the palatability and the magnitude of the reinforcement were assessed in an attempt to reestablish the original preinactivation breaking point. It was hypothesized that an increase in the strength or magnitude of the reinforcement would promote an increase in the breaking point of the animal even when the cerebellum was inactivated. The results indicated that with both strategies animals effectively reestablished original breaking points. The results of this study will inform the current literature regarding the modification of behavior after brain injury and further the understanding of the behavioral deficits associated with cerebellar dysfunction.

  20. Nystagmus in SCA territory cerebellar infarction: pattern and a possible mechanism.

    PubMed

    Lee, Hyung; Kim, Hyun-Ah

    2013-04-01

    To investigate the frequency and pattern of nystagmus associated with isolated cerebellar infarction in the territory of the superior cerebellar artery (SCA) and to discuss its possible mechanism. We identified 41 consecutive patients with isolated SCA territory cerebellar infarction diagnosed by MRI. Each patient completed a standardised dizziness questionnaire and underwent neurotological evaluations. Eye movements were recorded using 3-dimensional video-oculography during the acute period. Approximately half (19/41) of the patients experienced true vertigo early in the course of the SCA distribution infarct. 11 (27%) of the 41 patients showed spontaneous nystagmus (SN) or direction changed bidirectional gaze-evoked nystagmus (GEN). SN was observed in 10 patients (24%) and the horizontal component of SN was predominant in most case (80%, 8/10) and always beat towards the lesion side. Direction changed bidirectional GEN was observed in five patients and was mostly (4/5) accompanied by SN. Lesion subtraction analyses revealed that damage to the rostral anterior cerebellum including the ala of the central lobule and part of the quadrangular lobule was more frequent in patients with nystagmus compared to patients without nystagmus (9/11, 82% vs 11/30, 37%) (p=0.015). In most (82%, 9/11) patients with SN or GEN, the nystagmus subsided within 1 week after hospitalisation. Vertigo and nystagmus in SCA territory cerebellar infarction are more common than previously thought. Ipsilesional SN may result from damage to the anterior lobe of the cerebellum, which transmits the vestibular output to the fastigial nucleus.

  1. Structural MRI in Frontotemporal Dementia: Comparisons between Hippocampal Volumetry, Tensor-Based Morphometry and Voxel-Based Morphometry

    PubMed Central

    Muñoz-Ruiz, Miguel Ángel; Hartikainen, Päivi; Koikkalainen, Juha; Wolz, Robin; Julkunen, Valtteri; Niskanen, Eini; Herukka, Sanna-Kaisa; Kivipelto, Miia; Vanninen, Ritva; Rueckert, Daniel; Liu, Yawu; Lötjönen, Jyrki; Soininen, Hilkka

    2012-01-01

    Background MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods. Objective To compare FTD with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy. Methods Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups. Results We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55). Conclusion Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD. PMID:23285078

  2. Risk factors for development of postoperative cerebellar mutism syndrome in children after medulloblastoma surgery.

    PubMed

    Pols, San Y C V; van Veelen, Marie Lise C; Aarsen, Femke K; Gonzalez Candel, Antonia; Catsman-Berrevoets, Coriene E

    2017-07-01

    OBJECTIVE Postoperative cerebellar mutism syndrome (pCMS) occurs in 7%-50% of children after cerebellar tumor surgery. Typical features include a latent onset of 1-2 days after surgery, transient mutism, emotional lability, and a wide variety of motor and neurobehavioral abnormalities. Sequelae of this syndrome usually persist long term. The principal causal factor is bilateral surgical damage (regardless of tumor location) to any component of the proximal efferent cerebellar pathway, which leads to temporary dysfunction of cerebral cortical regions as a result of diaschisis. Tumor type, cerebellar midline location, and brainstem involvement are risk factors for pCMS that have been identified repeatedly, but they do not explain its latent onset. Ambiguous or negative results for other factors, such as hydrocephalus, postoperative meningitis, length of vermian incision, and tumor size, have been reached. The aim of this study was to identify perioperative clinical, radiological, and laboratory factors that also increase risk for the development of pCMS. The focus was on factors that might explain the delayed onset of pCMS and thus might provide a time window for taking precautionary measures to prevent pCMS or reduce its severity. The study was focused specifically on children who had undergone surgery for medulloblastoma. METHODS In this single-center retrospective cohort study, the authors included 71 children with medulloblastoma, 28 of whom developed pCMS after primary resection. Clinical and laboratory data were collected prospectively and analyzed systematically. Variables were included for univariate and multivariate analysis. RESULTS Univariate regression analysis revealed 7 variables that had a significant influence on pCMS onset, namely, tumor size, maximum tumor diameter > 5 cm, tumor infiltration or compression of the brainstem, significantly larger decreases in hemoglobin (p = 0.010) and hematocrit (p = 0.003) in the pCMS group after surgery than in the

  3. Ruptured Distal Posterior Inferior Cerebellar Artery (PICA) Aneurysms Associated with Cerebellar Arterial Venous Malformations (AVMs): A Case Series and Review of the Literature Demonstrating the Need for Angiographic Evaluation and Feasibility of Endovascular Treatment.

    PubMed

    Case, David; Kumpe, David; Cava, Luis; Neumann, Robert; White, Andrew; Roark, Christopher; Seinfeld, Joshua

    2017-01-01

    The characteristics, diagnosis, and preferred management strategies for distal posterior inferior cerebellar artery (PICA) aneurysms associated with cerebellar arteriovenous malformation (AVMs) are poorly understood. We present a case series with attention to aneurysm angioarchitecture, diagnostic imaging, treatment approaches, and a thorough review of the literature. With this information, we demonstrate a specific anatomical pattern for these aneurysms, an underreported need for conventional digital subtraction angiography (DSA) during evaluation, along with the utility of endovascular treatment with liquid embolic agents. Neurosurgical patients from 2005 to 2016 were reviewed to identify PICA aneurysms along with distal PICA aneurysms. Details of their presentation, imaging studies, associated AVMs and treatment were recorded. A thorough literature search of previous case series and case reports of distal PICA aneurysms with and without associated small cerebellar AVMs was performed with PubMed and Google Scholar. Thirty-four patients with PICA aneurysms were identified at our institution, 12 of which were in a distal segment. All 12 of these patients underwent DSA as a part of their evaluation. Of the 12 patients with distal PICA aneurysms, 9 presented with subarachnoid hemorrhage and intraventricular hemorrhage. Five of these patients had a small occult cerebellar AVM. All nine patients presenting with a ruptured distal PICA aneurysm had a Fischer grade 4 subarachnoid hemorrhage. Of the five patients with a small occult cerebellar AVM, the AVM nidus was missed on computed tomography angiogram (CTA) interpretation but easily visualized with DSA. CTA followed by DSA with concurrent endovascular treatment was performed in 9 of the 12 patients with distal PICA aneurysms. Two of the 12 patients were treated with microsurgical clip ligation, and one mycotic aneurysm was identified and treated with antibiotics. Parent vessel sacrifice was used distal to the aneurysm

  4. Cerebellar degeneration following neuroleptic malignant syndrome.

    PubMed Central

    Lal, V.; Sardana, V.; Thussu, A.; Sawhney, I. M.; Prabhakar, S.

    1997-01-01

    A 55-year-old woman with a history of bipolar affective disorder developed hyperpyrexia, rigidity and depressed consciousness (neuroleptic malignant syndrome) after commencing neuroleptic therapy. On regaining consciousness, she was mute and had signs suggesting pancerebellar involvement. Hyperpyrexia, which is a cardinal feature of neuroleptic malignant syndrome, may have caused cerebellar damage. Neuroleptic malignant syndrome needs both early recognition and prompt treatment to obviate devastating complications. PMID:9519191

  5. Gray matter changes in right superior temporal gyrus in criminal psychopaths. Evidence from voxel-based morphometry.

    PubMed

    Müller, Jürgen L; Gänssbauer, Susanne; Sommer, Monika; Döhnel, Katrin; Weber, Tatjana; Schmidt-Wilcke, Tobias; Hajak, Göran

    2008-08-30

    "Psychopathy" according to the PCL-R describes a specific subgroup of antisocial personality disorder with a high risk for criminal relapses. Lesion and imaging studies point towards frontal or temporal brain regions connected with disturbed social behavior, antisocial personality disorder (APD) and psychopathy. Morphologically, some studies described a reduced prefrontal brain volume, whereas others reported on temporal lobe atrophy. To further investigate whether participants with psychopathy according to the Psychopathy Checklist-Revised Version (PCL-R) show abnormalities in brain structure, we used voxel-based morphometry (VBM) to investigate region-specific changes in gray matter in 17 forensic male inpatients with high PCL-R scores (PCL-R>28) and 17 male control subjects with low PCL-R scores (PCL<10). We found significant gray matter reductions in frontal and temporal brain regions in psychopaths compared with controls. In particular, we found a highly significant volume loss in the right superior temporal gyrus. This is the first study to show that psychopathy is associated with a decrease in gray matter in both frontal and temporal brain regions, in particular in the right superior temporal gyrus, supporting the hypothesis that a disturbed frontotemporal network is critically involved in the pathogenesis of psychopathy.

  6. Reference Charts for Fetal Cerebellar Vermis Height: A Prospective Cross-Sectional Study of 10605 Fetuses

    PubMed Central

    Cignini, Pietro; Giorlandino, Maurizio; Brutti, Pierpaolo; Mangiafico, Lucia; Aloisi, Alessia; Giorlandino, Claudio

    2016-01-01

    Objective To establish reference charts for fetal cerebellar vermis height in an unselected population. Methods A prospective cross-sectional study between September 2009 and December 2014 was carried out at ALTAMEDICA Fetal–Maternal Medical Centre, Rome, Italy. Of 25203 fetal biometric measurements, 12167 (48%) measurements of the cerebellar vermis were available. After excluding 1562 (12.8%) measurements, a total of 10605 (87.2%) fetuses were considered and analyzed once only. Parametric and nonparametric quantile regression models were used for the statistical analysis. In order to evaluate the robustness of the proposed reference charts regarding various distributional assumptions on the ultrasound measurements at hand, we compared the gestational age-specific reference curves we produced through the statistical methods used. Normal mean height based on parametric and nonparametric methods were defined for each week of gestation and the regression equation expressing the height of the cerebellar vermis as a function of gestational age was calculated. Finally the correlation between dimension/gestation was measured. Results The mean height of the cerebellar vermis was 12.7mm (SD, 1.6mm; 95% confidence interval, 12.7–12.8mm). The regression equation expressing the height of the CV as a function of the gestational age was: height (mm) = -4.85+0.78 x gestational age. The correlation between dimension/gestation was expressed by the coefficient r = 0.87. Conclusion This is the first prospective cross-sectional study on fetal cerebellar vermis biometry with such a large sample size reported in literature. It is a detailed statistical survey and contains new centile-based reference charts for fetal height of cerebellar vermis measurements. PMID:26812238

  7. Effects of Cerebellar Disease on Sequences of Rapid Eye Movements

    PubMed Central

    King, Susan; Chen, Athena L.; Joshi, Anand; Serra, Alessandro; Leigh, R. John

    2011-01-01

    Summary Studying saccades can illuminate the more complex decision-making processes required for everyday movements. The double-step task, in which a target jumps to two successive locations before the subject has time to react, has proven a powerful research tool to investigate the brain’s ability to program sequential responses. We asked how patients with a range of cerebellar disorders responded to the double-step task, specifically, whether the initial saccadic response made to a target is affected by the appearance of a second target jump. We also sought to determine whether cerebellar patients were able to make corrective saccades towards the remembered second target location, if it were turned off soon after presentation. We tested saccades to randomly interleaved single- and double-step target jumps to eight locations on a circle. Patient’s initial responses to double-step stimuli showed 50% more error than saccades to single target jumps, and often, they failed to make a saccade to the first target jump. The presence of a second target jump had similar, but smaller effects in control subjects (error increased by 18%). During memory-guided double-step trials, both patients and controls made corrective saccades in darkness to the remembered location of the second jump. We conclude that in cerebellar patients, the second target jump interferes with programming of the saccade to the first target jump of a double-step stimulus; this defect highlights patients’ impaired ability to respond appropriately to sudden, conflicting changes in their environment. Conversely, since cerebellar patients can make corrective memory-guided saccades in darkness, they retain the ability to remember spatial locations, possibly due to non-retinal neural signals (corollary discharge) from cerebral hemispheric areas concerned with spatial localization. PMID:21385592

  8. Cortical morphometry in frontoparietal and default mode networks in math-gifted adolescents.

    PubMed

    Navas-Sánchez, Francisco J; Carmona, Susana; Alemán-Gómez, Yasser; Sánchez-González, Javier; Guzmán-de-Villoria, Juan; Franco, Carolina; Robles, Olalla; Arango, Celso; Desco, Manuel

    2016-05-01

    Math-gifted subjects are characterized by above-age performance in intelligence tests, exceptional creativity, and high task commitment. Neuroimaging studies reveal enhanced functional brain organization and white matter microstructure in the frontoparietal executive network of math-gifted individuals. However, the cortical morphometry of these subjects remains largely unknown. The main goal of this study was to compare the cortical morphometry of math-gifted adolescents with that of an age- and IQ-matched control group. We used surface-based methods to perform a vertex-wise analysis of cortical thickness and surface area. Our results show that math-gifted adolescents present a thinner cortex and a larger surface area in key regions of the frontoparietal and default mode networks, which are involved in executive processing and creative thinking, respectively. The combination of reduced cortical thickness and larger surface area suggests above-age neural maturation of these networks in math-gifted individuals. Hum Brain Mapp 37:1893-1902, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Grey matter volume and thickness abnormalities in young people with a history of childhood abuse.

    PubMed

    Lim, L; Hart, H; Mehta, M; Worker, A; Simmons, A; Mirza, K; Rubia, K

    2018-04-01

    Childhood abuse is associated with abnormalities in brain structure and function. Few studies have investigated abuse-related brain abnormalities in medication-naïve, drug-free youth that also controlled for psychiatric comorbidities by inclusion of a psychiatric control group, which is crucial to disentangle the effects of abuse from those associated with the psychiatric conditions. Cortical volume (CV), cortical thickness (CT) and surface area (SA) were measured in 22 age- and gender-matched medication-naïve youth (aged 13-20) exposed to childhood abuse, 19 psychiatric controls matched for psychiatric diagnoses and 27 healthy controls. Both region-of-interest (ROI) and whole-brain analyses were conducted. For the ROI analysis, the childhood abuse group compared with healthy controls only, had significantly reduced CV in bilateral cerebellum and reduced CT in left insula and right lateral orbitofrontal cortex (OFC). At the whole-brain level, relative to healthy controls, the childhood abuse group showed significantly reduced CV in left lingual, pericalcarine, precuneus and superior parietal gyri, and reduced CT in left pre-/postcentral and paracentral regions, which furthermore correlated with greater abuse severity. They also had increased CV in left inferior and middle temporal gyri relative to healthy controls. Abnormalities in the precuneus, temporal and precentral regions were abuse-specific relative to psychiatric controls, albeit at a more lenient level. Groups did not differ in SA. Childhood abuse is associated with widespread structural abnormalities in OFC-insular, cerebellar, occipital, parietal and temporal regions, which likely underlie the abnormal affective, motivational and cognitive functions typically observed in this population.

  10. Improved motor performance in Dyt1 ΔGAG heterozygous knock-in mice by cerebellar Purkinje-cell specific Dyt1 conditional knocking-out.

    PubMed

    Yokoi, Fumiaki; Dang, Mai Tu; Li, Yuqing

    2012-05-01

    Early-onset generalized torsion dystonia (dystonia 1) is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most patients have a 3-base pair deletion (ΔGAG) in one allele of DYT1, corresponding to a loss of a glutamic acid residue (ΔE) in the C-terminal region of the protein. Functional alterations in basal ganglia circuits and the cerebellum have been reported in dystonia. Pharmacological manipulations or mutations in genes that result in functional alterations of the cerebellum have been reported to have dystonic symptoms and have been used as phenotypic rodent models. Additionally, structural lesions in the abnormal cerebellar circuits, such as cerebellectomy, have therapeutic effects in these models. A previous study has shown that the Dyt1 ΔGAG heterozygous knock-in (KI) mice exhibit motor deficits in the beam-walking test. Both Dyt1 ΔGAG heterozygous knock-in (KI) and Dyt1 Purkinje cell-specific knockout (Dyt1 pKO) mice exhibit dendritic alterations of cerebellar Purkinje cells. Here, Dyt1 pKO mice exhibited significantly less slip numbers in the beam-walking test, suggesting better motor performance than control littermates, and normal gait. Furthermore, Dyt1 ΔGAG KI/Dyt1 pKO double mutant mice exhibited significantly lower numbers of slips than Dyt1 ΔGAG heterozygous KI mice, suggesting Purkinje-cell specific knockout of Dyt1 wild-type (WT) allele in Dyt1 ΔGAG heterozygous KI mice rescued the motor deficits. The results suggest that molecular lesions of torsinA in Purkinje cells by gene therapy or intervening in the signaling pathway downstream of the cerebellar Purkinje cells may rescue motor symptoms in dystonia 1. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Improved motor performance in Dyt1 ΔGAG heterozygous knock-in mice by cerebellar Purkinje-cell specific Dyt1 conditional knocking-out

    PubMed Central

    Yokoi, Fumiaki; Dang, Mai Tu; Li, Yuqing

    2012-01-01

    Early-onset generalized torsion dystonia (dystonia 1) is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most patients have a 3-base pair deletion (ΔGAG) in one allele of DYT1, corresponding to a loss of a glutamic acid residue (ΔE) in the C-terminal region of the protein. Functional alterations in basal ganglia circuits and the cerebellum have been reported in dystonia. Pharmacological manipulations or mutations in genes that result in functional alterations of the cerebellum have been reported to have dystonic symptoms and have been used as phenotypic rodent models. Additionally, structural lesions in the abnormal cerebellar circuits, such as cerebellectomy, have therapeutic effects in these models. A previous study has shown that the Dyt1 ΔGAG heterozygous knock-in (KI) mice exhibit motor deficits in the beam-walking test. Both Dyt1 ΔGAG heterozygous knock-in (KI) and Dyt1 Purkinje cell-specific knockout (Dyt1 pKO) mice exhibit dendritic alterations of cerebellar Purkinje cells. Here, Dyt1 pKO mice exhibited significantly less slip numbers in the beam-walking test, suggesting better motor performance than control littermates, and normal gait. Furthermore, Dyt1 ΔGAG KI/Dyt1 pKO double mutant mice exhibited significantly lower numbers of slips than Dyt1 ΔGAG heterozygous KI mice, suggesting Purkinje-cell specific knockout of Dyt1 wild-type (WT) allele in Dyt1 ΔGAG heterozygous KI mice rescued the motor deficits. The results suggest that molecular lesions of torsinA in Purkinje cells by gene therapy or intervening in the signaling pathway downstream of the cerebellar Purkinje cells may rescue motor symptoms in dystonia 1. PMID:22391119

  12. Eye hyperdeviation in mouse cerebellar mutants is comparable to the gravity-dependent component of human downbeat nystagmus.

    PubMed

    Stahl, John S; Oommen, Brian S

    2008-01-01

    Humans with cerebellar degeneration commonly exhibit downbeat nystagmus (DBN). DBN has gravity-independent and -dependent components, and the latter has been proposed to reflect hyperactive tilt maculo-ocular reflexes (tilt-MOR). Mice with genetically determined cerebellar ataxia do not exhibit DBN, but they do exhibit tonic hyperdeviation of the eyes, which we have proposed to be the DBN equivalent. As such, the tilt-MOR might be predicted to be hyperactive in these mutant mice. We measured the tilt-MOR in 10 normal C57BL/6 mice and in 6 tottering, a mutant exhibiting ataxia and ocular motor abnormalities due to mutation of the P/Q calcium channel. Awake mice were placed in body orientations spanning 360 degrees about the pitch axis. The absolute, equilibrium vertical angular deviations of one eye were measured using infrared videooculography. In both strains, eye elevation varied quasi-sinusoidally with tilt angle in the range of 90 degrees nose-up to 90 degrees nose-down. Beyond this range the eye returned to a neutral position. Deviation over +/-30 degrees of tilt was an approximately linear function of the projection of the gravity vector into the animal's horizontal plane, and can thus be summarized by its slope (sensitivity). Sensitivity measured 14.9 degrees/g for C57BL/6 and 20.3 degrees/g for tottering, a statistically significant difference. Thus the pitch otolithic reflex of the ataxic mutants is hyperactive relative to controls and could explain tonic hyperdeviation of the eyes, consistent with the idea that the tonic hyperdeviation is analogous to DBN.

  13. Increased Cerebellar Functional Connectivity With the Default-Mode Network in Unaffected Siblings of Schizophrenia Patients at Rest.

    PubMed

    Guo, Wenbin; Liu, Feng; Zhang, Zhikun; Liu, Guiying; Liu, Jianrong; Yu, Liuyu; Xiao, Changqing; Zhao, Jingping

    2015-11-01

    The default-mode network (DMN) is vital in the neurobiology of schizophrenia, and the cerebellum participates in the high-order cognitive network such as the DMN. However, the specific contribution of the cerebellum to the DMN abnormalities remains unclear in unaffected siblings of schizophrenia patients. Forty-six unaffected siblings of schizophrenia patients and 46 healthy controls were recruited for a resting-state scan. The images were analyzed using the functional connectivity (FC) method. The siblings showed significantly increased FCs between the left Crus I and the left superior medial prefrontal cortex (MPFC), as well as between the lobule IX and the bilateral MPFC (orbital part) and right superior MPFC compared with the controls. No significantly decreased FC was observed in the siblings relative to the controls. The analyses were replicated in 49 first-episode, drug-naive patients with schizophrenia, and the results showed that the siblings and the patients shared increased FCs between the left Crus I and the left superior MPFC, as well as between the lobule IX and the left MPFC (orbital part) compared with the controls. These findings suggest that increased cerebellar-DMN connectivities emerge earlier than illness onset, which highlight the contribution of the cerebellum to the DMN alterations in unaffected siblings. The shared increased cerebellar-DMN connectivities between the patients and the siblings may be used as candidate endophenotypes for schizophrenia. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Cerebellar contributions to motor control and language comprehension: searching for common computational principles.

    PubMed

    Moberget, Torgeir; Ivry, Richard B

    2016-04-01

    The past 25 years have seen the functional domain of the cerebellum extend beyond the realm of motor control, with considerable discussion of how this subcortical structure contributes to cognitive domains including attention, memory, and language. Drawing on evidence from neuroanatomy, physiology, neuropsychology, and computational work, sophisticated models have been developed to describe cerebellar function in sensorimotor control and learning. In contrast, mechanistic accounts of how the cerebellum contributes to cognition have remained elusive. Inspired by the homogeneous cerebellar microanatomy and a desire for parsimony, many researchers have sought to extend mechanistic ideas from motor control to cognition. One influential hypothesis centers on the idea that the cerebellum implements internal models, representations of the context-specific dynamics of an agent's interactions with the environment, enabling predictive control. We briefly review cerebellar anatomy and physiology, to review the internal model hypothesis as applied in the motor domain, before turning to extensions of these ideas in the linguistic domain, focusing on speech perception and semantic processing. While recent findings are consistent with this computational generalization, they also raise challenging questions regarding the nature of cerebellar learning, and may thus inspire revisions of our views on the role of the cerebellum in sensorimotor control. © 2016 New York Academy of Sciences.

  15. Altered microstructural connectivity of the superior cerebellar peduncle is related to motor dysfunction in children with autistic spectrum disorders.

    PubMed

    Hanaie, Ryuzo; Mohri, Ikuko; Kagitani-Shimono, Kuriko; Tachibana, Masaya; Azuma, Junji; Matsuzaki, Junko; Watanabe, Yoshiyuki; Fujita, Norihiko; Taniike, Masako

    2013-10-01

    Many studies have reported motor impairments in autistic spectrum disorders (ASD). However, the brain mechanism underlying motor impairment in ASD remains unclear. Recent neuroimaging studies have suggested that underconnectivity between the cerebellum and other brain regions contributes to the features of ASD. In this study, we investigated the microstructural integrity of the cerebellar pathways, including the superior, middle, and inferior cerebellar peduncles, of children with and without ASD by using diffusion tensor imaging (DTI) tractography to determine whether the microstructural integrity of the cerebellar pathways is related to motor function in children with ASD. Thirteen children with ASD and 11 age-, gender-, handedness-, and IQ-matched typically developing (TD) controls were enrolled in this study. DTI outcome measurements, such as fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), for the cerebellar pathways were calculated. The Movement Assessment Battery for Children 2 (M-ABC 2) was used for assessing motor functions. There were no significant differences between the two groups in RD. However, compared to the TD subjects, patients with ASD had a significantly lower FA in the right superior cerebellar peduncle and lower AD in the left superior cerebellar peduncle, in addition to a significantly lower score in ball skills and the total test score of M-ABC 2. There was a significant positive correlation between the total test score of M-ABC 2 and FA in the right superior cerebellar peduncle in the ASD group. These findings suggest that the altered microstructural integrity of the superior cerebellar peduncle may be related to motor impairment in ASD.

  16. Cerebellar Lingula Size and Experiential Risk Factors Associated with High Levels of Alcohol and Drug Use in Young Adults

    PubMed Central

    Anderson, Carl M.; Rabi, Keren; Lukas, Scott E.; Teicher, Martin H.

    2014-01-01

    Previous studies have reported cerebellar abnormalities or static ataxia associated with risk for chronic use of alcohol and drugs. Adverse childhood experience (ACE) is another strong risk factor for later substance abuse. We therefore, sought to ascertain the relationship between morphological phenotypes of the lingula (Lobule I) of the anterior cerebellar vermis (ACV), and exposure to emotional (EM) versus physical (PM) maltreatment,on the degree of ongoing alcohol or drug use. The study design consisted of a cross-sectional in vivo neuroimaging study, utilizing retrospective assessment of maltreatment history and self-reports of alcohol and substance use. Study participants were 153 subjects (54M/99F, 21.9±2.2 years) selected for imaging from a database of 1,402 community participants 18–25 years of age, who completed a detailed online screening instrument, and met rigorous inclusion/exclusion criteria. Subjects were exposed to only physical abuse or harsh corporal punishment (PM group, n=37); parental verbal abuse and/or witnessing domestic violence (EM group, n= 58); or had no history of maltreatment or Axis I disorders (n=58). The main outcomes measures consisted of the grey matter volume of Lobule I as measured by manual tracing, number and type of alcoholic beverages consumed during a drinking session, number of sessions per month, and monthly drug use, along with family history of drug and alcohol abuse. Lingula thickness was not attenuated by alcohol use or maltreatment history. However, increased lingula thickness was associated with greater consumption of drugs and hard liquor, particularly in physically maltreated subjects who consumed 2.5- and 2.7-fold more alcohol, and used drugs 6.1- and 7.8-fold more frequently than controls or EM subjects, respectively. In conclusion, physical maltreatment was observed to interact with cerebellar morphology resulting in a strong association with alcohol and substance use. Lingula thickness may represent a

  17. CNS development under altered gravity: cerebellar glial and neuronal protein expression in rat neonates exposed to hypergravity

    NASA Astrophysics Data System (ADS)

    Nguon, K.; Li, G.-H.; Sajdel-Sulkowska, E. M.

    2004-01-01

    The future of space exploration depends on a solid understanding of the developmental process under microgravity, specifically in relation to the central nervous system (CNS). We have previously employed a hypergravity paradigm to assess the impact of altered gravity on the developing rat cerebellum [Exp. Biol. Med. 226 (2000) 790]. The present study addresses the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of selected glial and neuronal cerebellar proteins in rat neonates exposed to hypergravity (1.5 G) from embryonic day (E)11 to postnatal day (P)6 or P9 (the time of maximal cerebellar changes) comparing them against their expression in rat neonates developing under normal gravity. Proteins were analyzed by quantitative Western blots of cerebellar homogenates; RNA analysis was performed in the same samples using quantitative PCR. Densitometric analysis of Western blots suggested a reduction in glial (glial acidic protein, GFAP) and neuronal (neuronal cell adhesion moiecule, NCAM-L1, synaptophysin) proteins, but the changes in individual cerebellar proteins in hypergravity-exposed neonates appeared both age- and gender-specific. RNA analysis suggested a reduction in GFAP and synaptophysin mRNAs on P6. These data suggest that exposure to hypergravity may interfere with the expression of selected cerebellar proteins. These changes in protein expression may be involved in mediating the effect of hypergravity on the developing rat cerebellum.

  18. Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups

    PubMed Central

    Sveinsdóttir, Kristbjörg; Länsberg, John-Kalle; Sveinsdóttir, Snjólaug; Garwicz, Martin; Ohlsson, Lennart; Hellström, Ann; Smith, Lois; Gram, Magnus; Ley, David

    2018-01-01

    Cerebellar growth is impeded following very preterm birth in human infants and the observed reduction in cerebellar volume is associated with neurodevelopmental impairment. Decreased levels of circulating insulin-like growth factor 1 (IGF-1) are associated with decreased cerebellar volume. The relationship between preterm birth, circulating IGF-1, and key cell populations supporting cerebellar proliferation is unknown. The aim of this study was to evaluate the effect of preterm birth on postnatal growth, circulating IGF-1, and cerebellar maturation in a preterm rabbit pup model. Preterm rabbit pups (PT) were delivered by cesarean section at day 29 of gestation, cared for in closed incubators with humidified air, and gavage fed with formula. Control term pups (T) delivered by spontaneous vaginal delivery at day 32 of gestation were housed and fed by their lactating doe. In vivo perfusion-fixation for immunohistochemical evaluation of cerebellar proliferation, cell maturation, and apoptosis was performed at repeated time points in PT and T pups. Results show that the mean weight of the pups and circulating IGF-1 protein levels were lower in the PT group at all time points (p < 0.05) than in the T group. Postnatal weight development correlated with circulating IGF-1 (r2 = 0.89) independently of gestational age at birth and postnatal age. The proliferative (Ki-67-positive) portion of the external granular layer (EGL) was decreased in the PT group at postnatal day 2 (P2) compared to in the T group (p = 0.01). Purkinje cells exhibited decreased calbindin staining at P0 (p = 0.003), P2 (p = 0.004), and P5 (p = 0.04) in the PT group compared to in the T group. Staining for sonic hedgehog was positive in neuronal EGL progenitors and Purkinje cells at early time points but was restricted to a well-defined Purkinje cell monolayer at later time points. Preterm birth in rabbit pups is associated with lower circulating levels of IGF-1, decreased postnatal growth, and decreased

  19. Development of motor coordination and cerebellar structure in male and female rat neonates exposed to hypergravity

    NASA Astrophysics Data System (ADS)

    Nguon, K.; Ladd, B.; Baxter, M. G.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that the developing rat cerebellum is affected by exposure to hypergravity. In the present study, we explored the hypothesis that the changes in cerebellar structure in hypergravity-exposed rat neonates may affect their motor coordination. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravitational loading. To test this hypothesis, we compared motor behavior, cerebellar structure, and protein expression in rat neonates exposed to 1.5 1.75G on a 24-ft centrifuge daily for 22.5 h starting on gestational day (G) 10, through birth on G22/G23 and through postnatal day (P) 21. Exposure to hypergravity impacted the neurodevelopmental process as indicated by: (1) impaired righting response on P3, more than doubling the righting time at 1.75G, and (2) delayed onset of the startle response by one day, from P9 in controls to P10 in hypergravity-exposed pups. Hypergravity exposure resulted in impaired motor functions as evidenced by performance on a rotarod on P21; the duration of the stay on the rotarod recorded for 1.75G pups of both sexes was one tenth that of the stationary control (SC) pups. These changes in motor behavior were associated with cerebellar changes: (1) cerebellar mass on P6 was decreased by 7.5% in 1.5G-exposed male pups, 27.5% in 1.75G-exposed male pups, 17.5% in 1.5G-exposed female pups, and 22.5% in 1.75G female pups and (2) changes in the expression of glial and neuronal proteins. The results of this study suggest that perinatal exposure to hypergravity affects cerebellar development as evidenced by decreased cerebellar mass and altered cerebellar protein expression; cerebellar changes observed in hypergravity-exposed rat neonates are associated with impaired motor behavior. Furthermore, the response to hypergravity appears to be different in male and female neonates. If one accepts that the hypergravity paradigm is a useful animal model with which to predict those biological processes

  20. Abnormal electroretinogram associated with developmental brain anomalies.

    PubMed Central

    Cibis, G W; Fitzgerald, K M

    1995-01-01

    PURPOSE: We have encountered abnormal ERGs associated with optic nerve hypoplasia, macular, optic nerve and chorioretinal colobomata and developmental brain anomalies. Brain anomalies include cortical dysgenesis, lissencephaly, porencephaly, cerebellar and corpus callosum hypoplasia. We describe six exemplar cases. METHODS: Scotopic and photopic ERGs adherent to international standards were performed as well as photopic ERGs to long-duration stimuli. CT or MRI studies were also done. The ERGs were compared to age-matched normal control subjects. RESULTS: ERG changes include reduced amplitude b-waves to blue and red stimuli under scotopic testing conditions. Implicit times were often delayed. The photopic responses also showed reduced amplitude a- and b-waves with implicit time delays. The long-duration photopic ERG done in one case shows attenuation of both ON- and OFF-responses. CONCLUSIONS: Common underlying developmental genetic or environmental unifying casualties are speculated to be at fault in causing these cases of associated retinal and brain abnormalities. No single etiology is expected. Multiple potential causes acting early in embryogenesis effecting neuronal induction, migration and differentiation are theorized. These occur at a time when brain and retinal cells are sufficiently undifferentiated to be similarly effected. We call these cases examples of Brain Retina Neuroembryodysgenesis (BRNED). Homeobox and PAX genes with global neuronal developmental influences are gene candidates to unify the observed disruption of brain and retinal cell development. The ERG can provide a valuable clinical addition in understanding and ultimately classifying these disorders. Images FIGURE 1 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 PMID:8719676

  1. From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study

    PubMed Central

    Aghakhanyan, Gayane; Bonanni, Paolo; Randazzo, Giovanna; Nappi, Sara; Tessarotto, Federica; De Martin, Lara; Frijia, Francesca; De Marchi, Daniele; De Masi, Francesco; Kuppers, Beate; Lombardo, Francesco; Caramella, Davide; Montanaro, Domenico

    2016-01-01

    Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS. PMID:27626634

  2. Static Posturography and Falls According to Pyramidal, Sensory and Cerebellar Functional Systems in People with Multiple Sclerosis

    PubMed Central

    Kalron, Alon; Givon, Uri; Frid, Lior; Dolev, Mark; Achiron, Anat

    2016-01-01

    Balance impairment is common in people with multiple sclerosis (PwMS) and frequently impacts quality of life by decreasing mobility and increasing the risk of falling. However, there are only scarce data examining the contribution of specific neurological functional systems on balance measures in MS. Therefore, the primary aim of our study was to examine the differences in posturography parameters and fall incidence according to the pyramidal, cerebellar and sensory systems functional systems in PwMS. The study included 342 PwMS, 211 women and mean disease duration of 8.2 (S.D = 8.3) years. The study sample was divided into six groups according to the pyramidal, cerebellar and sensory functional system scores, derived from the Expanded Disability Status Scale (EDSS) data. Static postural control parameters were obtained from the Zebris FDM-T Treadmill (zebris® Medical GmbH, Germany). Participants were defined as "fallers" and "non-fallers" based on their fall history. Our findings revealed a trend that PwMS affected solely in the pyramidal system, have reduced stability compared to patients with cerebellar and sensory dysfunctions. Moreover, the addition of sensory impairments to pyramidal dysfunction does not exacerbate postural control. The patients in the pure sensory group demonstrated increased stability compared to each of the three combined groups; pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups. As for fall status, the percentage of fallers in the pure pyramidal, cerebellar and sensory groups were 44.3%, 33.3% and 19.5%, respectively. As for the combined functional system groups, the percentage of fallers in the pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups were 59.7%, 40.7% and 65%, respectively. This study confirms that disorders in neurological functional systems generate different effects on postural control and incidence of falls in the MS population. From a clinical standpoint, the

  3. Principal Component Analysis of Cerebellar Shape on MRI Separates SCA Types 2 and 6 into Two Archetypal Modes of Degeneration

    PubMed Central

    Jung, Brian C.; Choi, Soo I.; Du, Annie X.; Cuzzocreo, Jennifer L.; Geng, Zhuo Z.; Ying, Howard S.; Perlman, Susan L.; Toga, Arthur W.; Prince, Jerry L.

    2014-01-01

    Although “cerebellar ataxia” is often used in reference to a disease process, presumably there are different underlying pathogenetic mechanisms for different subtypes. Indeed, spinocerebellar ataxia (SCA) types 2 and 6 demonstrate complementary phenotypes, thus predicting a different anatomic pattern of degeneration. Here, we show that an unsupervised classification method, based on principal component analysis (PCA) of cerebellar shape characteristics, can be used to separate SCA2 and SCA6 into two classes, which may represent disease-specific archetypes. Patients with SCA2 (n=11) and SCA6 (n=7) were compared against controls (n=15) using PCA to classify cerebellar anatomic shape characteristics. Within the first three principal components, SCA2 and SCA6 differed from controls and from each other. In a secondary analysis, we studied five additional subjects and found that these patients were consistent with the previously defined archetypal clusters of clinical and anatomical characteristics. Secondary analysis of five subjects with related diagnoses showed that disease groups that were clinically and pathophysiologically similar also shared similar anatomic characteristics. Specifically, Archetype #1 consisted of SCA3 (n=1) and SCA2, suggesting that cerebellar syndromes accompanied by atrophy of the pons may be associated with a characteristic pattern of cerebellar neurodegeneration. In comparison, Archetype #2 was comprised of disease groups with pure cerebellar atrophy (episodic ataxia type 2 (n=1), idiopathic late-onset cerebellar ataxias (n=3), and SCA6). This suggests that cerebellar shape analysis could aid in discriminating between different pathologies. Our findings further suggest that magnetic resonance imaging is a promising imaging biomarker that could aid in the diagnosis and therapeutic management in patients with cerebellar syndromes. PMID:22258915

  4. Pharmacological treatments of cerebellar ataxia.

    PubMed

    Ogawa, Masafumi

    2004-01-01

    The confirmed pharmacological treatment of cerebellar ataxia is still lacking. In a recent preliminary trial, we showed that D-cycloserine, a partial NMDA allosteric agonist, may relieve the symptoms. In this paper, major clinical trials to relieve ataxic symptoms are reviewed. Previous studies showed some efficacy of physostigmine in ataxic patients. However, physostigmine did not improve the ataxia in a recent double-blind crossover study. The replacement therapy of the deficient cholinergic system with choline or choline derivatives was tried in patients with Friedreich's ataxia and other ataxic patients, but the result was not definitive. A levorotatory form of hydroxytryptophan (a serotonin precursor), a serotoninergic 5-HT1A agonist, a serotoninergic 5-HT3 antagonist, and a serotonin reuptake inhibitor were also used for the therapy for ataxia. In a double-blind randomized study, buspirone, a 5-HT1A agonist was active in cerebellar ataxia, but the effect is partial and not major. The effects of the studies with the other serotoninergic drugs were not consistent. The effect of sulfamethoxazole-trimethoprim therapy in spinocerebellar ataxia type3/Machado-Joseph disease (MJD) was reported, although the therapy improved spasticity or rigidity, rather than ataxia. In contrast to previous studies, sulfamethoxazole-trimethoprim therapy in MJD had no effect in a 2001 double-blind crossover study. The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy. However, a well-designed double-blind crossover trial is needed to confirm the effect.

  5. A reexamination of age-related variation in body weight and morphometry of Maryland nutria

    USGS Publications Warehouse

    Sherfy, M.H.; Mollett, T.A.; McGowan, K.R.; Daugherty, S.L.

    2006-01-01

    Age-related variation in morphometry has been documented for many species. Knowledge of growth patterns can be useful for modeling energetics, detecting physiological influences on populations, and predicting age. These benefits have shown value in understanding population dynamics of invasive species, particularly in developing efficient control and eradication programs. However, development and evaluation of descriptive and predictive models is a critical initial step in this process. Accordingly, we used data from necropsies of 1,544 nutria (Myocastor coypus) collected in Maryland, USA, to evaluate the accuracy of previously published models for prediction of nutria age from body weight. Published models underestimated body weights of our animals, especially for ages <3. We used cross-validation procedures to develop and evaluate models for describing nutria growth patterns and for predicting nutria age. We derived models from a randomly selected model-building data set (n = 192-193 M, 217-222 F) and evaluated them with the remaining animals (n = 487-488 M, 642-647 F). We used nonlinear regression to develop Gompertz growth-curve models relating morphometric variables to age. Predicted values of morphometric variables fell within the 95% confidence limits of their true values for most age classes. We also developed predictive models for estimating nutria age from morphometry, using linear regression of log-transformed age on morphometric variables. The evaluation data set corresponded with 95% prediction intervals from the new models. Predictive models for body weight and length provided greater accuracy and less bias than models for foot length and axillary girth. Our growth models accurately described age-related variation in nutria morphometry, and our predictive models provided accurate estimates of ages from morphometry that will be useful for live-captured individuals. Our models offer better accuracy and precision than previously published models

  6. Model-Driven Analysis of Eyeblink Classical Conditioning Reveals the Underlying Structure of Cerebellar Plasticity and Neuronal Activity.

    PubMed

    Antonietti, Alberto; Casellato, Claudia; D'Angelo, Egidio; Pedrocchi, Alessandra

    The cerebellum plays a critical role in sensorimotor control. However, how the specific circuits and plastic mechanisms of the cerebellum are engaged in closed-loop processing is still unclear. We developed an artificial sensorimotor control system embedding a detailed spiking cerebellar microcircuit with three bidirectional plasticity sites. This proved able to reproduce a cerebellar-driven associative paradigm, the eyeblink classical conditioning (EBCC), in which a precise time relationship between an unconditioned stimulus (US) and a conditioned stimulus (CS) is established. We challenged the spiking model to fit an experimental data set from human subjects. Two subsequent sessions of EBCC acquisition and extinction were recorded and transcranial magnetic stimulation (TMS) was applied on the cerebellum to alter circuit function and plasticity. Evolutionary algorithms were used to find the near-optimal model parameters to reproduce the behaviors of subjects in the different sessions of the protocol. The main finding is that the optimized cerebellar model was able to learn to anticipate (predict) conditioned responses with accurate timing and success rate, demonstrating fast acquisition, memory stabilization, rapid extinction, and faster reacquisition as in EBCC in humans. The firing of Purkinje cells (PCs) and deep cerebellar nuclei (DCN) changed during learning under the control of synaptic plasticity, which evolved at different rates, with a faster acquisition in the cerebellar cortex than in DCN synapses. Eventually, a reduced PC activity released DCN discharge just after the CS, precisely anticipating the US and causing the eyeblink. Moreover, a specific alteration in cortical plasticity explained the EBCC changes induced by cerebellar TMS in humans. In this paper, for the first time, it is shown how closed-loop simulations, using detailed cerebellar microcircuit models, can be successfully used to fit real experimental data sets. Thus, the changes of the

  7. Magnetic resonance imaging depiction of acquired Dyke-Davidoff-Masson syndrome with crossed cerebro-cerebellar diaschisis: Report of two cases.

    PubMed

    Gupta, Ranjana; Joshi, Sandeep; Mittal, Amit; Luthra, Ishita; Mittal, Puneet; Verma, Vibha

    2015-01-01

    Acquired Dyke-Davidoff-Masson syndrome, also known as hemispheric atrophy, is characterized by loss of volume of one cerebral hemisphere from an insult in early life. Crossed cerebellar diaschisis refers to dysfunction/atrophy of cerebellar hemisphere which is secondary to contralateral supratentorial insult. We describe magnetic resonance imaging findings in two cases of acquired Dyke-Davidoff-Masson syndrome with crossed cerebro-cerebellar diaschisis.

  8. Ultrastructural study of the GABAergic and cerebellar input to the nucleus reticularis tegmenti pontis.

    PubMed

    Verveer, C; Hawkins, R K; Ruigrok, T J; De Zeeuw, C I

    1997-08-22

    The nucleus reticularis tegmenti pontis is an intermediate of the cerebrocerebellar pathway and serves as a relay centre for sensorimotor and visual information. The central nuclei of the cerebellum provide a dense projection to the nucleus reticularis tegmenti pontis, but it is not known to what extent this projection is excitatory or inhibitory, and whether the terminals of this projection contact the neurons in the nucleus reticularis tegmenti pontis that give rise to the mossy fibre collaterals innervating the cerebellar nuclei. In the present study the nucleus reticularis tegmenti pontis of the cat was investigated at the ultrastructural level following anterograde and retrograde transport of wheat germ agglutinin coupled to horseradish peroxidase (WGA-HRP) from the cerebellar nuclei combined with postembedding GABA immunocytochemistry. The neuropil of this nucleus was found to contain many WGA-HRP labeled terminals, cell bodies and dendrites, but none of these pre- or postsynaptic structures was double labeled with GABA. The vast majority of the WGA-HRP labeled terminals contained clear spherical vesicles, showed asymmetric synapses, and contacted intermediate or distal dendrites. Many of the postsynaptic elements of the cerebellar afferents in the nucleus reticularis tegmenti pontis were retrogradely labeled with WGA-HRP, while relatively few were GABAergic. We conclude that all cerebellar terminals in the nucleus reticularis tegmenti pontis of the cat are nonGABAergic and excitatory, and that they contact predominantly neurons that project back to the cerebellum. Thus, the reciprocal circuit between the cerebellar nuclei and the nucleus reticularis tegmenti pontis appears to be well designed to function as an excitatory reverberating loop.

  9. Autosomal dominant cerebellar ataxia with slow ocular saccades, neuropathy and orthostatism: a novel entity?

    PubMed

    Wictorin, Klas; Brådvik, Björn; Nilsson, Karin; Soller, Maria; van Westen, Danielle; Bynke, Gunnel; Bauer, Peter; Schöls, Ludger; Puschmann, Andreas

    2014-07-01

    We describe the clinical characteristics of a Swedish family with autosomal dominant cerebellar ataxia, sensory and autonomic neuropathy, additional neurological features and unknown genetic cause. Fourteen affected family members were identified. Their disorder was characterized by neurological examination, MRI, electroneurography, electromyography, MIBG-scintigraphy, and tilt-testing. The disorder presented as a balance and gait disturbance starting between 16 and 47 years of age. Cerebellar ataxia progressed slowly over the course of decades, and MRI showed mild to moderate cerebellar atrophy. Sensory axonal polyneuropathy was the most prominent additional feature and occurred in all patients examined. Autonomic neuropathy caused pronounced orthostatic dysregulation in at least four patients. Several affected members showed muscle wasting, and mild upper or lower motor neuron signs were documented. Patients had no nystagmus but slow or hypometric horizontal saccades and ocular motor apraxia. Cognition remained unimpaired, and there were no non-neurological disease manifestations. The disorder affected men and women in successive generations in a pattern compatible with autosomal dominant inheritance without evidence of anticipation. A second family where 7 members had very similar symptoms was identified and its origin traced back to the same village in southern Sweden as that of the first family's ancestors. All relevant known genetic causes of cerebellar ataxia were excluded by a novel next-generation sequencing approach. We present two probably related Swedish families with a characteristic and novel clinical syndrome of cerebellar ataxia and sensory polyneuropathy. The study serves as a basis for the mapping of the underlying genetic cause. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Comparative analysis of cadherin expression and connectivity patterns in the cerebellar system of ferret and mouse.

    PubMed

    Neudert, Franziska; Nuernberger, Krishna-K Monique; Redies, Christoph

    2008-12-20

    The cerebellum shows remarkable variations in the relative size of its divisions among vertebrate species. In the present study, we compare the cerebella of two mammals (ferret and mouse) by mapping the expression of three cadherins (cadherin-8, protocadherin-7, and protocadherin-10) at similar postnatal stages. The three cadherins are expressed differentially in parasagittal stripes in the cerebellar cortex, in the portions of the deep cerebellar nuclei, in the divisions of the inferior olivary nucleus, and in the lateral vestibular nucleus. The expression profiles suggest that the cadherin-positive structures are interconnected. The expression patterns resemble each other in ferret and mouse, although some differences can be observed. The general resemblance indicates that cerebellar organization is based on a common set of embryonic divisions in the two species. Consequently, the large differences in cerebellar morphology between the two species are more likely caused by differential growth of these embryonic divisions than by differences in early embryonic patterning. Based on the cadherin expression patterns, a model of corticonuclear projection territories in ferret and mouse is proposed. In summary, our results indicate that the cerebellar systems of rodents and carnivores display a relatively large degree of similarity in their molecular and functional organization.

  11. Disrupted Cerebro-cerebellar Intrinsic Functional Connectivity in Young Adults with High-functioning Autism Spectrum Disorder: A Data-driven, Whole-brain, High Temporal Resolution fMRI Study.

    PubMed

    Arnold Anteraper, Sheeba; Guell, Xavier; D'Mello, Anila; Joshi, Neha; Whitfield-Gabrieli, Susan; Joshi, Gagan

    2018-06-13

    To examine the resting-state functional-connectivity (RsFc) in young adults with high-functioning autism spectrum disorder (HF-ASD) using state-of-the-art fMRI data acquisition and analysis techniques. Simultaneous multi-slice, high temporal resolution fMRI acquisition; unbiased whole-brain connectome-wide multivariate pattern analysis (MVPA) techniques for assessing RsFc; and post-hoc whole-brain seed-to-voxel analyses using MVPA results as seeds. MVPA revealed two clusters of abnormal connectivity in the cerebellum. Whole-brain seed-based functional connectivity analyses informed by MVPA-derived clusters showed significant under connectivity between the cerebellum and social, emotional, and language brain regions in the HF-ASD group compared to healthy controls. The results we report are coherent with existing structural, functional, and RsFc literature in autism, extend previous literature reporting cerebellar abnormalities in the neuropathology of autism, and highlight the cerebellum as a potential target for therapeutic, diagnostic, predictive, and prognostic developments in ASD. The description of functional connectivity abnormalities using whole-brain, data-driven analyses as reported in the present study may crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.

  12. Spontaneous Cerebellar Hematoma: Decision Making in Conscious Adults.

    PubMed

    Alkosha, Hazem M; Ali, Nabil Mansour

    2017-06-01

    To detect predictors of the clinical course and outcome of cerebellar hematoma in conscious patients that may help in decision making. This study entails retrospective and prospective review and collection of the demographic, clinical, and radiologic data of 92 patients with cerebellar hematoma presented conscious and initially treated conservatively. Primary outcome was deterioration lower than a Glasgow Coma Scale score of 14 and secondary outcome was Glasgow Outcome Scale score at discharge and 3 months later. Relevant data to primary outcome were used to create a prediction model and derive a risk score. The model was validated using a bootstrap technique and performance measures of the score were presented. Surgical interventions and secondary outcomes were correlated to the score to explore its use in future decision making. Demographic and clinical data showed no relevance to outcome. The relevant initial computed tomography criteria were used to build up the prediction model. A score was derived after the model proved to be valid using internal validation with bootstrapping technique. The score (0-6) had a cutoff value of ≥2, with sensitivity of 93.3% and specificity of 88.0%. It was found to have a significant negative association with the onset of neurologic deterioration, end point Glasgow Coma Scale scores and the Glasgow Outcome Scale scores at discharge. The score was positively correlated to the aggressiveness of surgical interventions and the length of hospital stay. Early definitive management is critical in conscious patients with cerebellar hematomas and can improve outcome. Our proposed score is a simple tool with high discrimination power that may help in timely decision making in those patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Methionine stimulates motor impairment and cerebellar mercury deposition in methylmercury-exposed mice.

    PubMed

    Zimmermann, Luciana T; dos Santos, Danúbia B; Colle, Dirleise; dos Santos, Alessandra A; Hort, Mariana A; Garcia, Solange C; Bressan, Lucas Paines; Bohrer, Denise; Farina, Marcelo

    2014-01-01

    Methylmercury (MeHg) is a highly toxic environmental contaminant that produces neurological and developmental impairments in animals and humans. Although its neurotoxic properties have been widely reported, the molecular mechanisms by which MeHg enters the cells and exerts toxicity are not yet completely understood. Taking into account that MeHg is found mostly bound to sulfhydryl-containing molecules such as cysteine in the environment and based on the fact that the MeHg-cysteine complex (MeHg-S-Cys) can be transported via the L-type neutral amino acid carrier transport (LAT) system, the potential beneficial effects of L-methionine (L-Met, a well known LAT substrate) against MeHg (administrated as MeHg-S-Cys)-induced neurotoxicity in mice were investigated. Mice were exposed to MeHg (daily subcutaneous injections of MeHg-S-Cys, 10 mg Hg/kg) and/or L-Met (daily intraperitoneal injections, 250 mg/kg) for 10 consecutive days. After treatments, the measured hallmarks of toxicity were mostly based on behavioral parameters related to motor performance, as well as biochemical parameters related to the cerebellar antioxidant glutathione (GSH) system. MeHg significantly decreased motor activity (open-field test) and impaired motor performance (rota-rod task) compared with controls, as well as producing disturbances in the cerebellar antioxidant GSH system. Interestingly, L-Met administration did not protect against MeHg-induced behavioral and cerebellar changes, but rather increased motor impairments in animals exposed to MeHg. In agreement with this observation, cerebellar levels of mercury (Hg) were higher in animals exposed to MeHg plus L-Met compared to those only exposed to MeHg. However, this event was not observed in kidney and liver. These results are the first to demonstrate that L-Met enhances cerebellar deposition of Hg in mice exposed to MeHg and that this higher deposition may be responsible for the greater motor impairment observed in mice simultaneously

  14. Early VGLUT1-specific parallel fiber synaptic deficits and dysregulated cerebellar circuit in the KIKO mouse model of Friedreich ataxia.

    PubMed

    Lin, Hong; Magrane, Jordi; Clark, Elisia M; Halawani, Sarah M; Warren, Nathan; Rattelle, Amy; Lynch, David R

    2017-12-19

    Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with progressive ataxia that affects both the peripheral and central nervous system (CNS). While later CNS neuropathology involves loss of large principal neurons and glutamatergic and GABAergic synaptic terminals in the cerebellar dentate nucleus, early pathological changes in FRDA cerebellum remain largely uncharacterized. Here, we report early cerebellar VGLUT1 (SLC17A7)-specific parallel fiber (PF) synaptic deficits and dysregulated cerebellar circuit in the frataxin knock-in/knockout (KIKO) FRDA mouse model. At asymptomatic ages, VGLUT1 levels in cerebellar homogenates are significantly decreased, whereas VGLUT2 (SLC17A6) levels are significantly increased, in KIKO mice compared with age-matched controls. Additionally, GAD65 (GAD2) levels are significantly increased, while GAD67 (GAD1) levels remain unaltered. This suggests early VGLUT1-specific synaptic input deficits, and dysregulation of VGLUT2 and GAD65 synaptic inputs, in the cerebellum of asymptomatic KIKO mice. Immunohistochemistry and electron microscopy further show specific reductions of VGLUT1-containing PF presynaptic terminals in the cerebellar molecular layer, demonstrating PF synaptic input deficiency in asymptomatic and symptomatic KIKO mice. Moreover, the parvalbumin levels in cerebellar homogenates and Purkinje neurons are significantly reduced, but preserved in other interneurons of the cerebellar molecular layer, suggesting specific parvalbumin dysregulation in Purkinje neurons of these mice. Furthermore, a moderate loss of large principal neurons is observed in the dentate nucleus of asymptomatic KIKO mice, mimicking that of FRDA patients. Our findings thus identify early VGLUT1-specific PF synaptic input deficits and dysregulated cerebellar circuit as potential mediators of cerebellar dysfunction in KIKO mice, reflecting developmental features of FRDA in this mouse model. © 2017. Published by The Company of

  15. CNS development under altered gravity: cerebellar glial and neuronal protein expression in rat neonates exposed to hypergravity

    NASA Technical Reports Server (NTRS)

    Nguon, K.; Li, G-H; Sajdel-Sulkowska, E. M.

    2004-01-01

    The future of space exploration depends on a solid understanding of the developmental process under microgravity, specifically in relation to the central nervous system (CNS). We have previously employed a hypergravity paradigm to assess the impact of altered gravity on the developing rat cerebellum. The present study addresses the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of selected glial and neuronal cerebellar proteins in rat neonates exposed to hypergravity (1.5 G) from embryonic day (E)11 to postnatal day (P)6 or P9 (the time of maximal cerebellar changes) comparing them against their expression in rat neonates developing under normal gravity. Proteins were analyzed by quantitative Western blots of cerebellar homogenates; RNA analysis was performed in the same samples using quantitative PCR. Densitometric analysis of Western blots suggested a reduction in glial (glial acidic protein, GFAP) and neuronal (neuronal cell adhesion molecule, NCAM-L1, synaptophysin) proteins, but the changes in individual cerebellar proteins in hypergravity-exposed neonates appeared both age- and gender-specific. RNA analysis suggested a reduction in GFAP and synaptophysin mRNAs on P6. These data suggest that exposure to hypergravity may interfere with the expression of selected cerebellar proteins. These changes in protein expression may be involved in mediating the effect of hypergravity on the developing rat cerebellum. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

  16. Abnormal ventricular development in preterm neonates with visually normal MRIs

    NASA Astrophysics Data System (ADS)

    Shi, Jie; Wang, Yalin; Lao, Yi; Ceschin, Rafael; Mi, Liang; Nelson, Marvin D.; Panigrahy, Ashok; Leporé, Natasha

    2015-12-01

    Children born preterm are at risk for a wide range of neurocognitive and neurobehavioral disorders. Some of these may stem from early brain abnormalities at the neonatal age. Hence, a precise characterization of neonatal neuroanatomy may help inform treatment strategies. In particular, the ventricles are often enlarged in neurocognitive disorders, due to atrophy of surrounding tissues. Here we present a new pipeline for the detection of morphological and relative pose differences in the ventricles of premature neonates compared to controls. To this end, we use a new hyperbolic Ricci flow based mapping of the ventricular surfaces of each subjects to the Poincaré disk. Resulting surfaces are then registered to a template, and a between group comparison is performed using multivariate tensor-based morphometry. We also statistically compare the relative pose of the ventricles within the brain between the two groups, by performing a Procrustes alignment between each subject's ventricles and an average shape. For both types of analyses, differences were found in the left ventricles between the two groups.

  17. A severe form of epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

    PubMed

    Okumura, Akihisa; Lee, Tsubasa; Ikeno, Mitsuru; Shimojima, Keiko; Kajino, Kazunori; Inoue, Yuka; Yoshikawa, Naomi; Suganuma, Hiroki; Suzuki, Mitsuyoshi; Hisata, Ken; Shoji, Hiromichi; Takanashi, Jun-ichi; Barkovich, A James; Shimizu, Toshiaki; Yamamoto, Toshiyuki; Hayashi, Masaharu

    2012-11-01

    Here we report a boy with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma. The patient had epidermal nevi and complicated brain malformations including macrocephaly with polymicrogyria, dysmorphic and enlarged midbrain tectum, enlarged cerebellar hemispheres with small and maloriented folia. The patient died after surgical resection of medulloblastoma which was newly recognized on MRI at 51 days of age. Postmortem pathological examinations showed very unique and bizarre malformation of the midbrain and hindbrain. The cerebellar cortex exhibited a coarse, irregular and bumpy surface, blurred border between the Purkinje cell layer and internal granule cell layer, and many foci of heterotopia in the cerebellar white matter. The brainstem showed multiple anomalies, including enlargement of superior colliculi, hypoplasia of pyramidal tracts and dysplasia of inferior olivary nuclei. The unusual constellation of brain malformations of our patient will widen the spectrum of epidermal nevus syndrome. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  18. Differences between Spinocerebellar Ataxias and Multiple System Atrophy-Cerebellar Type on Proton Magnetic Resonance Spectroscopy

    PubMed Central

    Chen, Hung-Chieh; Soong, Bing-Wen; Guo, Wan Yuo; Wu, Hsiu-Mei; Chang, Cheng-Yen

    2012-01-01

    Purpose A broad spectrum of diseases can manifest cerebellar ataxia. In this study, we investigated whether proton magnetic resonance spectroscopy (MRS) may help differentiate spinocerebellar ataxias (SCA) from multiple systemic atrophy- cerebellar type (MSA-C). Material and Methods This prospective study recruited 156 patients with ataxia, including spinocerebellar ataxia (SCA) types 1, 2, 3, 6 and 17 (N = 94) and MSA-C (N = 62), and 44 healthy controls. Single voxel proton MRS in the cerebellar hemispheres and vermis were measured. The differences were evaluated using nonparametric statistic tests. Results When compared with healthy controls, the cerebellar and vermis NAA/Cr and NAA/Cho were lower in all patients(p<0.002). The Cho/Cr was lower in SCA2 and MSA-C (p<0.0005). The NAA/Cr and Cho/Cr were lower in MSA-C or SCA2 comparing with SCA3 or SCA6. The MRS features of SCA1 were in between (p<0.018). The cerebellar NAA/Cho was lower in SCA2 than SCA1, SCA3 or SCA6 (p<0.04). The cerebellar NAA/Cho in MSA-C was lower than SCA3 (p<0.0005). In the early stages of diseases (SARA score<10), significant lower NAA/Cr and NAA/Cho in SCA2, SCA3, SCA6 or MSA-C were observed comparing with healthy controls (p<0.017). The Cho/Cr was lower in MSA-C or SCA2 (p<0.0005). Patients with MSA-C and SCA2 had lower NAA/Cr and Cho/Cr than SCA3 or SCA6 (p<0.016). Conclusion By using MRS, significantly lower NAA/Cr, Cho/Cr and NAA/Cho in the cerebellar hemispheres and vermis were found in patients with ataxia (SCAs and MSA-C). Rapid neuronal degeneration and impairment of membrane activities were observed more often in patients with MSA-C than those with SCA, even in early stages. MRS could also help distinguish between SCA2 and other subtypes of SCAs. MRS ratios may be of use as biomarkers in early stages of disease and should be further assessed in a longitudinal study. PMID:23118909

  19. Sex differences in impulsivity and brain morphometry in methamphetamine users

    PubMed Central

    Kogachi, Shannon; Chang, Linda; Alicata, Daniel; Cunningham, Eric; Ernst, Thomas

    2016-01-01

    Methamphetamine (METH) is an addictive stimulant, and METH users have abnormal brain structures and function. The aims of this study were to investigate the relationships between impulsivity, brain structures, and possible sex-specific differences between METH users and non-drug using Controls. Structural MRI and the Barratt Impulsiveness Scale (BIS) questionnaire were completed in 124 subjects: 62 METH (ages 41.2 ± 1.4 years, 34 males) and 62 Controls (ages 43.3 ± 2.3 years, 36 males). Independent and interactive effects of METH use status and sex were evaluated. Relationships between METH usage characteristics, brain morphometry, and impulsivity scores were examined. METH users had higher impulsivity scores, on both the Cognitive and Behavioral Factors from the BIS (p < 0.0001–0.0001). Compared with same-sex Controls, male METH users had larger, while female METH users had smaller, right superior frontal cortex (interaction-p = 0.0005). The male METH users with larger frontal volumes and female METH users with smaller or thinner frontal cortices had greater Cognitive impulsivity (interaction-p ≤ 0.05). Only female METH users showed relatively larger nucleus accumbens (interaction-p = 0.03). Greater impulsivity and thinner frontal cortices in METH users are validated. Larger superior frontal cortex in male METH users with greater cognitive impulsivity suggest decreased dendritic pruning during adolescence might have contributed to their impulsive and drug use behaviors. In the female METH users, smaller frontal cortices and the associated greater impulsivity suggest greater neurotoxicity to these brain regions, while their relatively larger nucleus accumbens suggest an estrogen-mediated neuroprotective glial response. Men and women may be affected differently by METH use. PMID:27095357

  20. Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis.

    PubMed

    Pardini, Matteo; Sudre, Carole H; Prados, Ferran; Yaldizli, Özgür; Sethi, Varun; Muhlert, Nils; Samson, Rebecca S; van de Pavert, Steven H; Cardoso, M Jorge; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

    2016-11-01

    To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm 3 ) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.