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Komal Bharti, Antonio Suppa, Sara Pietracupa, Neeraj Upadhyay, Costanza Giannì, Giorgio Leodori, Francesca Di Biasio, Nicola Modugno, Nikolaos Petsas, Giovanni Grillea, Alessandro Zampogna, Alfredo Berardelli, Patrizia Pantano
In this study, we aimed to evaluate the importance of cerebellum in freezing of gait (FOG) pathophysiology. Due to the fundamental role of the cerebellum in posture and gait control, we examined cerebellar structural and functional connectivity (FC) in patients with PD and FOG. We recruited 15 PD with FOG (PD-FOG), 16 PD without FOG (PD-nFOG) patients, and 16 healthy subjects (HS). The FOG Questionnaire (FOG-Q) assessed FOG severity. Three tesla-MRI study included resting-state functional MRI, diffusion tensor imaging (DTI), and 3D T1-w images...
November 3, 2018: Cerebellum
Le Duy Do, Stephanie L Gupton, Kunikazu Tanji, Joubert Bastien, Sabine Brugière, Yohann Couté, Isabelle Quadrio, Veronique Rogemond, Nicole Fabien, Virginie Desestret, Jerome Honnorat
To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67, and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, 36 patients with lung adenocarcinoma and PNS, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases...
October 22, 2018: Cerebellum
Mario Manto, Hiroshi Mitoma, Christiane S Hampe
Anti-GAD65 antibodies (anti-GAD65 Abs) are associated with cerebellar ataxia (CA). The significance of anti-GAD65 Abs has been a focus of debates. Since GAD65 is intracellularly located and associated with type 1 diabetes mellitus and different clinical neurological phenotypes such as CA, stiff-person syndrome, and epilepsy, some researchers have argued that anti-GAD65 Abs have no pathogenic roles. On the other hand, recent physiological studies in vitro and in vivo have elucidated that binding of GAD65 by anti-GAD65 Abs elicits loss of GAD65 functions pertaining GABA release with an epitope dependence, leading to the development of CA...
October 20, 2018: Cerebellum
Franziska Hoche, Maureen P Daly, Yogesh K Chutake, Eve Valera, Janet C Sherman, Jeremy D Schmahmann
Ataxia-telangiectasia (AT) is an autosomal recessive, multisystem disease causing cerebellar ataxia, mucocutaneous telangiectasias, immunodeficiency, and malignancies. A pilot study reported cognitive and behavioral manifestations characteristic of the cerebellar cognitive affective / Schmahmann syndrome (CCAS). We set out to test and further define these observations because a more comprehensive understanding of the spectrum of impairments in AT is essential for optimal management. Twenty patients (12 males; 9...
October 18, 2018: Cerebellum
Karsten Mueller, Robert Jech, Tommaso Ballarini, Štefan Holiga, Filip Růžička, Fabian A Piecha, Harald E Möller, Josef Vymazal, Evžen Růžička, Matthias L Schroeter
Levodopa has been the mainstay of symptomatic therapy for Parkinson's disease (PD) for the last five decades. However, it is associated with the development of motor fluctuations and dyskinesia, in particular after several years of treatment. The aim of this study was to shed light on the acute brain functional reorganization in response to a single levodopa dose. Functional magnetic resonance imaging (fMRI) was performed after an overnight withdrawal of dopaminergic treatment and 1 h after a single dose of 250 mg levodopa in a group of 24 PD patients...
October 8, 2018: Cerebellum
Chama Belkhiria, Eya Mssedi, Christophe Habas, Tarak Driss, Giovanni de Marco
In this study, we used fMRI to identify brain regions associated with concentration (sustained attention) during a motor preparation task. In comparison with a non-concentration task, increased activities were observed (P < 0.05, FWE-corrected P values) in cerebellar lobules VI and VII, motor cortex, pre-supplementary motor area (pre-SMA), thalamus, red nucleus (RN), and caudate nucleus (CN). Moreover, analysis of effective connectivity inter-areal (psychophysiological interactions) showed that during preparation, concentration-related brain activity increase was dependent on Cerebello-thalamo-pre-SMA-RN and Pre-SMA-CN-thalamo-M1 loops...
October 1, 2018: Cerebellum
Alessandra Zanatta, Carlos Henrique Ferreira Camargo, Francisco Manoel Branco Germiniani, Salmo Raskin, Ana Chrystina de Souza Crippa, Hélio Afonso Ghizoni Teive
Spinocerebellar ataxia type 2 (SCA2) is characterized by a progressive cerebellar syndrome, and additionally saccadic slowing, cognitive dysfunction, and sleep disorders. The aim of this study was to assess the frequency of abnormal findings in sleep recordings of patients with SCA2. Seventeen patients with genetically confirmed SCA2 from the Movement Disorders Outpatient group of the Hospital de Clínicas da UFPR were evaluated with a structured medical interview and the Scale for the Assessment and Rating of Ataxia (SARA)...
September 28, 2018: Cerebellum
Martin Bareš, Richard Apps, Laura Avanzino, Assaf Breska, Egidio D'Angelo, Pavel Filip, Marcus Gerwig, Richard B Ivry, Charlotte L Lawrenson, Elan D Louis, Nicholas A Lusk, Mario Manto, Warren H Meck, Hiroshi Mitoma, Elijah A Petter
Time perception is an essential element of conscious and subconscious experience, coordinating our perception and interaction with the surrounding environment. In recent years, major technological advances in the field of neuroscience have helped foster new insights into the processing of temporal information, including extending our knowledge of the role of the cerebellum as one of the key nodes in the brain for this function. This consensus paper provides a state-of-the-art picture from the experts in the field of the cerebellar research on a variety of crucial issues related to temporal processing, drawing on recent anatomical, neurophysiological, behavioral, and clinical research...
September 27, 2018: Cerebellum
Chih-Chun Lin, Shi-Rui Gan, Deepak Gupta, Armin Alaedini, Peter H Green, Sheng-Han Kuo
Genetic mutations in transglutaminase 6 (TGM6) are recently identified to be associated with spinocerebellar ataxia type 35 (SCA35). We report a Hispanic SCA35 patient, who was confirmed to have a heterozygous, single-nucleotide deletion in TGM6, causing a frameshift mutation with a premature stop codon. An immune-mediated ataxia previously found to be associated with autoantibody reactivity to TG6 may share a similar pathomechanism to SCA35, suggesting a converging role for TG6 in cerebellar function.
September 18, 2018: Cerebellum
Lucas Schenatto Sena, Raphael Machado Castilhos, Eduardo Preusser Mattos, Gabriel Vasata Furtado, José Luiz Pedroso, Orlando Barsottini, Maria Marla Paiva de Amorim, Clecio Godeiro, Maria Luiza Saraiva Pereira, Laura Bannach Jardim
Spinocerebellar ataxia type 2 (SCA2) is caused by an unstable expanded CAG repeat tract (CAGexp) at ATXN2. Although prone to selective forces such as anticipation, SCA2 frequency seems to be stable in populations. Our aim was to estimate reproductive success, segregation patterns, and role of anticipation in SCA2. Adult subjects from families with molecular diagnosis provided data about all his/her relatives. Affected and unaffected sibs older than 65.7 years of age were used to estimate reproductive success and segregation patterns...
September 15, 2018: Cerebellum
Cullen B Owens, Casper de Boer, Giulia Gennari, Robin Broersen, Johan J Pel, Brian Miller, Wesley Clapp, Ysbrand D van der Werf, Chris I De Zeeuw
Cerebellar plasticity is a critical mechanism for optimal feedback control. While Purkinje cell activity of the oculomotor vermis predicts eye movement speed and direction, more lateral areas of the cerebellum may play a role in more complex tasks, including decision-making. It is still under question how this motor-cognitive functional dichotomy between medial and lateral areas of the cerebellum plays a role in optimal feedback control. Here we show that elite athletes subjected to a trajectory prediction, go/no-go task manifest superior subsecond trajectory prediction accompanied by optimal eye movements and changes in cognitive load dynamics...
September 14, 2018: Cerebellum
Christine Y Kim, Lan Luo, Qiping Yu, Ana Mirallave, Rachel Saunders-Pullman, Richard B Lipton, Elan D Louis, Seth L Pullman
To investigate changes in tremor severity over repeated spiral drawings to assess whether learning deficits can be evaluated directly in a limb in essential tremor (ET). A motor learning deficit in ET, possibly mediated by cerebellar pathways, has been established in eye-blink conditioning studies, but not paradigms measuring from an affected, tremulous limb. Computerized spiral analysis captures multiple characteristics of Archimedean spirals and quantifies performance through calculated indices. Sequential spiral drawing has recently been suggested to demonstrate improvement across trials among ET subjects...
September 11, 2018: Cerebellum
Katharina M Steiner, Yvonne Gisbertz, Dae-In Chang, Björn Koch, Ellen Uslar, Jens Claassen, Elke Wondzinski, Thomas M Ernst, Sophia L Göricke, Mario Siebler, Dagmar Timmann
Extinction of conditioned aversive responses (CR) has been shown to be context-dependent. The hippocampus and prefrontal cortex are of particular importance. The cerebellum may contribute to context-related processes because of its known connections with the hippocampus and prefrontal cortex. Context dependency of extinction can be demonstrated by the renewal effect. When CR acquisition takes place in context A and is extinguished in context B, renewal refers to the recovery of the CR in context A (A-B-A paradigm)...
August 28, 2018: Cerebellum
Tomoo Hirano
Cerebellar Purkinje neurons are arguably some of the most conspicuous neurons in the vertebrate central nervous system. They have characteristic planar fan-shaped dendrites which branch extensively and fill spaces almost completely with little overlap. This dendritic morphology is well suited to receiving a single or a few excitatory synaptic inputs from each of more than 100,000 parallel fibers which run orthogonally to Purkinje cell dendritic trees. In contrast, another type of excitatory input to a Purkinje neuron is provided by a single climbing fiber, which forms some hundreds to thousands of synapses with a Purkinje neuron...
December 2018: Cerebellum
Kim van Dun, Hiroshi Mitoma, Mario Manto
Non-invasive stimulation of the cerebellum is growingly applied both in the clinic and in research settings to modulate the activities of cerebello-cerebral loops. The anatomical location of the cerebellum, the high responsiveness of the cerebellar cortex to magnetic/electrical stimuli, and the implication of the cerebellum in numerous cerebello-cerebral networks make the cerebellum an ideal target for investigations and therapeutic purposes. In this mini-review, we discuss the potentials of cerebellar neuromodulation in major brain disorders in order to encourage large-scale sham-controlled research and explore this therapeutic aid further...
December 2018: Cerebellum
Kazuto Fujishima, Kelly Kawabata Galbraith, Mineko Kengaku
Cerebellar Purkinje cells arborize unique dendrites that exhibit a planar, fan shape. The dendritic branches fill the space of their receptive field with little overlap. This dendritic arrangement is well-suited to form numerous synapses with the afferent parallel fibers of the cerebellar granule cells in a non-redundant manner. Purkinje cell dendritic arbor morphology is achieved by a combination of dynamic local branch growth behaviors, including elongation, branching, and retraction. Impacting these behaviors, the self-avoidance of each branch terminal is essential to form the non-overlapping dendritic configuration...
December 2018: Cerebellum
Aparna Suvrathan, Jennifer L Raymond
Climbing fiber-driven long-term depression (LTD) of parallel fiber synapses onto cerebellar Purkinje cells has long been investigated as a putative mechanism of motor learning. We recently discovered that the rules governing the induction of LTD at these synapses vary across different regions of the cerebellum. Here, we discuss the design of LTD induction protocols in light of this heterogeneity in plasticity rules. The analytical advantages of the cerebellum provide an opportunity to develop a deeper understanding of how the specific plasticity rules at synapses support the implementation of learning...
December 2018: Cerebellum
Kazuya Nozawa, Ayumi Hayashi, Junko Motohashi, Yukari H Takeo, Keiko Matsuda, Michisuke Yuzaki
Synapses are precisely established, maintained, and modified throughout life by molecules called synaptic organizers, which include neurexins and neuroligins (Nlgn). Despite the importance of synaptic organizers in defining functions of neuronal circuits, the cellular and subcellular localization of many synaptic organizers has remained largely elusive because of the paucity of specific antibodies for immunohistochemical studies. In the present study, rather than raising specific antibodies, we generated knock-in mice in which a hemagglutinin (HA) epitope was inserted in the Nlgn1 gene...
December 2018: Cerebellum
Martha L Streng, Laurentiu S Popa, Timothy J Ebner
The climbing fiber-Purkinje cell circuit is one of the most powerful and highly conserved in the central nervous system. Climbing fibers exert a powerful excitatory action that results in a complex spike in Purkinje cells and normal functioning of the cerebellum depends on the integrity of climbing fiber-Purkinje cell synapse. Over the last 50 years, multiple hypotheses have been put forward on the role of the climbing fibers and complex spikes in cerebellar information processing and motor control. Central to these theories is the nature of the interaction between the low-frequency complex spike discharge and the high-frequency simple spike firing of Purkinje cells...
December 2018: Cerebellum
Swati Khare, Kira Galeano, Yalan Zhang, Jerelyn A Nick, Harry S Nick, S H Subramony, Jacinda Sampson, Leonard K Kaczmarek, Michael F Waters
Mutations in the potassium channel gene KCNC3 (Kv3.3) cause the autosomal dominant neurological disease, spinocerebellar ataxia 13 (SCA13). In this study, we expand the genotype-phenotype repertoire of SCA13 by describing the novel KCNC3 deletion p.Pro583_Pro585del highlighting the allelic heterogeneity observed in SCA13 patients. We characterize adult-onset, progressive clinical symptoms of two afflicted kindred and introduce the symptom of profound spasticity not previously associated with the SCA13 phenotype...
October 2018: Cerebellum
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