Global motion perception is related to motor function in 4.5-year-old children born at risk of abnormal development

PubMed Central

Chakraborty, Arijit; Anstice, Nicola S.; Jacobs, Robert J.; Paudel, Nabin; LaGasse, Linda L.; Lester, Barry M.; McKinlay, Christopher J. D.; Harding, Jane E.; Wouldes, Trecia A.; Thompson, Benjamin

2017-01-01

Global motion perception is often used as an index of dorsal visual stream function in neurodevelopmental studies. However, the relationship between global motion perception and visuomotor control, a primary function of the dorsal stream, is unclear. We measured global motion perception (motion coherence threshold; MCT) and performance on standardized measures of motor function in 606 4.5-year-old children born at risk of abnormal neurodevelopment. Visual acuity, stereoacuity and verbal IQ were also assessed. After adjustment for verbal IQ or both visual acuity and stereoacuity, MCT was modestly, but significantly, associated with all components of motor function with the exception of gross motor scores. In a separate analysis, stereoacuity, but not visual acuity, was significantly associated with both gross and fine motor scores. These results indicate that the development of motion perception and stereoacuity are associated with motor function in pre-school children. PMID:28435122

Age-Dependent Relationship between Socio-Adaptability and Motor Coordination in High Functioning Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Kostrubiec, Viviane; Huys, Raoul; Jas, Brunhilde; Kruck, Jeanne

2018-01-01

Abnormal perceptual-motor coordination is hypothesized here to be involved in social deficits of autism spectrum disorder (ASD). To test this hypothesis, high functioning children with ASD and typical controls, similar in age as well as verbal and perceptive performance, performed perceptual-motor coordination tasks and several social competence…

Neural autoantibodies and neurophysiologic abnormalities in patients exposed to molds in water-damaged buildings.

PubMed

Campbell, Andrew W; Thrasher, Jack D; Madison, Roberta A; Vojdani, Aristo; Gray, Michael R; Johnson, Al

2003-08-01

Adverse health effects of fungal bioaerosols on occupants of water-damaged homes and other buildings have been reported. Recently, it has been suggested that mold exposure causes neurological injury. The authors investigated neurological antibodies and neurophysiological abnormalities in patients exposed to molds at home who developed symptoms of peripheral neuropathy (i.e., numbness, tingling, tremors, and muscle weakness in the extremities). Serum samples were collected and analyzed with the enzyme-linked immunosorbent assay (ELISA) technique for antibodies to myelin basic protein, myelin-associated glycoprotein, ganglioside GM1, sulfatide, myelin oligodendrocyte glycoprotein, alpha-B-crystallin, chondroitin sulfate, tubulin, and neurofilament. Antibodies to molds and mycotoxins were also determined with ELISA, as reported previously. Neurophysiologic evaluations for latency, amplitude, and velocity were performed on 4 motor nerves (median, ulnar, peroneal, and tibial), and for latency and amplitude on 3 sensory nerves (median, ulnar, and sural). Patients with documented, measured exposure to molds had elevated titers of antibodies (immunoglobulin [Ig]A, IgM, and IgG) to neural-specific antigens. Nerve conduction studies revealed 4 patient groupings: (1) mixed sensory-motor polyneuropathy (n = 55, abnormal), (2) motor neuropathy (n = 17, abnormal), (3) sensory neuropathy (n = 27, abnormal), and (4) those with symptoms but no neurophysiological abnormalities (n = 20, normal controls). All groups showed significantly increased autoantibody titers for all isotypes (IgA, IgM, and IgG) of antibodies to neural antigens when compared with 500 healthy controls. Groups 1 through 3 also exhibited abnormal neurophysiologic findings. The authors concluded that exposure to molds in water-damaged buildings increased the risk for development of neural autoantibodies, peripheral neuropathy, and neurophysiologic abnormalities in exposed individuals.

Speech and oromotor outcome in adolescents born preterm: relationship to motor tract integrity.

PubMed

Northam, Gemma B; Liégeois, Frédérique; Chong, Wui K; Baker, Kate; Tournier, Jacques-Donald; Wyatt, John S; Baldeweg, Torsten; Morgan, Angela

2012-03-01

To assess speech abilities in adolescents born preterm and investigate whether there is an association between specific speech deficits and brain abnormalities. Fifty adolescents born prematurely (<33 weeks' gestation) with a spectrum of brain injuries were recruited (mean age, 16 years). Speech examination included tests of speech-sound processing and production and speech and oromotor control. Conventional magnetic resonance imaging and diffusion-weighted imaging was acquired in all adolescents born preterm and 30 term-born control subjects. Radiological ratings of brain injury were recorded and the integrity of the primary motor projections was measured (corticospinal tract and speech-motor corticobulbar tract [CST/CBT]). There were no clinical diagnoses of developmental dysarthria, dyspraxia, or a speech-sound disorder, but difficulties in speech and oromotor control were common. A regression analysis revealed that presence of a neurologic impairment, and diffusion-weighted imaging abnormalities in the left CST/CBT were significant independent predictors of poor speech and oromotor outcome. These left-lateralized abnormalities were most evident at the level of the posterior limb of the internal capsule. Difficulties in speech and oromotor control are common in adolescents born preterm, and adolescents with injury to the CST/CBT pathways in the left-hemisphere may be most at risk. Copyright © 2012 Mosby, Inc. All rights reserved.

Triple stimulation technique in patients with spinocerebellar ataxia type 6.

PubMed

Sakuma, Kenji; Adachi, Yoshiki; Fukuda, Hiroki; Kai, Tohru; Nakashima, Kenji

2005-11-01

To establish further evidence that SCA6 may not be a pure cerebellar syndrome. Seven patients with genetically confirmed SCA6 and 9 age-matched normal controls were studied. Recordings of the CMAP were obtained from the right first dorsal interosseus muscle. Transcranial magnetic stimulation of the left motor cortex was applied to the contralateral scalp with a plane figure-of-8 coil. Conventional transcranial magnetic stimulation (TMS), central motor conduction time (CMCT) by F-wave method and the triple stimulation technique (TST) amplitude ratio (TST test/TST control) were investigated. The mean resting motor threshold and mean CMCT did not show significant differences between normal controls and patients, but the mean TST amplitude ratio was significantly smaller in patients than in controls. An abnormal TST represents upper motor neuron loss, central axon lesions or conduction blocks, or inexcitability in response to TMS. The lack of pathological changes in the corticospinal tract of patients with SCA6 indicates that this abnormality may be caused by crossed cerebellar diaschisis, or a functional disorder in the brain resulting from CACNA1A mutations. TST is a useful method for quantifying corticospinal tract dysfunction.

Sensorimotor integration and psychopathology: motor control abnormalities related to psychiatric disorders.

PubMed

Velasques, Bruna; Machado, Sergio; Paes, Flávia; Cunha, Marlo; Sanfim, Antonio; Budde, Henning; Cagy, Mauricio; Anghinah, Renato; Basile, Luis F; Piedade, Roberto; Ribeiro, Pedro

2011-12-01

Recent evidence is reviewed to examine relationships among sensorimotor and cognitive aspects in some important psychiatry disorders. This study reviews the theoretical models in the context of sensorimotor integration and the abnormalities reported in the most common psychiatric disorders, such as Alzheimer's disease, autism spectrum disorder and squizophrenia. The bibliographical search used Pubmed/Medline, ISI Web of Knowledge, Cochrane data base and Scielo databases. The terms chosen for the search were: Alzheimer's disease, AD, autism spectrum disorder, and Squizophrenia in combination with sensorimotor integration. Fifty articles published in English and were selected conducted from 1989 up to 2010. We found that the sensorimotor integration process plays a relevant role in elementary mechanisms involved in occurrence of abnormalities in most common psychiatric disorders, participating in the acquisition of abilities that have as critical factor the coupling of different sensory data which will constitute the basis of elaboration of consciously goal-directed motor outputs. Whether these disorders are associated with an abnormal peripheral sensory input or defective central processing is still unclear, but some studies support a central mechanism. Sensorimotor integration seems to play a significant role in the disturbances of motor control, like deficits in the feedforward mechanism, typically seen in AD, autistic and squizophrenic patients.

Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders.

PubMed

Walther, Sebastian; Stegmayer, Katharina; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Viher, Petra V

2017-09-01

Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs.

PubMed

Ando, Hiroyuki; Mochiki, Erito; Ohno, Tetsuro; Yanai, Mitsuhiro; Toyomasu, Yoshitaka; Ogata, Kyoichi; Tabe, Yuichi; Aihara, Ryuusuke; Nakabayashi, Toshihiro; Asao, Takayuki; Kuwano, Hiroyuki

2014-11-14

To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs. Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did. After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity.

Temporal Expectation in Focal Hand Dystonia

ERIC Educational Resources Information Center

Avanzino, Laura; Martino, Davide; Martino, Isadora; Pelosin, Elisa; Vicario, Carmelo M.; Bove, Marco; Defazio, Gianni; Abbruzzese, Giovanni

2013-01-01

Patients with writer's cramp present sensory and representational abnormalities relevant to motor control, such as impairment in the temporal discrimination between tactile stimuli and in pure motor imagery tasks, like the mental rotation of corporeal and inanimate objects. However, only limited information is available on the ability of patients…

Weak Responses to Auditory Feedback Perturbation during Articulation in Persons Who Stutter: Evidence for Abnormal Auditory-Motor Transformation

PubMed Central

Cai, Shanqing; Beal, Deryk S.; Ghosh, Satrajit S.; Tiede, Mark K.; Guenther, Frank H.; Perkell, Joseph S.

2012-01-01

Previous empirical observations have led researchers to propose that auditory feedback (the auditory perception of self-produced sounds when speaking) functions abnormally in the speech motor systems of persons who stutter (PWS). Researchers have theorized that an important neural basis of stuttering is the aberrant integration of auditory information into incipient speech motor commands. Because of the circumstantial support for these hypotheses and the differences and contradictions between them, there is a need for carefully designed experiments that directly examine auditory-motor integration during speech production in PWS. In the current study, we used real-time manipulation of auditory feedback to directly investigate whether the speech motor system of PWS utilizes auditory feedback abnormally during articulation and to characterize potential deficits of this auditory-motor integration. Twenty-one PWS and 18 fluent control participants were recruited. Using a short-latency formant-perturbation system, we examined participants’ compensatory responses to unanticipated perturbation of auditory feedback of the first formant frequency during the production of the monophthong [ε]. The PWS showed compensatory responses that were qualitatively similar to the controls’ and had close-to-normal latencies (∼150 ms), but the magnitudes of their responses were substantially and significantly smaller than those of the control participants (by 47% on average, p<0.05). Measurements of auditory acuity indicate that the weaker-than-normal compensatory responses in PWS were not attributable to a deficit in low-level auditory processing. These findings are consistent with the hypothesis that stuttering is associated with functional defects in the inverse models responsible for the transformation from the domain of auditory targets and auditory error information into the domain of speech motor commands. PMID:22911857

Recording In Vivo Human Colonic Motility: What Have We Learnt Over the Past 100 Years?

PubMed

Dinning, Phil G

To understand the abnormalities that underpin functional gut disorders we must first gain insight into the normal patterns of gut motility. While detailed information continually builds on the motor patterns (and mechanisms that control them) of the human esophagus and anorectum, our knowledge of normal and abnormal motility in the more inaccessible regions of the gut remains poor. This particularly true of the human colon. Investigation of in vivo colonic motor patterns is achieved through measures of transit (radiology, scintigraphy and, more recently, "smart pills") or by direct real-time recording of colonic contractility (intraluminal manometry). This short review will provide an overview of findings from the past and present and attempt to piece together the complex nature of colonic motor patterns. In doing so it will build a profile of human colonic motility and determine the likely mechanisms that control this motility.

Global motion perception is related to motor function in 4.5-year-old children born at risk of abnormal development.

PubMed

Chakraborty, Arijit; Anstice, Nicola S; Jacobs, Robert J; Paudel, Nabin; LaGasse, Linda L; Lester, Barry M; McKinlay, Christopher J D; Harding, Jane E; Wouldes, Trecia A; Thompson, Benjamin

2017-06-01

Global motion perception is often used as an index of dorsal visual stream function in neurodevelopmental studies. However, the relationship between global motion perception and visuomotor control, a primary function of the dorsal stream, is unclear. We measured global motion perception (motion coherence threshold; MCT) and performance on standardized measures of motor function in 606 4.5-year-old children born at risk of abnormal neurodevelopment. Visual acuity, stereoacuity and verbal IQ were also assessed. After adjustment for verbal IQ or both visual acuity and stereoacuity, MCT was modestly, but significantly, associated with all components of motor function with the exception of fine motor scores. In a separate analysis, stereoacuity, but not visual acuity, was significantly associated with both gross and fine motor scores. These results indicate that the development of motion perception and stereoacuity are associated with motor function in pre-school children. Copyright © 2017 Elsevier Ltd. All rights reserved.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Kinematical analysis of handwriting movements in depressed patients.

PubMed

Mergl, R; Juckel, G; Rihl, J; Henkel, V; Karner, M; Tigges, P; Schröter, A; Hegerl, U

2004-05-01

Motor disturbances are a relevant aspect of depression. Kinematical analysis of movements can be applied to explore which type of motor dysfunction is associated with depression. We hypothesized that depressed patients draw and write significantly slower than controls and that motor disturbances become more pronounced under bi-manual demands. We examined 37 depressed patients and 37 healthy controls using a digitizing graphic tablet and subsequent kinematical analysis of handwriting and rapid drawing movements. Depressed patients performed drawing with significantly less regular velocity than controls (P < 0.001), but normal velocity. Motor differences between patients and controls did not increase under bi-manual demands. Handwriting of patients was abnormally slow (P = 0.04). Irregular patterns of velocity peaks in depressed patients point to basal ganglia dysfunction and/or deficient activity of the sensorimotor cortex and the supplementary motor area as a possible substrate of hand-motor disturbances in depression.

Striatal dysfunction increases basal ganglia output during motor cortex activation in parkinsonian rats.

PubMed

Belluscio, Mariano A; Riquelme, Luis A; Murer, M Gustavo

2007-05-01

During movement, inhibitory neurons in the basal ganglia output nuclei show complex modulations of firing, which are presumptively driven by corticostriatal and corticosubthalamic input. Reductions in discharge should facilitate movement by disinhibiting thalamic and brain stem nuclei while increases would do the opposite. A proposal that nigrostriatal dopamine pathway degeneration disrupts trans-striatal pathways' balance resulting in sustained overactivity of basal ganglia output nuclei neurons and Parkinson's disease clinical signs is not fully supported by experimental evidence, which instead shows abnormal synchronous oscillatory activity in animal models and patients. Yet, the possibility that variation in motor cortex activity drives transient overactivity in output nuclei neurons in parkinsonism has not been explored. In Sprague-Dawley rats with 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions, approximately 50% substantia nigra pars reticulata (SNpr) units show abnormal cortically driven slow oscillations of discharge. Moreover, these units selectively show abnormal responses to motor cortex stimulation consisting in augmented excitations of an odd latency, which overlapped that of inhibitory responses presumptively mediated by the trans-striatal direct pathway in control rats. Delivering D1 or D2 dopamine agonists into the striatum of parkinsonian rats by reverse microdialysis reduced these abnormal excitations but had no effect on pathological oscillations. The present study establishes that dopamine-deficiency related changes of striatal function contribute to producing abnormally augmented excitatory responses to motor cortex stimulation in the SNpr. If a similar transient overactivity of basal ganglia output were driven by motor cortex input during movement, it could contribute to impeding movement initiation or execution in Parkinson's disease.

Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs

PubMed Central

Ando, Hiroyuki; Mochiki, Erito; Ohno, Tetsuro; Yanai, Mitsuhiro; Toyomasu, Yoshitaka; Ogata, Kyoichi; Tabe, Yuichi; Aihara, Ryuusuke; Nakabayashi, Toshihiro; Asao, Takayuki; Kuwano, Hiroyuki

2014-01-01

AIM: To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. METHODS: After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs. RESULTS: Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did. CONCLUSION: After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity. PMID:25400453

Abnormal sensory reactivity in preterm infants during the first year correlates with adverse neurodevelopmental outcomes at 2 years of age.

PubMed

Chorna, Olena; Solomon, Jessica E; Slaughter, James C; Stark, Ann R; Maitre, Nathalie L

2014-11-01

Sensory experience is the basis for learning in infancy. In older children, abnormal sensory reactivity is associated with behavioural and developmental disorders. We hypothesised that in preterm infants, abnormal sensory reactivity during infancy would be associated with perinatal characteristics and correlate with 2-year neurodevelopmental outcomes. We conducted a prospective observational study of infants with birth weight ≤1500 g using the Test of Sensory Function in Infants (TSFI) in the first year. Infants with gestational age ≤30 weeks were tested with the Bayley Scales of Infant and Toddler Development III (BSID III) at 24 months. Of the 72 participants evaluated at 4-12 months corrected age (median 8 months), 59 (82%) had a least one TSFI score concerning for abnormal sensory reactivity. Lower gestational age was associated with abnormal reactivity to deep pressure and vestibular stimulation (p<0.001). Poor ocular-motor control predicted worse cognitive and motor scores in early childhood (OR 16.7; p=0.004), but was tightly correlated to the presence of severe white matter injury. Poor adaptive motor function in response to tactile stimuli predicted worse BSID III motor (p=0.01) and language scores (p=0.04) at 2 years, even after adjusting for confounders. Abnormal sensory reactivity is common in preterm infants; is associated with immaturity at birth, severe white matter injury and lower primary caregiver education; and predicts neurodevelopmental delays. Early identification of abnormal sensory reactivity of very preterm infants may promote parental support and education and may facilitate improved neurodevelopment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Esophageal dysmotility in children with eosinophilic esophagitis: a study using prolonged esophageal manometry.

PubMed

Nurko, Samuel; Rosen, Rachel; Furuta, Glenn T

2009-12-01

The pathophysiology of dysphagia in patients with eosinophilic esophagitis (EoE) is unknown but may be related to abnormal esophageal motor function. Symptoms rarely occur during stationary esophageal manometry, so it has been difficult to establish an association between symptoms and motor events. Our aim was to evaluate esophageal motor function in children with EoE with the use of stationary manometry and ambulatory prolonged esophageal manometry and pH-metry (PEMP). PEMP was performed in children with EoE and compared with controls and children with gastroesophageal reflux disease (GERD). Peristalsis was considered effective when the esophageal contractions had a normal amplitude and propagation. Results are expressed as mean+/-s.e. Seventeen patients with EoE, 13 with GERD, and 11 controls were studied. Values are expressed as mean+/-s.e. Stationary manometry identified abnormal peristalsis in 41% of children with EoE. During PEMP, children with EoE had an increased number of isolated (16.7+/-3.8 vs. 9.5+/-1.6 vs. 6.5+/-1.1; P<0.03) and high-amplitude contractions (4.1+/-1.2 vs. 1.8+/-0.8 vs. 0.1+/-0.1; P<0.03), and higher percentage ineffective peristalsis both during fasting (70.5%+/-2.5 vs. 57.8%+/-3.0 vs. 53.8%+/-1.9; P<0.05) and during meals (68.4+/-3.4 vs. 55.3+/-2.8 vs. 48.1+/-2.8; P<0.05) when compared with children with GERD and controls. Thirteen patients with EoE experienced 21 episodes of dysphagia, and all correlated with simultaneous abnormal motor function. PEMP allowed the detection of ineffective peristalsis in children with EoE. Symptoms observed in children with EoE may be related to esophageal motor dysfunction.

Motor current signature analysis method for diagnosing motor operated devices

DOEpatents

Haynes, Howard D.; Eissenberg, David M.

1990-01-01

A motor current noise signature analysis method and apparatus for remotely monitoring the operating characteristics of an electric motor-operated device such as a motor-operated valve. Frequency domain signal analysis techniques are applied to a conditioned motor current signal to distinctly identify various operating parameters of the motor driven device from the motor current signature. The signature may be recorded and compared with subsequent signatures to detect operating abnormalities and degradation of the device. This diagnostic method does not require special equipment to be installed on the motor-operated device, and the current sensing may be performed at remote control locations, e.g., where the motor-operated devices are used in accessible or hostile environments.

Wii-Based Exercise Program to Improve Physical Fitness, Motor Proficiency and Functional Mobility in Adults with Down Syndrome

ERIC Educational Resources Information Center

Silva, V.; Campos, C.; Sá, A.; Cavadas, M.; Pinto, J.; Simões, P.; Machado, S.; Murillo-Rodríguez, E.; Barbosa-Rocha, N.

2017-01-01

Background: People with Down syndrome (DS) usually display reduced physical fitness (aerobic capacity, muscle strength and abnormal body composition), motor proficiency impairments (balance and postural control) and physical functional limitations. Exergames can be an appealing alternative to enhance exercise engagement and compliance, whilst…

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models.

PubMed

Yokoi, Fumiaki; Dang, Mai T; Zhou, Tong; Li, Yuqing

2012-02-15

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ε-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ε-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ε-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ε-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients.

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

Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study.

PubMed

Vollmar, Christian; O'Muircheartaigh, Jonathan; Barker, Gareth J; Symms, Mark R; Thompson, Pamela; Kumari, Veena; Duncan, John S; Janz, Dieter; Richardson, Mark P; Koepp, Matthias J

2011-06-01

Juvenile myoclonic epilepsy is the most frequent idiopathic generalized epilepsy syndrome. It is characterized by predominant myoclonic jerks of upper limbs, often provoked by cognitive activities, and typically responsive to treatment with sodium valproate. Neurophysiological, neuropsychological and imaging studies in juvenile myoclonic epilepsy have consistently pointed towards subtle abnormalities in the medial frontal lobes. Using functional magnetic resonance imaging with an executive frontal lobe paradigm, we investigated cortical activation patterns and interaction between cortical regions in 30 patients with juvenile myoclonic epilepsy and 26 healthy controls. With increasing cognitive demand, patients showed increasing coactivation of the primary motor cortex and supplementary motor area. This effect was stronger in patients still suffering from seizures, and was not seen in healthy controls. Patients with juvenile myoclonic epilepsy showed increased functional connectivity between the motor system and frontoparietal cognitive networks. Furthermore, we found impaired deactivation of the default mode network during cognitive tasks with persistent activation in medial frontal and central regions in patients. Coactivation in the motor cortex and supplementary motor area with increasing cognitive load and increased functional coupling between the motor system and cognitive networks provide an explanation how cognitive effort can cause myoclonic jerks in juvenile myoclonic epilepsy. The supplementary motor area represents the anatomical link between these two functional systems, and our findings may be the functional correlate of previously described structural abnormalities in the medial frontal lobe in juvenile myoclonic epilepsy.

Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3.

PubMed

Wadman, Renske I; Vrancken, Alexander F J E; van den Berg, Leonard H; van der Pol, W Ludo

2012-11-13

Spinal muscular atrophy (SMA) is pathologically characterized by degeneration of anterior horn cells. Recent observations in animal models of SMA and muscle tissue from patients with SMA suggest additional abnormalities in the development and maturation of the neuromuscular junction. We therefore evaluated neuromuscular junction function in SMA with repetitive nerve stimulation. In this case-control study, repetitive nerve stimulation was performed in 35 patients with SMA types 2, 3, and 4, 20 healthy controls, and 5 controls with motor neuron disease. Pathologic decremental responses (>10%) during 3-Hz repetitive nerve stimulation were observed in 17 of 35 patients (49%) with SMA types 2 and 3, but not in healthy controls or controls with motor neuron disease. None of the patients or controls had an abnormal incremental response of >60%. The presence of an abnormal decremental response was not specific for the type of SMA, nor was it associated with compound muscle action potential amplitude, clinical scores, or disease duration. Two of 4 patients with SMA type 3 who tried pyridostigmine reported increased stamina. These data suggest dysfunction of the neuromuscular junction in patients with SMA types 2 and 3. Therefore, drugs that facilitate neuromuscular transmission are candidate drugs for evaluation in carefully designed, placebo-controlled, clinical trials.

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models

PubMed Central

Yokoi, Fumiaki; Dang, Mai T.; Zhou, Tong; Li, Yuqing

2012-01-01

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ɛ-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ɛ-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ɛ-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ɛ-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients. PMID:22080833

No Proprioceptive Deficits in Autism despite Movement-Related Sensory and Execution Impairments

ERIC Educational Resources Information Center

Fuentes, Christina T.; Mostofsky, Stewart H.; Bastian, Amy J.

2011-01-01

Autism spectrum disorder (ASD) often involves sensory and motor problems, yet the proprioceptive sense of limb position has not been directly assessed. We used three tasks to assess proprioception in adolescents with ASD who had motor and sensory perceptual abnormalities, and compared them to age- and IQ-matched controls. Results showed no group…

Early physiological abnormalities after simian immunodeficiency virus infection.

PubMed

Horn, T F; Huitron-Resendiz, S; Weed, M R; Henriksen, S J; Fox, H S

1998-12-08

Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction.

Early physiological abnormalities after simian immunodeficiency virus infection

PubMed Central

Horn, Thomas F. W.; Huitron-Resendiz, Salvador; Weed, Michael R.; Henriksen, Steven J.; Fox, Howard S.

1998-01-01

Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction. PMID:9844017

Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis.

PubMed

Zhong, Jidan; Nantes, Julia C; Holmes, Scott A; Gallant, Serge; Narayanan, Sridar; Koski, Lisa

2016-12-01

Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting-state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting-state fMRI, T1-weighted and T2-weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease-related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting-state fMRI, T1-weighted, T2-weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262-4275, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Gross Motor Development, Movement Abnormalities, and Early Identification of Autism

PubMed Central

Young, Gregory S.; Goldring, Stacy; Greiss-Hess, Laura; Herrera, Adriana M.; Steele, Joel; Macari, Suzanne; Hepburn, Susan; Rogers, Sally J.

2015-01-01

Gross motor development (supine, prone, rolling, sitting, crawling, walking) and movement abnormalities were examined in the home videos of infants later diagnosed with autism (regression and no regression subgroups), developmental delays (DD), or typical development. Group differences in maturity were found for walking, prone, and supine, with the DD and Autism-No Regression groups both showing later developing motor maturity than typical children. The only statistically significant differences in movement abnormalities were in the DD group; the two autism groups did not differ from the typical group in rates of movement abnormalities or lack of protective responses. These findings do not replicate previous investigations suggesting that early motor abnormalities seen on home video can assist in early identification of autism. PMID:17805956

Esophageal motor abnormalities in eosinophilic esophagitis identified by high-resolution manometry.

PubMed

Martín Martín, Leticia; Santander, Cecilio; Lopez Martín, Mari Carmen; Espinoza-Ríos, Jorge; Chavarría-Herbozo, Carlos; Gisbert, Javier P; Moreno-Otero, Ricardo

2011-09-01

Esophageal motility abnormalities, as measured by conventional manometry (CM), are non-specific in the majority of patients with eosinophilic esophagitis (EoE). Moreover, the study of CM is limited by poor interobserver agreement. The aims of the present study were: (i) to assess the esophageal patterns in EoE by a topographic analysis of high-resolution manometry (HRM) data; and (ii) to establish a relationship between motility abnormalities and symptoms of EoE, such as dysphagia and bolus impaction. All adult patients with EoE diagnosed according to histological criteria, and controls with gastroesophageal reflux disease symptoms and dysphagia, were included. HRM was done in EoE patients and controls. For the analysis of data, the Chicago classification was followed. HRM was performed in 21 patients with EoE, as well as in 21 controls. Of the 21 patients with EoE, 10 (48%) showed pan-esophageal pressurization, six (28%) showed peristaltic dysfunction, and in five cases (24%), HRM was normal. There was no pan-esophageal pressurization in controls. Nine of 10 patients with pan-esophageal pressurization required endoscopic bolus removal (P < 0.05); none had obstructive endoscopy findings. The most frequent esophageal motor abnormality measured by HRM was a pan-esophageal pressurization. Bolus impaction in patients with EoE was associated with pan-esophageal pressurization. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Motility abnormalities in esophageal body in GERD: are they truly related to reflux?

PubMed

Ciriza de los Ríos, C; García Menéndez, L; Díez Hernández, A; Fernández Eroles, A L; Vega Fernández, A; Enguix Armada, A

2005-03-01

Esophageal motility abnormalities have been observed in patients with gastroesophageal reflux disease. The aim of the present study was to determine if esophageal motor disorders in patients with a positive response to the omeprazole test are related to the existence of reflux or they are concomitant findings. A 24-hour pH monitoring and a stationary manometry were performed on 128 patients: 49 of them had normal manometry, 31 hypotensive lower esophageal sphincter, 29 motor disorder in esophageal body, and 19 hypotensive lower esophageal sphincter and motor disorder in esophageal body. We found an association between the presence of abnormal reflux and motor disorder in esophageal body (chi test; P < 0.05). However, ineffective esophageal motility was the disorder most strongly related to reflux, whereas the hypercontractile disorders were not clearly attributed to it. Esophageal manometric abnormalities should be considered cautiously before considering a motor disorder as a consequence of abnormal reflux.

Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.

PubMed

da Silva, O; Alexandrou, D; Knoppert, D; Young, G B

1999-03-01

To describe the association between opioid administration in the newborn period and neurologic abnormalities. Case reports of two infants who presented with seizure activity and abnormal electroencephalograms associated with opiate administration, and reversed by naloxone. The first was a preterm infant who developed a burst-suppression pattern on the electroencephalogram while receiving a continuous infusion of morphine and muscle paralysis. Naloxone injection during the electroencephalogram recording reversed the burst-suppression pattern. The second was a term infant receiving fentanyl infusion for pain control following surgery, who presented with motor seizure that was only partially controlled with barbiturates. An abnormal electroencephalogram recording during the opiate infusion improved with naloxone administration. Our observations indicate a potential for neurologic abnormalities, including induction of seizure activity and electroencephalogram abnormalities, suggesting caution when opiates are used for sedation and/or pain control in the newborn period.

Lower urinary tract dysfunction in critical illness polyneuropathy.

PubMed

Reitz, André

2013-01-01

Critical illness polyneuropathy is a frequent complication of critical illness in intensive care units. Reports on autonomic systems like lower urinary tract and bowel functions in patients with CIP are not available in medical literature. This study performed during primary rehabilitation of patients with critical illness polyneuropathy explores if sensory and motor pathways controlling the lower urinary tract function are affected from the disease. Neurourological examinations, urodynamics, electromyography and lower urinary tract imaging were performed in 28 patients with critical illness polyneuropathy. Sacral sensation was impaired in 1 patient (4%). Sacral reflexes were absent in 8 patients (30%). Anal sphincter resting tone was reduced in 3 (12%), anal sphincter voluntary contraction was absent or reduced in 8 patients (30%). Urodynamic findings were detrusor overactivity and detrusor overactivity incontinence in 9 (37.5%), incomplete voiding in 8 (30%), abnormal sphincter activity in 4 (16%), abnormal bladder sensation in 4 (16%) and detrusor acontractility in 2 patients (8.3%). Morphological abnormalities of the lower urinary tract had 10 patients (41.6%). Sensory and motor pathways controlling the lower urinary tract might be affected from CIP. During urodynamics dysfunctions of the storage as well as the voiding phase were found. Morphological lower urinary tract abnormalities were common.

Abnormal Corpus Callosum Connectivity, Socio-Communicative Deficits, and Motor Deficits in Children with Autism Spectrum Disorder: A Diffusion Tensor Imaging Study

ERIC Educational Resources Information Center

Hanaie, Ryuzo; Mohri, Ikuko; Kagitani-Shimono, Kuriko; Tachibana, Masaya; Matsuzaki, Junko; Watanabe, Yoshiyuki; Fujita, Norihiko; Taniike, Masako

2014-01-01

In addition to social and communicative deficits, many studies have reported motor deficits in autism spectrum disorder (ASD). This study investigated the macro and microstructural properties of the corpus callosum (CC) of 18 children with ASD and 12 typically developing controls using diffusion tensor imaging tractography. We aimed to explore…

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 schizophrenia. PMID:25852520

Use of radioisotopic esophageal transit in the assessment of patients with symptoms of reflux and non-specific esophageal motor disorders.

PubMed

Iascone, C; Di Giulio, E; Maffi, C; Ruperto, M

2004-01-01

The purposes of this study were to assess the esophageal clearance of a radioisotopic bolus in patients with symptoms of reflux and evaluate the impact of manometric abnormalities on scintigraphic esophageal transit. Esophageal clearance was assessed in a supine position and indicated by the retained radioactivity in the esophagus at 10, 20, 30 and 40 s after the ingestion of a liquid bolus labeled with 2 mCi 99 mTc-SC. The study included 214 consecutive patients with symptoms of reflux and 11 normal controls. The results were compared to the motility findings detected on manometry performed on a separate occasion. Esophageal manometry was normal in 93 patients. Nonspecific esophageal motor disorders were identified in 121 patients and were classified into: 'predominantly nonpropagated activity', 'predominantly low-amplitude peristaltic contractions' and 'miscellaneous disorders' diagnosed in 27, 47 and 47 patients, respectively. The radionuclide clearance was significantly delayed in the overall group of patients compared with that of normal controls (P < 0.001); in patients with reflux symptoms and nonspecific esophageal motor disorders compared with patients with reflux symptoms and 'normal manometry' (P < 0.01 at 20 s); and in patients with reflux symptoms and 'normal manometry' compared with the control group (P < 0.01 at 20 s). Abnormal radioisotope clearances were detected in 88% of patients with 'predominantly nonpropagated activity', in 70% of patients with 'predominantly low-amplitude peristaltic contractions' and in 57% of patients with 'miscellaneous disorders'. Radioisotopic esophageal clearance abnormalities are frequently observed in patients with reflux symptoms and are more likely to be associated to hypomotility disorders, i.e. nonpropagated motor activity or low-amplitude contractions.

Electrophysiological signs of supplementary-motor-area deficits in high-functioning autism but not Asperger syndrome: an examination of internally cued movement-related potentials.

PubMed

Enticott, Peter G; Bradshaw, John L; Iansek, Robert; Tonge, Bruce J; Rinehart, Nicole J

2009-10-01

Motor dysfunction is common to both autism and Asperger syndrome, but the underlying neurophysiological impairments are unclear. Neurophysiological examinations of motor dysfunction can provide information about likely sites of functional impairment and can contribute to the debate about whether autism and Asperger syndrome are variants of the same disorder or fundamentally distinct neurodevelopmental conditions. We investigated the neurophysiology of internally determined motor activity in autism and Asperger syndrome via examination of movement-related potentials (MRPs). We used electroencephalography to investigate MRPs, via an internally cued movement paradigm, in the following three groups: (1) individuals with high-functioning autism (14 males, one female; mean age 13 y 1 mo, SD 4 y 2 mo, range 7 y 8 mo to 20 y 9 mo; mean Full-scale IQ 93.40, SD 20.72); (2) individuals with Asperger syndrome (10 males, two females; mean age 13 y 7 mo, SD 3 y 9 mo, range 8 y 11 mo to 20 y 4 mo; mean Full-scale IQ 103.25, SD 19.37), and (3) a healthy control group (13 males, seven females; mean age 14 y 0 mo, SD 3 y 11 mo; range 8 y 4 mo to 21 y 0 mo; mean Full-scale IQ 114.25, SD 11.29). Abnormal MRPs can reflect disruption of motor-related neural networks involving the basal ganglia, thalamus, and supplementary motor area. There was evidence for abnormal MRPs in autism (e.g. increased post-movement cortical activity, abnormal peak time) but not in Asperger syndrome. The results support basal ganglia, thalamus, and supplementary motor area involvement as a likely source of motor dysfunction in autism, and provide further evidence for the neurobiological separateness of autism and Asperger syndrome.

Developmental kinesiology: three levels of motor control in the assessment and treatment of the motor system.

PubMed

Kobesova, Alena; Kolar, Pavel

2014-01-01

Three levels of sensorimotor control within the central nervous system (CNS) can be distinguished. During the neonatal stage, general movements and primitive reflexes are controlled at the spinal and brain stem levels. Analysis of the newborn's spontaneous general movements and the assessment of primitive reflexes is crucial in the screening and early recognition of a risk for abnormal development. Following the newborn period, the subcortical level of the CNS motor control emerges and matures mainly during the first year of life. This allows for basic trunk stabilization, a prerequisite for any phasic movement and for the locomotor function of the extremities. At the subcortical level, orofacial muscles and afferent information are automatically integrated within postural-locomotor patterns. Finally, the cortical (the highest) level of motor control increasingly becomes activated. Cortical control is important for the individual qualities and characteristics of movement. It also allows for isolated segmental movement and relaxation. A child with impaired cortical motor control may be diagnosed with developmental dyspraxia or developmental coordination disorder. Human ontogenetic models, i.e., developmental motor patterns, can be used in both the diagnosis and treatment of locomotor system dysfunction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dissociated functional connectivity profiles for motor and attention deficits in acute right-hemisphere stroke

PubMed Central

Ramsey, Lenny; Rengachary, Jennifer; Zinn, Kristi; Siegel, Joshua S.; Metcalf, Nicholas V.; Strube, Michael J.; Snyder, Abraham Z.; Corbetta, Maurizio; Shulman, Gordon L.

2016-01-01

Strokes often cause multiple behavioural deficits that are correlated at the population level. Here, we show that motor and attention deficits are selectively associated with abnormal patterns of resting state functional connectivity in the dorsal attention and motor networks. We measured attention and motor deficits in 44 right hemisphere-damaged patients with a first-time stroke at 1–2 weeks post-onset. The motor battery included tests that evaluated deficits in both upper and lower extremities. The attention battery assessed both spatial and non-spatial attention deficits. Summary measures for motor and attention deficits were identified through principal component analyses on the raw behavioural scores. Functional connectivity in structurally normal cortex was estimated based on the temporal correlation of blood oxygenation level-dependent signals measured at rest with functional magnetic resonance imaging. Any correlation between motor and attention deficits and between functional connectivity in the dorsal attention network and motor networks that might spuriously affect the relationship between each deficit and functional connectivity was statistically removed. We report a double dissociation between abnormal functional connectivity patterns and attention and motor deficits, respectively. Attention deficits were significantly more correlated with abnormal interhemispheric functional connectivity within the dorsal attention network than motor networks, while motor deficits were significantly more correlated with abnormal interhemispheric functional connectivity patterns within the motor networks than dorsal attention network. These findings indicate that functional connectivity patterns in structurally normal cortex following a stroke link abnormal physiology in brain networks to the corresponding behavioural deficits. PMID:27225794

Regaining motor control in musician's dystonia by restoring sensorimotor organisation

PubMed Central

Rosenkranz, Karin; Butler, Katherine; Williamon, Aaron; Rothwell, John C.

2010-01-01

Professional musicians are an excellent human model of long term effects of skilled motor training on the structure and function of the motor system. However, such effects are accompanied by an increased risk of developing motor abnormalities, in particular musician's dystonia. Previously we found that there was an expanded spatial integration of proprioceptive input into the hand area of motor cortex (sensorimotor organisation, SMO) in healthy musicians as tested with a transcranial magnetic stimulation (TMS) paradigm. In musician's dystonia, this expansion was even larger, resulting in a complete lack of somatotopic organisation. We hypothesised that the disordered motor control in musician's dystonia is a consequence of the disordered SMO. In the present paper we test this idea by giving pianists with musician's dystonia 15 min experience of a modified proprioceptive training task. This restored SMO towards that seen in healthy pianists. Crucially, motor control of the affected task improved significantly and objectively as measured with a MIDI piano, and the amount of behavioural improvement was significantly correlated to the degree of sensorimotor re-organisation. In healthy pianists and non-musicians, the SMO and motor performance remained essentially unchanged. These findings suggest a link between the differentiation of SMO in the hand motor cortex and the degree of motor control of intensively practiced tasks in highly skilled individuals. PMID:19923295

Ulnar neuropathy at or distal to the wrist: traumatic versus cumulative stress cases.

PubMed

Chiodo, Anthony; Chadd, Edmund

2007-04-01

To identify clinical and electromyographic characteristics of ulnar neuropathy at or below the wrist, comparing those caused by unitary trauma with those caused by suspected cumulative stress. Retrospective case series. University hospital electromyography laboratory. Patients with electrodiagnostic evidence of an ulnar neuropathy at or distal to the wrist over a 3-year period. Forty-seven hands from 42 patients (age range, 20-80y; mean, 52y) were identified and evaluated in this study. Record review of clinical history, physical examination, electromyography, and treatment. Etiology of injury, physical signs and symptoms, and electromyographic testing results. Ulnar neuropathy at or distal to the wrist is commonly mischaracterized because of other mononeuropathies in the upper extremity and because of peripheral polyneuropathy. Ulnar neuropathy because of cumulative stress presents typically with sensory symptoms (63%) and a normal examination (71%), whereas trauma cases present with motor with or without sensory symptoms (92%) with motor abnormalities (92%) confirmed on examination. Traumatic cases are characterized by electromyography by decreased sensory and motor-evoked amplitudes, prolonged motor distal latencies, and abnormal needle examination. The amplitude changes are noted comparing with laboratory norms and comparing side to side. No characteristic pattern of abnormalities on electromyography is noted in the cumulative stress cases. Patients with no motor symptoms, regardless of etiology, are more apt to have sensory distal latency prolongation, whereas those with motor symptoms have motor amplitude and needle examination abnormalities. Traumatic ulnar neuropathy at or distal to the wrist is characterized by motor symptoms and sensory and motor axonal loss by electromyography, whereas cumulative stress cases have sensory symptoms and electromyographic findings that are highly variable and noncharacteristic. Patients with no motor symptoms are more apt to show sensory distal latency abnormalities on electromyography, whereas those with motor symptoms show motor-evoked amplitude and needle electromyography abnormalities.

Behavioural and neural basis of anomalous motor learning in children with autism.

PubMed

Marko, Mollie K; Crocetti, Deana; Hulst, Thomas; Donchin, Opher; Shadmehr, Reza; Mostofsky, Stewart H

2015-03-01

Autism spectrum disorder is a developmental disorder characterized by deficits in social and communication skills and repetitive and stereotyped interests and behaviours. Although not part of the diagnostic criteria, individuals with autism experience a host of motor impairments, potentially due to abnormalities in how they learn motor control throughout development. Here, we used behavioural techniques to quantify motor learning in autism spectrum disorder, and structural brain imaging to investigate the neural basis of that learning in the cerebellum. Twenty children with autism spectrum disorder and 20 typically developing control subjects, aged 8-12, made reaching movements while holding the handle of a robotic manipulandum. In random trials the reach was perturbed, resulting in errors that were sensed through vision and proprioception. The brain learned from these errors and altered the motor commands on the subsequent reach. We measured learning from error as a function of the sensory modality of that error, and found that children with autism spectrum disorder outperformed typically developing children when learning from errors that were sensed through proprioception, but underperformed typically developing children when learning from errors that were sensed through vision. Previous work had shown that this learning depends on the integrity of a region in the anterior cerebellum. Here we found that the anterior cerebellum, extending into lobule VI, and parts of lobule VIII were smaller than normal in children with autism spectrum disorder, with a volume that was predicted by the pattern of learning from visual and proprioceptive errors. We suggest that the abnormal patterns of motor learning in children with autism spectrum disorder, showing an increased sensitivity to proprioceptive error and a decreased sensitivity to visual error, may be associated with abnormalities in the cerebellum. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Predicting motor development in very preterm infants at 12 months' corrected age: the role of qualitative magnetic resonance imaging and general movements assessments.

PubMed

Spittle, Alicia J; Boyd, Roslyn N; Inder, Terrie E; Doyle, Lex W

2009-02-01

The objective of this study was to compare the predictive value of qualitative MRI of brain structure at term and general movements assessments at 1 and 3 months' corrected age for motor outcome at 1 year's corrected age in very preterm infants. Eighty-six very preterm infants (<30 weeks' gestation) underwent MRI at term-equivalent age, were evaluated for white matter abnormality, and had general movements assessed at 1 and 3 months' corrected age. Motor outcome at 1 year's corrected age was evaluated with the Alberta Infant Motor Scale, the Neuro-Sensory Motor Development Assessment, and the diagnosis of cerebral palsy by the child's pediatrician. At 1 year of age, the Alberta Infant Motor Scale categorized 30 (35%) infants as suspicious/abnormal; the Neuro-Sensory Motor Development Assessment categorized 16 (18%) infants with mild-to-severe motor dysfunction, and 5 (6%) infants were classified with cerebral palsy. White matter abnormality at term and general movements at 1 and 3 months significantly correlated with Alberta Infant Motor Scale and Neuro-Sensory Motor Development Assessment scores at 1 year. White matter abnormality and general movements at 3 months were the only assessments that correlated with cerebral palsy. All assessments had 100% sensitivity in predicting cerebral palsy. White matter abnormality demonstrated the greatest accuracy in predicting combined motor outcomes, with excellent levels of specificity (>90%); however, the sensitivity was low. On the other hand, general movements assessments at 1 month had the highest sensitivity (>80%); however, the overall accuracy was relatively low. Neuroimaging (MRI) and functional (general movements) examinations have important complementary roles in predicting motor development of very preterm infants.

Impaired eye movements in presymptomatic spinocerebellar ataxia type 6.

PubMed

Christova, Peka; Anderson, John H; Gomez, Christopher M

2008-04-01

Early detection of impaired neurological function in neurodegenerative diseases may aid in understanding disease pathogenesis and timing of therapeutic trials. To identify early abnormalities of ocular motor function in individuals who have the spinocerebellar ataxia type 6 (SCA6) gene (CACNA1A) but no clinical symptoms. Physiological techniques were used to record and analyze eye movements and postural sway. Four presymptomatic and 5 ataxic patients with SCA6, genetically identified, and 10 healthy controls. Presymptomatic individuals had normal postural sway but definite ocular motor abnormalities. Two had a low-amplitude horizontal gaze-evoked nystagmus, 1 of whom had a significantly decreased eye velocity for upward saccades and an abnormal frequency of square-wave jerks. Another had abnormal square-wave jerks and a fourth had a reduced gain for pursuit tracking. Not all of the presymptomatic patients had the same findings, but a multivariate analysis discriminated the presymptomatic patients, as a group, from healthy controls and the ataxic patients. Among the earliest functional deficits in SCA6 are eye movement abnormalities, including impaired saccade velocity, saccade metrics, and pursuit gain. This suggests that early functional impairments are caused by cellular dysfunction and/or loss in the posterior cerebellar vermis and flocculus. These findings might help to determine the timing of a treatment and to define variables that could be used as outcome measures for the efficacy of therapeutic trials.

Ocular Fixation Abnormality in Patients with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Shirama, Aya; Kanai, Chieko; Kato, Nobumasa; Kashino, Makio

2016-01-01

We examined the factors that influence ocular fixation control in adults with autism spectrum disorder (ASD) including sensory information, individuals' motor characteristics, and inhibitory control. The ASD group showed difficulty in maintaining fixation especially when there was no fixation target. The fixational eye movement characteristics of…

Computerized measures of finger tapping: reliability, malingering and traumatic brain injury.

PubMed

Hubel, Kerry A; Yund, E William; Herron, Timothy J; Woods, David L

2013-01-01

We analyzed computerized finger tapping metrics in four experiments. Experiment 1 showed tapping-rate differences associated with hand dominance, digits, sex, and fatigue that replicated those seen in a previous, large-scale community sample. Experiment 2 revealed test-retest correlations (r = .91) that exceeded those reported in previous tapping studies. Experiment 3 investigated subjects simulating symptoms of traumatic brain injury (TBI); 62% of malingering subjects produced abnormally slow tapping rates. A tapping-rate malingering index, based on rate-independent tapping patterns, provided confirmatory evidence of malingering in 48% of the subjects with abnormal tapping rates. Experiment 4 compared tapping in 24 patients with mild TBI (mTBI) and a matched control group; mTBI patients showed slowed tapping without evidence of malingering. Computerized finger tapping measures are reliable measures of motor speed, useful in detecting subjects performing with suboptimal effort, and are sensitive to motor abnormalities following mTBI.

Reproducibility patterns of multiple rapid swallows during high resolution esophageal manometry provide insights into esophageal pathophysiology.

PubMed

Price, L H; Li, Y; Patel, A; Gyawali, C Prakash

2014-05-01

Multiple rapid swallows (MRS) during esophageal high resolution manometry (HRM) assess esophageal neuromuscular integrity by evaluating postdeglutitive inhibition and rebound contraction, but most reports performed only a single MRS sequence. We assessed patterns of MRS reproducibility during clinical HRM in comparison to a normal cohort. Consecutive clinical HRM studies were included if two separate MRS sequences (four to six rapid swallows ≤4 s apart) were successfully performed. Chicago Classification diagnoses were identified; contraction wave abnormalities were additionally recorded. MRS-induced inhibition (contraction ≤3 cm during inhibition phase) and rebound contraction was assessed, and findings compared to 18 controls (28.0 ± 0.7 year, 50.0% female). Reproducibility consisted of similar inhibition and contraction responses with both sequences; discordance was segregated into inhibition and contraction phases. Multiple rapid swallows were successfully performed in 89.3% patients and all controls; 225 subjects (56.2 ± 0.9 year, 62.7% female) met study inclusion criteria. Multiple rapid swallows were reproducible in 76.9% patients and 94.4% controls (inhibition phase: 88.0% vs 94.4%, contraction phase 86.7% vs 100%, respectively, p = ns). A gradient of reproducibility was noted, highest in well-developed motor disorders (achalasia spectrum, hypermotility disorders, and aperistalsis, 91.7-100%, p = ns compared to controls); and lower in lesser motor disorders (contraction wave abnormalities, esophageal body hypomotility) or normal studies (62.2-70.8%, p < 0.0001 compared to well-developed motor disorders). Inhibition phase was most discordant in contraction wave abnormalities, while contraction phase was most discordant when studies were designated normal. Multiple rapid swallows are highly reproducible, especially in well-developed motor disorders, and complement the standard wet swallow manometry protocol. © 2014 John Wiley & Sons Ltd.

Abnormal motor patterns in the framework of the equilibrium-point hypothesis: a cause for dystonic movements?

PubMed

Latash, M L; Gutman, S R

1994-01-01

Until now, the equilibrium-point hypothesis (lambda model) of motor control has assumed nonintersecting force-length characteristics of the tonic stretch reflex for individual muscles. Limited data from animal experiments suggest, however, that such intersections may occur. We have assumed the possibility of intersection of the characteristics of the tonic stretch reflex and performed a computer simulation of movement trajectories and electromyographic patterns. The simulation has demonstrated, in particular, that a transient change in the slope of the characteristic of an agonist muscle may lead to temporary movement reversals, hesitations, oscillations, and multiple electromyographic bursts that are typical of movements of patients with dystonia. The movement patterns of three patients with idiopathic dystonia during attempts at fast single-joint movements (in the elbow, wrist, and ankle) were recorded and compared with the results of the computer simulation. This approach considers that motor disorders in dystonia result from faulty control patterns that may not correlate with any morphological or neurophysiological changes. It provides a basis for the high variability of dystonic movements. The uniqueness of abnormal motor patterns in dystonia, that precludes statistical analysis across patients, may result from subtle differences in the patterns of intersecting characteristics of the tonic stretch reflex. The applicability of our analysis to disordered multijoint movement patterns is discussed.

Knockout of Foxp2 disrupts vocal development in mice.

PubMed

Castellucci, Gregg A; McGinley, Matthew J; McCormick, David A

2016-03-16

The FOXP2 gene is important for the development of proper speech motor control in humans. However, the role of the gene in general vocal behavior in other mammals, including mice, is unclear. Here, we track the vocal development of Foxp2 heterozygous knockout (Foxp2+/-) mice and their wildtype (WT) littermates from juvenile to adult ages, and observe severe abnormalities in the courtship song of Foxp2+/- mice. In comparison to their WT littermates, Foxp2+/- mice vocalized less, produced shorter syllable sequences, and possessed an abnormal syllable inventory. In addition, Foxp2+/- song also exhibited irregular rhythmic structure, and its development did not follow the consistent trajectories observed in WT vocalizations. These results demonstrate that the Foxp2 gene is critical for normal vocal behavior in juvenile and adult mice, and that Foxp2 mutant mice may provide a tractable model system for the study of the gene's role in general vocal motor control.

Repeater F-waves are signs of motor unit pathology in polio survivors.

PubMed

Hachisuka, Akiko; Komori, Tetsuo; Abe, Tatsuya; Hachisuka, Kenji

2015-05-01

The purpose of this study was to determine whether F-waves reveal electrophysiological features of anterior horn cells in polio survivors. Forty-three polio survivors and 20 healthy controls underwent motor nerve conduction studies of the median and tibial nerves bilaterally, including sampling of F-waves elicited by 100 stimuli and the determination of motor unit number estimation (MUNE). A significant increase in abnormally stereotyped ("repeater") F-waves and a reduction of F-wave persistence were observed in both nerves in the polio group as compared with the control group. Repeater F-waves had a negative correlation with MUNE. These trends in F-wave persistence and repeater F-waves after motor unit loss are characteristic findings in polio survivors. Repeater F-waves are a sign of motor unit pathology. © 2014 The Authors. Muscle & Nerve Published by Wiley Periodicals, Inc.

Electromyographic studies of motor control in humans.

PubMed

Shahani, B T; Wierzbicka, M M

1987-11-01

Electromyography and electroneurography have proved to be useful in investigation and understanding of a variety of neurologic disorders. In most laboratories, however, these electrodiagnostic techniques have been used to help in the diagnosis of diseases that affect the peripheral nerves, neuromuscular junctions, or skeletal muscle fibers. Although major advances in electronic and computer technology have made it possible to study, quantitate, and document reflex activity in intact human subjects, most neurologists still rely on gross clinical observations and most electromyographers continue to use conventional techniques of EMG and nerve conduction studies to differentiate "myopathy" from "neuropathy." This article is a review of some of the electromyographic techniques that have been used in the authors' laboratory for the study of normal and abnormal motor control in man and the treatment of patients with disorders of motor control.

Deep-brain stimulator and control of Parkinson's disease

NASA Astrophysics Data System (ADS)

Varadan, Vijay K.; Harbaugh, Robert; Abraham, Jose K.

2004-07-01

The design of a novel feedback sensor system with wireless implantable polymer MEMS sensors for detecting and wirelessly transmitting physiological data that can be used for the diagnosis and treatment of various neurological disorders, such as Parkinson's disease, epilepsy, head injury, stroke, hydrocephalus, changes in pressure, patient movements, and tremors is presented in this paper. The sensor system includes MEMS gyroscopes, accelerometers, and pressure sensors. This feedback sensor system focuses on the development and integration of implantable systems with various wireless sensors for medical applications, particularly for the Parkinson's disease. It is easy to integrate and modify the sensor network feed back system for other neurological disorders mentioned above. The monitoring and control of tremor in Parkinson's disease can be simulated on a skeleton via wireless telemetry system communicating with electroactive polymer actuator, and microsensors attached to the skeleton hand and legs. Upon sensing any abnormal motor activity which represent the characteristic rhythmic motion of a typical Parkinson's (PD) patient, these sensors will generate necessary control pulses which will be transmitted to a hat sensor system on the skeleton head. Tiny inductively coupled antennas attached to the hat sensor system can receive these control pulses, demodulate and deliver it to actuate the parts of the skeleton to control the abnormal motor activity. This feedback sensor system can further monitor and control depending on the amplitude of the abnormal motor activity. This microsystem offers cost effective means of monitoring and controlling of neurological disorders in real PD patients. Also, this network system offers a remote monitoring of the patients conditions without visiting doctors office or hospitals. The data can be monitored using PDA and can be accessed using internet (or cell phone). Cellular phone technology will allow a health care worker to be automatically notified if monitoring indicates an emergency situation. The main advantage of such system is that it can effectively monitor large number of patients at the same time, which helps to compensate the present shortage of health care workers.

Surmounting retraining limits in musicians' dystonia by transcranial stimulation.

PubMed

Furuya, Shinichi; Nitsche, Michael A; Paulus, Walter; Altenmüller, Eckart

2014-05-01

Abnormal cortical excitability is evident in various movement disorders that compromise fine motor control. Here we tested whether skilled finger movements can be restored in musicians with focal hand dystonia through behavioral training assisted by transcranial direct current stimulation to the motor cortex of both hemispheres. The bilateral motor cortices of 20 pianists (10 with focal dystonia, 10 healthy controls) were electrically stimulated noninvasively during bimanual mirrored finger movements. We found improvement in the rhythmic accuracy of sequential finger movements with the affected hand during and after cathodal stimulation over the affected cortex and simultaneous anodal stimulation over the unaffected cortex. The improvement was retained 4 days after intervention. Neither a stimulation with the reversed montage of electrodes nor sham stimulation yielded any improvement. Furthermore, the amount of improvement was positively correlated with the severity of the symptoms. Bihemispheric stimulation without concurrent motor training failed to improve fine motor control, underlining the importance of combined retraining and stimulation for restoring the dystonic symptoms. For the healthy pianists, none of the stimulation protocols enhanced movement accuracy. These results suggest a therapeutic potential of behavioral training assisted by bihemispheric, noninvasive brain stimulation in restoring fine motor control in focal dystonia. © 2014 American Neurological Association.

Biomechanics of normal and pathological gait: implications for understanding human locomotor control.

PubMed

Winter, D A

1989-12-01

The biomechanical (kinetic) analysis of human gait reveals the integrated and detailed motor patterns that are essential in pinpointing the abnormal patterns in pathological gait. In a similar manner, these motor patterns (moments, powers, and EMGs) can be used to identify synergies and to validate theories of CNS control. Based on kinetic and EMG patterns for a wide range of normal subjects and cadences, evidence is presented that both supports and negates the central pattern generator theory of locomotion. Adaptive motor patterns that are evident in peripheral gait pathologies reinforce a strong peripheral rather than a central control. Finally, a three-component subtask theory of human gait is presented and is supported by reference to the motor patterns seen in a normal gait. The identified subtasks are (a) support (against collapse during stance); (b) dynamic balance of the upper body, also during stance; and (c) feedforward control of the foot trajectory to achieve safe ground clearance and a gentle heel contact.

Control of Visually Guided Saccades in Multiple Sclerosis: Disruption to Higher-Order Processes

ERIC Educational Resources Information Center

Fielding, Joanne; Kilpatrick, Trevor; Millist, Lynette; White, Owen

2009-01-01

Ocular motor abnormalities are a common feature of multiple sclerosis (MS), with more salient deficits reflecting tissue damage within brainstem and cerebellar circuits. However, MS may also result in disruption to higher level or cognitive control processes governing eye movement, including attentional processes that enhance the neural processing…

Manometric evaluation of the esophagus in patients with Behçet's disease.

PubMed

Bektas, Mehmet; Altan, Mehmet; Alkan, Murat; Ormeci, Necati; Soykan, Irfan

2007-01-01

Gastrointestinal (GI) involvement in Behçet's disease (BD) mainly appears in mucosa and affects 5-40% of patients, however the effects of the disease on lower esophageal sphincter (LES) pressure and esophageal contractions are not well known. The aims of this study were to evaluate esophageal motor function and to identify whether there was any specific motility pattern for patients with BD who had upper GI symptoms without endoscopic abnormality. 25 patients with BD, with a mean age of 43.1 (range 20-66) years, were admitted to our clinic whose main complaints were dyspeptic such as reflux, epigastric pain, vomiting and bloating. 25 healthy and age-matched individuals were also included in the study as controls. After one night fasting, LES pressure and esophageal contractions were measured. Esophageal motor abnormalities were detected in 16% (4/25) of these patients with manometric studies (non-specific esophageal motor disorder in 1, esophageal hypomotility in 2, and LES hypotension in 1 patient); 16% (4/25) of these patients had endoscopic findings and overall 32% (8/25) of the cases showed esophageal pathology. All cases with esophageal motor abnormalities were suffering from reflux and endoscopy showed grade B esophagitis in 2 of these cases. Median LES pressure and LES relaxation were significantly lower in patients with BD compared to the control group (16.8 +/- 10.5 vs. 20.4 +/- 6.1, p = 0.02, and 92.1 +/- 10.1 vs. 96.4 +/- 4.5, p = 0.03 respectively). Esophageal involvement in BD is significantly high. We propose manometric studies are necessary to evaluate esophageal manifestations in BD patients with esophageal symptoms even without endoscopic findings.

Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD

PubMed Central

Hu, Yang; Yu, Shu-Yang; Zuo, Li-Jun; Piao, Ying-Shan; Cao, Chen-Jie; Wang, Fang; Chen, Ze-Jie; Du, Yang; Lian, Teng-Hong; Liu, Gai-Fen; Wang, Ya-Jie; Chan, Piu; Chen, Sheng-Di; Wang, Xiao-Min; Zhang, Wei

2015-01-01

Objective To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). Methods Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. Results (1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. Conclusions PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation. PMID:26431210

Components of Motor Deficiencies in ADHD and Possible Interventions.

PubMed

Dahan, Anat; Ryder, Chen Hanna; Reiner, Miriam

2018-05-15

There is a growing body of evidence pointing at several types of motor abnormalities found in attention-deficit/hyperactivity disorder (ADHD). In this article we review findings stemming from different paradigms, and suggest an interweaving approach to the different stages involved in the motor regulation process. We start by reviewing various aspects of motor abnormalities found in ADHD and related brain mechanisms. Then, we classify reported motor impairments associated with ADHD, into four classes of motor stages: Attention to the task, motion preparation, motion execution and motion monitoring. Motor abnormalities and corresponding neural activations are analyzed in the context of each of the four identified motor patterns, along with the interactions among them and with other systems. Given the specifications and models of the role of the four motor impairments in ADHD, we ask what treatments correspond to the identified motor impairments. We analyze therapeutic interventions targeting motor difficulties most commonly experienced among individuals with ADHD; first, Neurofeedback training and EMG-biofeedback. As some of the identified components of attention, planning and monitoring have been shown to be linked to abnormal oscillation patterns in the brain, we examine neurofeedback interventions aimed to address these types of oscillations: Theta/beta frequency training and SCP neurofeedback targeted at elevating the CNV component. Additionally we discuss EMG-Biofeedback interventions targeted at feedback on motor activity. Further we review physical activity and motor interventions aimed at improving motor difficulties, associated with ADHD. These kinds of interventions are shown to be helpful not only in aspects of physical ability, but also in enhancing cognition and executive functioning. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia.

PubMed

Belvisi, Daniele; Suppa, Antonio; Marsili, Luca; Di Stasio, Flavio; Parvez, Ahmad Khandker; Agostino, Rocco; Fabbrini, Giovanni; Berardelli, Alfredo

2013-02-01

Idiopathic focal hand dystonia (FHD) arises from abnormal plasticity in the primary motor cortex (M1) possibly reflecting abnormal sensori-motor integration processes. In this transcranial magnetic stimulation (TMS) study in FHD, we evaluated changes in motor evoked potentials (MEPs) after intermittent theta burst stimulation (iTBS) and paired associative stimulation (PAS), techniques that elicit different forms of experimentally-induced long-term potentiation (LTP)-like plasticity in M1. We also examined behaviorally-induced LTP-like plasticity as reflected by early motor learning of a simple motor task. We studied 14 patients with FHD and 14 healthy subjects. MEPs were recorded before and after iTBS and PAS at the 25 ms interstimulus interval (PAS(25)) in separate sessions. Subjects did a simple motor task entailing repetitive index finger abductions. To measure early motor learning we tested practice-related improvement in peak velocity and peak acceleration. In FHD patients iTBS failed to elicit the expected MEP changes and PAS(25) induced abnormally increased MEPs in target and non-target muscles. In the experiment testing early motor learning, patients lacked the expected practice-related changes in kinematic variables. In FHD, the degree of early motor learning correlated with patients' clinical features. We conclude that experimentally-induced (iTBS and PAS) and behaviorally-induced LTP-like plasticity are both altered in FHD. Copyright © 2012 Elsevier Inc. All rights reserved.

Idling speed control system of an internal combustion engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyazaki, M.; Ishii, M.; Kako, H.

1986-09-16

This patent describes an idling speed control system of an internal combustion engine comprising: a valve device which controls the amount of intake air for the engine; an actuator which includes an electric motor for variably controlling the opening of the value device; rotation speed detector means for detecting the rotation speed of the engine; idling condition detector means for detecting the idling condition of the engine; feedback control means responsive to the detected output of the idling condition detector means for generating feedback control pulses to intermittently drive the electric motor so that the detected rotation speed of themore » engine under the idling condition may converge into a target idling rotation speed; and control means responsive to the output of detector means that detects an abnormally low rotation speed of the engine detected by the rotation speed detector means for generating control pulses that do not overlap the feedback control pulses to drive the electric motor in a predetermined direction.« less

Running wheel exercise reduces α-synuclein aggregation and improves motor and cognitive function in a transgenic mouse model of Parkinson's disease

PubMed Central

Barkow, Jessica Cummiskey; Freed, Curt R.

2017-01-01

Exercise has been recommended to improve motor function in Parkinson patients, but its value in altering progression of disease is unknown. In this study, we examined the neuroprotective effects of running wheel exercise in mice. In adult wild-type mice, one week of running wheel activity led to significantly increased DJ-1 protein concentrations in muscle and plasma. In DJ-1 knockout mice, running wheel performance was much slower and Rotarod performance was reduced, suggesting that DJ-1 protein is required for normal motor activity. To see if exercise can prevent abnormal protein deposition and behavioral decline in transgenic animals expressing a mutant human form of α-synuclein in all neurons, we set up running wheels in the cages of pre-symptomatic animals at 12 months old. Activity was monitored for a 3-month period. After 3 months, motor and cognitive performance on the Rotarod and Morris Water Maze were significantly better in running animals compared to control transgenic animals with locked running wheels. Biochemical analysis revealed that running mice had significantly higher DJ-1, Hsp70 and BDNF concentrations and had significantly less α-synuclein aggregation in brain compared to control mice. By contrast, plasma concentrations of α-synuclein were significantly higher in exercising mice compared to control mice. Our results suggest that exercise may slow the progression of Parkinson’s disease by preventing abnormal protein aggregation in brain. PMID:29272304

Multimodality Instrument for Tissue Characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2000-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip is discussed. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network, program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration.

Growth hormone improves body composition and motor development in infants with Prader-Willi syndrome after six months.

PubMed

Whitman, Barbara; Carrel, Aaron; Bekx, Tracy; Weber, Colleen; Allen, David; Myers, Susan

2004-04-01

Infants with Prader-Willi syndrome (PWS) show abnormalities of body composition. Children with PWS treated with growth hormone (GH) demonstrate improved body composition and motor skills. To assess body composition and motor changes in infants with PWS following 6 months GH therapy. Twenty-five infants with PWS (mean age 15.5 mo) underwent dual energy X-ray absorptiometry (DEXA) assessment of body composition, and motor assessment with the Toddler Infant Motor Evaluation (TIME). Patients were then randomized to treatment (Genotropin, 1 mg/m2/day) or control, with reassessment at 6 months. GH treatment significantly increased lean body mass (6.4 +/- 2.4 kg to 8.9 +/- 2.7 kg) and decreased body fat (27.6 +/- 9.9% to 22.4 +/- 10.3%). Age equivalent motor scores improved 4 months in the treated group vs 2 months in controls (p < 0.01). Infants with PWS show significant body composition and motor development improvement following 6 months GH therapy. We are investigating whether this improvement leads to long-term reductions in obesity.

Grey matter abnormalities in children and adolescents with functional neurological symptom disorder.

PubMed

Kozlowska, Kasia; Griffiths, Kristi R; Foster, Sheryl L; Linton, James; Williams, Leanne M; Korgaonkar, Mayuresh S

2017-01-01

Functional neurological symptom disorder refers to the presence of neurological symptoms not explained by neurological disease. Although this disorder is presumed to reflect abnormal function of the brain, recent studies in adults show neuroanatomical abnormalities in brain structure . These structural brain abnormalities have been presumed to reflect long-term adaptations to the disorder, and it is unknown whether child and adolescent patients, with illness that is typically of shorter duration, show similar deficits or have normal brain structure. High-resolution, three-dimensional T1-weighted magnetic resonance images (MRIs) were acquired in 25 patients (aged 10-18 years) and 24 healthy controls. Structure was quantified in terms of grey matter volume using voxel-based morphometry. Post hoc, we examined whether regions of structural difference related to a measure of motor readiness to emotional signals and to clinical measures of illness duration, illness severity, and anxiety/depression. Patients showed greater volumes in the left supplementary motor area (SMA) and right superior temporal gyrus (STG) and dorsomedial prefrontal cortex (DMPFC) (corrected p < 0.05). Previous studies of adult patients have also reported alterations of the SMA. Greater SMA volumes correlated with faster reaction times in identifying emotions but not with clinical measures. The SMA, STG, and DMPFC are known to be involved in the perception of emotion and the modulation of motor responses. These larger volumes may reflect the early expression of an experience-dependent plasticity process associated with increased vigilance to others' emotional states and enhanced motor readiness to organize self-protectively in the context of the long-standing relational stress that is characteristic of this disorder.

Impaired Interlimb Coordination of Voluntary Leg Movements in Poststroke Hemiparesis

PubMed Central

Tseng, Shih-Chiao

2010-01-01

Appropriate interlimb coordination of the lower extremities is particularly important for a variety of functional human motor behaviors such as jumping, kicking a ball, or simply walking. Specific interlimb coordination patterns may be especially impaired after a lesion to the motor system such as stroke, yet this has not been thoroughly examined to date. The purpose of this study was to investigate the motor deficits in individuals with chronic stroke and hemiparesis when performing unilateral versus bilateral inphase versus bilateral antiphase voluntary cyclic ankle movements. We recorded ankle angular trajectories and muscle activity from the dorsiflexors and plantarflexors and compared these between subjects with stroke and a group of healthy age-matched control subjects. Results showed clear abnormalities in both the kinematics and EMG of the stroke subjects, with significant movement degradation during the antiphase task compared with either the unilateral or the inphase task. The abnormalities included prolonged cycle durations, reduced ankle excursions, decreased agonist EMG bursts, and reduced EMG modulation across movement phases. By comparison, the control group showed nearly identical performance across all task conditions. These findings suggest that stroke involving the corticospinal system projection to the leg specifically impairs one or more components of the neural circuitry involved in lower extremity interlimb coordination. The express susceptibility of the antiphase pattern to exaggerated motor deficits could contribute to functional deficits in a number of antiphase leg movement tasks, including walking. PMID:20463199

Decomposing mechanisms of abnormal saccade generation in schizophrenia patients: Contributions of volitional initiation, motor preparation, and fixation release.

PubMed

Reuter, Benedikt; Elsner, Björn; Möllers, David; Kathmann, Norbert

2016-11-01

Clinical and theoretical models suggest deficient volitional initiation of action in schizophrenia patients. Recent research provided an experimental model of testing this assumption using saccade tasks. However, inconsistent findings necessitate a specification of conditions on which the deficit may occur. The present study sought to detect mechanisms that may contribute to poor performance. Sixteen schizophrenia patients and 16 healthy control participants performed visually guided and two types of volitional saccade tasks. All tasks varied as to whether the initial fixation stimulus disappeared (fixation stimulus offset) or continued during saccade initiation, and whether a direction cue allowed motor preparation of the specific saccade. Saccade latencies of the two groups were differentially affected by task type, fixation stimulus offset, and cueing, suggesting abnormal volitional saccade generation, fixation release, and motor preparation in schizophrenia. However, substantial performance deficits may only occur if all affected processes are required in a task. © 2016 Society for Psychophysiological Research.

Deficits in vision and visual attention associated with motor performance of very preterm/very low birth weight children.

PubMed

Geldof, Christiaan J A; van Hus, Janeline W P; Jeukens-Visser, Martine; Nollet, Frans; Kok, Joke H; Oosterlaan, Jaap; van Wassenaer-Leemhuis, Aleid G

2016-01-01

To extend understanding of impaired motor functioning of very preterm (VP)/very low birth weight (VLBW) children by investigating its relationship with visual attention, visual and visual-motor functioning. Motor functioning (Movement Assessment Battery for Children, MABC-2; Manual Dexterity, Aiming & Catching, and Balance component), as well as visual attention (attention network and visual search tests), vision (oculomotor, visual sensory and perceptive functioning), visual-motor integration (Beery Visual Motor Integration), and neurological status (Touwen examination) were comprehensively assessed in a sample of 106 5.5-year-old VP/VLBW children. Stepwise linear regression analyses were conducted to investigate multivariate associations between deficits in visual attention, oculomotor, visual sensory, perceptive and visual-motor integration functioning, abnormal neurological status, neonatal risk factors, and MABC-2 scores. Abnormal MABC-2 Total or component scores occurred in 23-36% of VP/VLBW children. Visual and visual-motor functioning accounted for 9-11% of variance in MABC-2 Total, Manual Dexterity and Balance scores. Visual perceptive deficits only were associated with Aiming & Catching. Abnormal neurological status accounted for an additional 19-30% of variance in MABC-2 Total, Manual Dexterity and Balance scores, and 5% of variance in Aiming & Catching, and neonatal risk factors for 3-6% of variance in MABC-2 Total, Manual Dexterity and Balance scores. Motor functioning is weakly associated with visual and visual-motor integration deficits and moderately associated with abnormal neurological status, indicating that motor performance reflects long term vulnerability following very preterm birth, and that visual deficits are of minor importance in understanding motor functioning of VP/VLBW children. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neural synchrony within the motor system: what have we learned so far?

PubMed Central

van Wijk, Bernadette C. M.; Beek, Peter J.; Daffertshofer, Andreas

2012-01-01

Synchronization of neural activity is considered essential for information processing in the nervous system. Both local and inter-regional synchronization are omnipresent in different frequency regimes and relate to a variety of behavioral and cognitive functions. Over the years, many studies have sought to elucidate the question how alpha/mu, beta, and gamma synchronization contribute to motor control. Here, we review these studies with the purpose to delineate what they have added to our understanding of the neural control of movement. We highlight important findings regarding oscillations in primary motor cortex, synchronization between cortex and spinal cord, synchronization between cortical regions, as well as abnormal synchronization patterns in a selection of motor dysfunctions. The interpretation of synchronization patterns benefits from combining results of invasive and non-invasive recordings, different data analysis tools, and modeling work. Importantly, although synchronization is deemed to play a vital role, it is not the only mechanism for neural communication. Spike timing and rate coding act together during motor control and should therefore both be accounted for when interpreting movement-related activity. PMID:22969718

Social context modulates cognitive markers in Obsessive-Compulsive Disorder.

PubMed

Santamaría-García, Hernando; Soriano-Mas, Carles; Burgaleta, Miguel; Ayneto, Alba; Alonso, Pino; Menchón, José M; Cardoner, Narcis; Sebastián-Gallés, Nuria

2017-08-03

Error monitoring, cognitive control and motor inhibition control are proposed as cognitive alterations disrupted in obsessive-compulsive disorder (OCD). OCD has also been associated with an increased sensitivity to social evaluations. The effect of a social simulation over electrophysiological indices of cognitive alterations in OCD was examined. A case-control cross-sectional study measuring event-related potentials (ERP) for error monitoring (Error-Related Negativity), cognitive control (N2) and motor control (LRP) was conducted. We analyzed twenty OCD patients and twenty control participants. ERP were recorded during a social game consisting of a visual discrimination task, which was performed in the presence of a simulated superior or an inferior player. Significant social effects (different ERP amplitudes in Superior vs. Inferior player conditions) were found for OCD patients, but not for controls, in all ERP components. Performing the task against a simulated inferior player reduced abnormal ERP responses in OCD to levels observed in controls. The hierarchy-induced ERP effects were accompanied effects over reaction times in OCD patients. Social context modulates signatures of abnormal cognitive functioning in OCD, therefore experiencing a social superiority position impacts over cognitive processes in OCD such as error monitoring mechanisms. These results open the door for the research of new therapeutic choices.

Changes in Motor Development During a 4-Year Follow-up on Children With Univentricular Heart Defects.

PubMed

Mäenpää, Heidi; Häkkinen, Arja; Sarajuuri, Anne

2016-01-01

To compare changes in motor development from 1 to 5 years of age among 18 children with hypoplastic left heart syndrome and 12 with univentricular heart to 42 children without heart defect. Motor development was assessed with the Alberta Infant Motor Scale and Movement Assessment Battery for Children (Movement ABC). Children with hypoplastic left heart syndrome or univentricular heart had significantly lower scores on the Alberta Infant Motor Scale test at the age of 1 and on the Movement ABC test at the age of 5 years compared with controls. Children with clear abnormalities on brain magnetic resonance imaging had lower scores compared with those with normal images or mild changes, and their relative motor scores decreased during follow-up. Some children with univentricular heart defects may benefit from physiotherapeutic interventions to support their motor development.

Ankle Training With a Robotic Device Improves Hemiparetic Gait After a Stroke

PubMed Central

Forrester, Larry W.; Roy, Anindo; Krebs, Hermano Igo; Macko, Richard F.

2013-01-01

Background Task-oriented therapies such as treadmill exercise can improve gait velocity after stroke, but slow velocities and abnormal gait patterns often persist, suggesting a need for additional strategies to improve walking. Objectives To determine the effects of a 6-week visually guided, impedance controlled, ankle robotics intervention on paretic ankle motor control and gait function in chronic stroke. Methods This was a single-arm pilot study with a convenience sample of 8 stroke survivors with chronic hemiparetic gait, trained and tested in a laboratory. Subjects trained in dorsiflexion–plantarflexion by playing video games with the robot during three 1-hour training sessions weekly, totaling 560 repetitions per session. Assessments included paretic ankle ranges of motion, strength, motor control, and overground gait function. Results Improved paretic ankle motor control was seen as increased target success, along with faster and smoother movements. Walking velocity also increased significantly, whereas durations of paretic single support increased and double support decreased. Conclusions Robotic feedback training improved paretic ankle motor control with improvements in floor walking. Increased walking speeds were comparable with reports from other task-oriented, locomotor training approaches used in stroke, suggesting that a focus on ankle motor control may provide a valuable adjunct to locomotor therapies. PMID:21115945

Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment

PubMed Central

Zhou, Joanne; Butler, Erin E.; Rose, Jessica

2017-01-01

Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP. PMID:28367118

Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders

PubMed Central

Redle, Erin; Vannest, Jennifer; Maloney, Thomas; Tsevat, Rebecca K.; Eikenberry, Sarah; Lewis, Barbara; Shriberg, Lawrence D.; Tkach, Jean; Holland, Scott K.

2014-01-01

Children with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. Methods This case-control study included 12 children with PSD (mean age 7.42 years, 4 female) and 12 controls (mean age 7.44 years, 4 female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. Results Children with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. Conclusions Over-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD. PMID:25481413

Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?

PubMed Central

Wandschneider, Britta; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Duncan, John S.

2014-01-01

Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18–65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22–54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23–46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy. PMID:25001494

Hand-arm vibration syndrome: clinical characteristics, conventional electrophysiology and quantitative sensory testing.

PubMed

Rolke, Roman; Rolke, Silke; Vogt, Thomas; Birklein, Frank; Geber, Christian; Treede, Rolf-Detlef; Letzel, Stephan; Voelter-Mahlknecht, Susanne

2013-08-01

Workers exposed to vibrating tools may develop hand-arm vibration syndrome (HAVS). We assessed the somatosensory phenotype using quantitative sensory testing (QST) in comparison to electrophysiology to characterize (1) the most sensitive QST parameter for detecting sensory loss, (2) the correlation of QST and electrophysiology, and (3) the frequency of a carpal tunnel syndrome (CTS) in HAVS. QST, cold provocation tests, fine motor skills, and median nerve neurography were used. QST included thermal and mechanical detection and pain thresholds. Thirty-two patients were examined (54 ± 11 years, 91% men) at the more affected hand compared to 16 matched controls. Vibration detection threshold was the most sensitive parameter to detect sensory loss that was more pronounced in the sensitivity range of Pacinian (150 Hz, x12) than Meissner's corpuscles (20 Hz, x3). QST (84% abnormal) was more sensitive to detect neural dysfunction than conventional electrophysiology (37% abnormal). Motor (34%) and sensory neurography (25%) were abnormal in HAVS. CTS frequency was not increased (9.4%). Findings are consistent with a mechanically-induced, distally pronounced motor and sensory neuropathy independent of CTS. HAVS involves a neuropathy predominantly affecting large fibers with a sensory damage related to resonance frequencies of vibrating tools. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Knockout of Foxp2 disrupts vocal development in mice

PubMed Central

Castellucci, Gregg A.; McGinley, Matthew J.; McCormick, David A.

2016-01-01

The FOXP2 gene is important for the development of proper speech motor control in humans. However, the role of the gene in general vocal behavior in other mammals, including mice, is unclear. Here, we track the vocal development of Foxp2 heterozygous knockout (Foxp2+/−) mice and their wildtype (WT) littermates from juvenile to adult ages, and observe severe abnormalities in the courtship song of Foxp2+/− mice. In comparison to their WT littermates, Foxp2+/− mice vocalized less, produced shorter syllable sequences, and possessed an abnormal syllable inventory. In addition, Foxp2+/− song also exhibited irregular rhythmic structure, and its development did not follow the consistent trajectories observed in WT vocalizations. These results demonstrate that the Foxp2 gene is critical for normal vocal behavior in juvenile and adult mice, and that Foxp2 mutant mice may provide a tractable model system for the study of the gene’s role in general vocal motor control. PMID:26980647

The non-motor syndrome of primary dystonia: clinical and pathophysiological implications

PubMed Central

Stamelou, Maria; Edwards, Mark J.; Hallett, Mark

2012-01-01

Dystonia is typically considered a movement disorder characterized by motor manifestations, primarily involuntary muscle contractions causing twisting movements and abnormal postures. However, growing evidence indicates an important non-motor component to primary dystonia, including abnormalities in sensory and perceptual functions, as well as neuropsychiatric, cognitive and sleep domains. Here, we review this evidence and discuss its clinical and pathophysiological implications. PMID:21933808

Early progressive encephalopathy in boys and MECP2 mutations.

PubMed

Kankirawatana, P; Leonard, H; Ellaway, C; Scurlock, J; Mansour, A; Makris, C M; Dure, L S; Friez, M; Lane, J; Kiraly-Borri, C; Fabian, V; Davis, M; Jackson, J; Christodoulou, J; Kaufmann, W E; Ravine, D; Percy, A K

2006-07-11

MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

Excitability properties of motor axons in adults with cerebral palsy

PubMed Central

Klein, Cliff S.; Zhou, Ping; Marciniak, Christina

2015-01-01

Cerebral palsy (CP) is a permanent disorder caused by a lesion to the developing brain that significantly impairs motor function. The neurophysiological mechanisms underlying motor impairment are not well understood. Specifically, few have addressed whether motoneuron or peripheral axon properties are altered in CP, even though disruption of descending inputs to the spinal cord may cause them to change. In the present study, we have compared nerve excitability properties in seven adults with CP and fourteen healthy controls using threshold tracking techniques by stimulating the median nerve at the wrist and recording the compound muscle action potential over the abductor pollicis brevis. The excitability properties in the CP subjects were found to be abnormal. Early and late depolarizing and hyperpolarizing threshold electrotonus was significantly larger (i.e., fanning out), and resting current–threshold (I/V) slope was smaller, in CP compared to control. In addition resting threshold and rheobase tended to be larger in CP. According to a modeling analysis of the data, an increase in leakage current under or through the myelin sheath, i.e., the Barrett–Barrett conductance, combined with a slight hyperpolarization of the resting membrane potential, best explained the group differences in excitability properties. There was a trend for those with greater impairment in gross motor function to have more abnormal axon properties. The findings indicate plasticity of motor axon properties far removed from the site of the lesion. We suspect that this plasticity is caused by disruption of descending inputs to the motoneurons at an early age around the time of their injury. PMID:26089791

Milk fat globule membrane supplementation with voluntary running exercise attenuates age-related motor dysfunction by suppressing neuromuscular junction abnormalities in mice.

PubMed

Yano, Michiko; Minegishi, Yoshihiko; Sugita, Satoshi; Ota, Noriyasu

2017-10-15

Age-related loss of skeletal muscle mass and function attenuates physical performance, and maintaining fine muscle innervation is known to play an important role in its prevention. We had previously shown that consumption of milk fat globule membrane (MFGM) with habitual exercise improves the muscle mass and motor function in humans and mice. Improvement of neuromuscular junction (NMJ) was suggested as one of the mechanisms underlying these effects. In this study, we evaluated the effect of MFGM intake combined with voluntary running (MFGM-VR) on morphological changes of NMJ and motor function in aging mice. Seven months following the intervention, the MFGM-VR group showed a significantly improved motor coordination in the rotarod test and muscle force in the grip strength test compared with the control group at 13 and 14months of age, respectively. In 14-month old control mice, the extensor digitorum longus muscle showed increased abnormal NMJs, such as fragmentation and denervation, compared with 6-month old young mice. However, such age-related deteriorations of NMJs were significantly suppressed in the MFGM-VR group. Increase in the expression of NMJ formation-related genes, such as agrin and LDL Receptor Related Protein 4 (LRP4), might contribute to this beneficial effect. Rotarod performance and grip strength showed significant negative correlation with the status of denervation and fragmentation of NMJs. These results suggest that MFGM intake with voluntary running exercise effectively suppresses age-related morphological deterioration of NMJ, thus contributing to improvement of motor function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Toll-like receptor 9 deficiency impacts sensory and motor behaviors.

PubMed

Khariv, Veronika; Pang, Kevin; Servatius, Richard J; David, Brian T; Goodus, Matthew T; Beck, Kevin D; Heary, Robert F; Elkabes, Stella

2013-08-01

Toll-like receptors (TLRs) mediate the induction of the innate immune system in response to pathogens, injury and disease. However, they also play non-immune roles and are expressed in the central nervous system (CNS) during prenatal and postnatal stages including adulthood. Little is known about their roles in the CNS in the absence of pathology. Several members of the TLR family have been implicated in the development of neural and cognitive function although the contribution of TLR9 to these processes has not been well defined. The current studies were undertaken to determine whether developmental TLR9 deficiency affects motor, sensory or cognitive functions. We report that TLR9 deficient (TLR9(-/-)) mice show a hyper-responsive sensory and motor phenotype compared to wild type (TLR9(+/+)) controls. This is indicated by hypersensitivity to thermal stimuli in the hot plate paw withdrawal test, enhanced motor-responsivity under anxious conditions in the open field test and greater sensorimotor reactivity in the acoustic startle response. Prepulse inhibition (PPI) of the acoustic startle response was also enhanced, which indicates abnormal sensorimotor gating. In addition, subtle, but significant, gait abnormalities were noted in the TLR9(-/-) mice on the horizontal balance beam test with higher foot slip numbers than TLR9(+/+) controls. In contrast, spatial learning and memory, assessed by the Morris water maze, was similar in the TLR9(-/-) and TLR9(+/+) mice. These findings support the notion that TLR9 is important for the appropriate development of sensory and motor behaviors. Copyright © 2013 Elsevier Inc. All rights reserved.

Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease.

PubMed

Parker, Krystal L; Kim, Youngcho; Alberico, Stephanie L; Emmons, Eric B; Narayanan, Nandakumar S

2016-03-01

Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases.

Speed, Variability, and Timing of Motor Output in ADHD: Which Measures are Useful for Endophenotypic Research?

PubMed Central

Altink, Marieke E.; Oosterlaan, Jaap; Beem, Leo; Buschgens, Cathelijne J. M.; Buitelaar, Jan; Sergeant, Joseph A.

2007-01-01

Attention-Deficit/Hyperactivity Disorder (ADHD) shares a genetic basis with motor coordination problems and probably motor timing problems. In line with this, comparable problems in motor timing should be observed in first degree relatives and might, therefore, form a suitable endophenotypic candidate. This hypothesis was investigated in 238 ADHD-families (545 children) and 147 control-families (271 children). A motor timing task was administered, in which children had to produce a 1,000 ms interval. In addition to this task, two basic motor tasks were administered to examine speed and variability of motor output, when no timing component was required. Results indicated that variability in motor timing is a useful endophenotypic candidate: It was clearly associated with ADHD, it was also present in non-affected siblings, and it correlated within families. Accuracy (under- versus over-production) in motor timing appeared less useful: Even though accuracy was associated with ADHD (probands and affected siblings had a tendency to under-produce the 1,000 ms interval compared to controls), non-affected siblings did not differ from controls and sibling correlations were only marginally significant. Slow and variable motor output without timing component also appears present in ADHD, but not in non-affected siblings, suggesting these deficits not to be related to a familial vulnerability for ADHD. Deficits in motor timing could not be explained by deficits already present in basic motor output without a timing component. This suggests abnormalities in motor timing were predominantly related to deficient motor timing processes and not to general deficient motor functioning. The finding that deficits in motor timing run in ADHD-families suggests this to be a fruitful domain for further exploration in relation to the genetic underpinnings of ADHD. PMID:18071893

Motor trajectories from birth to 5 years of children born at less than 30 weeks' gestation: early predictors and functional implications. Protocol for a prospective cohort study.

PubMed

Spittle, Alicia J; McGinley, Jennifer L; Thompson, Deanne; Clark, Ross; FitzGerald, Tara L; Mentiplay, Benjamin F; Lee, Katherine J; Olsen, Joy E; Burnett, Alice; Treyvaud, Karli; Josev, Elisha; Alexander, Bonnie; Kelly, Claire E; Doyle, Lex W; Anderson, Peter J; Cheong, Jeanie Ly

2016-10-01

Motor impairments are one of the most frequently reported adverse neurodevelopmental consequences in children born < 30 weeks' gestation. Up to 15% of children born at < 30 weeks have cerebral palsy and an additional 50% have mild to severe motor impairment at school age. The first 5 years of life are critical for the development of fundamental motor skills. These skills form the basis for more complex skills that are required to competently and confidently participate in schooling, sporting and recreational activities. In children born at < 30 weeks' gestation, the trajectory of motor development from birth to 5 years is not fully understood. The neural alterations that underpin motor impairments in these children are also unclear. It is essential to determine if early clinical evaluations and neuroimaging biomarkers can predict later motor impairment and associated functional problems at 5 years of age. This will help to identify children who will benefit the most from early intervention and improve functional outcomes at school age. The primary aim of this study is to compare the prevalence of motor impairment from birth to 5 years of age between children born at < 30 weeks and term-born controls, and to determine whether persistent abnormal motor assessments in the newborn period in those born at < 30 weeks predict abnormal motor functioning at 5 years of age. Secondary aims for children born at < 30 weeks and term-born children are: 1) to determine whether novel early magnetic resonance imaging-based structural or functional biomarkers that can predict motor impairments at 5 years are detectable in the neonatal period; 2) to investigate the association between motor impairments and concurrent deficits in body structure and function at 5 years of age; and 3) to explore how motor impairments at 5 years (including abnormalities of gait, postural control and strength) are associated with concurrent functional outcomes, including physical activity, cognitive ability, learning ability, and behavioural and emotional problems. Prospective longitudinal cohort study. 150 preterm children (born at < 30 weeks' gestation) and 151 term-born children (born at > 36 completed weeks' gestation and weighing > 2499g) admitted to the Royal Women's Hospital, Melbourne, were recruited at birth and will be invited to participate in a 5-year follow-up study. This study will examine previously collected data (from birth to 2 years) that comprise detailed motor assessments, and structural and functional brain MRI images. At 5 years, preterm and term, children will be examined using comprehensive motor assessments, including: the Movement Assessment Battery for Children (2nd edition) and measures of gait function through spatiotemporal (assessed with the GAITRite® Walkway) and dynamic postural control (assessed with Microsoft Kinect) variables; and hand grip strength (assessed with a dynamometer); and measures of physical activity (assessed using accelerometry), cognitive development (assessed with Wechsler Preschool and Primary Scale of Intelligence), and emotional and behavioural status (assessed with the Strengths and Difficulties Questionnaire and the Developmental and Wellbeing Assessment). At the 5-year assessment, parents/caregivers will be asked to complete questionnaires on demographics, physical activity, activities of daily living, behaviour, additional therapy (eg, physiotherapy and occupational therapy), and motor function (assessed with Pediatric Evaluation of Disability Inventory, Pediatric Quality of Life Questionnaire, the Little Developmental Co-ordination Questionnaire and an activity diary). For the primary aim, the prevalence of motor impairment from birth to 5 years will be compared between children born at < 30 weeks and at term, using the proportion of children classified as abnormal at each of the time points (term age, 1, 2 and 5 years). Persistent motor impairments during the neonatal period will be assessed as a predictor of severity of motor impairment at 5 years of age in children born < 30 weeks using linear regression. Models will be fitted using generalised estimating equations to allow for the clustering of multiple births. Analysis will be repeated with adjustment for predictors of motor outcome, including additional therapy, sex, brain injury and chronic lung disease. Understanding the developmental precursors of motor impairment in children born before 30 weeks is essential for limiting disruption to skill development, and potential secondary impacts on physical activity, participation, academic achievement, self-esteem and associated outcomes (such as obesity, poor physical fitness and social isolation). An improved understanding of motor skill development will enable targeting of interventions and streamlining of services to children at highest risk of motor impairments. Copyright © 2016 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Motor cortical hyperexcitability in idiopathic scoliosis: could focal dystonia be a subclinical etiological factor?

PubMed Central

Tormos, José María; Barrios, Carlos; Pascual-Leone, Alvaro

2009-01-01

The aetiology of idiopathic scoliosis (IS) remains unknown; however, there is a growing body of evidence suggesting that the spine deformity could be the expression of a subclinical nervous system disorder. A defective sensory input or an anomalous sensorimotor integration may lead to an abnormal postural tone and therefore the development of a spine deformity. Inhibition of the motor cortico-cortical excitability is abnormal in dystonia. Therefore, the study of cortico-cortical inhibition may shed some insight into the dystonia hypothesis regarding the pathophysiology of IS. Paired pulse transcranial magnetic stimulation was used to study cortico-cortical inhibition and facilitation in nine adolescents with IS, five teenagers with congenital scoliosis (CS) and eight healthy age-matched controls. The effect of a previous conditioning stimulus (80% intensity of resting motor threshold) on the amplitude of the motor-evoked potential induced by the test stimulus (120% of resting motor threshold) was examined at various interstimulus intervals (ISIs) in both abductor pollicis brevis muscles. The results of healthy adolescents and those with CS showed a marked inhibitory effect of the conditioning stimulus on the response to the test stimulus at interstimulus intervals shorter than 6 ms. These findings do not differ from those reported for normal adults. However, children with IS revealed an abnormally reduced cortico-cortical inhibition at the short ISIs. Cortico-cortical inhibition was practically normal on the side of the scoliotic convexity while it was significantly reduced on the side of the scoliotic concavity. In conclusion, these findings support the hypothesis that a dystonic dysfunction underlies in IS. Asymmetrical cortical hyperexcitability may play an important role in the pathogenesis of IS and represents an objective neurophysiological finding that could be used clinically. PMID:20033462

Spasmodic Dysphonia: a Laryngeal Control Disorder Specific to Speech

PubMed Central

Ludlow, Christy L.

2016-01-01

Spasmodic dysphonia (SD) is a rare neurological disorder that emerges in middle age, is usually sporadic, and affects intrinsic laryngeal muscle control only during speech. Spasmodic bursts in particular laryngeal muscles disrupt voluntary control during vowel sounds in adductor SD and interfere with voice onset after voiceless consonants in abductor SD. Little is known about its origins; it is classified as a focal dystonia secondary to an unknown neurobiological mechanism that produces a chronic abnormality of laryngeal motor neuron regulation during speech. It develops primarily in females and does not interfere with breathing, crying, laughter, and shouting. Recent postmortem studies have implicated the accumulation of clusters in the parenchyma and perivascular regions with inflammatory changes in the brainstem in one to two cases. A few cases with single mutations in THAP1, a gene involved in transcription regulation, suggest that a weak genetic predisposition may contribute to mechanisms causing a nonprogressive abnormality in laryngeal motor neuron control for speech but not for vocal emotional expression. Research is needed to address the basic cellular and proteomic mechanisms that produce this disorder to provide intervention that could target the pathogenesis of the disorder rather than only providing temporary symptom relief. PMID:21248101

Spasmodic dysphonia: a laryngeal control disorder specific to speech.

PubMed

Ludlow, Christy L

2011-01-19

Spasmodic dysphonia (SD) is a rare neurological disorder that emerges in middle age, is usually sporadic, and affects intrinsic laryngeal muscle control only during speech. Spasmodic bursts in particular laryngeal muscles disrupt voluntary control during vowel sounds in adductor SD and interfere with voice onset after voiceless consonants in abductor SD. Little is known about its origins; it is classified as a focal dystonia secondary to an unknown neurobiological mechanism that produces a chronic abnormality of laryngeal motor neuron regulation during speech. It develops primarily in females and does not interfere with breathing, crying, laughter, and shouting. Recent postmortem studies have implicated the accumulation of clusters in the parenchyma and perivascular regions with inflammatory changes in the brainstem in one to two cases. A few cases with single mutations in THAP1, a gene involved in transcription regulation, suggest that a weak genetic predisposition may contribute to mechanisms causing a nonprogressive abnormality in laryngeal motor neuron control for speech but not for vocal emotional expression. Research is needed to address the basic cellular and proteomic mechanisms that produce this disorder to provide intervention that could target the pathogenesis of the disorder rather than only providing temporary symptom relief.

Evaluation of Esophageal Motor Function With High-resolution Manometry

PubMed Central

2013-01-01

For several decades esophageal manometry has been the test of choice to evaluate disorders of esophageal motor function. The recent introduction of high-resolution manometry for the study of esophageal motor function simplified performance of esophageal manometry, and revealed previously unidentified patterns of normal and abnormal esophageal motor function. Presentation of pressure data as color contour plots or esophageal pressure topography led to the development of new tools for analyzing and classifying esophageal motor patterns. The current standard and still developing approach to do this is the Chicago classification. While this methodical approach is improving our diagnosis of esophageal motor disorders, it currently does not address all motor abnormalities. We will explore the Chicago classification and disorders that it does not address. PMID:23875094

Absent movement-related cortical potentials in children with primary motor stereotypies.

PubMed

Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A; Vorbach, Sherry; Singer, Harvey S; Hallett, Mark

2014-08-01

The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown, with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about 1 second before the onset of a voluntary movement. Early MRCPs preceded self-paced arm movements in 8 of 10 children with motor stereotypies and in 6 of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. © 2013 International Parkinson and Movement Disorder Society.

Absent movement-related cortical potentials in children with primary motor stereotypies

PubMed Central

Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A.; Vorbach, Sherry; Singer, Harvey S.; Hallett, Mark

2013-01-01

Background The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Methods Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about one second before the onset of a voluntary movement. Results Early MRCPs preceded self-paced arm movements in 8 out of 10 children with motor stereotypies and in 6 out of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Conclusions Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. PMID:24259275

Visual-Spatial Orienting in Autism.

ERIC Educational Resources Information Center

Wainwright, J. Ann; Bryson, Susan E.

1996-01-01

Visual-spatial orienting in 10 high-functioning adults with autism was examined. Compared to controls, subjects responded faster to central than to lateral stimuli, and showed a left visual field advantage for stimulus detection only when laterally presented. Abnormalities in attention shifting and coordination of attentional and motor systems are…

Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson's disease.

PubMed

Melloni, Margherita; Sedeño, Lucas; Hesse, Eugenia; García-Cordero, Indira; Mikulan, Ezequiel; Plastino, Angelo; Marcotti, Aida; López, José David; Bustamante, Catalina; Lopera, Francisco; Pineda, David; García, Adolfo M; Manes, Facundo; Trujillo, Natalia; Ibáñez, Agustín

2015-07-08

Impairments of action language have been documented in early stage Parkinson's disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxel-based morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies.

Understanding the role of the primary somatosensory cortex: Opportunities for rehabilitation

PubMed Central

Borich, M.R.; Brodie, S.M.; Gray, W.A.; Ionta, S.; Boyd, L.A.

2016-01-01

Emerging evidence indicates impairments in somatosensory function may be a major contributor to motor dysfunction associated with neurologic injury or disorders. However, the neuroanatomical substrates underlying the connection between aberrant sensory input and ineffective motor output are still under investigation. The primary somatosensory cortex (S1) plays a critical role in processing afferent somatosensory input and contributes to the integration of sensory and motor signals necessary for skilled movement. Neuroimaging and neurostimulation approaches provide unique opportunities to non-invasively study S1 structure and function including connectivity with other cortical regions. These research techniques have begun to illuminate casual contributions of abnormal S1 activity and connectivity to motor dysfunction and poorer recovery of motor function in neurologic patient populations. This review synthesizes recent evidence illustrating the role of S1 in motor control, motor learning and functional recovery with an emphasis on how information from these investigations may be exploited to inform stroke rehabilitation to reduce motor dysfunction and improve therapeutic outcomes. PMID:26164474

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

PubMed

Melzer, Tracy R; Watts, Richard; MacAskill, Michael R; Pearson, John F; Rüeger, Sina; Pitcher, Toni L; Livingston, Leslie; Graham, Charlotte; Keenan, Ross; Shankaranarayanan, Ajit; Alsop, David C; Dalrymple-Alford, John C; Anderson, Tim J

2011-03-01

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

Influence of Deep Breathing on Heart Rate Variability in Parkinson's Disease: Co-relation with Severity of Disease and Non-Motor Symptom Scale Score.

PubMed

Bidikar, Mukta Pritam; Jagtap, Gayatri J; Chakor, Rahul T

2014-07-01

Dysautonomia and non-motor symptoms (NMS) in Parkinson's disease (PD) are frequent, disabling and reduce quality of life of patient. There is a paucity of studies on autonomic dysfunction in PD in Indian population. The study aimed to evaluate autonomic dysfunction in PD patients and co-relate the findings with severity of PD and Non-Motor Symptoms Scale (NMSS) score. We evaluated autonomic function in 30 diagnosed patients of PD (age 55-70 years) and 30 healthy age-matched controls by 3 min deep breathing test (DBT). NMSS was used to identify non-motor symptoms and Hoehn and Yahr (HY) Scale to grade severity of PD. The DBT findings were co-related with severity of PD (HY staging) and NMSS score. DBT was found to be abnormal in 40% while it was on borderline in 33.3% of PD patients. There was a statistically significant difference (p<0.01) between patients and control group for the DBT. NMS were reported across all the stages of PD but with variable frequency and severity for individual symptom. A negative co-relation was found between results of deep breathing test and clinical severity of disease and NMSS score. Abnormalities of autonomic function and NMS were integral and present across all the stages of PD patients. Early recognition and treatment of these may decrease morbidity and improve quality of life of PD patients.

Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders.

PubMed

Redle, Erin; Vannest, Jennifer; Maloney, Thomas; Tsevat, Rebecca K; Eikenberry, Sarah; Lewis, Barbara; Shriberg, Lawrence D; Tkach, Jean; Holland, Scott K

2015-02-09

Children with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. This case-control study included 12 children with PSD (mean age 7.42 years, four female) and 12 controls (mean age 7.44 years, four female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. Children with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. Over-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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

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.

Identification of abnormal motor cortex activation patterns in children with cerebral palsy by functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Khan, Bilal; Tian, Fenghua; Behbehani, Khosrow; Romero, Mario I.; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Reid, Dahlia; Liu, Hanli; Alexandrakis, George

2010-05-01

We demonstrate the utility of functional near-infrared spectroscopy (fNIRS) as a tool for physicians to study cortical plasticity in children with cerebral palsy (CP). Motor cortex activation patterns were studied in five healthy children and five children with CP (8.4+/-2.3 years old in both groups) performing a finger-tapping protocol. Spatial (distance from center and area difference) and temporal (duration and time-to-peak) image metrics are proposed as potential biomarkers for differentiating abnormal cortical activation in children with CP from healthy pediatric controls. In addition, a similarity image-analysis concept is presented that unveils areas that have similar activation patterns as that of the maximum activation area, but are not discernible by visual inspection of standard activation images. Metrics derived from the images presenting areas of similarity are shown to be sensitive identifiers of abnormal activation patterns in children with CP. Importantly, the proposed similarity concept and related metrics may be applicable to other studies for the identification of cortical activation patterns by fNIRS.

Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

PubMed

Kita, Hitoshi; Kita, Takako

2011-07-13

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Writer's cramp: increased dorsal premotor activity during intended writing.

PubMed

Delnooz, Cathérine C S; Helmich, Rick C; Medendorp, W P; Van de Warrenburg, Bart P C; Toni, Ivan

2013-03-01

Simple writer's cramp (WC) is a task-specific form of dystonia, characterized by abnormal movements and postures of the hand during writing. It is extremely task-specific, since dystonic symptoms can occur when a patient uses a pencil for writing, but not when it is used for sharpening. Maladaptive plasticity, loss of inhibition, and abnormal sensory processing are important pathophysiological elements of WC. However, it remains unclear how those elements can account for its task-specificity. We used fMRI to isolate cerebral alterations associated with the task-specificity of simple WC. Subjects (13 simple WC patients, 20 matched controls) imagined grasping a pencil to either write with it or sharpen it. On each trial, we manipulated the pencil's position and the number of imagined movements, while monitoring variations in motor output with electromyography. We show that simple WC is characterized by abnormally increased activity in the dorsal premotor cortex (PMd) when imagined actions are specifically related to writing. This cerebral effect was independent from the known deficits in dystonia in generating focal motor output and in processing somatosensory feedback. This abnormal activity of the PMd suggests that the task-specific element of simple WC is primarily due to alterations at the planning level, in the computations that transform a desired action outcome into the motor commands leading to that action. These findings open the way for testing the therapeutic value of interventions that take into account the computational substrate of task-specificity in simple WC, e.g. modulations of PMd activity during the planning phase of writing. Copyright © 2011 Wiley Periodicals, Inc.

Evaluation of mirrored muscle activity in patients with Complex Regional Pain Syndrome.

PubMed

Bank, Paulina J M; Peper, C Lieke E; Marinus, Johan; Beek, Peter J; van Hilten, Jacobus J

2014-10-01

Motor dysfunction in Complex Regional Pain Syndrome (CRPS) has been associated with bilateral changes in central motor processing, suggesting abnormal coupling between the affected and unaffected limb. We evaluated the occurrence of involuntary muscle activity in a limb during voluntary movements of the contralateral limb (i.e., mirror activity) in unilaterally affected patients to examine disinhibition of contralateral motor activity in CRPS. Mirror activity was examined during unimanual rhythmic flexion-extension movements of the wrist through in-depth analysis of electromyography recordings from the passive arm in 20 CRPS patients and 40 controls. The number of mirror-epochs was comparable for both arms in both CRPS patients and controls. Mirror-epochs in the affected arm of patients were comparable to those in controls. Mirror-epochs in the unaffected arm were shorter and showed less resemblance (in terms of rhythm and timing) to activity of the homologous muscle in the moving arm compared to mirror-epochs in controls. No evidence for disinhibition of contralateral motor activity was found during unimanual movement. Although motor dysfunction in CRPS has been associated with bilateral changes in cortical motor processing, the present findings argue against disinhibition of interhemispheric projections to homologous muscles in the contralateral limb during unimanual movement. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Movement disorder symptoms associated with Unified ...

EPA Pesticide Factsheets

Objectives: The UPDRS is a commonly used neurological measurement to assess the presence and severity of parkinsonian symptoms. It has also been used to assess symptoms associated with Mn exposure. Objectives: to determine 1) if movement disorder symptoms were associated with UPDRS: Activities of Daily Living (ADL) and Motor abnormalities; and 2) which symptoms were most related to increased abnormalities on these UPDRS subscales. Participants & Methods: Correlations between self-reported movement disorder symptoms from a health questionnaire and scores obtained on UPDRS: ADL and Motor subscales, and the Bradykinesia domain of the Motor subscale, were assessed during a medical examination among 185 Mn-exposed participants from two Ohio towns. Partial correlations were used for statistical analyses, controlling for age, sex, education and a history of musculoskeletal disease.Results: The presence of movement disorder symptoms was positively associated with ADL (pr =0.647, p = <0.001), Motor (pr =0.449, p = <0.001), and Bradykinesia (pr =0.418, p = <0.001) domains on the UPDRS. Specific movement disorder symptoms most strongly associated with increased ADL and Motor scores included having difficulty getting out of chairs (pr =0.458, p = <0.001), writing (pr =0.481, p = <0.001), skilled movements (pr =0.478, p = <0.001), loss of coordination/balance (pr =0.457, p = <0.001), changes in walking (pr =0.412, p = <0.001) and slowness of movement (pr =0.539, p = <0.0

Complex movement disorders at disease onset in childhood narcolepsy with cataplexy

PubMed Central

Pizza, Fabio; Palaia, Vincenzo; Franceschini, Christian; Poli, Francesca; Moghadam, Keivan K.; Cortelli, Pietro; Nobili, Lino; Bruni, Oliviero; Dauvilliers, Yves; Lin, Ling; Edwards, Mark J.; Mignot, Emmanuel; Bhatia, Kailash P.

2011-01-01

Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of hypocretin-producing neurons in the hypothalamus of likely autoimmune aetiology. Noting that children with narcolepsy often display complex abnormal motor behaviours close to disease onset that do not meet the classical definition of cataplexy, we systematically analysed motor features in 39 children with narcolepsy with cataplexy in comparison with 25 age- and sex-matched healthy controls. We found that patients with narcolepsy with cataplexy displayed a complex array of ‘negative’ (hypotonia) and ‘active’ (ranging from perioral movements to dyskinetic–dystonic movements or stereotypies) motor disturbances. ‘Active’ and ‘negative’ motor scores correlated positively with the presence of hypotonic features at neurological examination and negatively with disease duration, whereas ‘negative’ motor scores also correlated negatively with age at disease onset. These observations suggest that paediatric narcolepsy with cataplexy often co-occurs with a complex movement disorder at disease onset, a phenomenon that may vanish later in the course of the disease. Further studies are warranted to assess clinical course and whether the associated movement disorder is also caused by hypocretin deficiency or by additional neurochemical abnormalities. PMID:21930661

Cognitive slowing in Parkinson disease is accompanied by hypofunctioning of the striatum.

PubMed

Sawamoto, N; Honda, M; Hanakawa, T; Aso, T; Inoue, M; Toyoda, H; Ishizu, K; Fukuyama, H; Shibasaki, H

2007-03-27

To investigate whether cognitive slowing in Parkinson disease (PD) reflects disruption of the basal ganglia or dysfunction of the frontal lobe by excluding an influence of abnormal brain activity due to motor deficits. We measured neuronal activity during a verbal mental-operation task with H(2)(15)O PET. This task enabled us to evaluate brain activity change associated with an increase in the cognitive speed without an influence on motor deficits. As the speed of the verbal mental-operation task increased, healthy controls exhibited proportional increase in activities in the anterior striatum and medial premotor cortex, suggesting the involvement of the corticobasal ganglia circuit in normal performance of the task. By contrast, patients with PD lacked an increase in the striatal activity, whereas the medial premotor cortex showed a proportional increase. Although the present study chose a liberal threshold and needs subsequent confirmation, the findings suggest that striatal disruption resulting in abnormal processing in the corticobasal ganglia circuit may contribute to cognitive slowing in Parkinson disease, as is the case in motor slowing.

Zebrafish embryos exposed to alcohol undergo abnormal development of motor neurons and muscle fibers.

PubMed

Sylvain, Nicole J; Brewster, Daniel L; Ali, Declan W

2010-01-01

Children exposed to alcohol in utero have significantly delayed gross and fine motor skills, as well as deficiencies in reflex development. The reasons that underlie the motor deficits caused by ethanol (EtOH) exposure remain to be fully elucidated. The present study was undertaken to investigate the effects of embryonic alcohol exposure (1.5%, 2% and 2.5% EtOH) on motor neuron and muscle fiber morphology in 3 days post fertilization (dpf) larval zebrafish. EtOH treated fish exhibited morphological deformities and fewer bouts of swimming in response to touch, compared with untreated fish. Immunolabelling with anti-acetylated tubulin indicated that fish exposed to 2.5% EtOH had significantly higher rates of motor neuron axon defects. Immunolabelling of primary and secondary motor neurons, using znp-1 and zn-8, revealed that fish exposed to 2% and 2.5% EtOH exhibited significantly higher rates of primary and secondary motor neuron axon defects compared to controls. Examination of red and white muscle fibers revealed that fish exposed to EtOH had significantly smaller fibers compared with controls. These findings indicate that motor neuron and muscle fiber morphology is affected by early alcohol exposure in zebrafish embryos, and that this may be related to deficits in locomotion. Copyright 2010 Elsevier Inc. All rights reserved.

Altered intra- and inter-network functional coupling of resting-state networks associated with motor dysfunction in stroke.

PubMed

Zhao, Zhiyong; Wu, Jie; Fan, Mingxia; Yin, Dazhi; Tang, Chaozheng; Gong, Jiayu; Xu, Guojun; Gao, Xinjie; Yu, Qiurong; Yang, Hao; Sun, Limin; Jia, Jie

2018-04-24

Motor functions are supported through functional integration across the extended motor system network. Individuals following stroke often show deficits on motor performance requiring coordination of multiple brain networks; however, the assessment of connectivity patterns after stroke was still unclear. This study aimed to investigate the changes in intra- and inter-network functional connectivity (FC) of multiple networks following stroke and further correlate FC with motor performance. Thirty-three left subcortical chronic stroke patients and 34 healthy controls underwent resting-state functional magnetic resonance imaging. Eleven resting-state networks were identified via independent component analysis (ICA). Compared with healthy controls, the stroke group showed abnormal FC within the motor network (MN), visual network (VN), dorsal attention network (DAN), and executive control network (ECN). Additionally, the FC values of the ipsilesional inferior parietal lobule (IPL) within the ECN were negatively correlated with the Fugl-Meyer Assessment (FMA) scores (hand + wrist). With respect to inter-network interactions, the ipsilesional frontoparietal network (FPN) decreased FC with the MN and DAN; the contralesional FPN decreased FC with the ECN, but it increased FC with the default mode network (DMN); and the posterior DMN decreased FC with the VN. In sum, this study demonstrated the coexistence of intra- and inter-network alterations associated with motor-visual attention and high-order cognitive control function in chronic stroke, which might provide insights into brain network plasticity following stroke. © 2018 Wiley Periodicals, Inc.

Action-effect binding is decreased in motor conversion disorder: implications for sense of agency.

PubMed

Kranick, Sarah M; Moore, James W; Yusuf, Nadia; Martinez, Valeria T; LaFaver, Kathrin; Edwards, Mark J; Mehta, Arpan R; Collins, Phoebe; Harrison, Neil A; Haggard, Patrick; Hallett, Mark; Voon, Valerie

2013-07-01

The abnormal movements seen in motor conversion disorder are affected by distraction and entrainment, similar to voluntary movement. Unlike voluntary movement, however, patients lack a sense of control for the abnormal movements, a failure of "self-agency." The action-effect binding paradigm has been used to quantify the sense of self-agency, because subjective contraction of time between an action and its effect only occurs if the patient feels that they are the agent responsible for the action. We used this paradigm, coupled with emotional stimuli, to investigate the sense of agency with voluntary movements in patients with motor conversion disorder. Twenty patients with motor conversion disorder and 20 age-matched and sex-matched healthy volunteers used a rotating clock to judge the time of their own voluntary key presses (action) and a subsequent auditory tone (effect) after they completed conditioning blocks in which high, medium, and low tones were coupled to images of happy, fearful, and neutral faces. The results replicated those produced previously: it was reported that an effect after a voluntary action occurred earlier, and the preceding action occurred later, compared with trials that used only key presses or tones. Patients had reduced overall binding scores relative to healthy volunteers, suggesting a reduced sense of agency. There was no effect of the emotional stimuli (faces) or other interaction effects. Healthy volunteers with subclinical depressive symptoms had higher overall binding scores. We demonstrate that patients with motor conversion disorder have decreased action-effect binding for normal voluntary movements compared with healthy volunteers, consistent with the greater experience of lack of control. Copyright © 2013 Movement Disorder Society.

Autism spectrum disorder and early motor abnormalities: Connected or coincidental companions?

PubMed

Setoh, Peipei; Marschik, Peter B; Einspieler, Christa; Esposito, Gianluca

2017-01-01

Research in the past decade has produced a growing body of evidence showing that motor abnormalities in individuals with autism spectrum disorder (ASD) are the rule rather than the exception. The paper by Chinello and colleagues furthers our understanding of the importance of studying motor functions in ASD by testing a non-clinical population of parents-infant triads. Chinello and colleagues' findings seem to suggest that subclinical motor impairments may exist in the typical population with inherited non-clinical ASD traits. Chinello and colleagues' discovery also urges us to ask why motor abnormalities exist in typically developing infants when their parents present some subclinical ASD traits. We believe that there are at least two possibilities. In the first possible scenario, motor impairments and ASD traits form a single cluster of symptoms unique to a subgroup of individuals with autism. A second possible scenario is that motor atypicalities are the first warning signs of vulnerability often associated with atypical development. In conclusion, Chinello et al.'s findings inform us that subclinical atypical phenotypes such as sociocommunicative anomalies may be related to subclinical motor performances in the next generation. This adds to our knowledge by shedding some light on the relation of vulnerability in one domain with vulnerability in another domain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Postlingual deaf speech and the role of audition in speech production: comments on Waldstein's paper [R.S. Waldstein, J. Acoust. Soc. Am. 88, 2099-2114 (1990)].

PubMed

Sapir, S; Canter, G J

1991-09-01

Using acoustic analysis techniques, Waldstein [J. Acoust. Soc. Am. 88, 2099-2114 (1990] reported abnormal speech findings in postlingual deaf speakers. She interpreted her findings to suggest that auditory feedback is important in motor speech control. However, it is argued here that Waldstein's interpretation may be unwarranted without addressing the possibility of neurologic deficits (e.g., dysarthria) as confounding (or even primary) causes of the abnormal speech in her subjects.

Megakaryocyte and platelet abnormalities in a patient with a W33C mutation in the conserved SH3-like domain of myosin heavy chain IIA.

PubMed

Kahr, Walter H A; Savoia, Anna; Pluthero, Fred G; Li, Ling; Christensen, Hilary; De Rocco, Daniela; Traivaree, Chanchai; Butchart, Sheila E; Curtin, Julie; Stollar, Elliott J; Forman-Kay, Julie D; Blanchette, Victor S

2009-12-01

Heterozygous mutations in MYH9, which encodes non-muscle myosin heavy chain IIA (MHC-IIA), result in autosomal dominant inherited MYH9-related disorders characterised by macro-thrombocytopenia, granulocyte inclusions, variable sensorineural deafness, cataracts and nephritis. MHC-IIA is assembled into a complex consisting of two pairs of light chains and two heavy chains, where the latter contain a neck region, SH3-like, motor and rod domains. We describe a patient with a Trp33Cys missense mutation in the SH3-like domain of MHC-IIA. Abnormal platelet function was observed using platelet aggregometry with the agonists epinephrine and adenosine diphosphate (ADP). Patient granulocytes and megakaryocytes, but not platelets, contained abnormal MHC-IIA inclusions visualised by confocal immunofluorescence or electron microscopy. Megakaryocytes grown in culture were smaller and contained hypolobulated nuclei compared to controls. Bone marrow-derived megakaryocytes revealed a preponderance of immature forms, the presence of structurally diverse inclusion bodies, and frequent emperipolesis as assessed by electron microscopy. Platelets and leukocytes contained indistinguishable amounts of total MHC-IIA determined by immunoblotting. Molecular modelling studies indicated that mutation of Trp33 destabilises the interface between the SH3-like and motor domain of MHC-IIA, which is close to previously described motor domain mutations, implying an important structural and/or functional role for this region in MHC-IIA.

Muscle synergies in children with dystonia capture "healthy" patterns regardless the altered motor performance.

PubMed

Lunardini, Francesca; Casellato, Claudia; Bertucco, Matteo; Sanger, Terence D; Pedrocchi, Alessandra

2015-01-01

Muscle synergies are hypothesized to represent motor modules recruited by the nervous system to flexibly perform subtasks necessary to achieve movement. Muscle synergy analysis may offer a better view of the neural structure underlying motor behaviors and how they change in motor deficits and rehabilitation. The aim of this study is to investigate if muscle synergies are able to encode regularities in the musculoskeletal system organization and dynamic behavior of patients with dystonia, or if they are altered as a consequence of the nervous system dysfunction in dystonia. To do so, we applied muscle synergies analysis to muscle activity recorded during the execution of upper limb writing tasks in 10 children with dystonia and 9 age-matched healthy controls. We show that, although children with dystonia present movement abnormalities compared to control subjects, the muscle synergies extracted from the two groups are very similar, and that the two groups share a significant number of motor modules. Our finding therefore suggests that a regular modular organization of upper limb muscle coordination is preserved for childhood dystonia.

Movement Disorders and Other Motor Abnormalities in Adults With 22q11.2 Deletion Syndrome

PubMed Central

Boot, Erik; Butcher, Nancy J; van Amelsvoort, Thérèse AMJ; Lang, Anthony E; Marras, Connie; Pondal, Margarita; Andrade, Danielle M; Fung, Wai Lun Alan; Bassett, Anne S

2015-01-01

Movement abnormalities are frequently reported in children with 22q11.2 deletion syndrome (22q11.2DS), but knowledge in this area is scarce in the increasing adult population. We report on five individuals illustrative of movement disorders and other motor abnormalities in adults with 22q11.2DS. In addition to an increased susceptibility to neuropsychiatric disorders, seizures, and early-onset Parkinson disease, the underlying brain dysfunction associated with 22q11.2DS may give rise to an increased vulnerability to multiple movement abnormalities, including those influenced by medications. Movement abnormalities may also be secondary to treatable endocrine diseases and congenital musculoskeletal abnormalities. We propose that movement abnormalities may be common in adults with 22q11.2DS and discuss the implications and challenges important to clinical practice. PMID:25684639

Abnormal laughter-like vocalisations replacing speech in primary progressive aphasia

PubMed Central

Rohrer, Jonathan D.; Warren, Jason D.; Rossor, Martin N.

2009-01-01

We describe ten patients with a clinical diagnosis of primary progressive aphasia (PPA) (pathologically confirmed in three cases) who developed abnormal laughter-like vocalisations in the context of progressive speech output impairment leading to mutism. Failure of speech output was accompanied by increasing frequency of the abnormal vocalisations until ultimately they constituted the patient's only extended utterance. The laughter-like vocalisations did not show contextual sensitivity but occurred as an automatic vocal output that replaced speech. Acoustic analysis of the vocalisations in two patients revealed abnormal motor features including variable note duration and inter-note interval, loss of temporal symmetry of laugh notes and loss of the normal decrescendo. Abnormal laughter-like vocalisations may be a hallmark of a subgroup in the PPA spectrum with impaired control and production of nonverbal vocal behaviour due to disruption of fronto-temporal networks mediating vocalisation. PMID:19435636

Abnormal laughter-like vocalisations replacing speech in primary progressive aphasia.

PubMed

Rohrer, Jonathan D; Warren, Jason D; Rossor, Martin N

2009-09-15

We describe ten patients with a clinical diagnosis of primary progressive aphasia (PPA) (pathologically confirmed in three cases) who developed abnormal laughter-like vocalisations in the context of progressive speech output impairment leading to mutism. Failure of speech output was accompanied by increasing frequency of the abnormal vocalisations until ultimately they constituted the patient's only extended utterance. The laughter-like vocalisations did not show contextual sensitivity but occurred as an automatic vocal output that replaced speech. Acoustic analysis of the vocalisations in two patients revealed abnormal motor features including variable note duration and inter-note interval, loss of temporal symmetry of laugh notes and loss of the normal decrescendo. Abnormal laughter-like vocalisations may be a hallmark of a subgroup in the PPA spectrum with impaired control and production of nonverbal vocal behaviour due to disruption of fronto-temporal networks mediating vocalisation.

Abnormal short-latency synaptic plasticity in the motor cortex of subjects with Becker muscular dystrophy: a rTMS study.

PubMed

Golaszewski, Stefan; Schwenker, Kerstin; Bergmann, Jürgen; Brigo, Francesco; Christova, Monica; Trinka, Eugen; Nardone, Raffaele

2016-01-01

We used repetitive transcranial magnetic stimulation (rTMS) to further investigate motor cortex excitability in 13 patients with Becker muscular dystrophy (BMD), six of them with slight mental retardation. RTMS delivered at 5Hz frequency and suprathreshold intensity progressively increases the size of motor evoked potentials (MEPs) in healthy subjects; the rTMS-induced facilitation of MEPs was significantly reduced in the BMD patients mentally retarded or classified as borderline when compared with age-matched control subjects and the BMD patients with normal intelligence. The increase in the duration of the cortical silent period was similar in both patient groups and controls. These findings suggest an altered cortical short-term synaptic plasticity in glutamate-dependent excitatory circuits within the motor cortex in BMD patients with intellectual disabilities. RTMS studies may shed new light on the physiological mechanisms of cortical involvement in dystrophinopathies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Motor cortical oscillations are abnormally suppressed during repetitive movement in patients with Parkinson's disease.

PubMed

Stegemöller, Elizabeth L; Allen, David P; Simuni, Tanya; MacKinnon, Colum D

2016-01-01

Impaired repetitive movement in persons with Parkinson's disease (PD) is associated with reduced amplitude, paradoxical hastening and hesitations or arrest at higher movement rates. This study examined the effects of movement rate and medication on movement-related cortical oscillations in persons with PD. Nine participants with PD were studied off and on medication and compared to nine control participants. Participants performed index finger movements cued by tones from 1 to 3 Hz. Movement-related oscillations were derived from electroencephalographic recordings over the region of the contralateral sensorimotor cortex (S1/M1) during rest, listening, or synchronized movement. At rest, spectral power recorded over the region of the contralateral S1/M1 was increased in the alpha band and decreased in the beta band in participants with PD relative to controls. During movement, the level of alpha and beta band power relative to baseline was significantly reduced in the PD group, off and on medication, compared to controls. Reduced movement amplitude and hastening at movement rates near 2 Hz was associated with abnormally suppressed and persistent desynchronization of oscillations in alpha and beta bands. Motor cortical oscillations in the alpha and beta bands are abnormally suppressed in PD, particularly during higher rate movements. These findings contribute to the understanding of mechanisms underlying impaired repetitive movement in PD. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome.

PubMed

Worbe, Yulia; Marrakchi-Kacem, Linda; Lecomte, Sophie; Valabregue, Romain; Poupon, Fabrice; Guevara, Pamela; Tucholka, Alan; Mangin, Jean-François; Vidailhet, Marie; Lehericy, Stephane; Hartmann, Andreas; Poupon, Cyril

2015-02-01

Gilles de la Tourette syndrome is a childhood-onset syndrome characterized by the presence and persistence of motor and vocal tics. A dysfunction of cortico-striato-pallido-thalamo-cortical networks in this syndrome has been supported by convergent data from neuro-pathological, electrophysiological as well as structural and functional neuroimaging studies. Here, we addressed the question of structural integration of cortico-striato-pallido-thalamo-cortical networks in Gilles de la Tourette syndrome. We specifically tested the hypothesis that deviant brain development in Gilles de la Tourette syndrome could affect structural connectivity within the input and output basal ganglia structures and thalamus. To this aim, we acquired data on 49 adult patients and 28 gender and age-matched control subjects on a 3 T magnetic resonance imaging scanner. We used and further implemented streamline probabilistic tractography algorithms that allowed us to quantify the structural integration of cortico-striato-pallido-thalamo-cortical networks. To further investigate the microstructure of white matter in patients with Gilles de la Tourette syndrome, we also evaluated fractional anisotropy and radial diffusivity in these pathways, which are both sensitive to axonal package and to myelin ensheathment. In patients with Gilles de la Tourette syndrome compared to control subjects, we found white matter abnormalities in neuronal pathways connecting the cerebral cortex, the basal ganglia and the thalamus. Specifically, striatum and thalamus had abnormally enhanced structural connectivity with primary motor and sensory cortices, as well as paracentral lobule, supplementary motor area and parietal cortices. This enhanced connectivity of motor cortex positively correlated with severity of tics measured by the Yale Global Tics Severity Scale and was not influenced by current medication status, age or gender of patients. Independently of the severity of tics, lateral and medial orbito-frontal cortex, inferior frontal, temporo-parietal junction, medial temporal and frontal pole also had enhanced structural connectivity with the striatum and thalamus in patients with Gilles de la Tourette syndrome. In addition, the cortico-striatal pathways were characterized by elevated fractional anisotropy and diminished radial diffusivity, suggesting microstructural axonal abnormalities of white matter in Gilles de la Tourette syndrome. These changes were more prominent in females with Gilles de la Tourette syndrome compared to males and were not related to the current medication status. Taken together, our data showed widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways in patients with Gilles de la Tourette, which likely result from abnormal brain development in this syndrome. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Electrophysiological correlates of motor conversion disorder.

PubMed

Liepert, Joachim; Hassa, Thomas; Tüscher, Oliver; Schmidt, Roger

2008-11-15

In patients with a functional (psychogenic) paresis, motor conduction tests are, by definition, normal. We investigated whether these patients exhibit an abnormal motor excitability. Four female patients with a functional paresis of the left upper extremity were studied using transcranial magnetic stimulation (TMS). We investigated motor thresholds, intracortical inhibition and intracortical facilitation at rest. Corticospinal excitability was evaluated by single pulse TMS during rest and during imagination of tonic index finger adductions. Data obtained from the affected first dorsal interosseous muscle were compared with the unaffected hand and with a healthy age-matched control group. Three patients demonstrated a flaccid paresis, one patient had a psychogenic dystonia. Motor thresholds, short interval intracortical inhibition and intracortical facilitation recorded from the affected side were normal. In healthy subjects, movement imagination produced an increase of corticospinal excitability. In the patients, motor imagery with the affected index finger resulted in a decrease of corticospinal excitability compared to rest, being significantly different from the unaffected side and from the control group. We suggest that suppression of corticospinal excitability during movement imagination is an electrophysiological correlate of the patients' inability to move voluntarily and provides some insight into the pathophysiology of this disorder.

Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson's Disease.

PubMed

San Luciano, Marta; Wang, Cuiling; Ortega, Roberto A; Yu, Qiping; Boschung, Sarah; Soto-Valencia, Jeannie; Bressman, Susan B; Lipton, Richard B; Pullman, Seth; Saunders-Pullman, Rachel

2016-01-01

Pre-clinical markers of Parkinson's Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD.

Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson’s Disease

PubMed Central

San Luciano, Marta; Wang, Cuiling; Ortega, Roberto A.; Yu, Qiping; Boschung, Sarah; Soto-Valencia, Jeannie; Bressman, Susan B.; Lipton, Richard B.; Pullman, Seth; Saunders-Pullman, Rachel

2016-01-01

Introduction Pre-clinical markers of Parkinson’s Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. Methods 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. Results All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Conclusion Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD. PMID:27732597

Dysarthria and broader motor speech deficits in Dravet syndrome.

PubMed

Turner, Samantha J; Brown, Amy; Arpone, Marta; Anderson, Vicki; Morgan, Angela T; Scheffer, Ingrid E

2017-02-21

To analyze the oral motor, speech, and language phenotype in 20 children and adults with Dravet syndrome (DS) associated with mutations in SCN1A . Fifteen verbal and 5 minimally verbal DS patients with SCN1A mutations (aged 15 months-28 years) underwent a tailored assessment battery. Speech was characterized by imprecise articulation, abnormal nasal resonance, voice, and pitch, and prosody errors. Half of verbal patients had moderate to severely impaired conversational speech intelligibility. Oral motor impairment, motor planning/programming difficulties, and poor postural control were typical. Nonverbal individuals had intentional communication. Cognitive skills varied markedly, with intellectual functioning ranging from the low average range to severe intellectual disability. Language impairment was congruent with cognition. We describe a distinctive speech, language, and oral motor phenotype in children and adults with DS associated with mutations in SCN1A. Recognizing this phenotype will guide therapeutic intervention in patients with DS. © 2017 American Academy of Neurology.

Dysarthria and broader motor speech deficits in Dravet syndrome

PubMed Central

Turner, Samantha J.; Brown, Amy; Arpone, Marta; Anderson, Vicki; Morgan, Angela T.

2017-01-01

Objective: To analyze the oral motor, speech, and language phenotype in 20 children and adults with Dravet syndrome (DS) associated with mutations in SCN1A. Methods: Fifteen verbal and 5 minimally verbal DS patients with SCN1A mutations (aged 15 months-28 years) underwent a tailored assessment battery. Results: Speech was characterized by imprecise articulation, abnormal nasal resonance, voice, and pitch, and prosody errors. Half of verbal patients had moderate to severely impaired conversational speech intelligibility. Oral motor impairment, motor planning/programming difficulties, and poor postural control were typical. Nonverbal individuals had intentional communication. Cognitive skills varied markedly, with intellectual functioning ranging from the low average range to severe intellectual disability. Language impairment was congruent with cognition. Conclusions: We describe a distinctive speech, language, and oral motor phenotype in children and adults with DS associated with mutations in SCN1A. Recognizing this phenotype will guide therapeutic intervention in patients with DS. PMID:28148630

EEG low-resolution brain electromagnetic tomography (LORETA) in Huntington's disease.

PubMed

Painold, Annamaria; Anderer, Peter; Holl, Anna K; Letmaier, Martin; Saletu-Zyhlarz, Gerda M; Saletu, Bernd; Bonelli, Raphael M

2011-05-01

Previous studies have shown abnormal electroencephalography (EEG) in Huntington's disease (HD). The aim of the present investigation was to compare quantitatively analyzed EEGs of HD patients and controls by means of low-resolution brain electromagnetic tomography (LORETA). Further aims were to delineate the sensitivity and utility of EEG LORETA in the progression of HD, and to correlate parameters of cognitive and motor impairment with neurophysiological variables. In 55 HD patients and 55 controls a 3-min vigilance-controlled EEG (V-EEG) was recorded during midmorning hours. Power spectra and intracortical tomography were computed by LORETA in seven frequency bands and compared between groups. Spearman rank correlations were based on V-EEG and psychometric data. Statistical overall analysis by means of the omnibus significance test demonstrated significant (p < 0.01) differences between HD patients and controls. LORETA theta, alpha and beta power were decreased from early to late stages of the disease. Only advanced disease stages showed a significant increase in delta power, mainly in the right orbitofrontal cortex. Correlation analyses revealed that a decrease of alpha and theta power correlated significantly with increasing cognitive and motor decline. LORETA proved to be a sensitive instrument for detecting progressive electrophysiological changes in HD. Reduced alpha power seems to be a trait marker of HD, whereas increased prefrontal delta power seems to reflect worsening of the disease. Motor function and cognitive function deteriorate together with a decrease in alpha and theta power. This data set, so far the largest in HD research, helps to elucidate remaining uncertainties about electrophysiological abnormalities in HD.

The Role of the Orbitofrontal Cortex in Normally Developing Compulsive-Like Behaviors and Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Evans, David W.; Lewis, Marc D.; Iobst, Emily

2004-01-01

Mounting evidence concerning obsessive-compulsive disorders points to abnormal functioning of the orbitofrontal cortices. First, patients with obsessive-compulsive disorder (OCD) perform poorly on tasks that rely on response suppression/motor inhibition functions mediated by the orbitofrontal cortex relative to both normal and clinical controls.…

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.

Primary motor cortex of the parkinsonian monkey: altered encoding of active movement

PubMed Central

Pasquereau, Benjamin; DeLong, Mahlon R.

2016-01-01

Abnormalities in the movement-related activation of the primary motor cortex (M1) are thought to be a major contributor to the motor signs of Parkinson’s disease. The existing evidence, however, variably indicates that M1 is under-activated with movement, overactivated (due to a loss of functional specificity) or activated with abnormal timing. In addition, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those gaps in knowledge were addressed by studying the extracellular activity of antidromically-identified lamina 5b pyramidal-tract type neurons (n = 153) and intratelencephalic-type corticostriatal neurons (n = 126) in the M1 of two monkeys as they performed a step-tracking arm movement task. We compared movement-related discharge before and after the induction of parkinsonism by administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and quantified the spike rate encoding of specific kinematic parameters of movement using a generalized linear model. The fraction of M1 neurons with movement-related activity declined following MPTP but only marginally. The strength of neuronal encoding of parameters of movement was reduced markedly (mean 29% reduction in the coefficients from the generalized linear model). This relative decoupling of M1 activity from kinematics was attributable to reductions in the coefficients that estimated the spike rate encoding of movement direction (−22%), speed (−40%), acceleration (−49%) and hand position (−33%). After controlling for MPTP-induced changes in motor performance, M1 activity related to movement itself was reduced markedly (mean 36% hypoactivation). This reduced activation was strong in pyramidal tract-type neurons (−50%) but essentially absent in corticostriatal neurons. The timing of M1 activation was also abnormal, with earlier onset times, prolonged response durations, and a 43% reduction in the prevalence of movement-related changes beginning in the 150-ms period that immediately preceded movement. Overall, the results are consistent with proposals that under-activation and abnormal timing of movement-related activity in M1 contribute to parkinsonian motor signs but are not consistent with the idea that a loss of functional specificity plays an important role. Given that pyramidal tract-type neurons form the primary efferent pathway that conveys motor commands to the spinal cord, the dysfunction of movement-related activity in pyramidal tract-type neurons is likely to be a central factor in the pathophysiology of parkinsonian motor signs. PMID:26490335

Developing biologically-based assessment tools for physical therapy management of neck pain.

PubMed

MacDermid, Joy C; Gross, Anita R; Galea, Victoria; McLaughlin, Laurie M; Parkinson, William L; Woodhouse, Linda J

2009-05-01

Neck pain is a common and episodic condition that is treated using a spectrum of interventions known to be moderately effective but is associated with a significant incidence of chronic pain. Recently, there has been increased focus on defining biological aspects of neck pain. Studies have indicated that neurophysiological, biomechanical, and motor control abnormalities are present and may be useful either in prognosis or classification. We review some of these findings in the context of our own work defining biological markers that may form the basis for clinical tests that can be used for prognosis, classification, or outcome evaluation in patients with neck pain. We have identified abnormalities in neurophysiology using quantitative sensory testing (vibration, touch, and current perception) and response to cold provocation that are related to neck disability. We have identified altered muscle biochemistry by measuring circulating muscle proteins in a lumbar surgery model and are now applying those methods to whiplash injury. We have incorporated capnography into treatment to address central physiological changes present in some patients by monitoring and training CO2 levels. We have developed an innovative new test, the Neck Walk Index, that captures abnormal control of head movement during slow gait as a means of differentiating patients with neck pain from either unaffected controls or individuals with other pathologies. We have used time-varying 3-dimensional joint orientation kinematics to assess deficits in motor control during an upper extremity reach task, the results showing that poor coordination and control of the shoulder girdle leads to shoulder guarding and inconsistencies in elbow joint movement. Despite some promising early results, future research is needed to determine how these measures help clinicians to diagnose, evaluate, and forecast future outcome for patients who present with neck pain. Diagnosis, level 5.

Sensory tricks and brain excitability in cervical dystonia: a transcranial magnetic stimulation study.

PubMed

Amadio, Stefano; Houdayer, Elise; Bianchi, Francesca; Tesfaghebriel Tekle, Habtom; Urban, Ivan Pietro; Butera, Calogera; Guerriero, Roberta; Cursi, Marco; Leocani, Letizia; Comi, Giancarlo; Del Carro, Ubaldo

2014-08-01

Sensory tricks such as touching the face with fingertips often improve cervical dystonia [CD]. This study is to determine whether sensory tricks modulate motor cortex excitability, assessed by paired-pulse transcranial magnetic stimulation [p-pTMS]. Eight patients with rotational CD underwent p-pTMS, at rest and when the sensory trick was applied. To test intracortical inhibition [ICI] and facilitation [ICF], the amplitude ratio between conditioned and unconditioned cortical motor evoked potentials was measured at several interstimulus intervals (ISI 1, 3, 15, and 20 ms) and compared with controls mimicking patients' sensory tricks. At rest, a significant ICF enhancement was found at ISIs 15 through 20 in patients compared with controls, whereas no significant ICI changes were observed. Sensory tricks significantly reduced the abnormal ICF in patients and did not induce any change in controls. In our CD patients, sensory tricks seem to improve dystonia through an inhibitory effect on motor cortex excitability. © 2014 International Parkinson and Movement Disorder Society.

Infant and child motor development.

PubMed

Edwards, Sara L; Sarwark, John F

2005-05-01

Identifying infant and child developmental delay is a skill important for orthopaedic surgeons to master because they often are asked to distinguish between normal and abnormal movement. An emphasis has been placed on early detection and referral for intervention, which has been shown to enhance the lives of the infant or child and his or her family. Appropriate recognition of delay is necessary for referral to early intervention services, which serve to help these children overcome or improve motor dysfunction and to help families grow more confident in caring for children with special needs. We define early intervention, discuss normal and abnormal motor development, and provide useful examination tools to assess motor development.

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units

PubMed Central

Sanchez, Gabriel N.; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L.; Schnitzer, Mark J.

2017-01-01

SUMMARY Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle’s contractile units. Despite the motor unit’s centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. PMID:26687220

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

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units.

PubMed

Sanchez, Gabriel N; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L; Schnitzer, Mark J

2015-12-16

Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle's contractile units. Despite the motor unit's centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. Copyright © 2015 Elsevier Inc. All rights reserved.

Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson's disease.

PubMed

Cury, Rubens G; Galhardoni, Ricardo; Teixeira, Manoel J; Dos Santos Ghilardi, Maria G; Silva, Valquiria; Myczkowski, Martin L; Marcolin, Marco A; Barbosa, Egberto R; Fonoff, Erich T; Ciampi de Andrade, Daniel

2016-12-01

Subthalamic deep brain stimulation (STN-DBS) is used to treat refractory motor complications in Parkinson disease (PD), but its effects on nonmotor symptoms remain uncertain. Up to 80% of patients with PD may have pain relief after STN-DBS, but it is unknown whether its analgesic properties are related to potential effects on sensory thresholds or secondary to motor improvement. We have previously reported significant and long-lasting pain relief after DBS, which did not correlate with motor symptomatic control. Here we present secondary data exploring the effects of DBS on sensory thresholds in a controlled way and have explored the relationship between these changes and clinical pain and motor improvement after surgery. Thirty-seven patients were prospectively evaluated before STN-DBS and 12 months after the procedure compared with healthy controls. Compared with baseline, patients with PD showed lower thermal and mechanical detection and higher cold pain thresholds after surgery. There were no changes in heat and mechanical pain thresholds. Compared with baseline values in healthy controls, patients with PD had higher thermal and mechanical detection thresholds, which decreased after surgery toward normalization. These sensory changes had no correlation with motor or clinical pain improvement after surgery. These data confirm the existence of sensory abnormalities in PD and suggest that STN-DBS mainly influenced the detection thresholds rather than painful sensations. However, these changes may depend on the specific effects of DBS on somatosensory loops with no correlation to motor or clinical pain improvement.

Increased task-uncorrelated muscle activity in childhood dystonia.

PubMed

Lunardini, Francesca; Maggioni, Serena; Casellato, Claudia; Bertucco, Matteo; Pedrocchi, Alessandra L G; Sanger, Terence D

2015-06-12

Even if movement abnormalities in dystonia are obvious on observation-based examinations, objective measures to characterize dystonia and to gain insights into its pathophysiology are still strongly needed. We hypothesize that motor abnormalities in childhood dystonia are partially due to the inability to suppress involuntary variable muscle activity irrelevant to the achievement of the desired motor task, resulting in the superposition of unwanted motion components on the desired movement. However, it is difficult to separate and quantify appropriate and inappropriate motor signals combined in the same muscle, especially during movement. We devise an innovative and practical method to objectively measure movement abnormalities during the performance of a continuous figure-eight writing task in 7 children with dystonia and 9 age-matched healthy controls. During the execution of a continuous writing task, muscle contractions should occur at frequencies that match the frequencies of the writing outcome. We compare the power spectra of kinematic trajectories and electromyographic signals of 8 upper limb muscles to separate muscle activity with the same frequency content of the figure-eight movement (task-correlated) from activity occurring at frequencies extraneous to the task (task-uncorrelated). Children with dystonia present a greater magnitude of task-uncorrelated muscle components. The motor performance achieved by children with dystonia is characterized by an overall lower quality, with high spatial and temporal variability and an altered trade-off between speed and accuracy. Findings are consistent with the hypothesis that, in childhood dystonia, the ability to appropriately suppress variable and uncorrelated elements of movement is impaired. Here we present a proof-of-concept of a promising tool to characterize the phenomenology of movement disorders and to inform the design of neurorehabilitation therapies.

Learning fast accurate movements requires intact frontostriatal circuits

PubMed Central

Shabbott, Britne; Ravindran, Roshni; Schumacher, Joseph W.; Wasserman, Paula B.; Marder, Karen S.; Mazzoni, Pietro

2013-01-01

The basal ganglia are known to play a crucial role in movement execution, but their importance for motor skill learning remains unclear. Obstacles to our understanding include the lack of a universally accepted definition of motor skill learning (definition confound), and difficulties in distinguishing learning deficits from execution impairments (performance confound). We studied how healthy subjects and subjects with a basal ganglia disorder learn fast accurate reaching movements. We addressed the definition and performance confounds by: (1) focusing on an operationally defined core element of motor skill learning (speed-accuracy learning), and (2) using normal variation in initial performance to separate movement execution impairment from motor learning abnormalities. We measured motor skill learning as performance improvement in a reaching task with a speed-accuracy trade-off. We compared the performance of subjects with Huntington's disease (HD), a neurodegenerative basal ganglia disorder, to that of premanifest carriers of the HD mutation and of control subjects. The initial movements of HD subjects were less skilled (slower and/or less accurate) than those of control subjects. To factor out these differences in initial execution, we modeled the relationship between learning and baseline performance in control subjects. Subjects with HD exhibited a clear learning impairment that was not explained by differences in initial performance. These results support a role for the basal ganglia in both movement execution and motor skill learning. PMID:24312037

A common optimization principle for motor execution in healthy subjects and parkinsonian patients.

PubMed

Baraduc, Pierre; Thobois, Stéphane; Gan, Jing; Broussolle, Emmanuel; Desmurget, Michel

2013-01-09

Recent research on Parkinson's disease (PD) has emphasized that parkinsonian movement, although bradykinetic, shares many attributes with healthy behavior. This observation led to the suggestion that bradykinesia in PD could be due to a reduction in motor motivation. This hypothesis can be tested in the framework of optimal control theory, which accounts for many characteristics of healthy human movement while providing a link between the motor behavior and a cost/benefit trade-off. This approach offers the opportunity to interpret movement deficits of PD patients in the light of a computational theory of normal motor control. We studied 14 PD patients with bilateral subthalamic nucleus (STN) stimulation and 16 age-matched healthy controls, and tested whether reaching movements were governed by similar rules in these two groups. A single optimal control model accounted for the reaching movements of healthy subjects and PD patients, whatever the condition of STN stimulation (on or off). The choice of movement speed was explained in all subjects by the existence of a preset dynamic range for the motor signals. This range was idiosyncratic and applied to all movements regardless of their amplitude. In PD patients this dynamic range was abnormally narrow and correlated with bradykinesia. STN stimulation reduced bradykinesia and widened this range in all patients, but did not restore it to a normal value. These results, consistent with the motor motivation hypothesis, suggest that constrained optimization of motor effort is the main determinant of movement planning (choice of speed) and movement production, in both healthy and PD subjects.

Early motor repertoire in very low birth weight infants in India is associated with motor development at one year.

PubMed

Adde, Lars; Thomas, Niranjan; John, Hima B; Oommen, Samuel; Vågen, Randi Tynes; Fjørtoft, Toril; Jensenius, Alexander Refsum; Støen, Ragnhild

2016-11-01

Most studies on Prechtl's method of assessing General Movements (GMA) in young infants originate in Europe. To determine if motor behavior at an age of 3 months post term is associated with motor development at 12 months post age in VLBW infants in India. 243 VLBW infants (135 boys, 108 girls; median gestational age 31wks, range 26-39wks) were video-recorded at a median age of 11wks post term (range 9-16wks). Certified and experienced observers assessed the videos by the "Assessment of Motor Repertoire - 2-5 Months". Fidgety movements (FMs) were classified as abnormal if absent, sporadic or exaggerated, and as normal if intermittently or continually present. The motor behaviour was evaluated by repertoire of co-existent other movements (age-adequacy) and concurrent motor repertoire. In addition, videos of 215 infants were analyzed by computer and the variability of the spatial center of motion (C SD ) was calculated. The Peabody Developmental Motor Scales was used to assess motor development at 12 months. Abnormal FMs, reduced age adequacy, and an abnormal concurrent motor repertoire were significantly associated with lower Gross Motor and Total Motor Quotient (GMQ, TMQ) scores (p < 0.05). The C SD was higher in children with TMQ scores <90 (-1SD) than in children with higher TMQ scores (p = 0.002). Normal FMs (assessed by Gestalt perception) and a low variability of the spatial center of motion (assessed by computer-based video analysis) predicted higher Peabody scores in 12-month-old infants born in India with a very low birth weight. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Improving motor activity assessment in depression: which sensor placement, analytic strategy and diurnal time frame are most powerful in distinguishing patients from controls and monitoring treatment effects.

PubMed

Reichert, Markus; Lutz, Alexander; Deuschle, Michael; Gilles, Maria; Hill, Holger; Limberger, Matthias F; Ebner-Priemer, Ulrich W

2015-01-01

Abnormalities in motor activity represent a central feature in major depressive disorder. However, measurement issues are poorly understood, limiting the use of objective measurement of motor activity for diagnostics and treatment monitoring. To improve measurement issues, especially sensor placement, analytic strategies and diurnal effects, we assessed motor activity in depressed patients at the beginning (MD; n=27) and after anti-depressive treatment (MD-post; n=18) as well as in healthy controls (HC; n=16) using wrist- and chest-worn accelerometers. We performed multiple analyses regarding sensor placements, extracted features, diurnal variation, motion patterns and posture to clarify which parameters are most powerful in distinguishing patients from controls and monitoring treatment effects. Whereas most feature-placement combinations revealed significant differences between groups, acceleration (wrist) distinguished MD from HC (d=1.39) best. Frequency (vertical axis chest) additionally differentiated groups in a logistic regression model (R2=0.54). Accordingly, both amplitude (d=1.16) and frequency (d=1.04) showed alterations, indicating reduced and decelerated motor activity. Differences between MD and HC in gestures (d=0.97) and walking (d=1.53) were found by data analysis from the wrist sensor. Comparison of motor activity at the beginning and after MD-treatment largely confirms our findings. Sample size was small, but sufficient for the given effect sizes. Comparison of depressed in-patients with non-hospitalized controls might have limited motor activity differences between groups. Measurement of wrist-acceleration can be recommended as a basic technique to capture motor activity in depressed patients as it records whole body movement and gestures. Detailed analyses showed differences in amplitude and frequency denoting that depressed patients walked less and slower.

Improving Motor Activity Assessment in Depression: Which Sensor Placement, Analytic Strategy and Diurnal Time Frame Are Most Powerful in Distinguishing Patients from Controls and Monitoring Treatment Effects

PubMed Central

Deuschle, Michael; Gilles, Maria; Hill, Holger; Limberger, Matthias F.; Ebner-Priemer, Ulrich W.

2015-01-01

Background Abnormalities in motor activity represent a central feature in major depressive disorder. However, measurement issues are poorly understood, limiting the use of objective measurement of motor activity for diagnostics and treatment monitoring. Methods To improve measurement issues, especially sensor placement, analytic strategies and diurnal effects, we assessed motor activity in depressed patients at the beginning (MD; n=27) and after anti-depressive treatment (MD-post; n=18) as well as in healthy controls (HC; n=16) using wrist- and chest-worn accelerometers. We performed multiple analyses regarding sensor placements, extracted features, diurnal variation, motion patterns and posture to clarify which parameters are most powerful in distinguishing patients from controls and monitoring treatment effects. Results Whereas most feature-placement combinations revealed significant differences between groups, acceleration (wrist) distinguished MD from HC (d=1.39) best. Frequency (vertical axis chest) additionally differentiated groups in a logistic regression model (R2=0.54). Accordingly, both amplitude (d=1.16) and frequency (d=1.04) showed alterations, indicating reduced and decelerated motor activity. Differences between MD and HC in gestures (d=0.97) and walking (d=1.53) were found by data analysis from the wrist sensor. Comparison of motor activity at the beginning and after MD-treatment largely confirms our findings. Limitations Sample size was small, but sufficient for the given effect sizes. Comparison of depressed in-patients with non-hospitalized controls might have limited motor activity differences between groups. Conclusions Measurement of wrist-acceleration can be recommended as a basic technique to capture motor activity in depressed patients as it records whole body movement and gestures. Detailed analyses showed differences in amplitude and frequency denoting that depressed patients walked less and slower. PMID:25885258

Motor-based bodily self is selectively impaired in eating disorders.

PubMed

Campione, Giovanna Cristina; Mansi, Gianluigi; Fumagalli, Alessandra; Fumagalli, Beatrice; Sottocornola, Simona; Molteni, Massimo; Micali, Nadia

2017-01-01

Body representation disturbances in body schema (i.e. unconscious sensorimotor body representations for action) have been frequently reported in eating disorders. Recently, it has been proposed that body schema relies on adequate functioning of the motor system, which is strongly implicated in discriminating between one's own and someone else's body. The present study aimed to investigate the motor-based bodily self in eating disorders and controls, in order to examine the role of the motor system in body representation disturbances at the body schema level. Female outpatients diagnosed with eating disorders (N = 15), and healthy controls (N = 18) underwent a hand laterality task, in which their own (self-stimuli) and someone else's hands (other-stimuli) were displayed at different orientations. Participants had to mentally rotate their own hand in order to provide a laterality judgement. Group differences in motor-based bodily self-recognition-i.e. whether a general advantage occurred when implicitly processing self- vs. other-stimuli - were evaluated, by analyzing response times and accuracy by means of mixed ANOVAs. Patients with eating disorders did not show a temporal advantage when mentally rotating self-stimuli compared to other-stimuli, as opposed to controls (F(1, 31) = 5.6, p = 0.02; eating disorders-other = 1092 ±256 msec, eating disorders-self = 1097±254 msec; healthy controls-other = 1239±233 msec, healthy controls -self = 1192±232 msec). This study provides initial indication that high-level motor functions might be compromised as part of body schema disturbances in eating disorders. Further larger investigations are required to test motor system abnormalities in the context of body schema disturbance in eating disorders.

Response Inhibition and Interference Control in Obsessive–Compulsive Spectrum Disorders

PubMed Central

van Velzen, Laura S.; Vriend, Chris; de Wit, Stella J.; van den Heuvel, Odile A.

2014-01-01

Over the past 20 years, motor response inhibition and interference control have received considerable scientific effort and attention, due to their important role in behavior and the development of neuropsychiatric disorders. Results of neuroimaging studies indicate that motor response inhibition and interference control are dependent on cortical–striatal–thalamic–cortical (CSTC) circuits. Structural and functional abnormalities within the CSTC circuits have been reported for many neuropsychiatric disorders, including obsessive–compulsive disorder (OCD) and related disorders, such as attention-deficit hyperactivity disorder, Tourette’s syndrome, and trichotillomania. These disorders also share impairments in motor response inhibition and interference control, which may underlie some of their behavioral and cognitive symptoms. Results of task-related neuroimaging studies on inhibitory functions in these disorders show that impaired task performance is related to altered recruitment of the CSTC circuits. Previous research has shown that inhibitory performance is dependent upon dopamine, noradrenaline, and serotonin signaling, neurotransmitters that have been implicated in the pathophysiology of these disorders. In this narrative review, we discuss the common and disorder-specific pathophysiological mechanisms of inhibition-related dysfunction in OCD and related disorders. PMID:24966828

Dendritic spine dysgenesis contributes to hyperreflexia after spinal cord injury

PubMed Central

Bandaru, Samira P.; Liu, Shujun; Waxman, Stephen G.

2014-01-01

Hyperreflexia and spasticity are chronic complications in spinal cord injury (SCI), with limited options for safe and effective treatment. A central mechanism in spasticity is hyperexcitability of the spinal stretch reflex, which presents symptomatically as a velocity-dependent increase in tonic stretch reflexes and exaggerated tendon jerks. In this study we tested the hypothesis that dendritic spine remodeling within motor reflex pathways in the spinal cord contributes to H-reflex dysfunction indicative of spasticity after contusion SCI. Six weeks after SCI in adult Sprague-Dawley rats, we observed changes in dendritic spine morphology on α-motor neurons below the level of injury, including increased density, altered spine shape, and redistribution along dendritic branches. These abnormal spine morphologies accompanied the loss of H-reflex rate-dependent depression (RDD) and increased ratio of H-reflex to M-wave responses (H/M ratio). Above the level of injury, spine density decreased compared with below-injury spine profiles and spine distributions were similar to those for uninjured controls. As expected, there was no H-reflex hyperexcitability above the level of injury in forelimb H-reflex testing. Treatment with NSC23766, a Rac1-specific inhibitor, decreased the presence of abnormal dendritic spine profiles below the level of injury, restored RDD of the H-reflex, and decreased H/M ratios in SCI animals. These findings provide evidence for a novel mechanistic relationship between abnormal dendritic spine remodeling in the spinal cord motor system and reflex dysfunction in SCI. PMID:25505110

Airway somatosensory deficits and dysphagia in Parkinson's disease.

PubMed

Hammer, Michael J; Murphy, Caitlin A; Abrams, Trisha M

2013-01-01

Individuals with Parkinson's disease (PD) often experience substantial impairment of swallow control, and are typically unaware of the presence or severity of their impairments suggesting that these individuals may also experience airway sensory deficits. However, the degree to which impaired swallow function in PD may relate to airway sensory deficits has yet to be formally tested. The purpose of this study was to examine whether airway sensory function is associated with swallow impairment in PD. Eighteen PD participants and 18 healthy controls participated in this study and underwent endoscopic assessment of airway somatosensory function, endoscopic assessment of swallow function, and clinical ratings of swallow and disease severity. PD participants exhibited abnormal airway somatosensory function and greater swallow impairment compared with healthy controls. Swallow and sensory deficits in PD were correlated with disease severity. Moreover, PD participants reported similar self-rated swallow function as healthy controls, and swallow deficits were correlated with sensory function suggesting an association between impaired sensory function and poor self-awareness of swallow deficits in PD. These results suggest that control of swallow is influenced by airway somatosensory function, that swallow-related deficits in PD are related to abnormal somatosensation, and that swallow and airway sensory function may degrade as a function of disease severity. Therefore, the basal ganglia and related neural networks may play an important role to integrate airway sensory input for swallow-related motor control. Furthermore, the airway deficits observed in PD suggest a disintegration of swallow-related sensory and motor control.

Mitochondrial dynamics and bioenergetic dysfunction is associated with synaptic alterations in mutant SOD1 motor neurons

PubMed Central

Magrané, Jordi; Sahawneh, Mary Anne; Przedborski, Serge; Estévez, Álvaro G.; Manfredi, Giovanni

2012-01-01

Mutations in Cu,Zn superoxide dismutase (SOD1) cause familial amyotrophic lateral sclerosis (FALS), a rapidly fatal motor neuron disease. Mutant SOD1 has pleiotropic toxic effects on motor neurons, among which mitochondrial dysfunction has been proposed as one of the contributing factors in motor neuron demise. Mitochondria are highly dynamic in neurons; they are constantly reshaped by fusion and move along neurites to localize at sites of high-energy utilization, such as synapses. The finding of abnormal mitochondria accumulation in neuromuscular junctions, where the SOD1-FALS degenerative process is though to initiate, suggests that impaired mitochondrial dynamics in motor neurons may be involved in pathogenesis. We addressed this hypothesis by live imaging microscopy of photo-switchable fluorescent mitoDendra in transgenic rat motor neurons expressing mutant or wild type human SOD1. We demonstrate that mutant SOD1 motor neurons have impaired mitochondrial fusion in axons and cell bodies. Mitochondria also display selective impairment of retrograde axonal transport, with reduced frequency and velocity of movements. Fusion and transport defects are associated with smaller mitochondrial size, decreased mitochondrial density, and defective mitochondrial membrane potential. Furthermore, mislocalization of mitochondria at synapses among motor neurons, in vitro, correlates with abnormal synaptic number, structure, and function. Dynamics abnormalities are specific to mutant SOD1 motor neuron mitochondria, since they are absent in wild type SOD1 motor neurons, they do not involve other organelles, and they are not found in cortical neurons. Taken together, these results suggest that impaired mitochondrial dynamics may contribute to the selective degeneration of motor neurons in SOD1-FALS. PMID:22219285

Increased frequency of severe major anomalies in children conceived by intracytoplasmic sperm injection.

PubMed

Sanchez-Albisua, I; Borell-Kost, S; Mau-Holzmann, U A; Licht, P; Krägeloh-Mann, I

2007-02-01

The neurodevelopmental outcome of children born after intracytoplasmic sperm injection (ICSI) is controversial. We compared the medical and developmental outcome of 34 singletons born after ICSI (20 males, 14 females; mean ages of 18 mo and 40 mo [SD 9 mo]; range 2 y 10 mo-4 y 8 mo) with 39 case control studies (21 males, 18 females; mean ages of 18 mo and 40 mo [SD 4 mo]; range 3 y-4 y 1 mo). Each child was assessed physically and tested in three development domains (fine motor, gross motor, and language). Five children born after ICSI versus two control children (p=0.2) had major congenital anomalies (MaCAs). Four children born after ICSI versus no control children had severe MaCAs (p=0.04). These were defined as having a significant impact on development or causing chronic disease: Angelman syndrome (n=1), lissencephaly (n=1), Hanhart syndrome (n=1), and persistent hyperinsulinemic hypoglycaemia of infancy (n=1). Karyotyping in 23 children born after ICSI revealed no abnormalities. An imprinting defect was found in the child with Angelman syndrome. Results of developmental assessment were in all cases normal at the age of 18 months except for the three children with Angelman and Hanhart syndromes, and lissencephaly. At the second assessment, five more children born after ICSI and four control children showed abnormalities in one or more developmental domains. We conclude that there seems to be a higher frequency of severe major anomalies in children born after ICSI. An increased risk for imprinting defects cannot be excluded. If we exclude children with severe MaCAs, the incidence of an abnormal somatic or neurodevelopmental outcome in the fourth year of life in children born after ICSI is similar to that of spontaneously conceived children.

Multimodality instrument for tissue characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2004-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration. The use of this system will make surgical procedures safer, more accurate, and more efficient. Other applications of this system include the detection, prognosis and treatment of breast cancer, prostate cancer, spinal diseases, and use in general exploratory surgery.

Cognitive dysfunction in Body Dysmorphic Disorder: New implications for nosological systems & neurobiological models

PubMed Central

Jefferies-Sewell, K; Chamberlain, SR; Fineberg, NA; Laws, KR

2017-01-01

Background Body dysmorphic disorder (BDD) is a debilitating disorder, characterised by obsessions and compulsions relating specifically to perceived appearance, newly classified within the DSM-5 Obsessive-Compulsive and Related Disorders grouping. Until now, little research has been conducted into the cognitive profile of this disorder. Materials and Methods Participants with BDD (n=12) and healthy controls (n=16) were tested using a computerised neurocognitive battery investigating attentional set-shifting (Intra/Extra Dimensional Set Shift Task), decision-making (Cambridge Gamble Task), motor response-inhibition (Stop-Signal Reaction Time Task) and affective processing (Affective Go-No Go Task). The groups were matched for age, IQ and education. Results In comparison to controls, patients with BDD showed significantly impaired attentional set shifting, abnormal decision-making, impaired response inhibition and greater omission and commission errors on the emotional processing task. Conclusions Despite the modest sample size, our results showed that individuals with BDD performed poorly compared to healthy controls on tests of cognitive flexibility, reward and motor impulsivity and affective processing. Results from separate studies in OCD patients suggest similar cognitive dysfunction. Therefore, these findings are consistent with the re-classification of BDD alongside OCD. These data also hint at additional areas of decision-making abnormalities that might contribute specifically to the psychopathology of BDD. PMID:27899165

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.

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

Long-term Outcomes of Patients With Normal or Minor Motor Function Abnormalities Detected by High-resolution Esophageal Manometry.

PubMed

Ravi, Karthik; Friesen, Laurel; Issaka, Rachel; Kahrilas, Peter J; Pandolfino, John E

2015-08-01

High-resolution manometry (HRM) expands recognition of minor esophageal motor abnormalities, but the clinical significance of these is unclear. We aimed to determine the outcomes of minor esophageal motor abnormalities. We reviewed HRM tracings from patients who underwent esophageal manometry at Northwestern Memorial Hospital from July 2004 through October 2005 by using the Chicago classification (version 2.0). We identified 301 patients with normal findings or minor manometric abnormalities (weak peristalsis, hypertensive peristalsis, frequent failed peristalsis, or rapid contractions with normal latency). Ninety-eight patients participated in a phone survey in which they were asked questions from the impact dysphagia questionnaire (mean follow-up period, 6 years 5 months). Of 301 patients assessed, 166 had normal findings from HRM, 82 had weak peristalsis, 34 had hypertensive peristalsis, 17 had frequent failed peristalsis, and 2 had rapid contractions with normal latency. The primary indications for HRM of dysphagia (44%) and gastroesophageal reflux disease (63%) were unrelated to manometric findings. There were no endoscopic or videofluoroscopic differences between patients with minor manometric abnormalities. Of 98 patients with follow-up, findings from HRM were normal in 63, weak peristalsis was observed in 23, hypertensive peristalsis was observed in 10, and frequent failed peristalsis was observed in 2. No patients underwent surgical myotomy, pneumatic dilation, or botulinum toxin injection. Use of proton pump inhibitors and rates of fundoplication were similar, regardless of manometric findings. Sixteen patients (16%) had significant dysphagia at follow-up; hypertensive peristalsis was the most likely to be symptomatic. Patients with normal and minor esophageal motor abnormalities report minimal symptoms and have few medical interventions related to esophageal dysfunction during long-term follow-up. Therefore, identification of normal and minor motor function is likely a good prognostic indicator. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cross-species assessments of motor and exploratory behavior related to bipolar disorder.

PubMed

Henry, Brook L; Minassian, Arpi; Young, Jared W; Paulus, Martin P; Geyer, Mark A; Perry, William

2010-07-01

Alterations in exploratory behavior are a fundamental feature of bipolar mania, typically characterized as motor hyperactivity and increased goal-directed behavior in response to environmental cues. In contrast, abnormal exploration associated with schizophrenia and depression can manifest as prominent withdrawal, limited motor activity, and inattention to the environment. While motor abnormalities are cited frequently as clinical manifestations of these disorders, relatively few empirical studies have quantified human exploratory behavior. This article reviews the literature characterizing motor and exploratory behavior associated with bipolar disorder and genetic and pharmacological animal models of the illness. Despite sophisticated assessment of exploratory behavior in rodents, objective quantification of human motor activity has been limited primarily to actigraphy studies with poor cross-species translational value. Furthermore, symptoms that reflect the cardinal features of bipolar disorder have proven difficult to establish in putative animal models of this illness. Recently, however, novel tools such as the human behavioral pattern monitor provide multivariate translational measures of motor and exploratory activity, enabling improved understanding of the neurobiology underlying psychiatric disorders.

Experimenting With Baroreceptor Reflexes

NASA Technical Reports Server (NTRS)

Eckberg, Dwain L.; Goble, Ross L.

1988-01-01

Carotid arteries stimulated by pressure or suction on neck. Baro-Cuff is silicone-rubber chamber that fits on front of subject's neck. Electronic system, stepping motor, bellows, and umbilical tube furnish controlled pressure to chamber. Pressure sensor provides feedback to microprocessor in electronic system. Developed to study blood-pressure-reflex responses of astronauts in outer space. Useful for terrestrial studies of patients with congestive heart failure, chronic diabetes mellitus, and other conditions in which blood-pressure-reflex controls behave abnormally.

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.

Anticholinesterase Effect on Motor Kinematic Measures and Brain Activation in Parkinson’s Disease

PubMed Central

Mentis, Marc J.; Delalot, Dominique; Naqvi, Hassan; Gordon, Mark F.; Gudesblatt, Mark; Edwards, Christine; Donatelli, Luke; Dhawan, Vijay; Eidelberg, David

2015-01-01

Anticholinesterase (AChE) drugs are being prescribed off label for nonmotor symptoms in Parkinson’s disease (PD). Theoretically, these drugs can impair motor function. A small literature suggests AChE therapy has little effect on clinical motor evaluation; however, no study has made objective motor kinematic measures or evaluated brain function. We hypothesized that even if clinical examination was normal in PD patients on dopamine therapy, (1) sensitive kinematic measures would be abnormal during AChE therapy or (2) normal kinematic measures would be maintained by compensatory brain activation. We carried out a randomized, double-blind, placebo-controlled trial of 8 weeks donepezil (10 mg/day) in 17 PD subjects. Subjects carried out a computerized motor task during a positron emission tomography (PET) scan before starting the drug and again after 8 weeks of donepezil or placebo. Kinematic measures of motor function and PET scans were analyzed to compare the effects of donepezil and placebo. Neither placebo nor donepezil altered motor kinematic measures. Furthermore, movement integrity while on donepezil was maintained without compensatory brain activity. Donepezil 10 mg/day can be given for nonmotor symptoms in PD without adverse motor effects or compensatory brain activity. PMID:16228997

Assessment of specific characteristics of abnormal general movements: does it enhance the prediction of cerebral palsy?

PubMed

Hamer, Elisa G; Bos, Arend F; Hadders-Algra, Mijna

2011-08-01

Abnormal general movements at around 3 months corrected age indicate a high risk of cerebral palsy (CP). We aimed to determine whether specific movement characteristics can improve the predictive power of definitely abnormal general movements. Video recordings of 46 infants with definitely abnormal general movements at 9 to 13 weeks corrected age (20 males; 26 females; median gestational age 30wks; median birthweight 1200g) were analysed for the following characteristics: presence of fidgety, cramped synchronized, stiff, or jerky movements and asymmetrical tonic neck reflex pattern. Neurological condition (presence or absence of CP), gross motor development (Alberta Infant Motor Scales), quality of motor behaviour (Infant Motor Profile), functional mobility (Pediatric Evaluation of Disability Inventory), and Mental Developmental Index (Bayley Scales) were assessed at 18 months corrected age. Infants were excluded from participating in the study if they had severe congenital anomalies or if their caregivers had an insufficient knowledge of the Dutch language. Of the 46 assessed infants, 10 developed spastic CP (Gross Motor Function Classification System levels I to V; eight bilateral spastic CP, two unilateral spastic CP). The absence of fidgety movements and the presence of predominantly stiff movements were associated with CP (Fisher's exact test, p=0.018 and p=0.007 respectively) and lower Infant Motor Profile scores (Mann-Whitney U test, p=0.015 and p=0.022 respectively); stiff and predominantly stiff movements were associated with lower Alberta Infant Motor Scales scores (Mann-Whitney U test, p=0.01 and p=0.004 respectively). Cramped synchronized movements and the asymmetrical tonic neck reflex pattern were not related to outcome. None of the movement characteristics were associated with Pediatric Evaluation of Disability Inventory scores or the Mental Developmental Index. The assessment of fidgety movements and movement stiffness may improve the predictive power of definitely abnormal general movements for developmental outcome. However, the presence of fidgety movements does not preclude the development of CP. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

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

Cortical folding in post-traumatic stress disorder after motor vehicle accidents: Regional differences in gyrification.

PubMed

Chu, Chun; Xie, Bing; Qiu, Mingguo; Liu, Kaijun; Tan, Liwen; Wu, Yi; Chen, Wei; Zhang, Shaoxiang

2017-04-01

Structural and functional magnetic resonance imaging (MRI) studies have revealed evidence of brain abnormalities in post-traumatic stress disorder (PTSD) patients. Cortical complexity and local gyrification index (lGI) reflect potential biological processes associated with normal or abnormal cognitive functioning. In the current study, lGI was used to explore cortical folding in PTSD patients involved in motor vehicle accidents (MVA). MRI brain scans were acquired from 18 PTSD patients who had suffered MVA at least 6 months previously and 18 healthy control subjects. All MRI images were obtained on a 3-T Siemens MRI machine and the cortical folding was analyzed using the workflow provided by software FreeSurfer. A general FreeSurfer's general linear model was used in the group analysis. In addition, correlation analysis was performed between the average of lGI extracted from the significantly different areas and the data for the clinical scale. The PTSD patients had significantly greater Clinician-Administered PTSD Scale scores than the control group. The patients showed significantly reduced lGI in the left lateral orbitofrontal cortex, consistent with findings of previous volumetric studies on PTSD. But there were no significant correlations in the left lateral orbitofrontal cortex between Clinician-Administered PTSD Scale scores and lGI. We suggest that abnormal gyrification in PTSD patients can be an important indicator of neurodevelopment deficits and may indeed be a biological marker for PTSD. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Neurological abnormalities in recent-onset schizophrenia and asperger-syndrome.

PubMed

Hirjak, Dusan; Wolf, Robert Christian; Koch, Sabine C; Mehl, Laura; Kelbel, Janna K; Kubera, Katharina Maria; Traeger, Tanja; Fuchs, Thomas; Thomann, Philipp Arthur

2014-01-01

Neurological abnormalities including a variety of subtle deficits such as discrete impairments in sensory integration, motor coordination (MOCO), and sequencing of complex motor acts are frequently found in patients with schizophrenia (SZ) and commonly referred to as neurological soft signs (NSS). Asperger-syndrome (AS) is characterized by sensory-motor difficulties as well. However, the question whether the two disorders share a common or a disease-specific pattern of NSS remains unresolved. A total of 78 age- and education-matched participants [26 patients with recent-onset SZ, 26 individuals with AS, and 26 healthy controls (HC)] were recruited for the study. Analyses of covariance (ANCOVAs), with age, years of education, and medication included as covariates, were used to examine group differences on total NSS and the five subscale scores. Discriminant analyses were employed to identify the NSS subscales that maximally discriminate between the three groups. Significant differences among the three groups were found in NSS total score and on the five NSS subscales. The clinical groups differed significantly in the NSS subscale MOCO. The correct discriminant rate between patients with SZ and individuals with AS was 61.5%. The correct discriminant rate was 92.3% between individuals with AS and HC, and 80.8% between SZ patients and HC, respectively. Our findings provide new evidence for the presence of NSS in AS and lend further support to previously reported difficulties in movement control in this disorder. According to the present results, SZ and AS seem to be characterized by both quantitative and qualitative NSS expression.

A loud auditory stimulus overcomes voluntary movement limitation in cervical dystonia.

PubMed

Serranová, Tereza; Jech, Robert; Martí, Maria José; Modreanu, Raluca; Valldeoriola, Francesc; Sieger, Tomáš; Růžička, Evžen; Valls-Solé, Josep

2012-01-01

Patients with cervical dystonia (CD) present with an impaired performance of voluntary neck movements, which are usually slow and limited. We hypothesized that such abnormality could involve defective preparation for task execution. Therefore, we examined motor preparation in CD patients using the StartReact method. In this test, a startling auditory stimulus (SAS) is delivered unexpectedly at the time of the imperative signal (IS) in a reaction time task to cause a faster execution of the prepared motor programme. We expected that CD patients would show an abnormal StartReact phenomenon. Fifteen CD patients and 15 age matched control subjects (CS) were asked to perform a rotational movement (RM) to either side as quick as possible immediately after IS perception (a low intensity electrical stimulus to the II finger). In randomly interspersed test trials (25%) a 130 dB SAS was delivered simultaneously with the IS. We recorded RMs in the horizontal plane with a high speed video camera (2.38 ms per frame) in synchronization with the IS. The RM kinematic-parameters (latency, velocity, duration and amplitude) were analyzed using video-editing software and screen protractor. Patients were asked to rate the difficulty of their RMs in a numerical rating scale. In control trials, CD patients executed slower RMs (repeated measures ANOVA, p<0.10(-5)), and reached a smaller final head position angle relative to the midline (p<0.05), than CS. In test trials, SAS improved all RMs in both groups (p<0.10(-14)). In addition, patients were more likely to reach beyond their baseline RM than CS (χ(2), p<0.001) and rated their performance better than in control trials (t-test, p<0.01). We found improvement of kinematic parameters and subjective perception of motor performance in CD patients with StartReact testing. Our results suggest that CD patients reach an adequate level of motor preparation before task execution.

Decreased Connectivity and Cerebellar Activity in Autism during Motor Task Performance

ERIC Educational Resources Information Center

Mostofsky, Stewart H.; Powell, Stephanie K.; Simmonds, Daniel J.; Goldberg, Melissa C.; Caffo, Brian; Pekar, James J.

2009-01-01

Although motor deficits are common in autism, the neural correlates underlying the disruption of even basic motor execution are unknown. Motor deficits may be some of the earliest identifiable signs of abnormal development and increased understanding of their neural underpinnings may provide insight into autism-associated differences in parallel…

Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy

PubMed Central

Sampaio, Hugo; Mowat, David; Roscioli, Tony

2017-01-01

Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis. PMID:28634552

Abnormal behavior and associated risk factors in captive baboons (Papio hamadryas spp.).

PubMed

Lutz, Corrine K; Williams, Priscilla C; Sharp, R Mark

2014-04-01

Abnormal behavior, ranging from motor stereotypies to self-injurious behavior, has been documented in captive nonhuman primates, with risk factors including nursery rearing, single housing, and veterinary procedures. Much of this research has focused on macaque monkeys; less is known about the extent of and risk factors for abnormal behavior in baboons. Because abnormal behavior can be indicative of poor welfare, either past or present, the purpose of this study was to survey the presence of abnormal behavior in captive baboons and to identify potential risk factors for these behaviors with an aim of prevention. Subjects were 144 baboons (119 females, 25 males) aged 3-29 (median = 9.18) years temporarily singly housed for research or clinical reasons. A 15-min focal observation was conducted on each subject using the Noldus Observer® program. Abnormal behavior was observed in 26% of the subjects, with motor stereotypy (e.g., pace, rock, swing) being the most common. Motor stereotypy was negatively associated with age when first singly housed (P < 0.005) while self-directed behavior (e.g., hair pull, self-bite) was positively associated with the lifetime number of days singly housed (P < 0.05) and the average number of blood draws per year (P < 0.05). In addition, abnormal appetitive behavior was associated with being male (P < 0.05). Although the baboons in this study exhibited relatively low levels of abnormal behavior, the risk factors for these behaviors (e.g., social restriction, routine veterinary procedures, and sex) appear to remain consistent across primate species. © 2013 Wiley Periodicals, Inc.

Laminar-specific distribution of zinc: evidence for presence of layer IV in forelimb motor cortex in the rat.

PubMed

Alaverdashvili, Mariam; Hackett, Mark J; Pickering, Ingrid J; Paterson, Phyllis G

2014-12-01

The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a "Zn valley" in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding is also critical for future investigation of the biochemical mechanisms through which therapeutic interventions can enhance neural plasticity, particularly through Zn dependent pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Laminar-specific distribution of zinc: Evidence for presence of layer IV in forelimb motor cortex in the rat

PubMed Central

Alaverdashvili, Mariam; Hackett, Mark J.; Pickering, Ingrid J.; Paterson, Phyllis G.

2015-01-01

The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a “Zn valley” in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding is also critical for future investigation of the biochemical mechanisms through which therapeutic interventions can enhance neural plasticity, particularly through Zn dependent pathways. PMID:25192655

Spine Topographical Distribution of Skin α-Synuclein Deposits in Idiopathic Parkinson Disease.

PubMed

Donadio, Vincenzo; Incensi, Alex; Rizzo, Giovanni; Scaglione, Cesa; Capellari, Sabina; Fileccia, Enrico; Avoni, Patrizia; Liguori, Rocco

2017-05-01

Phosphorylated α-synuclein (p-syn) in skin nerves mainly in the proximal sites is a promising neurodegenerative biomarker for idiopathic Parkinson disease (IPD). However, the p-syn spine distribution particularly in patients with unilateral motor dysfunctions remains undefined. This study aimed to investigate in IPD p-syn differences between left and right cervical spine sites in patients with prevalent unilateral motor symptoms, and cervical and thoracic spine sites in patients with bilateral motor symptoms. We enrolled 28 IPD patients fulfilling clinical diagnostic criteria associated with abnormal nigro-striatal DatScan and cardiac MIBG: 15 with prevalently unilateral motor symptoms demonstrated by DatScan; 13 with bilateral motor symptoms and DatScan abnormalities. Patients underwent skin biopsy searching for intraneural p-syn deposits: skin samples were taken from C7 paravertebral left and right sites in unilateral patients and from cervical (C7) and thoracic (Th12) paravertebral spine regions in bilateral patients. Unilateral patients displayed 20% of abnormal p-syn deposits in the affected motor site, 60% in both sites and 20% only in the non-affected site. P-syn was found in all patients in C7 but in only 62% of patients in Th12. Our data showed that cervical p-syn deposits displayed a uniform distribution between both sides not following the motor dysfunction in unilateral patients, and skin nerve p-syn deposits demonstrated a spine gradient with the cervical site expressing the highest positivity. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Abnormal Olfaction in Parkinson's Disease Is Related to Faster Disease Progression.

PubMed

Cavaco, Sara; Gonçalves, Alexandra; Mendes, Alexandre; Vila-Chã, Nuno; Moreira, Inês; Fernandes, Joana; Damásio, Joana; Teixeira-Pinto, Armando; Bastos Lima, António

2015-01-01

A possible association between olfactory dysfunction and Parkinson's disease (PD) severity has been a topic of contention for the past 40 years. Conflicting reports may be partially explained by procedural differences in olfactory assessment and motor symptom evaluation. One hundred and sixty-six nondemented PD patients performed the Brief-Smell Identification Test and test scores below the estimated 20th percentile as a function of sex, age, and education (i.e., 80% specificity) were considered demographically abnormal. Patients underwent motor examination after 12 h without antiparkinsonian medication. Eighty-two percent of PD patients had abnormal olfaction. Abnormal performance on the Brief-Smell Identification Test was associated with higher disease severity (i.e., Hoehn and Yahr, Unified Parkinson's Disease Rating Scale-III, Freezing of Gait questionnaire, and levodopa equivalent dose), even when disease duration was taken into account. Abnormal olfaction in PD is associated with increased severity and faster disease progression.

Plasticity of cortical inhibition in dystonia is impaired after motor learning and Paired-Associative Stimulation

PubMed Central

Meunier, Sabine; Russmann, Heike; Shamim, Ejaz; Lamy, Jean-Charles; Hallett, Mark

2012-01-01

Summary Artificial induction of plasticity by paired associative stimulation (PAS) in healthy subjects (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory ones. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long interval intracortical inhibition (LICI, reflecting activity of GABAB interneurons) and long latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced LTP-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task.“ PMID:22429246

Treatment implications of high-resolution manometry findings: options for patients with esophageal dysmotility.

PubMed

Bolkhir, Ahmed; Gyawali, C Prakash

2014-03-01

High-resolution manometry (HRM) has significantly impacted diagnosis and management of achalasia in particular, and has improved characterization of other motor disorders. Achalasia, the most profound esophageal motor disorder, is characterized by esophageal outflow obstruction from abnormal relaxation of the lower esophageal sphincter (LES) during swallowing, and presents with transit symptoms (dysphagia, regurgitation). Esophageal body motor disorders include both inhibitory nerve dysfunction associated with hypermotility or spasm, and hypomotility disorders with poor contraction. The implications of hypermotility disorders are both perceptive and obstructive. On the other hand, hypomotility disorders have reflux implications because of abnormal barrier function at the LES, and abnormal bolus clearance. Esophageal outflow obstruction in achalasia responds favorably to disruption of the LES, and outcome may be predicted by HRM subtyping of achalasia. Identification of dominant (perceptive vs. obstructive) mechanisms of symptom generation help direct therapy of hypermotility disorders, while hypomotility disorders typically require management of concurrent reflux disease.

Feedforward control strategies of subjects with transradial amputation in planar reaching.

PubMed

Metzger, Anthony J; Dromerick, Alexander W; Schabowsky, Christopher N; Holley, Rahsaan J; Monroe, Brian; Lum, Peter S

2010-01-01

The rate of upper-limb amputations is increasing, and the rejection rate of prosthetic devices remains high. People with upper-limb amputation do not fully incorporate prosthetic devices into their activities of daily living. By understanding the reaching behaviors of prosthesis users, researchers can alter prosthetic devices and develop training protocols to improve the acceptance of prosthetic limbs. By observing the reaching characteristics of the nondisabled arms of people with amputation, we can begin to understand how the brain alters its motor commands after amputation. We asked subjects to perform rapid reaching movements to two targets with and without visual feedback. Subjects performed the tasks with both their prosthetic and nondisabled arms. We calculated endpoint error, trajectory error, and variability and compared them with those of nondisabled control subjects. We found no significant abnormalities in the prosthetic limb. However, we found an abnormal leftward trajectory error (in right arms) in the nondisabled arm of prosthetic users in the vision condition. In the no-vision condition, the nondisabled arm displayed abnormal leftward endpoint errors and abnormally higher endpoint variability. In the vision condition, peak velocity was lower and movement duration was longer in both arms of subjects with amputation. These abnormalities may reflect the cortical reorganization associated with limb loss.

Non-achalasic motor disorders of the oesophagus.

PubMed

Sifrim, Daniel; Fornari, Fernando

2007-01-01

Motor abnormalities of the oesophagus are characterised by a chronic impairment of the neuromuscular structures that co-ordinate oesophageal function. The best-defined entity is achalasia, which is discussed in a separate chapter. Other motor disorders with clinical relevance include diffuse oesophageal spasm, oesophageal dysmotility associated with scleroderma, and ineffective oesophageal motility. These non-achalasic motor disorders have variable prevalence but they could be associated with invalidating symptoms such as dysphagia, chest pain and gastro-oesophageal reflux disease. New oesophageal diagnostic techniques, including high-resolution manometry, high-frequency intraluminal ultrasound and intraluminal impedance, allow (1) better definition of peristalsis and sphincter function, (2) assessment of changes in oesophageal wall thickness, and (3) evaluation of pressure gradients within the oesophagus and across the sphincters that can produce normal or abnormal patterns of bolus transport. This chapter discusses recent advances in physiology, pathophysiology, diagnosis and treatment of non-achalasic oesophageal motor disorders.

Neonatal Brain MRI and Motor Outcome at School Age in Children with Neonatal Encephalopathy: A Review of Personal Experience

PubMed Central

Mercuri, Eugenio; Barnett, Anna L.

2003-01-01

The aim of this paper is to review (i) the spectrum of neuromotor function at school age in children who had been born full-term and presented with neonatal encephalopathy (NE) and low Apgar scores and (ii) the relation between the presence/absence of such difficulties and neonatal brain MRI. Motor outcome appears to be mainly related to the severity of basal ganglia and internal capsule involvement. Severe basal ganglia lesions were always associated with the most severe outcome, microcephaly, tetraplegia, and severe global delay, whereas more discrete basal ganglia lesions were associated with athetoid cerebral palsy, with normal cognitive development or minor neuro-motor abnormalities. White matter lesions were associated with abnormal motor outcome only if the internal capsule was involved. Children with moderate white matter changes but normal internal capsule, had normal motor outcome at school age. PMID:14640307

Subtle abnormalities of gait detected early in vitamin B6 deficiency in aged and weanling rats with hind leg gait analysis.

PubMed

Schaeffer, M C; Cochary, E F; Sadowski, J A

1990-04-01

Motor abnormalities have been observed in every species made vitamin B6 deficient, and have been detected and quantified early in vitamin B6 deficiency in young adult female Long-Evans rats with hind leg gait analysis. Our objective was to determine if hind leg gait analysis could be used to detect vitamin B6 deficiency in weanling (3 weeks) and aged (23 months) Fischer 344 male rats. Rats (n = 10 per group) were fed: the control diet ad libitum (AL-CON); the control diet devoid of added pyridoxine hydrochloride (DEF); or the control diet pair-fed to DEF (PF-CON). At 10 weeks, plasma pyridoxal phosphate concentration confirmed deficiency in both age groups. Gait abnormalities were detected in the absence of gross motor disturbances in both aged and weanling DEF rats at 2-3 weeks. Width of step was significantly reduced (16%, p less than 0.003) in DEF aged rats compared to AL- and PF-CON. This pattern of response was similar to that reported previously in young adult rats. In weanling rats, pair feeding alone reduced mean width of step (+/- SEM) by 25% compared to ad libitum feeding (2.7 +/- 0.1 vs 3.6 +/- 0.1 cm for PF- vs AL-CON, respectively, p less than 0.05). In DEF weanling rats, width (3.0 +/- 0.1 cm) was increased compared to PF-CON (11%, p less than 0.05) but decreased compared to AL-CON (16%, p less than 0.05). Width of step was significantly altered early in B6 deficiency in rats of different ages and strains and in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and electrodiagnostic characteristics of nitrous oxide-induced neuropathy in Taiwan.

PubMed

Li, Han-Tao; Chu, Chun-Che; Chang, Kuo-Hsuan; Liao, Ming-Feng; Chang, Hong-Shiu; Kuo, Hung-Chou; Lyu, Rong-Kuo

2016-10-01

Nitrous oxide-induced neuropathy is toxic neuropathy occasionally encountered in Taiwanese neurological clinics. Only several case reports described their electrodiagnostic features. We used a case-control design to investigate the detailed electrodiagnostic characteristics and possible factors relating to severe nerve injury. We retrospectively reviewed 33 patients with nitrous oxide-induced neuropathy over a 10-year period and reported their demographic data, spinal cord MRI, laboratory examinations and nerve conduction studies. 56 healthy controls' nerve conduction studies were collected for comparison analysis. We noted significant motor and sensory amplitudes reduction, conduction velocities slowing, and latencies prolongation in most tested nerves compared to the controls. Similar nerve conduction study characteristics with prominent lower limbs' motor and sensory amplitudes reduction was observed in patient groups with or without abnormal vitamin B12 and/or homocysteine levels. Among those with lower limbs' motor or sensory amplitudes reduction <20% of the lower limit of normal, higher homocysteine levels were detected. Severe impairments of the lower limbs' sensory and motor amplitudes were frequently noted in patients with nitrous oxide exposure. Nitrous oxide exposure itself is an important factor for the development of neuropathy. Our study contributes to the understanding of electrodiagnostic features underlying the nitrous oxide-induced neuropathy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

An anticholinergic reverses motor control and corticostriatal LTD deficits in Dyt1 ΔGAG knock-in mice

PubMed Central

Dang, Mai T.; Yokoi, Fumiaki; Cheetham, Chad C.; Lu, Jun; Vo, Viet; Lovinger, David M.; Li, Yuqing

2011-01-01

DYT1 early-onset generalized torsion dystonia is an inherited movement disorder associated with mutations in DYT1 that codes for torsinA protein. The most common mutation seen in this gene is a trinucleotide deletion of GAG. We previously reported a motor control deficit on a beam-walking task in our Dyt1 ΔGAG knock-in heterozygous mice. In this report we show the reversal of this motor deficit with the anticholinergic trihexyphenidyl (THP), a drug commonly used to treat movement problems in dystonia patients. THP also restored the reduced corticostriatal long-term depression (LTD) observed in these mice. Corticostriatal LTD has long been known to be dependent on D2 receptor activation. In this mouse model, striatal D2 receptors were expressed at lower quantities in comparison to wild-type mice. Furthermore, the mice were also partially resistant to FPL64176, an agonist of L-type calcium channels that have been previously reported to cause severe dystonic-like symptoms in wild-type mice. Our findings collectively suggest that altered communication between cholinergic interneurons and medium spiny neurons is responsible for the LTD deficit and that this synaptic plasticity modification may be involved in the striatal motor control abnormalities in our mouse model of DYT1 dystonia. PMID:21995941

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.

Functional activity of the sensorimotor cortex and cerebellum relates to cervical dystonia symptoms.

PubMed

Burciu, Roxana G; Hess, Christopher W; Coombes, Stephen A; Ofori, Edward; Shukla, Priyank; Chung, Jae Woo; McFarland, Nikolaus R; Wagle Shukla, Aparna; Okun, Michael S; Vaillancourt, David E

2017-09-01

Cervical dystonia (CD) is the most common type of focal dystonia, causing abnormal movements of the neck and head. In this study, we used noninvasive imaging to investigate the motor system of patients with CD and uncover the neural correlates of dystonic symptoms. Furthermore, we examined whether a commonly prescribed anticholinergic medication in CD has an effect on the dystonia-related brain abnormalities. Participants included 16 patients with CD and 16 healthy age-matched controls. We collected functional MRI scans during a force task previously shown to extensively engage the motor system, and diffusion and T1-weighted MRI scans from which we calculated free-water and brain tissue densities. The dystonia group was also scanned ca. 2 h after a 2-mg dose of trihexyphenidyl. Severity of dystonia was assessed pre- and post-drug using the Burke-Fahn-Marsden Dystonia Rating Scale. Motor-related activity in CD was altered relative to controls in the primary somatosensory cortex, cerebellum, dorsal premotor and posterior parietal cortices, and occipital cortex. Most importantly, a regression model showed that increased severity of symptoms was associated with decreased functional activity of the somatosensory cortex and increased activity of the cerebellum. Structural imaging measures did not differ between CD and controls. The single dose of trihexyphenidyl altered the fMRI signal in the somatosensory cortex but not in the cerebellum. Symptom severity was not significantly reduced post-treatment. Findings show widespread changes in functional brain activity in CD and most importantly that dystonic symptoms relate to disrupted activity in the somatosensory cortex and cerebellum. Hum Brain Mapp 38:4563-4573, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Sleep disturbances in preschool age children with cerebral palsy: a questionnaire study.

PubMed

Romeo, Domenico M; Brogna, Claudia; Musto, Elisa; Baranello, Giovanni; Pagliano, Emanuela; Casalino, Tiziana; Ricci, Daniela; Mallardi, Maria; Sivo, Serena; Cota, Francesco; Battaglia, Domenica; Bruni, Oliviero; Mercuri, Eugenio

2014-09-01

The study aimed to analyze (i) the prevalence of sleep disorders in pre-school children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC), (ii) the possible association with motor, cognitive and behavioral problems, and (iii) the possible differences with typically developing children matched for age and gender. One-hundred children with CP (age range: 3-5 years, mean: 3.8 years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Preschool and Primary Scale of Intelligence, and the Child Behaviour Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. Further 100 healthy children matched for age and sex were assessed using the SDSC. An abnormal total sleep score was found in 13% of children with CP while 35% had an abnormal score on at least one SDSC factor. SDSC total score was significantly associated with pathological internalizing scores on CBCL and active epilepsy on multivariate analysis. CP group reported higher significant median scores on SDSC total, parasomnias, and difficulty in initiating and maintaining sleep factors. In pre-school children sleep disorders are more common in children with CP than in healthy control group and are often associated with epilepsy and behavioral problems. Copyright © 2014 Elsevier B.V. All rights reserved.

Abnormal corticospinal excitability in patients with disorders of consciousness.

PubMed

Lapitskaya, Natallia; Gosseries, Olivia; De Pasqua, Victor; Pedersen, Asger Roer; Nielsen, Joergen Feldbaek; de Noordhout, Alain Maertens; Laureys, Steven

2013-07-01

Transcranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in patients in vegetative state (VS) (now known as unresponsive wakefulness syndrome, UWS) and minimally conscious (MCS) states due to severe brain damage remains largely unknown. It was hypothesized that cortical motor excitability would be decreased and would correlate to the level of consciousness in patients with disorders of consciousness. Corticospinal excitability was assessed in 47 patients (24 VS/UWS and 23 MCS) and 14 healthy controls. The test parameters included maximal peak-to-peak M-wave (Mmax), F-wave persistence, peripheral and central motor conduction times, sensory (SEP) and motor evoked (MEP) potential latencies and amplitudes, resting motor threshold (RMT), stimulus/response curves, and short latency afferent inhibition (SAI). TMS measurements were correlated to the level of consciousness (assessed using the Coma Recovery Scale-Revised). On average, the patient group had lower Mmax, lower MEP and SEP amplitudes, higher RMTs, narrower stimulus/response curves, and reduced SAI compared to the healthy controls (P < 0.05). The SAI alterations were correlated to the level of consciousness (P < 0.05). The findings demonstrated the impairment of the cortical inhibitory circuits in patients with disorders of consciousness. Moreover, the significant relationship was found between cortical inhibition and clinical consciousness dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

Impairment of a parieto-premotor network specialized for handwriting in writer's cramp

PubMed Central

Najee-ullah, Muslimah 'Ali; Hallett, Mark

2016-01-01

Handwriting with the dominant hand is a highly skilled task singularly acquired in humans. This skill is the isolated deficit in patients with writer's cramp (WC), a form of dystonia with maladaptive plasticity, acquired through intensive and repetitive motor practice. When a skill is highly trained, a motor program is created in the brain to execute the same movement kinematics regardless of the effector used for the task. The task- and effector-specific symptoms in WC suggest that a problem particularly occurs in the brain when the writing motor program is carried out by the dominant hand. In the present MRI study involving 12 WC patients (with symptoms only affecting the right dominant hand during writing) and 15 age matched unaffected controls we showed that: (1) the writing program recruited the same network regardless of the effector used to write in both groups; (2) dominant handwriting recruited a segregated parieto-premotor network only in the control group; (3) local structural alteration of the premotor area, the motor component of this network, predicted functional connectivity deficits during dominant handwriting and symptom duration in the patient group. Dysfunctions and structural abnormalities of a segregated parieto-premotor network in WC patients suggest that network specialization in focal brain areas is crucial for well-learned motor skill. PMID:27466043

Structural and functional abnormalities of the motor system in developmental stuttering

PubMed Central

Watkins, Kate E.; Smith, Stephen M.; Davis, Steve; Howell, Peter

2007-01-01

Summary Though stuttering is manifest in its motor characteristics, the cause of stuttering may not relate purely to impairments in the motor system as stuttering frequency is increased by linguistic factors, such as syntactic complexity and length of utterance, and decreased by changes in perception, such as masking or altering auditory feedback. Using functional and diffusion imaging, we examined brain structure and function in the motor and language areas in a group of young people who stutter. During speech production, irrespective of fluency or auditory feedback, the people who stuttered showed overactivity relative to controls in the anterior insula, cerebellum and midbrain bilaterally and underactivity in the ventral premotor, Rolandic opercular and sensorimotor cortex bilaterally and Heschl’s gyrus on the left. These results are consistent with a recent meta-analysis of functional imaging studies in developmental stuttering. Two additional findings emerged from our study. First, we found overactivity in the midbrain, which was at the level of the substantia nigra and extended to the pedunculopontine nucleus, red nucleus and subthalamic nucleus. This overactivity is consistent with suggestions in previous studies of abnormal function of the basal ganglia or excessive dopamine in people who stutter. Second, we found underactivity of the cortical motor and premotor areas associated with articulation and speech production. Analysis of the diffusion data revealed that the integrity of the white matter underlying the underactive areas in ventral premotor cortex was reduced in people who stutter. The white matter tracts in this area via connections with posterior superior temporal and inferior parietal cortex provide a substrate for the integration of articulatory planning and sensory feedback, and via connections with primary motor cortex, a substrate for execution of articulatory movements. Our data support the conclusion that stuttering is a disorder related primarily to disruption in the cortical and subcortical neural systems supporting the selection, initiation and execution of motor sequences necessary for fluent speech production. PMID:17928317

Structural and functional abnormalities of the motor system in developmental stuttering.

PubMed

Watkins, Kate E; Smith, Stephen M; Davis, Steve; Howell, Peter

2008-01-01

Though stuttering is manifest in its motor characteristics, the cause of stuttering may not relate purely to impairments in the motor system as stuttering frequency is increased by linguistic factors, such as syntactic complexity and length of utterance, and decreased by changes in perception, such as masking or altering auditory feedback. Using functional and diffusion imaging, we examined brain structure and function in the motor and language areas in a group of young people who stutter. During speech production, irrespective of fluency or auditory feedback, the people who stuttered showed overactivity relative to controls in the anterior insula, cerebellum and midbrain bilaterally and underactivity in the ventral premotor, Rolandic opercular and sensorimotor cortex bilaterally and Heschl's gyrus on the left. These results are consistent with a recent meta-analysis of functional imaging studies in developmental stuttering. Two additional findings emerged from our study. First, we found overactivity in the midbrain, which was at the level of the substantia nigra and extended to the pedunculopontine nucleus, red nucleus and subthalamic nucleus. This overactivity is consistent with suggestions in previous studies of abnormal function of the basal ganglia or excessive dopamine in people who stutter. Second, we found underactivity of the cortical motor and premotor areas associated with articulation and speech production. Analysis of the diffusion data revealed that the integrity of the white matter underlying the underactive areas in ventral premotor cortex was reduced in people who stutter. The white matter tracts in this area via connections with posterior superior temporal and inferior parietal cortex provide a substrate for the integration of articulatory planning and sensory feedback, and via connections with primary motor cortex, a substrate for execution of articulatory movements. Our data support the conclusion that stuttering is a disorder related primarily to disruption in the cortical and subcortical neural systems supporting the selection, initiation and execution of motor sequences necessary for fluent speech production.

Cross-species assessments of Motor and Exploratory Behavior related to Bipolar Disorder

PubMed Central

Henry, Brook L.; Minassian, Arpi; Young, Jared W.; Paulus, Martin P.; Geyer, Mark A.; Perry, William

2010-01-01

Alterations in exploratory behavior are a fundamental feature of bipolar mania, typically characterized as motor hyperactivity and increased goal-directed behavior in response to environmental cues. In contrast, abnormal exploration associated with schizophrenia and depression can manifest as prominent withdrawal, limited motor activity, and inattention to the environment. While motor abnormalities are cited frequently as clinical manifestations of these disorders, relatively few empirical studies have quantified human exploratory behavior. This article reviews the literature characterizing motor and exploratory behavior associated with bipolar disorder and genetic and pharmacological animal models of the illness. Despite sophisticated assessment of exploratory behavior in rodents, objective quantification of human motor activity has been limited primarily to actigraphy studies with poor cross-species translational value. Furthermore, symptoms that reflect the cardinal features of bipolar disorder have proven difficult to establish in putative animal models of this illness. Recently, however, novel tools such as the Human Behavioral Pattern Monitor provide multivariate translational measures of motor and exploratory activity, enabling improved understanding of the neurobiology underlying psychiatric disorders. PMID:20398694

Effects of information processing speed on learning, memory, and executive functioning in people living with HIV/AIDS.

PubMed

Fellows, Robert P; Byrd, Desiree A; Morgello, Susan

2014-01-01

It is unclear whether or to what degree literacy, aging, and other neurologic abnormalities relate to cognitive deficits among people living with HIV/AIDS in the combined antiretroviral therapy (CART) era. The primary aim of this study was to simultaneously examine the association of age, HIV-associated motor abnormalities, major depressive disorder, and reading level with information processing speed, learning, memory, and executive functions, and to determine whether processing speed mediated any of the relationships between cognitive and noncognitive variables. Participants were 186 racially and ethnically diverse men and women living with HIV/AIDS who underwent comprehensive neurological, neuropsychological, and medical evaluations. Structural equation modeling was utilized to assess the extent to which information processing speed mediated the relationship between age, motor abnormalities, major depressive disorder, and reading level with other cognitive abilities. Age, motor dysfunction, reading level, and current major depressive disorder were all significantly associated with information processing speed. Information processing speed fully mediated the effects of age on learning, memory, and executive functioning and partially mediated the effect of major depressive disorder on learning and memory. The effect of motor dysfunction on learning and memory was fully mediated by processing speed. These findings provide support for information processing speed as a primary deficit, which may account, at least in part, for many of the other cognitive abnormalities recognized in complex HIV/AIDS populations. The association of age and information processing speed may account for HIV/aging synergies in the generation of CART-era cognitive abnormalities.

Effects of Early Motor Intervention in the Prone Position of Full-Term Infants through the First Year of Life.

ERIC Educational Resources Information Center

Douret, L.

1993-01-01

Full-term infants who had slept in the prone position since birth were followed to detect early postural abnormalities and differentiate potential peripheral abnormality from abnormalities of a central origin. Results showed that disappearance of initial signs of abnormality appeared to be muscular, and symptoms disappeared faster when a motor…

Early rearing interacts with temperament and housing to influence the risk for motor stereotypy in rhesus monkeys (Macaca mulatta).

PubMed

Vandeleest, Jessica J; McCowan, Brenda; Capitanio, John P

2011-06-01

Laboratory and zoo housed non-human primates sometimes exhibit abnormal behaviors that are thought to reflect reduced wellbeing. Previous research attempted to identify risk factors to aid in the prevention and treatment of these behaviors, and focused on demographic (e.g. sex or age) and experience-related (e.g. single housing or nursery rearing) factors. However, not all animals that display abnormal behavior possess these risk factors and some individuals that possess a risk factor do not show behavioral abnormalities. We hypothesized that other aspects of early experience and individual characteristics might identify animals that were more likely to display one specific abnormal behavior, motor stereotypy (MS). Using logistic regression we explored the influence of early rearing (involving four different types of rearing conditions), and variation in temperament, on likelihood of displaying MS while controlling for previously identified risk factors. Analyses indicated that having a greater proportion of life lived indoors, a greater proportion of life-indoors singly-housed, and a greater number of anesthesias and blood draws significantly increased the risk of displaying MS (P < 0.001). Rearing condition failed to independently predict the display of MS; however significant interactions indicated that single housing had a greater impact on risk for indoor-reared animals versus outdoor-reared animals, and for indoor mother-reared animals versus nursery-reared animals. There were no main effects of temperament, although interactions with rearing were evident: scoring high on Gentle or Nervous was a risk factor for indoor-reared animals but not outdoor-reared animals. The final model accounted for approximately 69.3 % of the variance in the display of MS, and correctly classified 90.6% of animals. These results indicate that previously identified risk factors may impact animals differently depending on the individual's early rearing condition. These results are also the first in non-human primates to demonstrate that individual difference factors, like temperament, could be additional tools to identify animals at highest risk for motor stereotypy.

Characterization of esophageal pressure-flow abnormalities in patients with non-obstructive dysphagia and normal manometry findings.

PubMed

Chen, Chien-Lin; Yi, Chih-Hsun; Liu, Tso-Tsai; Hsu, Ching-Sheng; Omari, Taher I

2013-06-01

Patients with non-obstructive dysphagia (NOD) report symptoms of impaired esophageal bolus transit without evidence of bolus stasis. In such patients, manometric investigation may diagnose esophageal motility disorders; however, many have normal motor patterns. We hypothesized that patients with NOD would demonstrate evidence of high flow-resistance during bolus passage which in turn would relate to the reporting of bolus hold up perception. Esophageal pressure-impedance recordings of 5 mL liquid and viscous swallows from 18 NOD patients (11 male; 19-71 years) and 17 control subjects (9 male; 25-60 years) were analyzed. The relationship between intrabolus pressure and bolus flow timing in the esophagus was assessed using the pressure flow index (PFI). Bolus perception was assessed swallow by swallow using standardized descriptors. NOD patients were characterized by a higher PFI than controls. The PFI defined a pressure-flow abnormality in all patients who appeared normal based on the assessment esophageal motor patterns and bolus clearance. The PFI was higher for individual swallows during which subjects reported perception of bolus passage. Bolus flow-resistance is higher in NOD patients compared with controls as well as higher in relation to perception of bolus transit, suggesting the presence of an esophageal motility disorder despite normal findings on conventional analysis. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

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

Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naïve adolescents with depression compared to controls.

PubMed

Halari, Rozmin; Simic, Mima; Pariante, Carmine M; Papadopoulos, Andrew; Cleare, Anthony; Brammer, Michael; Fombonne, Eric; Rubia, Katya

2009-03-01

There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naïve adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naïve adolescents with a first-episode of MDD aged 14-17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. This study shows first evidence that medication-naïve adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.

Disrupted implicit motor sequence learning in schizophrenia and bipolar disorder revealed with ambidextrous Serial Reaction Time Task.

PubMed

Chrobak, Adrian Andrzej; Siuda-Krzywicka, Katarzyna; Siwek, Grzegorz Przemysław; Tereszko, Anna; Janeczko, Weronika; Starowicz-Filip, Anna; Siwek, Marcin; Dudek, Dominika

2017-10-03

Impairment of implicit motor sequence learning was shown in schizophrenia (SZ) and, most recently, in bipolar disorder (BD), and was connected to cerebellar abnormalities. The goal of this study was to compare implicit motor sequence learning in BD and SZ. We examined 33 patients with BD, 33 patients with SZ and 31 healthy controls with a use of ambidextrous Serial Reaction Time Task (SRTT), which allows exploring asymmetries in performance depending on the hand used. BD and SZ patients presented impaired implicit motor sequence learning, although the pattern of their impairments was different. While BD patients showed no signs of implicit motor sequence learning for both hands, the SZ group presented some features of motor learning when performing with the right, but not with the left hand. To our best knowledge this is the first study comparing implicit motor sequence learning in BD and SZ. We show that both diseases share impairments in this domain, however in the case of SZ this impairment differs dependently on the hand performing SRTT. We propose that implicit motor sequence learning impairments constitute an overlapping symptom in BD and SZ and suggest further neuroimaging studies to verify cerebellar underpinnings as its cause. Copyright © 2017 Elsevier Inc. All rights reserved.

Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction.

PubMed

Yuan, Kai; Jin, Chenwang; Cheng, Ping; Yang, Xuejuan; Dong, Tao; Bi, Yanzhi; Xing, Lihong; von Deneen, Karen M; Yu, Dahua; Liu, Junyu; Liang, Jun; Cheng, Tingting; Qin, Wei; Tian, Jie

2013-01-01

The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA). However, few functional magnetic resonance imaging (fMRI) studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD) during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF) method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC), the left precuneus, the left supplementary motor area (SMA), the right parahippocampal gyrus (PHG) and the bilateral middle cingulate cortex (MCC). The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA.

Behavioral, Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder

PubMed Central

Sokhadze, Estate M.; Tasman, Allan; Sokhadze, Guela E.; El-Baz, Ayman S.; Casanova, Manuel F.

2015-01-01

Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80% of subjects with autism display “motor dyspraxia” or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N=30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more refined specifics of dyspraxia symptoms to investigate functional connectivity abnormalities underlying motor skills deficits in autism. PMID:26377686

Altered Brain Network in Amyotrophic Lateral Sclerosis: A Resting Graph Theory-Based Network Study at Voxel-Wise Level.

PubMed

Zhou, Chaoyang; Hu, Xiaofei; Hu, Jun; Liang, Minglong; Yin, Xuntao; Chen, Lin; Zhang, Jiuquan; Wang, Jian

2016-01-01

Amyotrophic lateral sclerosis (ALS) is a rare degenerative disorder characterized by loss of upper and lower motor neurons. Neuroimaging has provided noticeable evidence that ALS is a complex disease, and shown that anatomical and functional lesions extend beyond precentral cortices and corticospinal tracts, to include the corpus callosum; frontal, sensory, and premotor cortices; thalamus; and midbrain. The aim of this study is to investigate graph theory-based functional network abnormalities at voxel-wise level in ALS patients on a whole brain scale. Forty-three ALS patients and 44 age- and sex-matched healthy volunteers were enrolled. The voxel-wise network degree centrality (DC), a commonly employed graph-based measure of network organization, was used to characterize the alteration of whole brain functional network. Compared with the controls, the ALS patients showed significant increase of DC in the left cerebellum posterior lobes, bilateral cerebellum crus, bilateral occipital poles, right orbital frontal lobe, and bilateral prefrontal lobes; significant decrease of DC in the bilateral primary motor cortex, bilateral sensory motor region, right prefrontal lobe, left bilateral precuneus, bilateral lateral temporal lobes, left cingulate cortex, and bilateral visual processing cortex. The DC's z-scores of right inferior occipital gyrus were significant negative correlated with the ALSFRS-r scores. Our findings confirm that the regions with abnormal network DC in ALS patients were located in multiple brain regions including primary motor, somatosensory and extra-motor areas, supporting the concept that ALS is a multisystem disorder. Specifically, our study found that DC in the visual areas was altered and ALS patients with higher DC in right inferior occipital gyrus have more severity of disease. The result demonstrated that the altered DC value in this region can probably be used to assess severity of ALS.

Muscle synergy analysis in children with cerebral palsy

NASA Astrophysics Data System (ADS)

Tang, Lu; Li, Fei; Cao, Shuai; Zhang, Xu; Wu, De; Chen, Xiang

2015-08-01

Objective. To explore the mechanism of lower extremity dysfunction of cerebral palsy (CP) children through muscle synergy analysis. Approach. Twelve CP children were involved in this study, ten adults (AD) and eight typically developed (TD) children were recruited as a control group. Surface electromyographic (sEMG) signals were collected bilaterally from eight lower limb muscles of the subjects during forward walking at a comfortable speed. A nonnegative matrix factorization algorithm was used to extract muscle synergies. In view of muscle synergy differences in number, structure and symmetry, a model named synergy comprehensive assessment (SCA) was proposed to quantify the abnormality of muscle synergies. Main results. There existed larger variations between the muscle synergies of the CP group and the AD group in contrast with the TD group. Fewer mature synergies were recruited in the CP group, and many abnormal synergies specific to the CP group appeared. Specifically, CP children were found to recruit muscle synergies with a larger difference in structure and symmetry between two legs of one subject and different subjects. The proposed SCA scale demonstrated its great potential to quantitatively assess the lower-limb motor dysfunction of CP children. SCA scores of the CP group (57.00 ± 16.78) were found to be significantly less (p < 0.01) than that of the control group (AD group: 95.74 ± 2.04; TD group: 84.19 ± 11.76). Significance. The innovative quantitative results of this study can help us to better understand muscle synergy abnormality in CP children, which is related to their motor dysfunction and even the physiological change in their nervous system.

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.

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

White and gray matter damage in primary progressive MS

PubMed Central

Chard, Declan; Altmann, Daniel R.; Tozer, Daniel; Miller, David H.; Thompson, Alan J.; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-01

Objective: The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex (“primary WM damage model”); and (2) cortical abnormalities predict later changes in connected WM tracts (“primary GM damage model”). Methods: Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. Results: The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. Conclusion: These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. PMID:26674332

White and gray matter damage in primary progressive MS: The chicken or the egg?

PubMed

Bodini, Benedetta; Chard, Declan; Altmann, Daniel R; Tozer, Daniel; Miller, David H; Thompson, Alan J; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-12

The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. © 2015 American Academy of Neurology.

Neurological Abnormalities in Recent-Onset Schizophrenia and Asperger-Syndrome

PubMed Central

Hirjak, Dusan; Wolf, Robert Christian; Koch, Sabine C.; Mehl, Laura; Kelbel, Janna K.; Kubera, Katharina Maria; Traeger, Tanja; Fuchs, Thomas; Thomann, Philipp Arthur

2014-01-01

Background: Neurological abnormalities including a variety of subtle deficits such as discrete impairments in sensory integration, motor coordination (MOCO), and sequencing of complex motor acts are frequently found in patients with schizophrenia (SZ) and commonly referred to as neurological soft signs (NSS). Asperger-syndrome (AS) is characterized by sensory-motor difficulties as well. However, the question whether the two disorders share a common or a disease-specific pattern of NSS remains unresolved. Method: A total of 78 age- and education-matched participants [26 patients with recent-onset SZ, 26 individuals with AS, and 26 healthy controls (HC)] were recruited for the study. Analyses of covariance (ANCOVAs), with age, years of education, and medication included as covariates, were used to examine group differences on total NSS and the five subscale scores. Discriminant analyses were employed to identify the NSS subscales that maximally discriminate between the three groups. Results: Significant differences among the three groups were found in NSS total score and on the five NSS subscales. The clinical groups differed significantly in the NSS subscale MOCO. The correct discriminant rate between patients with SZ and individuals with AS was 61.5%. The correct discriminant rate was 92.3% between individuals with AS and HC, and 80.8% between SZ patients and HC, respectively. Conclusion: Our findings provide new evidence for the presence of NSS in AS and lend further support to previously reported difficulties in movement control in this disorder. According to the present results, SZ and AS seem to be characterized by both quantitative and qualitative NSS expression. PMID:25147527

Magnetization transfer and adiabatic R 1ρ MRI in the brainstem of Parkinson's disease.

PubMed

Tuite, Paul J; Mangia, Silvia; Tyan, Andrew E; Lee, Michael K; Garwood, Michael; Michaeli, Shalom

2012-06-01

In addition to classic midbrain pathology, Parkinson's disease (PD) is accompanied by changes in pontine and medullary brainstem structures. These additional abnormalities may underlie non-motor features as well as play a role in motor disability. Using novel magnetic resonance imaging (MRI) methods based on rotating frame adiabatic R(1ρ) (i.e., measurements of longitudinal relaxation during adiabatic full passage pulses) and modified magnetization transfer (MT) MRI mapping, we sought to identify brainstem alterations in nine individuals with mild-moderate PD (off medication) and ten age-matched controls at 4 T. We discovered significant differences in MRI parameters between midbrain and medullary brainstem structures in control subjects as compared to PD patients. These findings support the presence of underlying functional/structural brainstem changes in mild-moderate PD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease.

PubMed

Grafton, S T; Turner, R S; Desmurget, M; Bakay, R; Delong, M; Vitek, J; Crutcher, M

2006-04-25

To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related "overactivity" compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.

[Neurological soft signs in schizophrenia: correlations with age, sex, educational status and psychopathology].

PubMed

Panagiotidis, P; Kaprinis, G; Iacovides, A; Fountoulakis, K

2013-01-01

Though the pathobiology of schizophrenia can be examined in multiple levels, the organic notion of brain disease suggests that neurological features will be present. One straightforward, inexpensive method of investigating brain dysfunction in schizophrenia is thought the bedside assessment of neurological abnormalities with a standard neurological examination. Neurological abnormalities are traditionally classified as "hard signs" (impairments in basic motor, sensory, and reflex behaviors, which do not appear to be affected in schizophrenia) and "soft signs", which refer to more complex phenomena such as abnormalities in motor control, integrative sensory function, sensorimotor integration, and cerebral laterality. Additionally, neurological soft signs (NSS) are minor motor and sensory abnormalities that are considered to be normal in the course of early development but abnormal when elicited in later life or persist beyond childhood. Soft signs also, have no definitive localizing significance but are indicative of subtle brain dysfunction. Most authors believe that they are a reflection not only of deficient integration between the sensory and motor systems, but also of dysfunctional neuronal circuits linking subcortical brain structures such as the basal ganglia, the brain stem, and the limbic system. Throughout the last four decades, studies have consistently shown that NSS are more frequently present in patients with schizophrenia than in normal subjects and non-psychotic psychiatric patients. However, the functional relevance of NSS remains unclear and their specificity has often been challenged, even though there is indication for a relative specificity with regard to diagnosis, or symptomatology. Many studies have considered soft signs as categorical variables thus hampering the evaluation of fluctuation with symptomatology and/or treatment, whereas other studies included insufficient number of assessed signs, or lacked a comprehensive assessment of extrapyramidal symptomatology. Factors such as sex, age or family history of schizophrenia, are said to influence the performance of neurological examination, whereas relative few studies have provided longitudinal follow-up data on neurological soft signs in a sufficient number of patients, in order to address a possible deterioration of neurological functions. Finally, one additional difficulty when analyzing the NSS literature lies in the diversity of symptoms that are evaluated in the studies and/or non-standardized procedures or scoring. We will review some basic issues concerning recurrent difficulties in the measurement and definition of soft signs, as well as controversies on the significance of these signs with respect to clinical subtyping of schizophrenia, and social and demographic variables.

Energy Homeostasis and Abnormal RNA Metabolism in Amyotrophic Lateral Sclerosis

PubMed Central

Liu, Yu-Ju; Tsai, Po-Yi; Chern, Yijuang

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is clinically characterized by progressive muscle weakness and impaired voluntary movement due to the loss of motor neurons in the brain, brain stem and spinal cord. To date, no effective treatment is available. Ample evidence suggests that impaired RNA homeostasis and abnormal energy status are two major pathogenesis pathways in ALS. In the present review article, we focus on recent studies that report molecular insights of both pathways, and discuss the possibility that energy dysfunction might negatively regulate RNA homeostasis via the impairment of cytoplasmic-nuclear shuttling in motor neurons and subsequently contribute to the development of ALS. PMID:28522961

Developing Gene Silencing for the Study and Treatment of Dystonia

DTIC Science & Technology

2016-10-01

eliminate the symptoms? Are the motor deficits in DYT1 dystonia reversible? We propose to use a novel rat model of DYT1 dystonia and infuse antisense...suppressing expression of mutant torsinA in striatum or cerebellum using AAV1 reverses the motor phenotype in aged DYT1 rats . 4. IMPACT What was...different areas of the brain, and w e w ill measure if they are able to reverse known abnormalities that occur in the brain of DYT1 rats , including abnormal

Brain-computer interfaces in neurological rehabilitation.

PubMed

Daly, Janis J; Wolpaw, Jonathan R

2008-11-01

Recent advances in analysis of brain signals, training patients to control these signals, and improved computing capabilities have enabled people with severe motor disabilities to use their brain signals for communication and control of objects in their environment, thereby bypassing their impaired neuromuscular system. Non-invasive, electroencephalogram (EEG)-based brain-computer interface (BCI) technologies can be used to control a computer cursor or a limb orthosis, for word processing and accessing the internet, and for other functions such as environmental control or entertainment. By re-establishing some independence, BCI technologies can substantially improve the lives of people with devastating neurological disorders such as advanced amyotrophic lateral sclerosis. BCI technology might also restore more effective motor control to people after stroke or other traumatic brain disorders by helping to guide activity-dependent brain plasticity by use of EEG brain signals to indicate to the patient the current state of brain activity and to enable the user to subsequently lower abnormal activity. Alternatively, by use of brain signals to supplement impaired muscle control, BCIs might increase the efficacy of a rehabilitation protocol and thus improve muscle control for the patient.

Plasticity of cortical inhibition in dystonia is impaired after motor learning and paired-associative stimulation.

PubMed

Meunier, Sabine; Russmann, Heike; Shamim, Ejaz; Lamy, Jean-Charles; Hallett, Mark

2012-03-01

Artificial induction of plasticity by paired associative stimulation (PAS) in healthy volunteers (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory networks. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long-interval intracortical inhibition (LICI, reflecting activity of GABA(B) interneurons) and long-latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced long-term potentiation (LTP)-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Improved lower extremity pedaling mechanics in individuals with stroke under maximal workloads.

PubMed

Linder, Susan M; Rosenfeldt, Anson B; Bazyk, Andrew S; Koop, Mandy Miller; Ozinga, Sarah; Alberts, Jay L

2018-05-01

Background Individuals with stroke present with motor control deficits resulting in the abnormal activation and timing of agonist and antagonist muscles and inefficient movement patterns. The analysis of pedaling biomechanics provides a window into understanding motor control deficits, which vary as a function of workload. Understanding the relationship between workload and motor control is critical when considering exercise prescription during stroke rehabilitation. Objectives To characterize pedaling kinematics and motor control processes under conditions in which workload was systematically increased to an eventual patient-specific maximum. Methods A cohort study was conducted in which 18 individuals with chronic stroke underwent a maximal exertion cardiopulmonary exercise test on a stationary cycle ergometer, during which pedaling torque was continuously recorded. Measures of force production, pedaling symmetry, and pedaling smoothness were obtained. Results Mean Torque increased significantly (p < 0.05) for both legs from initial to terminal workloads. Mean torque Symmetry Index, calculated for down and upstroke portions of the pedaling action, improved from 0.37(0.29) to 0.29(0.35) during downstroke (p = 0.007), and worsened during the upstroke: -0.37(0.38) to -0.62(0.46) (p < 0.001) from initial to terminal workloads. Low Torque Duration improved from initial to terminal workloads, decreasing from 121.1(52.9) to 58.1(39.6) degrees (p < 0.001), respectively. Smoothness of pedaling improved significantly from initial to terminal workloads (p < 0.001). Conclusions Improved pedaling kinematics at terminal workloads indicate that individuals with stroke demonstrate improved motor control with respect to the timing, sequencing, and activation of hemiparetic lower extremity musculature compared to lower workloads. Therapeutic prescription involving higher resistance may be necessary to sufficiently engage and activate the paretic lower extremity.

An electrophysiological follow up of patients with n-hexane polyneuropathy.

PubMed Central

Chang, Y C

1991-01-01

Electroneurographic (ENeG) and evoked potential (EP) studies were regularly performed on 11 printing workers with n-hexane polyneuropathy after cessation of exposure. At the initial examination, the ENeG studies simulated a demyelinative process. Further slowing of nerve conduction velocity, or further decreasing of action potential amplitude, or both in the follow up ENeG study were found in about half the patients. The motor distal latency did not worsen. Nerve conduction returned to normal earlier in the sensory than in the motor nerves. After the patients had regained full motor capability, conduction velocities in motor nerves were still significantly slowed. These ENeG characteristics correlate with the pathological and pathophysiological changes in experimental hexa-carbon neuropathies. The initial findings from the EP studies indicated a conduction abnormality in the central nervous system (CNS). Delayed worsening occurred in the amplitude of visual EPs in three patients. On serial follow up, the interpeak latency and interpeak amplitude of visual EPs improved little. Residual abnormalities were also found in the interpeak latency of auditory EPs in the brainstem and in the absolute latency of scalp somatosensory EPs from the peroneal nerve. Astroglial proliferation in the CNS probably impedes recovery of the abnormalities in EP. PMID:1993154

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

Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation

PubMed Central

Civier, Oren; Bullock, Daniel; Max, Ludo; Guenther, Frank H.

2013-01-01

A typical white-matter integrity and elevated dopamine levels have been reported for individuals who stutter. We investigated how such abnormalities may lead to speech dysfluencies due to their effects on a syllable-sequencing circuit that consists of basal ganglia (BG), thalamus, and left ventral premotor cortex (vPMC). “Neurally impaired” versions of the neurocomputational speech production model GODIVA were utilized to test two hypotheses: (1) that white-matter abnormalities disturb the circuit via corticostriatal projections carrying copies of executed motor commands, and (2) that dopaminergic abnormalities disturb the circuit via the striatum. Simulation results support both hypotheses: in both scenarios, the neural abnormalities delay readout of the next syllable’s motor program, leading to dysfluency. The results also account for brain imaging findings during dysfluent speech. It is concluded that each of the two abnormality types can cause stuttering moments, probably by affecting the same BG-thalamus-vPMC circuit. PMID:23872286

Relationship of neuromotor disturbances to psychosis symptoms in first-episode neuroleptic-naive schizophrenia patients.

PubMed

Cortese, Leonardo; Caligiuri, Michael P; Malla, Ashok K; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

2005-06-01

From the very inception of the modern diagnostic scheme for psychotic disorders, abnormalities in motor function have been observed in these conditions. Despite convergence from multiple areas of research supporting the notion that multiple frontal-subcortical circuits regulate motor and limbic behavior, the precise relationship between motor abnormalities and psychopathology has not been elucidated. The goals of this study were to examine the prevalence of extrapyramidal signs (EPS) in first-episode schizophrenia patients and their relationships to three psychopathological dimensions (positive psychosis syndrome, negative syndrome, and disorganization). We assessed EPS using traditional observer-based as well as quantitative instrumental measures in 39 neuroleptic-naive first-episode schizophrenia subjects. Subjects were followed for 6 months after initiating antipsychotic treatment to examine the stability of motor-limbic relationships. Four main findings emerged from this study. First, depending on the measure used the prevalence of dyskinesia prior to treatment ranged from 13% to 20%. The prevalence of parkinsonism ranged from 18% to 28%. Second, severity of dyskinesia was associated with the positive psychotic syndrome; whereas parkinsonism was associated with the positive psychosis, negative syndrome and disorganization. Third, psychopathology improved significantly across all symptom dimensions following antipsychotic treatment, while EPS remained stable. This suggests that some motor abnormalities in schizophrenia may reflect trait characteristics. Fourth, abnormalities on the pre-treatment instrumental measure of parkinsonism predicted greater improvement on positive psychosis symptoms following treatment (p=0.008). Our findings support the notion that neuromotor disturbances may be a core feature of schizophrenia in a substantial proportion of patients and implicate multiple fronto-striatal circuits regulating limbic and neuromotor behavior in schizophrenia.

Rapid treatment-induced brain changes in pediatric CRPS.

PubMed

Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

2016-03-01

To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.

Selective motor control correlates with gait abnormality in children with cerebral palsy.

PubMed

Chruscikowski, Emily; Fry, Nicola R D; Noble, Jonathan J; Gough, Martin; Shortland, Adam P

2017-02-01

Children with bilateral cerebral palsy (CP) commonly have limited selective motor control (SMC). This affects their ability to complete functional tasks. The impact of impaired SMC on walking has yet to be fully understood. Measures of SMC have been shown to correlate with specific characteristics of gait, however the impact of SMC on overall gait pattern has not been reported. This study explored SMC data collected as part of routine gait analysis in children with bilateral CP. As part of their clinical assessment, SMC was measured with the Selective Control Assessment of the Lower Extremities (SCALE) in 194 patients with bilateral cerebral palsy attending for clinical gait analysis at a single centre. Their summed SCALE score was compared with overall gait impairment, as measured by Gait Profile Score (GPS). Score on SCALE showed a significant negative correlation with GPS (r s =-0.603, p<0.001). Cerebral injuries in CP result in damage to the motor tracts responsible for SMC. Our results indicate that this damage is also associated with changes in the development of walking pattern in children with CP. Copyright © 2016 Elsevier B.V. All rights reserved.

Neurodevelopmental, functional and growth status of term low birth weight infants at eighteen months.

PubMed

Juneja, M; Shankar, A; Ramji, S

2005-11-01

This study was done to evaluate the neurodevelopmental, functional and growth status of term infants weighing 2000 g or less at 18 months, and to analyze major medical and social factors associated with an adverse neurodevelopmental and/or functional outcome. All infants were assessed for growth, audio-visual, neurological impairment, and motor and mental development using Indian modification of Bayley Scales of infant development. A detailed history was also taken. Term infants with birth weight of >2500 g without any antenatal or neonatal complications served as controls. Fifty low birth weight (LBW) term infants and 30 controls were evaluated. The mean mental development Quotient for LBW infants [91.51(16.97)] was significantly lower than that of Controls [102.02(8.4)]; the mean motor development Quotient however was comparable. The LBW infants were significantly lagging in terms of weight, length and head circumference at assessment. Neonatal complications were associated with an abnormal motor outcome while lower Socio-economic status and maternal education were related to adverse mental status. We concluded that Term LBW infants are at a significant disadvantage in terms of growth and mental scores at 18 months.

Identification of the effects of peripheral nerves injury on the muscle control - A review

NASA Astrophysics Data System (ADS)

Cabaj, Anna; Zmyslowski, Wojciech

2011-01-01

Impairment of motor function following peripheral nerve injury is a serious clinical problem. Generally nerve injury leads to erroneous control of muscle activity that results in gait and voluntary movement abnormalities followed by muscle atrophy. This article presents a review of studies on the effects of peripheral nerve injury on the motor system performed on animal models. We focused our attention on the results that are fundamental for better understanding of the degenerative and regenerative processes induced by nerve injury as well as of the mechanisms of structural changes in neuronal networks controlling movement. Quoted results are also important for clinical applications because they allow to develop new diagnostic and therapeutic techniques that can be used after nerve injury inducing motor deficits. However, till now no efficient therapy inducing satisfactory recovery was found. There is still a need to continue an advanced basic research directed to develop effective therapies. Thus the aim of this review is to compare the results of recent studies performed on various animal models in order to propose new methods for identification of mechanisms responsible for muscle deficits and propose targets for new pharmacological therapies.

Oligonucleotide therapeutics in neurodegenerative diseases.

PubMed

Scoles, Daniel R; Pulst, Stefan M

2018-03-21

Therapeutics that directly target RNAs are promising for a broad spectrum of disorders, including the neurodegenerative diseases. This is exemplified by the FDA approval of Nusinersen, an antisense oligonucleotide (ASO) therapeutic for spinal muscular atrophy (SMA). RNA targeting therapeutics are currently under development for amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias. We have used an ASO approach toward developing a treatment for spinocerebellar ataxia type 2 (SCA2), for targeting the causative gene ATXN2. We demonstrated that reduction of ATXN2 expression in SCA2 mice treated by intracerebroventicular injection (ICV) of ATXN2 ASO delayed motor phenotype onset, improved the expression of several genes demonstrated abnormally reduced by transcriptomic profiling of SCA2 mice, and restored abnormal Purkinje cell firing frequency in acute cerebellar sections. Here we discuss RNA abnormalities in disease and the prospects of targeting neurodegenerative diseases at the level of RNA control using ASOs and other RNA-targeted therapeutics.

Tissue-specific models of spinal muscular atrophy confirm a critical role of SMN in motor neurons from embryonic to adult stages.

PubMed

Laird, Angela S; Mackovski, Nikolce; Rinkwitz, Silke; Becker, Thomas S; Giacomotto, Jean

2016-05-01

Spinal muscular atrophy (SMA) is an autosomal recessive disease linked to survival motor neuron (SMN) protein deficiency. While SMN protein is expressed ubiquitously, its deficiency triggers tissue-specific hallmarks, including motor neuron death and muscle atrophy, leading to impaired motor functions and premature death. Here, using stable miR-mediated knockdown technology in zebrafish, we developed the first vertebrate system allowing transgenic spatio-temporal control of the smn1 gene. Using this new model it is now possible to investigate normal and pathogenic SMN function(s) in specific cell types, independently or in synergy with other cell populations. We took advantage of this new system to first test the effect of motor neuron or muscle-specific smn1 silencing. Anti-smn1 miRNA expression in motor neurons, but not in muscles, reproduced SMA hallmarks, including abnormal motor neuron development, poor motor function and premature death. Interestingly, smn1 knockdown in motor neurons also induced severe late-onset phenotypes including scoliosis-like body deformities, weight loss, muscle atrophy and, seen for the first time in zebrafish, reduction in the number of motor neurons, indicating motor neuron degeneration. Taken together, we have developed a new transgenic system allowing spatio-temporal control of smn1 expression in zebrafish, and using this model, we have demonstrated that smn1 silencing in motor neurons alone is sufficient to reproduce SMA hallmarks in zebrafish. It is noteworthy that this research is going beyond SMA as this versatile gene-silencing transgenic system can be used to knockdown any genes of interest, filling the gap in the zebrafish genetic toolbox and opening new avenues to study gene functions in this organism. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Relationship between characteristics on magnetic resonance imaging and motor outcomes in children with cerebral palsy and white matter injury.

PubMed

Reid, Susan M; Ditchfield, Michael R; Bracken, Jenny; Reddihough, Dinah S

2015-01-01

In a population cohort of children with white matter injury (WMI) and cerebral palsy (CP), we aimed to describe the magnetic resonance imaging (MRI) characteristics, identify key structure-function relationships, and classify the severity of WMI in a clinically relevant way. Stratified on MRI laterality/symmetry, variables indicating the extent and location of cerebral abnormalities for 272 children with CP and WMI on chronic-phase MRI were related to gross motor function and motor topography using univariable and multivariable approaches. We found that symmetrical involvement, severe WM loss in the hemispheres and corpus callosum, and cerebellar involvement were the strongest predictors of poor gross motor function, but the final model explained only a small proportion of the variability. Bilateral, extensive WM loss was more likely to result in quadriplegia, whereas volume loss in the posterior-mid WM more frequently resulted in diplegia. The extent and location of MRI abnormalities differed according to laterality/symmetry; asymmetry was associated with less extensive hemispheric involvement than symmetrical WMI, and unilateral lesions were more focal and located more anteriorly. In summary, laterality/symmetry of WMI, possibly reflecting different pathogenic mechanisms, together with extent of WM loss and cerebellar abnormality predicted gross motor function in CP, but to a limited extent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preterm and term-equivalent age general movements and 1-year neurodevelopmental outcomes for infants born before 30 weeks' gestation.

PubMed

Olsen, Joy E; Allinson, Leesa G; Doyle, Lex W; Brown, Nisha C; Lee, Katherine J; Eeles, Abbey L; Cheong, Jeanie L Y; Spittle, Alicia J

2018-01-01

To examine the associations between Prechtl's General Movements Assessment (GMA), conducted from birth to term-equivalent age, and neurodevelopmental outcomes at 12 months corrected age, in infants born very preterm. One hundred and thirty-seven infants born before 30 weeks' gestation had serial GMA (categorized as 'normal' or 'abnormal') before term and at term-equivalent age. At 12 months corrected age, neurodevelopment was assessed using the Alberta Infant Motor Scale (AIMS); Neurological, Sensory, Motor, Developmental Assessment (NSMDA); and Touwen Infant Neurological Examination (TINE). The relationships between GMA at four time points and 12-month neurodevelopmental assessments were examined using regression models. Abnormal GMA at all time points were associated with worse continuous scores on the AIMS, NSMDA, and TINE (p<0.05). Abnormal GMA before term and at term-equivalent age were associated with increased odds of mild-severe dysfunction on the NSMDA (odds ratio [OR] 4.26, 95% confidence interval [CI] 1.55-11.71, p<0.01; and OR 4.16, 95% CI 1.55-11.17, p<0.01 respectively) and abnormal GMA before term with increased odds of suboptimal-abnormal motor function on the TINE (OR 2.75, 95% CI 1.10-6.85, p=0.03). Abnormal GMA before term and at term-equivalent age were associated with worse neurodevelopment at 12 months corrected age in children born very preterm. Abnormal general movements before term predict developmental deficits at 1 year in infants born very preterm. General Movements Assessment before term identifies at-risk infants born very preterm. © 2017 Mac Keith Press.

Prenatal stress exposure alters postnatal behavioral expression under conditions of novelty challenge in rhesus monkey infants.

PubMed

Schneider, M L

1992-11-01

This prospective study investigated whether mild maternal stress during pregnancy could alter the behavioral and affective responses in rhesus monkey infants in a complex, novel environment. Twenty-four rhesus monkey infants were tested on three occasions at 6 months of age in a novel environment. Twelve infants were derived from mothers exposed to a daily 10-min mild stressor from Day 90 to Day 145 postconception, while 12 were derived from mothers undisturbed during pregnancy. Prenatally stressed infants demonstrated more disturbance behavior, and lower levels of gross motor/exploratory behavior. Moreover, half of the prenatally stressed infants showed an abnormal response, falling asleep, while none of the control infants displayed this behavior. Males exhibited more clinging to surrogates, while females spent more time in gross motor/exploratory behaviors, with prenatally stressed males tending to spend the least time in gross motor/exploratory activity.

Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors.

PubMed

Quintana, Albert; Sanz, Elisenda; Wang, Wengang; Storey, Granville P; Güler, Ali D; Wanat, Matthew J; Roller, Bryan A; La Torre, Anna; Amieux, Paul S; McKnight, G Stanley; Bamford, Nigel S; Palmiter, Richard D

2012-11-01

The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear. We found that, in the absence of GPR88, MSNs showed increased glutamatergic excitation and reduced GABAergic inhibition, which promoted enhanced firing rates in vivo, resulting in hyperactivity, poor motor coordination and impaired cue-based learning in mice. Targeted viral expression of GPR88 in MSNs rescued the molecular and electrophysiological properties and normalized behavior, suggesting that aberrant MSN activation in the absence of GPR88 underlies behavioral deficits and its dysfunction may contribute to behaviors observed in neuropsychiatric disease.

Functional neurological symptom disorder (conversion disorder): A role for microglial-based plasticity mechanisms?

PubMed

Stephenson, Chris P; Baguley, Ian J

2018-02-01

Functional Neurological Symptom Disorder (FND) is a relatively common neurological condition, accounting for approximately 3-6% of neurologist referrals. FND is considered a transient disorder of neuronal function, sometimes linked to physical trauma and psychological stress. Despite this, chronic disability is common, for example, around 40% of adults with motor FND have permanent disability. Building on current theoretical models, this paper proposes that microglial dysfunction could perpetuate functional changes within acute motor FND, thus providing a pathophysiological mechanism underlying the chronic stage of the motor FND phenotypes seen clinically. Core to our argument is microglia's dual role in modulating neuroimmunity and their control of synaptic plasticity, which places them at a pathophysiological nexus wherein coincident physical trauma and psychological stress could cause long-term change in neuronal networks without producing macroscopic structural abnormality. This model proposes a range of hypotheses that are testable with current technologies. Copyright © 2017. Published by Elsevier Ltd.

An anticholinergic reverses motor control and corticostriatal LTD deficits in Dyt1 ΔGAG knock-in mice.

PubMed

Dang, Mai T; Yokoi, Fumiaki; Cheetham, Chad C; Lu, Jun; Vo, Viet; Lovinger, David M; Li, Yuqing

2012-01-15

DYT1 early-onset generalized torsion dystonia is an inherited movement disorder associated with mutations in DYT1 that codes for torsinA protein. The most common mutation seen in this gene is a trinucleotide deletion of GAG. We previously reported a motor control deficit on a beam-walking task in our Dyt1 ΔGAG knock-in heterozygous mice. In this report we show the reversal of this motor deficit with the anticholinergic trihexyphenidyl (THP), a drug commonly used to treat movement problems in dystonia patients. THP also restored the reduced corticostriatal long-term depression (LTD) observed in these mice. Corticostriatal LTD has long been known to be dependent on D2 receptor activation. In this mouse model, striatal D2 receptors were expressed at lower quantities in comparison to wild-type mice. Furthermore, the mice were also partially resistant to FPL64176, an agonist of L-type calcium channels that have been previously reported to cause severe dystonic-like symptoms in wild-type mice. Our findings collectively suggest that altered communication between cholinergic interneurons and medium spiny neurons is responsible for the LTD deficit and that this synaptic plasticity modification may be involved in the striatal motor control abnormalities in our mouse model of DYT1 dystonia. Copyright © 2011 Elsevier B.V. All rights reserved.

Functional magnetic resonance imaging of chronic dysarthric speech after childhood brain injury: reliance on a left-hemisphere compensatory network.

PubMed

Morgan, Angela T; Masterton, Richard; Pigdon, Lauren; Connelly, Alan; Liégeois, Frédérique J

2013-02-01

Severe and persistent speech disorder, dysarthria, may be present for life after brain injury in childhood, yet the neural correlates of this chronic disorder remain elusive. Although abundant literature is available on language reorganization after lesions in childhood, little is known about the capacity of motor speech networks to reorganize after injury. Here, we examine the structural and functional neural correlates associated with chronic dysarthria after childhood-onset traumatic brain injury. Forty-nine participants aged 12 years 3 months to 24 years 11 months were recruited to the study: (i) a group with chronic dysarthria (n = 17); matched for age and sex with two control groups of (ii) healthy control subjects (n = 17); and (iii) individuals without dysarthria after traumatic brain injury (n = 15). A high-resolution 3D T(1)-weighted whole-brain data set was acquired for voxel-based morphometry analyses of group differences in grey matter. Functional magnetic resonance imaging was used to localize activation associated with speaking single words (baseline: listening to words). Group differences on voxel-based morphometry revealed widespread grey matter reductions in the dysarthric group compared with healthy control subjects, including in numerous speech motor regions bilaterally, such as the cerebellum, the basal ganglia and primary motor cortex representation of the articulators. Relative to the non-dysarthric traumatic brain injury group, individuals with dysarthria showed reduced grey matter bilaterally in the ventral sensorimotor cortex, but this reduction was concomitant with increased functional activation only in the left-hemisphere cluster during speech. Finally, increased recruitment of Broca's area (Brodmann area 45, pars triangularis) but not its right homologue, correlated with better speech outcome, suggesting that this 'higher-level' area may be more critically involved with production when associated motor speech regions are damaged. We suggest that the bilateral morphological abnormalities within cortical speech networks in childhood prevented reorganization of speech function from the left- to right-hemisphere. Rather, functional reorganization involved over-recruitment of left-hemisphere motor regions, a reorganization method that was only partly relatively effective, given the presence of persisting yet mild speech deficits. The bilateral structural abnormalities found to limit functional reorganization here, may also be critical to poor speech prognosis for populations with congenital, degenerative or acquired neurological disorders throughout the lifespan.

Pathophysiology of motor dysfunction in a childhood motor neuron disease caused by mutations in the riboflavin transporter.

PubMed

Menezes, Manoj P; Farrar, Michelle A; Webster, Richard; Antony, Jayne; O'Brien, Katherine; Ouvrier, Robert; Kiernan, Matthew C; Burns, Joshua; Vucic, Steve

2016-01-01

Brown-Vialetto-Van Laere (BVVL) syndrome is a progressive motor and sensory neuronopathy secondary to mutations in SLC52A2 encoding the riboflavin transporter type 2 (RFVT2). The phenotype is characterized by early childhood onset hearing loss and sensory ataxia followed by progressive upper limb weakness, optic atrophy, bulbar weakness and respiratory failure. To gain further insight into disease pathophysiology and response to riboflavin supplementation, the present study investigated whether axonal ion channel or membrane abnormalities were a feature of BVVL. Axonal excitability studies and clinical assessments were prospectively undertaken on six patients with BVVL secondary to riboflavin transporter deficiency type 2 (age range 10-21 years) at baseline and after 12 months of riboflavin (1000 mg daily) therapy. At baseline, depolarizing and hyperpolarizing threshold electrotonus was 'fanned out' and superexcitability was increased, while the resting current-threshold gradient and refractoriness were significantly reduced in BVVL patients when compared to controls. Mathematical modeling suggested that functional alterations of myelin underlay these findings with an increase in myelin permeability. Riboflavin therapy resulted in partial normalization of the axonal excitability findings, paralleled by maintenance of muscle strength. The present study established that abnormalities in myelin permeability at the paranode was a feature of BVVL and were partially normalized with riboflavin therapy. This study reveals a novel pathophysiological process for motor nerve dysfunction in BVVL. It also indicates that nerve excitability studies may be further developed in larger cohorts as a potential biomarker to identify treatment response for BVVL patients. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

Impairment of a parieto-premotor network specialized for handwriting in writer's cramp.

PubMed

Gallea, Cecile; Horovitz, Silvina G; Najee-Ullah, Muslimah 'Ali; Hallett, Mark

2016-12-01

Handwriting with the dominant hand is a highly skilled task singularly acquired in humans. This skill is the isolated deficit in patients with writer's cramp (WC), a form of dystonia with maladaptive plasticity, acquired through intensive and repetitive motor practice. When a skill is highly trained, a motor program is created in the brain to execute the same movement kinematics regardless of the effector used for the task. The task- and effector-specific symptoms in WC suggest that a problem particularly occurs in the brain when the writing motor program is carried out by the dominant hand. In this MRI study involving 12 WC patients (with symptoms only affecting the right dominant hand during writing) and 15 age matched unaffected controls we showed that: (1) the writing program recruited the same network regardless of the effector used to write in both groups; (2) dominant handwriting recruited a segregated parieto-premotor network only in the control group; (3) local structural alteration of the premotor area, the motor component of this network, predicted functional connectivity deficits during dominant handwriting and symptom duration in the patient group. Dysfunctions and structural abnormalities of a segregated parieto-premotor network in WC patients suggest that network specialization in focal brain areas is crucial for well-learned motor skill. Hum Brain Mapp 37:4363-4375, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Motor Development of Premature Infants Born between 32 and 34 Weeks

PubMed Central

Prins, S. A.; von Lindern, J. S.; van Dijk, S.; Versteegh, F. G. A.

2010-01-01

Little is known about motor development in late preterm born infants. Our objective was to determine long-term outcome of motor skills of infants born between 32 and 34 weeks. All infants were assessed at corrected ages of 3 and 9 months, using the Alberta Infant Motor Scale. At corrected ages of 4 years, the Movement Assessment Battery for Children was done. Seventy infants were seen at 4 years of age (median of 3 assessments per infant). Abnormal assessment at 3 or 9 months of age resulted in normal outcome in almost 80% at 4 years. On the other hand, a normal outcome in the first year of life resulted in an abnormal outcome at 4 years in 10% of the infants. Our results suggest that long-term followup of these late preterm born infants is necessary, as the assessments in the first year do not predict the long-term outcome. PMID:20885965

New concepts of the reinnervated motor unit revealed by vaccine-associated poliomyelitis.

PubMed

Wiechers, D O

1988-04-01

A late onset of slowly progressive muscle weakness 30-40 years after acute polio is well known. Previous studies by the author and others have demonstrated transmission abnormalities within the reinnervated motor unit. These transmission abnormalities shown by motor unit action potential (MUAP) instability in size and shape with repetitive discharges occurs in postpolio patients who are and who are not complaining of progressive muscle weakness. Although some reinnervated MUAPs do seem to stabilize their neuromuscular transmission with time in mildly affected muscles, the question arises as to whether or not some MUAPs ever stabilize after polio. Two cases of acute polio personally followed by the author, one over a 9 1/2 year period, are presented. In both cases, in muscles where there are more deinnervated muscle fibers than could possibly be reinnervated, the MUAPs have remained unstable. New concepts of function in the reinnervated motor unit following polio are presented.

Robotic exoskeleton assessment of transient ischemic attack.

PubMed

Simmatis, Leif; Krett, Jonathan; Scott, Stephen H; Jin, Albert Y

2017-01-01

We used a robotic exoskeleton to quantify specific patterns of abnormal upper limb motor behaviour in people who have had transient ischemic attack (TIA). A cohort of people with TIA was recruited within two weeks of symptom onset. All individuals completed a robotic-based assessment of 8 behavioural tasks related to upper limb motor and proprioceptive function, as well as cognitive function. Robotic task performance was compared to a large cohort of controls without neurological impairments corrected for the influence of age. Impairment in people with TIA was defined as performance below the 5th percentile of controls. Participants with TIA were also assessed with the National Institutes of Health Stroke Scale (NIHSS) score, Chedoke-McMaster Stroke Assessment (CMSA) of the arm, the Behavioural Inattention Test (BIT), the Purdue pegboard test (PPB), and the Montreal Cognitive Assessment (MoCA). Age-related white matter change (ARWMC), prior infarction and cella-media index (CMI) were assessed from baseline CT scan that was performed within 24 hours of TIA. Acute infarction was assessed from diffusion-weighted imaging in a subset of people with TIA. Twenty-two people with TIA were assessed. Robotic assessment showed impaired upper limb motor function in 7/22 people with TIA patients and upper limb sensory impairment in 4/22 individuals. Cognitive tasks involving robotic assessment of the upper limb were completed in 13 participants, of whom 8 (61.5%) showed significant impairment. Abnormal performance in the CMSA arm inventory was present in 12/22 (54.5%) participants. ARWMC was 11.8 ± 6.4 and CMI was 5.4 ± 1.5. DWI was positive in 0 participants. Quantitative robotic assessment showed that people who have had a TIA display a spectrum of upper limb motor and sensory performance deficits as well as cognitive function deficits despite resolution of symptoms and no evidence of tissue infarction.

The pre-morbid personality of patients with Parkinson's disease.

PubMed Central

Todes, C J; Lees, A J

1985-01-01

A review of the extensive descriptive literature suggests that many Parkinsonian patients exhibit an emotional and attitudinal inflexibility, a lack of affect and a predisposition to depressive illness, which may antecede the development of motor abnormalities by several decades. Introspective, over-controlled, anhedonic personality traits together with suppressed aggresivity are frequently found. It is unclear whether these behavioural patterns are relevant aetiological factors or prodromal symptoms of the disease. PMID:3884742

Disruption of Functional Organization Within the Primary Motor Cortex in Children With Autism

PubMed Central

Nebel, Mary Beth; Joel, Suresh E.; Muschelli, John; Barber, Anita D.; Caffo, Brian S.; Pekar, James J.; Mostofsky, Stewart H.

2013-01-01

Accumulating evidence suggests that motor impairments are prevalent in autism spectrum disorder (ASD), relate to the social and communicative deficits at the core of the diagnosis and may reflect abnormal connectivity within brain networks underlying motor control and learning. Parcellation of resting-state functional connectivity data using spectral clustering approaches has been shown to be an effective means of visualizing functional organization within the brain but has most commonly been applied to explorations of normal brain function. This article presents a parcellation of a key area of the motor network, the primary motor cortex (M1), a key area of the motor control network, in adults, typically developing (TD) children and children with ASD and introduces methods for selecting the number of parcels, matching parcels across groups and testing group differences. The parcellation is based solely on patterns of connectivity between individual M1 voxels and all voxels outside of M1, and within all groups, a gross dorsomedial to ventrolateral organization emerged within M1 which was left–right symmetric. Although this gross organizational scheme was present in both groups of children, statistically significant group differences in the size and segregation of M1 parcels within regions of the motor homunculus corresponding to the upper and lower limbs were observed. Qualitative comparison of the M1 parcellation for children with ASD with that of younger and older TD children suggests that these organizational differences, with a lack of differentiation between lower limb/trunk regions and upper limb/hand regions, may be due, at least in part, to a delay in functional specialization within the motor cortex. PMID:23118015

Compartmentalized Regulation of Parkin-Mediated Mitochondrial Quality Control in the Drosophila Nervous System In Vivo.

PubMed

Sung, Hyun; Tandarich, Lauren C; Nguyen, Kenny; Hollenbeck, Peter J

2016-07-13

In neurons, the normal distribution and selective removal of mitochondria are considered essential for maintaining the functions of the large asymmetric cell and its diverse compartments. Parkin, a E3 ubiquitin ligase associated with familial Parkinson's disease, has been implicated in mitochondrial dynamics and removal in cells including neurons. However, it is not clear how Parkin functions in mitochondrial turnover in vivo, or whether Parkin-dependent events of the mitochondrial life cycle occur in all neuronal compartments. Here, using the live Drosophila nervous system, we investigated the involvement of Parkin in mitochondrial dynamics, distribution, morphology, and removal. Contrary to our expectations, we found that Parkin-deficient animals do not accumulate senescent mitochondria in their motor axons or neuromuscular junctions; instead, they contain far fewer axonal mitochondria, and these displayed normal motility behavior, morphology, and metabolic state. However, the loss of Parkin did produce abnormal tubular and reticular mitochondria restricted to the motor cell bodies. In addition, in contrast to drug-treated, immortalized cells in vitro, mature motor neurons rarely displayed Parkin-dependent mitophagy. These data indicate that the cell body is the focus of Parkin-dependent mitochondrial quality control in neurons, and argue that a selection process allows only healthy mitochondria to pass from cell bodies to axons, perhaps to limit the impact of mitochondrial dysfunction. Parkin has been proposed to police mitochondrial fidelity by binding to dysfunctional mitochondria via PTEN (phosphatase and tensin homolog)-induced putative kinase 1 (PINK1) and targeting them for autophagic degradation. However, it is unknown whether and how the PINK1/Parkin pathway regulates the mitochondrial life cycle in neurons in vivo Using Drosophila motor neurons, we show that parkin disruption generates an abnormal mitochondrial network in cell bodies in vivo and reduces the number of axonal mitochondria without producing any defects in their axonal transport, morphology, or metabolic state. Furthermore, while cultured neurons display Parkin-dependent axonal mitophagy, we find this is vanishingly rare in vivo under normal physiological conditions. Thus, both the spatial distribution and mechanism of mitochondrial quality control in vivo differ substantially from those observed in vitro. Copyright © 2016 the authors 0270-6474/16/367375-17$15.00/0.

Compartmentalized Regulation of Parkin-Mediated Mitochondrial Quality Control in the Drosophila Nervous System In Vivo

PubMed Central

Sung, Hyun; Tandarich, Lauren C.; Nguyen, Kenny

2016-01-01

In neurons, the normal distribution and selective removal of mitochondria are considered essential for maintaining the functions of the large asymmetric cell and its diverse compartments. Parkin, a E3 ubiquitin ligase associated with familial Parkinson's disease, has been implicated in mitochondrial dynamics and removal in cells including neurons. However, it is not clear how Parkin functions in mitochondrial turnover in vivo, or whether Parkin-dependent events of the mitochondrial life cycle occur in all neuronal compartments. Here, using the live Drosophila nervous system, we investigated the involvement of Parkin in mitochondrial dynamics, distribution, morphology, and removal. Contrary to our expectations, we found that Parkin-deficient animals do not accumulate senescent mitochondria in their motor axons or neuromuscular junctions; instead, they contain far fewer axonal mitochondria, and these displayed normal motility behavior, morphology, and metabolic state. However, the loss of Parkin did produce abnormal tubular and reticular mitochondria restricted to the motor cell bodies. In addition, in contrast to drug-treated, immortalized cells in vitro, mature motor neurons rarely displayed Parkin-dependent mitophagy. These data indicate that the cell body is the focus of Parkin-dependent mitochondrial quality control in neurons, and argue that a selection process allows only healthy mitochondria to pass from cell bodies to axons, perhaps to limit the impact of mitochondrial dysfunction. SIGNIFICANCE STATEMENT Parkin has been proposed to police mitochondrial fidelity by binding to dysfunctional mitochondria via PTEN (phosphatase and tensin homolog)-induced putative kinase 1 (PINK1) and targeting them for autophagic degradation. However, it is unknown whether and how the PINK1/Parkin pathway regulates the mitochondrial life cycle in neurons in vivo. Using Drosophila motor neurons, we show that parkin disruption generates an abnormal mitochondrial network in cell bodies in vivo and reduces the number of axonal mitochondria without producing any defects in their axonal transport, morphology, or metabolic state. Furthermore, while cultured neurons display Parkin-dependent axonal mitophagy, we find this is vanishingly rare in vivo under normal physiological conditions. Thus, both the spatial distribution and mechanism of mitochondrial quality control in vivo differ substantially from those observed in vitro. PMID:27413149

[Focal dystonia in musicians: Phenomenology and musical triggering factors].

PubMed

Aránguiz, R; Chana-Cuevas, P; Alburquerque, D; Curinao, X

2015-06-01

Dystonias are defined as a joint sustained and involuntary contraction of agonist and antagonist muscles, which can cause torsion, repetitive abnormal involuntary movements, and/or abnormal postures. One special group of dystonias are those known as occupational, which include dystonia disorders triggered by a repetitive motor activity associated with a specific professional activity or task. Musicians are a population particularly vulnerable to these types of dystonia, which are presented as a loss of coordination and voluntary motor control movements highly trained in musical interpretation. Our aim is to describe a clinical series of focal dystonias in musicians evaluated and treated in our centre. Data is presented on a clinical series of 12 musicians with occupational dystonia. Their history and phenomenology are described, as well as well as their outcome after therapy. Demographic details: Mean age 34.8 ± 11.8 years, 10 males (83.3%) and 2 females (16.7%). History of trauma in dystonic segment, 6 patients (50%); family history of neurological diseases in first-degree relatives, 6 patients (50%); occupational history according to music category, 8 patients (66.6%) were classical musicians and 4 patients (33.3%) were popular musicians. The dystonia syndrome was characterised by having a mean age of onset of 28.2 ± 11.3 years (range 18-57 years). The segment affected was the hand (91.7%) in 11 patients. Of all the musicians seen in the clinic, 9 of them (75%) received therapy. The majority of patients appeared to have triggering factors specific to musical execution and linked to the requirement of fine motor control. It should be mentioned that 50% of the musicians treated maintained their professional activity or position in the orchestra to which they belonged. The majority of our phenomenological findings are consistent with those reported in the current literature. However, it is worth mentioning the presence of triggering factors attributed to the specific requirements of performing music, linked to the participation of fine motor control. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

The affective modulation of motor awareness in anosognosia for hemiplegia: Behavioural and lesion evidence

PubMed Central

Besharati, Sahba; Forkel, Stephanie J.; Kopelman, Michael; Solms, Mark; Jenkinson, Paul M.; Fotopoulou, Aikaterini

2014-01-01

The possible role of emotion in anosognosia for hemiplegia (i.e., denial of motor deficits contralateral to a brain lesion), has long been debated between psychodynamic and neurocognitive theories. However, there are only a handful of case studies focussing on this topic, and the precise role of emotion in anosognosia for hemiplegia requires empirical investigation. In the present study, we aimed to investigate how negative and positive emotions influence motor awareness in anosognosia. Positive and negative emotions were induced under carefully-controlled experimental conditions in right-hemisphere stroke patients with anosognosia for hemiplegia (n = 11) and controls with clinically normal awareness (n = 10). Only the negative, emotion induction condition resulted in a significant improvement of motor awareness in anosognosic patients compared to controls; the positive emotion induction did not. Using lesion overlay and voxel-based lesion-symptom mapping approaches, we also investigated the brain lesions associated with the diagnosis of anosognosia, as well as with performance on the experimental task. Anatomical areas that are commonly damaged in AHP included the right-hemisphere motor and sensory cortices, the inferior frontal cortex, and the insula. Additionally, the insula, putamen and anterior periventricular white matter were associated with less awareness change following the negative emotion induction. This study suggests that motor unawareness and the observed lack of negative emotions about one's disabilities cannot be adequately explained by either purely motivational or neurocognitive accounts. Instead, we propose an integrative account in which insular and striatal lesions result in weak interoceptive and motivational signals. These deficits lead to faulty inferences about the self, involving a difficulty to personalise new sensorimotor information, and an abnormal adherence to premorbid beliefs about the body. PMID:25481471

The affective modulation of motor awareness in anosognosia for hemiplegia: behavioural and lesion evidence.

PubMed

Besharati, Sahba; Forkel, Stephanie J; Kopelman, Michael; Solms, Mark; Jenkinson, Paul M; Fotopoulou, Aikaterini

2014-12-01

The possible role of emotion in anosognosia for hemiplegia (i.e., denial of motor deficits contralateral to a brain lesion), has long been debated between psychodynamic and neurocognitive theories. However, there are only a handful of case studies focussing on this topic, and the precise role of emotion in anosognosia for hemiplegia requires empirical investigation. In the present study, we aimed to investigate how negative and positive emotions influence motor awareness in anosognosia. Positive and negative emotions were induced under carefully-controlled experimental conditions in right-hemisphere stroke patients with anosognosia for hemiplegia (n = 11) and controls with clinically normal awareness (n = 10). Only the negative, emotion induction condition resulted in a significant improvement of motor awareness in anosognosic patients compared to controls; the positive emotion induction did not. Using lesion overlay and voxel-based lesion-symptom mapping approaches, we also investigated the brain lesions associated with the diagnosis of anosognosia, as well as with performance on the experimental task. Anatomical areas that are commonly damaged in AHP included the right-hemisphere motor and sensory cortices, the inferior frontal cortex, and the insula. Additionally, the insula, putamen and anterior periventricular white matter were associated with less awareness change following the negative emotion induction. This study suggests that motor unawareness and the observed lack of negative emotions about one's disabilities cannot be adequately explained by either purely motivational or neurocognitive accounts. Instead, we propose an integrative account in which insular and striatal lesions result in weak interoceptive and motivational signals. These deficits lead to faulty inferences about the self, involving a difficulty to personalise new sensorimotor information, and an abnormal adherence to premorbid beliefs about the body. Copyright © 2014 Elsevier Ltd. All rights reserved.

Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation

PubMed Central

Wallentin, Mikkel; Skakkebæk, Anne; Bojesen, Anders; Fedder, Jens; Laurberg, Peter; Østergaard, John R.; Hertz, Jens Michael; Pedersen, Anders Degn; Gravholt, Claus Højbjerg

2016-01-01

Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49) responded to whether the words “GREEN” or “RED” were displayed in green or red (incongruent versus congruent colors). One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying “GREEN” or “RED” had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system. PMID:26958463

Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation.

PubMed

Wallentin, Mikkel; Skakkebæk, Anne; Bojesen, Anders; Fedder, Jens; Laurberg, Peter; Østergaard, John R; Hertz, Jens Michael; Pedersen, Anders Degn; Gravholt, Claus Højbjerg

2016-01-01

Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49) responded to whether the words "GREEN" or "RED" were displayed in green or red (incongruent versus congruent colors). One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying "GREEN" or "RED" had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system.

Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor.

PubMed

Lalonde, R; Hayzoun, K; Selimi, F; Mariani, J; Strazielle, C

2003-11-01

Grid2(ho/ho) is a loss of function gene mutation resulting in abnormal dendritic arborizations of Purkinje cells. These mutants were compared in a series of motor coordination tests requiring balance and equilibrium to nonataxic controls (Grid2(ho/+)) and to a double mutant (Grid2(ho/Lc)) with an inserted Lc mutation. The performance of Grid2(ho/ho) mutant mice was poorer than that of controls on stationary beam, coat hanger, unsteady platform, and rotorod tests. Grid2(ho/Lc) did not differ from Grid2(Lc/+) mice. However, the insertion of the Lc mutation in Grid2(ho/Lc) potentiated the deficits found in Grid2(ho/ho) in stationary beam, unsteady platform, and rotorod tests. These results indicate a deleterious effect of the Lc mutation on Grid2-deficient mice.

Long-term increase in coherence between the basal ganglia and motor cortex after asphyxial cardiac arrest and resuscitation in developing rats.

PubMed

Aravamuthan, Bhooma R; Shoykhet, Michael

2015-10-01

The basal ganglia are vulnerable to injury during cardiac arrest. Movement disorders are a common morbidity in survivors. Yet, neuronal motor network changes post-arrest remain poorly understood. We compared function of the motor network in adult rats that, during postnatal week 3, underwent 9.5 min of asphyxial cardiac arrest (n = 9) or sham intervention (n = 8). Six months after injury, we simultaneously recorded local field potentials (LFP) from the primary motor cortex (MCx) and single neuron firing and LFP from the rat entopeduncular nucleus (EPN), which corresponds to the primate globus pallidus pars interna. Data were analyzed for firing rates, power, and coherence between MCx and EPN spike and LFP activity. Cardiac arrest survivors display chronic motor deficits. EPN firing rate is lower in cardiac arrest survivors (19.5 ± 2.4 Hz) compared with controls (27.4 ± 2.7 Hz; P < 0.05). Cardiac arrest survivors also demonstrate greater coherence between EPN single neurons and MCx LFP (3-100 Hz; P < 0.001). This increased coherence indicates abnormal synchrony in the neuronal motor network after cardiac arrest. Increased motor network synchrony is thought to be antikinetic in primary movement disorders. Characterization of motor network synchrony after cardiac arrest may help guide management of post-hypoxic movement disorders.

Impairments of Social Motor Coordination in Schizophrenia

PubMed Central

Varlet, Manuel; Marin, Ludovic; Raffard, Stéphane; Schmidt, R. C.; Capdevielle, Delphine; Boulenger, Jean-Philippe; Del-Monte, Jonathan; Bardy, Benoît G.

2012-01-01

It has been demonstrated that motor coordination of interacting people plays a crucial role in the success of social exchanges. Abnormal movements have been reported during interpersonal interactions of patients suffering from schizophrenia and a motor coordination breakdown could explain this social interaction deficit, which is one of the main and earliest features of the illness. Using the dynamical systems framework, the goal of the current study was (i) to investigate whether social motor coordination is impaired in schizophrenia and (ii) to determine the underlying perceptual or cognitive processes that may be affected. We examined intentional and unintentional social motor coordination in participants oscillating hand-held pendulums from the wrist. The control group consisted of twenty healthy participant pairs while the experimental group consisted of twenty participant pairs that included one participant suffering from schizophrenia. The results showed that unintentional social motor coordination was preserved while intentional social motor coordination was impaired. In intentional coordination, the schizophrenia group displayed coordination patterns that had lower stability and in which the patient never led the coordination. A coupled oscillator model suggests that the schizophrenia group coordination pattern was due to a decrease in the amount of available information together with a delay in information transmission. Our study thus identified relational motor signatures of schizophrenia and opens new perspectives for detecting the illness and improving social interactions of patients. PMID:22272247

The Moving Rubber Hand Illusion Reveals that Explicit Sense of Agency for Tapping Movements Is Preserved in Functional Movement Disorders.

PubMed

Marotta, Angela; Bombieri, Federica; Zampini, Massimiliano; Schena, Federico; Dallocchio, Carlo; Fiorio, Mirta; Tinazzi, Michele

2017-01-01

Functional movement disorders (FMD) are characterized by motor symptoms (e.g., tremor, gait disorder, and dystonia) that are not compatible with movement abnormalities related to a known organic cause. One key clinical feature of FMD is that motor symptoms are similar to voluntary movements but are subjectively experienced as involuntary by patients. This gap might be related to abnormal self-recognition of bodily action, which involves two main components: sense of agency and sense of body ownership. The aim of this study was to systematically investigate whether this function is altered in FMD, specifically focusing on the subjective feeling of agency, body ownership, and their interaction during normal voluntary movements. Patients with FMD ( n = 21) and healthy controls ( n = 21) underwent the moving Rubber Hand Illusion (mRHI), in which passive and active movements can differentially elicit agency, ownership or both. Explicit measures of agency and ownership were obtained via a questionnaire. Patients and controls showed a similar pattern of response: when the rubber hand was in a plausible posture, active movements elicited strong agency and ownership; implausible posture of the rubber hand abolished ownership but not agency; passive movements suppressed agency but not ownership. These findings suggest that explicit sense of agency and body ownership are preserved in FMD. The latter finding is shared by a previous study in FMD using a static version of the RHI, whereas the former appears to contrast with studies demonstrating altered implicit measures of agency (e.g., sensory attenuation). Our study extends previous findings by suggesting that in FMD: (i) the sense of body ownership is retained also when interacting with the motor system; (ii) the subjective experience of agency for voluntary tapping movements, as measured by means of mRHI, is preserved.

Neurophysiological Changes Measured Using Somatosensory Evoked Potentials.

PubMed

Macerollo, Antonella; Brown, Matt J N; Kilner, James M; Chen, Robert

2018-05-01

Measurements of somatosensory evoked potentials (SEPs), recorded using electroencephalography during different phases of movement, have been fundamental in understanding the neurophysiological changes related to motor control. SEP recordings have also been used to investigate adaptive plasticity changes in somatosensory processing related to active and observational motor learning tasks. Combining noninvasive brain stimulation with SEP recordings and intracranial SEP depth recordings, including recordings from deep brain stimulation electrodes, has been critical in identifying neural areas involved in specific temporal stages of somatosensory processing. Consequently, this fundamental information has furthered our understanding of the maladaptive plasticity changes related to pathophysiology of diseases characterized by abnormal movements, such as Parkinson's disease, dystonia, and functional movement disorders. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

[The role of 2,3-DPG in nerve conduction of children with type 1 diabetes].

PubMed

Pańkowska, Ewa; Szypowska, Agnieszka; Wysocka, Marta; Lipka, Maria

2005-01-01

Neuropathy is one of the chronic complications of diabetes, and it is uncommon in children and adolescents. It can be recognized in a short period after the onset of diabetes and not always is connected with poor metabolic control. Hypoxia is considered as one from greatest factors diabetic neuropathy and oxygen transport to tissue partially depends on the diphosphoglycerate (2,3 DPG) concentration. As showed recent clinical studies, its concentration in children with diabetes can be abnormal. To assess the role of 2,3 DPG in nerve conduction velocity, as well as qualification of risk factors. To study were included randomly selected 37 patients with diabetes type 1, average age 15.5+/-2.25 years, with a duration of diabetes of more than 5 years (av 9.64+/-1.95 years), treated with intensive insulin therapy (MDI and CSII), without metabolic acidosis pH - 7.35. The nerve conduction velocity was measured in the sensor and motor nerves. HbA1c and 2,3 DPG were assessed additionally. Changes in motor nerve conduction velocity were observed at 22 patients. Average value of HbA1c in the studied group was 8.22+/-1.2%, Average concentration of 2,3 DPG was 6.15+/-1.67 mmol/l (3.84-11 mmol/l), in group with nerve dysfunction was lower - 5.86+/-1.69 mmol/l vs. 6.38+/-1.67, but this difference was not statistically significant. The lower value of 2,3 DPG significantly correlated with abnormal results of electroneurography test, especially with motor and sensor nerve latency (r=-0.34, p=0.038; r=-0.4, p=0.013) but not correlated with HbA1c (r= -0,19;p= 0,25), age of patients (r=0.008; p=0.96) and diabetes duration (r=-0.16; p=0.31). Nerve dysfunction is common in children with type 1 diabetes despite metabolic control and duration of diabetes. 2,3 DPG can be an independent factor of diabetes neuropathy correlated with abnormal value of the nerve conduction test.

Distal small bowel motility and lipid absorption in patients following abdominal aortic aneurysm repair surgery

PubMed Central

Fraser, Robert J; Ritz, Marc; Matteo, Addolorata C Di; Vozzo, Rosalie; Kwiatek, Monika; Foreman, Robert; Stanley, Brendan; Walsh, Jack; Burnett, Jim; Jury, Paul; Dent, John

2006-01-01

AIM: To investigate distal small bowel motility and lipid absorption in patients following elective abdominal aortic aneurysm (AAA) repair surgery. METHODS: Nine patients (aged 35-78 years; body mass index (BMI) range: 23-36 kg/m2) post-surgery for AAA repair, and seven healthy control subjects (20-50 years; BMI range: 21-29 kg/m2) were studied. Continuous distal small bowel manometry was performed for up to 72 h, during periods of fasting and enteral feeding (Nutrison®). Recordings were analyzed for the frequency, origin, length of migration, and direction of small intestinal burst activity. Lipid absorption was assessed on the first day and the third day post surgery in a subset of patients using the 13C-triolein-breath test, and compared with healthy controls. Subjects received a 20-min intraduodenal infusion of 50 mL liquid feed mixed with 200 μL 13C-triolein. End-expiratory breath samples were collected for 6 h and analyzed for 13CO2 concentration. RESULTS: The frequency of burst activity in the proximal and distal small intestine was higher in patients than in healthy subjects, under both fasting and fed conditions (P < 0.005). In patients there was a higher proportion of abnormally propagated bursts (71% abnormal), which began to normalize by d 3 (25% abnormal) post-surgery. Lipid absorption data was available for seven patients on d 1 and four patients on d 3 post surgery. In patients, absorption on d 1 post-surgery was half that of healthy control subjects (AUC 13CO2 1 323 ± 244 vs 2 646 ±365; P < 0.05, respectively), and was reduced to the one-fifth that of healthy controls by d 3 (AUC 13CO2 470 ± 832 vs 2 646 ± 365; P < 0.05, respectively). CONCLUSION: Both proximal and distal small intestinal motor activity are transiently disrupted in critically ill patients immediately after major surgery, with abnormal motility patterns extending as far as the ileum. These motor disturbances may contribute to impaired absorption of enteral nutrition, especially when intraluminal processing is necessary for efficient digestion. PMID:16489672

The Validity of Two Neuromotor Assessments for Predicting Motor Performance at 12 Months in Preterm Infants.

PubMed

Song, You Hong; Chang, Hyun Jung; Shin, Yong Beom; Park, Young Sook; Park, Yun Hee; Cho, Eun Sol

2018-04-01

To evaluate the validity of the Test of Infant Motor Performance (TIMP) and general movements (GMs) assessment for predicting Alberta Infant Motor Scale (AIMS) score at 12 months in preterm infants. A total of 44 preterm infants who underwent the GMs and TIMP at 1 month and 3 months of corrected age (CA) and whose motor performance was evaluated using AIMS at 12 months CA were included. GMs were judged as abnormal on basis of poor repertoire or cramped-synchronized movements at 1 month CA and abnormal or absent fidgety movement at 3 months CA. TIMP and AIMS scores were categorized as normal (average and low average and >5th percentile, respectively) or abnormal (below average and far below average or <5th percentile, respectively). Correlations between GMs and TIMP scores at 1 month and 3 months CA and the AIMS classification at 12 months CA were examined. The TIMP score at 3 months CA and GMs at 1 month and 3 months CA were significantly correlated with the motor performance at 12 months CA. However, the TIMP score at 1 month CA did not correlate with the AIMS classification at 12 months CA. For infants with normal GMs at 3 months CA, the TIMP score at 3 months CA correlated significantly with the AIMS classification at 12 months CA. Our findings suggest that neuromotor assessment using GMs and TIMP could be useful to identify preterm infants who are likely to benefit from intervention.

Amelioration of Behavioral Abnormalities in BH4-deficient Mice by Dietary Supplementation of Tyrosine

PubMed Central

Kwak, Sang Su; Jeong, Mikyoung; Choi, Ji Hye; Kim, Daesoo; Min, Hyesun; Yoon, Yoosik; Hwang, Onyou; Meadows, Gary G.; Joe, Cheol O.

2013-01-01

This study reports an amelioration of abnormal motor behaviors in tetrahydrobiopterin (BH4)-deficient Spr −/− mice by the dietary supplementation of tyrosine. Since BH4 is an essential cofactor for the conversion of phenylalanine into tyrosine as well as the synthesis of dopamine neurotransmitter within the central nervous system, the levels of tyrosine and dopamine were severely reduced in brains of BH4-deficient Spr −/− mice. We found that Spr −/− mice display variable ‘open-field’ behaviors, impaired motor functions on the ‘rotating rod’, and dystonic ‘hind-limb clasping’. In this study, we report that these aberrant motor deficits displayed by Spr −/− mice were ameliorated by the therapeutic tyrosine diet for 10 days. This study also suggests that dopamine deficiency in brains of Spr −/− mice may not be the biological feature of aberrant motor behaviors associated with BH4 deficiency. Brain levels of dopamine (DA) and its metabolites in Spr −/− mice were not substantially increased by the dietary tyrosine therapy. However, we found that mTORC1 activity severely suppressed in brains of Spr −/− mice fed a normal diet was restored 10 days after feeding the mice the tyrosine diet. The present study proposes that brain mTORC1 signaling pathway is one of the potential targets in understanding abnormal motor behaviors associated with BH4-deficiency. PMID:23577163

GAME (Goals - Activity - Motor Enrichment): protocol of a single blind randomised controlled trial of motor training, parent education and environmental enrichment for infants at high risk of cerebral palsy.

PubMed

Morgan, Catherine; Novak, Iona; Dale, Russell C; Guzzetta, Andrea; Badawi, Nadia

2014-10-07

Cerebral palsy is the most common physical disability of childhood and early detection is possible using evidence based assessments. Systematic reviews indicate early intervention trials rarely demonstrate efficacy for improving motor outcomes but environmental enrichment interventions appear promising. This study is built on a previous pilot study and has been designed to assess the effectiveness of a goal - oriented motor training and enrichment intervention programme, "GAME", on the motor outcomes of infants at very high risk of cerebral palsy (CP) compared with standard community based care. A two group, single blind randomised controlled trial (n = 30) will be conducted. Eligible infants are those diagnosed with CP or designated "at high risk of CP" on the basis of the General Movements Assessment and/or abnormal neuroimaging. A physiotherapist and occupational therapist will deliver home-based GAME intervention at least fortnightly until the infant's first birthday. The intervention aims to optimize motor function and engage parents in developmental activities aimed at enriching the home learning environment. Primary endpoint measures will be taken 16 weeks after intervention commences with the secondary endpoint at 12 months and 24 months corrected age. The primary outcome measure will be the Peabody Developmental Motor Scale second edition. Secondary outcomes measures include the Gross Motor Function Measure, Bayley Scales of Infant and Toddler Development, Affordances in the Home Environment for Motor Development - Infant Scale, and the Canadian Occupational Performance Measure. Parent well-being will be monitored using the Depression Anxiety and Stress Scale. This paper presents the background, design and intervention protocol of a randomised trial of a goal driven, motor learning approach with customised environmental interventions and parental education for young infants at high risk of cerebral palsy. This trial is registered on the Australian New Zealand Clinical Trial register: ACTRN12611000572965.

High resolution manometry findings in patients with esophageal epiphrenic diverticula.

PubMed

Vicentine, Fernando P P; Herbella, Fernando A M; Silva, Luciana C; Patti, Marco G

2011-12-01

The pathophysiology of esophageal epiphrenic diverticula is still uncertain even though a concomitant motility disorder is found in the majority of patients in different series. High resolution manometry may allow detection of motor abnormalities in a higher number of patients with esophageal epiphrenic diverticula compared with conventional manometry. This study aims to evaluate the high resolution manometry findings in patients with esophageal epiphrenic diverticula. Nine individuals (mean age 63 ± 10 years, 4 females) with esophageal epiphrenic diverticula underwent high resolution manometry. A single diverticulum was observed in eight patients and multiple diverticula in one. Visual analysis of conventional tracings and color pressure plots for identification of segmental abnormalities was performed by two researchers experienced in high resolution manometry. Upper esophageal sphincter was normal in all patients. Esophageal body was abnormal in eight patients; lower esophageal sphincter was abnormal in seven patients. Named esophageal motility disorders were found in seven patients: achalasia in six, diffuse esophageal spasm in one. In one patient, a segmental hypercontractile zone was noticed with pressure of 196 mm Hg. High resolution manometry demonstrated motor abnormalities in all patients with esophageal epiphrenic diverticula.

Spectrum of gross motor function in extremely low birth weight children with cerebral palsy at 18 months of age.

PubMed

Vohr, Betty R; Msall, Michael E; Wilson, Dee; Wright, Linda L; McDonald, Scott; Poole, W Kenneth

2005-07-01

The purpose of this study was to evaluate the relationship between cerebral palsy (CP) diagnoses as measured by the topographic distribution of the tone abnormality with level of function on the Gross Motor Function Classification System (GMFCS) and developmental performance on the Bayley Scales of Infant Development II (BSID-II). It was hypothesized that (1) the greater the number of limbs involved, the higher the GMFCS and the lower the BSID-II Motor Scores and (2) there would be a spectrum of function and skill achievement on the GMFCS and BSID-II Motor Scores for children in each of the CP categories. A multicenter, longitudinal cohort study was conducted of 1860 extremely low birth weight (ELBW) infants who were born between August 1, 1995 and February 1, 1998, and evaluated at 18 to 22 months' corrected age. Children were categorized into impairment groups on the basis of the typography of neurologic findings: spastic quadriplegia, triplegia, diplegia, hemiplegia, monoplegia, hypotonic and/or athetotic CP, other abnormal neurologic findings, and normal. The neurologic category then was compared with GMFCS level and BSID-II Motor Scores. A total of 282 (15.2%) of the 1860 children evaluated had CP. Children with more limbs involved had more abnormal GMFCS levels and lower BSID-II scores, reflecting more severe functional limitations. However, for each CP diagnostic category, there was a spectrum of gross motor functional levels and BSID-II scores. Although more than 1 (26.6%) in 4 of the children with CP had moderate to severe gross motor functional impairment, 1 (27.6%) in 4 had motor functional skills that allowed for ambulation. Given the range of gross motor skill outcomes for specific types of CP, the GMFCS is a better indicator of gross motor functional impairment than the traditional categorization of CP that specifies the number of limbs with neurologic impairment. The neurodevelopmental assessment of young children is optimized by combining a standard neurologic examination with measures of gross and fine motor function (GMFCS and Bayley Psychomotor Developmental Index). Additional studies to examine longer term functional motor and adaptive-functional developmental skills are required to devise strategies that delineate therapies to optimize functional performance.

Neurofeedback Control of the Human GABAergic System Using Non-invasive Brain Stimulation.

PubMed

Koganemaru, Satoko; Mikami, Yusuke; Maezawa, Hitoshi; Ikeda, Satoshi; Ikoma, Katsunori; Mima, Tatsuya

2018-06-01

Neurofeedback has been a powerful method for self-regulating brain activities to elicit potential ability of human mind. GABA is a major inhibitory neurotransmitter in the central nervous system. Transcranial magnetic stimulation (TMS) is a tool that can evaluate the GABAergic system within the primary motor cortex (M1) using paired-pulse stimuli, short intracortical inhibition (SICI). Herein we investigated whether neurofeedback learning using SICI enabled us to control the GABAergic system within the M1 area. Forty-five healthy subjects were randomly divided into two groups: those receiving SICI neurofeedback learning or those receiving no neurofeedback (control) learning. During both learning periods, subjects made attempts to change the size of a circle, which was altered according to the degree of SICI in the SICI neurofeedback learning group, and which was altered independent of the degree of SICI in the control learning group. Results demonstrated that the SICI neurofeedback learning group showed a significant enhancement in SICI. Moreover, this group showed a significant reduction in choice reaction time compared to the control group. Our findings indicate that humans can intrinsically control the intracortical GABAergic system within M1 and can thus improve motor behaviors by SICI neurofeedback learning. SICI neurofeedback learning is a novel and promising approach to control our neural system and potentially represents a new therapy for patients with abnormal motor symptoms caused by CNS disorders. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Proximal movements compensate for distal forelimb movement impairments in a reach-to-eat task in Huntington's disease: new insights into motor impairments in a real-world skill.

PubMed

Klein, Alexander; Sacrey, Lori-Ann R; Dunnett, Stephen B; Whishaw, Ian Q; Nikkhah, Guido

2011-02-01

Huntington's disease (HD) causes severe motor impairments that are characterized by chorea, dystonia, and impaired fine motor control. The motor deficits include deficits in the control of the forelimb, but as yet there has been no comprehensive assessment of the impairments in arm, hand and digit movements as they are used in every-day tasks. The present study investigated the reaching of twelve HD subjects and twelve age-matched control subjects on a reach-to-eat task. The subjects were asked to reach for a small food item, with the left or the right hand, and then bring it to the mouth for eating. The task assesses the major features of skilled forelimb use, including orienting to a target, transport of the hand to a target, use of a precision grasp of the target, limb withdrawal to the mouth, and release of the food item into the mouth, and the integration of the movements into a smooth act. The movements were analyzed frame-by-frame by scoring the video record using an established movement element rating scale and by biometric analysis to describe limb trajectory. All HD subjects displayed greater reliance on more proximal movements in reaching. They also displayed overall jerkiness, a significant impairment in end point error correction (i.e. no smooth trajectories), deficits in timing and terminating motion (overshooting the target), impairments in rotation of the hand, abnormalities in grasping, and impairments in releasing the food item to the mouth. Although impairment in the control of the distal segments of the limb was common to all subjects, the intrusion of choreatic movements produced a pattern of highly variable performance between subjects. The quantification of reaching performance as measured by this analysis provides new insights into the impairments of HD subjects, allows an easily administered and inexpensive way to document the many skilled limb movement abnormalities, and relates the impairments to a real-world context. The protocol can serve as a useful clinical tool to evaluate innovative therapeutic interventions in HD such as physiotherapy, drug therapy, or functional neurosurgical procedures. Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Electrophysiological appraisal of relative segmental motoneurone pool excitability in flexor and extensor.

PubMed Central

Fisher, M A

1978-01-01

F responses recorded from flexor and extensor muscles were analysed in 18 normal subjects and in 16 patients with motor system abnormalities. The prominence of the F responses was evaluated quantitatively by determining the persistence--that is, the fraction of measurable F responses which actually occur after a series of supramaximal stimuli--and average amplitude of the F responses. In the normal resting state, the data are consistent with the hypothesis that the "central excitatory states" of motoneurones is greater in the antigravity muscles than in those muscles not stretched by gravity. This pattern was disrupted in eight of the 16 patients with motor system abnormalities caused by central nervous system lesions. These changes reflect a clinically testable aspect of the pathophysiology of certain motor system disorders. PMID:690640

Electroclinical findings of minor motor events during sleep in temporal lobe epilepsy.

PubMed

Giuliano, Loretta; Uccello, Denise; Fatuzzo, Daniela; Mainieri, Greta; Zappia, Mario; Sofia, Vito

2017-07-01

It is well known that sleep-related motor seizures can originate from the temporal lobe. However, little is known about the clinical features of minor motor manifestations during sleep in patients with temporal lobe epilepsy. The main objective of our study was to verify the existence of minor motor events during sleep in patients with mesial temporal lobe epilepsy (MTLE) and to define their clinical features and electroencephalography (EEG) correlations. We enrolled in the study patients with diagnosis of symptomatic MTLE and a group of healthy controls. All patients and controls underwent long-term video -EEG monitoring, including at least one night of nocturnal sleep. We analyzed all the movements recorded during nocturnal sleep of patients and controls and their electroencephalographic correlations. We analyzed the nocturnal sleep of 15 patients with symptomatic MTLE (8 males and 7 females; mean age ± standard deviation [SD]31.8 ± 14.9 years) and of 15 healthy controls (6 males and 9 females; mean age ± SD 32.8 ± 11.2 years). The analysis of movements during sleep revealed significant differences between groups, with the patients presenting significantly more movements in sleep than healthy controls (56.7 ± 39.2 vs. 15 ± 6.1; p < 0.001) with significant differences regarding oroalimentary automatisms, limb dystonia, straightening movements and gestural automatisms. EEG analysis showed that the proportion of movements preceded by EEG abnormalities was significantly higher in patients than in controls (57.8 ± 35.9 movements vs. 16.6 ± 13.4 movements; p < 0.001). The results of our study demonstrated the presence of minor motor events during sleep in patients with MTLE, suggesting an epileptic origin of these episodes. The study of nocturnal sleep in MTLE patients is useful in helping the clinicians in the diagnostic and therapeutic workup of these patients. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Purkinje cell heterotopy with cerebellar hypoplasia in two free-living American kestrels (Falco sparverius)

USDA-ARS?s Scientific Manuscript database

Two wild fledgling kestrels exhibited lack of motor coordination, postural reaction deficits, and abnormal propioception. At necropsy, the cerebellum and brainstem were markedly underdeveloped. Microscopically, there was Purkinje cells heterotopy, abnormal circuitry, and hypoplasia with defective fo...

Task-specific Dystonias

PubMed Central

Torres-Russotto, Diego; Perlmutter, Joel S.

2009-01-01

Task-specific dystonias are primary focal dystonias characterized by excessive muscle contractions producing abnormal postures during selective motor activities that often involve highly skilled, repetitive movements. Historically these peculiar postures were considered psychogenic but have now been classified as forms of dystonia. Writer’s cramp is the most commonly identified task-specific dystonia and has features typical of this group of disorders. Symptoms may begin with lack of dexterity during performance of a specific motor task with increasingly abnormal posturing of the involved body part as motor activity continues. Initially, the dystonia may manifest only during the performance of the inciting task, but as the condition progresses it may also occur during other activities or even at rest. Neurological exam is usually unremarkable except for the dystonia-related abnormalities. Although the precise pathophysiology remains unclear, increasing evidence suggests reduced inhibition at different levels of the sensorimotor system. Symptomatic treatment options include oral medications, botulinum toxin injections, neurosurgical procedures, and adaptive strategies. Prognosis may vary depending upon body part involved and specific type of task affected. Further research may reveal new insights into the etiology, pathophysiology, natural history, and improved treatment of these conditions. PMID:18990127

Can cerebral MRI at age 1 year predict motor and intellectual outcomes in very-low-birthweight children?

PubMed

Skranes, J; Vik, T; Nilsen, G; Smevik, O; Andersson, H W; Brubakk, A M

1998-04-01

This follow-up study reports on cerebral MRI findings in 20 very-low-birthweight (VLBW) infants without disabilities at age 1 year in relation to motor, intellectual, and perceptual function at age 6 years. MRI findings, anthropometrics, and Bayley Scales of Infant Development scores at age 1 year as predictors of psychomotor status at age 6 years are also evaluated and compared. Outcome parameters were the Peabody Developmental Motor Scales and the Wechsler Preschool and Primary Scale of Intelligence. The results show that infants with myelin hyperintensities including the centrum semiovale or with occipital hyperintensities with associated ventricular dilatation at age 1 scored lower on the Peabody Gross Motor Locomotion Scale at age 6 than infants with normal myelination or with isolated occipital hyperintensities. This may indicate damage to motor fibers caused by perinatal periventricular leukomalacia. No relation was found between abnormal MRI findings at age 1 and later fine motor, intellectual, and perceptual function. Comparing different age 1-year predictors, an abnormality score defined by MRI was used as an independent predictor of gross motor locomotion function at age 6 years. However, the Bayley Mental Development Index scores and weight at age 1 were more important predictors of later motor and intellectual outcome, respectively, than MRI findings. It is recommended that cerebral MRI should not be used routinely to examine VLBW infants without disabilities at 1 year of age.

Diabetes and driving safety: science, ethics, legality and practice.

PubMed

Cox, Daniel J; Singh, Harsimran; Lorber, Daniel

2013-04-01

Diabetes affects over 25 million people in the United States, most of whom are over the age of 16 and many of whom are licensed to drive a motor vehicle. Safe operation of a motor vehicle requires complex interactions of cognitive and motor functions and medical conditions that affect these functions often will increase the risk of motor vehicle accidents (MVA). In the case of diabetes, hypoglycemia is the most common factor that has been shown to increase MVA rates. When people with diabetes are compared with nondiabetic controls, systematic analyses show that the relative risk of MVA is increased by between 12% and 19% (Relative Risk Ratio 1.12-1.19). In comparison, the RRR for attention deficit hyperactivity disorder is 4.4 and for sleep apnea is 2.4. Epidemiologic research suggests that patients at risk for hypoglycemia-related MVAs may have some characteristics in common, including a history of severe hypoglycemia or of hypoglycemia-related driving mishaps. Experimental studies also have shown that people with a history of hypoglycemia-related driving mishaps have abnormal counter-regulatory responses to hypoglycemia and greater cognitive impairments during moderate hypoglycemia.

Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case-Control Pilot Study.

PubMed

Pedapati, Ernest V; Gilbert, Donald L; Erickson, Craig A; Horn, Paul S; Shaffer, Rebecca C; Wink, Logan K; Laue, Cameron S; Wu, Steve W

2016-09-01

This case-control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. We studied youth with ASD aged 11-18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing.

Generalized epilepsy syndromes and callosal thickness: Differential effects between patients with juvenile myoclonic epilepsy and those with generalized tonic-clonic seizures alone.

PubMed

Anastasopoulou, Stavroula; Kurth, Florian; Luders, Eileen; Savic, Ivanka

2017-01-01

The definition of two well-studied genetic generalized epilepsy syndromes (GGE) - juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures alone (GTCS) - suggests the absence of structural cerebral abnormalities. Nevertheless, there are various reports of such abnormalities (especially in JME), where effects mainly occur within thalamus and mesial prefrontal regions. This raises the question of whether JME is particularly linked to midline structure abnormalities, which may also involve the corpus callosum. We studied callosal morphology in a well-matched sample of 22 JME patients, 15 GTCS patients, and 42 controls (CTL) for all of whom we obtained T1-weighted data on a 3T MRI scanner. More specifically, we measured callosal thickness at 100 equidistant points across the callosal surface, and subsequently compared the three groups (JME, GTCS, and CTL) against each other. Significant differences between JME patients and controls were observed within the callosal genu, anterior midbody, and isthmus, with thinner regions in JME patients. There were no significant differences between GTCS patients and controls, and also not between JME patients and GTCS patients. The present outcomes point to callosal abnormalities in JME patients suggesting an impairment of interhemisperic communication between prefrontal, motor, parietal and temporal cortices. These findings further support the notion that structural aberrations are present and differentiated across GGE syndromes, with significant callosal deviations from normality in JME. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Ventral striatal hyperconnectivity during rewarded interference control in adolescents with ADHD.

PubMed

Ma, Ili; van Holstein, Mieke; Mies, Gabry W; Mennes, Maarten; Buitelaar, Jan; Cools, Roshan; Cillessen, Antonius H N; Krebs, Ruth M; Scheres, Anouk

2016-09-01

Attention-deficit/hyperactivity disorder (ADHD) is characterized by cognitive deficits (e.g., interference control) and altered reward processing. Cognitive control is influenced by incentive motivation and according to current theoretical models, ADHD is associated with abnormal interactions between incentive motivation and cognitive control. However, the neural mechanisms by which reward modulates cognitive control in individuals with ADHD are unknown. We used event-related functional resonance imaging (fMRI) to study neural responses during a rewarded Stroop color-word task in adolescents (14-17 years) with ADHD (n = 25; 19 boys) and healthy controls (n = 33; 22 boys). Adolescents with ADHD showed increased reward signaling within the superior frontal gyrus and ventral striatum (VS) relative to controls. Importantly, functional connectivity analyses revealed a hyperconnectivity between VS and motor control regions in the ADHD group, as a function of reward-cognitive control integration. Connectivity was associated with performance improvement in controls but not in the ADHD group, suggesting inefficient connectivity. Adolescents with ADHD show increased neural sensitivity to rewards and its interactions with interference control in VS and motor regions, respectively. The findings support theoretical models of altered reward-cognitive control integration in individuals with ADHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of prenatal dexamethasone treatment on physical growth, pituitary-adrenal hormones, and performance of motor, motivational, and cognitive tasks in juvenile and adolescent common marmoset monkeys.

PubMed

Hauser, Jonas; Knapman, Alana; Zürcher, Nicole R; Pilloud, Sonia; Maier, Claudia; Diaz-Heijtz, Rochellys; Forssberg, Hans; Dettling, Andrea; Feldon, Joram; Pryce, Christopher R

2008-12-01

Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to prevent respiratory distress syndrome in preterm infants, but there is emerging evidence of subsequent neurobehavioral abnormalities (e.g. problems with inattention/hyperactivity). In the present study, we exposed pregnant common marmosets (Callithrix jacchus, primates) to daily repeated DEX (5 mg/kg by mouth) during either early (d 42-48) or late (d 90-96) pregnancy (gestation period of 144 days). Relative to control, and with a longitudinal design, we investigated DEX effects in offspring in terms of physical growth, plasma ACTH and cortisol titers, social and maintenance behaviors, skilled motor reaching, motivation for palatable reward, and learning between infancy and adolescence. Early DEX resulted in reduced sociability in infants and increased motivation for palatable reward in adolescents. Late DEX resulted in a mild transient increase in knee-heel length in infants and enhanced reversal learning of stimulus-reward association in adolescents. There was no effect of either early or late DEX on basal plasma ACTH or cortisol titers. Both treatments resulted in impaired skilled motor reaching in juveniles, which attenuated in early DEX but persisted in late DEX across test sessions. The increased palatable-reward motivation and decreased social motivation observed in early DEX subjects provide experimental support for the clinical reports that prenatal glucocorticoid treatment impairs social development and predisposes to metabolic syndrome. These novel primate findings indicate that fetal glucocorticoid overexposure can lead to abnormal development of motor, affective, and cognitive behaviors. Importantly, the outcome is highly dependent upon the timing of glucocorticoid overexposure.

Abnormally reduced primary motor cortex output is related to impaired hand function in chronic stroke.

PubMed

Buetefisch, Cathrin M; Pirog Revill, Kathleen; Haut, Marc W; Kowalski, Greg M; Wischnewski, Miles; Pifer, Marissa; Belagaje, Samir R; Nahab, Fadi; Cobia, Derin J; Hu, Xiaoping; Drake, Daniel; Hobbs, Gerald

2018-06-20

Stroke often involves primary motor cortex (M1) and its corticospinal projections (CST). As hand function is critically dependent on these structures, its recovery is often incomplete. The neuronal substrate supporting affected hand function is not well understood but likely involves reorganized M1 and CST of the lesioned hemisphere (M1 IL and CST IL ). We hypothesized that affected hand function in chronic stroke is related to structural and functional reorganization of M1 IL and CST IL . We tested 18 patients with chronic ischemic stroke involving M1 or CST. Their hand function was compared to 18 age matched healthy subjects. M1 IL thickness and CST IL fractional anisotropy (FA) were determined with MRI and compared to measures of the other hemisphere. Transcranial magnetic stimulation (TMS) was applied to M1 IL to determine its input output function (stimulus response curve, SRC). The plateau of the SRC (MEPmax), inflection point and slope parameters of the curve were extracted. Results were compared to measures in 12 age matched healthy controls. MEPmax of M1 IL was significantly smaller (p=0.02) in the patients, indicating reduced CST IL motor output, and was correlated with impaired hand function (p=0.02). M1 IL thickness (p<0.01) and CST IL -FA (p<0.01) were reduced but did not correlate with hand function. The results indicate that employed M1 IL or CST IL structural measures do not explain the extent of impairment in hand function once M1 and CST are sufficiently functional for TMS to evoke a motor potential. Instead, impairment of hand function is best explained by the abnormally low output from M1 IL .

Quantitative assessment of motor speech abnormalities in idiopathic rapid eye movement sleep behaviour disorder.

PubMed

Rusz, Jan; Hlavnička, Jan; Tykalová, Tereza; Bušková, Jitka; Ulmanová, Olga; Růžička, Evžen; Šonka, Karel

2016-03-01

Patients with idiopathic rapid eye movement sleep behaviour disorder (RBD) are at substantial risk for developing Parkinson's disease (PD) or related neurodegenerative disorders. Speech is an important indicator of motor function and movement coordination, and therefore may be an extremely sensitive early marker of changes due to prodromal neurodegeneration. Speech data were acquired from 16 RBD subjects and 16 age- and sex-matched healthy control subjects. Objective acoustic assessment of 15 speech dimensions representing various phonatory, articulatory, and prosodic deviations was performed. Statistical models were applied to characterise speech disorders in RBD and to estimate sensitivity and specificity in differentiating between RBD and control subjects. Some form of speech impairment was revealed in 88% of RBD subjects. Articulatory deficits were the most prominent findings in RBD. In comparison to controls, the RBD group showed significant alterations in irregular alternating motion rates (p = 0.009) and articulatory decay (p = 0.01). The combination of four distinctive speech dimensions, including aperiodicity, irregular alternating motion rates, articulatory decay, and dysfluency, led to 96% sensitivity and 79% specificity in discriminating between RBD and control subjects. Speech impairment was significantly more pronounced in RBD subjects with the motor score of the Unified Parkinson's Disease Rating Scale greater than 4 points when compared to other RBD individuals. Simple quantitative speech motor measures may be suitable for the reliable detection of prodromal neurodegeneration in subjects with RBD, and therefore may provide important outcomes for future therapy trials. Copyright © 2015 Elsevier B.V. All rights reserved.

MRI abnormalities of peripheral nerve and muscle are common in amyotrophic lateral sclerosis and share features with multifocal motor neuropathy

PubMed Central

Staff, Nathan P.; Amrami, Kimberly K.; Howe, Benjamin M.

2015-01-01

Introduction MRI of peripheral nerve and muscle in patients with ALS may be performed to investigate alternative diagnoses including multifocal motor neuropathy (MMN). MRI findings of peripheral nerve and muscle are not well described in these conditions, making interpretation of results difficult. Methods We examined systematically the peripheral nerve and muscle MRI findings in patients with ALS (n=60) and MMN (n=8). Results In patients with ALS and MMN, abnormal MRIs were common (85% and 75%, respectively) but did not correlate with disease severity. Peripheral nerve MRI abnormalities were similar in frequency (ALS: 58% vs. MMN: 63%) with most changes being of mild-to-moderate severity. Muscle MRI changes were more common in ALS (57% vs. 33%), and no muscle atrophy was seen in patients with MMN. Discussion MRI abnormalities of peripheral nerve and muscle in ALS and MMN are common and share some features. PMID:25736373

Nonverbal expressive behaviour in schizophrenia and social phobia.

PubMed

Del-Monte, Jonathan; Raffard, Stéphane; Salesse, Robin N; Marin, Ludovic; Schmidt, Richard C; Varlet, Manuel; Bardy, Benoît G; Philippe Boulenger, Jean; Christine Gély-Nargeot, Marie; Capdevielle, Delphine

2013-11-30

Expressive behaviour plays a crucial role in the success of social interactions. Abnormality of expressive behaviour has been reported in interpersonal interactions of patients suffering from schizophrenia and social phobia, two debilitating mental disorders with important social deficits. However, no study has compared the expressive behaviour in these two disorders. Thirty schizophrenia patients, 21 social phobia patients and 30 healthy controls were evaluated and compared on expressive, cognitive and clinical dimensions. Expressive behaviour was assessed using the Motor Affective subscale of the Motor-Affective-Social-Scale (MASS). Covariables include the Positive and Negative Syndrome Scale (PANSS), the anxiety level Liebowitz-Social-Anxiety-Scale (LSAS) and cognitive tasks. After controlling for depression, schizophrenia and social phobia patients both exhibited significantly fewer expressive behaviours compared to healthy controls. Moreover, our results showed specific signatures: schizophrenia patients performed fewer spontaneous gestures (hand gestures and smiles) whereas social phobia patients had an impaired ability to produce voluntary smiles in comparison to healthy controls. Interestingly, poor social functioning was significantly correlated with a decrease of expressive behaviour for schizophrenia patients. Expressive behaviour is impaired in different ways in social phobia and schizophrenia and is associated in schizophrenia with poorer social functioning. The Motor Affective subscale of the MASS is an interesting tool for assessing the dysfunction of interpersonal expressive behaviour in mental disorders. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Inter-relation between "classic" motor neuron disease and frontotemporal dementia: neuropsychological and single photon emission computed tomography study.

PubMed Central

Talbot, P R; Goulding, P J; Lloyd, J J; Snowden, J S; Neary, D; Testa, H J

1995-01-01

The purpose of this study was to examine the possible association between "classic" motor neuron disease (cMND) and frontotemporal dementia (FTD), using neuropsychological evaluation and single photon emission computed tomography (SPECT). Psychological tests assessing language, perceptuospatial, memory, and "frontal lobe" functions were given to patients with cMND and test scores were compared with those of normal control subjects. 99mTc-HMPAO SPECT was performed on patients with cMND, FTD and motor neuron disease (FTD/MND), FTD alone, and normal control subjects. Regional cerebral blood flow indices (rCBFi) were determined in 36 cortical regions, and differences between grouped rCBFi data were investigated by canonical discriminant analysis. There were significant group differences in the scores of picture sequencing and token tests in patients with cMND compared with normal controls. Regional CBFi data showed frontal and anterior temporal reductions in patients with cMND compared with normal controls. A similar pattern of SPECT abnormality was seen in patients with FTD/MND and FTD alone, but to a more pronounced degree than in patients with cMND. Neuropsychological and SPECT findings in cMND, FTD/MND, and FTD showed a common pattern of cerebral involvement, most pronounced in the second two conditions. It is suggested that cMND, FTD/MND, and FTD represent a clinical range of a pathological continuum. Images PMID:7745399

The Neurocognitive and MRI Outcomes of West Nile Virus Infection: Preliminary Analysis Using an External Control Group.

PubMed

Murray, Kristy O; Nolan, Melissa S; Ronca, Shannon E; Datta, Sushmita; Govindarajan, Koushik; Narayana, Ponnada A; Salazar, Lucrecia; Woods, Steven P; Hasbun, Rodrigo

2018-01-01

To understand the long-term neurological outcomes resultant of West Nile virus (WNV) infection, participants from a previously established, prospective WNV cohort were invited to take part in a comprehensive neurologic and neurocognitive examination. Those with an abnormal exam finding were invited for MRI to evaluate cortical thinning and regional brain atrophy following infection. Correlations of presenting clinical syndrome with neurologic and neurocognitive dysfunctions were evaluated, as well as correlations of neurocognitive outcomes with MRI results. From 2002 to 2012, a total of 262 participants with a history of WNV infection were enrolled as research participants in a longitudinal cohort study, and 117 completed comprehensive neurologic and neurocognitive evaluations. Abnormal neurological exam findings were identified in 49% (57/117) of participants, with most abnormalities being unilateral. The most common abnormalities included decreased strength (26%; 30/117), abnormal reflexes (14%; 16/117), and tremors (10%; 12/117). Weakness and decreased reflexes were consistent with lower motor neuron damage in a significant proportion of patients. We observed a 22% overall rate of impairment on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), with impairments observed in immediate (31%) and delayed memory (25%). On MRI, participants showed significant cortical thinning as compared to age- and gender-matched controls in both hemispheres, with affected regions primarily occurring in the frontal and limbic cortices. Regional atrophy occurred in the cerebellum, brain stem, thalamus, putamen, and globus pallidus. This study provides valuable new information regarding the neurological outcomes following WNV infection, with MRI evidence of significant cortical thinning and regional atrophy; however, it is important to note that the results may include systemic bias due to the external control group. Considering no effective treatment measures are available, strategies to prevent infection are key.

Abnormal intrinsic functional hubs in alcohol dependence: evidence from a voxelwise degree centrality analysis.

PubMed

Luo, Xiaoping; Guo, Linghong; Dai, Xi-Jian; Wang, Qinglai; Zhu, Wenzhong; Miao, Xinjun; Gong, Honghan

2017-01-01

To explore the abnormal intrinsic functional hubs in alcohol dependence using voxelwise degree centrality analysis approach, and their relationships with clinical features. Twenty-four male alcohol dependence subjects free of medicine (mean age, 50.21±9.62 years) and 24 age- and education-matched male healthy controls (mean age, 50.29±8.92 years) were recruited. The alcohol use disorders identification test and the severity of alcohol dependence questionnaire (SADQ) were administered to assess the severity of alcohol craving. Voxelwise degree centrality approach was used to assess the abnormal intrinsic functional hubs features in alcohol dependence. Simple linear regression analysis was performed to investigate the relationships between the clinical features and abnormal intrinsic functional hubs. Compared with healthy controls, alcohol dependence subjects exhibited significantly different degree centrality values in widespread left lateralization brain areas, including higher degree centrality values in the left precentral gyrus (BA 6), right hippocampus (BA 35, 36), and left orbitofrontal cortex (BA 11) and lower degree centrality values in the left cerebellum posterior lobe, bilateral secondary visual network (BA 18), and left precuneus (BA 7, 19). SADQ revealed a negative linear correlation with the degree centrality value in the left precentral gyrus ( R 2 =0.296, P =0.006). The specific abnormal intrinsic functional hubs appear to be disrupted by alcohol intoxication, which implicates at least three principal neural systems: including cerebellar, executive control, and visual cortex, which may further affect the normal motor behavior such as an explicit type of impaired driving behavior. These findings expand our understanding of the functional characteristics of alcohol dependence and may provide a new insight into the understanding of the dysfunction and pathophysiology of alcohol dependence.

Motor development and sensory processing: A comparative study between preterm and term infants.

PubMed

Cabral, Thais Invenção; Pereira da Silva, Louise Gracelli; Tudella, Eloisa; Simões Martinez, Cláudia Maria

2014-10-16

Infants born preterm and/or with low birth weight may present a clinical condition of organic instability and usually face a long period of hospitalization in the Neonatal Intensive Care Units, being exposed to biopsychosocial risk factors to their development due to decreased spontaneous movement and excessive sensory stimuli. This study assumes that there are relationships between the integration of sensory information of preterm infants, motor development and their subsequent effects. To evaluate the sensory processing and motor development in preterm infants aged 4-6 months and compare performance data with their peers born at term. This was a cross-sectional and comparative study consisting of a group of preterm infants (n=15) and a group of term infants (n=15), assessed using the Test of Sensory Functions in Infants (TSFI) and the Alberta Infant Motor Scale (AIMS). The results showed no significant association between motor performance on the AIMS scale (total score) and sensory processing in the TSFI (total score). However, all infants who scored abnormal in the total TSFI score, subdomain 1, and subdomain 5 presented motor performance at or below the 5th percentile on the AIMS scale. Since all infants who presented definite alteration in tolerating tactile deep pressure and poor postural control are at risk of delayed gross motor development, there may be peculiarities not detected by the tests used that seem to establish some relationship between sensory processing and motor development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Congenital sensory neuropathy

PubMed Central

Barry, J. E.; Hopkins, I. J.; Neal, B. W.

1974-01-01

Two infants with sporadic congenital sensory neuropathy are described. The criteria of generalized lack of superficial sensory appreciation, hypotonia, areflexia, together with histological evidence of abnormalities of sensory neural structures in skin and peripheral nerves have been met. No abnormality of motor or autonomic nerves was shown. ImagesFIG. PMID:4131674

The effect of sensory uncertainty due to amblyopia (lazy eye) on the planning and execution of visually-guided 3D reaching movements.

PubMed

Niechwiej-Szwedo, Ewa; Goltz, Herbert C; Chandrakumar, Manokaraananthan; Wong, Agnes M F

2012-01-01

Impairment of spatiotemporal visual processing in amblyopia has been studied extensively, but its effects on visuomotor tasks have rarely been examined. Here, we investigate how visual deficits in amblyopia affect motor planning and online control of visually-guided, unconstrained reaching movements. Thirteen patients with mild amblyopia, 13 with severe amblyopia and 13 visually-normal participants were recruited. Participants reached and touched a visual target during binocular and monocular viewing. Motor planning was assessed by examining spatial variability of the trajectory at 50-100 ms after movement onset. Online control was assessed by examining the endpoint variability and by calculating the coefficient of determination (R(2)) which correlates the spatial position of the limb during the movement to endpoint position. Patients with amblyopia had reduced precision of the motor plan in all viewing conditions as evidenced by increased variability of the reach early in the trajectory. Endpoint precision was comparable between patients with mild amblyopia and control participants. Patients with severe amblyopia had reduced endpoint precision along azimuth and elevation during amblyopic eye viewing only, and along the depth axis in all viewing conditions. In addition, they had significantly higher R(2) values at 70% of movement time along the elevation and depth axes during amblyopic eye viewing. Sensory uncertainty due to amblyopia leads to reduced precision of the motor plan. The ability to implement online corrections depends on the severity of the visual deficit, viewing condition, and the axis of the reaching movement. Patients with mild amblyopia used online control effectively to compensate for the reduced precision of the motor plan. In contrast, patients with severe amblyopia were not able to use online control as effectively to amend the limb trajectory especially along the depth axis, which could be due to their abnormal stereopsis.

The Effect of Sensory Uncertainty Due to Amblyopia (Lazy Eye) on the Planning and Execution of Visually-Guided 3D Reaching Movements

PubMed Central

Niechwiej-Szwedo, Ewa; Goltz, Herbert C.; Chandrakumar, Manokaraananthan; Wong, Agnes M. F.

2012-01-01

Background Impairment of spatiotemporal visual processing in amblyopia has been studied extensively, but its effects on visuomotor tasks have rarely been examined. Here, we investigate how visual deficits in amblyopia affect motor planning and online control of visually-guided, unconstrained reaching movements. Methods Thirteen patients with mild amblyopia, 13 with severe amblyopia and 13 visually-normal participants were recruited. Participants reached and touched a visual target during binocular and monocular viewing. Motor planning was assessed by examining spatial variability of the trajectory at 50–100 ms after movement onset. Online control was assessed by examining the endpoint variability and by calculating the coefficient of determination (R2) which correlates the spatial position of the limb during the movement to endpoint position. Results Patients with amblyopia had reduced precision of the motor plan in all viewing conditions as evidenced by increased variability of the reach early in the trajectory. Endpoint precision was comparable between patients with mild amblyopia and control participants. Patients with severe amblyopia had reduced endpoint precision along azimuth and elevation during amblyopic eye viewing only, and along the depth axis in all viewing conditions. In addition, they had significantly higher R2 values at 70% of movement time along the elevation and depth axes during amblyopic eye viewing. Conclusion Sensory uncertainty due to amblyopia leads to reduced precision of the motor plan. The ability to implement online corrections depends on the severity of the visual deficit, viewing condition, and the axis of the reaching movement. Patients with mild amblyopia used online control effectively to compensate for the reduced precision of the motor plan. In contrast, patients with severe amblyopia were not able to use online control as effectively to amend the limb trajectory especially along the depth axis, which could be due to their abnormal stereopsis. PMID:22363549

[Magnetic resonance imaging features in two Chinese family with congenital fibrosis of extraocular muscles].

PubMed

Wu, Li; Zhou, Lian-Hong; Liu, Chang-Sheng; Cha, Yun-Fei; Wang, Jiong; Xing, Yi-Qiao

2009-11-01

The aim of this article was to investigate the structural basis of ocular motility and visual abnormalities in humans with congenital fibrosis of the extraocular muscles (CFEOM). 17 volunteers from 2 CFEOM pedigrees Clinical ophthalmic and motility examed and 18 normal control subjects were correlated with thin-sectioned magnetic resonance imaging (MRI) across the orbit and the brain-stem level. Subjects with CFEOM had severe bilateral blepharoptosis, limited supraduction, and variable ophthalmoplegia. In affected subjects, MRI demonstrated atrophy of the levator palpebrae superioris, all EOMs, and the optic nerves, and small or absent orbital motor nerves. The oculomotor nerve was most severely hypoplastic, but the abducens was also affected. Subjects with CFEOM exhibited subclinical but highly significant reduction from normal in mean optic nerve size (P < 0.05). There are also some difference between the two CFEOM pedigrees. These findings suggest that neuronal disease is primary in CFEOM, with myopathy arising secondary to abnormal innervation and the oculomotor nucleus and trochlear nucleus of the abnormalities defects.

Neurophysiological Outcomes of mTBI

DTIC Science & Technology

2017-03-28

position : an experimental approach to timing and working memory deficits in schizophrenia. Journal of abnormal psychology . 2004 Nov; 113(4 ):509 . Gilaie...clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing. Journal of abnormal child psychology . 2003 Jun 1 ;31 (3) :301-13...disorder (ADHD). Journal of abnormal child psychology . 2005 Oct 1 ;33(5):639-54. Toplak ME, Ruckl idge JJ , Hetherington R, John SC, Tannock R. Time

Esophageal hypomotility and spastic motor disorders: current diagnosis and treatment.

PubMed

Valdovinos, Miguel A; Zavala-Solares, Monica R; Coss-Adame, Enrique

2014-11-01

Esophageal hypomotility (EH) is characterized by abnormal esophageal peristalsis, either from a reduction or absence of contractions, whereas spastic motor disorders (SMD) are characterized by an increase in the vigor and/or propagation velocity of esophageal body contractions. Their pathophysiology is not clearly known. The reduced excitation of the smooth muscle contraction mediated by cholinergic neurons and the impairment of inhibitory ganglion neuronal function mediated by nitric oxide are likely mechanisms of the peristaltic abnormalities seen in EH and SMD, respectively. Dysphagia and chest pain are the most frequent clinical manifestations for both of these dysfunctions, and gastroesophageal reflux disease (GERD) is commonly associated with these motor disorders. The introduction of high-resolution manometry (HRM) and esophageal pressure topography (EPT) has significantly enhanced the ability to diagnose EH and SMD. Novel EPT metrics in particular the development of the Chicago Classification of esophageal motor disorders has enabled improved characterization of these abnormalities. The first step in the management of EH and SMD is to treat GERD, especially when esophageal testing shows pathologic reflux. Smooth muscle relaxants (nitrates, calcium channel blockers, 5-phosphodiesterase inhibitors) and pain modulators may be useful in the management of dysphagia or pain in SMD. Endoscopic Botox injection and pneumatic dilation are the second-line therapies. Extended myotomy of the esophageal body or peroral endoscopic myotomy (POEM) may be considered in highly selected cases but lack evidence.

Equine protozoal myeloencephalitis due to Neospora hughesi and equine motor neuron disease in a mule.

PubMed

Finno, Carrie J; Eaton, Joshua Seth; Aleman, Monica; Hollingsworth, Steven R

2010-07-01

A 23-year-old female mule was presented for bilateral ocular abnormalities and an abnormal pelvic limb gait. Anisocoria, unilateral enophthalmos, medial strabismus, ptosis, pupillary light reflex deficits, and bilateral reticulated pigmentary retinopathy were observed on ophthalmic examination. Neurologic abnormalities included right-sided facial nerve paralysis, extensive symmetric muscle atrophy, and asymmetric pelvic limb ataxia with an abnormal pelvic limb gait. A positive titer (1:40) for equine protozoal myeloencephalitis (EPM) associated with Neospora hughesi was obtained from cerebrospinal fluid with minimal (<1 red blood cell/microL) blood contamination. Muscle biopsies of the sacrocaudalis dorsalis medialis muscle revealed predominantly type I neurogenic muscle atrophy, consistent with a diagnosis of equine motor neuron disease (EMND). Treatment included a 2-month course of ponazuril (5 mg/kg PO q24 h), vitamin E (8000 IU PO q24 h), and selenium (2 mg PO q24 h). Clinical improvement was not observed after 2 months although the mule remained stable. Clinical deterioration was reported upon discontinuation of the ponazuril after a 2-month course. Concurrent disease with EPM associated with N. hughesi and EMND should be considered in cases demonstrating cranial nerve abnormalities, pronounced symmetric muscle atrophy, unusual asymmetric gait abnormalities, and reticulated pigmentary retinopathy.

Extent and Location of the Excitatory and Inhibitory Cortical Hand Representation Maps: A Navigated Transcranial Magnetic Stimulation Study.

PubMed

Pitkänen, Minna; Kallioniemi, Elisa; Julkunen, Petro

2015-09-01

Voluntary muscle action and control are modulated by the primary motor cortex, which is characterized by a well-defined somatotopy. Muscle action and control depend on a sensitive balance between excitatory and inhibitory mechanisms in the cortex and in the corticospinal tract. The cortical locations evoking excitatory and inhibitory responses in brain stimulation can be mapped, for example, as a pre-surgical procedure. The purpose of this study was to find the differences between excitatory and inhibitory motor representations mapped using navigated transcranial magnetic stimulation (nTMS). The representations of small hand muscles were mapped to determine the areas and the center of gravities (CoGs) in both hemispheres of healthy right-handed volunteers. The excitatory representations were obtained via resting motor evoked potential (MEP) mapping, with and without a stimulation grid. The inhibitory representations were mapped using the grid and measuring corticospinal silent periods (SPs) during voluntary muscle contraction. The excitatory representations were larger on the dominant hemisphere compared with the non-dominant (p < 0.05). The excitatory CoGs were more medial (p < 0.001) and anterior (p < 0.001) than the inhibitory CoGs. The use of the grid did not influence the areas or the CoGs. The results support the common hypothesis that the MEP and SP representations are located at adjacent sites. Furthermore, the dominant hemisphere seems to be better organized for controlling excitatory motor functions with respect to TMS. In addition, the inhibitory representations could provide further information about motor reorganization and aid in surgery planning when the functional cortical representations are located in abnormal cortical regions.

Pulmonary function in patients with Huntington’s Disease

PubMed Central

2014-01-01

Background Huntington’s disease (HD) is a neurodegenerative disorder characterized by progressive motor, cognitive and psychiatric disturbances. Chest muscle rigidity, respiratory muscle weakness, difficulty in clearing airway secretions and swallowing abnormalities have been described in patients with neurodegenerative disorders including HD. However limited information is available regarding respiratory function in HD patients. The purpose of this study was to investigate pulmonary function of patients with HD in comparison to healthy volunteers, and its association with motor severity. Methods Pulmonary function measures were taken from 18 (11 male, 7 female) manifest HD patients (53 ± 10 years), and 18 (10 male, 8 female) healthy volunteers (52 ± 11 years) with similar anthropometric and life-style characteristics to the recruited HD patients. Motor severity was quantified by the Unified Huntington’s Disease Rating Scale-Total Motor Score (UHDRS-TMS). Maximum respiratory pressure was measured on 3 separate days with a week interval to assess test-retest reliability. Results The test-retest reliability of maximum inspiratory and expiratory pressure measurements was acceptable for both HD patient and control groups (ICC ≥0.92), but the values over 3 days were more variable in the HD group (CV < 11.1%) than in the control group (CV < 7.6%). The HD group showed lower respiratory pressure, forced vital capacity, peak expiratory flow and maximum voluntary ventilation than the control group (p < 0.05). Forced vital capacity, maximum voluntary ventilation and maximum respiratory pressures were negatively (r = -0.57; -0.71) correlated with the UHDRS-TMS (p < 0.05). Conclusion Pulmonary function is decreased in manifest HD patients, and the magnitude of the decrease is associated with motor severity. PMID:24886346

Differences in short-term primary motor cortex synaptic potentiation as assessed by repetitive transcranial magnetic stimulation in migraine patients with and without aura.

PubMed

Conte, Antonella; Barbanti, Piero; Frasca, Vittorio; Iacovelli, Elisa; Gabriele, Maria; Giacomelli, Elena; Aurilia, Cinzia; Pichiorri, Floriana; Gilio, Francesca; Inghilleri, Maurizio

2010-01-01

To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate-dependent short-term synaptic potentiation and GABA-dependent inhibitory cortical interneuron excitability as assessed by 5Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5Hz-rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5Hz-rTMS in the three groups tested. The 5Hz-rTMS-induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5Hz-rTMS both outside and during the attack suggesting that glutamate-dependent short-term M1 cortical potentiation patterns differ in migraine with and without aura. Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Disturbances of motor unit rate modulation are prevalent in muscles of spastic-paretic stroke survivors

PubMed Central

Heckman, C. J.; Powers, R. K.; Rymer, W. Z.; Suresh, N. L.

2014-01-01

Stroke survivors often exhibit abnormally low motor unit firing rates during voluntary muscle activation. Our purpose was to assess the prevalence of saturation in motor unit firing rates in the spastic-paretic biceps brachii muscle of stroke survivors. To achieve this objective, we recorded the incidence and duration of impaired lower- and higher-threshold motor unit firing rate modulation in spastic-paretic, contralateral, and healthy control muscle during increases in isometric force generated by the elbow flexor muscles. Impaired firing was considered to have occurred when firing rate became constant (i.e., saturated), despite increasing force. The duration of impaired firing rate modulation in the lower-threshold unit was longer for spastic-paretic (3.9 ± 2.2 s) than for contralateral (1.4 ± 0.9 s; P < 0.001) and control (1.1 ± 1.0 s; P = 0.005) muscles. The duration of impaired firing rate modulation in the higher-threshold unit was also longer for the spastic-paretic (1.7 ± 1.6 s) than contralateral (0.3 ± 0.3 s; P = 0.007) and control (0.1 ± 0.2 s; P = 0.009) muscles. This impaired firing rate of the lower-threshold unit arose, despite an increase in the overall descending command, as shown by the recruitment of the higher-threshold unit during the time that the lower-threshold unit was saturating, and by the continuous increase in averages of the rectified EMG of the biceps brachii muscle throughout the rising phase of the contraction. These results suggest that impairments in firing rate modulation are prevalent in motor units of spastic-paretic muscle, even when the overall descending command to the muscle is increasing. PMID:24572092

Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6-hydroxydopamine lesioned rat without sensitizing motor behaviours.

PubMed

Lane, E L; Cheetham, S C; Jenner, P

2005-01-01

BTS 74 398 (1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-(3-diaminethylaminopropylthio)ethanone monocitrate) is a monoamine reuptake inhibitor that reverses motor deficits in MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmosets without provoking established dyskinesia. However, it is not known whether BTS 74 398 primes the basal ganglia for dyskinesia induction. In this study, the ability of BTS 74 398 to sensitize 6-hydroxydopamine (6-OHDA)-lesioned rats for the production of abnormal motor behaviours and the induction of striatal DeltaFosB were determined in comparison with l-3,4-dihydroxyphenylalanine methyl ester (L-dopa). Acute administration of BTS 74 398 induced a dose-dependent ipsilateral circling response in unilaterally 6-OHDA-lesioned rats whereas L-dopa produced dose-dependent contraversive rotation. The ipsilateral circling response to BTS 74 398 did not alter during 21 days of administration. In contrast, L-dopa treatment for 21 days caused a marked increase in rotational response. Repeated administration of both L-dopa and BTS 74 398 increased general motor activity and stereotypic behaviour. In L-dopa-treated rats, orolingual, locomotive, forelimb and axial abnormal movements developed whereas BTS 74 398 produced only locomotion with a side bias but no other abnormal movements. Sensitization of circling responses and the development of abnormal movements in 6-OHDA-lesioned rats have been associated with the potential of dopaminergic drugs to induce dyskinesia. Furthermore, striatal DeltaFosB immunoreactivity, shown to correlate with dyskinesia induction, was increased by L-dopa but was unaffected by repeated BTS 74 398 administration. The lack of such changes following repeated BTS 74 398 treatment suggests that it may be an effective antiparkinsonian therapy that is unlikely to produce involuntary movements.

Motor Deficits and Decreased Striatal Dopamine Receptor 2 Binding Activity in the Striatum-Specific Dyt1 Conditional Knockout Mice

PubMed Central

Yokoi, Fumiaki; Dang, Mai Tu; Li, Jianyong; Standaert, David G.; Li, Yuqing

2011-01-01

DYT1 early-onset generalized dystonia is a hyperkinetic movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Recently, significant progress has been made in studying pathophysiology of DYT1 dystonia using targeted mouse models. Dyt1 ΔGAG heterozygous knock-in (KI) and Dyt1 knock-down (KD) mice exhibit motor deficits and alterations of striatal dopamine metabolisms, while Dyt1 knockout (KO) and Dyt1 ΔGAG homozygous KI mice show abnormal nuclear envelopes and neonatal lethality. However, it has not been clear whether motor deficits and striatal abnormality are caused by Dyt1 mutation in the striatum itself or the end results of abnormal signals from other brain regions. To identify the brain region that contributes to these phenotypes, we made a striatum-specific Dyt1 conditional knockout (Dyt1 sKO) mouse. Dyt1 sKO mice exhibited motor deficits and reduced striatal dopamine receptor 2 (D2R) binding activity, whereas they did not exhibit significant alteration of striatal monoamine contents. Furthermore, we also found normal nuclear envelope structure in striatal medium spiny neurons (MSNs) of an adult Dyt1 sKO mouse and cerebral cortical neurons in cerebral cortex-specific Dyt1 conditional knockout (Dyt1 cKO) mice. The results suggest that the loss of striatal torsinA alone is sufficient to produce motor deficits, and that this effect may be mediated, at least in part, through changes in D2R function in the basal ganglia circuit. PMID:21931745

Electroacupuncture remediates glial dysfunction and ameliorates neurodegeneration in the astrocytic α-synuclein mutant mouse model.

PubMed

Deng, Jiahui; Lv, E; Yang, Jian; Gong, Xiaoli; Zhang, Wenzhong; Liang, Xibin; Wang, Jiazeng; Jia, Jun; Wang, Xiaomin

2015-05-28

The acupuncture or electroacupuncture (EA) shows the therapeutic effect on various neurodegenerative diseases. This effect was thought to be partially achieved by its ability to alleviate existing neuroinflammation and glial dysfunction. In this study, we systematically investigated the effect of EA on abnormal neurochemical changes and motor symptoms in a mouse neurodegenerative disease model. The transgenic mouse which expresses a mutant α-synuclein (α-syn) protein, A53T α-syn, in brain astrocytic cells was used. These mice exhibit extensive neuroinflammatory and motor phenotypes of neurodegenerative disorders. In this study, the effects of EA on these phenotypic changes were examined in these mice. EA improved the movement detected in multiple motor tests in A53T mutant mice. At the cellular level, EA significantly reduced the activation of microglia and prevented the loss of dopaminergic neurons in the midbrain and motor neurons in the spinal cord. At the molecular level, EA suppressed the abnormal elevation of proinflammatory factors (tumor necrosis factor-α and interleukin-1β) in the striatum and midbrain of A53T mice. In contrast, EA increased striatal and midbrain expression of a transcription factor, nuclear factor E2-related factor 2, and its downstream antioxidants (heme oxygenase-1 and glutamate-cysteine ligase modifier subunits). These results suggest that EA possesses the ability to ameliorate mutant α-syn-induced motor abnormalities. This ability may be due to that EA enhances both anti-inflammatory and antioxidant activities and suppresses aberrant glial activation in the diseased sites of brains.

Functional Magnetic Resonance Imaging of Working Memory and Executive Dysfunction in Systemic Lupus Erythematosus and Antiphospholipid Antibody-Positive Patients.

PubMed

Kozora, E; Uluğ, A M; Erkan, D; Vo, A; Filley, C M; Ramon, G; Burleson, A; Zimmerman, R; Lockshin, M D

2016-11-01

Standardized cognitive tests and functional magnetic resonance imaging (fMRI) studies of systemic lupus erythematosus (SLE) patients demonstrate deficits in working memory and executive function. These neurobehavioral abnormalities are not well studied in antiphospholipid syndrome, which may occur independently of or together with SLE. This study compares an fMRI paradigm involving motor skills, working memory, and executive function in SLE patients without antiphospholipid antibody (aPL) (the SLE group), aPL-positive non-SLE patients (the aPL-positive group), and controls. Brain MRI, fMRI, and standardized cognitive assessment results were obtained from 20 SLE, 20 aPL-positive, and 10 healthy female subjects with no history of neuropsychiatric abnormality. Analysis of fMRI data showed no differences in performance across groups on bilateral motor tasks. When analysis of variance was used, significant group differences were found in 2 executive function tasks (word generation and word rhyming) and in a working memory task (N-Back). Patients positive for aPL demonstrated higher activation in bilateral frontal, temporal, and parietal cortices compared to controls during working memory and executive function tasks. SLE patients also demonstrated bilateral frontal and temporal activation during working memory and executive function tasks. Compared to controls, both aPL-positive and SLE patients had elevated cortical activation, primarily in the frontal lobes, during tasks involving working memory and executive function. These findings are consistent with cortical overactivation as a compensatory mechanism for early white matter neuropathology in these disorders. © 2016, American College of Rheumatology.

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.

Motor development in 3-month-old healthy term-born infants is associated with cognitive and behavioural outcomes at early school age.

PubMed

Hitzert, Marrit M; Roze, Elise; Van Braeckel, Koenraad N J A; Bos, Arend F

2014-09-01

To determine whether motor development at 3 months of age is associated with cognitive, motor, and behavioural outcomes in healthy children at early school age. In this cohort study, we included 74 term-born, healthy children (44 males, 30 females; median gestational age 40.1 wks, range 38.0-42.6 wks). From video recordings (median 12.9 wks, range 9.3-18.6 wks), we assessed the quality of fidgety movements, and calculated a motor optimality score. At school age (median 5 y 11 mo, range 5 y 8 mo-7 y 6 mo), we performed detailed cognitive, motor, and behavioural assessments. We examined whether aspects of motor development were associated with functional outcomes. An age-adequate motor repertoire, in particular the presence of antigravity, midline leg, and manipulation movements, was related to poorer cognition, whereas variable finger postures was related to better cognition. Children with a monotonous concurrent motor repertoire had better ball skills but experienced more behavioural problems. The presence of antigravity movements tended to be associated with abnormal recognition (odds ratio [OR] 4.4, 95% confidence interval [CI], 0.9-21; R(2) =0.17; p=0.070), where the absence of variable finger postures was associated with borderline and abnormal visual-spatial perception (OR 20, 95% CI, 1.7-238; R(2) =0.39; p=0.018). Detailed aspects of motor development at 3 months of age are associated with cognition and behaviour, but not with motor outcome, in healthy children at early school age. Our findings suggest that early motor development may be the basis for later cognitive and behavioural performance. Since the associations were only moderate, possible environmental influences should be acknowledged. © 2014 Mac Keith Press.

Pump Coupling & Motor bearing damage detection using Condition Monitoring at DTPS

NASA Astrophysics Data System (ADS)

Bari, H. M.; Deshpande, A. A.; Jalkote, P. S.; Patil, S. S.

2012-05-01

This paper shares a success story out of the implementation of Co-ordinated Condition Monitoring techniques at DTPS, wherein imminent Mis-alignment of HT auxiliary BFP - 1B and Motor bearing failure of ID FAN - 1B was diagnosed. On 30/12/2010, Booster Pump DE horizontal reading increased from 4.8 to 5.1 and then upto 5.9 mm/sec. It was suspected that Booster pump was mis-aligned with Motor. To confirm misalignment, Phase Analysis was also done which showed that Coupling phase difference was 180 Degrees. Vibration & Phase Analysis helped in diagnosing the exact root cause of abnormity in advance, saving plant from huge losses which could have caused total cost of £ 104,071. On 06/01/2011, ID fan 1B Motor NDE & DE horizontal vibration readings deviated from 0.5 to 0.8 and 0.6 to 0.8 mm/sec (RMS) respectively. Noise level increased from 99.1 to 101.9 db. It was suspected that Motor bearings had loosened over the shaft. Meanwhile, after opening of Motor, Inner race of NDE side was found cracked and loosened over the shaft. Vibration Analysis & Noise Monitoring helped in diagnosing the exact root cause of abnormity in advance, saving plant from huge losses which could have caused total cost of £ 308,857.

[Abnormalities in gastric mechanic sensitivity, gastric emptying and electrogastrography in non organic dyspepsia (NOD)].

PubMed

López Gastón, A; López DeLuise, G A; Sarmiento, A; Andrusch, A

1997-01-01

The aim was to study the alterations in mechanosensitivity, gastric emptying, and electrogastrography (E.G.G.) in a population of patients suffering from N.O.D. eighteen controls (9 males, 9 females, mean age 49.33 years old < SEM 3.62, range 24-74) and 32 patients with N.O.D. (22 males, 21 females, mean age 55.72 years old, SEM 2.87, range 17-86) were studied. Gastric mechano-sensitivity with a latex balloon of low compliance inflated "in phasic" was investigated, and intra balloon pressure was recorded. Gastric emptying with a mixed meal marked with 99 Tc in the solid phase, containing 250 Cal, was studied. E.G.G. was studied using two skin surface electrodes Ag-2C1Ag placed on epigastric area following a probalistic antral axe. Only dominant frequency in each block was considered, and % of total abnormalities on total recording time lesser than 2 c.p.m or more than 4 c.p.m. was considered. Recordings were taken during fast time during 30 minutes, and 30 minutes after a meal containing 250 Cal. Analysis with F.F.T, and spectral running. In 67.92% a delay in gastric emptying was observed. 56.3% did not complete 700 ml. of balloon inflation because of pain, Vs 16.8% in controls (p < 0.001) The slopes of intra-balloon pressure were not different in both groups. (Variance, F-NS). Mean E.C.A was 2.99 c.p.m in control, Vs 3.46 in fasting and 3.64 in postprandial period in N.O.D. (p = NS) Differences in fasting and postprandial % of arrhythmias total time recording were significant in N.O.D. ("t". 0.02 > p 0.01). Twenty percent of controls showed isolated tachygastria, but dominant frequencies never were higher than 6 c.p.m and never last more than 8% of the total recording time. Sixty eight point seventy five percent of N.O.D. showed arrhythmias. 48% of tachygastrias were in the range 30-60% of total recording time. No differences in gastric emptying between patient presenting pain with = < 700 ml. and < 700 ml. of balloon inflation were seen. Patients with sensorial threshold = < 700 ml. showed less frequent tachygastria (0.01 < p < 0.01). Patients with delayed gastric emptying showed more frequent tachygastria (94.7%, 0.05 < p < 0.02) a) E.G.G. abnormalities would more frequent in "motor" subpopulation; b) No association between abnormalities in gastric emptying, abnormal thresholds in mechanosensitivity and/or E.G.G. and any clinical subtype of Dyspepsia can be showed; h) although gastric arrhythmia was more frequent in motor than in sensorial abnormalities, it may represents a more generalized disturbance in central modulation in afferents and efferents inputs and outputs.

L-Dopa Modulates Functional Connectivity in Striatal Cognitive and Motor Networks: A Double-Blind Placebo-Controlled Study

PubMed Central

Kelly, Clare; de Zubicaray, Greig; Di Martino, Adriana; Copland, David A.; Reiss, Philip T.; Klein, Donald F.; Castellanos, F. Xavier; Milham, Michael P.; McMahon, Katie

2010-01-01

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults. We examined the FC of 6 striatal regions-of-interest previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., Cerebral Cortex, 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. While L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions. PMID:19494158

Autism as a developmental disorder in intentional movement and affective engagement

PubMed Central

Trevarthen, Colwyn; Delafield-Butt, Jonathan T.

2013-01-01

We review evidence that autistic spectrum disorders have their origin in early prenatal failure of development in systems that program timing, serial coordination and prospective control of movements, and that regulate affective evaluations of experiences. There are effects in early infancy, before medical diagnosis, especially in motor sequencing, selective or exploratory attention, affective expression and intersubjective engagement with parents. These are followed by retardation of cognitive development and language learning in the second or third year, which lead to a diagnosis of ASD. The early signs relate to abnormalities that have been found in brain stem systems and cerebellum in the embryo or early fetal stage, before the cerebral neocortex is functional, and they have clear consequences in infancy when neocortical systems are intensively elaborated. We propose, with evidence of the disturbances of posture, locomotion and prospective motor control in children with autism, as well as of their facial expression of interest and affect, and attention to other persons' expressions, that examination of the psychobiology of motor affective disorders, rather than later developing cognitive or linguistic ones, may facilitate early diagnosis. Research in this area may also explain how intense interaction, imitation or “expressive art” therapies, which respond intimately with motor activities, are effective at later stages. Exceptional talents of some autistic people may be acquired compensations for basic problems with expectant self-regulations of movement, attention and emotion. PMID:23882192

Patients with symptoms of delayed gastric emptying have a high prevalence of oesophageal dysmotility, irrespective of scintigraphic evidence of gastroparesis.

PubMed

Triadafilopoulos, George; Nguyen, Linda; Clarke, John O

2017-01-01

Patients with symptoms suggestive of gastroparesis exhibit several symptoms, such as epigastric pain, postprandial fullness, bloating and regurgitation. It is uncertain if such symptoms reflect underlying oesophageal motor disorder. To examine whether patients with epigastric pain and postprandial distress syndrome suggestive of functional dyspepsia and/or gastroparesis also have concomitant oesophageal motility abnormalities and, if so, whether there are any associations between these disturbances. In this retrospective cohort study, consecutive patients with functional gastrointestinal symptoms suggestive of gastric neuromuscular dysfunction (gastroparesis or functional dyspepsia) underwent clinical assessment, gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring using standard protocols. We studied 61 patients with various functional upper gastrointestinal symptoms who underwent gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring. Forty-four patients exhibited gastroparesis by gastric scintigraphy. Oesophageal motility disorders were found in 68% and 42% of patients with or without scintigraphic evidence of gastroparesis respectively, suggesting of overlapping gastric and oesophageal neuromuscular disorder. Forty-three per cent of patients with gastroparesis had abnormal oesophageal acid exposure with mean % pH <4.0 of 7.5 in contrast to 38% of those symptomatic controls with normal gastric emptying, with mean %pH <4.0 of 5.4 (NS). Symptoms of epigastric pain, heartburn/regurgitation, bloating, nausea, vomiting, dysphagia, belching and weight loss could not distinguish patients with or without gastroparesis, although weight loss was significantly more prevalent and severe (p<0.002) in patients with gastroparesis. There was no relationship between oesophageal symptoms and motor or pH abnormalities in either groups. Irrespective of gastric emptying delay by scintigraphy, patients with symptoms suggestive of gastric neuromuscular dysfunction have a high prevalence of oesophageal motor disorder and pathological oesophageal acid exposure that may contribute to their symptoms and may require therapy. High-resolution oesophageal manometry and pH monitoring are non-invasive and potentially useful in the assessment and management of these patients.

Postnatal colonization with human "infant-type" Bifidobacterium species alters behavior of adult gnotobiotic mice.

PubMed

Luk, Berkley; Veeraragavan, Surabi; Engevik, Melinda; Balderas, Miriam; Major, Angela; Runge, Jessica; Luna, Ruth Ann; Versalovic, James

2018-01-01

Accumulating studies have defined a role for the intestinal microbiota in modulation of host behavior. Research using gnotobiotic mice emphasizes that early microbial colonization with a complex microbiota (conventionalization) can rescue some of the behavioral abnormalities observed in mice that grow to adulthood completely devoid of bacteria (germ-free mice). However, the human infant and adult microbiomes vary greatly, and effects of the neonatal microbiome on neurodevelopment are currently not well understood. Microbe-mediated modulation of neural circuit patterning in the brain during neurodevelopment may have significant long-term implications that we are only beginning to appreciate. Modulation of the host central nervous system by the early-life microbiota is predicted to have pervasive and lasting effects on brain function and behavior. We sought to replicate this early microbe-host interaction by colonizing gnotobiotic mice at the neonatal stage with a simplified model of the human infant gut microbiota. This model consortium consisted of four "infant-type" Bifidobacterium species known to be commensal members of the human infant microbiota present in high abundance during postnatal development. Germ-free mice and mice neonatally-colonized with a complex, conventional murine microbiota were used for comparison. Motor and non-motor behaviors of the mice were tested at 6-7 weeks of age, and colonization patterns were characterized by 16S ribosomal RNA gene sequencing. Adult germ-free mice were observed to have abnormal memory, sociability, anxiety-like behaviors, and motor performance. Conventionalization at the neonatal stage rescued these behavioral abnormalities, and mice colonized with Bifidobacterium spp. also exhibited important behavioral differences relative to the germ-free controls. The ability of Bifidobacterium spp. to improve the recognition memory of both male and female germ-free mice was a prominent finding. Together, these data demonstrate that the early-life gut microbiome, and human "infant-type" Bifidobacterium species, affect adult behavior in a strongly sex-dependent manner, and can selectively recapitulate the results observed when mice are colonized with a complex microbiota.

Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia.

PubMed

Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

2016-01-01

Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug's side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy.

30 CFR 18.48 - Circuit-interrupting devices.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and.... Such a switch shall be designed to prevent electrical connection to the machine frame when the cable is... motor in the event the belt is stopped, or abnormally slowed down. Note: Short transfer-type conveyors...

Motor neuronopathy with dropped hands and downbeat nystagmus: a distinctive disorder? A case report.

PubMed

Thakore, Nimish J; Pioro, Erik P; Rucker, Janet C; Leigh, R John

2006-01-12

Eye movements are clinically normal in most patients with motor neuron disorders until late in the disease course. Rare patients are reported to show slow vertical saccades, impaired smooth pursuit, and gaze-evoked nystagmus. We report clinical and oculomotor findings in three patients with motor neuronopathy and downbeat nystagmus, a classic sign of vestibulocerebellar disease. All patients had clinical and electrodiagnostic features of anterior horn cell disease. Involvement of finger and wrist extensors predominated, causing finger and wrist drop. Bulbar or respiratory dysfunction did not occur. All three had clinically evident downbeat nystagmus worse on lateral and downgaze, confirmed on eye movement recordings using the magnetic search coil technique in two patients. Additional oculomotor findings included alternating skew deviation and intermittent horizontal saccadic oscillations, in one patient each. One patient had mild cerebellar atrophy, while the other two had no cerebellar or brainstem abnormality on neuroimaging. The disorder is slowly progressive, with survival up to 30 years from the time of onset. The combination of motor neuronopathy, characterized by early and prominent wrist and finger extensor weakness, and downbeat nystagmus with or without other cerebellar eye movement abnormalities may represent a novel motor neuron syndrome.

Motor neuronopathy with dropped hands and downbeat nystagmus: A distinctive disorder? A case report

PubMed Central

Thakore, Nimish J; Pioro, Erik P; Rucker, Janet C; Leigh, R John

2006-01-01

Background Eye movements are clinically normal in most patients with motor neuron disorders until late in the disease course. Rare patients are reported to show slow vertical saccades, impaired smooth pursuit, and gaze-evoked nystagmus. We report clinical and oculomotor findings in three patients with motor neuronopathy and downbeat nystagmus, a classic sign of vestibulocerebellar disease. Case presentation All patients had clinical and electrodiagnostic features of anterior horn cell disease. Involvement of finger and wrist extensors predominated, causing finger and wrist drop. Bulbar or respiratory dysfunction did not occur. All three had clinically evident downbeat nystagmus worse on lateral and downgaze, confirmed on eye movement recordings using the magnetic search coil technique in two patients. Additional oculomotor findings included alternating skew deviation and intermittent horizontal saccadic oscillations, in one patient each. One patient had mild cerebellar atrophy, while the other two had no cerebellar or brainstem abnormality on neuroimaging. The disorder is slowly progressive, with survival up to 30 years from the time of onset. Conclusion The combination of motor neuronopathy, characterized by early and prominent wrist and finger extensor weakness, and downbeat nystagmus with or without other cerebellar eye movement abnormalities may represent a novel motor neuron syndrome. PMID:16409626

Development of oral motor behavior related to the skill assisted spoon feeding.

PubMed

van den Engel-Hoek, Lenie; van Hulst, Karen C M; van Gerven, Marjo H J C; van Haaften, Leenke; de Groot, Sandra A F

2014-05-01

Milestones in the typical development of eating skills are considered to be nippling (breast or bottle), eating from a spoon, drinking from a cup, biting and chewing. The purpose of this research was to study the development and consolidation of oral motor behavior related to the skill assisted spoon feeding in young infants. The present study longitudinally investigated the development of this skill in 39 healthy children from the start of spoon feeding until the skill was acquired. The Observation List Spoon Feeding with 7 observation items for oral motor behavior and 6 items for abnormal behavior was used. Results showed that infants between 4 and 8 months of age needed 5.7 weeks (SD 2.1), with a range of 8 weeks (from 2 to 10 weeks) to acquire this skill. No significant correlation (p=.109) between age at start spoon feeding and weeks needed to develop the skill was found. During this period oral motor behavior consolidated and abnormal behavior diminished. With this study it is shown that the period in weeks needed to acquire the oral motor behavior for the skill assisted spoon feeding is important in case of feeding problems. Copyright © 2014 Elsevier Inc. All rights reserved.

Motor testing at 1 year improves the prediction of motor and mental outcome at 2 years after perinatal hypoxic-ischaemic encephalopathy.

PubMed

van Schie, Petra E M; Becher, Jules G; Dallmeijer, Annet J; Barkhof, Frederik; Van Weissenbruch, Mirjam M; Vermeulen, R Jeroen

2010-01-01

To investigate the predictive value of motor testing at 1 year for motor and mental outcome at 2 years after perinatal hypoxic-ischaemic encephalopathy (HIE) in term neonates. Motor and mental outcome at 2 years was assessed with the Bayley Scales of Infant Development, 2nd edition (BSID-II) in 32 surviving children (20 males, 12 females; mean gestational age 40.2 wk, SD 1.4; mean birthweight 3217g, SD 435) participating in a prospective cohort study of HIE. The predictive value of three motor tests (Alberta Infant Motor Scale [AIMS], BSID-II, and the Neurological Optimality Score [NOS]) at 1 year was analysed, in addition to predictions based on neonatal Sarnat staging and magnetic resonance imaging (MRI). Poor motor test results were defined as an AIMS z-score of <-2, a psychomotor developmental index of the BSID-II of <70, or a NOS of <26. Poor motor and poor mental outcome at 2 years was defined as a psychomotor developmental index or mental developmental index of the BSID-II of <70. Twelve children, all with Sarnat grade II, had a poor motor outcome and 12 children, of whom one had Sarnat grade I, had a poor mental outcome at 2 years. Nine children had cerebral palsy, of whom five had quadriplegia, three had dyskinesia, and one had hemiplegia. Poor motor tests at 1 year increased the probability of a poor motor outcome from 71% (range 92 to 100%), and a poor mental outcome from 59% (range 77 to 100%) in children with Sarnat grade II and abnormal MRI, assessed with the AIMS and BSID-II or NOS respectively. Additional motor testing at 1 year improves the prediction of motor and mental outcome at 2 years in children with Sarnat grade II and abnormal MRI.

Esophageal motor activity in children with gastro-esophageal reflux disease and esophagitis.

PubMed

Chitkara, Denesh K; Fortunato, Christine; Nurko, Samuel

2005-01-01

To evaluate esophageal body motor contractions occurring during esophageal reflux in pediatric patients with gastro-esophageal reflux disease (GERD). Patients referred for the evaluation of GERD who were evaluated with combined 24-hour pH probe and esophageal manometry test (MP24) were included. Patients were separated into the following groups: Group C -- normal pH probe and normal EGD; Group 1 -- abnormal pH probe and normal EGD; and Group 2 -- abnormal pH probe and EGD with histologic esophagitis. Esophageal motor function during reflux episodes was analyzed. Twenty-five patients were included. All had a normal stationary esophageal manometry. Patients in Groups 1 and 2 had significantly more gastroesophageal reflux by pH probe than Group C (P < 0.01). During the MP24, patients in Group 1 and 2 had significantly fewer contractions per minute pre-, during, and post-GER (P < 0.05). There were significant differences in the number of isolated and prolonged contractions (>7 sec) during prolonged GERD episodes >5 minutes (P < 0.05). Children with GERD have a decreased number and abnormal esophageal body contractions with esophageal reflux. This suggests that children with GERD with and without esophagitis have impaired esophageal body acid clearance.

Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson's Disease? The Potential Role of Zolpidem in the Treatment of Parkinson's Disease

PubMed Central

Daniele, Antonio; Panza, Francesco; Greco, Antonio; Logroscino, Giancarlo; Seripa, Davide

2016-01-01

At present, patients with advanced Parkinson's disease (PD) are unsatisfactorily controlled by currently used anti-Parkinsonian dopaminergic drugs. Various studies suggest that therapeutic strategies based on nondopaminergic drugs might be helpful in PD. Zolpidem, an imidazopyridine widely used as sleep inducer, shows high affinity only for GABAA receptors containing the α-1 subunit and facilitates GABAergic neurotransmission through a positive allosteric modulation of GABAA receptors. Various observations, although preliminary, consistently suggest that in PD patients zolpidem may induce beneficial (and sometimes remarkable) effects on motor symptoms even after single doses and may also improve dyskinesias. Since a high density of zolpidem binding sites is in the two main output structures of the basal ganglia which are abnormally overactive in PD (internal globus pallidus, GPi, and substantia nigra pars reticulata, SNr), it was hypothesized that in PD patients zolpidem may induce through GABAA receptors an inhibition of GPi and SNr (and, possibly, of the subthalamic nucleus also), resulting in an increased activity of motor cortical areas (such as supplementary motor area), which may give rise to improvement of motor symptoms of PD. Randomized clinical trials are needed in order to assess the efficacy, safety, and tolerability of zolpidem in treating motor symptoms of PD. PMID:27293955

Fail safe controllable output improved version of the Electromechanical battery

DOEpatents

Post, Richard F.

1999-01-01

Mechanical means are provided to control the voltages induced in the windings of a generator/motor. In one embodiment, a lever is used to withdraw or insert the entire stator windings from the cavity where the rotating field exists. In another embodiment, voltage control and/or switching off of the output is achievable with a variable-coupling generator/motor. A stator is made up of two concentric layers of windings, with a larger number of turns on the inner layer of windings than the outer layer of windings. The windings are to be connected in series electrically, that is, their voltages add vectorially. The mechanical arrangement is such that one or both of the windings can be rotated with respect to the other winding about their common central axis. Another improved design for the stator assembly of electromechanical batteries provides knife switch contacts that are in electrical contact with the stator windings. The operation of this embodiment depends on the fact that an abnormally large torque will be exerted on the stator structure during any short-circuit condition.

Fail safe controllable output improved version of the electromechanical battery

DOEpatents

Post, R.F.

1999-01-19

Mechanical means are provided to control the voltages induced in the windings of a generator/motor. In one embodiment, a lever is used to withdraw or insert the entire stator windings from the cavity where the rotating field exists. In another embodiment, voltage control and/or switching off of the output is achievable with a variable-coupling generator/motor. A stator is made up of two concentric layers of windings, with a larger number of turns on the inner layer of windings than the outer layer of windings. The windings are to be connected in series electrically, that is, their voltages add vectorially. The mechanical arrangement is such that one or both of the windings can be rotated with respect to the other winding about their common central axis. Another improved design for the stator assembly of electromechanical batteries provides knife switch contacts that are in electrical contact with the stator windings. The operation of this embodiment depends on the fact that an abnormally large torque will be exerted on the stator structure during any short-circuit condition. 4 figs.

Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

PubMed Central

Kishore, Asha; Popa, Traian

2014-01-01

The exact mechanisms that generate levodopa-induced dyskinesias (LID) during chronic levodopa therapy for Parkinson’s disease (PD) are not yet fully established. The most widely accepted theories incriminate the non-physiological synthesis, release and reuptake of dopamine generated by exogenously administered levodopa in the striatum, and the aberrant plasticity in the cortico-striatal loops. However, normal motor performance requires the correct recruitment of motor maps. This depends on a high level of synergy within the primary motor cortex (M1) as well as between M1 and other cortical and subcortical areas, for which dopamine is necessary. The plastic mechanisms within M1, which are crucial for the maintenance of this synergy, are disrupted both during “OFF” and dyskinetic states in PD. When tested without levodopa, dyskinetic patients show loss of treatment benefits on long-term potentiation and long-term depression-like plasticity of the intracortical circuits. When tested with the regular pulsatile levodopa doses, they show further impairment of the M1 plasticity, such as inability to depotentiate an already facilitated synapse and paradoxical facilitation in response to afferent input aimed at synaptic inhibition. Dyskinetic patients have also severe impairment of the associative, sensorimotor plasticity of M1 attributed to deficient cerebellar modulation of sensory afferents to M1. Here, we review the anatomical and functional studies, including the recently described bidirectional connections between the cerebellum and the basal ganglia that support a key role of the cerebellum in the generation of LID. This model stipulates that aberrant neuronal synchrony in PD with LID may propagate from the subthalamic nucleus to the cerebellum and “lock” the cerebellar cortex in a hyperactive state. This could affect critical cerebellar functions such as the dynamic and discrete modulation of M1 plasticity and the matching of motor commands with sensory information from the environment during motor performance. We propose that in dyskinesias, M1 neurons have lost the ability to depotentiate an activated synapse when exposed to acute pulsatile, non-physiological, dopaminergic surges and become abnormally receptive to unfiltered, aberrant, and non-salient afferent inputs from the environment. The motor program selection in response to such non-salient and behaviorally irrelevant afferent inputs would be abnormal and involuntary. The motor responses are worsened by the lack of normal subcortico–cortical inputs from cerebellum and basal ganglia, because of the aberrant plasticity at their own synapses. Artificial cerebellar stimulation might help re-establish the cerebellar and basal ganglia control over the non-salient inputs to the motor areas during synaptic dopaminergic surges. PMID:25183959

Neuronal Entropy-Rate Feature of Entopeduncular Nucleus in Rat Model of Parkinson's Disease.

PubMed

Darbin, Olivier; Jin, Xingxing; Von Wrangel, Christof; Schwabe, Kerstin; Nambu, Atsushi; Naritoku, Dean K; Krauss, Joachim K; Alam, Mesbah

2016-03-01

The function of the nigro-striatal pathway on neuronal entropy in the basal ganglia (BG) output nucleus, i.e. the entopeduncular nucleus (EPN) was investigated in the unilaterally 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In both control subjects and subjects with 6-OHDA lesion of dopamine (DA) the nigro-striatal pathway, a histological hallmark for parkinsonism, neuronal entropy in EPN was maximal in neurons with firing rates ranging between 15 and 25 Hz. In 6-OHDA lesioned rats, neuronal entropy in the EPN was specifically higher in neurons with firing rates above 25 Hz. Our data establishes that the nigro-striatal pathway controls neuronal entropy in motor circuitry and that the parkinsonian condition is associated with abnormal relationship between firing rate and neuronal entropy in BG output nuclei. The neuronal firing rates and entropy relationship provide putative relevant electrophysiological information to investigate the sensory-motor processing in normal condition and conditions such as movement disorders.

RELATIONSHIP BETWEEN ENTROPY OF SPIKE TIMING AND FIRING RATE IN ENTOPEDUNCULAR NUCLEUS NEURONS IN ANESTHETIZED RATS: FUNCTION OF THE NIGRO-STRIATAL PATHWAY

PubMed Central

Darbin, Olivier; Jin, Xingxing; von Wrangel, Christof; Schwabe, Kerstin; Nambu, Atsushi; Naritoku, Dean K; Krauss, Joachim K.; Alam, Mesbah

2016-01-01

The function of the nigro-striatal pathway on neuronal entropy in the basal ganglia (BG) output nucleus (entopeduncular nucleus, EPN) was investigated in the unilaterally 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson’s disease (PD). In both control subjects and subjects with 6-OHDA lesion of the nigro-striatal pathway, a histological hallmark for parkinsonism, neuronal entropy in EPN was maximal in neurons with firing rates ranging between 15Hz and 25 Hz. In 6-OHDA lesioned rats, neuronal entropy in the EPN was specifically higher in neurons with firing rates above 25Hz. Our data establishes that nigro-striatal pathway controls neuronal entropy in motor circuitry and that the parkinsonian condition is associated with abnormal relationship between firing rate and neuronal entropy in BG output nuclei. The neuronal firing rates and entropy relationship provide putative relevant electrophysiological information to investigate the sensory-motor processing in normal condition and conditions with movement disorders. PMID:26711712

The spectrum of motor function abnormalities in gastroesophageal reflux disease and Barrett's esophagus.

PubMed

Ang, D; Blondeau, K; Sifrim, D; Tack, J

2009-01-01

Barrett's esophagus has traditionally been regarded as the most severe end of the spectrum of gastroesophageal reflux disease and is of great clinical importance in view of the association with esophageal adenocarcinoma. Studies have documented high levels of esophageal acid exposure in Barrett's esophagus. Various pathogenetic mechanisms underlie this phenomenon. These include abnormalities in esophageal peristalsis, defective lower esophageal sphincter pressures, gastric dysmotility and bile reflux. Whilst these factors provide evidence for an acquired cause of Barrett's esophagus, an underlying genetic predisposition cannot be ruled out. Although the past decade has brought about many new discoveries in the pathogenesis of Barrett's esophagus, it has also added further controversy to this complex disorder. A detailed analysis of the gastrointestinal motor abnormalities occurring in Barrett's esophagus follows, with a review of the currently available literature and an update on this condition that continues to be of interest to the gastroenterologist.

Rapid Eye Movement Sleep Abnormalities in Children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

PubMed Central

Gaughan, Thomas; Buckley, Ashura; Hommer, Rebecca; Grant, Paul; Williams, Kyle; Leckman, James F.; Swedo, Susan E.

2016-01-01

Study Objectives: Polysomnographic investigation of sleep architecture in children presenting with pediatric acute-onset neuropsychiatric syndrome (PANS). Methods: Fifteen consecutive subjects meeting criteria for PANS (mean age = 7.2 y; range 3–10 y) underwent single-night full polysomnography (PSG) read by a pediatric neurologist. Results: Thirteen of 15 subjects (87%) had abnormalities detected with PSG. Twelve of 15 had evidence of rapid eye movement (REM) sleep motor disinhibition, as characterized by excessive movement, laughing, hand stereotypies, moaning, or the continuation of periodic limb movements during sleep (PLMS) into REM sleep. Conclusions: This study shows various forms of REM sleep motor disinhibition present in a population of children with PANS. Citation: Gaughan T, Buckley A, Hommer R, Grant P; Williams K, Leckman JF, Swedo SE. Rapid eye movement sleep abnormalities in children with pediatric acute-onset neuropsychiatric syndrome (PANS). J Clin Sleep Med 2016;12(7):1027–1032. PMID:27166296

Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control.

PubMed

Kullander, K; Croll, S D; Zimmer, M; Pan, L; McClain, J; Hughes, V; Zabski, S; DeChiara, T M; Klein, R; Yancopoulos, G D; Gale, N W

2001-04-01

Growing axons follow highly stereotypical pathways, guided by a variety of attractive and repulsive cues, before establishing specific connections with distant targets. A particularly well-known example that illustrates the complexity of axonal migration pathways involves the axonal projections of motor neurons located in the motor cortex. These projections take a complex route during which they first cross the midline, then form the corticospinal tract, and ultimately connect with motor neurons in the contralateral side of the spinal cord. These obligatory contralateral connections account for why one side of the brain controls movement on the opposing side of the body. The netrins and slits provide well-known midline signals that regulate axonal crossings at the midline. Herein we report that a member of the ephrin family, ephrin-B3, also plays a key role at the midline to regulate axonal crossing. In particular, we show that ephrin-B3 acts as the midline barrier that prevents corticospinal tract projections from recrossing when they enter the spinal gray matter. We report that in ephrin-B3(-/-) mice, corticospinal tract projections freely recross in the spinal gray matter, such that the motor cortex on one side of the brain now provides bilateral input to the spinal cord. This neuroanatomical abnormality in ephrin-B3(-/-) mice correlates with loss of unilateral motor control, yielding mice that simultaneously move their right and left limbs and thus have a peculiar hopping gait quite unlike the alternate step gait displayed by normal mice. The corticospinal and walking defects in ephrin-B3(-/-) mice resemble those recently reported for mice lacking the EphA4 receptor, which binds ephrin-B3 as well as other ephrins, suggesting that the binding of EphA4-bearing axonal processes to ephrin-B3 at the midline provides the repulsive signal that prevents corticospinal tract projections from recrossing the midline in the developing spinal cord.

Deficient "sensory" beta synchronization in Parkinson's disease.

PubMed

Degardin, A; Houdayer, E; Bourriez, J-L; Destée, A; Defebvre, L; Derambure, P; Devos, D

2009-03-01

Beta rhythm movement-related synchronization (beta synchronization) reflects motor cortex deactivation and sensory afference processing. In Parkinson's disease (PD), decreased beta synchronization after active movement reflects abnormal motor cortex idling and may be involved in the pathophysiology of akinesia. The objectives of the present study were to (i) compare event-related synchronization after active and passive movement and electrical nerve stimulation in PD patients and healthy, age-matched volunteers and (ii) evaluate the effect of levodopa. Using a 128-electrode EEG system, we studied beta synchronization after active and passive index finger movement and electrical median nerve stimulation in 13 patients and 12 control subjects. Patients were recorded before and after 150% of their usual morning dose of levodopa. The peak beta synchronization magnitude in the contralateral primary sensorimotor (PSM) cortex was significantly lower in PD patients after active movement, passive movement and electrical median nerve stimulation, compared with controls. Levodopa partially reversed the drop in beta synchronization after active movement but not after passive movement or electrical median nerve stimulation. If one considers that beta synchronization reflects sensory processing, our results suggest that integration of somaesthetic afferences in the PSM cortex is abnormal in PD during active and passive movement execution and after simple electrical median nerve stimulation. Better understanding of the mechanisms involved in the deficient beta synchronization observed here could prompt the development of new therapeutic approaches aimed at strengthening defective processes. The lack of full beta synchronization restoration by levodopa might be related to the involvement of non-dopaminergic pathways.

Discharge rates in electromyography distinguish early between peripheral and central paresis.

PubMed

Jürgens, Tim P; Puchner, Christoph; Schulte-Mattler, Wilhelm J

2012-10-01

Abnormally increased discharge rates (DRs) of motor unit potentials on concentric needle electromyography (CNEMG) indicate a loss of motor units in peripheral neurogenic lesions. To determine when increased DRs occur during the course of a peripheral nerve lesion, we retrospectively analyzed CNEMG recordings of 19 patients with acute weakness of peripheral origin. The initial CNEMG studies took place from 3.7 hours to 10 days after the onset of the lesion. Abnormally increased DRs (≥20/s) were found in all but 1 of the muscles in which MRC grade was <4. Peripheral neurogenic damage was confirmed in all patients thereafter. The DRs depended on neither the kind of lesion nor the time between onset and CNEMG examination. The measurement of DRs of motor unit potentials is helpful immediately after a sudden paresis of MRC grade 3 or worse to differentiate between a central and a peripheral lesion. Copyright © 2012 Wiley Periodicals, Inc.

Nucleus prepositus hypoglossi lesions produce a unique ocular motor syndrome

PubMed Central

Kim, Sung-Hee; Zee, David S.; du Lac, Sascha; Kim, Hyo Jung

2016-01-01

Objective: To describe the ocular motor abnormalities in 9 patients with a lesion involving the nucleus prepositus hypoglossi (NPH), a key constituent of a vestibular-cerebellar-brainstem neural network that ensures that the eyes are held steady in all positions of gaze. Methods: We recorded eye movements, including the vestibulo-ocular reflex during head impulses, in patients with vertigo and a lesion involving the NPH. Results: Our patients showed an ipsilesional-beating spontaneous nystagmus, horizontal gaze-evoked nystagmus more intense on looking toward the ipsilesional side, impaired pursuit more to the ipsilesional side, central patterns of head-shaking nystagmus, contralateral eye deviation, and decreased vestibulo-ocular reflex gain during contralesionally directed head impulses. Conclusions: We attribute these findings to an imbalance in the NPH–inferior olive–flocculus–vestibular nucleus loop, and the ocular motor abnormalities provide a new brainstem localization for patients with acute vertigo. PMID:27733568

Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

PubMed Central

Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

2011-01-01

SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

Sensorimotor integration: basic concepts, abnormalities related to movement disorders and sensorimotor training-induced cortical reorganization.

PubMed

Machado, Sergio; Cunha, Marlo; Velasques, Bruna; Minc, Daniel; Teixeira, Silmar; Domingues, Clayton A; Silva, Julio G; Bastos, Victor H; Budde, Henning; Cagy, Mauricio; Basile, Luis; Piedade, Roberto; Ribeiro, Pedro

2010-10-01

Sensorimotor integration is defined as the capability of the central nervous system to integrate different sources of stimuli, and parallelly, to transform such inputs in motor actions. To review the basic principles of sensorimotor integration, such as, its neural bases and its elementary mechanisms involved in specific goal-directed tasks performed by healthy subjects, and the abnormalities reported in the most common movement disorders, such as, Parkinson' disease, dystonia and stroke, like the cortical reorganization-related mechanisms. Whether these disorders are associated with an abnormal peripheral sensory input or defective central processing is still unclear, but most of the data support a central mechanism. We found that the sensorimotor integration process plays a potential role in elementary mechanisms involved in specific goal-directed tasks performed by healthy subjects and in occurrence of abnormalities in most common movement disorders and, moreover, play a potential role on the acquisition of abilities that have as critical factor the coupling of different sensory data which will constitute the basis of elaboration of motor outputs consciously goal-directed.

Impairment of sensory-motor plasticity in mild Alzheimer's disease.

PubMed

Terranova, Carmen; Carmen, Terranova; SantAngelo, Antonino; Antonino, Sant'Angelo; Morgante, Francesca; Francesca, Morgante; Rizzo, Vincenzo; Vincenzo, Rizzo; Allegra, Roberta; Roberta, Allegra; Arena, Maria Grazia; Grazia, Arena Maria; Ricciardi, Lucia; Lucia, Ricciardi; Ghilardi, Marie Felice; Felice, Ghilardi Maria; Girlanda, Paolo; Paolo, Girlanda; Quartarone, Angelo; Angelo, Quartarone

2013-01-01

Primary motor cortex (M1) is relatively spared in the early stages of Alzheimer's disease (AD). Aim of the present study was to investigate whether abnormal M1 synaptic plasticity is present at an early stage of AD. We employed an electrophysiological protocol, named rapid paired associative stimulation (rPAS), involving repetitive transcranial magnetic stimulation (rTMS) paired with electrical stimulation of the contralateral median nerve, that modifies corticospinal excitability and short latency afferent inhibition (SAI). We studied 10 patients with a diagnosis of probable mild AD according to the Mini Mental State Examination score (minimum 21) and 14 age-matched control subjects. Motor evoked potentials (MEP) amplitudes and short-afferent inhibition (SAI) were measured at baseline before and for up to 60 min after 5Hz-rPAS in abductor pollicis brevis (APB). rPAS consisted of 600 pairs of transcranial magnetic stimuli, at a rate of 5 Hz for 2 min, coupled with electrical median nerve stimulation preceding TMS over the contralateral M1 at an inter-stimulus interval of 25 ms. Baseline SAI was significantly reduced in AD patients. In the control subjects rPAS induced a significant increase in MEP amplitudes and a decrease of SAI in the APB muscle persistently for up to 1 h. Conversely 5Hz-rPAS did not induce any significant changes in MEP amplitudes and SAI in mild AD patients. Sensory-motor plasticity is impaired in the motor cortex of AD at an early stage of the disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Progesterone neuroprotection in the Wobbler mouse, a genetic model of spinal cord motor neuron disease.

PubMed

Gonzalez Deniselle, María Claudia; López-Costa, Juan José; Saavedra, Jorge Pecci; Pietranera, Luciana; Gonzalez, Susana L; Garay, Laura; Guennoun, Rachida; Schumacher, Michael; De Nicola, Alejandro F

2002-12-01

Motor neuron degeneration characterizes the spinal cord of patients with amyotrophic lateral sclerosis and the Wobbler mouse mutant. Considering that progesterone (PROG) provides neuroprotection in experimental ischemia and injury, its potential role in neurodegeneration was studied in the murine model. Two-month-old symptomatic Wobbler mice were left untreated or received sc a 20-mg PROG implant for 15 days. Both light and electron microscopy of Wobbler mice spinal cord showed severely affected motor neurons with profuse cytoplasmic vacuolation of the endoplasmic reticulum and/or Golgi apparatus and ruptured mitochondria with damaged cristae, a profile indicative of a type II cytoplasmic form of cell death. In contrast to untreated mice, neuropathology was less severe in Wobbler mice receiving PROG; including a reduction of vacuolation and of the number of vacuolated cells and better conservation of the mitochondrial ultrastructure. In biochemical studies, we determined the mRNA for the alpha3 subunit of Na,K-ATPase, a neuronal enzyme controlling ion fluxes, neurotransmission, membrane potential, and nutrient uptake. In untreated Wobbler mice, mRNA levels in motor neurons were reduced by half compared to controls, whereas PROG treatment of Wobbler mice restored the expression of alpha3 subunit Na,K-ATPase mRNA. Therefore, PROG was able to rescue motor neurons from degeneration, based on recovery of histopathological abnormalities and of mRNA levels of the sodium pump. However, because the gene mutation in Wobbler mice is still unknown, further studies are needed to unveil the action of PROG and the mechanism of neuronal death in this genetic model of neurodegeneration.

Parkinson's disease: increased motor network activity in the absence of movement.

PubMed

Ko, Ji Hyun; Mure, Hideo; Tang, Chris C; Ma, Yilong; Dhawan, Vijay; Spetsieris, Phoebe; Eidelberg, David

2013-03-06

We used a network approach to assess systems-level abnormalities in motor activation in humans with Parkinson's disease (PD). This was done by measuring the expression of the normal movement-related activation pattern (NMRP), a previously validated activation network deployed by healthy subjects during motor performance. In this study, NMRP expression was prospectively quantified in (15)O-water PET scans from a PD patient cohort comprised of a longitudinal early-stage group (n = 12) scanned at baseline and at two or three follow-up visits two years apart, and a moderately advanced group scanned on and off treatment with either subthalamic nucleus deep brain stimulation (n = 14) or intravenous levodopa infusion (n = 14). For each subject and condition, we measured NMRP expression during both movement and rest. Resting expression of the abnormal PD-related metabolic covariance pattern was likewise determined in the same subjects. NMRP expression was abnormally elevated (p < 0.001) in PD patients scanned in the nonmovement rest state. By contrast, network activity measured during movement did not differ from normal (p = 0.34). In the longitudinal cohort, abnormal increases in resting NMRP expression were evident at the earliest clinical stages (p < 0.05), which progressed significantly over time (p = 0.003). Analogous network changes were present at baseline in the treatment cohort (p = 0.001). These abnormalities improved with subthalamic nucleus stimulation (p < 0.005) but not levodopa (p = 0.25). In both cohorts, the changes in NMRP expression that were observed did not correlate with concurrent PD-related metabolic covariance pattern measurements (p > 0.22). Thus, the resting state in PD is characterized by changes in the activity of normal as well as pathological brain networks.

Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

PubMed Central

Tefera, Tesfaye W.; Borges, Karin

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily characterized by loss of motor neurons in brain and spinal cord. The death of motor neurons leads to denervation of muscle which in turn causes muscle weakness and paralysis, decreased respiratory function and eventually death. Growing evidence indicates disturbances in energy metabolism in patients with ALS and animal models of ALS, which are likely to contribute to disease progression. Particularly, defects in glucose metabolism and mitochondrial dysfunction limit the availability of ATP to CNS tissues and muscle. Several metabolic approaches improving mitochondrial function have been investigated in vitro and in vivo and showed varying effects in ALS. The effects of metabolic approaches in ALS models encompass delays in onset of motor symptoms, protection of motor neurons and extension of survival, which signifies an important role of metabolism in the pathogenesis of the disease. There is now an urgent need to test metabolic approaches in controlled clinical trials. In addition, more detailed studies to better characterize the abnormalities in energy metabolism in patients with ALS and ALS models are necessary to develop metabolically targeted effective therapies that can slow the progression of the disease and prolong life for patients with ALS. PMID:28119559

Stimulus Timing by People with Parkinson's Disease

ERIC Educational Resources Information Center

Wearden, J. H.; Smith-Spark, J. H.; Cousins, Rosanna; Edelstyn, N. M. J.; Cody, F. W. J.; O'Boyle, D. J.

2008-01-01

Previous literature suggests that Parkinson's disease is marked by deficits in timed behaviour. However, the majority of studies of central timing mechanisms in patients with Parkinson's disease have used timing tasks with a motor component. Since the motor abnormalities are a defining feature of the condition, the status of timing in Parkinson's…

Implicit Procedural Learning in Fragile X and Down Syndrome

ERIC Educational Resources Information Center

Bussy, G.; Charrin, E.; Brun, A.; Curie, A.; des Portes, V.

2011-01-01

Background: Procedural learning refers to rule-based motor skill learning and storage. It involves the cerebellum, striatum and motor areas of the frontal lobe network. Fragile X syndrome, which has been linked with anatomical abnormalities within the striatum, may result in implicit procedural learning deficit. Methods: To address this issue, a…

A Preliminary Transcranial Magnetic Stimulation Study of Cortical Inhibition and Excitability in High-Functioning Autism and Asperger Disorder

ERIC Educational Resources Information Center

Enticott, Peter G.; Rinehart, Nicole J.; Tonge, Bruce J.; Bradshaw, John L.; Fitzgerald, Paul B.

2010-01-01

Aim: Controversy surrounds the distinction between high-functioning autism (HFA) and Asperger disorder, but motor abnormalities are associated features of both conditions. This study examined motor cortical inhibition and excitability in HFA and Asperger disorder using transcranial magnetic stimulation (TMS). Method: Participants were diagnosed by…

Parallel changes in cortical neuron biochemistry and motor function in protein-energy malnourished adult rats.

PubMed

Alaverdashvili, Mariam; Hackett, Mark J; Caine, Sally; Paterson, Phyllis G

2017-04-01

While protein-energy malnutrition in the adult has been reported to induce motor abnormalities and exaggerate motor deficits caused by stroke, it is not known if alterations in mature cortical neurons contribute to the functional deficits. Therefore, we explored if PEM in adult rats provoked changes in the biochemical profile of neurons in the forelimb and hindlimb regions of the motor cortex. Fourier transform infrared spectroscopic imaging using a synchrotron generated light source revealed for the first time altered lipid composition in neurons and subcellular domains (cytosol and nuclei) in a cortical layer and region-specific manner. This change measured by the area under the curve of the δ(CH 2 ) band may indicate modifications in membrane fluidity. These PEM-induced biochemical changes were associated with the development of abnormalities in forelimb use and posture. The findings of this study provide a mechanism by which PEM, if not treated, could exacerbate the course of various neurological disorders and diminish treatment efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuropathology and Neurochemistry of Nonmotor Symptoms in Parkinson's Disease

PubMed Central

Ferrer, Isidro

2011-01-01

Parkinson disease (PD) is no longer considered a complex motor disorder characterized by Parkinsonism but rather a systemic disease with variegated non-motor deficits and neurological symptoms, including impaired olfaction, autonomic failure, cognitive impairment, and psychiatric symptoms. Many of these alterations appear before or in parallel with motor deficits and then worsen with disease progression. Although there is a close relation between motor symptoms and the presence of Lewy bodies (LBs) and neurites filled with abnormal α-synuclein, other neurological alterations are independent of the amount of α-synuclein inclusions in neurons and neurites, thereby indicating that different mechanisms probably converge in the degenerative process. Involvement of the cerebral cortex that may lead to altered behaviour and cognition are related to several convergent factors such as (a) abnormal α-synuclein and other proteins at the synapses, rather than LBs and neurites, (b) impaired dopaminergic, noradrenergic, cholinergic and serotoninergic cortical innervation, and (c) altered neuronal function resulting from reduced energy production and increased energy demands. These alterations appear at early stages of the disease and may precede by years the appearance of cell loss and cortical atrophy. PMID:21403906

[18F]fallypride characterization of striatal and extrastriatal D2/3 receptors in Parkinson's disease.

PubMed

Stark, Adam J; Smith, Christopher T; Petersen, Kalen J; Trujillo, Paula; van Wouwe, Nelleke C; Donahue, Manus J; Kessler, Robert M; Deutch, Ariel Y; Zald, David H; Claassen, Daniel O

2018-01-01

Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D 2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D 2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D 2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age- and sex-matched healthy controls (HCs) using PET imaging with [ 18 F]fallypride, a high affinity D 2/3 receptor ligand, to measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND ). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BP ND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D 2/3 receptors, where reduced BP ND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D 2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D 2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.

Abnormal Parietal Function in Conversion Paresis

PubMed Central

van Beilen, Marije; de Jong, Bauke M.; Gieteling, Esther W.; Renken, Remco; Leenders, Klaus L.

2011-01-01

The etiology of medically unexplained symptoms such as conversion disorder is poorly understood. This is partly because the interpretation of neuroimaging results in conversion paresis has been complicated by the use of different control groups, tasks and statistical comparisons. The present study includes these different aspects in a single data set. In our study we included both normal controls and feigners to control for conversion paresis. We studied both movement execution and imagery, and we contrasted both within-group and between-group activation. Moreover, to reveal hemisphere-specific effects that have not been reported before, we performed these analyses using both flipped and unflipped data. This approach resulted in the identification of abnormal parietal activation which was specific for conversion paresis patients. Patients also showed reduced activity in the prefrontal cortex, supramarginal gyrus and precuneus, including hemisphere-specific activation that is lateralized in the same hemisphere, regardless of right- or left-sided paresis. We propose that these regions are candidates for an interface between psychological mechanisms and disturbed higher-order motor control. Our study presents an integrative neurophysiological view of the mechanisms that contribute to the etiology of this puzzling psychological disorder, which can be further investigated with other types of conversion symptoms. PMID:22039428

Abnormal cortical synaptic plasticity in primary motor area in progressive supranuclear palsy.

PubMed

Conte, Antonella; Belvisi, Daniele; Bologna, Matteo; Ottaviani, Donatella; Fabbrini, Giovanni; Colosimo, Carlo; Williams, David R; Berardelli, Alfredo

2012-03-01

No study has yet investigated whether cortical plasticity in primary motor area (M1) is abnormal in patients with progressive supranuclear palsy (PSP). We studied M1 plasticity in 15 PSP patients and 15 age-matched healthy subjects. We used intermittent theta-burst stimulation (iTBS) to investigate long-term potentiation (LTP) and continuous TBS (cTBS) to investigate long-term depression (LTD)-like cortical plasticity in M1. Ten patients underwent iTBS again 1 year later. We also investigated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in M1 with paired-pulse transcranial magnetic stimulation, tested H reflex from upper limb flexor muscles before and after iTBS, and measured motor evoked potential (MEP) input-output (I/O) curves before and after iTBS. iTBS elicited a significantly larger MEP facilitation after iTBS in patients than in healthy subjects. Whereas in healthy subjects, cTBS inhibited MEP, in patients it significantly facilitated MEPs. In patients, SICI was reduced, whereas ICF was normal. H reflex size remained unchanged after iTBS. Patients had steeper MEP I/O slopes than healthy subjects at baseline and became even more steeper after iTBS only in patients. The iTBS-induced abnormal MEP facilitation in PSP persisted at 1-year follow-up. In conclusion, patients with PSP have abnormal M1 LTP/LTD-like plasticity. The enhanced LTP-like cortical synaptic plasticity parallels disease progression.

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 motor responses to life threatening challenges during sleep. These observations support the concept that abnormalities in a multi-neurotransmitter network within key nuclei of the medullary homeostatic system may underlie the pathogenesis of a subset of SIDS cases.

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 motor responses to life threatening challenges during sleep. These observations support the concept that abnormalities in a multi-neurotransmitter network within key nuclei of the medullary homeostatic system may underlie the pathogenesis of a subset of SIDS cases. PMID:28931039

Impaired thalamocortical connectivity in autism spectrum disorder: a study of functional and anatomical connectivity.

PubMed

Nair, Aarti; Treiber, Jeffrey M; Shukla, Dinesh K; Shih, Patricia; Müller, Ralph-Axel

2013-06-01

The thalamus plays crucial roles in the development and mature functioning of numerous sensorimotor, cognitive and attentional circuits. Currently limited evidence suggests that autism spectrum disorder may be associated with thalamic abnormalities, potentially related to sociocommunicative and other impairments in this disorder. We used functional connectivity magnetic resonance imaging and diffusion tensor imaging probabilistic tractography to study the functional and anatomical integrity of thalamo-cortical connectivity in children and adolescents with autism spectrum disorder and matched typically developing children. For connectivity with five cortical seeds (prefontal, parieto-occipital, motor, somatosensory and temporal), we found evidence of both anatomical and functional underconnectivity. The only exception was functional connectivity with the temporal lobe, which was increased in the autism spectrum disorders group, especially in the right hemisphere. However, this effect was robust only in partial correlation analyses (partialling out time series from other cortical seeds), whereas findings from total correlation analyses suggest that temporo-thalamic overconnectivity in the autism group was only relative to the underconnectivity found for other cortical seeds. We also found evidence of microstructural compromise within the thalamic motor parcel, associated with compromise in tracts between thalamus and motor cortex, suggesting that the thalamus may play a role in motor abnormalities reported in previous autism studies. More generally, a number of correlations of diffusion tensor imaging and functional connectivity magnetic resonance imaging measures with diagnostic and neuropsychological scores indicate involvement of abnormal thalamocortical connectivity in sociocommunicative and cognitive impairments in autism spectrum disorder.

Early electrophysiological findings in acute inflammatory demyelinating polyradiculoneuropathy variant of Guillain-Barre syndrome in the Pakistani population - a comparison with global data.

PubMed

Wali, Ahmad; Kanwar, Dureshahwar; Khan, Safoora A; Khan, Sara

2017-12-01

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy are the most common variants of Guillian-Barre syndrome documented in the Asian population. However, the variability of early neurophysiologic findings in the Asian population compared to western data has not been documented. Eighty-seven cases of AIDP were retrospectively reviewed for their demographic, clinical, electrophysiological, and laboratory data. Mean age of subjects was 31 ± 8 years with males more commonly affected. Motor symptoms (97%) at presentation predominated. Common early nerve conduction findings included low motor amplitudes (85%), recordable sural sensory responses (85%), and absent H-reflex responses (65%). Prolonged F-latencies were found most commonly in posterior tibial nerves (23%) in the lower limbs and median and ulnar nerves (18%) in the upper limbs. Blink reflex (BR) studies were performed in 57 patients and were abnormal in 80% of those with clinical facial weakness and in 17 of 52 patients (33%) with no clinical cranial nerve signs, suggesting subclinical cranial nerve involvement. Abnormal motor and sensory amplitudes are seen early. Prolonged distal latencies, temporal dispersion/conduction blocks and sural sparing pattern are other common early nerve conduction study findings of AIDP seen in the Pakistani population. There are no significant differences in abnormalities of conduction velocities and delayed reflex responses compared to published data. The BR can help in the early diagnosis of AIDP. © 2017 Peripheral Nerve Society.

Electrophysiological measurements of diabetic peripheral neuropathy: A systematic review.

PubMed

Shabeeb, Dheyauldeen; Najafi, Masoud; Hasanzadeh, Gholamreza; Hadian, Mohammed Reza; Musa, Ahmed Eleojio; Shirazi, Alireza

2018-03-28

Peripheral neuropathy is one of the main complications of diabetes mellitus. One of the features of diabetic nerve damage is abnormality of sensory and motor nerve conduction study. An electrophysiological examination can be reproduced and is also a non-invasive approach in the assessment of peripheral nerve function. Population-based and clinical studies have been conducted to validate the sensitivity of these methods. When the diagnosis was based on clinical electrophysiological examination, abnormalities were observed in all patients. In this research, using a review design, we reviewed the issue of clinical electrophysiological examination of diabetic peripheral neuropathy in articles from 2008 to 2017. For this purpose, PubMed, Scopus and Embase databases of journals were used for searching articles. The researchers indicated that diabetes (both types) is a very disturbing health issue in the modern world and should be given serious attention. Based on conducted studies, it was demonstrated that there are different procedures for prevention and treatment of diabetes-related health problems such as diabetic polyneuropathy (DPN). The first objective quantitative indication of the peripheral neuropathy is abnormality of sensory and motor nerve conduction tests. Electrophysiology is accurate, reliable and sensitive. It can be reproduced and also is a noninvasive approach in the assessment of peripheral nerve function. The methodological review has found that the best method for quantitative indication of the peripheral neuropathy compared with all other methods is clinical electrophysiological examination. For best results, standard protocols such as temperature control and equipment calibration are recommended. Copyright © 2018. Published by Elsevier Ltd.

Incidence and impact of CMV infection in very low birth weight infants.

PubMed

Turner, Kristen M; Lee, Henry C; Boppana, Suresh B; Carlo, Waldemar A; Randolph, David A

2014-03-01

Congenital cytomegalovirus (CMV) is the leading cause of nongenetic deafness in children in the United States and can cause neurodevelopmental impairment in term infants. Limited data exist regarding congenital CMV infections in preterm infants. We aimed to determine the incidence and association with outcomes of congenital CMV in very low birth weight (VLBW) preterm infants. VLBW infants born in 1993 to 2008 and admitted to the University of Alabama in Birmingham Regional Neonatal ICU were screened on admission for congenital CMV. CMV status and clinical outcomes were identified by using internal patient databases and hospital-based medical records. The primary outcome was death. Secondary outcomes included evidence of neurologic injury in the form of abnormal cranial ultrasound findings, sensorineural hearing loss, or abnormal motor development. Multivariate analysis was performed. Eighteen of 4594 VLBW infants had congenital CMV (0.39%; 95% confidence interval, 0.25%-0.62%). An additional 16 infants (0.35%; 95% confidence interval, 0.21%-0.57%) were identified who acquired CMV postnatally. Congenital CMV was not associated with death. Compared with controls, congenitally infected VLBW infants were more likely to have hearing loss at initial screening (67% vs. 9%, P < .0001) and confirmed at follow-up (83% vs. 2.1%, P < .0001). Congenital CMV was also associated with abnormal neuroimaging (72% vs. 25%, P < .0001) and adverse developmental motor outcomes (43% vs. 9%, P = .02). Acquired CMV was not associated with any adverse outcomes. Congenital CMV in VLBW infants is associated with high rates of neurologic injury and hearing loss but not death.

The Effectiveness of a Computer Game-Based Rehabilitation Platform for Children With Cerebral Palsy: Protocol for a Randomized Clinical Trial

PubMed Central

Parmar, Sanjay; Gandhi, Dorcas BC; Rempel, Gina Ruth; Restall, Gayle; Sharma, Monika; Narayan, Amitesh; Pandian, Jeyaraj; Naik, Nilashri; Savadatti, Ravi R; Kamate, Mahesh Appasaheb

2017-01-01

Background It is difficult to engage young children with cerebral palsy (CP) in repetitive, tedious therapy. As such, there is a need for innovative approaches and tools to motivate these children. We developed the low-cost, computer game-based rehabilitation platform CGR that combines fine manipulation and gross movement exercises with attention and planning game activities appropriate for young children with CP. Objective The objective of this study is to provide evidence of the therapeutic value of CGR to improve upper extremity (UE) motor function for children with CP. Methods This randomized controlled, single-blind, clinical trial with an active control arm will be conducted at 4 sites. Children diagnosed with CP between the ages of 4 and 10 years old with moderate UE impairments and fine motor control abnormalities will be recruited. Results We will test the difference between experimental and control groups using the Quality of Upper Extremity Skills Test (QUEST) and Peabody Developmental Motor Scales, Second Edition (PDMS-2) outcome measures. The parents of the children and the therapist experiences with the interventions and tools will be explored using semi-structured interviews using the qualitative description approach. Conclusions This research protocol, if effective, will provide evidence for the therapeutic value and feasibility of CGR in the pediatric rehabilitation of UE function. Trial Registration Clinicaltrials.gov NCT02728375; http:https://clinicaltrials.gov/ct2/show/NCT02728375 (Archived by WebCite at http://www.webcitation.org/6qDjvszvh) PMID:28526673

Gastroesophageal reflux disease-associated esophagitis induces endogenous cytokine production leading to motor abnormalities.

PubMed

Rieder, Florian; Cheng, Ling; Harnett, Karen M; Chak, Amitabh; Cooper, Gregory S; Isenberg, Gerard; Ray, Monica; Katz, Jeffry A; Catanzaro, Andrew; O'Shea, Robert; Post, Anthony B; Wong, Richard; Sivak, Michael V; McCormick, Thomas; Phillips, Manijeh; West, Gail A; Willis, Joseph E; Biancani, Piero; Fiocchi, Claudio

2007-01-01

Gastroesophageal reflux disease is a condition frequently associated with esophagitis and motor abnormalities. Recent evidence suggests that proinflammatory cytokines, such as interleukin (IL)-1beta and IL-6, may be implicated because they reduce esophageal muscle contractility, but these results derive from in vitro or animal models of esophagitis. This study used human esophageal cells and tissues to identify the cellular source of cytokines in human esophagitis investigate whether cytokines can be induced by gastric refluxate, and examine whether esophageal tissue- or cell-derived mediators affect muscle contractility. Endoscopic mucosal biopsy specimens were obtained from patients with and without esophagitis, organ-cultured, and undernatants were assessed for cytokine content. The cytokine profile of esophageal epithelial, fibroblast, and muscle cells was analyzed, and esophageal mucosa and cell products were tested in an esophageal circular muscle contraction assay. The mucosa of esophagitis patients produced significantly greater amounts of IL-1beta and IL-6 compared with those of control patients. Cultured esophageal epithelial cells produced IL-6, as did fibroblasts and muscle cells. Epithelial cells exposed to buffered, but not denatured, gastric juice produced IL-6. Undernatants of mucosal biopsy cultures from esophagitis patients reduced esophageal muscle contraction, as did supernatants from esophageal epithelial cell cultures. The human esophagus produces cytokines capable of reducing contractility of esophageal muscle cells. Exposure to gastric juice is sufficient to stimulate esophageal epithelial cells to produce IL-6, a cytokine able to alter esophageal contractility. These results indicate that classic cytokines are important mediators of the motor disturbances associated with human esophageal inflammation.

The role of white matter microstructure in inhibitory deficits in patients with schizophrenia.

PubMed

Du, Xiaoming; Kochunov, Peter; Summerfelt, Ann; Chiappelli, Joshua; Choa, Fow-Sen; Hong, L Elliot

Inhibitory-excitatory (I-E) imbalance has increasingly been proposed as a fundamental mechanism giving rise to many schizophrenia-related pathophysiology. The integrity of I-E functions should require precise and rapid electrical signal transmission. We hypothesized that part of the I-E abnormality in schizophrenia may originate from their known abnormal white matter connectivity that may interfere the I-E functions. We test this using short-interval intracortical inhibition (SICI) vs. intracortical facilitation (ICF) which is a non-invasive measurement of I-E signaling. SICI-ICF from left motor cortex and white matter microstructure were assessed in schizophrenia patients and healthy controls. Schizophrenia patients showed significantly reduced SICI but not ICF. White matter microstructure as measured by fraction anisotropy (FA) in diffusion tensor imaging had a significant effect on SICI in patients, such that weaker SICI was associated with lower FA in several white matter tracts, most strongly with left corona radiata (r = -0.68, p = 0.0002) that contains the fibers connecting with left motor cortex. Left corticospinal tract, which carries the motor fibers to peripheral muscular output, also showed significant correlation with SICI (r = -0.54, p = 0.005). Mediation analysis revealed that much of the schizophrenia disease effect on SICI can be accounted for by mediation through left corona radiata. SICI was also significantly associated with the performance of processing speed in patients. This study demonstrated the importance of structural circuitry integrity in inhibitory signaling in schizophrenia, and encouraged modeling the I-E dysfunction in schizophrenia from a circuitry perspective. Published by Elsevier Inc.

Intrinsic signature of essential tremor in the cerebello-frontal network

PubMed Central

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

2015-01-01

See Raethjen and Muthuraman (doi:10.1093/brain/awv238) for a scientific commentary on this article. Essential tremor is a movement disorder characterized by tremor during voluntary movements, mainly affecting the upper limbs. The cerebellum and its connections to the cortex are known to be involved in essential tremor, but no task-free intrinsic signatures of tremor related to structural cerebellar defects have so far been found in the cortical motor network. Here we used voxel-based morphometry, tractography and resting-state functional MRI at 3 T to compare structural and functional features in 19 patients with essential tremor and homogeneous symptoms in the upper limbs, and 19 age- and gender-matched healthy volunteers. Both structural and functional abnormalities were found in the patients' cerebellum and supplementary motor area. Relative to the healthy controls, the essential tremor patients' cerebellum exhibited less grey matter in lobule VIII and less effective connectivity between each cerebellar cortex and the ipsilateral dentate nucleus. The patient's supplementary motor area exhibited (i) more grey matter; (ii) a lower amplitude of low-frequency fluctuation of the blood oxygenation level-dependent signal; (iii) less effective connectivity between each supplementary motor area and the ipsilateral primary motor hand area, and (iv) a higher probability of connection between supplementary motor area fibres and the spinal cord. Structural and functional changes in the supplementary motor area, but not in the cerebellum, correlated with clinical severity. In addition, changes in the cerebellum and supplementary motor area were interrelated, as shown by a correlation between the lower amplitude of low-frequency fluctuation in the supplementary motor area and grey matter loss in the cerebellum. The structural and functional changes observed in the supplementary motor area might thus be a direct consequence of cerebellar defects: the supplementary motor area would attempt to reduce tremor in the motor output by reducing its communication with M1 hand areas and by directly modulating motor output via its corticospinal projections. PMID:26115677

BDNF Val66Met polymorphism is associated with abnormal interhemispheric transfer of a newly acquired motor skill.

PubMed

Morin-Moncet, Olivier; Beaumont, Vincent; de Beaumont, Louis; Lepage, Jean-Francois; Théoret, Hugo

2014-05-01

Recent data suggest that the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene can alter cortical plasticity within the motor cortex of carriers, which exhibits abnormally low rates of cortical reorganization after repetitive motor tasks. To verify whether long-term retention of a motor skill is also modulated by the presence of the polymorphism, 20 participants (10 Val66Val, 10 Val66Met) were tested twice at a 1-wk interval. During each visit, excitability of the motor cortex was measured by transcranial magnetic stimulations (TMS) before and after performance of a procedural motor learning task (serial reaction time task) designed to study sequence-specific learning of the right hand and sequence-specific transfer from the right to the left hand. Behavioral results showed a motor learning effect that persisted for at least a week and task-related increases in corticospinal excitability identical for both sessions and without distinction for genetic group. Sequence-specific transfer of the motor skill from the right hand to the left hand was greater in session 2 than in session 1 only in the Val66Met genetic group. Further analysis revealed that the sequence-specific transfer occurred equally at both sessions in the Val66Val genotype group. In the Val66Met genotype group, sequence-specific transfer did not occur at session 1 but did at session 2. These data suggest a limited impact of Val66Met polymorphism on the learning and retention of a complex motor skill and its associated changes in corticospinal excitability over time, and a possible modulation of the interhemispheric transfer of procedural learning. Copyright © 2014 the American Physiological Society.

Role of the Sensorimotor Cortex in Tourette Syndrome using Multimodal Imaging

PubMed Central

Tinaz, Sule; Belluscio, Beth A.; Malone, Patrick; van der Veen, Jan Willem; Hallett, Mark; Horovitz, Silvina G.

2016-01-01

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics. Most patients describe uncomfortable premonitory sensations preceding the tics and a subjective experience of increased sensitivity to tactile stimuli. These reports indicate that a sensory processing disturbance is an important component of TS together with motor phenomena. Thus, we focused our investigation on the role of the sensorimotor cortex (SMC) in TS using multimodal neuroimaging techniques. We measured the gamma-aminobutyric acid (GABA)+/Creatine (Cre) ratio in the SMC using GABA 1H magnetic resonance spectroscopy. We recorded the baseline beta activity in the SMC using magnetoencephalography and correlated GABA+/Cre ratio with baseline beta band power. Finally, we examined the resting state functional connectivity (FC) pattern of the SMC using functional magnetic resonance imaging (fMRI). GABA+/Cre ratio in the SMC did not differ between patients and controls. Correlation between the baseline beta band power and GABA+/Cre ratio was abnormal in patients. The anterior insula showed increased FC with the SMC in patients. These findings suggest that altered limbic input to the SMC and abnormal GABA-mediated beta oscillations in the SMC may underpin some of the sensorimotor processing disturbances in TS and contribute to tic generation. PMID:25044024

Phrenic Nerve Conduction Abnormalities Correlate with Diaphragmatic Descent in Chronic Obstructive Pulmonary Disease.

PubMed

El-Tantawi, Gihan A Younis; Imam, Mohamed H; Morsi, Tamer S

2015-01-01

Diaphragmatic weakness in chronic obstructive pulmonary disease (COPD) is ascribed to hyperinflation-induced diaphragm shortening as well as impairment in cellular and subcellular structures. Although phrenic neuropathy is known to cause diaphragmatic weakness, phrenic neuropathy is rarely considered in COPD. This work aimed at assessing phrenic nerve conduction in COPD and its relation to radiographic hyperinflation and pulmonary function. Forty COPD patients were evaluated. Radiographic parameters of lung hyperinflation were measured on postero-anterior and lateral chest x-ray films. Flow volume loop parameters were obtained from all patients. Motor conduction study of the phrenic nerves was performed and potentials were recorded over the xiphoid process and the ipsilateral 7th intercostal space. Twenty-seven healthy subjects were enrolled as controls. Parameters of phrenic nerve conduction differed significantly in patients compared to controls. Phrenic nerve abnormalities were detected in 17 patients (42.5%). Electrophysiological measures correlated with diaphragmatic angle of depression on lateral view films and with lung height on postero-anterior films. They did not correlate with the flow volume loop data or disease severity score. Phrenic nerve conduction abnormality is an appreciated finding in COPD. Nerve stretching associated with diaphragmatic descent can be a suggested mechanism for nerve lesion. The presence of phrenic neuropathy may be an additional contributing factor to diaphragmatic dysfunction in COPD patients.

Pre-movement planning processes in people with congenital mirror movements.

PubMed

Franz, E A; Fu, Y

2017-10-01

Pre-movement processes were investigated in people with Congenital mirrormovement (CMM), a rare disorder in which bilateral movement (mirroring) occurs in the upper distal extremities (primarily the hands and fingers) during intended unilateral movements. Abnormal density of ipsilateral corticospinal projections is an established hallmark of CMM. This study tested whether the Lateralised Readiness Potential (LRP), which reflects movement planning and readiness, is also abnormal in people with CMM. Twenty-eight neurologically-normal controls and 8 people with CMM were tested on a unimanual Go/No-go task while electroencephalography (EEG) was recorded to assess the LRP. No significant group differences were found in reaction time (RT). However, significantly smaller LRP amplitudes were found, on average, in the CMM group compared to Controls at central-motor (C3,C4) sites in stimulus-locked and response-locked epochs; similar group differences were also found at further frontal sites (F3,F4) during response-locked epochs. Abnormal brain activity in pre-movement processes associated with response planning and preparation is present in people with CMM. Aberrant bilateral activity during pre-movement processes is clearly implicated; whether part of the etiology of CMM, or as a mechanism of neuro-compensation, is not yet known. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Abnormal tactile temporal discrimination in psychogenic dystonia.

PubMed

Morgante, F; Tinazzi, M; Squintani, G; Martino, D; Defazio, G; Romito, L; Albanese, A; Di Matteo, A; Quartarone, A; Girlanda, P; Fiorio, M; Berardelli, A

2011-09-20

Neurophysiologic studies demonstrated that patients with primary torsion dystonia (PTD) and with psychogenic dystonia (Psy-D) share similar abnormalities in the motor system. In this study, we evaluated somatosensory function in Psy-D by testing temporal discrimination threshold (TDT), and compared the results with those obtained in patients with PTD. TDT of tactile stimuli was assessed in 10 patients with Psy-D, 10 patients with PTD, and 16 control subjects. The 2 groups of patients were matched for age, gender, disease duration, and distribution of dystonia. Tactile stimuli consisted of pairs of non-noxious electrical shocks delivered to the right or left hand at interstimulus interval increasing from 0 to 400 msec, in 10-msec steps. TDT was defined as the value at which subjects recognized the 2 stimuli as asynchronous. TDT was higher in Psy-D and PTD compared to control subjects, for both the right and the left hand. In a subgroup of patients with unilateral dystonia (Psy-D = 4, PTD = 5), TDT did not differ between the affected and the unaffected side in both groups of patients. Disease duration was not correlated to the increased TDT value. Our study suggests an impaired processing of somatosensory inputs in both Psy-D and PTD. These abnormalities might represent a neurophysiological trait predisposing to develop a dystonic posture triggered by psychiatric and psychological factors.

Control of Abnormal Synchronization in Neurological Disorders

PubMed Central

Popovych, Oleksandr V.; Tass, Peter A.

2014-01-01

In the nervous system, synchronization processes play an important role, e.g., in the context of information processing and motor control. However, pathological, excessive synchronization may strongly impair brain function and is a hallmark of several neurological disorders. This focused review addresses the question of how an abnormal neuronal synchronization can specifically be counteracted by invasive and non-invasive brain stimulation as, for instance, by deep brain stimulation for the treatment of Parkinson’s disease, or by acoustic stimulation for the treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation, we illustrate how insights into the dynamics of complex systems contribute to successful model-based approaches, which use methods from synergetics, non-linear dynamics, and statistical physics, for the development of novel therapies for normalization of brain function and synaptic connectivity. Based on the intrinsic multistability of the neuronal populations induced by spike timing-dependent plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between synaptic connectivity and dynamics of the neuronal networks in order to restore more physiological patterns of connectivity via desynchronization of neuronal activity. The very goal is to shift the neuronal population by stimulation from an abnormally coupled and synchronized state to a desynchronized regime with normalized synaptic connectivity, which significantly outlasts the stimulation cessation, so that long-lasting therapeutic effects can be achieved. PMID:25566174

Rebound nystagmus: EOG analysis of a case with a floccular tumour.

PubMed Central

Yamazaki, A; Zee, D S

1979-01-01

Eye movements were recorded and quantitatively analysed in a patient with a tumour initially involving the cerebellar flocculus. Ocular motor abnormalities included (1) impaired smooth pursuit, (2) impaired cancellation of the vestibulo-ocular reflex when fixating an object rotating with the head, and (3) gaze paretic and rebound nystagmus. Comparable findings have been reported in monkeys with experimental floccular lesions. The rebound nystagmus (but not the other ocular motor abnormalities) disappeared when the tumour appeared to invade the brain stem in the region near the vestibular nuclei. This finding suggests that the floccular lesion unmasked a bias which created rebound nystagmus and that the bias probably arose in the vestibular nuclei. PMID:508695

Are high lags of accommodation in myopic children due to motor deficits?

PubMed

Labhishetty, Vivek; Bobier, William R

2017-01-01

Children with a progressing myopia exhibit an abnormal pattern of high accommodative lags coupled with high accommodative convergence (AC/A) and high accommodative adaptation. This is not predicted by the current models of accommodation and vergence. Reduced accommodative plant gain and reduced sensitivity to blur have been suggested as potential causes for this abnormal behavior. These etiologies were tested by altering parameters (sensory, controller and plant gains) in the Simulink model of accommodation. Predictions were then compared to the static and dynamic blur accommodation (BA) measures taken using a Badal optical system on 12 children (6 emmetropes and 6 myopes, 8-13years) and 6 adults (20-35years). Other critical parameters such as CA/C, AC/A, and accommodative adaptation were also measured. Usable BA responses were classified as either typical or atypical. Typical accommodation data confirmed the abnormal pattern of myopia along with an unchanged CA/C. Main sequence relationship remained invariant between myopic and nonmyopic children. An overall reduction was noted in the response dynamics such as peak velocity and acceleration with age. Neither a reduced plant gain nor reduced blur sensitivity could predict the abnormal accommodative behavior. A model adjustment reflecting a reduced accommodative sensory gain (ASG) coupled with an increased AC cross-link gain and reduced vergence adaptive gain does predict the empirical findings. Empirical measures also showed a greater frequency of errors in accommodative response generation (atypical responses) in both myopic and control children compared to adults. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Moving Rubber Hand Illusion Reveals that Explicit Sense of Agency for Tapping Movements Is Preserved in Functional Movement Disorders

PubMed Central

Marotta, Angela; Bombieri, Federica; Zampini, Massimiliano; Schena, Federico; Dallocchio, Carlo; Fiorio, Mirta; Tinazzi, Michele

2017-01-01

Functional movement disorders (FMD) are characterized by motor symptoms (e.g., tremor, gait disorder, and dystonia) that are not compatible with movement abnormalities related to a known organic cause. One key clinical feature of FMD is that motor symptoms are similar to voluntary movements but are subjectively experienced as involuntary by patients. This gap might be related to abnormal self-recognition of bodily action, which involves two main components: sense of agency and sense of body ownership. The aim of this study was to systematically investigate whether this function is altered in FMD, specifically focusing on the subjective feeling of agency, body ownership, and their interaction during normal voluntary movements. Patients with FMD (n = 21) and healthy controls (n = 21) underwent the moving Rubber Hand Illusion (mRHI), in which passive and active movements can differentially elicit agency, ownership or both. Explicit measures of agency and ownership were obtained via a questionnaire. Patients and controls showed a similar pattern of response: when the rubber hand was in a plausible posture, active movements elicited strong agency and ownership; implausible posture of the rubber hand abolished ownership but not agency; passive movements suppressed agency but not ownership. These findings suggest that explicit sense of agency and body ownership are preserved in FMD. The latter finding is shared by a previous study in FMD using a static version of the RHI, whereas the former appears to contrast with studies demonstrating altered implicit measures of agency (e.g., sensory attenuation). Our study extends previous findings by suggesting that in FMD: (i) the sense of body ownership is retained also when interacting with the motor system; (ii) the subjective experience of agency for voluntary tapping movements, as measured by means of mRHI, is preserved. PMID:28634447

Multiple Factors Are Involved in the Dysarthria Associated with Parkinson's Disease: A Review with Implications for Clinical Practice and Research

ERIC Educational Resources Information Center

Sapir, Shimon

2014-01-01

Purpose: Motor speech abnormalities are highly common and debilitating in individuals with idiopathic Parkinson's disease (IPD). These abnormalities, collectively termed hypokinetic dysarthria (HKD), have been traditionally attributed to hypokinesia and bradykinesia secondary to muscle rigidity and dopamine deficits. However, the role of…

Pressure-flow characteristics of normal and disordered esophageal motor patterns.

PubMed

Singendonk, Maartje M J; Kritas, Stamatiki; Cock, Charles; Ferris, Lara F; McCall, Lisa; Rommel, Nathalie; van Wijk, Michiel P; Benninga, Marc A; Moore, David; Omari, Taher I

2015-03-01

To perform pressure-flow analysis (PFA) in a cohort of pediatric patients who were referred for diagnostic manometric investigation. PFA was performed using purpose designed Matlab-based software. The pressure-flow index (PFI), a composite measure of bolus pressurization relative to flow and the impedance ratio, a measure of the extent of bolus clearance failure were calculated. Tracings of 76 pediatric patients (32 males; 9.1 ± 0.7 years) and 25 healthy adult controls (7 males; 36.1 ± 2.2 years) were analyzed. Patients mostly had normal motility (50%) or a category 4 disorder and usually weak peristalsis (31.5%) according to the Chicago Classification. PFA of healthy controls defined reference ranges for PFI ≤142 and impedance ratio ≤0.49. Pediatric patients with pressure-flow (PF) characteristics within these limits had normal motility (62%), most patients with PF characteristics outside these limits also had an abnormal Chicago Classification (61%). Patients with high PFI and disordered motor patterns all had esophagogastric junction outflow obstruction. Disordered PF characteristics are associated with disordered esophageal motor patterns. By defining the degree of over-pressurization and/or extent of clearance failure, PFA may be a useful adjunct to esophageal pressure topography-based classification. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of Chronic Hypoxia in the Development of Neurocognitive Abnormalities in Preterm Infants with Bronchopulmonary Dysplasia

ERIC Educational Resources Information Center

Raman, Lakshmi; Georgieff, Michael K.; Rao, Raghavendra

2006-01-01

Bronchopulmonary dysplasia is the most common pulmonary morbidity in preterm infants and is associated with chronic hypoxia. Animal studies have demonstrated structural, neurochemical and functional alterations due to chronic hypoxia in the developing brain. Long-term impairments in visual-motor, gross and fine motor, articulation, reading,…

The neurological underpinnings of cluttering: Some initial findings.

PubMed

Ward, David; Connally, Emily L; Pliatsikas, Christos; Bretherton-Furness, Jess; Watkins, Kate E

2015-03-01

Cluttering is a fluency disorder characterised by overly rapid or jerky speech patterns that compromise intelligibility. The neural correlates of cluttering are unknown but theoretical accounts implicate the basal ganglia and medial prefrontal cortex. Dysfunction in these brain areas would be consistent with difficulties in selection and control of speech motor programs that are characteristic of speech disfluencies in cluttering. There is a surprising lack of investigation into this disorder using modern imaging techniques. Here, we used functional MRI to investigate the neural correlates of cluttering. We scanned 17 adults who clutter and 17 normally fluent control speakers matched for age and sex. Brain activity was recorded using sparse-sampling functional MRI while participants viewed scenes and either (i) produced overt speech describing the scene or (ii) read out loud a sentence provided that described the scene. Speech was recorded and analysed off line. Differences in brain activity for each condition compared to a silent resting baseline and between conditions were analysed for each group separately (cluster-forming threshold Z>3.1, extent p<0.05, corrected) and then these differences were further compared between the two groups (voxel threshold p<0.01, extent>30 voxels, uncorrected). In both conditions, the patterns of activation in adults who clutter and control speakers were strikingly similar, particularly at the cortical level. Direct group comparisons revealed greater activity in adults who clutter compared to control speakers in the lateral premotor cortex bilaterally and, as predicted, on the medial surface (pre-supplementary motor area). Subcortically, adults who clutter showed greater activity than control speakers in the basal ganglia. Specifically, the caudate nucleus and putamen were overactive in adults who clutter for the comparison of picture description with sentence reading. In addition, adults who clutter had reduced activity relative to control speakers in the lateral anterior cerebellum bilaterally. Eleven of the 17 adults who clutter also stuttered. This comorbid diagnosis of stuttering was found to contribute to the abnormal overactivity seen in the group of adults who clutter in the right ventral premotor cortex and right anterior cingulate cortex. In the remaining areas of abnormal activity seen in adults who clutter compared to controls, the subgroup who clutter and stutter did not differ from the subgroup who clutter but do not stutter. Our findings were in good agreement with theoretical predictions regarding the neural correlates of cluttering. We found evidence for abnormal function in the basal ganglia and their cortical output target, the medial prefrontal cortex. The findings are discussed in relation to models of cluttering that point to problems with motor control of speech. This paper reports findings on the neural correlates seen in adults who clutter, and offers hypotheses as to how these might map onto the behaviours seen amongst those who clutter. Readers will be able to (a) identify the structures that are implicated in the disorder of cluttering, (b) understand arguments relating these structures to the behavioural expression of the disorder, (c) understand some of the complexities in interpreting data pertaining to recovery from cluttering, (d) understand where future efforts in research into the neurological correlates of cluttering should be focussed. Copyright © 2015. Published by Elsevier Inc.

Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case–Control Pilot Study

PubMed Central

Gilbert, Donald L.; Erickson, Craig A.; Horn, Paul S.; Shaffer, Rebecca C.; Wink, Logan K.; Laue, Cameron S.; Wu, Steve W.

2016-01-01

Abstract Objective: This case–control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. Methods: We studied youth with ASD aged 11–18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. Results: Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. Conclusion: In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing. PMID:27007257

Inter-cortical Modulation from Premotor to Motor Plasticity.

PubMed

Huang, Ying-Zu; Chen, Rou-Shayn; Fong, Po-Yu; Rothwell, John C; Chuang, Wen-Li; Weng, Yi-Hsin; Lin, Wey-Yil; Lu, Chin-Song

2018-06-11

Plasticity is involved in daily activities but abnormal plasticity may be deleterious. In this study, we found that motor plasticity could be modulated by suppressing the premotor cortex with the theta burst form of repetitive transcranial magnetic stimulation. Such changes in motor plasticity were associated with reduced learning of a simple motor task. We postulate that the premotor cortex adjusts the amount of motor plasticity to modulate motor learning through heterosynaptic metaplasticity. The present results provide an insight into how the brain physiologically coordinates two different areas to bring them into a functional network. This concept could be employed to intervene in diseases with abnormal plasticity. Primary motor cortex (M1) plasticity is known to be influenced by the excitability and prior activation history of M1 itself. However, little is known about how its plasticity is influenced by other areas of the brain. In the present study on humans of either sex who were known to respond to theta burst stimulation from previous studies, we found plasticity of M1 could be modulated by suppressing the premotor cortex with the theta burst form of repetitive transcranial magnetic stimulation. Motor plasticity was distorted and disappeared 30 min and 120 min respectively after premotor excitability was suppressed. Further evaluation revealed that such changes in motor plasticity were associated with impaired learning of a simple motor task. We postulate that the premotor cortex modulates the amount of plasticity within M1 through heterosynaptic metaplasticity, and that this may impact on learning of a simple motor task previously shown to be directly affected by M1 plasticity. The present results provide an insight into how the brain physiologically coordinates two different areas to bring them into a functional network. Furthermore, such concepts could be translated into therapeutic approaches for diseases with aberrant plasticity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation of afferent pain pathways in adrenomyeloneuropathic patients.

PubMed

Yagüe, Sara; Veciana, Misericordia; Casasnovas, Carlos; Ruiz, Montserrat; Pedro, Jordi; Valls-Solé, Josep; Pujol, Aurora

2018-03-01

Patients with adrenomyeloneuropathy may have dysfunctions of visual, auditory, motor and somatosensory pathways. We thought on examining the nociceptive pathways by means of laser evoked potentials (LEPs), to obtain additional information on the pathophysiology of this condition. In 13 adrenomyeloneuropathic patients we examined LEPs to leg, arm and face stimulation. Normative data were obtained from 10 healthy subjects examined in the same experimental conditions. We also examined brainstem auditory evoked potentials (BAEPs), pattern reversal full-field visual evoked potentials (VEPs), motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs). Upper and lower limb MEPs and SEPs, as well as BAEPs, were abnormal in all patients, while VEPs were abnormal in 3 of them (23.1%). LEPs revealed abnormalities to stimulation of the face in 4 patients (30.7%), the forearm in 4 patients (30.7%) and the leg in 10 patients (76.9%). The pathologic process of adrenomyeloneuropathy is characterized by a preferential involvement of auditory, motor and somatosensory tracts and less severely of the visual and nociceptive pathways. This non-inflammatory distal axonopathy preferably damages large myelinated spinal tracts but there is also partial involvement of small myelinated fibres. LEPs studies can provide relevant information about afferent pain pathways involvement in adrenomyeloneuropathic patients. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Unknown Pseudocholinesterase Deficiency in a Patient Undergoing TIVA with Planned Motor Evoked Potential Monitoring: A Case Report.

PubMed

Binkley, Candace

2016-06-01

Pseudocholinesterase abnormalities are a genetic cause of aberrant metabolism of the depolarizing muscle relaxant succinylcholine. This article examines a case where succinylcholine was chosen to facilitate intubation due to its ultra short duration and the request of the surgeon to monitor motor evoked potentials. Following succinylcholine administration the neurophysiologist was unable to obtain motor evoked potentials. This case study highlights the intraoperative and postoperative management of an elderly patient with an unknown pseudocholinesterase deficiency.

Exploratory analysis of diffusion tensor imaging in children with attention deficit hyperactivity disorder: evidence of abnormal white matter structure.

PubMed

Pastura, Giuseppe; Doering, Thomas; Gasparetto, Emerson Leandro; Mattos, Paulo; Araújo, Alexandra Prüfer

2016-06-01

Abnormalities in the white matter microstructure of the attentional system have been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Diffusion tensor imaging (DTI) is a promising magnetic resonance imaging (MRI) technology that has increasingly been used in studies of white matter microstructure in the brain. The main objective of this work was to perform an exploratory analysis of white matter tracts in a sample of children with ADHD versus typically developing children (TDC). For this purpose, 13 drug-naive children with ADHD of both genders underwent MRI using DTI acquisition methodology and tract-based spatial statistics. The results were compared to those of a sample of 14 age- and gender-matched TDC. Lower fractional anisotropy was observed in the splenium of the corpus callosum, right superior longitudinal fasciculus, bilateral retrolenticular part of the internal capsule, bilateral inferior fronto-occipital fasciculus, left external capsule and posterior thalamic radiation (including right optic radiation). We conclude that white matter tracts in attentional and motor control systems exhibited signs of abnormal microstructure in this sample of drug-naive children with ADHD.

Clinical findings and electrodiagnostic testing in 108 consecutive cases of lumbosacral radiculopathy due to herniated disc.

PubMed

Mondelli, M; Aretini, A; Arrigucci, U; Ginanneschi, F; Greco, G; Sicurelli, F

2013-10-01

This prospective study aim to examine whether clinical findings and electrodiagnostic testing (EDX) in patients with lumbosacral monoradiculopathy due to herniated disc (HD) differ as a function of root involvement level (L5 vs. S1) and HD zone (paramedian vs. intraforaminal). All patients with L4, L5 or S1 monoradiculopathy were prospectively enrolled at four electromyography (EMG) labs over a 2-year period. The diagnosis was based on a congruence between patient history and MRI evidence of HD. We compared the sensitivities of clinical findings and EDX with respect to both root involvement level and HD zone. Multivariate logistic regression was performed in order to verify the association between abnormal EMG, clinical, and neuroradiological findings. One hundred and eight patients (mean age 47.7 years, 55% men) were consecutively enrolled. Sensory loss in the painful dermatome was the most frequent finding at physical examination (56% of cases). EMG was abnormal in at least one muscle supplied by femoral and sciatic nerves in 45 cases (42%). Inclusion of paraspinal muscles increased sensitivity to only 49% and that of proximal muscles was useless. Motor and sensory neurography was seldom abnormal. The most frequent motor neurographic abnormalities were a delay of F-wave minimum latency and decrease in the compound muscle action potential amplitude from extensor digitorum brevis and abductor hallucis in L5 and S1 radiculopathies, respectively. Sensory neurography was usually normal, the amplitude of sensory nerve action potential was seldom reduced when HD injured dorsal root ganglion or postganglionic root fibres. Multivariate logistic regression analysis showed that EMG abnormalities could be predicted by myotomal muscular weakness, abnormal deep reflexes, and paraesthesiae. The only clinical and electrophysiological differences with respect to root involvement level concerned deep reflexes and motor neurography of deep peroneal and tibial nerves. Only some EDX parameters are helpful for the diagnosis of lumbosacral radiculopathy. EMG was abnormal in less than 50% of cases and its abnormalities could be predicted by some clinical findings. However, neurography is useful as a tool for differential diagnosis between radiculopathy and more diffuse disorders of the peripheral nervous system (polyneuropathy, plexopathy). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease.

PubMed

Hickey, Patrick; Stacy, Mark

2016-01-01

Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming, and overall management.

Subjective complaints of cognitive symptoms are related to psychometric findings of memory deficits in patients with HIV-1 infection.

PubMed

Poutiainen, E; Elovaara, I

1996-05-01

Eighty-five subjects at various stages of human immunodeficiency virus (HIV-1) infection and 39 seronegative controls underwent neurological and neuropsychological evaluation to assess the relationship between cognitive test results and subjective complaints (cognitive, affective, motor, and other). The effect of psychiatric disorders on the association between cognitive performance and complaints of the patients was also examined. Patients with symptomatic infection had higher frequency of complaints than subjects at asymptomatic stage. Detailed neuropsychological examination confirmed a strong association between poor verbal memory and cognitive complaints. Poor performance on cognitive speed and flexibility was associated with motor complaints and motor abnormalities. These associations were not explained by psychiatric disorders or elevated depression questionnaire scores. Our observations indicate that, especially in symptomatic HIV-1 infection cognitive changes reported by patients often reflect "objective" cognitive decline, and may be the earliest signs of HIV-1 associated cognitive disorder. No direct relationship was observed between "subjective" complaints and neuropsychological performance of asymptomatic subjects. Understanding the significance of reported cognitive changes have important therapeutic implications.

Effects of active, passive and motor imagery paradigms on cerebral and peripheral hemodynamics in older volunteers: a functional TCD study.

PubMed

Salinet, Angela S M; Panerai, Ronney B; Robinson, Thompson G

2012-06-01

This study aimed to compare the response of metabolic-induced cerebral hemodynamic changes measured using transcranial Doppler (TCD) ultrasonography during passive, active and motor imagery paradigms, and associated peripheral hemodynamic responses. Continuous recordings of bilateral cerebral blood flow velocity (CBFv), blood pressure, heart rate and end-tidal CO(2) were performed in 12 right-handed subjects (aged ≥45 y) before, during and after 60 s of active, passive and mental-imagined paradigms. The results revealed no significant difference in CBFv responses between the paradigms and, furthermore, the temporal patterns of the hemodynamic responses showed some degree of similarity. Moreover, significant changes were seen in cerebral and peripheral hemodynamic responses for all paradigms. Our results suggest that active, passive and motor imagery paradigms can be used interchangeably to assess hemodynamic responses. This will enable more detailed noninvasive assessment in patients, where voluntary movement is not possible, but where abnormalities of cerebral hemodynamic control mechanisms can be anticipated. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Environmental enrichment mitigates the impact of ancestral stress on motor skill and corticospinal tract plasticity.

PubMed

McCreary, J Keiko; Erickson, Zachary T; Metz, Gerlinde A S

2016-10-06

An adverse fetal environment in utero has been associated with long-term alterations in brain structure and function, and a higher risk of neurological disorders in later life. A common consequence of early adverse experience is impaired motor system function. A causal relationship for stress-associated impairments and a suitable therapy, however, have not been determined yet. To investigate the impact of ancestral stress on corticospinal tract (CST) morphology and fine motor performance in rats, and to determine if adverse programming by ancestral stress can be mitigated by environmental enrichment therapy in rats. The study examined F3 offspring generated by three lineages; one with prenatal stress only in the F1 generation, one with compounding effects of multigenerational prenatal stress, and a non-stress control lineage. F3 offspring from each lineage were injected with biotinylated dextran amine (BDA) into the motor cortex for anterograde tracing of the CST. Examination of the CST revealed reduced axonal density in the ancestrally stressed lineages. These anatomical changes were associated with significant impairments in skilled walking, as indicated by reduced foot placement accuracy and disturbed inter-limb coordination. Therapeutic intervention by environmental enrichment reduced the neuromorphological consequences of ancestral stress and restored skilled walking ability. The data suggest a causal relationship between stress-induced abnormal CST function and loss of fine motor performance. Thus, ancestral stress may be a determinant of motor system development and motor skill. Environmental enrichment may represent an effective intervention for the adverse programming by ancestral stress and trauma. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Juvenile Onset HD

MedlinePlus

... the treating primary physician, neurologist, or psychiatrist including: Treating physician records documenting progression of motor, cognitive, and psychiatric symptoms, family history, and abnormal neurological exam findings consistent with ...

Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans

PubMed Central

Haagensen, Brian N.; Christensen, Mark S.; Madsen, Kristoffer H.; Rowe, James B.; Løkkegaard, Annemette; Siebner, Hartwig R.

2015-01-01

Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51–84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an aberrant reinforcement signal producing an abnormal motor drive that ultimately triggers involuntary movements. PMID:25882651

Progressive Motor Deficit is Mediated by the Denervation of Neuromuscular Junctions and Axonal Degeneration in Transgenic Mice Expressing Mutant (P301S) Tau Protein.

PubMed

Yin, Zhuoran; Valkenburg, Femke; Hornix, Betty E; Mantingh-Otter, Ietje; Zhou, Xingdong; Mari, Muriel; Reggiori, Fulvio; Van Dam, Debby; Eggen, Bart J L; De Deyn, Peter P; Boddeke, Erik

2017-01-01

Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we use a novel transgenic tau mouse line, Tau 58/4, with enhanced neuron-specific expression of P301S mutant tau to investigate the motor abnormalities in association with the peripheral nervous system. Using stationary beam, gait, and rotarod tests, motor deficits were found in Tau 58/4 mice already 3 months after birth, which deteriorated during aging. Hyperphosphorylated tau was detected in the cell bodies and axons of motor neurons. At the age of 9 and 12 months, significant denervation of the neuromuscular junction in the extensor digitorum longus muscle was observed in Tau 58/4 mice, compared to wild-type mice. Muscle hypotrophy was observed in Tau 58/4 mice at 9 and 12 months. Using electron microscopy, we observed ultrastructural changes in the sciatic nerve of 12-month-old Tau 58/4 mice indicative of the loss of large axonal fibers and hypomyelination (assessed by g-ratio). We conclude that the accumulated hyperphosphorylated tau in the axon terminals may induce dying-back axonal degeneration, myelin abnormalities, neuromuscular junction denervation, and muscular atrophy, which may be the mechanisms responsible for the deterioration of the motor function in Tau 58/4 mice. Tau 58/4 mice represent an interesting neuromuscular degeneration model, and the pathological mechanisms might be responsible for motor signs observed in some human tauopathies.

[Esophageal motor disorders in cirrhotic patients with esophageal varices non-submitted to endoscopic treatment].

PubMed

Flores, Priscila Pollo; Lemme, Eponina Maria de Oliveira; Coelho, Henrique Sérgio Moraes

2005-01-01

The hepatic cirrhosis has as one of the main morbid-mortality causes, the portal hypertension with the development of esophageal varices, the possibility of a digestive hemorrhage and worsening of hepatic insufficiency. It is important to identify causal predictive or aggravating factors and if possible to prevent them. In the last years, it has been observed the association of esophageal motor disorders and gastro-esophageal reflux in cirrhotic patients with esophageal varices. To study the prevalence of the esophageal motility disorders and among them, the ineffective esophageal motility, in patients with hepatic cirrhosis and esophageal varices, without previous endoscopic therapeutic and the predictive factors. Prospectively, it has been evaluate 74 patients suffering from liver cirrhosis and esophagic varices, without previous endoscopic treatment. All of them were submitted to a clinical protocol, esophageal manometry and 55 patients also held the ambulatory esophageal pHmetry. Esophageal motility disorders have been found in 44 patients (60%). The most prevalent was the ineffective esophageal motility, observed in 28%. The abnormal reflux disease was diagnosed through the pHmetry in 35% of the patients. There were no correlation between the manometrical abnormality in general and the ineffective esophageal motility in particular and the esophageal or gastroesophageal reflux disease symptoms, the abnormal reflux, the disease seriousness, the ascites presence and the gauge of the varices. The majority of cirrhotic patients with non-treated esophageal varices present esophageal motor disorders. No predictive factor was found. The clinical relevance of these findings need more researches in the scope to define the real meaning of theses abnormalities.

Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis

PubMed Central

Solanky, Bhavana S.; Muhlert, Nils; Tur, Carmen; Edden, Richard A. E.; Wheeler-Kingshott, Claudia A. M.; Miller, David H.; Thompson, Alan J.; Ciccarelli, Olga

2015-01-01

Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = −0.403 mM, 95% confidence intervals −0.792, −0.014, P = 0.043) and sensorimotor cortex (adjusted difference = −0.385 mM, 95% confidence intervals −0.667, −0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid concentration in the sensorimotor cortex. Specifically for each unit decrease in gamma-aminobutyric acid levels (in mM), there was a predicted −10.86 (95% confidence intervals −16.786 to −4.482) decrease in grip strength (kg force) (P < 0.001) and −8.74 (95% confidence intervals −13.943 to −3.015) decrease in muscle strength (P < 0.006). This study suggests that reduced gamma-aminobutyric acid levels reflect pathological abnormalities that may play a role in determining physical disability. These abnormalities may include decreases in the pre- and postsynaptic components of gamma-aminobutyric acid neurotransmission and in the density of inhibitory neurons. Additionally, the reduced gamma-aminobutyric acid concentration may contribute to the neurodegenerative process, resulting in increased firing of axons, with consequent increased energy demands, which may lead to neuroaxonal degeneration and loss of the compensatory mechanisms that maintain motor function. This study supports the idea that modulation of gamma-aminobutyric acid neurotransmission may be an important target for neuroprotection in multiple sclerosis. See De Stefano and Giorgio (doi:10.1093/brain/awv213) for a scientific commentary on this article. PMID:26304151

Disruption of Axonal Transport Perturbs Bone Morphogenetic Protein (BMP) - Signaling and Contributes to Synaptic Abnormalities in Two Neurodegenerative Diseases

PubMed Central

Kang, Min Jung; Hansen, Timothy J.; Mickiewicz, Monique; Kaczynski, Tadeusz J.; Fye, Samantha; Gunawardena, Shermali

2014-01-01

Formation of new synapses or maintenance of existing synapses requires the delivery of synaptic components from the soma to the nerve termini via axonal transport. One pathway that is important in synapse formation, maintenance and function of the Drosophila neuromuscular junction (NMJ) is the bone morphogenetic protein (BMP)-signaling pathway. Here we show that perturbations in axonal transport directly disrupt BMP signaling, as measured by its downstream signal, phospho Mad (p-Mad). We found that components of the BMP pathway genetically interact with both kinesin-1 and dynein motor proteins. Thick vein (TKV) vesicle motility was also perturbed by reductions in kinesin-1 or dynein motors. Interestingly, dynein mutations severely disrupted p-Mad signaling while kinesin-1 mutants showed a mild reduction in p-Mad signal intensity. Similar to mutants in components of the BMP pathway, both kinesin-1 and dynein motor protein mutants also showed synaptic morphological defects. Strikingly TKV motility and p-Mad signaling were disrupted in larvae expressing two human disease proteins; expansions of glutamine repeats (polyQ77) and human amyloid precursor protein (APP) with a familial Alzheimer's disease (AD) mutation (APPswe). Consistent with axonal transport defects, larvae expressing these disease proteins showed accumulations of synaptic proteins along axons and synaptic abnormalities. Taken together our results suggest that similar to the NGF-TrkA signaling endosome, a BMP signaling endosome that directly interacts with molecular motors likely exist. Thus problems in axonal transport occurs early, perturbs BMP signaling, and likely contributes to the synaptic abnormalities observed in these two diseases. PMID:25127478

White Matter Abnormalities and Dystonic Motor Disorder Associated with Mutations in the "SLC16A2" Gene

ERIC Educational Resources Information Center

Gika, Artemis D.; Siddiqui, Ata; Hulse, Anthony J.; Edward, Selvakumari; Fallon, Penny; McEntagart, Meriel E.; Jan, Wajanat; Josifova, Dragana; Lerman-Sagie, Tally; Drummond, James; Thompson, Edward; Refetoff, Samuel; Bonnemann, Carsten G.; Jungbluth, Heinz

2010-01-01

Aim: Mutations in the "SLC16A2" gene have been implicated in Allan-Herndon-Dudley syndrome (AHDS), an X-linked learning disability syndrome associated with thyroid function test (TFT) abnormalities. Delayed myelination is a non-specific finding in individuals with learning disability whose genetic basis is often uncertain. The aim of this study…

Pathophysiology of dysarthria in cerebral palsy.

PubMed Central

Neilson, P D; O'Dwyer, N J

1981-01-01

Electromyograms were recorded with hooked-wire electrodes from sixteen lip, tongue and jaw muscles in six normal and seven cerebral palsied adult subjects during a variety of speech and non-speech tasks. The recorded patterns of muscle activity fail to support a number of theories concerning the pathophysiology of dysarthria in cerebral palsy. There was no indication of weakness in individual articulator muscles. There was no evidence of uncontrolled sustained background activity or of abnormal tonic stretch reflex responses in lip or tongue muscles. Primitive or pathological reflexes could not be elicited by orofacial stimulation. No imbalance between positive and negative oral responses was observed. The view that random involuntary movement disrupts essentially normal voluntary control in athetosis was not supported. Each cerebral palsied subject displayed an idiosyncratic pattern of abnormal muscle activity which was reproduced across repetitions of the same phrase, indicating a consistent defect in motor programming. PMID:7334387

Cerebral morphology and functional sparing after prenatal frontal cortex lesions in rats.

PubMed

Kolb, B; Cioe, J; Muirhead, D

1998-03-01

Rats were given suction lesions of the presumptive frontal cortex on embryonic day 18 (E18) and subsequently tested, as adults, on tests of spatial navigation (Morris water task, radial arm maze), motor tasks (Whishaw reaching task, beam walking), and locomotor activity. Frontal cortical lesions at E18 affected cerebral morphogenesis, producing unusual morphological structures including abnormal patches of neurons in the cortex and white matter as well as neuronal bridges between the hemispheres. A small sample of E18 operates also had hydrocephaly. The animals with E18 lesions without hydrocephalus were behaviorally indistinguishable from littermate controls. The results demonstrate that animals with focal lesions of the presumptive frontal cortex have gross abnormalities in cerebral morphology but the lesions leave the functions normally subserved by the frontal cortex in adult rats unaffected. The results are discussed in the context of a hypothesis regarding the optimal times for functional recovery from cortical injury.

Spinal inhibition and motor function in adults with spastic cerebral palsy

PubMed Central

Condliffe, E. G.; Jeffery, D. T.; Emery, D. J.

2016-01-01

Key points Abnormal activation of motoneurons in the spinal cord by sensory pathways is thought to contribute to impaired movement control and spasticity in individuals with cerebral palsy.Here we use single motor unit recordings to show how individual motoneurons in the spinal cord respond to sensory inputs in a group of participants with cerebral palsy having different degrees of motor dysfunction.In participants who had problems walking independently and required assistive devices such as wheelchairs, sensory pathways only excited motoneurons in the spinal cord.In contrast, in participants with cerebral palsy who walked independently for long distances, sensory inputs both inhibited and excited motoneurons in the spinal cord, similar to what we found in uninjured control participants.These findings demonstrate that in individuals with severe cerebral palsy, inhibitory control of motoneurons from sensory pathways is reduced and may contribute to motor dysfunction and spasticity. Abstract Reduced inhibition of spinal motoneurons by sensory pathways may contribute to heightened reflex activity, spasticity and impaired motor function in individuals with cerebral palsy (CP). To measure if the activation of inhibitory post‐synaptic potentials (IPSPs) by sensory inputs is reduced in CP, the tonic discharge rate of single motor units from the soleus muscle was plotted time‐locked to the occurrence of a sensory stimulation to produce peri‐stimulus frequencygrams (PSFs). Stimulation to the medial arch of the foot was used to activate cutaneomuscular afferents in 17 adults with bilateral spastic CP and 15 neurologically intact (NI) peers. Evidence of IPSP activation from the PSF profiles, namely a marked pause or reduction in motor unit firing rates at the onset of the cutaneomuscular reflex, was found in all NI participants but in only half of participants with CP. In the other half of the participants with CP, stimulation of cutaneomuscular afferents produced a PSF profile indicative of a pure excitatory post‐synaptic potential, with firing rates increasing above the mean pre‐stimulus rate for 300 ms or more. The amplitude of motoneuron inhibition during the period of IPSP activation, as measured from the surface EMG, was less in participants with poor motor function as evaluated with the Gross Motor Functional Classification System (r = 0.72, P < 0.001) and the Functional Mobility Scale (r = −0.82, P < 0.001). These findings demonstrate that in individuals with CP, reduced activation of motoneuron IPSPs by sensory inputs is associated with reduced motor function and may contribute to enhanced reflexes and spasticity in CP. PMID:26842905

Manometric abnormalities of the oesophagus in patients with Parkinson's disease.

PubMed

Castell, J A; Johnston, B T; Colcher, A; Li, Q; Gideon, R M; Castell, D O

2001-08-01

Dysphagia in Parkinson's disease (PD) is known to correlate with abnormalities of oropharyngeal function. Oesophageal abnormalities have not been previously demonstrated to correlate with dysphagia. The aim of the study was to determine if motor dysfunction of the oesophageal body correlates with dysphagia or disease severity in PD. Twenty-two patients with PD were assessed for the severity of their dysphagia (scale of 1-7) and severity of PD (Hoehn and Yahr scale 1-4). All underwent oesophageal manometry. Dysphagia was present daily in 10 patients (45%). Parkinson's disease was graded as severe (Hoehn and Yahr > or =3) in eight (36%) patients. Oesophageal manometry was abnormal in 16 (73%) patients. Thirteen patients had either complete aperistalsis or multiple simultaneous contractions (diffuse oesophageal spasm). These findings were significantly more common in patients with daily dysphagia (90% vs. 33%; P < 0.005), and were not related to duration or severity of PD. We conclude that the presence of aperistalsis or multiple simultaneous contractions in the oesophagus does correlate with dysphagia and is independent of PD severity or duration. This may reflect selective involvement of either the dorsal motor nucleus of the vagus or the oesophageal myenteric plexus.

Comparing two motor assessment tools to evaluate neurobehavioral intervention effects in infants with very low birth weight at 1 year.

PubMed

Van Hus, Janeline W P; Jeukens-Visser, Martine; Koldewijn, Karen; Van Sonderen, Loekie; Kok, Joke H; Nollet, Frans; Van Wassenaer-Leemhuis, Aleid G

2013-11-01

Infants with very low birth weight (VLBW) are at increased risk for motor deficits, which may be reduced by early intervention programs. For detection of motor deficits and to monitor intervention, different assessment tools are available. It is important to choose tools that are sensitive to evaluate the efficacy of intervention on motor outcome. The purpose of this study was to compare the Alberta Infant Motor Scale (AIMS) and the Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development-Dutch Second Edition (BSID-II-NL) in their ability to evaluate effects of an early intervention, provided by pediatric physical therapists, on motor development in infants with VLBW at 12 months corrected age (CA). This was a secondary study in which data collected from a randomized controlled trial (RCT) were used. At 12 months CA, 116 of 176 infants with VLBW participating in an RCT on the effect of the Infant Behavioral Assessment and Intervention Program were assessed with both the AIMS and the PDI. Intervention effects on the AIMS and PDI were compared. Corrected for baseline differences, significant intervention effects were found for AIMS and PDI scores. The highest effect size was for the AIMS subscale sit. A significant reduction of abnormal motor development in the intervention group was found only with the AIMS. No Dutch norms are available for the AIMS. The responsiveness of the AIMS to detect intervention effects was better than that of the PDI. Therefore, caution is recommended in monitoring infants with VLBW only with the PDI, and the use of both the AIMS and the Bayley Scales of Infant Development is advised when evaluating intervention effects on motor development at 12 months CA.

Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis

PubMed Central

Iwai, Yuta; Shibuya, Kazumoto; Misawa, Sonoko; Sekiguchi, Yukari; Watanabe, Keisuke; Amino, Hiroshi; Kuwabara, Satoshi

2016-01-01

Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS), suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP) amplitude (index of motor neuronal loss) and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44), ALS patients (n = 140) had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p < 0.05), greater threshold changes in depolarizing threshold electrotonus (p < 0.05) and depolarizing current threshold relationship (i.e. less accommodation; (p < 0.05), greater superexcitability (a measure of fast potassium current; p < 0.05) and reduced late subexcitability (a measure of slow potassium current; p < 0.05), suggesting increased persistent sodium currents and decreased potassium currents. The reduced potassium currents were found even in the patient subgroups with normal CMAP (> 5mV). Regression analyses showed that SDTC (R = -0.22) and depolarizing threshold electrotonus (R = -0.22) increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS. PMID:27383069

Abnormal intrinsic esophageal innervation in congenital diaphragmatic hernia: a likely cause of motor dysfunction.

PubMed

Pederiva, Federica; Rodriguez, Jose I; Ruiz-Bravo, Elena; Martinez, Leopoldo; Tovar, Juan A

2009-03-01

Patients with congenital diaphragmatic hernia (CDH) often have dilated esophagus and gastroesophageal reflux. Sparse intrinsic esophageal innervation has been described in rats with CDH, but this issue has not been investigated in patients with CDH. The present study tests the hypothesis that innervatory anomalies could account for motor dysfunction in human CDH. The esophagi of CDH (n = 6) and control babies dead of other causes (n = 6) were included in paraffin, transversally sectioned, and immunostained with antineurofilament and anti-S-100 antibodies. The proportion of the section surface occupied by neural structures, the ganglionar surface, and the number of neurons per ganglion were measured in 2 to 5 low-power fields from the proximal and distal esophagus with the assistance of image analysis software. Mann-Whitney tests were used for comparing the results using a threshold of significance of P < .05. The percentage of neural/muscle surface was similar in the upper esophagus in both groups, but it was significantly decreased in the lower esophagus of patients with CDH in comparison with controls. There was a relative scarcity of neural tissue in the intermuscular plexus of the lower esophagus. On the other hand, the ganglionar surface and the number of neurons per ganglion were identical in both groups. These results were similar with both immunostainings. Intrinsic innervation of the lower esophagus in CDH is abnormal in terms of decreased density of neural structures in the intermuscular plexus. These neural crest-derived anomalies could explain in part the esophageal dysfunction in survivors of CDH.

[Role of short-latency somatosensory evoked potential in the diagnosis of chronic inflammatory demyelinating polyneuropathy].

PubMed

Sun, Rui-Di; Fu, Bing; Jiang, Jun

2017-05-01

To investigate the role of short-latency somatosensory evoked potential (SSEP) in the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). A total of 48 children with a confirmed or suspected CIDP and 40 healthy children were enrolled. Nerve electrophysiological examination and/or SSEP examination was performed (the children in the healthy control group only underwent SSEP examination). Four-lead electromyography was used for nerve electrophysiological examination, including at least 4 motor nerves and 2 sensory nerves. N6 (elbow potential), N13 (cervical cord potential), and N20 (cortex potential) of the median nerve and N8 (popliteal fossa potential), N22 (lumbar cord potential), and P39 (cortex potential) of the tibial nerve were observed by SSEP examination. Among the 48 children with CIDP, 35 had demyelination in both motor and sensory nerves, 8 had demyelination in sensory nerves, and 5 had axonal degeneration. SSEP examination showed that 7 had conduction abnormality in the trunk of the brachial plexus and/or the posterior root and 33 had damage in the lumbosacral plexus and/or the posterior root. The 40 children with abnormal findings of SSEP examination included 8 children with affected sensory nerves and 5 children with secondary axonal degeneration who did not meet the electrophysiological diagnostic criteria for CIDP. Compared with the healthy control group, the CIDP group had significantly prolonged latency periods of N13 and N22 (P<0.05). SSEP can be used for the auxiliary diagnosis of CIDP, especially in CIDP children with affected sensory nerves or secondary axonal degeneration.

The usefulness of videomanometry for studying pediatric esophageal motor disease.

PubMed

Kawahara, Hisayoshi; Kubota, Akio; Okuyama, Hiroomi; Oue, Takaharu; Tazuke, Yuko; Okada, Akira

2004-12-01

Abnormalities in esophageal motor function underlie various symptoms in the pediatric population. Manometry remains an important tool for studying esophageal motor function, whereas its analyses have been conducted with considerable subjective interpretation. The usefulness of videomanometry with topographic analysis was examined in the current study. Videomanometry was conducted in 5 patients with primary gastroesophageal reflux disease (GERD), 4 with postoperative esophageal atresia (EA), 1 with congenital esophageal stenosis (CES), and 1 with diffuse esophageal spasms (DES). Digitized videofluoroscopic images were recorded synchronously with manometric digital data in a personal computer. Manometric analysis was conducted with a view of concurrent esophageal contour and bolus transit. Primary GERD patients showed esophageal flow proceeding into the stomach during peristaltic contractions recorded manometrically, whereas patients with EA/CES frequently showed impaired esophageal transit during defective esophageal peristaltic contractions. A characteristic corkscrew appearance and esophageal flow in a to-and-fro fashion were seen with high-amplitude synchronous esophageal contractions in a DES patient. The topographic analysis showed distinctive images characteristic of each pathological condition. Videomanometry is helpful in interpreting manometric data by analyzing concurrent fluoroscopic images. Topographic analyses provide characteristic images reflecting motor abnormalities in pediatric esophageal disease.

Sleep disorders in children with cerebral palsy: neurodevelopmental and behavioral correlates.

PubMed

Romeo, Domenico M; Brogna, Claudia; Quintiliani, Michela; Baranello, Giovanni; Pagliano, Emanuela; Casalino, Tiziana; Sacco, Annalisa; Ricci, Daniela; Mallardi, Maria; Musto, Elisa; Sivo, Serena; Cota, Francesco; Battaglia, Domenica; Bruni, Oliviero; Mercuri, Eugenio

2014-02-01

We aimed to estimate the frequency of sleep disorders in children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC) and to evaluate the relations between sleep disorders and motor, cognitive, and behavioral problems. One hundred and sixty-five children with CP ages 6-16 years (mean age, 11years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Intelligence Scale for Children and the Child Behavior Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. An abnormal total sleep score was found in 19% of children with CP; more than 40% of children had an abnormal score on at least one SDSC factor. The SDSC total score was significantly associated (P<.01) with mental retardation, epilepsy, CBCL scores, and level 5 on the GMFCS. Our results confirm that sleep disorders are common in children with cerebral palsy. The relationship between motor and cognitive behavior and epilepsy should be further explored to better understand how these factors influence one another to identify effective treatments and to improve the well-being of the child. Copyright © 2014 Elsevier B.V. All rights reserved.

[Joubert syndrome and related disorders].

PubMed

Paprocka, Justyna; Jamroz, Ewa

2012-01-01

The cerebellum plays a role not only in motor control but also in motor learning and cognition. Joubert syndrome is a rare heterogeneous inherited genetic disorder characterized by ataxia, hypotonia, developmental delay, and at least one of the following features: neonatal respiratory disturbances or abnormal eye movement. The estimated frequency of Joubert syndrome in the United States is around 1 : 100 000. The term Joubert syndrome and related disorders (JSRD) has been recently coined to describe all disorders presenting with molar tooth sign on brain neuroimaging. Joubert syndrome is believed to be a representative of a new group of disorders named ciliopathies. The identification of seven causal genes (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67/MKS3, ARL13B, CC2D2A) has led to substantial progress in the understanding of the genetic basis of Joubert syndrome. The authors focus on clinical presentation of JSRD, differential diagnosis and molecular background.

A review of brain circuitries involved in stuttering

PubMed Central

Craig-McQuaide, Anna; Akram, Harith; Zrinzo, Ludvic; Tripoliti, Elina

2014-01-01

Stuttering has been the subject of much research, nevertheless its etiology remains incompletely understood. This article presents a critical review of the literature on stuttering, with particular reference to the role of the basal ganglia (BG). Neuroimaging and lesion studies of developmental and acquired stuttering, as well as pharmacological and genetic studies are discussed. Evidence of structural and functional changes in the BG in those who stutter indicates that this motor speech disorder is due, at least in part, to abnormal BG cues for the initiation and termination of articulatory movements. Studies discussed provide evidence of a dysfunctional hyperdopaminergic state of the thalamocortical pathways underlying speech motor control in stuttering. Evidence that stuttering can improve, worsen or recur following deep brain stimulation for other indications is presented in order to emphasize the role of BG in stuttering. Further research is needed to fully elucidate the pathophysiology of this speech disorder, which is associated with significant social isolation. PMID:25452719

Cell death cascade and molecular therapy in ADAR2-deficient motor neurons of ALS.

PubMed

Yamashita, Takenari; Kwak, Shin

2018-06-23

TAR DNA-binding protein (TDP-43) pathology in the motor neurons is the most reliable pathological hallmark of amyotrophic lateral sclerosis (ALS), and motor neurons bearing TDP-43 pathology invariably exhibit failure in RNA editing at the GluA2 glutamine/arginine (Q/R) site due to down-regulation of adenosine deaminase acting on RNA 2 (ADAR2). Conditional ADAR2 knockout (AR2) mice display ALS-like phenotype, including progressive motor dysfunction due to loss of motor neurons. Motor neurons devoid of ADAR2 express Q/R site-unedited GluA2, and AMPA receptors with unedited GluA2 in their subunit assembly are abnormally permeable to Ca 2+ , which results in progressive neuronal death. Moreover, analysis of AR2 mice has demonstrated that exaggerated Ca 2+ influx through the abnormal AMPA receptors overactivates calpain, a Ca 2+ -dependent protease, that cleaves TDP-43 into aggregation-prone fragments, which serve as seeds for TDP-43 pathology. Activated calpain also disrupts nucleo-cytoplasmic transport and gene expression by cleaving molecules involved in nucleocytoplasmic transport, including nucleoporins. These lines of evidence prompted us to develop molecular targeting therapy for ALS by normalization of disrupted intracellular environment due to ADAR2 down-regulation. In this review, we have summarized the work from our group on the cell death cascade in sporadic ALS and discussed a potential therapeutic strategy for ALS. Copyright © 2018 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group.

PubMed

Gyawali, C P; Roman, S; Bredenoord, A J; Fox, M; Keller, J; Pandolfino, J E; Sifrim, D; Tatum, R; Yadlapati, R; Savarino, E

2017-12-01

High-resolution manometry (HRM) has resulted in new revelations regarding the pathophysiology of gastro-esophageal reflux disease (GERD). The impact of new HRM motor paradigms on reflux burden needs further definition, leading to a modern approach to motor testing in GERD. Focused literature searches were conducted, evaluating pathophysiology of GERD with emphasis on HRM. The results were discussed with an international group of experts to develop a consensus on the role of HRM in GERD. A proposed classification system for esophageal motor abnormalities associated with GERD was generated. Physiologic gastro-esophageal reflux is inherent in all humans, resulting from transient lower esophageal sphincter (LES) relaxations that allow venting of gastric air in the form of a belch. In pathological gastro-esophageal reflux, transient LES relaxations are accompanied by reflux of gastric contents. Structural disruption of the esophagogastric junction (EGJ) barrier, and incomplete clearance of the refluxate can contribute to abnormally high esophageal reflux burden that defines GERD. Esophageal HRM localizes the LES for pH and pH-impedance probe placement, and assesses esophageal body peristaltic performance prior to invasive antireflux therapies and antireflux surgery. Furthermore, HRM can assess EGJ and esophageal body mechanisms contributing to reflux, and exclude conditions that mimic GERD. Structural and motor EGJ and esophageal processes contribute to the pathophysiology of GERD. A classification scheme is proposed incorporating EGJ and esophageal motor findings, and contraction reserve on provocative tests during HRM. © 2017 John Wiley & Sons Ltd.

Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia

PubMed Central

Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

2016-01-01

Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug’s side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy. PMID:27891079

A-waves increase the risk of developing neuropathy.

PubMed

Srotova, Iva; Vlckova, Eva; Dusek, Ladislav; Bednarik, Josef

2017-08-01

A-waves, which are observed following the M-wave during motor nerve conduction studies (NCS), are late responses that are frequently found in many types of neurogenic disorders. However, A-waves are also common in healthy individuals, where their significance remains unclear. The aim of this study was to examine whether the occurrence of A-waves does in fact represent an increased risk for the future development of changes upon NCS or needle electromyography (EMG) in the corresponding nerve. Nerve conduction studies/needle electromyography findings at control examination were evaluated in relation to the occurrence of initial A-waves in 327 individuals who had undergone repeated NCS/EMG examination and exhibited normal initial findings, with or without the occurrence of A-waves as the only acceptable abnormality. The odds ratio, which reflects the predictive power of the occurrence of A-waves at the initial testing for the development of an abnormality (neuropathy or radiculopathy) at the follow-up examination, ranged from 2.7 ( p  = .041) in the tibial nerve and 3.9 ( p  = .034) in peroneal one, to 30.0 ( p  = .002) in the ulnar nerve. A-waves constitute an initial abnormality in all nerves, and they may be predictive for the future development of broader NCS/EMG abnormalities in the corresponding nerve.

Volumetric structural brain abnormalities in men with schizophrenia or antisocial personality disorder.

PubMed

Barkataki, Ian; Kumari, Veena; Das, Mrigendra; Taylor, Pamela; Sharma, Tonmoy

2006-05-15

Brain abnormalities are found in association with antisocial personality disorder and schizophrenia, the two mental disorders most implicated in violent behaviour. Structural magnetic resonance imaging was used to investigate the whole brain, cerebellum, temporal lobe, lateral ventricles, caudate nucleus, putamen, thalamus, hippocampus, amygdala and the prefrontal, pre-motor, sensorimotor, occipito-parietal regions in 13 men with antisocial personality disorder, 13 men with schizophrenia and a history of violence, 15 men with schizophrenia without violent history and 15 healthy non-violent men. Compared to controls, the antisocial personality disorder group displayed reductions in whole brain volume and temporal lobe as well as increases in putamen volume. Both schizophrenia groups regardless of violence history exhibited increased lateral ventricle volume, while the schizophrenia group with violent history showed further abnormalities including reduced whole brain and hippocampal volumes and increased putamen size. The findings suggest that individuals with antisocial personality disorder as well as those with schizophrenia and a history of violence have common neural abnormalities, but also show neuro-anatomical differences. The processes by which they came to apparently common ground may, however, differ. The finding of temporal lobe reductions prevalent among those with antisocial personality disorder and hippocampal reduction in the violent men with schizophrenia contributes support for the importance of this region in mediating violent behaviour.

Amblyopia and Binocular Vision

PubMed Central

Birch, Eileen E.

2012-01-01

Amblyopia is the most common cause of monocular visual loss in children, affecting 1.3% to 3.6% of children. Current treatments are effective in reducing the visual acuity deficit but many amblyopic individuals are left with residual visual acuity deficits, ocular motor abnormalities, deficient fine motor skills, and risk for recurrent amblyopia. Using a combination of psychophysical, electrophysiological, imaging, risk factor analysis, and fine motor skill assessment, the primary role of binocular dysfunction in the genesis of amblyopia and the constellation of visual and motor deficits that accompany the visual acuity deficit has been identified. These findings motivated us to evaluate a new, binocular approach to amblyopia treatment with the goals of reducing or eliminating residual and recurrent amblyopia and of improving the deficient ocular motor function and fine motor skills that accompany amblyopia. PMID:23201436

Clinical study on the efficacy of Rajayapana Basti and Baladi Yoga in motor disabilities of cerebral palsy in children

PubMed Central

Shailaja, U.; Rao, Prasanna N.; Girish, K. J.; Arun Raj, G. R.

2014-01-01

Background: Cerebral palsy is a static encephalopathy that may be defined as a non-progressive disorder of posture and movement often associated with epilepsy and abnormalities in speech, vision and intellect resulting from a defect or lesion of the developing brain. There are 25 lakhs cerebral palsy affected children in India. Aim: To assess the efficacy of Rajayapana Basti (RB) and Baladi Yoga in motor disabilities of cerebral palsy in children. Materials and Methods: Total 98 children satisfying diagnostic criteria and between the age group of 2-10 years were included and randomly divided into two groups. In RB with Baladi group (n = 40) patients were treated with Mustadi Rajayapana Basti for 8 days, followed by oral administration of Baladi Yoga with honey and ghee for 60 days. Before administering Basti, patients were subjected to Sarvanga Abhyanga and Sastikashali Pinda Sveda. In the control group (n = 40), patients were given tablets of Godhuma Choorna for 60 days. Before administering the placebo tablet, the patients of the control group were given Sarvanga Abhyanga and Sastikashali Pinda Sveda for 8 days. The patients of the control group were given Basti with lukewarm water for 8 days. Results: RB group has shown improvements in understanding ability (13.43%), speech (10%) and performance skill (11.11%), in fine motor functions such as putting small object in to a container (14.3%), throws the ball in all direction (21.8%), use of thumb and index finger (10.93%), retaining 2 inch cube in fist (19.04%), folds paper and inserts into envelope (10.30%), in gross motor functions such as in crawling (26.7%), sitting (31.7%), standing (13.75%), walking (9.5%) and claps hands (13.9%) respectively. Conclusion: Mustadi RB along with Baladi Yoga provided a significant improvement in all the parameters and has promising result in managing motor disabilities of cerebral palsy in children. PMID:26664239

Clinical study on the efficacy of Rajayapana Basti and Baladi Yoga in motor disabilities of cerebral palsy in children.

PubMed

Shailaja, U; Rao, Prasanna N; Girish, K J; Arun Raj, G R

2014-01-01

Cerebral palsy is a static encephalopathy that may be defined as a non-progressive disorder of posture and movement often associated with epilepsy and abnormalities in speech, vision and intellect resulting from a defect or lesion of the developing brain. There are 25 lakhs cerebral palsy affected children in India. To assess the efficacy of Rajayapana Basti (RB) and Baladi Yoga in motor disabilities of cerebral palsy in children. Total 98 children satisfying diagnostic criteria and between the age group of 2-10 years were included and randomly divided into two groups. In RB with Baladi group (n = 40) patients were treated with Mustadi Rajayapana Basti for 8 days, followed by oral administration of Baladi Yoga with honey and ghee for 60 days. Before administering Basti, patients were subjected to Sarvanga Abhyanga and Sastikashali Pinda Sveda. In the control group (n = 40), patients were given tablets of Godhuma Choorna for 60 days. Before administering the placebo tablet, the patients of the control group were given Sarvanga Abhyanga and Sastikashali Pinda Sveda for 8 days. The patients of the control group were given Basti with lukewarm water for 8 days. RB group has shown improvements in understanding ability (13.43%), speech (10%) and performance skill (11.11%), in fine motor functions such as putting small object in to a container (14.3%), throws the ball in all direction (21.8%), use of thumb and index finger (10.93%), retaining 2 inch cube in fist (19.04%), folds paper and inserts into envelope (10.30%), in gross motor functions such as in crawling (26.7%), sitting (31.7%), standing (13.75%), walking (9.5%) and claps hands (13.9%) respectively. Mustadi RB along with Baladi Yoga provided a significant improvement in all the parameters and has promising result in managing motor disabilities of cerebral palsy in children.

Does a parent-administrated early motor intervention influence general movements and movement character at 3months of age in infants born preterm?

PubMed

Fjørtoft, Toril; Ustad, Tordis; Follestad, Turid; Kaaresen, Per Ivar; Øberg, Gunn Kristin

2017-09-01

Studies of preterm and term-born infants have shown absent fidgety movements and an abnormal movement character to be related to brain lesions and unfavourable neurological outcomes. The present study examines what effect a parent-administered early intervention program applied to preterm infants in a randomised control trial (RCT) between 34 and 36weeks gestational age has on their fidgety movements and overall movement character at three months of age. The study was part of the RCT in an early intervention programme including preterm infants born between 2010 and 2014 at three Norwegian university hospitals. 130 preterm infants participated in the study, with 59 of them in the control group and 71 in the intervention group. Fidgety movements and overall movement character at three months corrected age. No difference was found between the intervention group and the control group in terms of fidgety movements or movement character. Approximately half of the infants in both groups showed an abnormal movement character. No evidence was found in this RCT to suggest that an intervention at 34 to 37weeks gestational age has a significant effect on the fidgety movements or overall movement character of preterm infants. This is in line with the assumption that absent fidgety movements and an abnormal movement character are due to permanent brain injury and are therefore good predictors for later neurological impairments. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered default network resting state functional connectivity in patients with a first episode of psychosis.

PubMed

Alonso-Solís, Anna; Corripio, Iluminada; de Castro-Manglano, Pilar; Duran-Sindreu, Santiago; Garcia-Garcia, Manuel; Proal, Erika; Nuñez-Marín, Fidel; Soutullo, Cesar; Alvarez, Enric; Gómez-Ansón, Beatriz; Kelly, Clare; Castellanos, F Xavier

2012-08-01

Default network (DN) abnormalities have been identified in patients with chronic schizophrenia using "resting state" functional magnetic resonance imaging (R-fMRI). Here, we examined the integrity of the DN in patients experiencing their first episode of psychosis (FEP) compared with sex- and age-matched healthy controls. We collected R-fMRI data from 19 FEP patients (mean age 24.9 ± 4.8 yrs, 14 males) and 19 healthy controls (26.1 ± 4.8 yrs, 14 males) at 3T. Following standard preprocessing, we examined the functional connectivity (FC) of two DN subsystems and the two DN hubs (P<0.0045, corrected). Patients with FEP exhibited abnormal FC that appeared largely restricted to the dorsomedial prefrontal cortex (dMPFC) DN subsystem. Relative to controls, FEP patients exhibited weaker positive FC between dMPFC and posterior cingulate cortex (PCC) and precuneus, extending laterally through the parietal lobe to the posterior angular gyrus. Patients with FEP exhibited weaker negative FC between the lateral temporal cortex and the intracalcarine cortex, bilaterally. The PCC and temporo-parietal junction also exhibited weaker negative FC with the right fusiform gyrus extending to the lingual gyrus and lateral occipital cortex, in FEP patients, compared to controls. By contrast, patients with FEP showed stronger negative FC between the temporal pole and medial motor cortex, anterior precuneus and posterior mid-cingulate cortex. Abnormalities in the dMPFC DN subsystem in patients with a FEP suggest that FC patterns are altered even in the early stages of psychosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Altered Default Network Resting State Functional Connectivity in Patients with a First Episode of Psychosis

PubMed Central

Alonso-Solís, Anna; Corripio, Iluminada; de Castro-Manglano, Pilar; Duran-Sindreu, Santiago; Garcia-Garcia, Manuel; Proal, Erika; Nuñez-Marín, Fidel; Soutullo, Cesar; Alvarez, Enric; Gómez-Ansón, Beatriz; Kelly, Clare; Castellanos, F. Xavier

2012-01-01

Background Default network (DN) abnormalities have been identified in patients with chronic schizophrenia using “resting state” functional magnetic resonance imaging (R-fMRI). Here, we examined the integrity of the DN in patients experiencing their first episode of psychosis (FEP) compared with sex- and age-matched healthy controls. Methods We collected R-fMRI data from 19 FEP patients (mean age 24.9±4.8 yrs, 14 males) and 19 healthy controls (26.1±4.8 yrs, 14 males) at 3 Tesla. Following standard preprocessing, we examined the functional connectivity (FC) of two DN subsystems and the two DN hubs (P<0.0045, corrected). Results Patients with FEP exhibited abnormal FC that appeared largely restricted to the dorsomedial prefrontal cortex (dMPFC) DN subsystem. Relative to controls, FEP patients exhibited weaker positive FC between dMPFC and posterior cingulate cortex (PCC) and precuneus, extending laterally through the parietal lobe to the posterior angular gyrus. Patients with FEP exhibited weaker negative FC between the lateral temporal cortex and the intracalcarine cortex, bilaterally. The PCC and temporo-parietal junction also exhibited weaker negative FC with the right fusiform gyrus extending to the lingual gyrus and lateral occipital cortex, in FEP patients, compared to controls. By contrast, patients with FEP showed stronger negative FC between the temporal pole and medial motor cortex, anterior precuneus and posterior mid-cingulate cortex. Conclusions Abnormalities in the dMPFC DN subsystem in patients with a FEP suggest that FC patterns are altered even in the early stages of psychosis. PMID:22633527

Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon

PubMed Central

Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

2015-01-01

Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities. PMID:26304458

Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon.

PubMed

Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

2015-08-25

Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities.

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.

Arterial spin labelling detects posterior cortical hypoperfusion in non-demented patients with Parkinson's disease.

PubMed

Syrimi, Zoe Joanna; Vojtisek, Lubomir; Eliasova, Ilona; Viskova, Jana; Svatkova, Alena; Vanicek, Jiri; Rektorova, Irena

2017-05-01

While previous studies suggested that perfusion abnormalities in Parkinson's disease (PD) are driven by dementia, our study aimed to identify perfusion underpinning of cognitive alteration in non-demented PD patients. Cerebral blood flow was measured using arterial spin labelling (ASL) in 28 PD patients (age 65 years ± 9.9 SD) and 16 age-matched healthy controls (HC) (age 65 years ± 7.8 SD), who also underwent neurological and cognitive testing. The 3D pseudocontinuous ASL and T2-weighted scans from 22 PD patients and 16 HC were analysed in a voxel-wise manner using SPM8 software. Associations between the ASL values in volumes of interest (VOIs) and behavioural and cognitive measures were assessed by Spearman correlation analysis. Posterior cortical hypoperfusion was found in PD patients compared to HC in the left supramarginal gyrus/superior temporal gyrus (VOI1) and left posterior cingulate/precuneus (VOI2). Positive correlation was revealed between perfusion in the VOI2 and Addenbrooke's Cognitive Examination Revised (ACE-R) scores after filtering out the effect of age, levodopa equivalent dose (LED), and total intracranial volume (TIV) (R = 0.51, p = 0.04). Conversely, negative correlation between VOI1 and ACE-R was detected (R = -0.62, p = 0.01) after regressing out the effects of motor impairment, age, LED, and TIV. In non-demented subjects with PD, blood flow abnormalities in precuneus/posterior cingulate were linked to the level of motor impairment and global cognitive performance. Oppositely, perfusion abnormalities in supramarginal gyrus might serve as a compensatory mechanism for brain degeneration and decreased cognitive performance.

Patients with symptoms of delayed gastric emptying have a high prevalence of oesophageal dysmotility, irrespective of scintigraphic evidence of gastroparesis

PubMed Central

Triadafilopoulos, George; Nguyen, Linda; Clarke, John O

2017-01-01

Background Patients with symptoms suggestive of gastroparesis exhibit several symptoms, such as epigastric pain, postprandial fullness, bloating and regurgitation. It is uncertain if such symptoms reflect underlying oesophageal motor disorder. Aims To examine whether patients with epigastric pain and postprandial distress syndrome suggestive of functional dyspepsia and/or gastroparesis also have concomitant oesophageal motility abnormalities and, if so, whether there are any associations between these disturbances. Methods In this retrospective cohort study, consecutive patients with functional gastrointestinal symptoms suggestive of gastric neuromuscular dysfunction (gastroparesis or functional dyspepsia) underwent clinical assessment, gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring using standard protocols. Results We studied 61 patients with various functional upper gastrointestinal symptoms who underwent gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring. Forty-four patients exhibited gastroparesis by gastric scintigraphy. Oesophageal motility disorders were found in 68% and 42% of patients with or without scintigraphic evidence of gastroparesis respectively, suggesting of overlapping gastric and oesophageal neuromuscular disorder. Forty-three per cent of patients with gastroparesis had abnormal oesophageal acid exposure with mean % pH <4.0 of 7.5 in contrast to 38% of those symptomatic controls with normal gastric emptying, with mean %pH <4.0 of 5.4 (NS). Symptoms of epigastric pain, heartburn/regurgitation, bloating, nausea, vomiting, dysphagia, belching and weight loss could not distinguish patients with or without gastroparesis, although weight loss was significantly more prevalent and severe (p<0.002) in patients with gastroparesis. There was no relationship between oesophageal symptoms and motor or pH abnormalities in either groups. Conclusions Irrespective of gastric emptying delay by scintigraphy, patients with symptoms suggestive of gastric neuromuscular dysfunction have a high prevalence of oesophageal motor disorder and pathological oesophageal acid exposure that may contribute to their symptoms and may require therapy. High-resolution oesophageal manometry and pH monitoring are non-invasive and potentially useful in the assessment and management of these patients. PMID:29177065

Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis.

PubMed

Alshikho, Mohamad J; Zürcher, Nicole R; Loggia, Marco L; Cernasov, Paul; Chonde, Daniel B; Izquierdo Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

2016-12-13

In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [ 11 C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [ 11 C]-PBR28 uptake. In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [ 11 C]-PBR28 binding in the left motor cortex was correlated with FA (r = -0.68, p < 0.05) and cortical thickness (r = -0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = -0.77, p < 0.05), and cortical thickness (r = -0.75, p < 0.05) in the motor cortex. Increased uptake of the glial marker [ 11 C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. © 2016 American Academy of Neurology.

Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis

PubMed Central

Alshikho, Mohamad J.; Zürcher, Nicole R.; Loggia, Marco L.; Cernasov, Paul; Chonde, Daniel B.; Izquierdo Garcia, David; Yasek, Julia E.; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R.; Cudkowicz, Merit E.

2016-01-01

Objective: In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Methods: Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [11C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [11C]-PBR28 uptake. Results: In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [11C]-PBR28 binding in the left motor cortex was correlated with FA (r = −0.68, p < 0.05) and cortical thickness (r = −0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = −0.77, p < 0.05), and cortical thickness (r = −0.75, p < 0.05) in the motor cortex. Conclusions: Increased uptake of the glial marker [11C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. PMID:27837005

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.

Neuroimaging and Neurodevelopmental Outcome in Extremely Preterm Infants

PubMed Central

Barnes, Patrick D.; Bulas, Dorothy; Slovis, Thomas L.; Finer, Neil N.; Wrage, Lisa A.; Das, Abhik; Tyson, Jon E.; Stevenson, David K.; Carlo, Waldemar A.; Walsh, Michele C.; Laptook, Abbot R.; Yoder, Bradley A.; Van Meurs, Krisa P.; Faix, Roger G.; Rich, Wade; Newman, Nancy S.; Cheng, Helen; Heyne, Roy J.; Vohr, Betty R.; Acarregui, Michael J.; Vaucher, Yvonne E.; Pappas, Athina; Peralta-Carcelen, Myriam; Wilson-Costello, Deanne E.; Evans, Patricia W.; Goldstein, Ricki F.; Myers, Gary J.; Poindexter, Brenda B.; McGowan, Elisabeth C.; Adams-Chapman, Ira; Fuller, Janell; Higgins, Rosemary D.

2015-01-01

BACKGROUND: Extremely preterm infants are at risk for neurodevelopmental impairment (NDI). Early cranial ultrasound (CUS) is usual practice, but near-term brain MRI has been reported to better predict outcomes. We prospectively evaluated MRI white matter abnormality (WMA) and cerebellar lesions, and serial CUS adverse findings as predictors of outcomes at 18 to 22 months’ corrected age. METHODS: Early and late CUS, and brain MRI were read by masked central readers, in a large cohort (n = 480) of infants <28 weeks’ gestation surviving to near term in the Neonatal Research Network. Outcomes included NDI or death after neuroimaging, and significant gross motor impairment or death, with NDI defined as cognitive composite score <70, significant gross motor impairment, and severe hearing or visual impairment. Multivariable models evaluated the relative predictive value of neuroimaging while controlling for other factors. RESULTS: Of 480 infants, 15 died and 20 were lost. Increasing severity of WMA and significant cerebellar lesions on MRI were associated with adverse outcomes. Cerebellar lesions were rarely identified by CUS. In full multivariable models, both late CUS and MRI, but not early CUS, remained independently associated with NDI or death (MRI cerebellar lesions: odds ratio, 3.0 [95% confidence interval: 1.3–6.8]; late CUS: odds ratio, 9.8 [95% confidence interval: 2.8–35]), and significant gross motor impairment or death. In models that did not include late CUS, MRI moderate-severe WMA was independently associated with adverse outcomes. CONCLUSIONS: Both late CUS and near-term MRI abnormalities were associated with outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of near-term neuroimaging. PMID:25554820

Ocular motor characteristics of different subtypes of spinocerebellar ataxia: distinguishing features.

PubMed

Kim, Ji Sun; Kim, Ji Soo; Youn, Jinyoung; Seo, Dae-Won; Jeong, Yuri; Kang, Ji-Hoon; Park, Jeong Ho; Cho, Jin Whan

2013-08-01

Because of frequent involvement of the cerebellum and brainstem, ocular motor abnormalities are key features of spinocerebellar ataxias and may aid in differential diagnosis. Our objective for this study was to distinguish the subtypes by ophthalmologic features after head-shaking and positional maneuvers, which are not yet recognized as differential diagnostic tools in most common forms of spinocerebellar ataxias. Of the 302 patients with a diagnosis of cerebellar ataxia in 3 Korean University Hospitals from June 2011 to June 2012, 48 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, or 8 or with undetermined spinocerebellar ataxias were enrolled. All patients underwent a video-oculographic recording of fixation abnormalities, gaze-evoked nystagmus, positional and head-shaking nystagmus, and dysmetric saccades. Logistic regression analysis controlling for disease duration revealed that spontaneous and positional downbeat nystagmus and perverted head-shaking nystagmus were strong predictors for spinocerebellar ataxia 6, whereas saccadic intrusions and oscillations were identified as positive indicators of spinocerebellar ataxia 3. In contrast, the presence of gaze-evoked nystagmus and dysmetric saccades was a negative predictor of spinocerebellar ataxia 2. Positional maneuvers and horizontal head shaking occasionally induced or augmented saccadic intrusions/oscillations in patients with spinocerebellar ataxia types 1, 2, and 3 and undetermined spinocerebellar ataxia. The results indicated that perverted head-shaking nystagmus may be the most sensitive parameter for SCA6, whereas saccadic intrusions/oscillations are the most sensitive for spinocerebellar ataxia 3. In contrast, a paucity of gaze-evoked nystagmus and dysmetric saccades is more indicative of spinocerebellar ataxia 2. Head-shaking and positional maneuvers aid in defining ocular motor characteristics in spinocerebellar ataxias. © 2013 Movement Disorder Society. Copyright © 2013 Movement Disorder Society.

GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Facciolo, Rosa Maria, E-mail: rm.facciolo@unical.i; Crudo, Michele; Giusi, Giuseppina

2010-02-15

At date the major neuroreceptors i.e. gamma-aminobutyric acid{sub A} (GABA{sub A}R) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABA{sub A}R agonist (muscimol, MUS; 0,1 mug/g body weight) and/or its antagonist bicuculline (BIC; 1 mug/g body weight) have corroborated a GABA{sub A}ergic role on motor behaviors. In particular, MUS induced moderate (p < 0.05) and great (p < 0.01) increases of swimming towards food sources and resting states after 24 (1 dose) and 96 (4 doses) h treatmentmore » sessions, respectively, when compared to controls. Conversely, BIC caused a very strong (p < 0.001) reduction of the former behavior and in some cases convulsive swimming. From the correlation of BIC-dependent behavioral changes to neuronal morphological and ORXR transcriptional variations, it appeared that the disinhibitory action of GABA{sub A}R was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS + BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABA{sub A}R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.« less

Association between vestibular function and motor performance in hearing-impaired children.

PubMed

Maes, Leen; De Kegel, Alexandra; Van Waelvelde, Hilde; Dhooge, Ingeborg

2014-12-01

The clinical balance performance of normal-hearing (NH) children was compared with the balance performance of hearing-impaired (HI) children with and without vestibular dysfunction to identify an association between vestibular function and motor performance. Prospective study. Tertiary referral center. Thirty-six children (mean age, 7 yr 5 mo; range, 3 yr 8 mo-12 yr 11 mo) divided into three groups: NH children with normal vestibular responses, HI children with normal vestibular responses, and HI children with abnormal vestibular function. A vestibular test protocol (rotatory and collic vestibular evoked myogenic potential testing) in combination with three clinical balance tests (balance beam walking, one-leg hopping, one-leg stance). Clinical balance performance. HI children with abnormal vestibular test results obtained the lowest quotients of motor performance, which were significantly lower compared with the NH group (p < 0.001 for balance beam walking and one-leg stance; p = 0.003 for one-leg hopping). The balance performance of the HI group with normal vestibular responses was better in comparison with the vestibular impaired group but still significantly lower compared with the NH group (p = 0.020 for balance beam walking; p = 0.001 for one-leg stance; not significant for one-leg hopping). These results indicate an association between vestibular function and motor performance in HI children, with a more distinct motor deterioration if a vestibular impairment is superimposed to the auditory dysfunction.

Training based on mirror visual feedback influences transcallosal communication.

PubMed

Avanzino, Laura; Raffo, Alessia; Pelosin, Elisa; Ogliastro, Carla; Marchese, Roberta; Ruggeri, Piero; Abbruzzese, Giovanni

2014-08-01

Mirror visual feedback (MVF) therapy has been demonstrated to be successful in neurorehabilitation, probably inducing neuroplasticity changes in the primary motor cortex (M1). However, it is not known whether MVF training influences the hemispheric balance between the M1s. This topic is of extreme relevance when MVF training is applied to stroke rehabilitation, as the competitive interaction between the two hemispheres induces abnormal interhemispheric inhibition (IHI) that weakens motor function in stroke patients. In the present study, we evaluated, in a group of healthy subjects, the effect of motor training and MVF training on the excitability of the two M1s and the IHI between M1s. The IHI from the 'active' M1 to the opposite M1 (where 'active' means the M1 contralateral to the moving hand in the motor training and the M1 of the seen hand in the MVF training) increased, after training, in both the experimental conditions. Only after motor training did we observe an increase in the excitability of the active M1. Our findings show that training based on MVF may influence the excitability of the transcallosal pathway and support its use in disorders where abnormal IHI is a potential target, such as stroke, where an imbalance between the affected and unaffected M1s has been documented. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

WiiPD--an approach for the objective home assessment of Parkinson's disease.

PubMed

Synnott, J; Chen, L; Nugent, C D; Moore, G

2011-01-01

This paper introduces WiiPD, an approach to home-based objective assessment of Parkinson's disease. WiiPD aims to make use of the many capabilities of the Nintendo Wii Remote in combination with a number of bespoke data gathering methods to provide a rich and engaging user experience that can capture a wide range of motor and non-motor metrics. In this paper we discuss the architecture of the approach, and provide details of the implementation and testing of the motor-assessment component of the system. Initial results of testing on 6 users indicate that the system is able to differentiate between normal and abnormal motor performance, suggesting that the system has the potential to monitor the motor fluctuations associated with Parkinson's disease.

Abnormalities in early markers of muscle involvement support a delay in myogenesis in spinal muscular atrophy.

PubMed

Martínez-Hernández, Rebeca; Bernal, Sara; Alias, Laura; Tizzano, Eduardo F

2014-06-01

Spinal muscular atrophy (SMA) is characterized by loss of motor neurons in the spinal cord that results in muscle denervation and profound weakness in affected patients. We sought evidence for primary muscle involvement in the disease during human development by analyzing the expression of several muscle cytoskeletal components (i.e. slow, fast, and developmental myosin, desmin, and vimentin) in fetal or postnatal skeletal muscle samples from 5 SMA cases and 6 controls. At 14 weeks' gestation, SMA samples had higher percentages of myotubes expressing fast myosin and lower percentages of myotubes expressing slow myosin versus control samples. Desmin and vimentin were highly expressed at prenatal stages without notable differences between control and SMA samples, although both proteins showed persistent immunostaining in atrophic fibers in postnatal SMA samples. We also studied the expression of Pax7-positive nuclei as a marker of satellite cells and found no differences between control and SMA prenatal samples. There was, however, a significant increase in satellite cells in postnatal atrophic SMA fibers, suggesting an abnormal myogenic process. Together, these results support the hypothesis of a delay in muscle maturation as one of the primary pathologic components of SMA. Furthermore, myosins and Pax7 may be useful research markers of muscle involvement in this disease.

Pediatric endurance and limb strengthening for children with cerebral palsy (PEDALS) – a randomized controlled trial protocol for a stationary cycling intervention

PubMed Central

Fowler, Eileen G; Knutson, Loretta M; DeMuth, Sharon K; Sugi, Mia; Siebert, Kara; Simms, Victoria; Azen, Stanley P; Winstein, Carolee J

2007-01-01

Background In the past, effortful exercises were considered inappropriate for children with spastic cerebral palsy (CP) due to concern that they would escalate abnormalities including spasticity and abnormal movement patterns. Current scientific evidence indicates that these concerns were unfounded and that therapeutic interventions focused on muscle strengthening can lead to improved functional ability. However, few studies have examined the potential benefits of cardiorespiratory fitness exercises in this patient population. Methods/design The rationale and design of a randomized controlled trial examining the effects of a stationary cycling intervention for children with CP are outlined here. Sixty children with spastic diplegic CP between the ages of 7 and 18 years and Gross Motor Function Classification System (GMFCS) levels of I, II, or III will be recruited for this study. Participants will be randomly assigned to either an intervention (cycling) or a control (no cycling) group. The cycling intervention will be divided into strengthening and cardiorespiratory endurance exercise phases. During the strengthening phase, the resistance to lower extremity cycling will be progressively increased using a uniquely designed limb-loaded mechanism. The cardiorespiratory endurance phase will focus on increasing the intensity and duration of cycling. Children will be encouraged to exercise within a target heart rate (HR) range (70 – 80% maximum HR). Thirty sessions will take place over a 10–12 week period. All children will be evaluated before (baseline) and after (follow-up) the intervention period. Primary outcome measures are: knee joint extensor and flexor moments, or torque; the Gross Motor Function Measure (GMFM); the 600 Yard Walk-Run test and the Thirty-Second Walk test (30 sec WT). Discussion This paper presents the rationale, design and protocol for Pediatric Endurance and Limb Strengthening (PEDALS); a Phase I randomized controlled trial evaluating the efficacy of a stationary cycling intervention for children with spastic diplegic cerebral palsy. PMID:17374171

Neurobehavioral Abnormalities in First-Degree Relatives of Individuals With Autism

PubMed Central

Mosconi, Matthew W.; Kay, Margaret; D’Cruz, Anna-Maria; Guter, Stephen; Kapur, Kush; Macmillan, Carol; Stanford, Lisa D.; Sweeney, John A.

2011-01-01

Context Studying sensorimotor and neurocognitive impairments in unaffected family members of individuals with autism may help identify familial pathophysiological mechanisms associated with the disorder. Objective To determine whether atypical sensorimotor or neurocognitive characteristics associated with autism are present in first-degree relatives of individuals with autism. Design Case-control comparison of neurobehavioral functions. Setting University medical center. Participants Fifty-seven first-degree relatives of individuals with autism and 40 age-, sex-, and IQ-matched healthy control participants (aged 8–54 years). Main Outcome Measures Oculomotor tests of sensorimotor responses (saccades and smooth pursuit); procedural learning and response inhibition; neuropsychological tests of motor, memory, and executive functions; and psychological measures of social behavior, communication skills, and obsessive-compulsive behaviors. Results On eye movement testing, family members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and a higher rate of voluntary response inhibition errors relative to controls. They also showed lateralized deficits in procedural learning and open-loop pursuit gain (initial 100 milliseconds of pursuit) and increased variability in the accuracy of large-amplitude saccades that were confined to rightward movements. In neuropsychological studies, only executive functions were impaired relative to those of controls. Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls. Deficits across oculomotor, neuropsychological, and psychological domains were relatively independent from one another. Conclusions Family members of individuals with autism demonstrate oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits and left-lateralized alterations of frontotemporal circuitry and striatum. The left-lateralized alterations have not been identified in other neuropsychiatric disorders and are of interest given atypical brain lateralization and language development associated with the disorder. Similar oculomotor deficits have been reported in individuals with autism, suggesting that they may be familial and useful for studies of neurophysiological and genetic mechanisms in autism. PMID:20679591

Task-Rest Modulation of Basal Ganglia Connectivity in Mild to Moderate Parkinson’s Disease

PubMed Central

Müller-Oehring, Eva M.; Sullivan, Edith V.; Pfefferbaum, Adolf; Huang, Neng C.; Poston, Kathleen L.; Bronte-Stewart, Helen M.; Schulte, Tilman

2014-01-01

Parkinson’s disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG–cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen–medial parietal and pallidum–occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate–supramarginal gyrus and pallidum–inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal–cortical connectivity, specifically between caudate–prefrontal, caudate–precuneus, and putamen–motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance. PMID:25280970

Neurobehavioral abnormalities in first-degree relatives of individuals with autism.

PubMed

Mosconi, Matthew W; Kay, Margaret; D'Cruz, Anna-Maria; Guter, Stephen; Kapur, Kush; Macmillan, Carol; Stanford, Lisa D; Sweeney, John A

2010-08-01

Studying sensorimotor and neurocognitive impairments in unaffected family members of individuals with autism may help identify familial pathophysiological mechanisms associated with the disorder. To determine whether atypical sensorimotor or neurocognitive characteristics associated with autism are present in first-degree relatives of individuals with autism. Case-control comparison of neurobehavioral functions. University medical center. Fifty-seven first-degree relatives of individuals with autism and 40 age-, sex-, and IQ-matched healthy control participants (aged 8-54 years). Oculomotor tests of sensorimotor responses (saccades and smooth pursuit); procedural learning and response inhibition; neuropsychological tests of motor, memory, and executive functions; and psychological measures of social behavior, communication skills, and obsessive-compulsive behaviors. On eye movement testing, family members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and a higher rate of voluntary response inhibition errors relative to controls. They also showed lateralized deficits in procedural learning and open-loop pursuit gain (initial 100 milliseconds of pursuit) and increased variability in the accuracy of large-amplitude saccades that were confined to rightward movements. In neuropsychological studies, only executive functions were impaired relative to those of controls. Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls. Deficits across oculomotor, neuropsychological, and psychological domains were relatively independent from one another. Family members of individuals with autism demonstrate oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits and left-lateralized alterations of frontotemporal circuitry and striatum. The left-lateralized alterations have not been identified in other neuropsychiatric disorders and are of interest given atypical brain lateralization and language development associated with the disorder. Similar oculomotor deficits have been reported in individuals with autism, suggesting that they may be familial and useful for studies of neurophysiological and genetic mechanisms in autism.

Simpson-Golabi-Behmel syndrome types I and II.

PubMed

Tenorio, Jair; Arias, Pedro; Martínez-Glez, Víctor; Santos, Fernando; García-Miñaur, Sixto; Nevado, Julián; Lapunzina, Pablo

2014-09-20

Simpson-Golabi-Behmel syndrome (SGBS) is a rare overgrowth syndrome clinically characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features, macrocephaly, and organomegaly. Abnormalities of the skeletal system, heart, central nervous system, kidney, and gastrointestinal tract may also be observed. Intellectual disability, early motor milestones and speech delay are sometimes present; however, there are a considerable number of individuals with normal intelligence.

[Intellectual and motor development of extremely low birth weight (≤1000 g) children in the 7th year of life; a multicenter, cross-sectional study of children born in the Malopolska voivodship between 2002 and 2004].

PubMed

Kwinta, Przemko; Klimek, Małgorzata; Grudzień, Andrzej; Nitecka, Magdalena; Profus, Krzysztof; Gasińska, Monika; Pawlik, Dorota; Lauterbach, Ryszard; Olechowski, Wiesław; Pietrzyk, Jacek Józef

2012-01-01

A better understanding of the developmental problems in extremely low birth weight (ELBW) preterm infants may enhance their chances of proper adaptation to their environment and make it possible to retrospectively assess perinatal and neonatal methods of treatment. The aim of the study was to evaluate the cognitive and motor development of ELBW children born from 2002 to 2004 in the 7th year of life. Based on these results and perinatal mortality data, it was established what chance the children have to live free of severe complications. Two hundred and four alive newborns with birth weight .1000 g were born in the Malopolska voivodship between 1.09.2002 and 31.08.2004. One hundred and fifteen children (56%) died in early infancy. The study included 81 (91%) children out of the 89 surviving ones. Their mean gestational age at birth was 27.3 weeks. (SD: 2.1 weeks) and their mean birth weight was 840g (SD: 130g). Neurosensory disturbances were assessed in all the children and their cognitive development was evaluated with the use of the WISC-R (Wechsler Intelligence Scale for Children . Revised) scale. The children were divided into 3 groups: group I . normal development (full motor capacity and IQ >84 points and no vision or hearing impairment), group II . mild or moderate impairment (cerebral palsy level I, II or III according to the Gross Motor Function Classification System [GMCS], or IQ 40-84 points, or abnormal vision or hearing, or signs of the hyperactivity syndrome), group III . severe impairment (cerebral palsy level IV, and/or IQ <40 points, or deafness/blindness). Forty-five (56%) children were included in group I, 25 (30%) in group II and 11 (14%) in group III. Moreover, other neurologic abnormalities, such as uneven development, problems with concentration, or abnormal grapho-motor ability were highly prevalent in the group of ELBW children. The incidence of cerebral palsy in the population studied was 16%, the incidence of deafness and severe hearing impairment was 11%, and blindness and severe vision impairment . 12%. In general, the chance of survival free of severe complications was merely 15% in children with birthweight .700 g, 28% in children with birth weight 701- 800 g, 45% in children with birth weight 801-900 g, and 62% in children with birth weight 901-1000 g. 1. The data gathered in a regional study may yield valuable information useful in assessing the prognosis of the general health status of ELBW newborns. 2. Most of the children present uneven development, problems with concentration, or abnormal grapho-motor ability, which may be a cause of learning problems and abnormal relationships with peers. 3. A follow-up study up to adulthood is required for this group of ELBW newborns.

CONGENITAL ABNORMALITIES OF CRANIAL NERVE DEVELOPMENT: OVERVIEW, MOLECULAR MECHANISMS, AND FURTHER EVIDENCE OF HETEROGENEITY AND COMPLEXITY OF SYNDROMES WITH CONGENITAL LIMITATION OF EYE MOVEMENTS

PubMed Central

Traboulsi, Elias I

2004-01-01

ABSTRACT Purpose The clinical and molecular genetic classification of syndromes with congenital limitation of eye movements and evidence of cranial nerve dysgenesis continues to evolve. This monograph details clinical and molecular genetic data on a number of families and isolated patients with congenital fibrosis of the extraocular muscles (CFEOM) and related disorders, and presents an overview of the mechanisms of abnormal patterns of motor and sensory cranial nerve development in these rare syndromes. Methods Clinical examination of one patient with CFEOM1, one family with clinical features of CFEOM2, one family with recessive CFEOM3, one family with horizontal gaze palsy and progressive scoliosis (HGPPS), and four patients with various combinations of congenital cranial nerve abnormalities. Genotyping of families with CFEOM and HGPPS for polymorphic markers in the regions of the three known CFEOM loci and in the HGPPS region, and mutation analysis of the ARIX and KIF21A genes in patients with CFEOM were performed according to standard published protocols. Results The patient with CFEOM1 had the second most common mutation in KIF21A, a 2861 G>A mutation that resulted in an R954Q substitution. The family with CFEOM2 phenotype did not map to the CFEOM2 locus. The family with recessive CFEOM3 did not map to any of the known loci. The HGPPS family mapped to 11q23–q25. One patient had optic nerve hypoplasia and fifth nerve dysfunction. Two patients had the rare combination of Möbius syndrome and CFEOM. One patient had Möbius syndrome and fifth nerve dysfunction. Conclusions There is genetic heterogeneity in CFEOM2 and CFEOM3. Abnormalities in sensory nerves can also accompany abnormalities of motor nerves, further substantiating the effect of individual mutations on developing motor as well as sensory cranial nerve nuclei. PMID:15747768

Reading in Schizophrenic Subjects and Their Nonsymptomatic First-Degree Relatives

PubMed Central

Roberts, Eryl O.; Proudlock, Frank A.; Martin, Kate; Reveley, Michael A.; Al-Uzri, Mohammed; Gottlob, Irene

2013-01-01

Previous studies have demonstrated eye movement abnormalities during smooth pursuit and antisaccadic tasks in schizophrenia. However, eye movements have not been investigated during reading. The purpose of this study was to determine whether schizophrenic subjects and their nonsymptomatic first-degree relatives show eye movement abnormalities during reading. Reading rate, number of saccades per line, amplitudes of saccades, percentage regressions (reverse saccades), and fixation durations were measured using an eye tracker (EyeLink, SensoMotoric Instruments, Germany) in 38 schizophrenic volunteers, 14 nonaffected first-degree relatives, and 57 control volunteers matched for age and National Adult Reading Test scores. Parameters were examined when volunteers read full pages of text and text was limited to progressively smaller viewing areas around the point of fixation using a gaze-contingent window. Schizophrenic volunteers showed significantly slower reading rates (P = .004), increase in total number of saccades (P ≤ .001), and a decrease in saccadic amplitude (P = .025) while reading. Relatives showed a significant increase in total number of saccades (P = .013) and decrease in saccadic amplitude (P = .020). Limitation of parafoveal information by reducing the amount of visible characters did not change the reading rate of schizophrenics but controls showed a significant decrease in reading rate with reduced parafoveal information (P < .001). Eye movement abnormalities during reading of schizophrenic volunteers and their first-degree relatives suggest that visual integration of foveal and parafoveal information may be reduced in schizophrenia. Reading abnormalities in relatives suggest a genetic influence in reading ability in schizophrenia and rule out confounding effects of medication. PMID:22267532

Surface Electromyographic Examination of Poststroke Neuromuscular Changes in Proximal and Distal Muscles Using Clustering Index Analysis

PubMed Central

Tang, Weidi; Zhang, Xu; Tang, Xiao; Cao, Shuai; Gao, Xiaoping; Chen, Xiang

2018-01-01

Whether stroke-induced paretic muscle changes vary across different distal and proximal muscles remains unclear. The objective of this study was to compare paretic muscle changes between a relatively proximal muscle (the biceps brachii muscle) and two distal muscles (the first dorsal interosseous muscle and the abductor pollicis brevis muscle) following hemisphere stroke using clustering index (CI) analysis of surface electromyograms (EMGs). For each muscle, surface EMG signals were recorded from the paretic and contralateral sides of 12 stroke subjects versus the dominant side of eight control subjects during isometric muscle contractions to measure the consequence of graded levels of contraction (from a mild level to the maximal voluntary contraction). Across all examined muscles, it was found that partial paretic muscles had abnormally higher or lower CI values than those of the healthy control muscles, which exhibited a significantly larger variance in the CI via a series of homogeneity of variance tests (p < 0.05). This finding indicated that both neurogenic and myopathic changes were likely to take place in paretic muscles. When examining two distal muscles of individual stroke subjects, relatively consistent CI abnormalities (toward neuropathy or myopathy) were observed. By contrast, consistency in CI abnormalities were not found when comparing proximal and distal muscles, indicating differences in motor unit alternation between the proximal and distal muscles on the paretic sides of stroke survivors. Furthermore, CI abnormalities were also observed for all three muscles on the contralateral side. Our findings help elucidate the pathological mechanisms underlying stroke sequels, which might prove useful in developing improved stroke rehabilitation protocols. PMID:29379465

Inter-hemispheric functional connectivity disruption in children with prenatal alcohol exposure

PubMed Central

Wozniak, Jeffrey R.; Mueller, Bryon A.; Muetzel, Ryan L.; Bell, Christopher J.; Hoecker, Heather L.; Nelson, Miranda L.; Chang, Pi-Nian; Lim, Kelvin O.

2010-01-01

Background MRI studies, including recent diffusion tensor imaging (DTI) studies, have shown corpus callosum abnormalities in children prenatally exposed to alcohol, especially in the posterior regions. These abnormalities appear across the range of Fetal Alcohol Spectrum Disorders (FASD). Several studies have demonstrated cognitive correlates of callosal abnormalities in FASD including deficits in visual-motor skill, verbal learning, and executive functioning. The goal of this study was to determine if inter-hemispheric structural connectivity abnormalities in FASD are associated with disrupted inter-hemispheric functional connectivity and disrupted cognition. Methods Twenty-one children with FASD and 23 matched controls underwent a six minute resting-state functional MRI scan as well as anatomical imaging and DTI. Using a semiautomated method, we parsed the corpus callosum and delineated seven inter-hemispheric white matter tracts with DTI tractography. Cortical regions of interest (ROIs) at the distal ends of these tracts were identified. Right-left correlations in resting fMRI signal were computed for these sets of ROIs and group comparisons were done. Correlations with facial dysmorphology, cognition, and DTI measures were computed. Results A significant group difference in inter-hemispheric functional connectivity was seen in a posterior set of ROIs, the para-central region. Children with FASD had functional connectivity that was 12% lower than controls in this region. Sub-group analyses were not possible due to small sample size, but the data suggest that there were effects across the FASD spectrum. No significant association with facial dysmorphology was found. Para-central functional connectivity was significantly correlated with DTI mean diffusivity, a measure of microstructural integrity, in posterior callosal tracts in controls but not in FASD. Significant correlations were seen between these structural and functional measures and Wechsler perceptual reasoning ability. Conclusions Inter-hemispheric functional connectivity disturbances were observed in children with FASD relative to controls. The disruption was measured in medial parietal regions (para-central) that are connected by posterior callosal fiber projections. We have previously shown microstructural abnormalities in these same posterior callosal regions and the current study suggests a possible relationship between the two. These measures have clinical relevance as they are associated with cognitive functioning. PMID:21303384

Alteration of diffusion-tensor MRI measures in brain regions involved in early stages of Parkinson's disease.

PubMed

Chen, Nan-Kuei; Chou, Ying-Hui; Sundman, Mark; Hickey, Patrick; Kasoff, Willard S; Bernstein, Adam; Trouard, Theodore P; Lin, Tanya; Rapcsak, Steven Z; Sherman, Scott J; Weingarten, Carol

2018-06-07

Many non-motor symptoms (e.g., hyposmia) appear years before the cardinal motor features of Parkinson's disease (PD). It is thus desirable to be able to use noninvasive brain imaging methods, such as magnetic resonance imaging (MRI), to detect brain abnormalities in early PD stages. Among the MRI modalities, diffusion tensor imaging (DTI) is suitable for detecting changes of brain tissue structure due to neurological diseases. The main purpose of this study was to investigate whether DTI signals measured from brain regions involved in early stages of PD differ from those of healthy controls. To answer this question, we analyzed whole-brain DTI data of 30 early-stage PD patients and 30 controls using improved ROI based analysis methods. Results showed that 1) the fractional anisotropy (FA) values in the olfactory tract (connected with the olfactory bulb: one of the first structures affected by PD) are lower in PD patients than healthy controls; 2) FA values are higher in PD patients than healthy controls in the following brain regions: corticospinal tract, cingulum (near hippocampus), and superior longitudinal fasciculus (temporal part). Experimental results suggest that the tissue property, measured by FA, in olfactory regions is structurally modulated by PD with a mechanism that is different from other brain regions.

Activation properties of trigeminal motoneurons in participants with and without bruxism

PubMed Central

D'Amico, Jessica M.; Yavuz, Ş. Utku; Saraçoğlu, Ahmet; Atiş, Elif Sibel; Türker, Kemal S.

2013-01-01

In animals, sodium- and calcium-mediated persistent inward currents (PICs), which produce long-lasting periods of depolarization under conditions of low synaptic drive, can be activated in trigeminal motoneurons following the application of the monoamine serotonin. Here we examined if PICs are activated in human trigeminal motoneurons during voluntary contractions and under physiological levels of monoaminergic drive (e.g., serotonin and norepinephrine) using a paired motor unit analysis technique. We also examined if PICs activated during voluntary contractions are larger in participants who demonstrate involuntary chewing during sleep (bruxism), which is accompanied by periods of high monoaminergic drive. In control participants, during a slowly increasing and then decreasing isometric contraction, the firing rate of an earlier-recruited masseter motor unit, which served as a measure of synaptic input to a later-recruited test unit, was consistently lower during derecruitment of the test unit compared with at recruitment (ΔF = 4.6 ± 1.5 imp/s). The ΔF, therefore, is a measure of the reduction in synaptic input needed to counteract the depolarization from the PIC to provide an indirect estimate of PIC amplitude. The range of ΔF values measured in the bruxer participants during similar voluntary contractions was the same as in controls, suggesting that abnormally high levels of monoaminergic drive are not continually present in the absence of involuntary motor activity. We also observed a consistent “onion skin effect” during the moderately sized contractions (<20% of maximal), whereby the firing rate of higher threshold motor units discharged at slower rates (by 4–7 imp/s) compared with motor units with relatively lower thresholds. The presence of lower firing rates in the more fatigue-prone, higher threshold trigeminal motoneurons, in addition to the activation of PICs, likely facilitates the activation of the masseter muscle during motor activities such as eating, nonnutritive chewing, clenching, and yawning. PMID:24068753

Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of Schizophrenia.

PubMed

Guo, Xiaochuan; Hamilton, Peter J; Reish, Nicholas J; Sweatt, J David; Miller, Courtney A; Rumbaugh, Gavin

2009-06-01

Abnormal function of NMDA receptors is believed to be a contributing factor to the pathophysiology of schizophrenia. NMDAR subunits and postsynaptic-interacting proteins of these channels are abnormally expressed in some patients with this illness. In mice, reduced NMDAR expression leads to behaviors analogous to symptoms of schizophrenia, but reports of animals with mutations in core postsynaptic density proteins having similar a phenotype have yet to be reported. Here we show that reduced expression of the neuronal RasGAP and NMDAR-associated protein, SynGAP, results in abnormal behaviors strikingly similar to that reported in mice with reduced NMDAR function. SynGAP mutant mice exhibited nonhabituating and persistent hyperactivity that was ameliorated by the antipsychotic clozapine. An NMDAR antagonist, MK-801, induced hyperactivity in normal mice but SynGAP mutants were less responsive, suggesting that NMDAR hypofunction contributes to this behavioral abnormality. SynGAP mutants exhibited enhanced startle reactivity and impaired sensory-motor gating. These mice also displayed a complete lack of social memory and a propensity toward social isolation. Finally, SynGAP mutants had deficits in cued fear conditioning and working memory, indicating abnormal function of circuits that control emotion and choice. Our results demonstrate that SynGAP mutant mice have gross neurological deficits similar to other mouse models of schizophrenia. Because SynGAP interacts with NMDARs, and the signaling activity of this protein is regulated by these channels, our data in dicate that SynGAP lies downstream of NMDARs and is a required intermediate for normal neural circuit function and behavior. Taken together, these data support the idea that schizophrenia may arise from abnormal signaling pathways that are mediated by NMDA receptors.

Functional Analysis of Dopaminergic Systems in a DYT1 Knock-in Mouse Model of Dystonia

PubMed Central

Song, Chang-Hyun; Fan, Xueliang; Exeter, Cicely J.; Hess, Ellen J.; Jinnah, H. A.

2012-01-01

The dystonias are a group of disorders characterized by involuntary twisting movements and abnormal posturing. The most common of the inherited dystonias is DYT1 dystonia, which is due to deletion of a single GAG codon (ΔE) in the TOR1A gene that encodes torsinA. Since some forms of dystonia have been linked with dysfunction of brain dopamine pathways, the integrity of these pathways was explored in a knock-in mouse model of DYT1 dystonia. In DYT1(ΔE) knock-in mice, neurochemical measures revealed only small changes in the content of dopamine or its metabolites in tissue homogenates from caudoputamen or midbrain, but microdialysis studies revealed robust decreases in baseline and amphetamine-stimulated extracellular dopamine in the caudoputamen. Quantitative stereological methods revealed no evidence for striatal or midbrain atrophy, but substantia nigra neurons immunopositive for tyrosine hydroxylase were slightly reduced in numbers and enlarged in size. Behavioral studies revealed subtle abnormalities in gross motor activity and motor coordination without overt dystonia. Neuropharmacological challenges of dopamine systems revealed normal behavioral responses to amphetamine and a minor increase in sensitivity to haloperidol. These results demonstrate that this DYT1(ΔE) knock-in mouse model of dystonia harbors neurochemical and structural changes of the dopamine pathways, as well as motor abnormalities. PMID:22659308

Red nucleus and rubrospinal tract disorganization in the absence of Pou4f1

PubMed Central

Martinez-Lopez, Jesus E.; Moreno-Bravo, Juan A.; Madrigal, M. Pilar; Martinez, Salvador; Puelles, Eduardo

2015-01-01

The red nucleus (RN) is a neuronal population that plays an important role in forelimb motor control and locomotion. Histologically it is subdivided into two subpopulations, the parvocellular RN (pRN) located in the diencephalon and the magnocellular RN (mRN) in the mesencephalon. The RN integrates signals from motor cortex and cerebellum and projects to spinal cord interneurons and motor neurons through the rubrospinal tract (RST). Pou4f1 is a transcription factor highly expressed in this nucleus that has been related to its specification. Here we profoundly analyzed consequences of Pou4f1 loss-of-function in development, maturation and axonal projection of the RN. Surprisingly, RN neurons are specified and maintained in the mutant, no cell death was detected. Nevertheless, the nucleus appeared disorganized with a strong delay in radial migration and with a wider neuronal distribution; the neurons did not form a compacted population as they do in controls, Robo1 and Slit2 were miss-expressed. Cplx1 and Npas1, expressed in the RN, are transcription factors involved in neurotransmitter release, neuronal maturation and motor function processes among others. In our mutant mice, both transcription factors are lost, suggesting an abnormal maturation of the RN. The resulting altered nucleus occupied a wider territory. Finally, we examined RST development and found that the RN neurons were able to project to the spinal cord but their axons appeared defasciculated. These data suggest that Pou4f1 is necessary for the maturation of RN neurons but not for their specification and maintenance. PMID:25698939

Age and gender affect likely manometric diagnosis: Audit of a tertiary referral hospital clinical esophageal manometry service.

PubMed

Andrews, Jane M; Heddle, Richard; Hebbard, Geoffrey S; Checklin, Helen; Besanko, Laura; Fraser, Robert J

2009-01-01

Awareness of patient demographics, common diagnoses and associations between these may improve the use and interpretation of manometric investigations. The aim of the present study therefore was to determine whether age and/or gender affect manometric diagnosis in a clinical motility service. An audit of all 452 clinical manometry reports issued from December 2003 to July 2005 with respect to age, gender and diagnosis was carried out. Patients were divided by age (17-24 years n = 14, 25-44 years n = 87, 45-64 years n = 216 and >or=65 years n = 135), and gender and data compared using contingency tables. Women were more commonly referred overall (59%) and in each age bracket except <25 years (64% male). Men were more likely to have 'hypotensive' motor problems P = 0.01. With aging, normal motor function became less common (P = 0.013), with non-specific motor disorder, ineffective/hypotensive peristalsis and 'achalasia-like' conditions each more common (individual P = NS). Increasing age showed a trend for increased spastic motor disorders (P = 0.06). Gender did not, however, influence whether motility was abnormal (P = 0.5), spastic (P = 0.7) or whether a non-specific motor disorder was present (P = 0.1). In the total cohort, the principal manometric diagnoses were: non-specific motor disorder 33%, normal motility 29%, low basal lower esophageal sphincter pressure 18%, hypotensive/ineffective peristalsis 10%, achalasia/achalasia-like 6%, diffuse esophageal spasm 3% and other 1%. Aging leads to increasing esophageal motor abnormalities. Men and women have similar rates of dysfunction, although 'low-pressure problems' were more common in men.

Amblyopia and binocular vision.

PubMed

Birch, Eileen E

2013-03-01

Amblyopia is the most common cause of monocular visual loss in children, affecting 1.3%-3.6% of children. Current treatments are effective in reducing the visual acuity deficit but many amblyopic individuals are left with residual visual acuity deficits, ocular motor abnormalities, deficient fine motor skills, and risk for recurrent amblyopia. Using a combination of psychophysical, electrophysiological, imaging, risk factor analysis, and fine motor skill assessment, the primary role of binocular dysfunction in the genesis of amblyopia and the constellation of visual and motor deficits that accompany the visual acuity deficit has been identified. These findings motivated us to evaluate a new, binocular approach to amblyopia treatment with the goals of reducing or eliminating residual and recurrent amblyopia and of improving the deficient ocular motor function and fine motor skills that accompany amblyopia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Maternal Thyroid Function in Early Pregnancy and Neuropsychological Performance of the Child at 5 Years of Age.

PubMed

Andersen, Stine Linding; Andersen, Stig; Liew, Zeyan; Vestergaard, Peter; Olsen, Jørn

2018-02-01

Abnormal maternal thyroid function in pregnancy may impair fetal brain development, but more evidence is needed to refine and corroborate the hypothesis. To estimate the association between maternal thyroid function in early pregnancy and neuropsychological performance of the child at 5 years of age. Follow-up study. A cohort of 1153 women and their children sampled from the Danish National Birth Cohort. Maternal thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured in stored biobank sera from early pregnancy. Child neuropsychological test results (Wechsler Intelligence Scale/Test of Everyday Attention), test of motor function (Movement Assessment Battery), and results of parent and teacher reports (Behavior Rating Inventory of Executive Function/Strengths and Difficulties Questionnaire). Altogether 145 children (12.6%) were born to mothers with abnormal thyroid function in the early pregnancy. High maternal TSH and low fT4 were associated with lower child verbal intelligence quotient (adjusted mean difference TSH ≥ 10 mIU/L vs 0.1 to 2.49 mIU/L, -8.9 [95% confidence interval (CI), -15 to -2.4]; fT4 < 10 pmol/l vs 12.0 to 18.99 pmol/l, -13 [95% CI, -19 to -7.3]). Abnormal maternal thyroid function was also associated with adverse motor function and teacher-reported problems of executive function and behavior, and these associations were dominated by exposure to maternal hypothyroxinemia. Maternal thyroid hormone abnormalities were associated with adverse neuropsychological function of the child at 5 years of age. For intelligence, marked hypothyroidism was important, whereas for motor function and executive and behavior problems, maternal hypothyroxinemia was predominant. Copyright © 2017 Endocrine Society

Defective mitochondrial dynamics is an early event in skeletal muscle of an amyotrophic lateral sclerosis mouse model.

PubMed

Luo, Guo; Yi, Jianxun; Ma, Changling; Xiao, Yajuan; Yi, Frank; Yu, Tian; Zhou, Jingsong

2013-01-01

Mitochondria are dynamic organelles that constantly undergo fusion and fission to maintain their normal functionality. Impairment of mitochondrial dynamics is implicated in various neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is an adult-onset neuromuscular degenerative disorder characterized by motor neuron death and muscle atrophy. ALS onset and progression clearly involve motor neuron degeneration but accumulating evidence suggests primary muscle pathology may also be involved. Here, we examined mitochondrial dynamics in live skeletal muscle of an ALS mouse model (G93A) harboring a superoxide dismutase mutation (SOD1(G93A)). Using confocal microscopy combined with overexpression of mitochondria-targeted photoactivatable fluorescent proteins, we discovered abnormal mitochondrial dynamics in skeletal muscle of young G93A mice before disease onset. We further demonstrated that similar abnormalities in mitochondrial dynamics were induced by overexpression of mutant SOD1(G93A) in skeletal muscle of normal mice, indicating the SOD1 mutation drives ALS-like muscle pathology in the absence of motor neuron degeneration. Mutant SOD1(G93A) forms aggregates inside muscle mitochondria and leads to fragmentation of the mitochondrial network as well as mitochondrial depolarization. Partial depolarization of mitochondrial membrane potential in normal muscle by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) caused abnormalities in mitochondrial dynamics similar to that in the SOD1(G93A) model muscle. A specific mitochondrial fission inhibitor (Mdivi-1) reversed the SOD1(G93A) action on mitochondrial dynamics, indicating SOD1(G93A) likely promotes mitochondrial fission process. Our results suggest that accumulation of mutant SOD1(G93A) inside mitochondria, depolarization of mitochondrial membrane potential and abnormal mitochondrial dynamics are causally linked and cause intrinsic muscle pathology, which occurs early in the course of ALS and may actively promote ALS progression.

Abnormal externally guided movement preparation in recent-onset schizophrenia is associated with impaired selective attention to external input.

PubMed

Smid, Henderikus G O M; Westenbroek, Joanna M; Bruggeman, Richard; Knegtering, Henderikus; Van den Bosch, Robert J

2009-11-30

Several theories propose that the primary cognitive impairment in schizophrenia concerns a deficit in the processing of external input information. There is also evidence, however, for impaired motor preparation in schizophrenia. This provokes the question whether the impaired motor preparation in schizophrenia is a secondary consequence of disturbed (selective) processing of the input needed for that preparation, or an independent primary deficit. The aim of the present study was to discriminate between these hypotheses, by investigating externally guided movement preparation in relation to selective stimulus processing. The sample comprised 16 recent-onset schizophrenia patients and 16 controls who performed a movement-precuing task. In this task, a precue delivered information about one, two or no parameters of a movement summoned by a subsequent stimulus. Performance measures and measures derived from the electroencephalogram showed that patients yielded smaller benefits from the precues and showed less cue-based preparatory activity in advance of the imperative stimulus than the controls, suggesting a response preparation deficit. However, patients also showed less activity reflecting selective attention to the precue. We therefore conclude that the existing evidence for an impairment of externally guided motor preparation in schizophrenia is most likely due to a deficit in selective attention to the external input, which lends support to theories proposing that the primary cognitive deficit in schizophrenia concerns the processing of input information.

Patterns of structural reorganization of the corticospinal tract in children with Sturge-Weber syndrome

PubMed Central

Kamson, David O.; Juhász, Csaba; Shin, Joseph; Behen, Michael E.; Guy, William C.; Chugani, Harry T.; Jeong, Jeong-Won

2014-01-01

Background Reorganization of the corticospinal tract (CST) after early damage can limit motor deficit. In this study, we explored patterns of structural CST reorganization in children with Sturge-Weber syndrome. Methods Five children (age 1.5-7 years) with motor deficit due to unilateral Sturge-Weber syndrome were studied prospectively and longitudinally (1-2 years follow-up). CST segments belonging to hand and leg movements were separated, and their volume was measured by diffusion tensor imaging (DTI) tractography using a recently validated method. CST segmental volumes were normalized and compared between the SWS children and age-matched healthy controls. Volume changes during follow-up were also compared to clinical motor symptoms. Results In the SWS children, hand-related (but not leg-related) CST volumes were consistently decreased in the affected cerebral hemisphere at baseline. At follow-up, two distinct patterns of hand CST volume changes emerged: (i) Two children with extensive frontal lobe damage showed a CST volume decrease in the lesional hemisphere and a concomitant increase in the non-lesional (contralateral) hemisphere. These children developed good hand grasp but no fine motor skills. (ii) The three other children, with relative sparing of the frontal lobe, showed an interval increase of the normalized hand CST volume in the affected hemisphere; these children showed no gross motor deficit at follow-up. Conclusions DTI tractography can detect differential abnormalities in the hand CST segment both ipsi- and contralateral to the lesion. Interval increase in the CST hand segment suggests structural reorganization, whose pattern may determine clinical motor outcome and could guide strategies for early motor intervention. PMID:24507695

Patterns of structural reorganization of the corticospinal tract in children with Sturge-Weber syndrome.

PubMed

Kamson, David O; Juhász, Csaba; Shin, Joseph; Behen, Michael E; Guy, William C; Chugani, Harry T; Jeong, Jeong-Won

2014-04-01

Reorganization of the corticospinal tract after early damage can limit motor deficit. In this study, we explored patterns of structural corticospinal tract reorganization in children with Sturge-Weber syndrome. Five children (age 1.5-7 years) with motor deficit resulting from unilateral Sturge-Weber syndrome were studied prospectively and longitudinally (1-2 years follow-up). Corticospinal tract segments belonging to hand and leg movements were separated and their volume was measured by diffusion tensor imaging tractography using a recently validated method. Corticospinal tract segmental volumes were normalized and compared between the Sturge-Weber syndrome children and age-matched healthy controls. Volume changes during follow-up were also compared with clinical motor symptoms. In the Sturge-Weber syndrome children, hand-related (but not leg-related) corticospinal tract volumes were consistently decreased in the affected cerebral hemisphere at baseline. At follow-up, two distinct patterns of hand corticospinal tract volume changes emerged. (1) Two children with extensive frontal lobe damage showed a corticospinal tract volume decrease in the lesional hemisphere and a concomitant increase in the nonlesional (contralateral) hemisphere. These children developed good hand grasp but no fine motor skills. (2) The three other children, with relative sparing of the frontal lobe, showed an interval increase of the normalized hand corticospinal tract volume in the affected hemisphere; these children showed no gross motor deficit at follow-up. Diffusion tensor imaging tractography can detect differential abnormalities in the hand corticospinal tract segment both ipsi- and contralateral to the lesion. Interval increase in the corticospinal tract hand segment suggests structural reorganization, whose pattern may determine clinical motor outcome and could guide strategies for early motor intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

White Matter Injury and General Movements in High-Risk Preterm Infants.

PubMed

Peyton, C; Yang, E; Msall, M E; Adde, L; Støen, R; Fjørtoft, T; Bos, A F; Einspieler, C; Zhou, Y; Schreiber, M D; Marks, J D; Drobyshevsky, A

2017-01-01

Very preterm infants (birth weight, <1500 g) are at increased risk of cognitive and motor impairment, including cerebral palsy. These adverse neurodevelopmental outcomes are associated with white matter abnormalities on MR imaging at term-equivalent age. Cerebral palsy has been predicted by analysis of spontaneous movements in the infant termed "General Movement Assessment." The goal of this study was to determine the utility of General Movement Assessment in predicting adverse cognitive, language, and motor outcomes in very preterm infants and to identify brain imaging markers associated with both adverse outcomes and aberrant general movements. In this prospective study of 47 preterm infants of 24-30 weeks' gestation, brain MR imaging was performed at term-equivalent age. Infants underwent T1- and T2-weighted imaging for volumetric analysis and DTI. General movements were assessed at 10-15 weeks' postterm age, and neurodevelopmental outcomes were evaluated at 2 years by using the Bayley Scales of Infant and Toddler Development III. Nine infants had aberrant general movements and were more likely to have adverse neurodevelopmental outcomes, compared with infants with normal movements. In infants with aberrant movements, Tract-Based Spatial Statistics analysis identified significantly lower fractional anisotropy in widespread white matter tracts, including the corpus callosum, inferior longitudinal and fronto-occipital fasciculi, internal capsule, and optic radiation. The subset of infants having both aberrant movements and abnormal neurodevelopmental outcomes in cognitive, language, and motor skills had significantly lower fractional anisotropy in specific brain regions. Aberrant general movements at 10-15 weeks' postterm are associated with adverse neurodevelopmental outcomes and specific white matter microstructure abnormalities for cognitive, language, and motor delays. © 2017 by American Journal of Neuroradiology.

Identification of age-dependent motor and neuropsychological behavioural abnormalities in a mouse model of Mucopolysaccharidosis Type II

PubMed Central

Gleitz, Hélène F. E.; O’Leary, Claire; Holley, Rebecca J.

2017-01-01

Severe mucopolysaccharidosis type II (MPS II) is a progressive lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency in the iduronate-2-sulfatase enzyme that is involved in heparan sulphate and dermatan sulphate catabolism. In constitutive form, MPS II is a multi-system disease characterised by progressive neurocognitive decline, severe skeletal abnormalities and hepatosplenomegaly. Although enzyme replacement therapy has been approved for treatment of peripheral organs, no therapy effectively treats the cognitive symptoms of the disease and novel therapies are in development to remediate this. Therapeutic efficacy and subsequent validation can be assessed using a variety of outcome measures that are translatable to clinical practice, such as behavioural measures. We sought to consolidate current knowledge of the cognitive, skeletal and motor abnormalities present in the MPS II mouse model by performing time course behavioural examinations of working memory, anxiety, activity levels, sociability and coordination and balance, up to 8 months of age. Cognitive decline associated with alterations in spatial working memory is detectable at 8 months of age in MPS II mice using spontaneous alternation, together with an altered response to novel environments and anxiolytic behaviour in the open-field. Coordination and balance on the accelerating rotarod were also significantly worse at 8 months, and may be associated with skeletal changes seen in MPS II mice. We demonstrate that the progressive nature of MPS II disease is also seen in the mouse model, and that cognitive and motor differences are detectable at 8 months of age using spontaneous alternation, the accelerating rotarod and the open-field tests. This study establishes neurological, motor and skeletal measures for use in pre-clinical studies to develop therapeutic approaches in MPS II. PMID:28207863

Neuroprotective role of chrysin in attenuating loss of dopaminergic neurons and improving motor, learning and memory functions in rats.

PubMed

Ahmed, Muhammad Rashid; Shaikh, Masood Ahmed; Ul Haq, Syed Hafiz Imran; Nazir, Shakila

2018-01-01

Selective degeneration of dopaminergic neurons is the pathological hallmark of Parkinson disease (PD). Enhanced oxidative stress, lipid peroxidation and susceptibility of dopaminergic neurons to apoptotic cellular death are the leading pathogenetic mechanisms. Chrysin is an active flavonoid. Its neuroprotective effects have been reported. This study examined the neuroprotective effects of chrysin in ameliorating the dopaminergic neuronal degeneration and motor behavioral changes in rotenone model of PD. Thirty Sprague-Dawley rats were assigned into three groups: Control, rotenone-treated, and rotenone+chrysin treated groups. Rotenone was given at a dose of 3 mg/kg daily intraperitoneally, and chrysin was given at a dose of 50 mg/kg daily intraperitoneally for 4 weeks. Using five neurobehavioral assessment tests, evaluation was done weekly to record the motor behavioral changes. After 4 weeks, animals were sacrificed, brains were removed, and section from striatum and substantia nigra were stained using hematoxylin and eosin and cresyl violet stains. Immunohistochemical sections were also prepared using anti-tyrosine hydroxylase (TH) antibody. Rotenone-induced Parkinson like changes were evident from deteriorating motor behavior. These animals showed extensive loss of dopaminergic neurons, decreased immunoreactivity against anti-TH antibodies and number of TH positive dopaminergic neurons in the nigrostriatal region. Chrysin treated animals showed a significant reduction in motor behavioral changes, degeneration and loss of nigrostriatal dopaminergic neurons and increased immunoreactivity to anti-TH antibody. This study concludes that chrysin confers neuroprotection in rat model of PD. It attenuates the degeneration of the nigrostriatal dopaminergic neurons and motor behavioral abnormalities.

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.

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.

Robotic Exoskeletons: A Perspective for the Rehabilitation of Arm Coordination in Stroke Patients

PubMed Central

Jarrassé, Nathanaël; Proietti, Tommaso; Crocher, Vincent; Robertson, Johanna; Sahbani, Anis; Morel, Guillaume; Roby-Brami, Agnès

2014-01-01

Upper-limb impairment after stroke is caused by weakness, loss of individual joint control, spasticity, and abnormal synergies. Upper-limb movement frequently involves abnormal, stereotyped, and fixed synergies, likely related to the increased use of sub-cortical networks following the stroke. The flexible coordination of the shoulder and elbow joints is also disrupted. New methods for motor learning, based on the stimulation of activity-dependent neural plasticity have been developed. These include robots that can adaptively assist active movements and generate many movement repetitions. However, most of these robots only control the movement of the hand in space. The aim of the present text is to analyze the potential of robotic exoskeletons to specifically rehabilitate joint motion and particularly inter-joint coordination. First, a review of studies on upper-limb coordination in stroke patients is presented and the potential for recovery of coordination is examined. Second, issues relating to the mechanical design of exoskeletons and the transmission of constraints between the robotic and human limbs are discussed. The third section considers the development of different methods to control exoskeletons: existing rehabilitation devices and approaches to the control and rehabilitation of joint coordinations are then reviewed, along with preliminary clinical results available. Finally, perspectives and future strategies for the design of control mechanisms for rehabilitation exoskeletons are discussed. PMID:25520638

Motor stereotypy disorders.

PubMed

Muthugovindan, Deivasumathy; Singer, Harvey

2009-04-01

This review highlights recent advances in understanding the clinical features, prevalence, and outcomes of motor stereotypy disorders in typically developing children. Longitudinal data indicate that stereotypies in children with normal intelligence show an early age of onset, chronicity, and high prevalence of comorbid difficulties, including tics, obsessive-compulsive behaviors, and attention deficit hyperactivity disorder. The underlying abnormality remains unknown, but there is increasing evidence for Mendelian inheritance and a neurobiological mechanism. Primary motor stereotypies are relatively common in childhood and can be subdivided into three groups (common, head nodding, and complex motor). Movements are similar to those seen in children with autistic spectrum disorders, mental retardation, and sensory deprivation. The role of pharmacotherapy is not established and behavioral therapy can be beneficial.

Medically Unexplained Physical Symptoms in Military Health (Symptomes physiques medicalement inexpliques dans la sante militaire)

DTIC Science & Technology

2017-12-01

Development of Persistent Pain and psychological Morbidity after Motor Vehicle Collision: Integrating the Potential Role of Stress Response Systems... abnormalities of quantitative EEG which suggest a THE LONG-TERM COSTS OF TRAUMATIC STRESS: INTERTWINED PHYSICAL AND PSYCHOLOGICAL CONSEQUENCES STO-TR-HFM...S.A., Clauw, D.J., Abelson, J.L. et al., The development of persistent pain and psychological morbidity after motor vehicle collision: integrating

Practice guidelines on the use of esophageal manometry - A GISMAD-SIGE-AIGO medical position statement.

PubMed

Savarino, Edoardo; de Bortoli, Nicola; Bellini, Massimo; Galeazzi, Francesca; Ribolsi, Mentore; Salvador, Renato; Savarino, Vincenzo; Penagini, Roberto

2016-10-01

Patients with esophageal symptoms potentially associated to esophageal motor disorders such as dysphagia, chest pain, heartburn and regurgitation, represent one of the most frequent reasons for referral to gastroenterological evaluation. The utility of esophageal manometry in clinical practice is: (1) to accurately define esophageal motor function, (2) to identify abnormal motor function, and (3) to establish a treatment plan based on motor abnormalities. With this in mind, in the last decade, investigations and technical advances, with the introduction of high-resolution esophageal manometry, have enhanced our understanding and management of esophageal motility disorders. The following recommendations were developed to assist physicians in the appropriate use of esophageal manometry in modern patient care. They were discussed and approved after a comprehensive review of the medical literature pertaining to manometric techniques and their recent application. This position statement created under the auspices of the Gruppo Italiano di Studio per la Motilità dell'Apparato Digerente (GISMAD), Società Italiana di Gastroenterologia ed Endoscopia Digestiva (SIGE) and Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) is intended to help clinicians in applying manometric studies in the most fruitful manner within the context of their patients with esophageal symptoms. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

PubMed

Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

2014-06-01

Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic rates including hyperactivity in globus pallidus indicative of basal ganglia involvement. Changes in basal ganglia metabolism offer potential insight into targeting strategies for therapeutic deep brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions. Published by Oxford University Press on behalf of the Guarantors of Brain 2014. This work is written by US Government employees and is in the public domain in the US.

Trichloroethylene exposure aggravates behavioral abnormalities in mice that are deficient in superoxide dismutase.

PubMed

Otsuki, Noriyuki; Homma, Takujiro; Fujiwara, Hiroki; Kaneko, Kenya; Hozumi, Yasukazu; Shichiri, Mototada; Takashima, Mizuki; Ito, Junitsu; Konno, Tasuku; Kurahashi, Toshihiro; Yoshida, Yasukazu; Goto, Kaoru; Fujii, Satoshi; Fujii, Junichi

2016-08-01

Trichloroethylene (TCE) has been implicated as a causative agent for Parkinson's disease (PD). The administration of TCE to rodents induces neurotoxicity associated with dopaminergic neuron death, and evidence suggests that oxidative stress as a major player in the progression of PD. Here we report on TCE-induced behavioral abnormality in mice that are deficient in superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-deficient (Sod1(-/-)) mice were intraperitoneally administered TCE (500 mg/kg) over a period of 4 weeks. Although the TCE-administrated Sod1(-/-) mice showed marked abnormal motor behavior, no significant differences were observed among the experimental groups by biochemical and histopathological analyses. However, treating mouse neuroblastoma-derived NB2a cells with TCE resulted in the down regulation of the SOD1 protein and elevated oxidative stress under conditions where SOD1 production was suppressed. Taken together, these data indicate that SOD1 plays a pivotal role in protecting motor neuron function against TCE toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of changes in vertical occlusal dimension on heart rate fluctuations in guinea pigs.

PubMed

Taga, Hitoshi; Azuma, Yukio; Maehara, Kiyoshi; Nomura, Shuichi

2012-01-01

We have previously reported that the decrease of the vertical occlusal dimension (VOD) led to heart failure and abnormalities in creatine phosphokinase (CPK) in guinea pigs. In the present study, we investigated the autonomic activity and the origin of the abnormality in CPK under different occlusal conditions. Guinea pigs were separated into the following five groups: untreated control, reduced VOD, slit, restored VOD and increased VOD groups and compared for their electrocardiogram and heart rate fluctuations for two weeks using Fluclet, computer software. The control group revealed no changes in heart rate fluctuations or posture. The reduced VOD group exhibited a two-phase wave of heart rate fluctuations, with the first peak 0-2 days after teeth grinding, and the second peak starting from 4 days after teeth grinding until sudden death (usually 12th day), accompanied by head drop. The slit and the restored VOD groups exhibited only the first peak. The increased VOD group, with approximately 3 mm-thick acrylic pellets bonded to the posterior teeth, showed no heart rate fluctuations. Body weight loss was most prominent in the reduced VOD group, and became much milder in the order of increased VOD, restored and slit groups. The reduced VOD group exhibited transient elevation of skeletal muscle type of CPK isozyme activity within two days after treatment. The present study suggests that the first peak of heart rate fluctuations is caused by pulpal stimulation, and the second peak by excessive contraction (excessive excitation of the motor output system and the autonomic nervous system) of the masticatory muscles. On the other hand, increased VOD did not influence either the motor or the autonomic nervous system.

Speeded processing of grammar and tool knowledge in Tourette’s syndrome

PubMed Central

Walenski, Matthew; Mostofsky, Stewart H.; Ullman, Michael T.

2007-01-01

Tourette’s syndrome (TS) is a developmental disorder characterized by motor and verbal tics. The tics, which are fast and involuntary, result from frontal/basal-ganglia abnormalities that lead to unsuppressed behaviors. Language has not been carefully examined in TS. We tested the processing of two basic aspects of language: idiosyncratic and rule-governed linguistic knowledge. Evidence suggests that idiosyncratic knowledge (e.g., in irregular past-tense formation; bring-brought) is stored in a mental lexicon that depends on the temporal-lobe-based declarative memory system that also underlies conceptual knowledge. In contrast, evidence suggests that rule-governed combination (e.g., in regular past-tenses; walk + -ed) takes place in a mental grammar that relies on the frontal/basal-ganglia based procedural memory system, which also underlies motor skills such as how to use a hammer. We found that TS children were significantly faster than typically-developing control children at producing rule-governed past-tenses (slip-slipped, plim-plimmed, bring-bringed) but not irregular and other unpredictable past-tenses (bring-brought, splim-splam). They were also faster than controls at naming pictures of manipulated (hammer) but not non-manipulated (elephant) items. These data were not explained by a wide range of potentially confounding subject- and item-level factors. The results suggest that the processing of procedurally-based knowledge, both of grammar and of manipulated objects, is particularly speeded in TS. The frontal/basal-ganglia abnormalities may thus lead not only to tics, but to a wider range of rapid behaviors, including in the cognitive processing of rule-governed forms in language and other types of procedural knowledge. PMID:17493643

Neurological soft signs in persons with amnestic mild cognitive impairment and the relationships to neuropsychological functions.

PubMed

Li, Hui-Jie; Wang, Peng-Yun; Jiang, Yang; Chan, Raymond C K; Wang, Hua-Li; Li, Juan

2012-06-07

Neurological abnormalities have been reported in people with amnestic mild cognitive impairment (aMCI). The current study aimed to examine the prevalence of neurological soft signs (NSS) in this clinical group and to examine the relationship of NSS to other neuropsychological performances. Twenty-nine people with aMCI and 28 cognitively healthy elderly people were recruited for the present study. The NSS subscales (motor coordination, sensory integration, and disinhibition) of the Cambridge Neurological Inventory and a set of neuropsychological tests were administered to all the participants. People with aMCI exhibited significantly more motor coordination signs, disinhibition signs, and total NSS than normal controls. Correlation analysis showed that the motor coordination subscale score and total score of NSS were significantly inversely correlated with the combined Z-score of neuropsychological tests in aMCI group. These preliminary findings suggested that people with aMCI demonstrated a higher prevalence of NSS compared to healthy elderly people. Moreover, NSS was found to be inversely correlated with the neuropsychological performances in persons with aMCI. When taken together, these findings suggested that NSS may play a potential important role and serve as a tool to assist in the early detection of aMCI.

Spontaneous brain activity in the sensorimotor cortex in amyotrophic lateral sclerosis can be negatively regulated by corticospinal fiber integrity.

PubMed

Sako, Wataru; Abe, Takashi; Izumi, Yuishin; Yamazaki, Hiroki; Matsui, Naoko; Harada, Masafumi; Kaji, Ryuji

2017-05-01

Previous studies failed to detect reduced value of the amplitude of low frequency fluctuation (ALFF) derived from resting state functional magnetic resonance imaging in the primary motor cortex in amyotrophic lateral sclerosis (ALS) though primary motor cortex was mainly affected with ALS. We aimed to investigate the cause of masking the abnormality in the primary motor cortex in ALS and usefulness of ALFF for differential diagnosis among diseases showing muscle weakness. We enrolled ten patients with ALS and eleven disease controls showing muscle weakness. Voxel-wise analysis revealed that significant reduction of ALFF value was present in the right sensorimotor cortex in ALS. There was a significant negative correlation between ALFF value in the right sensorimotor cortex and fractional anisotropy (FA) value in the posterior limbs of the internal capsule (PLIC). For a diagnostic tool, the area under receiver operating characteristic curve improved if the ALS patients with disease duration >1 year were excluded. The present findings raised the possibility of usefulness of ALFF value in the sensorimotor cortex for differential diagnosis of ALS, and supported the notion that adjustment for FA value in the PLIC could improve accuracy.

Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load.

PubMed

Peluso, Michael J; Ferretti, Francesca; Peterson, Julia; Lee, Evelyn; Fuchs, Dietmar; Boschini, Antonio; Gisslén, Magnus; Angoff, Nancy; Price, Richard W; Cinque, Paola; Spudich, Serena

2012-09-10

To characterize HIV-infected patients with neurosymptomatic cerebrospinal fluid (CSF) 'escape', defined as detectable CSF HIV RNA in the setting of treatment-suppressed plasma levels or CSF RNA more than 1-log higher than plasma RNA. Retrospective case series. Four urban medical centers in the United States and Europe. Virologically controlled HIV-infected patients on antiretroviral therapy (ART) with progressive neurologic abnormalities who were determined to have CSF 'escape'. INTERVENTION Optimization of ART based upon drug susceptibility and presumed central nervous system exposure. Levels of CSF HIV RNA and inflammatory markers, clinical signs and symptoms, and MRI findings. Ten patients presented with new neurologic abnormalities, which included sensory, motor, and cognitive manifestations. Median CSF HIV RNA was 3900 copies/ml (range 134-9056), whereas median plasma HIV RNA was 62 copies/ml (range <50 to 380). Median CD4 T-cell count was 482 cells/μl (range 290-660). All patients had been controlled to less than 500 copies/ml for median 27.5 months (range 2-96) and five of 10 had been suppressed to less than 50 copies/ml for median 19.5 months (range 2-96). Patients had documentation of a stable ART regimen for median 21 months (range 9-60). All had CSF pleocytosis or elevated CSF protein; seven of eight had abnormalities on MRI; and six of seven harbored CSF resistance mutations. Following optimization of ART, eight of nine patients improved clinically. The development of neurologic symptoms in patients on ART with low or undetectable plasma HIV levels may be an indication of CSF 'escape'. This study adds to a growing body of literature regarding this rare condition in well controlled HIV infection.

Cerebrospinal Fluid HIV Escape Associated with Progressive Neurologic Dysfunction in Patients on Antiretroviral Therapy with Well-Controlled Plasma Viral Load

PubMed Central

Peluso, Michael J.; Ferretti, Francesca; Peterson, Julia; Lee, Evelyn; Fuchs, Dietmar; Boschini, Antonio; Gisslén, Magnus; Angoff, Nancy; Price, Richard W.; Cinque, Paola; Spudich, Serena

2013-01-01

Objective To characterize HIV-infected patients with neuro-symptomatic CSF ‘escape,’ defined as detectable CSF HIV RNA in the setting of treatment-suppressed plasma levels or CSF RNA >1 log higher than plasma RNA. Design Retrospective case series. Setting 4 urban medical centers in the United States and Europe. Subjects Virologically controlled HIV-infected patients on antiretroviral therapy (ART) with progressive neurologic abnormalities who were determined to have CSF ‘escape.’ Intervention Optimization of ART based upon drug susceptibility and presumed CNS exposure. Main outcome measures Levels of CSF HIV RNA and inflammatory markers, clinical signs and symptoms, magnetic resonance imaging findings. Results 10 patients presented with new neurological abnormalities, which included sensory, motor, and cognitive manifestations. Median CSF HIV RNA was 3900 copies/mL (range 134-9056), while median plasma HIV RNA was 62 copies/mL (range <50-380). Median CD4+ T cell count was 482 cells/mm3 (range, 290-660). All patients had been controlled <500 copies/mL for median 27.5 months (range, 2-96) and 5/10 had been suppressed <50 copies/mL for median 19.5 months (range, 2-96). Patients had documentation of a stable ART regimen for median 21 months (range 9-60). All had CSF pleocytosis or elevated CSF protein; 7/8 had abnormalities on MRI; and 6/7 harbored CSF resistance mutations. Following optimization of ART, 8/9 patients improved clinically. Conclusions The development of neurologic symptoms in patients on ART with low or undetectable plasma HIV levels may be an indication of CSF ‘escape.’ This study adds to a growing body of literature regarding this rare condition in well-controlled HIV infection. PMID:22614889

Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis.

PubMed

Cawley, Niamh; Solanky, Bhavana S; Muhlert, Nils; Tur, Carmen; Edden, Richard A E; Wheeler-Kingshott, Claudia A M; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2015-09-01

Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = -0.403 mM, 95% confidence intervals -0.792, -0.014, P = 0.043) and sensorimotor cortex (adjusted difference = -0.385 mM, 95% confidence intervals -0.667, -0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid concentration in the sensorimotor cortex. Specifically for each unit decrease in gamma-aminobutyric acid levels (in mM), there was a predicted -10.86 (95% confidence intervals -16.786 to -4.482) decrease in grip strength (kg force) (P < 0.001) and -8.74 (95% confidence intervals -13.943 to -3.015) decrease in muscle strength (P < 0.006). This study suggests that reduced gamma-aminobutyric acid levels reflect pathological abnormalities that may play a role in determining physical disability. These abnormalities may include decreases in the pre- and postsynaptic components of gamma-aminobutyric acid neurotransmission and in the density of inhibitory neurons. Additionally, the reduced gamma-aminobutyric acid concentration may contribute to the neurodegenerative process, resulting in increased firing of axons, with consequent increased energy demands, which may lead to neuroaxonal degeneration and loss of the compensatory mechanisms that maintain motor function. This study supports the idea that modulation of gamma-aminobutyric acid neurotransmission may be an important target for neuroprotection in multiple sclerosis.See De Stefano and Giorgio (doi:10.1093/brain/awv213) for a scientific commentary on this article. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[The cerebellum as a major player in motor disturbances related to Autistic Syndrome Disorders].

PubMed

Jaber, M

2017-04-01

Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with disturbances in communication, social interactions, cognition and affect. ASD are also accompanied by complex movement disorders, including ataxia. A special focus of recent research in this area is made on the striatum and the cerebellum, two structures known not only to control movement but also to be involved in cognitive functions such as memory and language. Dysfunction within the motor system may be associated with abnormal movements in ASD that are translated into ataxia, abnormal pattern of righting, gait sequencing, development of walking, and hand positioning. This line of study may generate new knowledge and understanding of motor symptoms associated with ASD and aims to deliver fresh perspectives for early diagnosis and therapeutic strategies against ASD. Despite the relative paucity of research in this area (compared to the social, linguistic, and behavioural disturbances in ASD), there is evidence that the frontostriatal motor system and/or the cerebellar motor systems may be the site of dysfunction in ASD. Indeed, the cerebellum seems to be essential in the development of basic social capabilities, communication, repetitive/restrictive behaviors, and motor and cognitive behaviors that are all impaired in ASD. Cerebellar neuropathology including cerebellar hypoplasia and reduced cerebellar Purkinje cell numbers are the most consistent neuropathologies linked to ASD. The functional state of the cerebellum and its impact on brain function in ASD is the focus of this review. This review starts by recapitulating historical findings pointing towards an implication of the cerebellum, and to a lesser extent the basal ganglia structures, in TSA. We then detail the structure/function of the cerebellum at the regional and cellular levels before describing human and animal findings indicating a role of the cerebellum and basal ganglia in ASD. Several studies have attempted to identify the nature of the motor system dysfunction in ASD, and it became apparent that the motor fronto-striatal and cerebellar systems are major sites of dysfunction in this psychiatric illness. Anomalies in these structures have been revealed both at the anatomical and functional levels in human patients as well as in animal models. These models are obtained by manipulation of genes that are often implicated in glutamate transmission, by lesions of brain structures among which the cerebellum, by pharmacological treatment with drugs such as the Valproate or by maternal infections with bacterial membrane extracts of double stranded RNA mimicking a viral infection. The "cognitive approach" has dominated ASD research for three decades and led to the design of interventional strategies, which have yielded satisfactory results. Nevertheless, new approaches and alternative hypotheses on the aetiology and diagnosis of ASD are needed. Research focused on motor rather than psychiatric symptoms may have a greater potential to elucidate the neurobiological basis of ASD. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients

ClinicalTrials.gov

2017-06-09

Charcot Marie Tooth Disease (CMT); Hereditary Sensory and Motor Neuropathy; Nerve Compression Syndromes; Tooth Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System

Nervous system (image)

MedlinePlus

Peripheral Neuropathy is not a distinct disease, but the manifestation of many conditions that damage the peripheral nerves ( ... abnormal. Damaged motor nerves impair movement or function. Peripheral neuropathy may be caused by direct or indirect injury, ...

Detecting acute neurotoxicity during platinum chemotherapy by neurophysiological assessment of motor nerve hyperexcitability

PubMed Central

2010-01-01

Background Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. Use was made of nerve conduction studies and needle electromyography (EMG) to assess motor nerve excitability in cancer patients during their first treatment cycle with platinum-based chemotherapy in this study. Methods Twenty-nine adult cancer patients had a neurophysiological assessment either before oxaliplatin plus capecitabine, on days 2 to 4 or 14 to 20 after oxaliplatin plus capecitabine, or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin, undertaken by a neurophysiologist who was blinded to patient and treatment details. Patients completed a symptom questionnaire at the end of the treatment cycle. Results Abnormal spontaneous high frequency motor fibre action potentials were detected in 100% of patients (n = 6) and 72% of muscles (n = 22) on days 2 to 4 post-oxaliplatin, and in 25% of patients (n = 8) and 13% of muscles (n = 32) on days 14 to 20 post-oxaliplatin, but in none of the patients (n = 14) or muscles (n = 56) tested prior to oxaliplatin or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin. Repetitive compound motor action potentials were less sensitive and less specific than spontaneous high frequency motor fibre action potentials for detection of acute oxaliplatin-induced motor nerve hyperexcitability but were present in 71% of patients (n = 7) and 32% of muscles (n = 32) on days 2 to 4 after oxaliplatin treatment. Acute neurotoxicity symptoms, most commonly cold-induced paraesthesiae and jaw or throat tightness, were reported by all patients treated with oxaliplatin (n = 22) and none of those treated with carboplatin plus paclitaxel or cisplatin (n = 6). Conclusions Abnormal spontaneous high frequency motor fibre activity is a sensitive and specific endpoint of acute oxaliplatin-induced motor nerve hyperexcitability, detectable on EMG on days 2 to 4 post-treatment. Objective EMG assessment of motor nerve excitability could compliment patient-reported symptomatic endpoints of acute oxaliplatin-induced neurotoxicity in future studies. PMID:20731872

Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia.

PubMed

Ueno, Tatsuya; Yamada, Junko; Nishijima, Haruo; Arai, Akira; Migita, Keisuke; Baba, Masayuki; Ueno, Shinya; Tomiyama, Masahiko

2014-04-01

Levodopa-induced dyskinesia (LID) is a major complication of long-term dopamine replacement therapy for Parkinson's disease, and becomes increasingly problematic in the advanced stage of the disease. Although the cause of LID still remains unclear, there is accumulating evidence from animal experiments that it results from maladaptive plasticity, resulting in supersensitive excitatory transmission at corticostriatal synapses. Recent work using transcranial magnetic stimulation suggests that the motor cortex displays the same supersensitivity in Parkinson's disease patients with LID. To date, the cellular mechanisms underlying the abnormal cortical plasticity have not been examined. The morphology of the dendritic spines has a strong relationship to synaptic plasticity. Therefore, we explored the spine morphology of pyramidal neurons in the motor cortex in a rat model of LID. We used control rats, 6-hydroxydopamine-lesioned rats (a model of Parkinson's disease), 6-hydroxydopamine-lesioned rats chronically treated with levodopa (a model of LID), and control rats chronically treated with levodopa. Because the direct pathway of the basal ganglia plays a central role in the development of LID, we quantified the density and size of dendritic spines in intratelencephalic (IT)-type pyramidal neurons in M1 cortex that project to the striatal medium spiny neurons in the direct pathway. The spine density was not different among the four groups. In contrast, spine size became enlarged in the Parkinson's disease and LID rat models. The enlargement was significantly greater in the LID model than in the Parkinson's disease model. This enlargement of the spines suggests that IT-type pyramidal neurons acquire supersensitivity to excitatory stimuli. To confirm this possibility, we monitored miniature excitatory postsynaptic currents (mEPSCs) in the IT-type pyramidal neurons in M1 cortex using whole-cell patch clamp. The amplitude of the mEPSCs was significantly increased in the LID model compared with the control. This indicates that the IT-type pyramidal neurons become hyperexcited in the LID model, paralleling the enlargement of spines. Thus, spine enlargement and the resultant hyperexcitability of IT-type pyramidal neurons in M1 cortex might contribute to the abnormal cortical neuronal plasticity in LID. Copyright © 2013 Elsevier Inc. All rights reserved.

Congenital cutis laxa with ligamentous laxity and delayed development, Dandy-Walker malformation and minor heart and osseous defects.

PubMed

Biver, A; De Rijcke, S; Toppet, V; Ledoux-Corbusier, M; Van Maldergem, L

1994-06-01

We present a female infant exhibiting congenital cutis laxa with retardation of growth and motor development, ligamentous laxity and congenital dislocation of the hips. This connective tissue disorder was associated with Dandy-Walker malformation, atrial and ventricular defect and minor bone abnormalities including multiple wormian bones, abnormal tubulation of long bones and absent twelfth pair of ribs. This association is believed to be unique.

Critical Involvement of the Motor Cortex in the Pathophysiology and Treatment of Parkinson’s Disease

PubMed Central

Lindenbach, David; Bishop, Christopher

2013-01-01

This review examines the involvement of the motor cortex in Parkinson’s disease (PD), a debilitating movement disorder typified by degeneration of dopamine cells of the substantia nigra. While much of PD research has focused on the caudate/putamen, many aspects of motor cortex function are abnormal in PD patients and in animal models of PD, implicating motor cortex involvement in disease symptoms and their treatment. Herein, we discuss several lines of evidence to support this hypothesis. Dopamine depletion alters regional metabolism in the motor cortex and also reduces interneuron activity, causing a breakdown in intracortical inhibition. This leads to functional reorganization of motor maps and excessive corticostriatal synchrony when movement is initiated. Recent work suggests that electrical stimulation of the motor cortex provides a clinical benefit for PD patients. Based on extant research, we identify a number of unanswered questions regarding the motor cortex in PD and argue that a better understanding of the contribution of the motor cortex to PD symptoms will facilitate the development of novel therapeutic approaches. PMID:24113323

Isolated cortical visual loss with subtle brain MRI abnormalities in a case of hypoxic-ischemic encephalopathy.

PubMed

Margolin, Edward; Gujar, Sachin K; Trobe, Jonathan D

2007-12-01

A 16-year-old boy who was briefly asystolic and hypotensive after a motor vehicle accident complained of abnormal vision after recovering consciousness. Visual acuity was normal, but visual fields were severely constricted without clear hemianopic features. The ophthalmic examination was otherwise normal. Brain MRI performed 11 days after the accident showed no pertinent abnormalities. At 6 months after the event, brain MRI demonstrated brain volume loss in the primary visual cortex and no other abnormalities. One year later, visual fields remained severely constricted; neurologic examination, including formal neuropsychometric testing, was normal. This case emphasizes the fact that hypoxic-ischemic encephalopathy (HIE) may cause enduring damage limited to primary visual cortex and that the MRI abnormalities may be subtle. These phenomena should be recognized in the management of patients with HIE.

Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM.

PubMed

Tamada, Hiromi; Kiryu-Seo, Sumiko; Hosokawa, Hiroki; Ohta, Keisuke; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Nakamura, Kei-Ichiro; Kiyama, Hiroshi

2017-08-01

Mitochondria undergo morphological changes through fusion and fission for their quality control, which are vital for neuronal function. In this study, we examined three-dimensional morphologies of mitochondria in motor neurons under normal, nerve injured, and nerve injured plus fission-impaired conditions using the focused ion beam/scanning electron microscopy (FIB/SEM), because the FIB/SEM technology is a powerful tool to demonstrate both 3D images of whole organelle and the intra-organellar structure simultaneously. Crossing of dynamin-related protein 1 (Drp1) gene-floxed mice with neuronal injury-specific Cre driver mice, Atf3:BAC Tg mice, allowed for Drp1 ablation specifically in injured neurons. FIB/SEM analysis demonstrated that somatic mitochondrial morphologies in motor neurons were not altered before or after nerve injury. However, the fission impairment resulted in prominent somatic mitochondrial enlargement, which initially induced complex morphologies with round regions and long tubular processes, subsequently causing a decrease in the number of processes and further enlargement of the round regions, which eventually resulted in big spheroidal mitochondria without processes. The abnormal mitochondria exhibited several degradative morphologies: local or total cristae collapse, vacuolization, and mitophagy. These suggest that mitochondrial fission is crucial for maintaining mitochondrial integrity in injured motor neurons, and multiple forms of mitochondria degradation may accelerate neuronal degradation. © 2017 Wiley Periodicals, Inc.

Linear and Nonlinear Analyses of the Cardiac Autonomic Control in Children With Developmental Coordination Disorder: A Case-Control Study.

PubMed

Cavalcante Neto, Jorge L; Zamunér, Antonio R; Moreno, Bianca C; Silva, Ester; Tudella, Eloisa

2018-01-01

Children with Developmental Coordination Disorder (DCD) and children at risk for DCD (r-DCD) present motor impairments interfering in their school, leisure and daily activities. In addition, these children may have abnormalities in their cardiac autonomic control, which together with their motor impairments, restrict their health and functionality. Therefore, this study aimed to assess the cardiac autonomic control, by linear and nonlinear analysis, at supine and during an orthostatic stimulus in DCD, r-DCD and typically developed children. Thirteen DCD children (11 boys and 2 girls, aged 8.08 ± 0.79 years), 19 children at risk for DCD (13 boys and 6 girls, aged 8.10 ± 0.96 years) and 18 typically developed children, who constituted the control group (CG) (10 boys and 8 girls, aged 8.50 ± 0.96 years) underwent a heart rate variability (HRV) examination. R-R intervals were recorded in order to assess the cardiac autonomic control using a validated HR monitor. HRV was analyzed by linear and nonlinear methods and compared between r-DCD, DCD, and CG. The DCD group presented blunted cardiac autonomic adjustment to the orthostatic stimulus, which was not observed in r-DCD and CG. Regarding nonlinear analysis of HRV, the DCD group presented lower parasympathetic modulation in the supine position compared to the r-DCD and CG groups. In the within group analysis, only the DCD group did not increase HR from supine to standing posture. Symbolic analysis revealed a significant decrease in 2LV ( p < 0.0001) and 2UV ( p < 0.0001) indices from supine to orthostatic posture only in the CG. In conclusion, r-DCD and DCD children present cardiac autonomic dysfunction characterized by higher sympathetic, lower parasympathetic and lower complexity of cardiac autonomic control in the supine position, as well as a blunted autonomic adjustment to the orthostatic stimulus. Therefore, cardiovascular health improvement should be part of DCD children's management, even in cases of less severe motor impairment.

Umbilical cord mesenchymal stem cell (UC-MSC) transplantations for cerebral palsy

PubMed Central

Dong, Huajiang; Li, Gang; Shang, Chongzhi; Yin, Huijuan; Luo, Yuechen; Meng, Huipeng; Li, Xiaohong; Wang, Yali; Lin, Ling; Zhao, Mingliang

2018-01-01

This study reports a case of a 4-year-old boy patient with abnormalities of muscle tone, movement and motor skills, as well as unstable gait leading to frequent falls. The results of the electroencephalogram (EEG) indicate moderately abnormal EEG, accompanied by irregular seizures. Based on these clinical characteristics, the patient was diagnosed with cerebral palsy (CP) in our hospital. In this study, the patient was treated with umbilical cord mesenchymal stem cell (UC-MSC) transplantation therapy. This patient received UC-MSC transplantation 3 times (5.3*107) in total. After three successive cell transplantations, the patient recovered well and showed obvious improvements in EEG and limb strength, motor function, and language expression. However, the improvement in intelligence quotient (IQ) was less obvious. These results indicate that UC-MSC transplantation is a promising treatment for cerebral palsy. PMID:29636880

Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

PubMed Central

Israelashvili, Michal; Loewenstern, Yocheved

2015-01-01

Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

Patterns of Weakness, Classification of Motor Neuron Disease & Clinical Diagnosis of Sporadic ALS

PubMed Central

Statland, Jeffrey M.; Barohn, Richard J.; McVey, April L.; Katz, Jonathan; Dimachkie, Mazen M.

2015-01-01

Synopsis When approaching the patient with suspected motor neuron disease (MND) the pattern of weakness on exam helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing, in the absence of other abnormalities on neuroimaging or serological testing. MNDs exist on a spectrum: from a pure lower motor neuron; to mixed upper and lower motor neuron; to a pure upper motor neuron variant in addition to regional variants restricted to the arms, legs or bulbar region. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic (~85%), which is invariably fatal. The only FDA approved treatments for ALS are riluzole, which prolongs life by about 3 months, and dextromethorphan/quinidine which provides symptomatic relief for pseudobulbar affect (inappropriate bouts of laughter or crying). Here we describe a pattern approach to identifying motor neuron disease, and clinical features of sporadic ALS. PMID:26515618

Prenatal alcohol exposure reduces the size of the forelimb representation in motor cortex in rat: an intracortical microstimulation (ICMS) mapping study.

PubMed

Xie, Ni; Yang, Qiuhong; Chappell, Tyson D; Li, Cheng-Xiang; Waters, Robert S

2010-03-01

Children with fetal alcohol spectrum disorder (FASD) often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although the underlying causes for these motor abnormalities are unknown, they likely involve interactions between sensory and motor systems. Rodent animal models have been used to study the effects of prenatal alcohol exposure (PAE) on skilled reaching and on the development and organization of somatosensory barrel field cortex. To this end, PAE delayed the development of somatosensory cortex, reduced the size of whisker and forelimb representations in somatosensory barrel field cortex, and delayed acquisition time to learn a skilled reaching task. However, whether PAE also affects the motor cortex (MI) remains to be determined. In the present study, we investigated the effect of PAE on the size of the forelimb representation in rat MI, thresholds for activation, and the overlap between motor and sensory cortical forelimb maps in sensorimotor cortex. Pregnant Sprague-Dawley rats were assigned to alcohol (Alc), pair-fed (PF), and chow-fed (CF) groups on gestation day 1 (GD1). Rats in the Alc group (n=4) were chronically intubated daily with binge doses of alcohol (6g/kg body weight) from GD1 to GD20 that resulted in averaged blood alcohol levels measured on GD10 (mean=191.5+/-41.9mg/dL) and on GD17 (mean=247.0+/-72.4mg/dL). PF (n=2) and CF (n=3) groups of pregnant rats served as controls. The effect of PAE on the various dependent measures was obtained from multiple male offspring from each dam within treatment groups, and litter means were compared between the groups from alcohol-treated and control (Ct: CF and PF) dams. At approximately 8 weeks of age, rats were anesthetized with ketamine/xylazine and the skull opened over sensorimotor cortex. A tungsten microelectrode was then inserted into the depths of layer V and intracortical microstimulation was used to deliver trains of pulses to evoke muscle contractions and/or movements; maximum stimulating < or =100microA. When a motor response was observed, the threshold for movement was measured and the motor receptive field projected to the cortical surface to serve as representative point for that location. A motor map for the forelimb representation was generated by systematically stimulating at adjacent sites until current thresholds reached the maximum and/or motor responses were no longer evoked. The major findings in this study were as follows: (1) PAE significantly reduced the area of the forelimb representation in the Alc offspring (6.01mm(2), standard error of the mean=+/-0.278) compared with the Ct offspring (8.03mm(2)+/-0.586), (2) PAE did not significantly reduce the averaged threshold for activation of movements between groups, (3) PAE significantly reduced the percent overlap (Alc=31.1%, Ct=55.4%) between the forelimb representation in sensory and motor cortices, and (4) no significant differences were observed in averaged body weight, hemisphere weight, or age of animal between treatment groups. These findings suggest that the effects of PAE are not restricted to somatosensory barrel field cortex but also involve the MI and may underlie deficits in motor control and sensorimotor integration observed among children with FASD. 2010. Published by Elsevier Inc.

Innervation zones of fasciculating motor units: observations by a linear electrode array.

PubMed

Jahanmiri-Nezhad, Faezeh; Barkhaus, Paul E; Rymer, William Z; Zhou, Ping

2015-01-01

This study examines the innervation zone (IZ) in the biceps brachii muscle in healthy subjects and those with amyotrophic lateral sclerosis (ALS) using a 20-channel linear electromyogram (EMG) electrode array. Raster plots of individual waveform potentials were studied to estimate the motor unit IZ. While this work mainly focused on fasciculation potentials (FPs), a limited number of motor unit potentials (MUPs) from voluntary activity of 12 healthy and seven ALS subjects were also examined. Abnormal propagation of MUPs and scattered IZs were observed in fasciculating units, compared with voluntarily activated MUPs in healthy and ALS subjects. These findings can be related to muscle fiber reinnervation following motor neuron degeneration in ALS and the different origin sites of FPs compared with voluntary MUPs.

Tone-deafness – a new disconnection syndrome?

PubMed Central

Loui, Psyche; Alsop, David; Schlaug, Gottfried

2009-01-01

Communicating with one’s environment requires efficient neural interaction between action and perception. Neural substrates ofsound perception and production are connected by the arcuate fasciculus (AF). While AF is known to be involved in language, its roles in non-linguistic functions are unexplored. Here we show that tone-deaf people, with impaired sound perception and production, have reduced AF connectivity. Diffusion tensor tractography and psychophysics were assessed in tone-deaf individuals and matched controls. Abnormally-reduced AF connectivity was observed in the tone-deaf. Furthermore, we observed relationships between AF and auditory-motor behavior: superior and inferior AF branches predict psychophysically-assessed pitch-discrimination and sound production-perception abilities respectively. This neural abnormality suggests that tone-deafness leads to a reduction in connectivity resulting in pitch-related impairments. Results support a dual-stream anatomy of sound production and perception implicated in vocal communications. By identifying white-matter differences and their psychophysical correlates, results contribute to our understanding of how neural connectivity subserves behavior. PMID:19692596

Oscillations in sensorimotor cortex in movement disorders: an electrocorticography study.

PubMed

Crowell, Andrea L; Ryapolova-Webb, Elena S; Ostrem, Jill L; Galifianakis, Nicholas B; Shimamoto, Shoichi; Lim, Daniel A; Starr, Philip A

2012-02-01

Movement disorders of basal ganglia origin may arise from abnormalities in synchronized oscillatory activity in a network that includes the basal ganglia, thalamus and motor cortices. In humans, much has been learned from the study of basal ganglia local field potentials recorded from temporarily externalized deep brain stimulator electrodes. These studies have led to the theory that Parkinson's disease has characteristic alterations in the beta frequency band (13-30 Hz) in the basal ganglia-thalamocortical network. However, different disorders have rarely been compared using recordings in the same structure under the same behavioural conditions, limiting straightforward assessment of current hypotheses. To address this, we utilized subdural electrocorticography to study cortical oscillations in the three most common movement disorders: Parkinson's disease, primary dystonia and essential tremor. We recorded local field potentials from the arm area of primary motor and sensory cortices in 31 subjects using strip electrodes placed temporarily during routine surgery for deep brain stimulator placement. We show that: (i) primary motor cortex broadband gamma power is increased in Parkinson's disease compared with the other conditions, both at rest and during a movement task; (ii) primary motor cortex high beta (20-30 Hz) power is increased in Parkinson's disease during the 'stop' phase of a movement task; (iii) the alpha-beta peaks in the motor and sensory cortical power spectra occur at higher frequencies in Parkinson's disease than in the other two disorders; and (iv) patients with dystonia have impaired movement-related beta band desynchronization in primary motor and sensory cortices. The findings support the emerging hypothesis that disease states reflect abnormalities in synchronized oscillatory activity. This is the first study of sensorimotor cortex local field potentials in the three most common movement disorders.

Altered Pharyngeal Muscles in Parkinson Disease

PubMed Central

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H.; Shill, Holly A.; Caviness, John N.; Samanta, Johan E.; Beach, Thomas G.

2012-01-01

Dysphagia (impaired swallowing) is common in Parkinson disease (PD) patients and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor (PC) and cricopharyngeal (CP) sphincter muscles in postmortem specimens from 8 PD and 4 age-matched control patients. Pharyngeal muscles in PD patients exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, the PD patients with dysphagia had a higher percentage of atrophic myofibers vs. with those without dysphagia and controls. The fast-to-slow fiber type transition is consistent with abnormalities in swallowing, slow movement of food and increased tone in the CP sphincter in PD patients. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in PD patients. PMID:22588389

Spiral analysis in Niemann-Pick disease type C.

PubMed

Hsu, Annie W; Piboolnurak, Panida A; Floyd, Alicia G; Yu, Qiping P; Wraith, James E; Patterson, Marc C; Pullman, Seth L

2009-10-15

Spiral analysis is a computerized method of analyzing upper limb motor physiology through the quantification of spiral drawing. The objective of this study was to determine whether spirals drawn by patients with Niemann-Pick disease type C (NPC) could be distinguished from those of controls, and to physiologically characterize movement abnormalities in NPC. Spiral data consisting of position, pressure, and time were collected from 14 NPC patients and 14 age-matched controls, and were analyzed by the Mann-Whitney U test. NPC spirals were characterized by: lower speed (2.67 vs. 9.56 cm/s, P < 0.001) and acceleration (0.10 vs. 2.04 cm/s(2), P < 0.001), higher loop width variability (0.88 vs. 0.28, P < 0.001), tremor (5/10 vs. 0/10 trials in the dominant hand, P < 0.001), and poor overall spiral rating (2.53 vs. 0.70, P < 0.005). NPC spirals also exhibited sustained drawing pressure profiles that were abnormally invariant with time. Other features, such as the tightness of loop widths, were normal. Our findings reveal that differing aspects of tremor, Parkinsonism, ataxia, and dystonia are quantifiable in NPC patients.

Altered pharyngeal muscles in Parkinson disease.

PubMed

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Beach, Thomas G

2012-06-01

Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in postmortem specimens from 8 subjects with PD and 4 age-matched control subjects. Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, subjects with PD with dysphagia had a higher percentage of atrophic myofibers versus with those without dysphagia and controls. The fast-to-slow fiber-type transition is consistent with abnormalities in swallowing, slow movement of food, and increased tone in the cricopharyngeal sphincter in subjects with PD. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in subjects with PD.

Attenuation of acoustic and tactile startle responses of vitamin B-6 deficient rats.

PubMed

Schaeffer, M C

1987-01-01

Vitamin B-6 deficient rats exhibit changes in behavior, sensory function, and other nervous system abnormalities such as convulsive seizures and motor disturbances. Sensorimotor reactivity was evaluated quantitatively by measuring auditory and tactile startle responses in 12 week old female Long-Evans rats fed a diet devoid of added vitamin B-6 (DEF) or a control diet, either ad lib (AL-CON) or pair-fed to deficient rats (PF-CON). Deficiency was confirmed with a tryptophan-load test administered to a separate group of rats fed simultaneously according to the same protocol. At week 18, body weight and feed efficiency were different among groups (p less than 0.001), and were lowest in DEF. Amplitude of response to both acoustic and tactile stimuli was depressed in DEF compared to both control groups, which generally did not differ in response. This effect was seen most dramatically in responses to the acoustic stimulus (p = 0.034), and especially to the first presentation (p = 0.017). Latency to maximum response was not affected by diet. Possible mechanisms for this nervous system abnormality, not previously reported in vitamin B-6 deficiency, are discussed.

Uncovering the Social Deficits in the Autistic Brain. A Source-Based Morphometric Study

PubMed Central

Grecucci, Alessandro; Rubicondo, Danilo; Siugzdaite, Roma; Surian, Luca; Job, Remo

2016-01-01

Autism is a neurodevelopmental disorder that mainly affects social interaction and communication. Evidence from behavioral and functional MRI studies supports the hypothesis that dysfunctional mechanisms involving social brain structures play a major role in autistic symptomatology. However, the investigation of anatomical abnormalities in the brain of people with autism has led to inconsistent results. We investigated whether specific brain regions, known to display functional abnormalities in autism, may exhibit mutual and peculiar patterns of covariance in their gray-matter concentrations. We analyzed structural MRI images of 32 young men affected by autistic disorder (AD) and 50 healthy controls. Controls were matched for sex, age, handedness. IQ scores were also monitored to avoid confounding. A multivariate Source-Based Morphometry (SBM) was applied for the first time on AD and controls to detect maximally independent networks of gray matter. Group comparison revealed a gray-matter source that showed differences in AD compared to controls. This network includes broad temporal regions involved in social cognition and high-level visual processing, but also motor and executive areas of the frontal lobe. Notably, we found that gray matter differences, as reflected by SBM, significantly correlated with social and behavioral deficits displayed by AD individuals and encoded via the Autism Diagnostic Observation Schedule scores. These findings provide support for current hypotheses about the neural basis of atypical social and mental states information processing in autism. PMID:27630538

Individuals with autism spectrum disorder show abnormalities during initial and subsequent phases of precision gripping

PubMed Central

Magnon, Grant C.; White, Stormi P.; Greene, Rachel K.; Vaillancourt, David E.

2014-01-01

Sensorimotor impairments are common in autism spectrum disorder (ASD), but they are not well understood. Here we examined force control during initial pulses and the subsequent rise, sustained, and relaxation phases of precision gripping in 34 individuals with ASD and 25 healthy control subjects. Participants pressed on opposing load cells with their thumb and index finger while receiving visual feedback regarding their performance. They completed 2- and 8-s trials during which they pressed at 15%, 45%, or 85% of their maximum force. Initial pulses guided by feedforward control mechanisms, sustained force output controlled by visual feedback processes, and force relaxation rates all were examined. Control subjects favored an initial pulse strategy characterized by a rapid increase in and then relaxation of force when the target force was low (Type 1). When the target force level or duration of trials was increased, control subjects transitioned to a strategy in which they more gradually increased their force, paused, and then increased their force again. Individuals with ASD showed a more persistent bias toward the Type 1 strategy at higher force levels and during longer trials, and their initial force output was less accurate than that of control subjects. Patients showed increased force variability compared with control subjects when attempting to sustain a constant force level. During the relaxation phase, they showed reduced rates of force decrease. These findings suggest that both feedforward and feedback motor control mechanisms are compromised in ASD and these deficits may contribute to the dyspraxia and sensorimotor abnormalities often seen in this disorder. PMID:25552638

Early Cognitive/Social Deficits and Late Motor Phenotype in Conditional Wild-Type TDP-43 Transgenic Mice.

PubMed

Alfieri, Julio A; Silva, Pablo R; Igaz, Lionel M

2016-01-01

Frontotemporal Dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative diseases associated to mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43). To investigate in depth the behavioral phenotype associated with this proteinopathy, we used as a model transgenic (Tg) mice conditionally overexpressing human wild-type TDP 43 protein (hTDP-43-WT) in forebrain neurons. We previously characterized these mice at the neuropathological level and found progressive neurodegeneration and other features that evoke human TDP-43 proteinopathies of the FTD/ALS spectrum. In the present study we analyzed the behavior of mice at multiple domains, including motor, social and cognitive performance. Our results indicate that young hTDP-43-WT Tg mice (1 month after post-weaning transgene induction) present a normal motor phenotype compared to control littermates, as assessed by accelerated rotarod performance, spontaneous locomotor activity in the open field test and a mild degree of spasticity shown by a clasping phenotype. Analysis of social and cognitive behavior showed a rapid installment of deficits in social interaction, working memory (Y-maze test) and recognition memory (novel object recognition test) in the absence of overt motor abnormalities. To investigate if the motor phenotype worsen with age, we analyzed the behavior of mice after long-term (up to 12 months) transgene induction. Our results reveal a decreased performance on the rotarod test and in the hanging wire test, indicating a motor phenotype that was absent in younger mice. In addition, long-term hTDP-43-WT expression led to hyperlocomotion in the open field test. In sum, these results demonstrate a time-dependent emergence of a motor phenotype in older hTDP-43-WT Tg mice, recapitulating aspects of clinical FTD presentations with motor involvement in human patients, and providing a complementary animal model for studying TDP-43 proteinopathies.

Aberrant regulation of DNA methylation in amyotrophic lateral sclerosis: a new target of disease mechanisms.

PubMed

Martin, Lee J; Wong, Margaret

2013-10-01

Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. A diagnosis is fatal owing to degeneration of motor neurons in brain and spinal cord that control swallowing, breathing, and movement. ALS can be inherited, but most cases are not associated with a family history of the disease. The mechanisms causing motor neuron death in ALS are still unknown. Given the suspected complex interplay between multiple genes, the environment, metabolism, and lifestyle in the pathogenesis of ALS, we have hypothesized that the mechanisms of disease in ALS involve epigenetic contributions that can drive motor neuron degeneration. DNA methylation is an epigenetic mechanism for gene regulation engaged by DNA methyltransferase (Dnmt)-catalyzed methyl group transfer to carbon-5 in cytosine residues in gene regulatory promoter and nonpromoter regions. Recent genome-wide analyses have found differential gene methylation in human ALS. Neuropathologic assessments have revealed that motor neurons in human ALS show significant abnormalities in Dnmt1, Dnmt3a, and 5-methylcytosine. Similar changes are seen in mice with motor neuron degeneration, and Dnmt3a was found abundantly at synapses and in mitochondria. During apoptosis of cultured motor neuron-like cells, Dnmt1 and Dnmt3a protein levels increase, and 5-methylcytosine accumulates. Enforced expression of Dnmt3a, but not Dnmt1, induces degeneration of cultured neurons. Truncation mutation of the Dnmt3a catalytic domain and Dnmt3a RNAi blocks apoptosis of cultured neurons. Inhibition of Dnmt catalytic activity with small molecules RG108 and procainamide protects motor neurons from excessive DNA methylation and apoptosis in cell culture and in a mouse model of ALS. Thus, motor neurons can engage epigenetic mechanisms to cause their degeneration, involving Dnmts and increased DNA methylation. Aberrant DNA methylation in vulnerable cells is a new direction for discovering mechanisms of ALS pathogenesis that could be relevant to new disease target identification and therapies for ALS.

Kinematic analysis of handwriting movements in patients with obsessive-compulsive disorder

PubMed Central

Mavrogiorgou, P; Mergl, R; Tigges, P; El Husseini, J; Schroter, A; Juckel, G; Zaudig, M; Hegerl, U

2001-01-01

OBJECTIVES—Basal ganglia dysfunction is supposed to play a part in the pathophysiology of obsessive-compulsive disorder (OCD). A new computer aided technique for the analysis of hand movements, allowing the detection of subtle motor performance abnormalities, was applied in this study of patients with OCD and healthy controls.
METHODS—Using a digitising graphic tablet, hand motor performance was studied in 22 unmedicated patients with OCD and compared with 22 healthy controls. All subjects drew superimposed concentric circles with both the right and the left hand, in addition to writing a given sentence, their personal signature, and letter sequences in four different sizes. Kinematic parameters were calculated to quantify hand motion.
RESULTS—Patients with OCD had significant impairments of handwriting performance, reflected by lower peak velocity (sentence t=3.6; p=0.001; signature t=2.8; p=0.01) and micrographia (sentence t=3.4; p=0.002; signature t=2.5; p=0.02), compared with controls and shortened acceleration phases per stroke (sentence t=2.4; p=0.02; signature t=4.1; p=0.000). By contrast, in repetitive drawing, patients with OCD had higher peak velocity than healthy controls (group×task interaction p<0.01). There were no significant differences in left and right hand performance between groups. Patients with early versus late age of onset differed in handwriting parameters, such as handwriting consistency. Greater severity of obsessions and compulsions correlated with increasingly poor handwriting performance in patients with OCD.
CONCLUSIONS—A subtle motor dysfunction in OCD can be detected with a digitising tablet. The findings show handwriting impairments in patients with OCD, in line with the assumption that basal ganglia dysfunction is part of OCD pathophysiology. Repetitive motor pattern performance was not impaired, but rather tended to be even better in patients with OCD than in controls. The findings also support the concept that patients with OCD with early versus late age of onset differ in pathophysiological mechanisms and basal ganglia dysfunction.

 PMID:11309453

Patients with mild cognitive impairment have an abnormal upper-alpha event-related desynchronization/synchronization (ERD/ERS) during a task of temporal attention.

PubMed

Caravaglios, Giuseppe; Muscoso, Emma Gabriella; Di Maria, Giulia; Costanzo, Erminio

2015-03-01

There are several evidences indicating that an impairment in attention-executive functions is present in prodromal Alzheimer's disease and predict future global cognitive decline. In particular, the issue of temporal orienting of attention in patients with mild cognitive impairment (MCI) due to Alzheimer's disease has been overlooked. The present research aimed to explore whether subtle deficits of cortical activation are present in these patients early in the course of the disease. We studied the upper-alpha event-related synchronization/desynchronization phenomenon during a paradigm of temporal orientation of attention. MCI patients (n = 27) and healthy elderly controls (n = 15) performed a task in which periodically omitted tones had to be predicted and their virtual onset time had to be marked by pressing a button. Single-trial responses were measured, respectively, before and after the motor response. Then, upper-alpha responses were compared to upper-alpha power during eyes-closed resting state. The time course of the task was characterized by two different behavioral conditions: (1) a pre-event epoch, in which the subject awaited the virtual onset of the omitted tone, (2) a post-event epoch (after button pressing), in which the subject was in a post-motor response condition. The principal findings are: (1) during the waiting epoch, only healthy elderly had an upper-alpha ERD at the level of both temporal and posterior brain regions; (2) during the post-motor epoch, the aMCI patients had a weaker upper-alpha ERS on prefrontal regions; (3) only healthy elderly showed a laterality effect: (a) during the waiting epoch, the upper-alpha ERD was greater at the level of the right posterior-temporal lead; during the post-motor epoch, the upper alpha ERS was greater on the left prefrontal lead. The relevance of these findings is that the weaker upper-alpha response observed in aMCI patients is evident even if the accuracy of the behavioral performance (i.e., button pressing) is still spared. This abnormal upper-alpha response might represent an early biomarker of the attention-executive network impairment in MCI due to Alzheimer's disease.

Whole-Brain DTI Assessment of White Matter Damage in Children with Bilateral Cerebral Palsy: Evidence of Involvement beyond the Primary Target of the Anoxic Insult.

PubMed

Arrigoni, F; Peruzzo, D; Gagliardi, C; Maghini, C; Colombo, P; Iammarrone, F Servodio; Pierpaoli, C; Triulzi, F; Turconi, A C

2016-07-01

Cerebral palsy is frequently associated with both motor and nonmotor symptoms. DTI can characterize the damage at the level of motor tracts but provides less consistent results in nonmotor areas. We used a standardized pipeline of analysis to describe and quantify the pattern of DTI white matter abnormalities of the whole brain in a group of children with chronic bilateral cerebral palsy and periventricular leukomalacia. We also explored potential correlations between DTI and clinical scale metrics. Twenty-five patients (mean age, 11.8 years) and 25 healthy children (mean age, 11.8 years) were studied at 3T with a 2-mm isotropic DTI sequence. Differences between patients and controls were assessed both voxelwise and in ROIs obtained from an existing DTI atlas. Clinical metrics included the Gross Motor Function Classification System, the Manual Ability Classification System, and intelligence quotient. The voxel-level and ROI-level analyses demonstrated highly significant (P < .001) modifications of DTI measurements in patients at several levels: cerebellar peduncles, corticospinal tracts and posterior thalamic radiations, posterior corpus callosum, external capsule, anterior thalamic radiation, superior longitudinal fasciculi and corona radiata, optic nerves, and chiasm. The reduction of fractional anisotropy values in significant tracts was between 8% and 30%. Statistically significant correlations were found between motor impairment and fractional anisotropy in corticospinal tracts and commissural and associative tracts of the supratentorial brain. We demonstrated the involvement of several motor and nonmotor areas in the chronic damage associated with periventricular leukomalacia and showed new correlations between motor skills and DTI metrics. © 2016 by American Journal of Neuroradiology.

Non-motor symptoms and cardiac innervation in SYNJ1-related parkinsonism.

PubMed

De Rosa, A; Pellegrino, T; Pappatà, S; Lieto, M; Bonifati, V; Palma, V; Topa, A; Santoro, L; Bilo, L; Cuocolo, A; De Michele, G

2016-02-01

PARK20 is a rare autosomal recessive parkinsonism related to the SYNJ1 gene and characterized by early-onset of disease and atypical signs such as supranuclear vertical gaze palsy, dementia, dystonia, and generalized tonic-clonic seizures. Non-motor features and cardiac sympathetic innervation were assessed in two siblings affected by parkinsonism who harboured the homozygous Arg258Gln mutation in the SYNJ1 gene. The Non-Motor Symptoms, the SCOPA-AUT, the Mayo Sleep Questionnaires and polysomnography were used to investigate non-motor signs (NMS), autonomic dysfunction and REM Behavioural Disorder (RBD). Cognitive functions were examined by an extensive battery of neuropsychological tests. In addition, motor and sensory nerve conduction studies and evoked laser potentials were performed. Cardiac sympathetic innervation was assessed in the two patients by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, computing early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR). Among the non-motor symptoms and autonomic signs, case 1 had cold intolerance, drooling and dysphagia, while case 2 had pain and urinary dysfunction. Both cases showed mood and behavioural disorders. RBD were not found, whereas the neuropsychological assessment revealed a progressive cognitive impairment. Neurophysiological studies revealed no abnormalities. Indexes of cardiac sympathetic innervation in the two patients did not differ from those of control subjects. Our findings expand the phenotypic profile of SYNJ1-related parkinsonism. Preserved cardiac sympathetic function and absence of RBD suggest that PARK20 should be explained by a pathogenic mechanism different from Lewy Body pathology, or that the latter is not as widespread as idiopathic Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Motor outcome at the age of one after perinatal hypoxic-ischemic encephalopathy.

PubMed

van Schie, P E M; Becher, J G; Dallmeijer, A J; Barkhof, F; Weissenbruch, M M; Vermeulen, R J

2007-04-01

The aim of this report is to describe the motor outcome in one year-old children who were born at full-term with perinatal hypoxic-ischemic encephalopathy (HIE). Relationships between motor ability tests and neurological examination at one year, and between these tests and neonatal brain magnetic resonance imaging (MRI) were investigated. 32 surviving children, born full-term with perinatal HIE, are included in this report. All children had a neonatal MRI. At one year, motor ability was assessed with the Alberta Infant Motor Scale and the Bayley Scales of Infant Development (2nd version). Neurological examinations included the neurological optimality score (NOS). At one year, 14 children (44%) had normal motor ability, nine (28%) had mildly delayed, and nine had significantly delayed motor ability. The NOS ranged from 14.6-27 points. All children with normal motor ability had (near) optimal NOS, however, not all children with high NOS had normal motor ability. Eleven children (34%) had normal neonatal MRI; at one year, six of them had normal, and five had mildly delayed motor ability. Eight children with normal motor ability showed abnormalities on neonatal MRI. Neonatal brain MRI does not predict motor outcome at one year. Motor ability tests and neurological examinations should be used in a complementary manner to describe outcome after HIE.

A Positive Vestibular/Ocular Motor Screening (VOMS) Is Associated With Increased Recovery Time After Sports-Related Concussion in Youth and Adolescent Athletes.

PubMed

Anzalone, Anthony J; Blueitt, Damond; Case, Tami; McGuffin, Tiffany; Pollard, Kalyssa; Garrison, J Craig; Jones, Margaret T; Pavur, Robert; Turner, Stephanie; Oliver, Jonathan M

2017-02-01

Vestibular and ocular motor impairments are routinely reported in patients with sports-related concussion (SRC) and may result in delayed return to play (RTP). The Vestibular/Ocular Motor Screening (VOMS) assessment has been shown to be consistent and sensitive in identifying concussion when used as part of a comprehensive examination. To what extent these impairments or symptoms are associated with length of recovery is unknown. To examine whether symptom provocation or clinical abnormality in specific domains of the VOMS results in protracted recovery (time from SRC to commencement of RTP protocol). Cohort study (prognosis); Level of evidence, 2. A retrospective chart review was conducted of 167 patients (69 girls, 98 boys; mean ± SD age, 15 ± 2 years [range, 11-19 years]) presenting with SRC in 2014. During the initial visit, VOMS was performed in which symptom provocation or clinical abnormality (eg, unsmooth eye movements) was documented by use of a dichotomous scale (0 = not present, 1 = present). The VOMS used in this clinic consisted of smooth pursuits (SMO_PUR), horizontal and vertical saccades (HOR_SAC and VER_SAC), horizontal and vertical vestibular ocular reflex (HOR_VOR and VER_VOR), near point of convergence (NPC), and accommodation (ACCOM). Domains were also categorized into ocular motor (SMO_PUR, HOR_SAC, VER_SAC, NPC, ACCOM) and vestibular (HOR_VOR, VER_VOR). Cox proportional hazard models were used to explore the relationship between the domains and recovery. Alpha was set at P ≤ .05. Symptom provocation and/or clinical abnormality in all domains except NPC ( P = .107) and ACCOM ( P = .234) delayed recovery (domain, hazard ratio [95% CI]: SMO_PUR, 0.65 [0.47-0.90], P = .009; HOR_SAC, 0.68 [0.50-0.94], P = .018; VER_SAC, 0.55 [0.40-0.75], P < .001; HOR_VOR, 0.68 [0.49-0.94], P = .018; VER_VOR, 0.60 [0.44-0.83], P = .002). The lowest crude hazard ratio was for ocular motor category (0.45 [0.32-0.63], P < .001). These data suggest that symptom provocation/clinical abnormality associated with all domains except NPC and ACCOM can delay recovery after SRC in youth and adolescents. Thus, the VOMS not only may augment current diagnostic tools but also may serve as a predictor of recovery time in patients with SRC. The findings of this study may lead to more effective prognosis of concussion in youth and adolescents.

Abnormal prefrontal cortex resting state functional connectivity and severity of internet gaming disorder.

PubMed

Jin, Chenwang; Zhang, Ting; Cai, Chenxi; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Zhang, Ming; Yuan, Kai

2016-09-01

Internet Gaming Disorder (IGD) among adolescents has become an important public concern and gained more and more attention internationally. Recent studies focused on IGD and revealed brain abnormalities in the IGD group, especially the prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender-matched healthy controls were recruited in our study. Voxel-based morphometric (VBM) and functional connectivity analysis were employed to investigate the abnormal structural and resting-state properties of several frontal regions in individuals with online gaming addiction. Relative to healthy comparison subjects, IGD subjects showed significant decreased gray matter volume in PFC regions including the bilateral dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right supplementary motor area (SMA) after controlling for age and gender effects. We chose these regions as the seeding areas for the resting-state analysis and found that IGD subjects showed decreased functional connectivity between several cortical regions and our seeds, including the insula, and temporal and occipital cortices. Moreover, significant decreased functional connectivity between some important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and our seeds were found in the IGD group and some of those changes were associated with the severity of IGD. Our results revealed the involvement of several PFC regions and related PFC-striatal circuits in the process of IGD and suggested IGD may share similar neural mechanisms with substance dependence at the circuit level.