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Sample records for abnormal motor behavior

  1. GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish

    SciTech Connect

    Facciolo, Rosa Maria; Crudo, Michele; Giusi, Giuseppina; Canonaco, Marcello

    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 treatment 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.

  2. The α4β2 nicotinic acetylcholine receptor modulates autism-like behavioral and motor abnormalities in pentylenetetrazol-kindled mice.

    PubMed

    Takechi, Kenshi; Suemaru, Katsuya; Kiyoi, Takeshi; Tanaka, Akihiro; Araki, Hiroaki

    2016-03-15

    Epilepsy is associated with several psychiatric disorders, including cognitive impairment, autism and attention deficit/hyperactivity disorder (ADHD). However, the psychopathology of epilepsy is frequently unrecognized and untreated in patients. In the present study, we investigated the effects of ABT-418, a neuronal nicotinic acetylcholine receptor agonist, on pentylenetetrazol (PTZ)-kindled mice with behavioral and motor abnormalities. PTZ-kindled mice displayed impaired motor coordination (in the rotarod test), anxiety (in the elevated plus maze test) and social approach impairment (in the three-chamber social test) compared with control mice. ABT-418 treatment (0.05mg/kg, intraperitoneally) alleviated these behavioral abnormalities in PTZ-kindled mice. Immunolabeling of tissue sections demonstrated that expression of the α4 nicotinic acetylcholine receptor subunit in the medial habenula was similar in control and PTZ-kindled mice. However, expression was significantly decreased in the piriform cortex in PTZ-kindled mice. In addition, we examined the expression of the synaptic adhesion molecule neuroligin 3 (NLG3). NLG3 expression in the piriform cortex was significantly higher in PTZ-kindled mice compared with control mice. Collectively, our findings suggest that ADHD-like or autistic-like behavioral abnormalities associated with epilepsy are closely related to the downregulation of the α4 nicotinic receptor and the upregulation of NLG3 in the piriform cortex. In summary, this study indicates that ABT-418 might have therapeutic potential for attentional impairment in epileptic patients with psychiatric disorders such as autism and ADHD. PMID:26868186

  3. Ocular motor abnormalities in neurodegenerative disorders

    PubMed Central

    Antoniades, C A; Kennard, C

    2015-01-01

    Eye movements are a source of valuable information to both clinicians and scientists as abnormalities of them frequently act as clues to the localization of a disease process. Classically, they are divided into two main types: those that hold the gaze, keeping images steady on the retina (vestibulo-ocular and optokinetic reflexes) and those that shift gaze and redirect the line of sight to a new object of interest (saccades, vergence, and smooth pursuit). Here we will review some of the major ocular motor abnormalities present in neurodegenerative disorders. PMID:25412716

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

    ERIC Educational Resources Information Center

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

    2008-01-01

    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…

  5. Behavioral abnormalities in captive nonhuman primates.

    PubMed

    Mallapur, Avanti; Choudhury, B C

    2003-01-01

    In this study, we dealt with 11 species of nonhuman primates across 10 zoos in India. We recorded behavior as instantaneous scans between 9 a.m. and 5 p.m. In the study, we segregated behaviors for analyses into abnormal, undesirable, active, and resting. The 4 types of abnormal behavior exhibited included floating limb, self-biting, self-clasping, and stereotypic pacing. In the study, we recorded 2 types of undesirable behavior: autoerotic stimulation and begging. Langurs and group-housed macaques did not exhibit undesirable behaviors. A male lion-tailed macaque and a male gibbon exhibited begging behavior. autoerotic stimulation and self-biting occurred rarely. Males exhibited higher levels of undesirable behavior than did females. Animals confiscated from touring zoos, circuses, and animal traders exhibited higher levels of abnormal behaviors than did animals reared in larger, recognized zoos. The stump-tailed macaque was the only species to exhibit floating limb, autoerotic stimulation, self-biting, and self-clasping. Our results show that rearing experience and group composition influence the proportions of abnormal behavior exhibited by nonhuman primates in captivity. The history of early social and environmental deprivation in these species of captive nonhuman primates probably is critical in the development of behavioral pathologies. Establishing this will require further research. PMID:14965782

  6. Personality theory, abnormal psychology, and psychological measurement. A psychological behaviorism.

    PubMed

    Staats, A W

    1993-01-01

    Behaviorism, because it has not had a theory of personality, has been separated from the rest of psychology, unable in large part to draw from or contribute to it. Traditional psychology has not had a theory of personality that says what personality is, how it comes about, or how it functions. An antagonism has resulted that weakens rather than complements each tradition. Psychological behaviorism presents a new type of theory of personality. Derived from experimentation, it is constructed from basic theories of emotion, language, and sensory-motor behavior. It says personality is composed of learned basic behavioral repertoires (BBRs) that affect behavior. Personality measurement instruments are analyzed in terms of the BBRs, beginning the behaviorization of this field and calling for much additional research. These multilevel developments are then basic in psychological behaviorism's theory of abnormal behavior and of clinical treatment. The approach opens many new avenues of empirical and theoretical work. PMID:8439278

  7. Abnormal behaviors detection using particle motion model

    NASA Astrophysics Data System (ADS)

    Chen, Yutao; Zhang, Hong; Cheng, Feiyang; Yuan, Ding; You, Yuhu

    2015-03-01

    Human abnormal behaviors detection is one of the most challenging tasks in the video surveillance for the public security control. Interaction Energy Potential model is an effective and competitive method published recently to detect abnormal behaviors, but their model of abnormal behaviors is not accurate enough, so it has some limitations. In order to solve this problem, we propose a novel Particle Motion model. Firstly, we extract the foreground to improve the accuracy of interest points detection since the complex background usually degrade the effectiveness of interest points detection largely. Secondly, we detect the interest points using the graphics features. Here, the movement of each human target can be represented by the movements of detected interest points of the target. Then, we track these interest points in videos to record their positions and velocities. In this way, the velocity angles, position angles and distance between each two points can be calculated. Finally, we proposed a Particle Motion model to calculate the eigenvalue of each frame. An adaptive threshold method is proposed to detect abnormal behaviors. Experimental results on the BEHAVE dataset and online videos show that our method could detect fight and robbery events effectively and has a promising performance.

  8. Role of movement in long-term basal ganglia changes: implications for abnormal motor responses

    PubMed Central

    Simola, Nicola; Morelli, Micaela; Frazzitta, Giuseppe; Frau, Lucia

    2013-01-01

    Abnormal involuntary movements (AIMs) and dyskinesias elicited by drugs that stimulate dopamine receptors in the basal ganglia are a major issue in the management of Parkinson’s disease (PD). Preclinical studies in dopamine-denervated animals have contributed to the modeling of these abnormal movements, but the precise neurochemical and functional mechanisms underlying these untoward effects are still elusive. It has recently been suggested that the performance of movement may itself promote the later emergence of drug-induced motor complications, by favoring the generation of aberrant motor memories in the dopamine-denervated basal ganglia. Our recent results from hemiparkinsonian rats subjected to the priming model of dopaminergic stimulation are in agreement with this. These results demonstrate that early performance of movement is crucial for the manifestation of sensitized rotational behavior, indicative of an abnormal motor response, and neurochemical modifications in selected striatal neurons following a dopaminergic challenge. Building on this evidence, this paper discusses the possible role of movement performance in drug-induced motor complications, with a look at the implications for PD management. PMID:24167489

  9. Abnormal Behavior in Relation to Cage Size in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Paulk, H. H.; And Others

    1977-01-01

    Examines the effects of cage size on stereotyped and normal locomotion and on other abnormal behaviors in singly caged animals, whether observed abnormal behaviors tend to co-occur, and if the development of an abnormal behavior repertoire leads to reduction in the number of normal behavior categories. (Author/RK)

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

    PubMed Central

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

    2015-01-01

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

  11. Abnormal dorsal premotor-motor inhibition in writer's cramp.

    PubMed

    Pirio Richardson, Sarah; Beck, Sandra; Bliem, Barbara; Hallett, Mark

    2014-05-01

    The authors hypothesized that a deficient premotor-motor inhibitory network contributes to the unwanted involuntary movements in dystonia. The authors studied nine controls and nine patients with writer's cramp (WC). Dorsal premotor-motor cortical inhibition (dPMI) was tested by applying conditioning transcranial magnetic stimulation (TMS) to the dorsal premotor cortex and then a test pulse to the ipsilateral motor cortex at an interval of 6 ms. The authors used an H-reflex in flexor carpi radialis paired with TMS over the premotor cortex to assess for spinal cord excitability change. Finally, the authors interrupted a choice reaction time task with TMS over dorsal premotor cortex to assess performance in a nondystonic task. The results showed that WC patients exhibited dPMI at rest (88.5%, the ratio of conditioned to unconditioned test pulse), in contrast to controls, who did not show dPMI (109.6%) (P = 0.0198). This difference between patients and controls persisted during contraction (100% vs. 112%) and pen-holding (95.6% vs. 111%). The H-reflex in the arm was not modulated by the premotor cortex stimulation. The WC patients made more errors, and the error rate improved with TMS over the premotor cortex. These results suggest that abnormal premotor-motor interactions may play a role in the pathophysiology of focal dystonia. The dPMI was not modulated by task in either group, but was constantly greater in the patients. The significance of the increased inhibition is likely to be compensatory. It appears to be a robust finding and, in combination with other features, could be further explored as a biomarker. PMID:24710852

  12. 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. PMID:24323406

  13. Abnormal behavior in caged birds kept as pets.

    PubMed

    van Hoek, C S; ten Cate, C

    1998-01-01

    There are a limited number of studies dealing with abnormal behavior in caged birds kept as pets. However, these studies demonstrate the presence of abnormal behavior in both songbirds and parrots. Ethological studies on these birds, as well as studies on domestic and zoo birds, indicate that inappropriate rearing and housing conditions may lead to behavioral abnormalities. Together these data indicate that behavioral abnormalities occur among both wild-caught and domesticated pet birds. The severity and magnitude of these abnormalities is probably underestimated, and there is a need for systematic studies on the nature, origin, variability, species-specificity, and reversibility of behavioral problems in pet birds. Abnormal behavior in caged birds may to some extent be prevented and reduced by environmental enrichment. However, most enrichment studies are anecdotal and not based on a thorough analysis of the behavioral abnormalities, which may lead to measures resulting in a reduction of symptoms rather than the underlying causes. Although it is likely that several of these problems could be reduced by modifying rearing and housing conditions, the current insights into the causal mechanisms underlying abnormal behavior of domesticated and wild-caught pet birds are limited, as are the insights into the possibilities of preventing or curing abnormal behavior. PMID:16363987

  14. Social Interaction and Repetitive Motor Behaviors

    ERIC Educational Resources Information Center

    Loftin, Rachel L.; Odom, Samuel L.; Lantz, Johanna F.

    2008-01-01

    Students with autism have difficulty initiating social interactions and may exhibit repetitive motor behavior (e.g., body rocking, hand flapping). Increasing social interaction by teaching new skills may lead to reductions in problem behavior, such as motor stereotypies. Additionally, self-monitoring strategies can increase the maintenance of…

  15. Neurobiology of social behavior abnormalities in autism and Williams syndrome.

    PubMed

    Barak, Boaz; Feng, Guoping

    2016-04-26

    Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities. PMID:27116389

  16. Neonatal White Matter Abnormality Predicts Childhood Motor Impairment in Very Preterm Children

    ERIC Educational Resources Information Center

    Spittle, Alicia J.; Cheong, Jeanie; Doyle, Lex W.; Roberts, Gehan; Lee, Katherine J.; Lim, Jeremy; Hunt, Rod W.; Inder, Terrie E.; Anderson, Peter J.

    2011-01-01

    Aim: Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor…

  17. Freud Was Right. . . about the Origins of Abnormal Behavior

    ERIC Educational Resources Information Center

    Muris, Peter

    2006-01-01

    Freud's psychodynamic theory is predominantly based on case histories of patients who displayed abnormal behavior. From a scientific point of view, Freud's analyses of these cases are unacceptable because the key concepts of his theory cannot be tested empirically. However, in one respect, Freud was totally right: most forms of abnormal behavior…

  18. Vinpocetine attenuates MPTP-induced motor deficit and biochemical abnormalities in Wistar rats.

    PubMed

    Sharma, S; Deshmukh, R

    2015-02-12

    Up-regulation in phosphodiesterase 1 (PDE1) expression and decreased levels of cyclic nucleotides (cAMP and cGMP) have been reported in patients and experimental animal models of Parkinson's disease (PD). Phosphodiesterase (PDE) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study is designed to investigate the effect of vinpocetine, a PDE1 inhibitor in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental PD-like symptoms in rats. To produce stable motor deficit, MPTP was repeatedly administered intranigrally (bilaterally) at an interval of 1 week (days 1, 7 and 14). Following development of stable motor deficit, which was observed after the third infusion of MPTP (day 14) in rats, the animals were treated with vinpocetine (5-, 10- and 20-mg/kg, i.p.) from days 15 to 28. Movement abnormalities were assessed by a battery of behavioral tests. Moreover, levels of malondialdehyde, nitrite and reduced glutathione were measured in striatal brain homogenate to confirm the role of oxidative and nitrosative stress in PD. Repeated intranigral administration of MPTP produced stable motor deficits, reduced the cyclic nucleotides and dopamine levels and caused elevation in oxidative-nitrosative stress markers. Chronic administration of vinpocetine (for 14 days) significantly and dose dependently attenuated movement disabilities and oxidative-nitrosative stress in MPTP-treated rats. Moreover, vinpocetine treatment enhances cyclic nucleotide levels and restores the dopamine level in MPTP-treated rats. The observed results of the present study are indicative of the therapeutic potential of vinpocetine in PD. PMID:25514048

  19. Risk factors for behavioral abnormalities in mild cognitive impairment and mild Alzheimer's disease

    PubMed Central

    Apostolova, Liana G.; Di, Li Jie; Duffy, Erin L.; Brook, Jenny; Elashoff, David; Tseng, Chi-Hong; Fairbanks, Lynn; Cummings, Jeffrey L.

    2014-01-01

    Background Behavioral symptoms are common in both MCI and AD. Methods We analyzed the Neuropsychiatric Inventory Questionnaire data of 3456 MCI and 2641 mild AD NACC participants. Using factor analysis and logistic regression we estimated the effects of age, sex, race, education, MMSE, functional impairment, marital status and family history on presence of behavioral symptoms. We also compared the observed prevalence of behavioral symptoms between amnestic and nonamnestic MCI. Results Four factors were identified: affective behaviors (depression, apathy and anxiety); distress/tension behaviors (irritability and agitation); impulse control behaviors (disinhibition, elation and aberrant motor behavior), and psychotic behaviors (delusions and hallucinations). Male gender was significantly associated with all factors. Younger age was associated with higher prevalence of distress/tension, impulse control and psychotic behaviors. Being married was protective against psychotic behaviors. Lower education was associated with the presence of distress/tension behaviors. Caucasians showed higher prevalence of affective behaviors. Functional impairment was strongly associated with all behavioral abnormalities. Amnestic MCI had more elation and agitation relative to nonamnestic MCI. Conclusions Younger age, male gender and greater functional impairment were associated with higher overall presence of behavioral abnormalities in MCI and mild AD. Marital status, lower education and race had effect on selected behaviors. PMID:24481207

  20. Motor Abnormalities in Premanifest Persons with Huntington’s Disease: The PREDICT-HD Study

    PubMed Central

    Biglan, Kevin M.; Ross, Christopher A.; Langbehn, Douglas R.; Aylward, Elizabeth H.; Stout, Julie C.; Queller, Sarah; Carlozzi, Noelle E.; Duff, Kevin; Beglinger, Leigh J.; Paulsen, Jane S.

    2011-01-01

    Background The PREDICT-HD study seeks to identify clinical and biological markers of Huntington’s disease in premanifest individuals who have undergone predictive genetic testing. Methods We compared baseline motor data between gene-expansion carriers (cases) and non gene-expansion carriers (controls) using T-tests and Chi-Square. Cases were categorized as near, mid or far from diagnosis using a CAG-based formula. Striatal volumes were calculated using volumetric MRI measurements. Multiple linear regression associated total motor score, motor domains and individual motor items with estimated diagnosis and striatal volumes. Results Elevated total motor scores at baseline were associated with higher genetic probability of disease diagnosis in the near future (partial R2 0.14, p<0.0001) and smaller striatal volumes (partial R2 0.15, p<0.0001). Nearly all motor domain scores showed greater abnormality with increasing proximity to diagnosis, although bradykinesia and chorea were most highly associated with diagnostic immediacy. Among individual motor items, worse scores on finger tapping, tandem gait, Luria, saccade initiation, and chorea show unique association with diagnosis probability. Conclusions Even in this premanifest population subtle motor abnormalities were associated with a higher probability of disease diagnosis and smaller striatal volumes. Longitudinal assessment will help inform whether motor items will be useful measures in preventive clinical trials. PMID:19562761

  1. Motor abnormalities in premanifest persons with Huntington's disease: the PREDICT-HD study.

    PubMed

    Biglan, Kevin M; Ross, Christopher A; Langbehn, Douglas R; Aylward, Elizabeth H; Stout, Julie C; Queller, Sarah; Carlozzi, Noelle E; Duff, Kevin; Beglinger, Leigh J; Paulsen, Jane S

    2009-09-15

    The PREDICT-HD study seeks to identify clinical and biological markers of Huntington's disease in premanifest individuals who have undergone predictive genetic testing. We compared baseline motor data between gene-expansion carriers (cases) and nongene-expansion carriers (controls) using t-tests and Chi-square. Cases were categorized as near, mid, or far from diagnosis using a CAG-based formula. Striatal volumes were calculated using volumetric magnetic resonance imaging measurements. Multiple linear regression associated total motor score, motor domains, and individual motor items with estimated diagnosis and striatal volumes. Elevated total motor scores at baseline were associated with higher genetic probability of disease diagnosis in the near future (partial R(2) 0.14, P < 0.0001) and smaller striatal volumes (partial R(2) 0.15, P < 0.0001). Nearly all motor domain scores showed greater abnormality with increasing proximity to diagnosis, although bradykinesia and chorea were most highly associated with diagnostic immediacy. Among individual motor items, worse scores on finger tapping, tandem gait, Luria, saccade initiation, and chorea show unique association with diagnosis probability. Even in this premanifest population, subtle motor abnormalities were associated with a higher probability of disease diagnosis and smaller striatal volumes. Longitudinal assessment will help inform whether motor items will be useful measures in preventive clinical trials. PMID:19562761

  2. Reversible motor and sensory neurophysiological abnormalities in cauda equina claudication.

    PubMed Central

    Saadeh, I K; Illis, L S; Jamshidi Fard, A R; Hughes, P J; Sedgwick, E M

    1994-01-01

    A case of cauda equina claudication with canal stenosis is presented. Neurophysiological studies show reversible changes during symptomatic and asymptomatic phases. The somatosensory evoked potential from the tibial nerve was reduced in amplitude. Central motor conduction time (CMCT) after transcranial magnetic stimulation of the brain was reversibly prolonged in the symptomatic phase. Reversible CMCT changes have not been previously shown. The findings are discussed in the light of the pathophysiology of ischaemic nerve. Images PMID:7931390

  3. Sensory abnormalities and pain in Parkinson disease and its modulation by treatment of motor symptoms.

    PubMed

    Cury, R G; Galhardoni, R; Fonoff, E T; Perez Lloret, S; Dos Santos Ghilardi, M G; Barbosa, E R; Teixeira, M J; Ciampi de Andrade, D

    2016-02-01

    Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain in PD and to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain in PD and the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms. PD patients have altered sensory and pain thresholds in the off-medication state. Both levodopa and DBS improve motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non-motor symptoms do not necessarily share the same mechanisms. Whether dopamine and DBS have a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism-based approach to pain in PD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related to PD before specific treatment can be instituted. PMID:26147660

  4. 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

  5. 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

  6. The Role of the Pediatric Cerebellum in Motor Functions, Cognition, and Behavior: A Clinical Perspective.

    PubMed

    Salman, Michael S; Tsai, Peter

    2016-08-01

    This article discusses the contribution of the pediatric cerebellum to locomotion, ocular motor control, speech articulation, cognitive function, and behavior modulation. Hypotheses on cerebellar function are discussed. Clinical features in patients with cerebellar disorders are outlined. Cerebellar abnormalities in cognitive and behavioral disorders are detailed. PMID:27423796

  7. Sb (111) Abnormal Behavior under Ion Etching

    NASA Astrophysics Data System (ADS)

    Smirnov, A. A.; Bozhko, S. I.; Ionov, A. M.; Protasova, S. G.; Chekmazov, S. V.; Kapustin, A. A.

    Due to a strong spin-orbit interaction (SOI), the surface states of Sb (111) are similar to those for topological insulators (TI) Sugawara et al. (2006). The surface states are protected by time-reversal symmetry and energy dispersion is a linear function of momentum. Defects in crystal structure lead to a local break of the surface translational symmetry and can modify surface states. It is the primary reason to study defects of Sb crystal structure and their effect on the surface states dispersion. Etching of the Sb (111) surface using Ar+ ions is a common way to create defects both in a bulk and on the surface of the crystal. Sb (111) ion etching at room temperature reveals anomalous behavior of surface crystal structure. It results in formation of flat terraces of 2 nm in size. Investigation of electronic structure of the etched Sb (111) surface has demonstrated increase of density of states (DOS) at the Fermi level. The results are discussed in terms of local break of conditions of Peierls transition.

  8. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.

    PubMed

    Hsiao, Elaine Y; McBride, Sara W; Hsien, Sophia; Sharon, Gil; Hyde, Embriette R; McCue, Tyler; Codelli, Julian A; Chow, Janet; Reisman, Sarah E; Petrosino, Joseph F; Patterson, Paul H; Mazmanian, Sarkis K

    2013-12-19

    Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders. PMID:24315484

  9. Dynamic Primitives of Motor Behavior

    PubMed Central

    Hogan, Neville; Sternad, Dagmar

    2013-01-01

    We present in outline a theory of sensorimotor control based on dynamic primitives, which we define as attractors. To account for the broad class of human interactive behaviors—especially tool use—we propose three distinct primitives: submovements, oscillations and mechanical impedances, the latter necessary for interaction with objects. Due to fundamental features of the neuromuscular system, most notably its slow response, we argue that encoding in terms of parameterized primitives may be an essential simplification required for learning, performance, and retention of complex skills. Primitives may simultaneously and sequentially be combined to produce observable forces and motions. This may be achieved by defining a virtual trajectory composed of submovements and/or oscillations interacting with impedances. Identifying primitives requires care: in principle, overlapping submovements would be sufficient to compose all observed movements but biological evidence shows that oscillations are a distinct primitive. Conversely, we suggest that kinematic synergies, frequently discussed as primitives of complex actions, may be an emergent consequence of neuromuscular impedance. To illustrate how these dynamic primitives may account for complex actions, we briefly review three types of interactive behaviors: constrained motion, impact tasks, and manipulation of dynamic objects. PMID:23124919

  10. Possible Electromagnetic Effects on Abnormal Animal Behavior Before an Earthquake

    PubMed Central

    Hayakawa, Masashi

    2013-01-01

    Simple Summary Possible electromagnetic effects on abnormal animal behavior before earthquakes. Abstract The former statistical properties summarized by Rikitake (1998) on unusual animal behavior before an earthquake (EQ) have first been presented by using two parameters (epicentral distance (D) of an anomaly and its precursor (or lead) time (T)). Three plots are utilized to characterize the unusual animal behavior; (i) EQ magnitude (M) versus D, (ii) log T versus M, and (iii) occurrence histogram of log T. These plots are compared with the corresponding plots for different seismo-electromagnetic effects (radio emissions in different frequency ranges, seismo-atmospheric and -ionospheric perturbations) extensively obtained during the last 15–20 years. From the results of comparisons in terms of three plots, it is likely that lower frequency (ULF (ultra-low-frequency, f ≤ 1 Hz) and ELF (extremely-low-frequency, f ≤ a few hundreds Hz)) electromagnetic emissions exhibit a very similar temporal evolution with that of abnormal animal behavior. It is also suggested that a quantity of field intensity multiplied by the persistent time (or duration) of noise would play the primary role in abnormal animal behavior before an EQ. PMID:26487307

  11. 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

  12. Motor Behavior Activates Bergmann Glial Networks

    PubMed Central

    Nimmerjahn, Axel; Mukamel, Eran A.; Schnitzer, Mark J.

    2010-01-01

    SUMMARY Although it is firmly established neuronal activity is a prime determinant of animal behavior, relationships between astrocytic excitation and animal behavior have remained opaque. Cerebellar Bergmann glia are radial astrocytes that are implicated in motor behavior and exhibit Ca2+-excitation. However, Ca2+-excitation in these cells has not previously been studied in behaving animals. Using two-photon microscopy we found that Bergmann glia exhibit three forms of Ca2+-excitation in awake behaving mice. Two of these are ongoing within the cerebellar vermis. During locomotor performance concerted Ca2+-excitation arises in networks of at least hundreds of Bergmann glia extending across several hundred microns or more. Concerted Ca2+-excitation was abolished by anesthesia or blockade of either neural activity or glutamatergic transmission. Thus, large networks of Bergmann glia can be activated by specific animal behaviors and undergo excitation of sufficient magnitude to potentially initiate macroscopic changes in brain dynamics or blood flow. PMID:19447095

  13. Computed tomographic findings in children with spastic diplegia: correlation with the severity of their motor abnormality.

    PubMed

    Yokochi, K; Horie, M; Inukai, K; Kito, H; Shimabukuro, S; Kodama, K

    1989-01-01

    Computed tomographic findings of 46 children with spastic diplegia examined at nine months to three years of age corrected for preterm births were analyzed. Both the size of the lateral ventricles measured by the width of the anterior horns, and the volume of the extracerebral low-density areas were enlarged in some patients. Both enlargements did not, however, correlate to the severity of the motor abnormality in the patients. The low-density areas of the periventricular white matter, especially adjacent to the trigone, were reduced in many children, probably due to the atrophy of the cerebral white matter having periventricular leukomalacia. The anterior expansion of the white matter reduction from the trigone corresponded to the severe motor abnormality in the children with spastic diplegia. PMID:2774092

  14. Behavioral Symptoms in Motor Neuron Disease and Their Negative Impact on Caregiver Burden

    PubMed Central

    Cui, Bo; Cui, Li-Ying; Liu, Ming-Sheng; Li, Xiao-Guang; Ma, Jun-Fang; Fang, Jia; Ding, Qing-Yun

    2015-01-01

    Background: The spectrum of abnormal behaviors in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) has been described, but its practical meaning, namely its impact on caregiver burden, has not been clearly documented in Chinese population. This study aimed to assess the distribution of abnormal behaviors in Chinese population, and to analyze the relationship between behavior changes and caregiver burden. Methods: Sixty-five patients with ALS/MND have been consecutively enrolled into registry platform of Peking Union Medical College Hospital. An investigation was performed to these patients and their caregivers using the revised ALS function rating scale, Frontal Behavioral Inventory-ALS version, the Frontal Assessment Battery, and the Caregiver Burden Inventory. Results: Twenty-eight (43.1%) patients displayed abnormal behaviors of varying degrees, with one fulfilling the diagnostic criteria of frontotemporal lobe degeneration. Irritability, logopenia, and inflexibility ranked top 3 of abnormal behavior list. Correlation analysis revealed that the degree of behavioral change and frontal cognitive status were significantly associated with caregiver burden, with more extensive impact from disinhibitive behaviors. Analysis of covariance analysis showed that after associated factors were corrected, caregivers of patients with moderate to severe behavior change reported significantly heavier developmental burden, physical burden, and total burden than those with no behavioral change. Conclusions: Neurobehavioral symptoms could present in around 40% of Chinese patients with ALS/MND, and the distribution of these behaviors was also unique. Besides, abnormal behaviors were highly related to caregivers’ burden. PMID:26315075

  15. Spent fuel behavior under abnormal thermal transients during dry storage

    SciTech Connect

    Stahl, D.; Landow, M.P.; Burian, R.J.; Pasupathi, V.

    1986-01-01

    This study was performed to determine the effects of abnormally high temperatures on spent fuel behavior. Prior to testing, calculations using the CIRFI3 code were used to determine the steady-state fuel and cask component temperatures. The TRUMP code was used to determine transient heating rates under postulated abnormal events during which convection cooling of the cask surfaces was obstructed by a debris bed covering the cask. The peak rate of temperature rise during the first 6 h was calculated to be about 15/sup 0/C/h, followed by a rate of about 1/sup 0/C/h. A Turkey Point spent fuel rod segment was heated to approx. 800/sup 0/C. The segment deformed uniformly with an average strain of 17% at failure and a local strain of 60%. Pretest characterization of the spent fuel consisted of visual examination, profilometry, eddy-current examination, gamma scanning, fission gas collection, void volume measurement, fission gas analysis, hydrogen analysis of the cladding, burnup analysis, cladding metallography, and fuel ceramography. Post-test characterization showed that the failure was a pinhole cladding breach. The results of the tests showed that spent fuel temperatures in excess of 700/sup 0/C are required to produce a cladding breach in fuel rods pressurized to 500 psing (3.45 MPa) under postulated abnormal thermal transient cask conditions. The pinhole cladding breach that developed would be too small to compromise the confinement of spent fuel particles during an abnormal event or after normal cooling conditions are restored. This behavior is similar to that found in other slow ramp tests with irradiated and nonirradiated rod sections and nonirradiated whole rods under conditions that bracketed postulated abnormal heating rates. This similarity is attributed to annealing of the irradiation-strengthened Zircaloy cladding during heating. In both cases, the failure was a benign, ductile pinhole rupture.

  16. A Behavior Analytic Approach to Exploratory Motor Behavior: How Can Caregivers Teach EM Behavior to Infants with Down Syndrome?

    ERIC Educational Resources Information Center

    Bauer, Sara M.; Jones, Emily A.

    2014-01-01

    Impairment in exploratory motor (EM) behavior is part of the Down syndrome behavioral phenotype. Exploratory motor behavior may be a pivotal skill for early intervention with infants with Down syndrome. Exploratory motor impairments are often attributed to general delays in motor development in infants with Down syndrome. A behavior analytic…

  17. Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia.

    PubMed

    Ruiz, Marta; Perez-Garcia, Georgina; Ortiz-Virumbrales, Maitane; Méneret, Aurelie; Morant, Andrika; Kottwitz, Jessica; Fuchs, Tania; Bonet, Justine; Gonzalez-Alegre, Pedro; Hof, Patrick R; Ozelius, Laurie J; Ehrlich, Michelle E

    2015-12-20

    DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain-containing apoptosis-associated protein] and is autosomal dominant and partially penetrant. Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown. Thap1 is a zinc-finger transcription factor, and most pathogenic THAP1 mutations are missense and are located in the DNA-binding domain. There are also nonsense mutations, which act as the equivalent of a null allele because they result in the generation of small mRNA species that are likely rapidly degraded via nonsense-mediated decay. The function of Thap1 in neurons is unknown, but there is a unique, neuronal 50-kDa Thap1 species, and Thap1 levels are auto-regulated on the mRNA level. Herein, we present the first characterization of two mouse models of DYT6, including a pathogenic knockin mutation, C54Y and a null mutation. Alterations in motor behaviors, transcription and brain structure are demonstrated. The projection neurons of the deep cerebellar nuclei are especially altered. Abnormalities vary according to genotype, sex, age and/or brain region, but importantly, overlap with those of other dystonia mouse models. These data highlight the similarities and differences in age- and cell-specific effects of a Thap1 mutation, indicating that the pathophysiology of THAP1 mutations should be assayed at multiple ages and neuronal types and support the notion of final common pathways in the pathophysiology of dystonia arising from disparate mutations. PMID:26376866

  18. Quantitative Gait Analysis Using a Motorized Treadmill System Sensitively Detects Motor Abnormalities in Mice Expressing ATPase Defective Spastin

    PubMed Central

    Connell, James W.; Allison, Rachel; Reid, Evan

    2016-01-01

    The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP. PMID:27019090

  19. Possible Electromagnetic Effects on Abnormal Animal Behavior Before an Earthquake.

    PubMed

    Hayakawa, Masashi

    2013-01-01

    The former statistical properties summarized by Rikitake (1998) on unusual animal behavior before an earthquake (EQ) have first been presented by using two parameters (epicentral distance (D) of an anomaly and its precursor (or lead) time (T)). Three plots are utilized to characterize the unusual animal behavior; (i) EQ magnitude (M) versus D, (ii) log T versus M, and (iii) occurrence histogram of log T. These plots are compared with the corresponding plots for different seismo-electromagnetic effects (radio emissions in different frequency ranges, seismo-atmospheric and -ionospheric perturbations) extensively obtained during the last 15-20 years. From the results of comparisons in terms of three plots, it is likely that lower frequency (ULF (ultra-low-frequency, f ≤ 1 Hz) and ELF (extremely-low-frequency, f ≤ a few hundreds Hz)) electromagnetic emissions exhibit a very similar temporal evolution with that of abnormal animal behavior. It is also suggested that a quantity of field intensity multiplied by the persistent time (or duration) of noise would play the primary role in abnormal animal behavior before an EQ. PMID:26487307

  20. REM sleep behavior disorder: motor manifestations and pathophysiology.

    PubMed

    Arnulf, Isabelle

    2012-05-01

    Patients with REM sleep behavior disorder (RBD) enact violent dreams during REM sleep in the absence of normal muscle atonia. This disorder is highly frequent in patients with synucleinopathies (60%-100% of patients) and rare in patients with other neurodegenerative disorders. The disorder is detected by interview plus video and sleep monitoring. Abnormal movements expose the patients and bed partners to a high risk of injury and sleep disruption. The disorder is usually alleviated with melatonin and clonazepam. Limb movements are mainly minor, jerky, fast, pseudohallucinatory, and repeated, with a limp wrist during apparently grasping movements, although body jerks and complex violent (fights) and nonviolent culturally acquired behaviors are also observed. Notably, parkinsonism disappears during RBD-associated complex behaviors in patients with Parkinson's disease and with multiple system atrophy, suggesting that the upper motor stream bypasses the basal ganglia during REM sleep. Longitudinal studies show that idiopathic RBD predisposes patients to later develop Parkinson's disease, dementia with Lewy bodies, and, more rarely, multiple system atrophy, with a rate of conversion of 46% within 5 years. During this time window, patients concomitantly develop nonmotor signs (decreased olfaction and color vision, orthostatic hypotension, altered visuospatial abilities, increased harm avoidance) and have abnormal test results (decreased putamen dopamine uptake, slower EEG). Patients with idiopathic RBD have higher and faster risk for conversion to Parkinson's disease and dementia with Lewy bodies if abnormalities in dopamine transporter imaging, transcranial sonography, olfaction, and color vision are found at baseline. They constitute a highly specific target for testing neuroprotective agents. PMID:22447623

  1. 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. PMID:27166294

  2. Role of nitric oxide on motor behavior.

    PubMed

    Del Bel, E A; Guimarães, F S; Bermúdez-Echeverry, M; Gomes, M Z; Schiaveto-de-souza, A; Padovan-Neto, F E; Tumas, V; Barion-Cavalcanti, A P; Lazzarini, M; Nucci-da-Silva, L P; de Paula-Souza, D

    2005-03-01

    The present review paper describes results indicating the influence of nitric oxide (NO) on motor control. Our last studies showed that systemic injections of low doses of inhibitors of NO synthase (NOS), the enzyme responsible for NO formation, induce anxiolytic effects in the elevated plus maze whereas higher doses decrease maze exploration. Also, NOS inhibitors decrease locomotion and rearing in an open field arena. These results may involve motor effects of this compounds, since inhibitors of NOS, NG-nitro-L-arginine (L-NOARG), N(G)-nitro-L-arginine methylester (L-NAME), N(G)-monomethyl-L-arginine (L-NMMA), and 7-Nitroindazole (7-NIO), induced catalepsy in mice. This effect was also found in rats after systemic, intracebroventricular or intrastriatal administration. Acute administration of L-NOARG has an additive cataleptic effect with haloperidol, a dopamine D2 antagonist. The catalepsy is also potentiated by WAY 100135 (5-HT1a receptor antagonist), ketanserin (5HT2a and alfal adrenergic receptor antagonist), and ritanserin (5-HT2a and 5HT2c receptor antagonist). Atropine sulfate and biperiden, antimuscarinic drugs, block L-NOARG-induced catalepsy in mice. L-NOARG subchronic administration in mice induces rapid tolerance (3 days) to its cataleptic effects. It also produces cross-tolerance to haloperidol-induced catalepsy. After subchronic L-NOARG treatment there is an increase in the density NADPH-d positive neurons in the dorsal part of nucleus caudate-putamen, nucleus accumbens, and tegmental pedunculupontinus nucleus. In contrast, this treatment decreases NADPH-d neuronal number in the substantia nigra compacta. Considering these results we suggest that (i) NO may modulate motor behavior, probably by interfering with dopaminergic, serotonergic, and cholinergic neurotransmission in the striatum; (ii) Subchronic NO synthesis inhibition induces plastic changes in NO-producing neurons in brain areas related to motor control and causes cross-tolerance to the

  3. Decomposition of abnormal free locomotor behavior in a rat model of Parkinson's disease

    PubMed Central

    Grieb, Benjamin; von Nicolai, Constantin; Engler, Gerhard; Sharott, Andrew; Papageorgiou, Ismini; Hamel, Wolfgang; Engel, Andreas K.; Moll, Christian K.

    2013-01-01

    Poverty of spontaneous movement, slowed execution and reduced amplitudes of movement (akinesia, brady- and hypokinesia) are cardinal motor manifestations of Parkinson's disease that can be modeled in experimental animals by brain lesions affecting midbrain dopaminergic neurons. Most behavioral investigations in experimental parkinsonism have employed short-term observation windows to assess motor impairments. We postulated that an analysis of longer-term free exploratory behavior could provide further insights into the complex fine structure of altered locomotor activity in parkinsonian animals. To this end, we video-monitored 23 h of free locomotor behavior and extracted several behavioral measures before and after the expression of a severe parkinsonian phenotype following bilateral 6-hydroxydopamine (6-OHDA) lesions of the rat dopaminergic substantia nigra. Unbiased stereological cell counting verified the degree of midbrain tyrosine hydroxylase positive cell loss in the substantia nigra and ventral tegmental area. In line with previous reports, overall covered distance and maximal motion speed of lesioned animals were found to be significantly reduced compared to controls. Before lesion surgery, exploratory rat behavior exhibited a bimodal distribution of maximal speed values obtained for single movement episodes, corresponding to a “first” and “second gear” of motion. 6-OHDA injections significantly reduced the incidence of second gear motion episodes and also resulted in an abnormal prolongation of these fast motion events. Likewise, the spatial spread of such episodes was increased in 6-OHDA rats. The increase in curvature of motion tracks was increased in both lesioned and control animals. We conclude that the discrimination of distinct modes of motion by statistical decomposition of longer-term spontaneous locomotion provides useful insights into the fine structure of fluctuating motor functions in a rat analog of Parkinson's disease. PMID:24348346

  4. Abnormal magnetization behaviors in Sm-Ni-Fe-Cu alloys

    NASA Astrophysics Data System (ADS)

    Yang, W. Y.; Zhang, Y. F.; Zhao, H.; Chen, G. F.; Zhang, Y.; Du, H. L.; Liu, S. Q.; Wang, C. S.; Han, J. Z.; Yang, Y. C.; Yang, J. B.

    2016-06-01

    The magnetization behaviors in Sm-Ni-Fe-Cu alloys at low temperatures have been investigated. It was found that the hysteresis loops show wasp-waisted character at low temperatures, which has been proved to be related to the existence of multi-phases, the Fe/Ni soft magnetic phases and the CaCu5-type hard magnetic phase. A smooth-jump behavior of the magnetization is observed at T>5 K, whereas a step-like magnetization process appears at T<5 K. The CaCu5-type phase is responsible for such abnormal magnetization behavior. The magnetic moment reversal model with thermal activation is used to explain the relation of the critical magnetic field (Hcm) to the temperature (T>5 K). The reversal of the moment direction has to cross over an energy barrier of about 6.6×10-15 erg. The step-like jumps of the magnetization below 5 K is proposed to be resulted from a sharp increase of the sample temperature under the heat released by the irreversible domain wall motion.

  5. 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

  6. Abnormal Dorsal Premotor-Motor Inhibition in Writer’s Cramp

    PubMed Central

    Richardson, Sarah Pirio; Beck, Sandra; Bliem, Barbara; Hallett, Mark

    2014-01-01

    Background We hypothesize that a deficient premotor-motor inhibitory network contributes to the unwanted involuntary movements in dystonia. Methods We studied nine controls and nine patients with writer’s cramp (WC). Dorsal premotor-motor cortical inhibition (dPMI) was tested by applying conditioning transcranial magnetic stimulation (TMS) to the dorsal premotor cortex and then a test pulse to the ipsilateral motor cortex at an interval of 6ms. We used an H-reflex in flexor carpi radialis paired with TMS over the premotor cortex to assess for spinal cord excitability change. Finally, we interrupted a choice reaction time task with TMS over dorsal premotor cortex to assess performance in a non-dystonic task. Results Our results showed that WC patients exhibited dPMI at rest (88.5%, the ratio of conditioned to unconditioned test pulse) in contrast to our controls who did not show dPMI (109.6%) (p=0.0198). This difference between patients and controls persisted during contraction (100% vs. 112%) and pen-holding (95.6% vs. 111%). The H-reflex in the arm was not modulated by the premotor cortex stimulation. WC patients made more errors and the error rate improved with TMS over the premotor cortex. Conclusions These results suggest that abnormal premotor-motor interactions may play a role in the pathophysiology of focal dystonia. dPMI was not modulated by task in either group, but was constantly greater in the patients. The significance of the increased inhibition is likely to be compensatory. It appears to be a robust finding and, in combination with other features, could be further explored as a biomarker. PMID:24710852

  7. [Histochemical findings of and fine structural changes in motor endplates in diseases with neuromuscular transmission abnormalities].

    PubMed

    Yoshimura, Toshiro; Motomura, Masakatsu; Tsujihata, Mitsuhiro

    2011-07-01

    We herein review the histochemical findings and fine structural changes of motor endplates associated with diseases causing neuromuscular transmission abnormalities. In anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG), type 2 fiber atrophy is observed, and the motor endplates show a reduction in the nerve terminal area, simplification of the postsynaptic membrane, decreased number of acetylcholine receptors, and deposition of immune complexes. In anti-MuSK antibody-positive MG, the fine structure shows a decrease in the postsynaptic membrane length, but the secondary synaptic cleft is preserved. There is no decrease in the number of AChRs, and there are no deposits of immune complexes at the motor endplates. Patients with Lambert-Eaton myasthenic syndrome show type 2 fiber atrophy, their motor endplates show a decrease in both the mean postsynaptic area and postsynaptic membrane length in the brachial biceps muscle. Congenital myasthenic syndrome with episodic apnea is characterized only by small-sized synaptic vesicles; the postsynaptic area is preserved. In subjects with congenital myasthenic syndrome with acetylcholinesterase deficiency, quantitative electron microscopy reveals a significant decrease in the nerve terminal size and presynaptic membrane length; further, the Schwann cell processes extend into the primary synaptic cleft, and partially or completely occlude the presynaptic membrane. The postsynaptic folds are degenerated, and associated with pinocytotic vesicles and labyrinthine membranous networks. Patients with slow-channel congenital myasthenia syndrome show type 1 fiber predominance, and their junctional folds are typically degenerated with widened synaptic space and loss of AChRs. Patients with AChR deficiency syndrome caused by recessive mutations in AChR subunits also show type 1 fiber predominance, and while most junctional folds are normal, some are simplified and have smaller than normal endplates. Rapsin and Mu

  8. Recruitment of rat diaphragm motor units across motor behaviors with different levels of diaphragm activation

    PubMed Central

    Seven, Yasin B.; Mantilla, Carlos B.

    2014-01-01

    Phrenic motor neurons are recruited across a range of motor behaviors to generate varying levels of diaphragm muscle (DIAm) force. We hypothesized that DIAm motor units are recruited in a fixed order across a range of motor behaviors of varying force levels, consistent with the Henneman Size Principle. Single motor unit action potentials and compound DIAm EMG activities were recorded in anesthetized, neurally intact rats across different motor behaviors, i.e., eupnea, hypoxia-hypercapnia (10% O2 and 5% CO2), deep breaths, sustained airway occlusion, and sneezing. Central drive [estimated by root-mean-squared (RMS) EMG value 75 ms after the onset of EMG activity (RMS75)], recruitment delay, and onset discharge frequencies were similar during eupnea and hypoxia-hypercapnia. Compared with eupnea, central drive increased (∼25%) during deep breaths, and motor units were recruited ∼12 ms earlier (P < 0.01). During airway occlusion, central drive was ∼3 times greater, motor units were recruited ∼30 ms earlier (P < 0.01), and motor unit onset discharge frequencies were significantly higher (P < 0.01). Recruitment order of motor unit pairs observed during eupnea was maintained for 98%, 87%, and 84% of the same pairs recorded during hypoxia-hypercapnia, deep breaths, and airway occlusion, respectively. Reversals in motor unit recruitment order were observed primarily if motor unit pairs were recruited <20 ms apart. These results are consistent with DIAm motor unit recruitment order being determined primarily by the intrinsic size-dependent electrophysiological properties of phrenic motor neurons. PMID:25257864

  9. Spatial organization of cortical and spinal neurons controlling motor behavior

    PubMed Central

    Levine, Ariel J; Lewallen, Kathryn A; Pfaff, Samuel L

    2013-01-01

    A major task of the central nervous system (CNS) is to control behavioral actions, which necessitates a precise regulation of muscle activity. The final components of the circuitry controlling muscles are the motorneurons, which settle into pools in the ventral horn of the spinal cord in positions that mirror the musculature organization within the body. This ‘musculotopic’ motor-map then becomes the internal CNS reference for the neuronal circuits that control motor commands. This review describes recent progress in defining the neuroanatomical organization of the higher-order motor circuits in the cortex and spinal cord, and our current understanding of the integrative features that contribute to complex motor behaviors. We highlight emerging evidence that cortical and spinal motor command centers are loosely organized with respect to the musculotopic spatial-map, but these centers also incorporate organizational features that associate with the function of different muscle groups during commonly enacted behaviors. PMID:22841417

  10. Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science

    PubMed Central

    2015-01-01

    Background Schizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations. Methods Male Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive animals without any manipulations. Adult animals were implanted with E-Mitter transponders intraabdominally to record body temperature and locomotor activity continuously. The circadian rhythm of these parameters and the acute effects of changes in light conditions were analyzed under undisturbed circumstances, and the effects of different interventions (handling, bed changing or intraperitoneal vehicle injection) were also determined. Results Decreased motor activity with fragmented pattern was observed in the new substrain. However, these animals had higher body temperature during the active phase, and they showed wider range of its alterations, too. The changes in light conditions and different interventions produced blunted hyperactivity and altered body temperature responses in the new substrain. Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups. Furthermore, the new substrain showed increased short- and long-term variabilities with lower degree of asymmetry suggesting autonomic dysregulation. Conclusions In summary, the new substrain with schizophrenia-related phenomena showed disturbed motor activity and thermoregulation suggesting that these objectively determined parameters can be biomarkers in translational research. PMID:26629908

  11. Early cognitive changes and nondementing behavioral abnormalities in Parkinson's disease.

    PubMed

    Levin, Bonnie E; Katzen, Heather L

    2005-01-01

    Early cognitive changes in patients with PD are often subtle and influenced by factors that interact with the disease process, including age of disease onset, medication, and the specific constellation of motor symptoms. These factors notwithstanding, ample evidence exists that specific cognitive changes occur early in the course of PD. This evidence does not imply that cognitive deficits are pervasive during the early stages. To the contrary, they are usually subtle and often difficult to detect without formal neuropsychological testing. Executive-function deficits are the most frequently reported cognitive problems and, given that executive skills are an integral part of many tasks, it follows that subtle difficulties may be seen on a wide range of cognitive measures, particularly in working memory and visuospatial dysfunction, two areas that rely heavily on executive skills. Whereas apraxia and language processing deficits occur infrequently, subtle changes in olfaction and contrast sensitivity have also been repeatedly observed. Finally, depressive symptoms are also common in the early stages of the disease. The significance of the early behavioral changes and their prognostic implications are largely unknown. Prospective studies are needed to understand the longitudinal course of early cognitive changes to determine whether they remain as circumscribed impairments or represent a precursor to a more widespread dementia. PMID:16383214

  12. Abnormal Elastic and Vibrational Behaviors of Magnetite at High Pressures

    NASA Astrophysics Data System (ADS)

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H.; Leu, Bogdan M.; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-09-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe2+-Fe3+-Fe2+ ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature.

  13. Abnormal Elastic and Vibrational Behaviors of Magnetite at High Pressures

    PubMed Central

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H.; Leu, Bogdan M.; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-01-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe2+-Fe3+-Fe2+ ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature. PMID:25186916

  14. Abnormal elastic and vibrational behaviors of magnetite at high pressures.

    PubMed

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H; Leu, Bogdan M; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-01-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe(2+)-Fe(3+)-Fe(2+) ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature. PMID:25186916

  15. EEG spectra, behavioral states and motor activity in rats exposed to acetylcholinesterase inhibitor chlorpyrifos.

    PubMed

    Timofeeva, Olga A; Gordon, Christopher J

    2002-06-01

    Exposure to organophosphates (OP) has been associated with sleep disorders such as insomnia and "excessive dreaming." The central mechanisms of these effects are not well understood. OPs inhibit acetylcholinesterase (AChE) activity, leading to a hyperactivity of the brain cholinergic systems that are involved in sleep regulation. We studied alterations in the EEG, behavioral states, motor activity and core temperature in rats orally administered with 10 or 40 mg/kg of the OP insecticide chlorpyrifos (CHP). Occipital EEG, motor activity and core temperature were recorded with telemetric transmitters. Behavioral sleep-wake states were visually scored. Both doses of CHP produced alterations of the EEG (decrease in power of sigma/beta and increase in slow theta and fast gamma bands) characteristic of arousal. EEG alterations were consistent with behavioral changes such as an increase in wakefulness and a decrease in sleep. Waking immobility was a prevalent behavior. We did not detect any overt signs of CHP toxicity, such as an abnormal posture or gait, suggesting that reduced locomotion can be a result of central effects of CHP (such as activation of cholinergic motor inhibitory system) rather than peripheral (such as an impairment of neuromuscular function). Changes in the EEG and behavior occurred independently of the decrease in core temperature. Increased wakefulness together with reduced motor activity after exposure to CHP seems to be a result of hyperactivity in brain cholinergic neuronal networks. PMID:12175464

  16. Abnormal motor cortex excitability during linguistic tasks in adductor-type spasmodic dysphonia.

    PubMed

    Suppa, A; Marsili, L; Giovannelli, F; Di Stasio, F; Rocchi, L; Upadhyay, N; Ruoppolo, G; Cincotta, M; Berardelli, A

    2015-08-01

    In healthy subjects (HS), transcranial magnetic stimulation (TMS) applied during 'linguistic' tasks discloses excitability changes in the dominant hemisphere primary motor cortex (M1). We investigated 'linguistic' task-related cortical excitability modulation in patients with adductor-type spasmodic dysphonia (ASD), a speech-related focal dystonia. We studied 10 ASD patients and 10 HS. Speech examination included voice cepstral analysis. We investigated the dominant/non-dominant M1 excitability at baseline, during 'linguistic' (reading aloud/silent reading/producing simple phonation) and 'non-linguistic' tasks (looking at non-letter strings/producing oral movements). Motor evoked potentials (MEPs) were recorded from the contralateral hand muscles. We measured the cortical silent period (CSP) length and tested MEPs in HS and patients performing the 'linguistic' tasks with different voice intensities. We also examined MEPs in HS and ASD during hand-related 'action-verb' observation. Patients were studied under and not-under botulinum neurotoxin-type A (BoNT-A). In HS, TMS over the dominant M1 elicited larger MEPs during 'reading aloud' than during the other 'linguistic'/'non-linguistic' tasks. Conversely, in ASD, TMS over the dominant M1 elicited increased-amplitude MEPs during 'reading aloud' and 'syllabic phonation' tasks. CSP length was shorter in ASD than in HS and remained unchanged in both groups performing 'linguistic'/'non-linguistic' tasks. In HS and ASD, 'linguistic' task-related excitability changes were present regardless of the different voice intensities. During hand-related 'action-verb' observation, MEPs decreased in HS, whereas in ASD they increased. In ASD, BoNT-A improved speech, as demonstrated by cepstral analysis and restored the TMS abnormalities. ASD reflects dominant hemisphere excitability changes related to 'linguistic' tasks; BoNT-A returns these excitability changes to normal. PMID:26061279

  17. Dorsal anterior cingulate cortex modulates supplementary motor area in coordinated unimanual motor behavior

    PubMed Central

    Asemi, Avisa; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A.; Bressler, Steven L.

    2015-01-01

    Motor control is integral to all types of human behavior, and the dorsal Anterior Cingulate Cortex (dACC) is thought to play an important role in the brain network underlying motor control. Yet the role of the dACC in motor control is under-characterized. Here we aimed to characterize the dACC’s role in adolescent brain network interactions during a simple motor control task involving visually coordinated unimanual finger movements. Network interactions were assessed using both undirected and directed functional connectivity analysis of functional Magnetic Resonance Imaging (fMRI) Blood-Oxygen-Level-Dependent (BOLD) signals, comparing the task with a rest condition. The relation between the dACC and Supplementary Motor Area (SMA) was compared to that between the dACC and Primary Motor Cortex (M1). The directed signal from dACC to SMA was significantly elevated during motor control in the task. By contrast, the directed signal from SMA to dACC, both directed signals between dACC and M1, and the undirected functional connections of dACC with SMA and M1, all did not differ between task and rest. Undirected coupling of dACC with both SMA and dACC, and only the dACC-to-SMA directed signal, were significantly greater for a proactive than a reactive task condition, suggesting that dACC plays a role in motor control by maintaining stimulus timing expectancy. Overall, these results suggest that the dACC selectively modulates the SMA during visually coordinated unimanual behavior in adolescence. The role of the dACC as an important brain area for the mediation of task-related motor control may be in place in adolescence, continuing into adulthood. The task and analytic approach described here should be extended to the study of healthy adults to examine network profiles of the dACC during basic motor behavior. PMID:26089783

  18. BETA-ENDORPHIN LEVELS IN LONGTAILED AND PIGTAILED MACAQUES VARY BY ABNORMAL BEHAVIOR RATING AND SEX

    PubMed Central

    Crockett, Carolyn M.; Sackett, Gene P.; Sandman, Curt A.; Chicz-DeMet, Aleksandra; Bentson, Kathleen L.

    2007-01-01

    Frequent or severe abnormal behavior may be associated with the release of endorphins that positively reinforce the behavior with an opiate euphoria or analgesia. One line of research exploring this association involves the superhormone, proopiomelanocortin (POMC). The products of POMC appear to be dysregulated in some human subjects who exhibit self-injurious behavior (SIB). Macaque monkeys have POMC very similar to humans, and some laboratory macaques display SIB or frequent stereotypies. We investigated associations between plasma levels of three immunoreactive POMC fragments with possible opioid action and abnormal behavior ratings in macaques. In 58 adult male and female macaques (24 Macaca fascicularis and 34 M. nemestrina), plasma levels of intact beta-endorphin (βE) and the N-terminal fragment (BEN) were significantly higher in animals with higher levels of abnormal behavior. The C-terminal fragment (BEC) was significantly higher in males but unrelated to ratings of abnormal behavior. Levels of ACTH, cortisol, and (βE-ACTH)/βE dysregulation index were unrelated to abnormal behavior. None of the POMC products differed significantly by subjects' species, age, or weight. The finding that intact beta-endorphin is positively related to abnormal behavior in two species of macaque is consistent with some previous research on human subjects and nonprimates. The positive relation of the N-terminal fragment of βE to abnormal behavior is a new finding. PMID:17719139

  19. Normal behavior and the clinical implications of abnormal behavior in guinea pigs.

    PubMed

    Bradley, T A

    2001-09-01

    Cavies are becoming more popular as pets because they are relatively easy to care for and provide never-ending love and entertainment with their curious but gentle nature. As with other species, the best way to learn about guinea pig behavior is to own guinea pigs. Understanding normal behavior provides the practitioner with the ability to more easily recognize pathology and abnormal behavior. This allows the veterinarian to provide necessary supportive care and pain management more quickly while performing diagnostics and determining the need for therapeutics. Understanding the behavior of cavies allows the clinician to better educate guinea pig-owning clients and to better and more quickly serve the needs of their guinea pig patients. PMID:11601108

  20. Transgenerational effects of environmental enrichment on repetitive motor behavior development.

    PubMed

    Bechard, Allison R; Lewis, Mark H

    2016-07-01

    The favorable consequences of environmental enrichment (EE) on brain and behavior development are well documented. Much less is known, however, about transgenerational benefits of EE on non-enriched offspring. We explored whether transgenerational effects of EE might extend to the development of repetitive motor behaviors in deer mice. Repetitive motor behaviors are invariant patterns of movement that, across species, can be reduced by EE. We found that EE not only attenuated the development of repetitive behavior in dams, but also in their non-enriched offspring. Moreover, maternal behavior did not seem to mediate the transgenerational effect we found, although repetitive behavior was affected by reproductive experience. These data support a beneficial transgenerational effect of EE on repetitive behavior development and suggest a novel benefit of reproductive experience. PMID:27059336

  1. Motor Network Plasticity and Low-Frequency Oscillations Abnormalities in Patients with Brain Gliomas: A Functional MRI Study

    PubMed Central

    Niu, Chen; Zhang, Ming; Min, Zhigang; Rana, Netra; Zhang, Qiuli; Liu, Xin; Li, Min; Lin, Pan

    2014-01-01

    Brain plasticity is often associated with the process of slow-growing tumor formation, which remodels neural organization and optimizes brain network function. In this study, we aimed to investigate whether motor function plasticity would display deficits in patients with slow-growing brain tumors located in or near motor areas, but who were without motor neurological deficits. We used resting-state functional magnetic resonance imaging to probe motor networks in 15 patients with histopathologically confirmed brain gliomas and 15 age-matched healthy controls. All subjects performed a motor task to help identify individual motor activity in the bilateral primary motor cortex (PMC) and supplementary motor area (SMA). Frequency-based analysis at three different frequencies was then used to investigate possible alterations in the power spectral density (PSD) of low-frequency oscillations. For each group, the average PSD was determined for each brain region and a nonparametric test was performed to determine the difference in power between the two groups. Significantly reduced inter-hemispheric functional connectivity between the left and right PMC was observed in patients compared with controls (P<0.05). We also found significantly decreased PSD in patients compared to that in controls, in all three frequency bands (low: 0.01–0.02 Hz; middle: 0.02–0.06 Hz; and high: 0.06–0.1 Hz), at three key motor regions. These findings suggest that in asymptomatic patients with brain tumors located in eloquent regions, inter-hemispheric connection may be more vulnerable. A comparison of the two approaches indicated that power spectral analysis is more sensitive than functional connectivity analysis for identifying the neurological abnormalities underlying motor function plasticity induced by slow-growing tumors. PMID:24806463

  2. Associations of postural knowledge and basic motor skill with dyspraxia in autism: implication for abnormalities in distributed connectivity and motor learning.

    PubMed

    Dowell, Lauren R; Mahone, E Mark; Mostofsky, Stewart H

    2009-09-01

    Children with autism often have difficulty performing skilled movements. Praxis performance requires basic motor skill, knowledge of representations of the movement (mediated by parietal regions), and transcoding of these representations into movement plans (mediated by premotor circuits). The goals of this study were (a) to determine whether dyspraxia in autism is associated with impaired representational ("postural") knowledge and (b) to examine the contributions of postural knowledge and basic motor skill to dyspraxia in autism. Thirty-seven children with autism spectrum disorder (ASD) and 50 typically developing (TD) children, ages 8-13, completed (a) an examination of basic motor skills, (b) a postural knowledge test assessing praxis discrimination, and (c) a praxis examination. Children with ASD showed worse basic motor skill and postural knowledge than did controls. The ASD group continued to show significantly poorer praxis than did controls after accounting for age, IQ, basic motor skill, and postural knowledge. Dyspraxia in autism appears to be associated with impaired formation of spatial representations, as well as transcoding and execution. Distributed abnormality across parietal, premotor, and motor circuitry, as well as anomalous connectivity, may be implicated. PMID:19702410

  3. Associations of Postural Knowledge and Basic Motor Skill with Dyspraxia in Autism: Implication for Abnormalities in Distributed Connectivity and Motor Learning

    PubMed Central

    Dowell, Lauren R.; Mahone, E. Mark; Mostofsky, Stewart H.

    2009-01-01

    Children with autism often have difficulty performing skilled movements. Praxis performance requires basic motor skill, knowledge of representations of the movement (mediated by parietal regions), and transcoding of these representations into movement plans (mediated by premotor circuits). The goals of this study were: (a) to determine whether dyspraxia in autism is associated with impaired representational (“postural”) knowledge, and (b) to examine the contributions of postural knowledge and basic motor skill to dyspraxia in autism. Thirty-seven children with autism spectrum disorder (ASD) and 50 typically developing (TD) children, ages 8–13, completed: (a) an examination of basic motor skills, (b) a postural knowledge test assessing praxis discrimination, and (c) a praxis examination. Children with ASD showed worse basic motor skill and postural knowledge than controls. The ASD group continued to show significantly poorer praxis than controls after accounting for age, IQ, basic motor skill, and postural knowledge. Dyspraxia in autism appears to be associated with impaired formation of spatial representations, as well as transcoding and execution. Distributed abnormality across parietal, premotor, and motor circuitry, as well as anomalous connectivity may be implicated. PMID:19702410

  4. Early phrenic motor neuron loss and transient respiratory abnormalities after unilateral cervical spinal cord contusion.

    PubMed

    Nicaise, Charles; Frank, David M; Hala, Tamara J; Authelet, Michèle; Pochet, Roland; Adriaens, Dominique; Brion, Jean-Pierre; Wright, Megan C; Lepore, Angelo C

    2013-06-15

    Contusion-type cervical spinal cord injury (SCI) is one of the most common forms of SCI observed in patients. In particular, injuries targeting the C3-C5 region affect the pool of phrenic motor neurons (PhMNs) that innervates the diaphragm, resulting in significant and often chronic respiratory dysfunction. Using a previously described rat model of unilateral midcervical C4 contusion with the Infinite Horizon Impactor, we have characterized the early time course of PhMN degeneration and consequent respiratory deficits following injury, as this knowledge is important for designing relevant treatment strategies targeting protection and plasticity of PhMN circuitry. PhMN loss (48% of the ipsilateral pool) occurred almost entirely during the first 24 h post-injury, resulting in persistent phrenic nerve axonal degeneration and denervation at the diaphragm neuromuscular junction (NMJ). Reduced diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation were observed as early as the first day post-injury (30% of pre-injury maximum amplitude), with slow functional improvement over time that was associated with partial reinnervation at the diaphragm NMJ. Consistent with ipsilateral diaphragmatic compromise, the injury resulted in rapid, yet only transient, changes in overall ventilatory parameters measured via whole-body plethysmography, including increased respiratory rate, decreased tidal volume, and decreased peak inspiratory flow. Despite significant ipsilateral PhMN loss, the respiratory system has the capacity to quickly compensate for partially impaired hemidiaphragm function, suggesting that C4 hemicontusion in rats is a model of SCI that manifests subacute respiratory abnormalities. Collectively, these findings demonstrate significant and persistent diaphragm compromise in a clinically relevant model of midcervical contusion SCI; however, the therapeutic window for PhMN protection is restricted to early time points post-injury. On

  5. A Framework to Describe, Analyze and Generate Interactive Motor Behaviors

    PubMed Central

    Jarrassé, Nathanaël; Charalambous, Themistoklis; Burdet, Etienne

    2012-01-01

    While motor interaction between a robot and a human, or between humans, has important implications for society as well as promising applications, little research has been devoted to its investigation. In particular, it is important to understand the different ways two agents can interact and generate suitable interactive behaviors. Towards this end, this paper introduces a framework for the description and implementation of interactive behaviors of two agents performing a joint motor task. A taxonomy of interactive behaviors is introduced, which can classify tasks and cost functions that represent the way each agent interacts. The role of an agent interacting during a motor task can be directly explained from the cost function this agent is minimizing and the task constraints. The novel framework is used to interpret and classify previous works on human-robot motor interaction. Its implementation power is demonstrated by simulating representative interactions of two humans. It also enables us to interpret and explain the role distribution and switching between roles when performing joint motor tasks. PMID:23226231

  6. Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: Modulation of histone deacetylase activity.

    PubMed

    Sharma, Sorabh; Taliyan, Rajeev; Singh, Sumel

    2015-09-15

    Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recent studies have investigated the involvement of epigenetic modifications in PD. Histone deacetylase (HDAC) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study was designed to investigate the effect of sodium butyrate, a HDAC inhibitor in 6-hydroxydopamine (6-OHDA) - induced experimental PD like symptoms in rats. To produce motor deficit, 6-OHDA was administered unilaterally in the right medial forebrain bundle. Three weeks after 6-OHDA administration, the rats were challenged with apomorphine. Following this, the animals were treated with sodium butyrate (150 and 300 mg/kg i.p.) once daily for 14 days. Movement abnormalities were assessed by battery of behavioral tests. Biochemically, oxidative stress markers, neuroinflammation and dopamine were measured in striatal brain homogenate. Further, to explore the molecular mechanism(s), we measured the level of global H3 histone acetylation and brain derived neurotrophic factor (BDNF). 6-OHDA administration results in significant motor deficit along with reduction in striatal dopamine level. 6-OHDA treated rats showed elevated oxidative stress and neuroinflammatory markers. Treatment with sodium butyrate results in significant attenuation of motor deficits and increased striatal dopamine level. Moreover, sodium butyrate treatment attenuated the oxidative stress and neuroinflammatory markers. These effects occur concurrently with increased global H3 histone acetylation and BDNF levels. Thus, the observed results of the present study are indicative for the therapeutic potential of HDAC inhibitors in PD. PMID:26048426

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

    PubMed

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

    2016-03-01

    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

  8. The Feldenkrais Method: A Dynamic Approach to Changing Motor Behavior.

    ERIC Educational Resources Information Center

    Buchanan, Patricia A.; Ulrich, Beverly D.

    2001-01-01

    Describes the Feldenkrais Method of somatic education, noting parallels with a dynamic systems theory (DST) approach to motor behavior. Feldenkrais uses movement and perception to foster individualized improvement in function. DST explains that a human-environment system continually adapts to changing conditions and assembles behaviors…

  9. Behavioral abnormalities in mice lacking mesenchyme-specific Pten.

    PubMed

    Borniger, Jeremy C; Cissé, Yasmine M; Cantemir-Stone, Carmen Z; Bolon, Brad; Nelson, Randy J; Marsh, Clay B

    2016-05-01

    Phosphatase and tensin homolog (Pten) is a negative regulator of cell proliferation and growth. Using a Cre-recombinase approach with Lox sequences flanking the fibroblast-specific protein 1 (Fsp1 aka S100A4; a mesenchymal marker), we probed sites of expression using a β-galactosidase Rosa26(LoxP) reporter allele; the transgene driving deletion of Pten (exons 4-5) was found throughout the brain parenchyma and pituitary, suggesting that deletion of Pten in Fsp1-positive cells may influence behavior. Because CNS-specific deletion of Pten influences social and anxiety-like behaviors and S100A4 is expressed in astrocytes, we predicted that loss of Pten in Fsp1-expressing cells would result in deficits in social interaction and increased anxiety. We further predicted that environmental enrichment would compensate for genetic deficits in these behaviors. We conducted a battery of behavioral assays on Fsp1-Cre;Pten(LoxP/LoxP) male and female homozygous knockouts (Pten(-/-)) and compared their behavior to Pten(LoxP/LoxP) (Pten(+/+)) conspecifics. Despite extensive physical differences (including reduced hippocampal size) and deficits in sensorimotor function, Pten(-/-) mice behaved remarkably similar to control mice on nearly all behavioral tasks. These results suggest that the social and anxiety-like phenotypes observed in CNS-specific Pten(-/-) mice may depend on neuronal Pten, as lack of Pten in Fsp1-expressing cells of the CNS had little effect on these behaviors. PMID:26876012

  10. Motor control of jaw movements: An fMRI study of parafunctional clench and grind behavior.

    PubMed

    Wong, Donald; Dzemidzic, Mario; Talavage, Thomas M; Romito, Laura M; Byrd, Kenneth E

    2011-04-01

    Jaw-clenching and tooth-grinding associated with bruxism can contribute to abnormal tooth wear and pain in the masticatory system. Clench and tooth-grinding jaw-movement tasks were evaluated in a block-design fMRI study comparing a dental-control (DC) group with a tooth-grinding (TG) group. Group classification was made prior to imaging based upon self-reported parafunctional clench and grind behavior and clinical evidence of abnormal tooth wear. Group differences in brain activation patterns were found for each task compared to the resting baseline. The DC group showed a more widely distributed pattern; more extensive activity in the supplementary motor area (SMA) proper that extended into the pre-SMA; and, for clench, activity in the left inferior parietal lobule (IPL). The DC group activated more than the TG subjects the left IPL for clench, and pre-SMA for grind. Neither task elicited more activity in the TG than DC subjects. Our group findings suggest that jaw-movement tasks executed by the TG group elicited (1) more efficient brain activation pattern consistent with other studies that found less extensive activity with executing "over-learned" tasks; (2) "underactive" SMA activity that underlies reduced motor planning; (3) decreased inferior parietal activity that is associated with lesser motor-attentional demands. Thus orofacial parafunctional habits may influence brain circuits recruited for jaw movements, providing a possible basis for understanding involuntary jaw movements in bruxism and oral movement disorders in general. PMID:21295015

  11. Motor resonance evoked by observation of subtle nonverbal behavior.

    PubMed

    van Ulzen, Niek R; Fiorio, Mirta; Cesari, Paola

    2013-01-01

    This study was designed to combine two, otherwise separated, fields of research regarding motor resonance and mimicry by adopting a naturalistic mimicry paradigm while probing motor resonance with transcranial magnetic stimulation (TMS). At stake was whether the motor system resonates instantaneously with unobtrusive nonverbal behavior of another person. We measured excitability in the left and right hand while participants viewed sequences of video clips and static images. In the video clips an actor performed several clerical tasks, while either inconspicuously touching his face (face-touching (FT) condition) or not (no face-touching (NFT) condition). We found that excitability was higher in the FT condition than in the NFT and baseline conditions. Furthermore, our data showed a general heightened excitability in the left motor cortex relative to the right. Taken together, the results suggest that observed hand-face gestures--even though outside the primary focus of attention and occurring inconspicuously throughout an ongoing action setting--can cause instantaneous resonant activity in the observer's motor system. It thus supports the idea of motor resonance involvement in mimicry and demonstrates that this can be studied using a naturalistic mimicry paradigm. PMID:23758553

  12. [Non-motor symptoms in Parkinson's disease: cognition and behavior].

    PubMed

    Bonnet, Anne Marie; Czernecki, Virginie

    2013-09-01

    Although the diagnosis of Parkinson disease is based on motor symptoms, it is now well known that non-motor symptoms are an integral part of this pathology, involving in fact multiple systems. These non-motor symptoms affect large population of patients and can appear sometimes before the motor disorders. The non-motor symptoms include mainly neuropsychological difficulties, neuropsychiatric symptoms, and autonomic disorders, but involve also pain and sleep disturbances for example. Depression may occur at any stage of the disease, and consists in major depressive disorder, minor depressive disorder, and dysthymia. During the course of the disease, 50% of patients experience anxiety. Apathy is present in up to 30-40% of patients, due to loss of motivation, appearing in emotional, intellectual and behavioral domains. Dopamine dysregulation syndrome and impulse control disorders are not rare, and in relation with dopaminergic therapies. Impulse control disorders include pathological gambling, hyper sexuality, compulsive shopping, and eating disorder. Visual hallucinations can occur in 30% of patients, mostly induced by dopaminergic therapies. Often, they have deeper impact on the quality of life than the motor symptoms themselves, which stay the focus of attention during consulting. Identifying those can help in providing better care with a positive impact on the quality of life of the patients. PMID:24026132

  13. Allergies: The Key to Many Childhood Behavior Abnormalities.

    ERIC Educational Resources Information Center

    Vass, Molly; Rasmussen, Betty

    1984-01-01

    Describes the role of allergies in childhood behavior problems and discusses the role of school counselors in identifying allergic responses. Includes a list of references and resources on allergies, nutrition, support groups, and environmental care units. (JAC)

  14. Causal Role of Motor Simulation in Turn-Taking Behavior

    PubMed Central

    Novembre, Giacomo; Keller, Peter E.; Pickering, Martin J.

    2015-01-01

    Overlap between sensory and motor representations has been documented for a range of human actions, from grasping (Rizzolatti et al., 1996b) to playing a musical instrument (Novembre and Keller, 2014). Such overlap suggests that individuals use motor simulation to predict the outcome of observed actions (Wolpert, 1997). Here we investigate motor simulation as a basis of human communication. Using a musical turn-taking task, we show that pianists call on motor representations of their partner's part to predict when to come in for their own turn. Pianists played alternating solos with a videoed partner, and double-pulse transcranial magnetic stimulation was applied around the turn-switch to temporarily disrupt processing in two cortical regions implicated previously in different forms of motor simulation: (1) the dorsal premotor cortex (dPMC), associated with automatic motor resonance during passive observation of hand actions, especially when the actions are familiar (Lahav et al., 2007); and (2) the supplementary motor area (SMA), involved in active motor imagery, especially when the actions are familiar (Baumann et al., 2007). Stimulation of the right dPMC decreased the temporal accuracy of pianists' (right-hand) entries relative to sham when the partner's (left-hand) part had been rehearsed previously. This effect did not occur for dPMC stimulation without rehearsal or for SMA stimulation. These findings support the role of the dPMC in predicting the time course of observed actions via resonance-based motor simulation during turn-taking. Because turn-taking spans multiple modes of human interaction, we suggest that simulation is a foundational mechanism underlying the temporal dynamics of joint action. SIGNIFICANCE STATEMENT Even during passive observation, seeing or hearing somebody execute an action from within our repertoire activates motor cortices of our brain. But what is the functional relevance of such “motor simulation”? By combining a musical duet

  15. Autism-related behavioral abnormalities in synapsin knockout mice

    PubMed Central

    Greco, Barbara; Managò, Francesca; Tucci, Valter; Kao, Hung-Teh; Valtorta, Flavia; Benfenati, Fabio

    2013-01-01

    Several synaptic genes predisposing to autism-spectrum disorder (ASD) have been identified. Nonsense and missense mutations in the SYN1 gene encoding for Synapsin I have been identified in families segregating for idiopathic epilepsy and ASD and genetic mapping analyses have identified variations in the SYN2 gene as significantly contributing to epilepsy predisposition. Synapsins (Syn I/II/III) are a multigene family of synaptic vesicle-associated phosphoproteins playing multiple roles in synaptic development, transmission and plasticity. Lack of SynI and/or SynII triggers a strong epileptic phenotype in mice associated with mild cognitive impairments that are also present in the non-epileptic SynIII−/− mice. SynII−/− and SynIII−/− mice also display schizophrenia-like traits, suggesting that Syns could be involved in the regulation of social behavior. Here, we studied social interaction and novelty, social recognition and social dominance, social transmission of food preference and social memory in groups of male SynI−/−, SynII−/− and SynIII−/− mice before and after the appearance of the epileptic phenotype and compared their performances with control mice. We found that deletion of Syn isoforms widely impairs social behaviors and repetitive behaviors, resulting in ASD-related phenotypes. SynI or SynIII deletion altered social behavior, whereas SynII deletion extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming. Social impairments of SynI−/− and SynII−/− mice were evident also before the onset of seizures. The results demonstrate an involvement of Syns in generation of the behavioral traits of ASD and identify Syn knockout mice as a useful experimental model of ASD and epilepsy. PMID:23280234

  16. HINT1 is involved in the behavioral abnormalities induced by social isolation rearing.

    PubMed

    Dang, Yong-hui; Liu, Peng; Ma, Rui; Chu, Zheng; Liu, You-ping; Wang, Jia-bei; Ma, Xian-cang; Gao, Cheng-ge

    2015-10-21

    Social isolation (SI) rearing has been demonstrated to induce behavioral abnormalities like anxiety, impulsivity, aggression, and learning and memory deficits which are relevant to core symptoms in patients with some certain neuropsychiatric disorders. But the underlying pathophysiological mechanisms remain unclear. Recent studies have revealed HINT1 has close relation with diverse neuropsychiatric diseases. In this present study, the SI rearing mice exhibited depression-like and aggressive behavior. Besides, HINT1 protein levels decreased in PFC but increased in HIP. Based on the data obtained, we concluded that HINT1 is involved in the behavioral abnormalities induced by social isolation and exerts distinct roles in different encephalic regions. PMID:26300541

  17. Abnormal Electrophysiological Motor Responses in Huntington’s Disease: Evidence of Premanifest Compensation

    PubMed Central

    Turner, Lauren M.; Croft, Rodney J.; Churchyard, Andrew; Looi, Jeffrey C. L.; Apthorp, Deborah; Georgiou-Karistianis, Nellie

    2015-01-01

    Background Huntington's disease (HD) causes progressive motor dysfunction through characteristic atrophy. Changes to neural structure begin in premanifest stages yet individuals are able to maintain a high degree of function, suggesting involvement of supportive processing during motor performance. Electroencephalography (EEG) enables the investigation of subtle impairments at the neuronal level, and possible compensatory strategies, by examining differential activation patterns. We aimed to use EEG to investigate neural motor processing (via the Readiness Potential; RP), premotor processing and sensorimotor integration (Contingent Negative Variation; CNV) during simple motor performance in HD. Methods We assessed neural activity associated with motor preparation and processing in 20 premanifest (pre-HD), 14 symptomatic HD (symp-HD), and 17 healthy controls. Participants performed sequential tapping within two experimental paradigms (simple tapping; Go/No-Go). RP and CNV potentials were calculated separately for each group. Results Motor components and behavioural measures did not distinguish pre-HD from controls. Compared to controls and pre-HD, symp-HD demonstrated significantly reduced relative amplitude and latency of the RP, whereas controls and pre-HD did not differ. However, early CNV was found to significantly differ between control and pre-HD groups, due to enhanced early CNV in pre-HD. Conclusions For the first time, we provide evidence of atypical activation during preparatory processing in pre-HD. The increased activation during this early stage of the disease may reflect ancillary processing in the form of recruitment of additional neural resources for adequate motor preparation, despite atrophic disruption to structure and circuitry. We propose an early adaptive compensation mechanism in pre-HD during motor preparation. PMID:26406226

  18. Increased cytoplasmic TARDBP mRNA in affected spinal motor neurons in ALS caused by abnormal autoregulation of TDP-43

    PubMed Central

    Koyama, Akihide; Sugai, Akihiro; Kato, Taisuke; Ishihara, Tomohiko; Shiga, Atsushi; Toyoshima, Yasuko; Koyama, Misaki; Konno, Takuya; Hirokawa, Sachiko; Yokoseki, Akio; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi; Onodera, Osamu

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder. In motor neurons of ALS, TAR DNA binding protein-43 (TDP-43), a nuclear protein encoded by TARDBP, is absent from the nucleus and forms cytoplasmic inclusions. TDP-43 auto-regulates the amount by regulating the TARDBP mRNA, which has three polyadenylation signals (PASs) and three additional alternative introns within the last exon. However, it is still unclear how the autoregulatory mechanism works and how the status of autoregulation in ALS motor neurons without nuclear TDP-43 is. Here we show that TDP-43 inhibits the selection of the most proximal PAS and induces splicing of multiple alternative introns in TARDBP mRNA to decrease the amount of cytoplasmic TARDBP mRNA by nonsense-mediated mRNA decay. When TDP-43 is depleted, the TARDBP mRNA uses the most proximal PAS and is increased in the cytoplasm. Finally, we have demonstrated that in ALS motor neurons—especially neurons with mislocalized TDP-43—the amount of TARDBP mRNA is increased in the cytoplasm. Our observations indicate that nuclear TDP-43 contributes to the autoregulation and suggests that the absence of nuclear TDP-43 induces an abnormal autoregulation and increases the amount of TARDBP mRNA. The vicious cycle might accelerate the disease progression of ALS. PMID:27257061

  19. Increased cytoplasmic TARDBP mRNA in affected spinal motor neurons in ALS caused by abnormal autoregulation of TDP-43.

    PubMed

    Koyama, Akihide; Sugai, Akihiro; Kato, Taisuke; Ishihara, Tomohiko; Shiga, Atsushi; Toyoshima, Yasuko; Koyama, Misaki; Konno, Takuya; Hirokawa, Sachiko; Yokoseki, Akio; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi; Onodera, Osamu

    2016-07-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder. In motor neurons of ALS, TAR DNA binding protein-43 (TDP-43), a nuclear protein encoded by TARDBP, is absent from the nucleus and forms cytoplasmic inclusions. TDP-43 auto-regulates the amount by regulating the TARDBP mRNA, which has three polyadenylation signals (PASs) and three additional alternative introns within the last exon. However, it is still unclear how the autoregulatory mechanism works and how the status of autoregulation in ALS motor neurons without nuclear TDP-43 is. Here we show that TDP-43 inhibits the selection of the most proximal PAS and induces splicing of multiple alternative introns in TARDBP mRNA to decrease the amount of cytoplasmic TARDBP mRNA by nonsense-mediated mRNA decay. When TDP-43 is depleted, the TARDBP mRNA uses the most proximal PAS and is increased in the cytoplasm. Finally, we have demonstrated that in ALS motor neurons-especially neurons with mislocalized TDP-43-the amount of TARDBP mRNA is increased in the cytoplasm. Our observations indicate that nuclear TDP-43 contributes to the autoregulation and suggests that the absence of nuclear TDP-43 induces an abnormal autoregulation and increases the amount of TARDBP mRNA. The vicious cycle might accelerate the disease progression of ALS. PMID:27257061

  20. Transformation of Context-dependent Sensory Dynamics into Motor Behavior

    PubMed Central

    Latorre, Roberto; Levi, Rafael; Varona, Pablo

    2013-01-01

    The intrinsic dynamics of sensory networks play an important role in the sensory-motor transformation. In this paper we use conductance based models and electrophysiological recordings to address the study of the dual role of a sensory network to organize two behavioral context-dependent motor programs in the mollusk Clione limacina. We show that: (i) a winner take-all dynamics in the gravimetric sensory network model drives the typical repetitive rhythm in the wing central pattern generator (CPG) during routine swimming; (ii) the winnerless competition dynamics of the same sensory network organizes the irregular pattern observed in the wing CPG during hunting behavior. Our model also shows that although the timing of the activity is irregular, the sequence of the switching among the sensory cells is preserved whenever the same set of neurons are activated in a given time window. These activation phase locks in the sensory signals are transformed into specific events in the motor activity. The activation phase locks can play an important role in motor coordination driven by the intrinsic dynamics of a multifunctional sensory organ. PMID:23459114

  1. Characterizing abnormal behavior in a large population of zoo-housed chimpanzees: prevalence and potential influencing factors.

    PubMed

    Jacobson, Sarah L; Ross, Stephen R; Bloomsmith, Mollie A

    2016-01-01

    Abnormal behaviors in captive animals are generally defined as behaviors that are atypical for the species and are often considered to be indicators of poor welfare. Although some abnormal behaviors have been empirically linked to conditions related to elevated stress and compromised welfare in primates, others have little or no evidence on which to base such a relationship. The objective of this study was to investigate a recent claim that abnormal behavior is endemic in the captive population by surveying a broad sample of chimpanzees (Pan troglodytes), while also considering factors associated with the origins of these behaviors. We surveyed animal care staff from 26 accredited zoos to assess the prevalence of abnormal behavior in a large sample of chimpanzees in the United States for which we had information on origin and rearing history. Our results demonstrated that 64% of this sample was reported to engage in some form of abnormal behavior in the past two years and 48% of chimpanzees engaged in abnormal behavior other than coprophagy. Logistic regression models were used to analyze the historical variables that best predicted the occurrence of all abnormal behavior, any abnormal behavior that was not coprophagy, and coprophagy. Rearing had opposing effects on the occurrence of coprophagy and the other abnormal behaviors such that mother-reared individuals were more likely to perform coprophagy, whereas non-mother-reared individuals were more likely to perform other abnormal behaviors. These results support the assertion that coprophagy may be classified separately when assessing abnormal behavior and the welfare of captive chimpanzees. This robust evaluation of the prevalence of abnormal behavior in our sample from the U.S. zoo population also demonstrates the importance of considering the contribution of historical variables to present behavior, in order to better understand the causes of these behaviors and any potential relationship to psychological

  2. Characterizing abnormal behavior in a large population of zoo-housed chimpanzees: prevalence and potential influencing factors

    PubMed Central

    Jacobson, Sarah L.; Bloomsmith, Mollie A.

    2016-01-01

    Abnormal behaviors in captive animals are generally defined as behaviors that are atypical for the species and are often considered to be indicators of poor welfare. Although some abnormal behaviors have been empirically linked to conditions related to elevated stress and compromised welfare in primates, others have little or no evidence on which to base such a relationship. The objective of this study was to investigate a recent claim that abnormal behavior is endemic in the captive population by surveying a broad sample of chimpanzees (Pan troglodytes), while also considering factors associated with the origins of these behaviors. We surveyed animal care staff from 26 accredited zoos to assess the prevalence of abnormal behavior in a large sample of chimpanzees in the United States for which we had information on origin and rearing history. Our results demonstrated that 64% of this sample was reported to engage in some form of abnormal behavior in the past two years and 48% of chimpanzees engaged in abnormal behavior other than coprophagy. Logistic regression models were used to analyze the historical variables that best predicted the occurrence of all abnormal behavior, any abnormal behavior that was not coprophagy, and coprophagy. Rearing had opposing effects on the occurrence of coprophagy and the other abnormal behaviors such that mother-reared individuals were more likely to perform coprophagy, whereas non-mother-reared individuals were more likely to perform other abnormal behaviors. These results support the assertion that coprophagy may be classified separately when assessing abnormal behavior and the welfare of captive chimpanzees. This robust evaluation of the prevalence of abnormal behavior in our sample from the U.S. zoo population also demonstrates the importance of considering the contribution of historical variables to present behavior, in order to better understand the causes of these behaviors and any potential relationship to psychological

  3. Dynamical movement primitives: learning attractor models for motor behaviors.

    PubMed

    Ijspeert, Auke Jan; Nakanishi, Jun; Hoffmann, Heiko; Pastor, Peter; Schaal, Stefan

    2013-02-01

    Nonlinear dynamical systems have been used in many disciplines to model complex behaviors, including biological motor control, robotics, perception, economics, traffic prediction, and neuroscience. While often the unexpected emergent behavior of nonlinear systems is the focus of investigations, it is of equal importance to create goal-directed behavior (e.g., stable locomotion from a system of coupled oscillators under perceptual guidance). Modeling goal-directed behavior with nonlinear systems is, however, rather difficult due to the parameter sensitivity of these systems, their complex phase transitions in response to subtle parameter changes, and the difficulty of analyzing and predicting their long-term behavior; intuition and time-consuming parameter tuning play a major role. This letter presents and reviews dynamical movement primitives, a line of research for modeling attractor behaviors of autonomous nonlinear dynamical systems with the help of statistical learning techniques. The essence of our approach is to start with a simple dynamical system, such as a set of linear differential equations, and transform those into a weakly nonlinear system with prescribed attractor dynamics by means of a learnable autonomous forcing term. Both point attractors and limit cycle attractors of almost arbitrary complexity can be generated. We explain the design principle of our approach and evaluate its properties in several example applications in motor control and robotics. PMID:23148415

  4. Bimanual non-congruent actions in motor neglect syndrome: a combined behavioral/fMRI study.

    PubMed

    Garbarini, F; Turella, L; Rabuffetti, M; Cantagallo, A; Piedimonte, A; Fainardi, E; Berti, A; Fadiga, L

    2015-01-01

    In Motor Neglect (MN) syndrome, a specific impairment in non-congruent bimanual movements has been described. In the present case-control study, we investigated the neuro-functional correlates of this behavioral deficit. Two right-brain-damaged (RBD) patients, one with (MN+) and one without (MN-) MN, were evaluated by means of functional Magnetic Resonance Imaging (fMRI) in a bimanual Circles-Lines (CL) paradigm. Patients were requested to perform right-hand movements (lines-drawing) and, simultaneously, congruent (lines-drawing) or non-congruent (circles-drawing) left-hand movements. In the behavioral task, MN- patient showed a bimanual-coupling-effect, while MN+ patient did not. The fMRI study showed that in MN-, a fronto-parietal network, mainly involving the pre-supplementary motor area (pre-SMA) and the posterior parietal cortex (PPC), was significantly more active in non-congruent than in congruent conditions, as previously shown in healthy subjects. On the contrary, MN+ patient showed an opposite pattern of activation both in pre-SMA and in PPC. Within this fronto-parietal network, the pre-SMA is supposed to exert an inhibitory influence on the default coupling of homologous muscles, thus allowing the execution of non-congruent movements. In MN syndrome, the described abnormal pre-SMA activity supports the hypothesis that a failure to inhibit ipsilesional motor programs might determine a specific impairment of non-congruent movements. PMID:26500520

  5. Bimanual non-congruent actions in motor neglect syndrome: a combined behavioral/fMRI study

    PubMed Central

    Garbarini, F.; Turella, L.; Rabuffetti, M.; Cantagallo, A.; Piedimonte, A.; Fainardi, E.; Berti, A.; Fadiga, L.

    2015-01-01

    In Motor Neglect (MN) syndrome, a specific impairment in non-congruent bimanual movements has been described. In the present case-control study, we investigated the neuro-functional correlates of this behavioral deficit. Two right-brain-damaged (RBD) patients, one with (MN+) and one without (MN−) MN, were evaluated by means of functional Magnetic Resonance Imaging (fMRI) in a bimanual Circles-Lines (CL) paradigm. Patients were requested to perform right-hand movements (lines-drawing) and, simultaneously, congruent (lines-drawing) or non-congruent (circles-drawing) left-hand movements. In the behavioral task, MN− patient showed a bimanual-coupling-effect, while MN+ patient did not. The fMRI study showed that in MN−, a fronto-parietal network, mainly involving the pre-supplementary motor area (pre-SMA) and the posterior parietal cortex (PPC), was significantly more active in non-congruent than in congruent conditions, as previously shown in healthy subjects. On the contrary, MN+ patient showed an opposite pattern of activation both in pre-SMA and in PPC. Within this fronto-parietal network, the pre-SMA is supposed to exert an inhibitory influence on the default coupling of homologous muscles, thus allowing the execution of non-congruent movements. In MN syndrome, the described abnormal pre-SMA activity supports the hypothesis that a failure to inhibit ipsilesional motor programs might determine a specific impairment of non-congruent movements. PMID:26500520

  6. Functional Measurement of Respiratory Muscle Motor Behaviors Using Transdiaphragmatic Pressure.

    PubMed

    Greising, Sarah M; Mantilla, Carlos B; Sieck, Gary C

    2016-01-01

    The diaphragm muscle must be able to generate sufficient forces to accomplish a range of ventilatory and non-ventilatory behaviors throughout life. Measurements of transdiaphragmatic pressure (Pdi) can be conducted during eupnea, hypoxia (10 % O2)-hypercapnia (5 % CO2), chemical airway stimulation (i.e., sneezing), spontaneously occurring deep breaths (i.e., sighs), sustained airway or tracheal occlusion, and maximal efforts elicited via bilateral phrenic nerve stimulation, representing the full range of motor behaviors available by the diaphragm muscle. We provide detailed methods on the in vivo measurements of Pdi in mice. PMID:27492181

  7. Abnormal repetitive behaviors in dogs and cats: a guide for practitioners.

    PubMed

    Tynes, Valarie V; Sinn, Leslie

    2014-05-01

    Abnormal repetitive behaviors (ARBs) represent a diverse group of behaviors whose underlying mechanism is poorly understood. Their neurobiology likely involves several different neurotransmitter systems. These behaviors have been referred to as compulsive disorders, obsessive compulsive disorders and stereotypies. Underlying medical conditions and pain can often cause changes in behavior that are mistaken for ARBs. A complete medical work-up is always indicated prior to reaching a presumptive diagnosis. The frequency of ARBs can be reduced but not always eliminated with the use of selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) in conjunction with behavior modification and environmental enrichment. PMID:24766699

  8. Chronic Assessment of Diaphragm Muscle EMG Activity across Motor Behaviors

    PubMed Central

    Mantilla, Carlos B.; Seven, Yasin B.; Hurtado-Palomino, Juan N.; Zhan, Wen-Zhi; Sieck, Gary C.

    2011-01-01

    The diaphragm muscle is main inspiratory muscle in mammals. Quantitative analyses documenting the reliability of chronic diaphragm EMG recordings are lacking. Assessment of ventilatory and non-ventilatory motor behaviors may facilitate evaluating diaphragm EMG activity over time. We hypothesized that normalization of diaphragm EMG amplitude across behaviors provides stable and reliable parameters for longitudinal assessments of diaphragm activity. We found that diaphragm EMG activity shows substantial intra-animal variability over 6 weeks, with coefficient of variation (CV) for different behaviors ~29–42%. Normalization of diaphragm EMG activity to near maximal behaviors (e.g., deep breathing) reduced intra-animal variability over time (CV ~22–29%). Plethysmographic measurements of eupneic ventilation were also stable over 6 weeks (CV ~13% for minute ventilation). Thus, stable and reliable measurements of diaphragm EMG activity can be obtained longitudinally using chronically implanted electrodes by examining multiple motor behaviors. By quantitatively determining the reliability of longitudinal diaphragm EMG analyses, we provide an important tool for evaluating the progression of diseases or injuries that impair ventilation. PMID:21414423

  9. The Feldenkrais Method: a dynamic approach to changing motor behavior.

    PubMed

    Buchanan, P A; Ulrich, B D

    2001-12-01

    This tutorial describes the Feldenkrais Method and points to parallels with a dynamic systems theory (DST) approach to motor behavior Feldenkrais is an educational system designed to use movement and perception to foster individualized improvement in function. Moshe Feldenkrais, its originator, believed his method enhanced people's ability to discover flexible and adaptable behavior and that behaviors are self-organized. Similarly, DST explains that a human-environment system is continually adapting to changing conditions and assembling behaviors accordingly. Despite little research, Feldenkrais is being used with people of widely ranging ages and abilities in varied settings. We propose that DSTprovides an integrated foundation for research on the Feldenkrais Method, suggest research questions, and encourage researchers to test the fundamental tenets of Feldenkrais. PMID:11770781

  10. Repetitive motor behavior: further characterization of development and temporal dynamics.

    PubMed

    Muehlmann, Amber M; Bliznyuk, Nikolay; Duerr, Isaac; Lewis, Mark H

    2015-03-01

    Repetitive behaviors are diagnostic for autism spectrum disorders, common in related neurodevelopmental disorders, and normative in typical development. In order to identify factors that mediate repetitive behavior development, it is necessary to characterize the expression of these behaviors from an early age. Extending previous findings, we characterized further the ontogeny of stereotyped motor behavior both in terms of frequency and temporal organization in deer mice. A three group trajectory model provided a good fit to the frequencies of stereotyped behavior across eight developmental time points. Group based trajectory analysis using a measure of temporal organization of stereotyped behavior also resulted in a three group solution. Additionally, as the frequency of stereotyped behavior increased with age, the temporal distribution of stereotyped responses became increasingly regular or organized indicating a strong association between these measures. Classification tree and principal components analysis showed that accurate classification of trajectory group could be done with fewer observations. This ability to identify trajectory group membership earlier in development allows for examination of a wide range of variables, both experiential and biological, to determine their impact on altering the expected trajectory of repetitive behavior across development. Such studies would have important implications for treatment efforts in neurodevelopmental disorders such as autism. PMID:25631623

  11. Olfaction in eating disorders and abnormal eating behavior: a systematic review

    PubMed Central

    Islam, Mohammed A.; Fagundo, Ana B.; Arcelus, Jon; Agüera, Zaida; Jiménez-Murcia, Susana; Fernández-Real, José M.; Tinahones, Francisco J.; de la Torre, Rafael; Botella, Cristina; Frühbeck, Gema; Casanueva, Felipe F.; Menchón, José M.; Fernandez-Aranda, Fernando

    2015-01-01

    The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior. PMID:26483708

  12. Teaching a Course in Abnormal Psychology and Behavior Intervention Skills for Nursing Home Aides.

    ERIC Educational Resources Information Center

    Glenwick, David S.; Slutzsky, Mitchel R.; Garfinkel, Eric

    2001-01-01

    Describes an 11-week course given at a nursing home to nursing home aides that focused on abnormal psychology and behavior intervention skills. Discusses the course goals, class composition, and course description. Addresses the problems and issues encountered with teaching this course to a nontraditional population in an unconventional setting.…

  13. Abnormal Nocturnal Behavior due to Hypoglycemia in a Patient with Type 2 Diabetes.

    PubMed

    Yang, Kwang Ik; Kim, Hyung Ki; Baek, Jeehun; Kim, Doh-Eui; Park, Hyung Kook

    2016-04-01

    Abnormal nocturnal behavior can have many causes, including primary sleep disorder, nocturnal seizures, and underlying medical or neurological disorders. A 79-year-old woman with type 2 diabetes was admitted for evaluation of abnormal nocturnal behavior. Every night at around 04:30 she was observed displaying abnormal behavior including leg shaking, fumbling with bedclothes, crawling around the room with her eyes closed, and non-responsiveness to verbal communication. Polysomnography with 20-channel electroencephalography (EEG) was performed. EEG showed that the posterior dominant rhythm was slower than that observed in the initial EEG, with diffuse theta and delta activities intermixed, and no epileptiform activity. The serum glucose level was 35 mg/dL at that time, and both the EEG findings and clinical symptoms were resolved after an intravenous injection of 50 mL of 50% glucose. These results indicate that nocturnal hypoglycemia should be considered as one of the possible etiologies in patients presenting with abnormal nocturnal behavior. PMID:26943712

  14. Neonatal Stroke Causes Poor Midline Motor Behaviors and Poor Fine and Gross Motor Skills during Early Infancy

    ERIC Educational Resources Information Center

    Chen, Chao-Ying; Lo, Warren D.; Heathcock, Jill C.

    2013-01-01

    Upper extremity movements, midline behaviors, fine, and gross motor skills are frequently impaired in hemiparesis and cerebral palsy. We investigated midline toy exploration and fine and gross motor skills in infants at risk for hemiplegic cerebral palsy. Eight infants with neonatal stroke (NS) and thirteen infants with typical development (TD)…

  15. LRRK2 phosphorylation level correlates with abnormal motor behaviour in an experimental model of levodopa-induced dyskinesias.

    PubMed

    Stanic, Jennifer; Mellone, Manuela; Cirnaru, Maria Daniela; Perez-Carrion, Maria; Zianni, Elisa; Di Luca, Monica; Gardoni, Fabrizio; Piccoli, Giovanni

    2016-01-01

    Levodopa (L-DOPA)-induced dyskinesias (LIDs) represent the major side effect in Parkinson's disease (PD) therapy. Leucine-rich repeat kinase 2 (LRRK2) mutations account for up to 13 % of familial cases of PD. LRRK2 N-terminal domain encompasses several serine residues that undergo phosphorylation influencing LRRK2 function. This work aims at investigating whether LRRK2 phosphorylation/function may be involved in the molecular pathways downstream D1 dopamine receptor leading to LIDs. Here we show that LRRK2 phosphorylation level at serine 935 correlates with LIDs induction and that inhibition of LRRK2 induces a significant increase in the dyskinetic score in L-DOPA treated parkinsonian animals. Our findings support a close link between LRKK2 functional state and L-DOPA-induced abnormal motor behaviour and highlight that LRRK2 phosphorylation level may be implicated in LIDs, calling for novel therapeutic strategies. PMID:27169991

  16. Regulation of motor function and behavior by atypical chemokine receptor 1.

    PubMed

    Schneider, Erich H; Fowler, Stephen C; Lionakis, Michail S; Swamydas, Muthulekha; Holmes, Gibran; Diaz, Vivian; Munasinghe, Jeeva; Peiper, Stephen C; Gao, Ji-Liang; Murphy, Philip M

    2014-09-01

    Atypical Chemokine Receptor 1 (ACKR1), previously known as Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for high selective expression on cerebellar Purkinje neurons. Although ACKR1 ligands activate Purkinje cells in vitro, evidence for ACKR1 regulation of brain function in vivo is lacking. Here we demonstrate that Ackr1 (-/-) mice have markedly impaired balance and ataxia on a rotating rod and increased tremor when injected with harmaline, which induces whole-body tremor by activating Purkinje cells. Ackr1 (-/-) mice also exhibited impaired exploratory behavior, increased anxiety-like behavior and frequent episodes of marked hypoactivity under low-stress conditions. Surprisingly, Ackr1 (+/-) had similar behavioral abnormalities, indicating pronounced haploinsufficiency. The behavioral phenotype of Ackr1 (-/-) mice was the opposite of mouse models of cerebellar degeneration, and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. Together, the results suggest that normal motor function and behavior may partly depend on negative regulation of Purkinje cell activity by Ackr1. PMID:24997773

  17. Assessments of Motor Abnormalities on the Grid-Walking and Foot-Fault Tests From Undernutrition in Wistar Rats.

    PubMed

    Horiquini Barbosa, Everton; Vallim, José Henrique; Lachat, João-José; de Castro, Vera Lucia S S

    2016-01-01

    This study was designed to verify whether different lactation conditions influenced nervous system development. The authors used motor tasks to verify changes in exploratory activity and muscle strength of weaned rats from different litter sizes and evaluated the applicability of the grid-walking test for assessing motor abnormalities caused by undernutrition. Alterations in litter size during the suckling period perturbed the nutritional status of pups, which exhibited body weight differences between the groups. Large-litter (L) pups showed significant delays in achieving developmental milestones and neurological reflexes compared to the small-litter (S) and medium-litter (M) pups. The S, M, and L group pups exhibited similar exploratory responses and muscle strength. In the grid-walking and foot-fault tests, the L group pups traveled shorter distances and, consequently, had less footsteps. However, the percentages of foot faults in the L group were higher than S and M groups. These results reflect delayed maturation of structures responsible for sensorimotor responses, such as the cerebellum, because much cerebellar maturation takes place postnatally. This is the first study to report that early undernutrition in pups resulted in suboptimal performances on the grid-walking and foot-fault tests and that the former test was sensitive to alterations caused by nutritional deficiency. PMID:25923475

  18. 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.

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

    PubMed Central

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

    2010-01-01

    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±2.3years 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. PMID:20615010

  20. Incidence and behavioral correlates of epileptiform abnormalities in autism spectrum disorders.

    PubMed

    Mulligan, Caitlin K; Trauner, Doris A

    2014-02-01

    Autism spectrum disorders (ASD) are associated with an increased incidence of epilepsy and of epileptiform discharges on electroencephalograms. It is unknown whether epileptiform discharges correlate with symptoms of ASD. We completed a retrospective chart review of 101 patients with ASD who had overnight electroencephalograms. We looked for a relationship between epileptiform abnormalities and diagnosis, history of regression, communication skills, and other features associated with ASD. There was a higher incidence of epileptiform activity in children with stereotypies and aggressive behavior. The incidence of epileptiform abnormalities was significantly lower in Asperger's compared with more severe forms of autism. Results suggest that increasing severity of autistic symptoms may be associated with higher likelihood of epileptiform abnormalities. Whether treatment alters outcome is unknown. PMID:23872941

  1. Localization of Motor Neurons and Central Pattern Generators for Motor Patterns Underlying Feeding Behavior in Drosophila Larvae.

    PubMed

    Hückesfeld, Sebastian; Schoofs, Andreas; Schlegel, Philipp; Miroschnikow, Anton; Pankratz, Michael J

    2015-01-01

    Motor systems can be functionally organized into effector organs (muscles and glands), the motor neurons, central pattern generators (CPG) and higher control centers of the brain. Using genetic and electrophysiological methods, we have begun to deconstruct the motor system driving Drosophila larval feeding behavior into its component parts. In this paper, we identify distinct clusters of motor neurons that execute head tilting, mouth hook movements, and pharyngeal pumping during larval feeding. This basic anatomical scaffold enabled the use of calcium-imaging to monitor the neural activity of motor neurons within the central nervous system (CNS) that drive food intake. Simultaneous nerve- and muscle-recordings demonstrate that the motor neurons innervate the cibarial dilator musculature (CDM) ipsi- and contra-laterally. By classical lesion experiments we localize a set of CPGs generating the neuronal pattern underlying feeding movements to the subesophageal zone (SEZ). Lesioning of higher brain centers decelerated all feeding-related motor patterns, whereas lesioning of ventral nerve cord (VNC) only affected the motor rhythm underlying pharyngeal pumping. These findings provide a basis for progressing upstream of the motor neurons to identify higher regulatory components of the feeding motor system. PMID:26252658

  2. Adaptive coding of orofacial and speech actions in motor and somatosensory spaces with and without overt motor behavior.

    PubMed

    Sato, Marc; Vilain, Coriandre; Lamalle, Laurent; Grabski, Krystyna

    2015-02-01

    Studies of speech motor control suggest that articulatory and phonemic goals are defined in multidimensional motor, somatosensory, and auditory spaces. To test whether motor simulation might rely on sensory-motor coding common with those for motor execution, we used a repetition suppression (RS) paradigm while measuring neural activity with sparse sampling fMRI during repeated overt and covert orofacial and speech actions. RS refers to the phenomenon that repeated stimuli or motor acts lead to decreased activity in specific neural populations and are associated with enhanced adaptive learning related to the repeated stimulus attributes. Common suppressed neural responses were observed in motor and posterior parietal regions in the achievement of both repeated overt and covert orofacial and speech actions, including the left premotor cortex and inferior frontal gyrus, the superior parietal cortex and adjacent intraprietal sulcus, and the left IC and the SMA. Interestingly, reduced activity of the auditory cortex was observed during overt but not covert speech production, a finding likely reflecting a motor rather an auditory imagery strategy by the participants. By providing evidence for adaptive changes in premotor and associative somatosensory brain areas, the observed RS suggests online state coding of both orofacial and speech actions in somatosensory and motor spaces with and without motor behavior and sensory feedback. PMID:25203272

  3. Localization of Motor Neurons and Central Pattern Generators for Motor Patterns Underlying Feeding Behavior in Drosophila Larvae

    PubMed Central

    Hückesfeld, Sebastian; Schoofs, Andreas; Schlegel, Philipp; Miroschnikow, Anton; Pankratz, Michael J.

    2015-01-01

    Motor systems can be functionally organized into effector organs (muscles and glands), the motor neurons, central pattern generators (CPG) and higher control centers of the brain. Using genetic and electrophysiological methods, we have begun to deconstruct the motor system driving Drosophila larval feeding behavior into its component parts. In this paper, we identify distinct clusters of motor neurons that execute head tilting, mouth hook movements, and pharyngeal pumping during larval feeding. This basic anatomical scaffold enabled the use of calcium-imaging to monitor the neural activity of motor neurons within the central nervous system (CNS) that drive food intake. Simultaneous nerve- and muscle-recordings demonstrate that the motor neurons innervate the cibarial dilator musculature (CDM) ipsi- and contra-laterally. By classical lesion experiments we localize a set of CPGs generating the neuronal pattern underlying feeding movements to the subesophageal zone (SEZ). Lesioning of higher brain centers decelerated all feeding-related motor patterns, whereas lesioning of ventral nerve cord (VNC) only affected the motor rhythm underlying pharyngeal pumping. These findings provide a basis for progressing upstream of the motor neurons to identify higher regulatory components of the feeding motor system. PMID:26252658

  4. Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs and Laying Hens

    PubMed Central

    Brunberg, Emma I.; Rodenburg, T. Bas; Rydhmer, Lotta; Kjaer, Joergen B.; Jensen, Per; Keeling, Linda J.

    2016-01-01

    Pigs and poultry are by far the most omnivorous of the domesticated farm animals and it is in their nature to be highly explorative. In the barren production environments, this motivation to explore can be expressed as abnormal oral manipulation directed toward pen mates. Tail biting (TB) in pigs and feather pecking (FP) in laying hens are examples of unwanted behaviors that are detrimental to the welfare of the animals. The aim of this review is to draw these two seemingly similar abnormalities together in a common framework, in order to seek underlying mechanisms and principles. Both TB and FP are affected by the physical and social environment, but not all individuals in a group express these behaviors and individual genetic and neurobiological characteristics play an important role. By synthesizing what is known about environmental and individual influences, we suggest a novel possible mechanism, common for pigs and poultry, involving the brain–gut–microbiota axis. PMID:27500137

  5. Cnga2 Knockout Mice Display Alzheimer's-Like Behavior Abnormities and Pathological Changes.

    PubMed

    Xie, Ao-Ji; Liu, En-Jie; Huang, He-Zhou; Hu, Yu; Li, Ke; Lu, Youming; Wang, Jian-Zhi; Zhu, Ling-Qiang

    2016-09-01

    Olfactory dysfunction is recognized as a potential risk factor for Alzheimer's disease (AD). We have reported previously that olfactory deprivation by olfactory bulbectomy (OBX) induced Alzheimer's-like pathological changes and behavioral abnormalities. However, the acute OBX model undergoes surgical-induced brain parenchyma loss and unexpected massive hemorrhage so that it cannot fully mimic the progressive olfactory loss and neurodegeneration in AD. Here, we employed the mice loss of cyclic nucleotide-gated channel alpha 2 (Cnga2) which is critical for olfactory sensory transduction, to investigate the role of olfactory dysfunction in AD pathological process. We found that impaired learning and memory abilities, loss of dendrite spines, as well as decrement of synaptic proteins were displayed in Cnga2 knockout mice. Moreover, Aβ overproduction, tau hyperphosphorylation, and somatodendritic translocation were also found in Cnga2 knockout mice. Our findings suggest that progressive olfactory loss leads to Alzheimer's-like behavior abnormities and pathological changes. PMID:26377105

  6. Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs and Laying Hens.

    PubMed

    Brunberg, Emma I; Rodenburg, T Bas; Rydhmer, Lotta; Kjaer, Joergen B; Jensen, Per; Keeling, Linda J

    2016-01-01

    Pigs and poultry are by far the most omnivorous of the domesticated farm animals and it is in their nature to be highly explorative. In the barren production environments, this motivation to explore can be expressed as abnormal oral manipulation directed toward pen mates. Tail biting (TB) in pigs and feather pecking (FP) in laying hens are examples of unwanted behaviors that are detrimental to the welfare of the animals. The aim of this review is to draw these two seemingly similar abnormalities together in a common framework, in order to seek underlying mechanisms and principles. Both TB and FP are affected by the physical and social environment, but not all individuals in a group express these behaviors and individual genetic and neurobiological characteristics play an important role. By synthesizing what is known about environmental and individual influences, we suggest a novel possible mechanism, common for pigs and poultry, involving the brain-gut-microbiota axis. PMID:27500137

  7. Trained, generalized, and collateral behavior changes of preschool children receiving gross-motor skills training.

    PubMed

    Kirby, K C; Holborn, S W

    1986-01-01

    Three preschool children participated in a behavioral training program to improve their gross-motor skills. Ten target behaviors were measured in the training setting to assess direct effects of the program. Generalization probes for two gross-motor behaviors, one fine-motor skill, and two social behaviors were conducted in other settings. Results indicated that the training program improved the gross-motor skills trained and that improvements sometimes generalized to other settings. Contrary to suggestions in educational literature, the gross-motor training program did not produce changes in fine-motor skills or social behaviors. Implications for educators and for the development of the technology of generalization are outlined. PMID:3771421

  8. Motor Behavior: From Telegraph Keys and Twins to Linear Slides and Stepping

    ERIC Educational Resources Information Center

    Thomas, Jerry R.

    2006-01-01

    Motor behavior is a significant area of scholarship with 64 Fellows from the American Academy of Kinesiology and Physical Education engaged in that work since 1930. This paper provides a brief overview of the history of research in motor development and motor control/learning, particularly noting the contributions to scholarship of Academy…

  9. Studies of planning behavior of aircraft pilots in normal, abnormal and emergency situations

    NASA Technical Reports Server (NTRS)

    Johannsen, G.; Rouse, W. B.; Hillmann, K.

    1981-01-01

    A methodology for the study of planning is presented and the results of applying the methodology within two experimental investigations of planning behavior of aircraft pilots in normal, abnormal, and emergency situations are discussed. Beyond showing that the methodology yields consistent results, these experiments also lead to concepts in terms of a dichotomy between event driven and time driven planning, subtle effects of automation on planning, and the relationship of planning to workload and flight performance.

  10. Mechanism of Cooperative Behavior in Systems of Slow and Fast Molecular Motors

    PubMed Central

    Larson, Adam G.; Landahl, Eric C.; Rice, Sarah E.

    2009-01-01

    Summary Two recent theoretical advances have described cargo transport by multiple identical motors and by multiple oppositely directed, but otherwise identical motors [1, 2]. Here we combine a similar theoretical approach with a simple experiment to describe the behavior of a system comprised of slow and fast molecular motors having the same directionality. We observed the movement of microtubules by mixtures of slow and fast kinesin motors attached to a glass coverslip in a classic sliding filament assay. The motors are identical, except that the slow ones contain five point mutations that collectively reduce their velocity ∼15-fold without compromising maximal ATPase activity. Our results indicate that a small fraction of fast motors are able to accelerate the dissociation of slow motors from microtubules. Because of this, a sharp, highly cooperative transition occurs from slow to fast microtubule movement as the relative number of fast motors in the assay is increased. Microtubules move at half-maximal velocity when only 15% of the motors in the assay are fast. Our model indicates that this behavior depends primarily on the relative motor velocities and the asymmetry between their forward and backward dissociation forces. It weakly depends on the number of motors and their processivity. We predict that movement of cargoes bound to two types of motors having very different velocities will be dominated by one or the other motor. Therefore, cargoes can potentially undergo abrupt changes in movement in response to regulatory mechanisms acting on only a small fraction of motors. PMID:19506764

  11. Brain gene expression differences are associated with abnormal tail biting behavior in pigs.

    PubMed

    Brunberg, E; Jensen, P; Isaksson, A; Keeling, L J

    2013-03-01

    Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P < 0.05) when tail biters were compared with neutral pigs, 130 when comparing receiver pigs with neutrals, and two when tail biters were compared with receivers. In the prefrontal cortex, seven transcripts were differently expressed in tail biters when compared with neutrals, seven in receivers vs. neutrals and none in the tail biters vs. receivers. In total, 19 genes showed a different expression pattern in neutral pigs when compared with both performers and receivers. This implies that the functions of these may provide knowledge about why the neutral pigs are not involved in tail biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior. PMID:23146156

  12. Mice lacking the Parkinson's related GPR37/PAEL receptor show non-motor behavioral phenotypes: age and gender effect.

    PubMed

    Mandillo, S; Golini, E; Marazziti, D; Di Pietro, C; Matteoni, R; Tocchini-Valentini, G P

    2013-06-01

    Non-motor symptoms in Parkinson's disease (PD) have been often described at different stages of the disease but they are poorly understood. We observed specific phenotypes related to these symptoms in mice lacking the PD-associated GPR37/PAEL receptor. GPR37 is an orphan G-protein-coupled receptor highly expressed in the mammalian central nervous system. It is a substrate of parkin and it is involved in the pathogenesis of PD. GPR37 interacts with the dopamine transporter (DAT), modulating nigro-striatal dopaminergic signaling and behavioral responses to amphetamine and cocaine. GPR37 knockout (KO) mice are resistant to MPTP and exhibit several motor behavioral abnormalities related to altered dopaminergic system function. To evaluate non-motor behavioral domains, adult and aged, male and female GPR37 KO mice and their wild-type (WT) littermates were analyzed in a series of cross-sectional studies. Aged GPR37 KO female mice showed mild improvements in olfactory function, while anxiety and depression-like behaviors appeared to be significantly increased. A reduction of the startle response to acoustic stimuli was observed only in adult GPR37 KO mice of both genders. Furthermore, HPLC analysis of major neurotransmitter levels revealed gender differences in the striatum, hippocampus and olfactory bulb of mutant mice. The absence of GPR37 receptor could have a neuroprotective effect in an age and gender-dependent manner, and the study of this receptor could be valuable in the search for novel therapeutic targets. PMID:23574697

  13. Consequences of long-term treatment with agomelatine on depressive-like behavior and neurobiological abnormalities in pinealectomized rats.

    PubMed

    Tchekalarova, Jana; Nenchovska, Zlatina; Atanasova, Dimitrina; Atanasova, Milena; Kortenska, Lidia; Stefanova, Miroslava; Alova, Liana; Lazarov, Nikolai

    2016-04-01

    Previous data have shown that the rat model of melatonin deficit can cause a number of neurobiological aberrations. The aim of the present study was to determine whether the antidepressant drug agomelatine, a MT1/MT2 melatoninergic receptor agonist/5-HT2C receptor antagonist is able to prevent some of the behavioral, biochemical and cellular abnormalities induced by pinealectomy. The injection of agomelatine (40 mg/kg, i.p. for 5 weeks)/vehicle started after pinealectomy/sham procedure in Wistar rats. Animals were tested in different behavioral tests for anxiety and depression during the period of agomelatine treatment (chronic effect) and two months later (plastic effect). The effect of agomelatine on KCl-evoked serotonin (5-HT) release from the hippocampus, the activity of the hypothalamic-pituitary-adrenal (HPA) axis and neuronal loss in pinealectomized rats were assessed. Our results showed that agomelatine not only did not prevent the disturbed emotional arousal/anxiety behavior in pinealectomized rats during the treatment but the enhanced motor activity and decreased anxiety state was still observed two months after the discontinuation of treatment. However, the drug corrected a depressive-like behavior (chronic and plastic effect), alleviated the enhanced KCl-evoked 5-HT release in the hippocampus, recovered the suppressed negative feedback inhibition of HPA axis and exerted a neuroprotection in pinealectomized rats. Our findings suggest that pinealectomy can model melancholic depression disorder while the antidepressant action of agomelatine is associated with a correction of 5-HT release in the hippocampus, dysregulated HPA system and neuroprotection in limbic structures. PMID:26779670

  14. Motor planning modulates sensory-motor control of collision avoidance behavior in the bullfrog, Rana catesbeiana

    PubMed Central

    Nakagawa, Hideki; Nishida, Yuuya

    2012-01-01

    Summary In this study, we examined the collision avoidance behavior of the frog, Rana catesbeiana to an approaching object in the upper visual field. The angular velocity of the frog's escape turn showed a significant positive correlation with the turn angle (r2 = 0.5741, P<0.05). A similar mechanism of velocity control has been known in head movements of the owl and in human saccades. By analogy, this suggests that the frog planned its escape velocity in advance of executing the turn, to make the duration of the escape behavior relatively constant. For escape turns less than 60°, the positive correlation was very strong (r2 = 0.7097, P<0.05). Thus, the frog controlled the angular velocity of small escape turns very accurately and completed the behavior within a constant time. On the other hand, for escape turns greater than 60°, the same correlation was not significant (r2 = 0.065, P>0.05). Thus, the frog was not able to control the velocity of the large escape turns accurately and did not complete the behavior within a constant time. In the latter case, there was a small but significant positive correlation between the threshold angular size and the angular velocity (r2 = 0.1459, P<0.05). This suggests that the threshold is controlled to compensate for the insufficient escape velocity achieved during large turn angles, and could explain a significant negative correlation between the turn angle and the threshold angular size (r2 = 0.1145, P<0.05). Thus, it is likely that the threshold angular size is also controlled by the turn angle and is modulated by motor planning. PMID:23213389

  15. Studies of planning behavior of aircraft pilots in normal, abnormal, and emergency situations

    NASA Technical Reports Server (NTRS)

    Johannsen, G.; Rouse, W. B.; Hillmann, K.

    1981-01-01

    A methodology for the study of human planning behavior in complex dynamic systems is presented and applied to the study of aircraft pilot behavior in normal, abnormal and emergency situations. The method measures the depth of planning, that is the level of detail employed with respect to a specific task, according to responses to a verbal questionnaire, and compares planning depth with variables relating to time, task criticality and the probability of increased task difficulty. In two series of experiments, depth of planning was measured on a five- or ten-point scale during various phases of flight in a HFB-320 simulator under normal flight conditions, abnormal scenarios involving temporary runway closure due to snow removal or temporary CAT-III conditions due to a dense fog, and emergency scenarios involving engine shut-down or hydraulic pressure loss. Results reveal a dichotomy between event-driven and time-driven planning, different effects of automation in abnormal and emergency scenarios and a low correlation between depth of planning and workload or flight performance.

  16. Abnormal animal behavior prior to the Vrancea (Romania) major subcrustal earthquakes

    NASA Astrophysics Data System (ADS)

    Constantin, Angela; Pantea, Aurelian

    2013-04-01

    The goal of this paper is to present some observations about abnormal animal behavior prior and during of some Romanian subcrustal earthquakes. The major Vrancea earthquakes of 4 March 1977 (Mw = 7.4, Imax = IX-X MSK), 30 August 1986 (Mw = 7.1, Io = VIII-IX MSK) and 30 May 1990 (Mw = 6.9, Io = VIII MSK), were preceded by extensive occurrences of anomalous animal behavior. These data were collected immediately after the earthquakes from the areas affected by these. Some species of animals became excited, nervous and panicked before and during the earthquakes, such as: dogs (barking and running in panic), cats, snakes, mice and rats (came into the houses and have lost their fear), birds (hens, geese, parrots), horses, fishes etc. These strange manifestations of the animals were observed on the entire territory of country, especially in the extra-Carpathian area. This unusual behavior was noticed within a few hours to days before the seismic events, but for the most of cases the time of occurrence was within two hours of the quakes. We can hope that maybe one day the abnormal animal behavior will be used as a reliable seismic precursor for the intermediate depth earthquakes.

  17. Antisocial behavior, psychopathic features and abnormalities in reward and punishment processing in youth.

    PubMed

    Byrd, Amy L; Loeber, Rolf; Pardini, Dustin A

    2014-06-01

    A better understanding of what leads youth to initially engage in antisocial behavior (ASB) and more importantly persist with such behaviors into adulthood has significant implications for prevention and intervention efforts. A considerable number of studies using behavioral and neuroimaging techniques have investigated abnormalities in reward and punishment processing as potential causal mechanisms underlying ASB. However, this literature has yet to be critically evaluated, and there are no comprehensive reviews that systematically examine and synthesize these findings. The goal of the present review is twofold. The first aim is to examine the extent to which youth with ASB are characterized by abnormalities in (1) reward processing; (2) punishment processing; or (3) both reward and punishment processing. The second aim is to evaluate whether aberrant reward and/or punishment processing is specific to or most pronounced in a subgroup of antisocial youth with psychopathic features. Studies utilizing behavioral methods are first reviewed, followed by studies using functional magnetic resonance imaging. An integration of theory and research across multiple levels of analysis is presented in order to provide a more comprehensive understanding of reward and punishment processing in antisocial youth. Findings are discussed in terms of developmental and contextual considerations, proposed future directions and implications for intervention. PMID:24357109

  18. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles.

    PubMed

    Hunt, W A; Joseph, J A; Rabin, B M

    1989-01-01

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied. PMID:11537313

  19. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    NASA Astrophysics Data System (ADS)

    Hunt, Walter A.; Joseph, James A.; Rabin, Bernard M.

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  20. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    SciTech Connect

    Hunt, W.A.; Joseph, J.A.; Rabin, B.M.

    1989-01-01

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  1. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A

    SciTech Connect

    Brunner, H.G. ); Nelen, M.; Ropers, H.H.; van Oost, B.A. )

    1993-10-22

    Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.

  2. Who Should Report Abnormal Behavior at Preschool Age? The Case of Behavioral Inhibition

    ERIC Educational Resources Information Center

    Ballespi, Sergi; Jane, Ma Claustre; Riba, Ma Dolors

    2012-01-01

    Children who are behaviorally "inhibited"--a condition at the extreme of the behavioral inhibition dimension--experience distress in uncertain social situations. Although parents and teachers are in the best position to detect this condition, they rarely agree. This study aims to analyze the agreement between parents and teachers and to examine…

  3. Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption.

    PubMed

    Pedron, Solène; Monnin, Julie; Haffen, Emmanuel; Sechter, Daniel; Van Waes, Vincent

    2014-03-01

    Successful available treatments to quit smoking remain scarce. Recently, the potential of transcranial direct current stimulation (tDCS) as a tool to reduce craving for nicotine has gained interest. However, there is no documented animal model to assess the neurobiological mechanisms of tDCS on addiction-related behaviors. To address this topic, we have developed a model of repeated tDCS in mice and used it to validate its effectiveness in relieving nicotine addiction. Anodal repeated tDCS was applied over the frontal cortex of Swiss female mice. The stimulation electrode (anode) was fixed directly onto the cranium, and the reference electrode was placed onto the ventral thorax. A 2 × 20 min/day stimulation paradigm for five consecutive days was used (0.2 mA). In the first study, we screened for behaviors altered by the stimulation. Second, we tested whether tDCS could alleviate abnormal behaviors associated with abstinence from nicotine consumption. In naive animals, repeated tDCS had antidepressant-like properties 3 weeks after the last stimulation, improved working memory, and decreased conditioned place preference for nicotine without affecting locomotor activity and anxiety-related behavior. Importantly, abnormal behaviors associated with chronic nicotine exposure (ie, depression-like behavior, increase in nicotine-induced place preference) were normalized by repeated tDCS. Our data show for the first time in an animal model that repeated tDCS is a promising, non-expensive clinical tool that could be used to reduce smoking craving and facilitate smoking cessation. Our animal model will be useful to investigate the mechanisms underlying the effects of tDCS on addiction and other psychiatric disorders. PMID:24154668

  4. A Huntingtin-based peptide inhibitor of caspase-6 provides protection from mutant Huntingtin-induced motor and behavioral deficits

    PubMed Central

    Aharony, Israel; Ehrnhoefer, Dagmar E.; Shruster, Adi; Qiu, Xiaofan; Franciosi, Sonia; Hayden, Michael R.; Offen, Daniel

    2015-01-01

    Over the past decade, increasing evidence has implied a significant connection between caspase-6 activity and the pathogenesis of Huntington's disease (HD). Consequently, inhibiting caspase-6 activity was suggested as a promising therapeutic strategy to reduce mutant Huntingtin toxicity, and to provide protection from mutant Huntingtin-induced motor and behavioral deficits. Here, we describe a novel caspase-6 inhibitor peptide based on the huntingtin caspase-6 cleavage site, fused with a cell-penetrating sequence. The peptide reduces mutant Huntingtin proteolysis by caspase-6, and protects cells from mutant Huntingtin toxicity. Continuous subcutaneous administration of the peptide protected pre-symptomatic BACHD mice from motor deficits and behavioral abnormalities. Moreover, administration of the peptide in an advanced disease state resulted in the partial recovery of motor performance, and an alleviation of depression-related behavior and cognitive deficits. Our findings reveal the potential of substrate-based caspase inhibition as a therapeutic strategy, and present a promising agent for the treatment of HD. PMID:25616965

  5. Monitoring tectal neuronal activities and motor behavior in zebrafish larvae.

    PubMed

    Sumbre, Germán; Poo, Mu-Ming

    2013-09-01

    To understand how visuomotor behaviors are controlled by the nervous system, it is necessary to monitor the activity of large populations of neurons with single-cell resolution over a large area of the brain in a relatively simple, behaving organism. The zebrafish larva, a small lower vertebrate with transparent skin, serves as an excellent model for this purpose. Immediately after the larva hatches, it needs to catch prey and avoid predators. This strong evolutionary pressure leads to the rapid development of functional sensory systems, particularly vision. By 5 d postfertilization (dpf), tectal cells show distinct visually evoked patterns of activation, and the larvae are able to perform a variety of visuomotor behaviors. During the early larval stage, zebrafish breathe mainly through the skin and can be restrained under the microscope using a drop of low-melting-point agarose, without the use of anesthetics. Moreover, the transparency of the skin, the small diameter of the neurons (4-5 µm), and the high-neuronal density enable the use of in vivo noninvasive imaging techniques to monitor neuronal activities of up to ∼500 cells within the central nervous system, still with single-cell resolution. This article describes a method for simultaneously monitoring spontaneous and visually evoked activities of large populations of neurons in the optic tectum of the zebrafish larva, using a synthetic calcium dye (Oregon Green BAPTA-1 AM) and a conventional confocal or two-photon scanning fluorescence microscope, together with a method for measuring the tail motor behavior of the head-immobilized zebrafish larva. PMID:24003199

  6. Dopamine-Dependent Compensation Maintains Motor Behavior in Mice with Developmental Ablation of Dopaminergic Neurons

    PubMed Central

    DeMaro, Joseph A.; Knoten, Amanda; Hoshi, Masato; Pehek, Elizabeth; Johnson, Eugene M.; Gereau, Robert W.

    2013-01-01

    The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and consequent depletion of striatal dopamine are known to underlie the motor deficits observed in Parkinson's disease (PD). Adaptive changes in dopaminergic terminals and in postsynaptic striatal neurons can compensate for significant losses of striatal dopamine, resulting in preservation of motor behavior. In addition, compensatory changes independent of striatal dopamine have been proposed based on PD therapies that modulate nondopaminergic circuits within the basal ganglia. We used a genetic strategy to selectively destroy dopaminergic neurons in mice during development to determine the necessity of these neurons for the maintenance of normal motor behavior in adult and aged mice. We find that loss of 90% of SNc dopaminergic neurons and consequent depletion of >95% of striatal dopamine does not result in changes in motor behavior in young-adult or aged mice as evaluated by an extensive array of motor behavior tests. Treatment of aged mutant mice with the dopamine receptor antagonist haloperidol precipitated motor behavior deficits in aged mutant mice, indicating that <5% of striatal dopamine is sufficient to maintain motor function in these mice. We also found that mutant mice exhibit an exaggerated response to l-DOPA compared with control mice, suggesting that preservation of motor function involves sensitization of striatal dopamine receptors. Our results indicate that congenital loss of dopaminergic neurons induces remarkable adaptions in the nigrostriatal system where limited amounts of dopamine in the dorsal striatum can maintain normal motor function. PMID:24155314

  7. A survey of abnormal repetitive behaviors in North American river otters housed in zoos.

    PubMed

    Morabito, Paige; Bashaw, Meredith J

    2012-01-01

    Stereotypic behaviors, indicating poor welfare and studied in a variety of species (especially carnivores), appear related to characteristics of current and past environments. Although North American river otters (Lontra canadensis) often develop abnormal, repetitive, possibly stereotypic behaviors, no published reports describe otter housing and management or characterize how these variables relate to abnormal repetitive behavior (ARB) occurrence. The first author developed surveys to gather data on housing, individual history, management, and the prevalence of ARBs in otters housed in facilities accredited by the Association of Zoos and Aquariums. Consistent with anecdotal evidence that otters are prone to ARBs, 46% of river otters in the study exhibit them. ARBs were mostly locomotor and often preceded feeding. Exhibits where otters were fed and trained housed a greater percentage of nonhuman animals with ARBs. This study supports the Tarou, Bloomsmith, and Maple (2005) report that more hands-on management is associated with higher levels of ARBs because management efforts are only for animals with ARBs. Escape motivation, breeding season, feeding cues, and ability to forage may affect ARBs in river otters and should be investigated. PMID:22742198

  8. Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors.

    PubMed

    Erbel-Sieler, Claudia; Dudley, Carol; Zhou, Yudong; Wu, Xinle; Estill, Sandi Jo; Han, Tina; Diaz-Arrastia, Ramon; Brunskill, Eric W; Potter, S Steven; McKnight, Steven L

    2004-09-14

    Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavior at weaning and increased locomotor activity. Immunohistochemical staining assays showed that the NPAS1 and NPAS3 proteins are expressed in inhibitory interneurons and that the viability and anatomical distribution of these neurons are unaffected by the absence of either transcription factor. Adult brain tissues from NPAS3- and NPAS1/NPAS3-deficient mice exhibited a distinct reduction in reelin, a large, secreted protein whose expression has been reported to be attenuated in the postmortem brain tissue of patients with schizophrenia. These observations raise the possibility that a regulatory program controlled in inhibitory interneurons by the NPAS1 and NPAS3 transcription factors may be either substantively or tangentially relevant to psychosis. PMID:15347806

  9. Elevated PEM (Phasic Electromyographic Metric) Rates Identify Rapid Eye Movement Behavior Disorder Patients on Nights Without Behavioral Abnormalities

    PubMed Central

    Bliwise, Donald L.; Rye, David B.

    2008-01-01

    Objective: To determine the validity of the phasic electromyographic metric (PEM) to differentiate patients with a history suggestive of rapid eye movement behavior disorder (REMBD) on laboratory nights without overt dream-enactment behavior. Methods: PEM was quantified as the % of 2.5-sec intervals with phasic muscle activity of 100-msec duration with an amplitude of at least 4 times background activity in 11 patients and 31 elderly controls. Data were derived from both REM and NREM sleep from 5 muscle groups (mentalis, left/right anterior tibialis, left/right brachioradialis). Results: Relative to controls, REMBD patients had significantly higher levels of PEM activity in all recordings. The largest differences occurred during REM sleep for the mentalis and brachioradialis channels. Similar results were obtained by limiting quantification of PEM to the final REM period of the night and could be accomplished by individuals with no previous familiarity with polysomnography. Discussion: PEM may be a useful metric to characterize the REM related phasic muscle activity on patients with a history of REMBD, even when no overt dream-enactment behaviors are detected on a laboratory night. Citation: Bliwise DL; Rye DB. Elevated PEM (phasic electromyographic metric) rates identify rapid eye movement behavior disorder patients on nights without behavioral abnormalities. SLEEP 2008;31(6):853–857. PMID:18548830

  10. Mandibular Motor Control During the Early Development of Speech and Nonspeech Behaviors

    PubMed Central

    Steeve, Roger W.; Moore, Christopher A.

    2014-01-01

    Purpose The mandible is often portrayed as a primary structure of early babble production, but empiricists still need to specify (a) how mandibular motor control and kinematics vary among different types of multisyllabic babble, (b) whether chewing or jaw oscillation relies on a coordinative infrastructure that can be exploited for early types of multisyllables, and (c) whether the organization of motor control and associated kinematics varies across the nonspeech behaviors that are candidate motor stereotypies for speech. Method Electromyographic signals were obtained from mandibular muscle groups, and associated kinematics were measured longitudinally from a typically developing infant from 9 to 22 months during jaw oscillation, chewing, and several types of early multisyllabic babble. Results Measures of early motor control and mandibular kinematics for multisyllabic productions indicated task-dependent changes across syllable types and significant differences across babble and nonspeech behaviors. Differences in motor control were also observed across nonspeech behaviors. Conclusions Motor control for babble appears to be influenced by the balanced interaction between developing motor and linguistic systems, such that variation in linguistic complexity systematically evinces changes in motor organization apparently to meet these demands. This same effect was noted among chewing and jaw oscillation; task-dependent changes in mandibular control were noted across behaviors. PMID:19717649

  11. A Model for the Transfer of Perceptual-Motor Skill Learning in Human Behaviors

    ERIC Educational Resources Information Center

    Rosalie, Simon M.; Muller, Sean

    2012-01-01

    This paper presents a preliminary model that outlines the mechanisms underlying the transfer of perceptual-motor skill learning in sport and everyday tasks. Perceptual-motor behavior is motivated by performance demands and evolves over time to increase the probability of success through adaptation. Performance demands at the time of an event…

  12. Genetic damage and the expression of behavioral abnormalities in the progeny of male rats exposed to ionizing radiation

    SciTech Connect

    Lowery, M.C.

    1987-01-01

    To determine the possible genetic nature of behavioral anomalies, an identifiable genetic endpoint, inherited chromosome translocations in the offspring, was selected to evaluate the relationship to behavior. Young adult male Fischer 344 rats were exposed to 50-300 rads of ionizing radiation. Two weeks following their irradiation, the males were mated with four virgin females for one week. During this time, fertilizing sperm were derived from post-meiotic spermatids, the stage of the spermatogenic cycle most sensitive to the mutagenic effects of radiation. Behavioral analyses of the resulting 390 offspring consisted of both motor reflex and motor coordination measurements as well as learning and retention parameters. Significant differences in performance were seen in several of the motor reflex measurements in progeny of males exposed to some of the higher doses of irradiation. A similar phenomenon was observed in the performance of a single learned behavior.

  13. Relationship between BDNF expression in major striatal afferents, striatum morphology and motor behavior in the R6/2 mouse model of Huntington's disease.

    PubMed

    Samadi, P; Boutet, A; Rymar, V V; Rawal, K; Maheux, J; Kvann, J-C; Tomaszewski, M; Beaubien, F; Cloutier, J F; Levesque, D; Sadikot, A F

    2013-02-01

    Patients with Huntington's disease (HD) and transgenic mouse models of HD show neuronal loss in the striatum as a major feature, which contributes to cognitive and motor manifestations. Reduced expression of the neurotrophin brain-derived neurotrophic factor (BDNF) in striatal afferents may play a role in neuronal loss. How progressive loss of BDNF expression in different cortical or subcortical afferents contributes to striatal atrophy and behavioral dysfunction in HD is not known, and may best be determined in animal models. We compared age-dependent alterations of BDNF mRNA expression in major striatal afferents from the cerebral cortex, thalamus and midbrain in the R6/2 transgenic mouse model of HD. Corresponding changes in striatal morphology were quantified using unbiased stereology. Changes in motor behavior were measured using an open field, grip strength monitor, limb clasping and a rotarod apparatus. BDNF expression in cortical limbic and midbrain striatal afferents is reduced by age 4 weeks, prior to onset of motor abnormalities. BDNF expression in motor cortex and thalamic afferents is reduced by 6 weeks, coinciding with early motor dysfunction and reduced striatum volume. BDNF loss in afferents progresses until death at 13-15 weeks, correlating with progressive striatal neuronal loss and motor abnormalities. Mutant huntingtin protein expression in R6/2 mice results in progressive loss of BDNF in both cortical and subcortical striatal afferents. BDNF loss in limbic and dopaminergic striatal inputs may contribute to cognitive/psychiatric dysfunction in HD. Subsequent BDNF loss in cortical motor and thalamic afferents may accelerate striatal degeneration, resulting in progressive involuntary movements. PMID:23006318

  14. Prenatal rapamycin results in early and late behavioral abnormalities in wildtype C57Bl/6 mice

    PubMed Central

    Tsai, Peter T.; Green-Colozzi, Emily; Goto, June; Anderl, Stefanie; Kwiatkowski, David; Sahin, Mustafa

    2012-01-01

    Mammalian target of rapamycin (mTOR) signaling has been shown to be deregulated in a number of genetic, neurodevelopmental disorders including Tuberous Sclerosis Complex, Neurofibromatosis, Fragile X, and Rett syndromes. As a result, mTOR inhibitors, such as rapamycin and its analogs, offer potential therapeutic avenues for these disorders. Some of these disorders – such as Tuberous Sclerosis Complex – can be diagnosed prenatally. Thus, prenatal administration of these inhibitors could potentially prevent the development of the devastating symptoms associated with these disorders. To assess the possible detrimental effects of prenatal rapamycin treatment, we evaluated both early and late behavioral effects of a single rapamycin treatment at embryonic day 16.5 in wildtype C57Bl/6 mice. This treatment adversely impacted early developmental milestones as well as motor function in adult animals. Rapamycin also resulted in anxiety-like behaviors during both early development and adulthood but did not affect adult social behaviors. Together, these results indicate that a single, prenatal rapamycin treatment not only adversely affects early postnatal development but also results in long lasting negative effects, persisting into adulthood. These findings are of importance in considering prenatal administration of rapamycin and related drugs in the treatment of patients with neurogenetic, neurodevelopmental disorders. PMID:23229624

  15. Reproductive and behavioral abnormalities in tree swallows with high levels of PCB contamination

    SciTech Connect

    McCarty, J.; Secord, A.; Tillitt, D.

    1995-12-31

    Tree Swallows (Tachycineta bicolor) breeding along the Hudson River forage extensively on PCB contaminated insects that emerge from the river. The authors studied the reproductive ecology and behavior of tree swallows breeding at several sites along the Hudson River. These sites vary in the severity of PCB contamination. PCB levels in both eggs and chicks were found to be among the highest ever reported in this species, with concentrations comparable to those found in aquatic organisms in the Hudson River. In 1994 reproductive success at PCB contaminated sites was significantly impaired, relative to other sites in New York. Reduced reproductive success was largely attributed to high levels of nest abandonment during incubation and reduced hatchability of eggs. Growth and development of nestlings was not significantly impaired. Abnormal nest building behavior was also noted in 1994, and this was studied in detail in 1995. Nests from contaminated areas are significantly smaller than those at a nearby reference site and at other sites in New York. The authors suggest that the reduced reproductive outputs at these sites are, in large part, a result of effects on the behavior of incubating females. The population-level implications of these patterns are unknown.

  16. The relationship of motor skills and adaptive behavior skills in young children with autism spectrum disorders

    PubMed Central

    MacDonald, Megan; Lord, Catherine; Ulrich, Dale

    2015-01-01

    Objective To determine the relationship of motor skills and the core behaviors of young children with autism, social affective skills and repetitive behaviors, as indicated through the calibrated autism severity scores. Design The univariate GLM tested the relationship of gross and fine motor skills measured by the gross motor scale and the fine motor scale of the MSEL with autism symptomology as measured by calibrated autism severity scores. Setting Majority of the data collected took place in an autism clinic. Participants A cohort of 159 young children with ASD (n=110), PDD-NOS (n=26) and non-ASD (developmental delay, n=23) between the ages of 12–33 months were recruited from early intervention studies and clinical referrals. Children with non-ASD (developmental delay) were included in this study to provide a range of scores indicted through calibrated autism severity. Interventions Not applicable. Main Outcome Measures The primary outcome measures in this study were calibrated autism severity scores. Results Fine motor skills and gross motor skills significantly predicted calibrated autism severity (p < 0.01). Children with weaker motor skills displayed higher levels of calibrated autism severity. Conclusions The fine and gross motor skills are significantly related to autism symptomology. There is more to focus on and new avenues to explore in the realm of discovering how to implement early intervention and rehabilitation for young children with autism and motor skills need to be a part of the discussion. PMID:25774214

  17. Variables influencing the origins of diverse abnormal behaviors in a large sample of captive chimpanzees (Pan troglodytes).

    PubMed

    Nash, L T; Fritz, J; Alford, P A; Brent, L

    1999-01-01

    The developmental origin of abnormal behaviors is generally associated with early rearing environments that lack sufficient physical and sensory stimulation. However, other factors should also be considered. A large sample of captive chimpanzees (128 males and 140 females) was surveyed for the presence or absence of 18 abnormal behaviors. Origin variables included the subject's source (zoo, pet, performer, or laboratory), rearing (mother- or hand-reared), and sex. Animals were assessed while held at the Primate Foundation of Arizona, University of Texas M. D. Anderson Cancer Center, or White Sands Research Center. There was a confound among origin variables; more hand-reared animals than expected were from laboratories. Logistic regression tested the relationship of rearing and source, with sex as a secondary predictor variable, to each of the abnormal behaviors. There was no clear association between any abnormal behavior and source. However, for coprophagy, relative to animals from the laboratory, zoo animals tended to show a higher prevalence, while performers tended to show a lower prevalence (when rearing and sex were controlled). Rocking and self-sucking were significantly more likely in hand-reared animals. Coprophagy and depilation of self were significantly more likely in mother-reared animals. When rearing and source were statistically controlled, the only significant sex difference was a higher prevalence of coprophagy in females and a higher prevalence of rocking in males. In a second, smaller sample of 25 males and 33 females from Southwest Foundation for Biomedical Research, no significant sex association was found for coprophagy, urophagy, rocking, or self-depilation. In this second sample, coprophagy was also significantly more likely in mother-reared than hand-reared subjects. The association of some abnormal behaviors with mother-rearing suggests that some form of social learning may be involved in the origin of some of these behavior patterns

  18. Motor and behavioral phenotype in conditional mutants with targeted ablation of cortical D1 dopamine receptor-expressing cells.

    PubMed

    Jiang, Luning; O'Leary, Claire; Kim, Hyun Ah; Parish, Clare L; Massalas, Jim; Waddington, John L; Ehrlich, Michelle E; Schütz, Günter; Gantois, Ilse; Lawrence, Andrew J; Drago, John

    2015-04-01

    D1-dopamine receptors (Drd1a) are highly expressed in the deep layers of the cerebral cortex and the striatum. A number of human diseases such as Huntington disease and schizophrenia are known to have cortical pathology involving dopamine receptor expressing neurons. To illuminate their functional role, we exploited a Cre/Lox molecular paradigm to generate Emx-1(tox) MUT mice, a transgenic line in which cortical Drd1a-expressing pyramidal neurons were selectively ablated. Emx-1(tox) MUT mice displayed prominent forelimb dystonia, hyperkinesia, ataxia on rotarod testing, heightened anxiety-like behavior, and age-dependent abnormalities in a test of social interaction. The latter occurred in the context of normal working memory on testing in the Y-maze and for novel object recognition. Some motor and behavioral abnormalities in Emx-1(tox) MUT mice overlapped with those in CamKIIα(tox) MUT transgenic mice, a line in which both striatal and cortical Drd1a-expressing cells were ablated. Although Emx-1(tox) MUT mice had normal striatal anatomy, both Emx-1(tox) MUT and CamKIIα(tox) MUT mice displayed selective neuronal loss in cortical layers V and VI. This study shows that loss of cortical Drd1a-expressing cells is sufficient to produce deficits in multiple motor and behavioral domains, independent of striatal mechanisms. Primary cortical changes in the D1 dopamine receptor compartment are therefore likely to model a number of core clinical features in disorders such as Huntington disease and schizophrenia. PMID:25684539

  19. Opposing effects of appetitive and aversive cues on go/no-go behavior and motor excitability.

    PubMed

    Chiu, Yu-Chin; Cools, Roshan; Aron, Adam R

    2014-08-01

    Everyday life, as well as psychiatric illness, is replete with examples where appetitive and aversive stimuli hijack the will, leading to maladaptive behavior. Yet the mechanisms underlying this phenomenon are not well understood. Here we investigate how motivational cues influence action tendencies in healthy individuals with a novel paradigm. Behaviorally, we observed that an appetitive cue biased go behavior (making a response), whereas an aversive cue biased no-go behavior (withholding a response). We hypothesized that the origin of this behavioral go/no-go bias occurs at the motor system level. To test this, we used single-pulse TMS as a motor system probe (rather than a disruptive tool) to index motivational biasing. We found that the appetitive cue biased the participants to go more by relatively increasing motor system excitability, and that the aversive cue biased participants to no-go more by relatively decreasing motor system excitability. These results show, first, that maladaptive behaviors arise from motivational cues quickly spilling over into the motor system and biasing behavior even before action selection and, second, that this occurs in opposing directions for appetitive and aversive cues. PMID:24564469

  20. Relationships between problematic behaviors and motor abilities of children with cerebral palsy

    PubMed Central

    Uesugi, Masayuki; Miyamoto, Akira; Nanba, Yosifumi; Otani, Yoshitaka; Takemasa, Seiichi; Hujii, Shun

    2015-01-01

    [Purpose] This study aimed to examine whether motor abilities of children with cerebral palsy are related to their problematic behaviors. [Subjects] The subjects were children with mental retardation who were undergoing physical therapy. [Methods] Twenty-one examiners, 13 physical therapists, and 8 occupational therapists treated and examined the subjects by using the Japanese version of the Aberrant Behavior Checklist. The Japanese version of the Aberrant Behavior Checklist scores were compared between the Gross Motor Function Classification System I to III (12 subjects) and Gross Motor Function Classification System IV and V groups (17 subjects). [Results] Lethargy and stereotypy scores significantly differed between the groups, proving that patients with Gross Motor Function Classification System levels IV and V have more severe problematic behaviors. [Conclusion] In this study, only five types of problematic behaviors, namely irritability, lethargy, stereotypy, hyperactivity, and inappropriate speech, were examined. Despite this limitation, the study clarifies that problematic behaviors of children with cerebral palsy, except lethargy and stereotypy, have little relationship with their motor abilities. PMID:26504335

  1. Response-Specific Effects of Pain Observation on Motor Behavior

    ERIC Educational Resources Information Center

    Morrison, India; Poliakoff, Ellen; Gordon, Lucy; Downing, Paul

    2007-01-01

    How does seeing a painful event happening to someone else influence the observer's own motor system? To address this question, we measured simple reaction times following videos showing noxious or innocuous implements contacting corporeal or noncorporeal objects. Key releases in a go/nogo task were speeded, and key presses slowed, after subjects…

  2. Post-impact behavior of composite solid rocket motor cases

    NASA Technical Reports Server (NTRS)

    Highsmith, Alton L.

    1992-01-01

    In recent years, composite materials have seen increasing use in advanced structural applications because of the significant weight savings they offer when compared to more traditional engineering materials. The higher cost of composites must be offset by the increased performance that results from reduced structural weight if these new materials are to be used effectively. At present, there is considerable interest in fabricating solid rocket motor cases out of composite materials, and capitalizing on the reduced structural weight to increase rocket performance. However, one of the difficulties that arises when composite materials are used is that composites can develop significant amounts of internal damage during low velocity impacts. Such low velocity impacts may be encountered in routine handling of a structural component like a rocket motor case. The ability to assess the reduction in structural integrity of composite motor cases that experience accidental impacts is essential if composite rocket motor cases are to be certified for manned flight. The study described herein was an initial investigation of damage development and reduction of tensile strength in an idealized composite subjected to low velocity impacts.

  3. Effects of Interventions Based in Behavior Analysis on Motor Skill Acquisition: A Meta-Analysis

    ERIC Educational Resources Information Center

    Alstot, Andrew E.; Kang, Minsoo; Alstot, Crystal D.

    2013-01-01

    Techniques based in applied behavior analysis (ABA) have been shown to be useful across a variety of settings to improve numerous behaviors. Specifically within physical activity settings, several studies have examined the effect of interventions based in ABA on a variety of motor skills, but the overall effects of these interventions are unknown.…

  4. The Development of Verbal Control over Motor Behavior: A Replication and Extension of Luria's Findings.

    ERIC Educational Resources Information Center

    Tinsley, Virginia S.; Waters, Harriet Salatas

    1982-01-01

    Two experiments replicate and extend Luria's (1959, 1961) findings on the development of verbal self-regulation during early childhood. Results support Luria's hypothesis that overt verbalizations facilitate control of motor behavior in young children and that language can play an active and integrative role in the development of behavioral and…

  5. Behavioral Prescription Guide. Manual IIb: Motor. Parent/Child Home Stimulation 'The Marshalltown Project.'

    ERIC Educational Resources Information Center

    Keiser, Arlene F.; And Others

    Presented is the Marshalltown Behavioral Prescription Guide for motor development which consists of incremental behavioral objectives and strategies to aid parents in the prescriptive teaching of handicapped and culturally deprived infants and preschool children. The guide is intended for use prior to a weekly home visit resulting in a weekly…

  6. Applying Behavioral Principles to Motor Vehicle Occupant Protection.

    ERIC Educational Resources Information Center

    Sleet, David A.; And Others

    1986-01-01

    Successful programs designed to encourage protective behaviors (e.g., wearing safety belts and using child safety seats) have applied such behavioral principles as a combination of rewards, feedback, guidance, contingency management, and modeling. (Author/DB)

  7. Loss of prion protein leads to age-dependent behavioral abnormalities and changes in cytoskeletal protein expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cellular prion protein (PrPC) is a multifunctional protein, whose exact physiological role remains elusive. Since previous studies indicated a neuroprotective function of PrPC, we investigated whether Prnp knockout mice(Prnp0/0)display age-dependent behavioral abnormalities. Matched sets of Prnp0/0 ...

  8. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice.

    PubMed

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-04-14

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  9. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice

    PubMed Central

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-01-01

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  10. Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder

    PubMed Central

    Blackmon, Karen; Ben-Avi, Emma; Wang, Xiuyuan; Pardoe, Heath R.; Di Martino, Adriana; Halgren, Eric; Devinsky, Orrin; Thesen, Thomas; Kuzniecky, Ruben

    2015-01-01

    Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD) than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC). Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE) open-access database, were analyzed to compare groups on (1) blinded review of high-resolution T1-weighted research sequences; and (2) quantitative measurement of white matter hypointensity (WMH) volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC), also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly. PMID:26693400

  11. Hypocretinergic neurons are activated in conjunction with goal-oriented survival-related motor behaviors.

    PubMed

    Torterolo, Pablo; Ramos, Oscar V; Sampogna, Sharon; Chase, Michael H

    2011-10-24

    Hypocretinergic neurons are located in the area of the lateral hypothalamus which is responsible for mediating goal-directed, survival-related behaviors. Consequently, we hypothesize that the hypocretinergic system functions to promote these behaviors including those patterns of somatomotor activation upon which they are based. Further, we hypothesize that the hypocretinergic system is not involved with repetitive motor activities unless they occur in conjunction with the goal-oriented behaviors that are governed by the lateral hypothalamus. In order to determine the veracity of these hypotheses, we examined Fos immunoreactivity (as a marker of neuronal activity) in hypocretinergic neurons in the cat during: a) Exploratory Motor Activity; b) Locomotion without Reward; c) Locomotion with Reward; and d) Wakefulness without Motor Activity. Significantly greater numbers of hypocretinergic neurons expressed c-fos when the animals were exploring an unknown environment during Exploratory Motor Activity compared with all other paradigms. In addition, a larger number of Hcrt+Fos+neurons were activated during Locomotion with Reward than during Wakefulness without Motor Activity. Finally, very few hypocretinergic neurons were activated during Locomotion without Reward and Wakefulness without Motor Activity, wherein there was an absence of goal-directed activities. We conclude that the hypocretinergic system does not promote wakefulness per se or motor activity per se but is responsible for mediating specific goal-oriented behaviors that take place during wakefulness. Accordingly, we suggest that the hypocretinergic system is responsible for controlling the somatomotor system and coordinating its activity with other systems in order to produce successful goal-oriented survival-related behaviors that are controlled by the lateral hypothalamus. PMID:21839102

  12. Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction

    PubMed Central

    Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Parvaz, Muhammad A.; Alia-Klein, Nelly; Volkow, Nora D.; Goldstein, Rita Z.

    2012-01-01

    Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) which was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. PMID:22775285

  13. Evoked Potentials in Motor Cortical Local Field Potentials Reflect Task Timing and Behavioral Performance

    PubMed Central

    Confais, Joachim; Ponce-Alvarez, Adrián; Diesmann, Markus; Riehle, Alexa

    2010-01-01

    Evoked potentials (EPs) are observed in motor cortical local field potentials (LFPs) during movement execution (movement-related potentials [MRPs]) and in response to relevant visual cues (visual evoked potentials [VEPs]). Motor cortical EPs may be directionally selective, but little is known concerning their relation to other aspects of motor behavior, such as task timing and performance. We recorded LFPs in motor cortex of two monkeys during performance of a precued arm-reaching task. A time cue at the start of each trial signaled delay duration and thereby the pace of the task and the available time for movement preparation. VEPs and MRPs were strongly modulated by the delay duration, VEPs being systematically larger in short-delay trials and MRPs larger in long-delay trials. Despite these systematic modulations related to the task timing, directional selectivity was similar in short and long trials. The behavioral reaction time was positively correlated with MRP size and negatively correlated with VEP size, within sessions. In addition, the behavioral performance improved across sessions, in parallel with a slow decrease in the size of VEPs and MRPs. Our results clearly show the strong influence of the behavioral context and performance on motor cortical population activity during movement preparation and execution. PMID:20884766

  14. 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…

  15. Structural behavior of solid rocket motor field joints

    NASA Technical Reports Server (NTRS)

    Card, Michael F.; Wingate, Robert T.

    1987-01-01

    Structural analysis studies conducted on three concepts for the Space Shuttle Solid Rocket Motor field joints are summarized. Deflections and stresses in the Challenger clevis-tang joint are compared with a proposed capture-tang replacement joint and with an alternate bolted joint design. Results indicate deflections and stresses are subsequently reduced in both the capture-tang and bolted joint concepts. The capture-tang and bolted joint designs are respectively 24 and 70 percent heavier than the baseline clevis-tang joint.

  16. Motor sequence learning and motor adaptation in primary cervical dystonia.

    PubMed

    Katschnig-Winter, Petra; Schwingenschuh, Petra; Davare, Marco; Sadnicka, Anna; Schmidt, Reinhold; Rothwell, John C; Bhatia, Kailash P; Edwards, Mark J

    2014-06-01

    Motor sequence learning and motor adaptation rely on overlapping circuits predominantly involving the basal ganglia and cerebellum. Given the importance of these brain regions to the pathophysiology of primary dystonia, and the previous finding of abnormal motor sequence learning in DYT1 gene carriers, we explored motor sequence learning and motor adaptation in patients with primary cervical dystonia. We recruited 12 patients with cervical dystonia and 11 healthy controls matched for age. Subjects used a joystick to move a cursor from a central starting point to radial targets as fast and accurately as possible. Using this device, we recorded baseline motor performance, motor sequence learning and a visuomotor adaptation task. Patients with cervical dystonia had a significantly higher peak velocity than controls. Baseline performance with random target presentation was otherwise normal. Patients and controls had similar levels of motor sequence learning and motor adaptation. Our patients had significantly higher peak velocity compared to controls, with similar movement times, implying a different performance strategy. The preservation of motor sequence learning in cervical dystonia patients contrasts with the previously observed deficit seen in patients with DYT1 gene mutations, supporting the hypothesis of differing pathophysiology in different forms of primary dystonia. Normal motor adaptation is an interesting finding. With our paradigm we did not find evidence that the previously documented cerebellar abnormalities in cervical dystonia have a behavioral correlate, and thus could be compensatory or reflect "contamination" rather than being directly pathological. PMID:24411324

  17. Stochastic kinetics of ribosomes: Single motor properties and collective behavior

    NASA Astrophysics Data System (ADS)

    Garai, Ashok; Chowdhury, Debanjan; Chowdhury, Debashish; Ramakrishnan, T. V.

    2009-07-01

    Syntheses of protein molecules in a cell are carried out by ribosomes. A ribosome can be regarded as a molecular motor which utilizes the input chemical energy to move on a messenger RNA (mRNA) track that also serves as a template for the polymerization of the corresponding protein. The forward movement, however, is characterized by an alternating sequence of translocation and pause. Using a quantitative model, which captures the mechanochemical cycle of an individual ribosome, we derive an exact analytical expression for the distribution of its dwell times at the successive positions on the mRNA track. Inverse of the average dwell time satisfies a “Michaelis-Menten-type” equation and is consistent with the general formula for the average velocity of a molecular motor with an unbranched mechanochemical cycle. Extending this formula appropriately, we also derive the exact force-velocity relation for a ribosome. Often many ribosomes simultaneously move on the same mRNA track, while each synthesizes a copy of the same protein. We extend the model of a single ribosome by incorporating steric exclusion of different individuals on the same track. We draw the phase diagram of this model of ribosome traffic in three-dimensional spaces spanned by experimentally controllable parameters. We suggest new experimental tests of our theoretical predictions.

  18. In vivo characterization of metabotropic glutamate receptor type 5 abnormalities in behavioral variant FTD.

    PubMed

    Leuzy, Antoine; Zimmer, Eduardo Rigon; Dubois, Jonathan; Pruessner, Jens; Cooperman, Cory; Soucy, Jean-Paul; Kostikov, Alexey; Schirmaccher, Esther; Désautels, René; Gauthier, Serge; Rosa-Neto, Pedro

    2016-04-01

    Although the pathogenesis underlying behavioral variant frontotemporal dementia (bvFTD) has yet to be fully understood, glutamatergic abnormalities have been hypothesized to play an important role. The aim of the present study was to determine the availability of the metabotropic glutamate receptor type 5 (mGluR5) using a novel positron emission tomography (PET) radiopharmaceutical with high selectivity for mGluR5 ([(11)C]ABP688) in a sample of bvFTD patients. In addition, we sought to determine the overlap between availability of mGluR5 and neurodegeneration, as measured using [(18)F]FDG-PET and voxel-based morphometry (VBM). Availability of mGluR5 and glucose metabolism ([(18)F]FDG) were measured in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [(11)C]ABP688 binding potential maps (BPND) were calculated using the cerebellum as a reference region, with [(18)F]FDG standardized uptake ratio maps (SUVR) normalized to the pons. Grey matter (GM) concentrations were determined using VBM. Voxel-based group differences were obtained using RMINC. BvFTD patients showed widespread decrements in [(11)C]ABP688 BPND throughout frontal, temporal and subcortical areas. These areas were likewise characterized by significant hypometabolism and GM loss, with overlap between reduced [(11)C]ABP688 BPND and hypometabolism superior to that for GM atrophy. Several regions were characterized only by decreased binding of [(11)C]ABP688. The present findings represent the first in vivo report of decreased availability of mGluR5 in bvFTD. This study suggests that glutamate excitotoxicity may play a role in the pathogenesis of bvFTD and that [(11)C]ABP688 may prove a suitable marker of glutamatergic neurotransmission in vivo. PMID:25596865

  19. Behavioral abnormalities are common and severe in patients with distal 22q11.2 microdeletions and microduplications

    PubMed Central

    Lindgren, Valerie; McRae, Anne; Dineen, Richard; Saulsberry, Alexandria; Hoganson, George; Schrift, Michael

    2015-01-01

    We describe six individuals with microdeletions and microduplications in the distal 22q11.2 region detected by microarray. Five of the abnormalities have breakpoints in the low-copy repeats (LCR) in this region and one patient has an atypical rearrangement. Two of the six patients with abnormalities in the region between LCR22 D–E have hearing loss, which has previously been reported only once in association with these abnormalities. We especially note the behavioral/neuropsychiatric problems, including the severity and early onset, in patients with distal 22q11.2 rearrangements. Our patients add to the genotype–phenotype correlations which are still being generated for these chromosomal anomalies. PMID:26247050

  20. Apparent and Actual Trajectory Control Depend on the Behavioral Context in Upper Limb Motor Tasks.

    PubMed

    Cluff, Tyler; Scott, Stephen H

    2015-09-01

    A central problem in motor neuroscience is to understand how we select, plan, and control motor actions. An influential idea is that the motor system computes and implements a desired limb trajectory, an intermediary control process between the behavioral goal (reach a spatial goal) and motor commands to move the limb. The most compelling evidence for trajectory control is that corrective responses are directed back toward the unperturbed trajectory when the limb is disturbed during movement. However, the idea of trajectory control conflicts with optimal control theories that emphasize goal-directed motor corrections. Here we show that corrective responses in human subjects can deviate back toward the unperturbed trajectory, but these reversals were only present when there were explicit limits on movement time. Our second experiment asked whether trajectory control could be generated if the trajectory was made an explicit goal of the task. Participants countered unexpected loads while reaching to a static goal, tracking a moving target, or maintaining their hand within a visually constrained path to a static goal. Corrective responses were directed back toward the constrained path or to intercept the moving target. However, corrections back to the unperturbed path disappeared when reaching to the static target. Long-latency muscle responses paralleled changes in the behavioral goal in both sets of experiments, but goal-directed responses were delayed by 15-25 ms when tracking the moving goal. Our results show the motor system can behave like a trajectory controller but only if a "desired trajectory" is the goal of the task. Significance statement: One of the most influential ideas in motor control is that the motor system computes a "desired trajectory" when reaching to a spatial goal. Here we revisit the experimental paradigm from seminal papers supporting trajectory control to illustrate that corrective responses appear to return to the original trajectory of the

  1. GLP-1 receptor agonist liraglutide reverses long-term atypical antipsychotic treatment associated behavioral depression and metabolic abnormalities in rats.

    PubMed

    Sharma, Ajaykumar N; Ligade, Sagar S; Sharma, Jay N; Shukla, Praveen; Elased, Khalid M; Lucot, James B

    2015-04-01

    Mood disorder patients that are on long-term atypical antipsychotics treatment frequently experience metabolic dysfunctions. In addition to this, accumulating evidences points to increased risk of structural abnormalities, brain volume changes, altered neuroplasticity and behavioral depression with long-term antipsychotics use. However, there is paucity of preclinical evidences for long-term antipsychotic associated depression-like behavior. The objectives of the present study were: (1) to evaluate influence of long-term antipsychotic (olanzapine) treatment on rat behavior in forced swim test (FST) as a model for depression and; (2) to examine impact of glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide - an antidiabetic medication for type II diabetes, on long-term olanzapine associated metabolic and behavioral changes in rats. Daily olanzapine treatment (0.5 mg/kg; p.o.) for 8-9 weeks significantly increased body weights, food and water intake, plasma cholesterol and triglycerides and immobility time in FST with parallel reduction in plasma HDL cholesterol levels. These results points to development of metabolic abnormalities and depression-like behavior with long-term olanzapine treatment. Acute liraglutide (50 μg/kg; i.p.) and imipramine (10 mg/kg, i. p.) treatment per se significantly decreased duration of immobility in FST compared to vehicle treated rats. Additionally, 3-week liraglutide treatment (50 μg/kg; i.p., daily) partially reversed metabolic abnormalities and depression-like behavior with long-term olanzapine-treatment in rats. None of these treatment regimens affected locomotor behavior of rats. In summary, add-on GLP-1 receptor agonists promise novel alternatives to counteract long-term antipsychotics associated behavioral and metabolic complications. PMID:25023888

  2. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs.

    PubMed

    Clark, Matt Q; McCumsey, Stephanie J; Lopez-Darwin, Sereno; Heckscher, Ellie S; Doe, Chris Q

    2016-01-01

    Drosophila larval crawling is an attractive system to study rhythmic motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors, including head casts, turning, and feeding. It is likely that some neurons (e.g., motor neurons) are used in all these behaviors, but the identity (or even existence) of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines-chosen for sparse neuronal expression-to ectopically express the warmth-inducible neuronal activator TrpA1, and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°). A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes, including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program. PMID:27172197

  3. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs

    PubMed Central

    Clark, Matt Q.; McCumsey, Stephanie J.; Lopez-Darwin, Sereno; Heckscher, Ellie S.; Doe, Chris Q.

    2016-01-01

    Drosophila larval crawling is an attractive system to study rhythmic motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors, including head casts, turning, and feeding. It is likely that some neurons (e.g., motor neurons) are used in all these behaviors, but the identity (or even existence) of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines—chosen for sparse neuronal expression—to ectopically express the warmth-inducible neuronal activator TrpA1, and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°). A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes, including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program. PMID:27172197

  4. Motor characteristics determine the rheological behavior of a suspension of microswimmers

    NASA Astrophysics Data System (ADS)

    Karmakar, Richa; Gulvady, Ranjit; Tirumkudulu, Mahesh S.; Venkatesh, K. V.

    2014-07-01

    A suspension of motile cells exhibits complex rheological properties due to their collective motion. We measure the shear viscosity of a suspension of Escherichia coli strains varying in motor characteristics such as duration of run and tumble. At low cell densities, all strains irrespective of their motor characteristics exhibit a linear increase in viscosity with cell density suggesting that the cells behave as a suspension of passive rods with an effective aspect ratio set by the motor characteristics of the bacteria. As the cell density is increased beyond a critical value, the viscosity drops sharply signaling the presence of strongly coordinated motion among bacteria. The critical density depends not only on the magnitude of shear but also the motor characteristics of individual cells. High shear rate disrupts the coordinated motion reducing its behavior, once again, to a suspension of inactive particles.

  5. Abnormal sexual behavior during sleep in temporal lobe epilepsy: a case report.

    PubMed

    Pelin, Zerrin; Yazla, Ece

    2012-06-01

    Herein, we describe a case who presented with abnormal sexual behaviour during sleep. Video-electroencephalography monitoring during sleep revealed an abnormality suggesting an epileptic basis. The patient was successfully treated with carbamazepin. The psychiatric symptoms that were thought to be related to abnormal sexual behaviours were controlled with antipsychotic treatment. Our findings strongly emphasize the fact that efforts should be spent to increase awareness of seizure activity at night, which can be misinterpreted as benign parasomnias. Such a misinterpretation may have serious consequences, such as insufficient seizure control, progressive personality changes, and cognitive impairment. PMID:25206999

  6. Ectopic cerebellar cell migration causes maldevelopment of Purkinje cells and abnormal motor behaviour in Cxcr4 null mice.

    PubMed

    Huang, Guo-Jen; Edwards, Andrew; Tsai, Cheng-Yu; Lee, Yi-Shin; Peng, Lei; Era, Takumi; Hirabayashi, Yoshio; Tsai, Ching-Yen; Nishikawa, Shin-Ichi; Iwakura, Yoichiro; Chen, Shu-Jen; Flint, Jonathan

    2014-01-01

    SDF-1/CXCR4 signalling plays an important role in neuronal cell migration and brain development. However, the impact of CXCR4 deficiency in the postnatal mouse brain is still poorly understood. Here, we demonstrate the importance of CXCR4 on cerebellar development and motor behaviour by conditional inactivation of Cxcr4 in the central nervous system. We found CXCR4 plays a key role in cerebellar development. Its loss leads to defects in Purkinje cell dentritogenesis and axonal projection in vivo but not in cell culture. Transcriptome analysis revealed the most significantly affected pathways in the Cxcr4 deficient developing cerebellum are involved in extra cellular matrix receptor interactions and focal adhesion. Consistent with functional impairment of the cerebellum, Cxcr4 knockout mice have poor coordination and balance performance in skilled motor tests. Together, these results suggest ectopic the migration of granule cells impairs development of Purkinje cells, causes gross cerebellar anatomical disruption and leads to behavioural motor defects in Cxcr4 null mice. PMID:24516532

  7. Early communicative behaviors and their relationship to motor skills in extremely preterm infants.

    PubMed

    Benassi, Erika; Savini, Silvia; Iverson, Jana M; Guarini, Annalisa; Caselli, Maria Cristina; Alessandroni, Rosina; Faldella, Giacomo; Sansavini, Alessandra

    2016-01-01

    Despite the predictive value of early spontaneous communication for identifying risk for later language concerns, very little research has focused on these behaviors in extremely low-gestational-age infants (ELGA<28 weeks) or on their relationship with motor development. In this study, communicative behaviors (gestures, vocal utterances and their coordination) were evaluated during mother-infant play interactions in 20 ELGA infants and 20 full-term infants (FT) at 12 months (corrected age for ELGA infants). Relationships between gestures and motor skills, evaluated using the Bayley-III Scales were also examined. ELGA infants, compared with FT infants, showed less advanced communicative, motor, and cognitive skills. Giving and representational gestures were produced at a lower rate by ELGA infants. In addition, pointing gestures and words were produced by a lower percentage of ELGA infants. Significant positive correlations between gestures (pointing and representational gestures) and fine motor skills were found in the ELGA group. We discuss the relevance of examining spontaneous communicative behaviors and motor skills as potential indices of early development that may be useful for clinical assessment and intervention with ELGA infants. PMID:26555385

  8. Measured particulate behavior in a subscale solid propellant rocket motor

    NASA Astrophysics Data System (ADS)

    Brennan, W. D.; Hovland, D. L.; Netzer, D. W.

    1992-10-01

    Particulate matter are sized in the exhaust nozzle and plume of small rocket motors of varying geometry to assess the effects of the expansion process on particle size. Both converging and converging-diverging nozzles are considered, and particle sizing is accomplished at pressures of up to 4.36 MPa with aluminum loadings of 2.0 and 4.7 percent. An instrument based on Fraunhofer diffraction is used to measure the particle-size distributions showing that: (1) high burning rates reduce particle agglomeration and increase C* efficiency; (2) high pressures lead to small and monomodal D32 entering the nozzle; and (3) D32 sizes increase appreciably at the tailoff. Some variations in plume signature are theorized to be caused by the tailoff phenomenon, and particle collisions and/or surface effects in the nozzle convergence are suggested by the reduced number of larger particles at the nozzle convergence.

  9. Motor Origin of Precise Synaptic Inputs onto Forebrain Neurons Driving a Skilled Behavior

    PubMed Central

    Vallentin, Daniela

    2015-01-01

    Sensory feedback is crucial for learning and performing many behaviors, but its role in the execution of complex motor sequences is poorly understood. To address this, we consider the forebrain nucleus HVC in the songbird, which contains the premotor circuitry for song production and receives multiple convergent sensory inputs. During singing, projection neurons within HVC exhibit precisely timed synaptic events that may represent the ongoing motor program or song-related sensory feedback. To distinguish between these possibilities, we recorded the membrane potential from identified HVC projection neurons in singing zebra finches. External auditory perturbations during song production did not affect synaptic inputs in these neurons. Furthermore, the systematic removal of three sensory feedback streams (auditory, proprioceptive, and vagal) did not alter the frequency or temporal precision of synaptic activity observed. These findings support a motor origin for song-related synaptic events and suggest an updated circuit model for generating behavioral sequences. PMID:25568122

  10. Reducing the Stress of Intensive Care: Effects on Motor and State Behavior. Conference Summary.

    ERIC Educational Resources Information Center

    Becker, Patricia T.

    This report presents outcome data on infant motor activity and behavioral state. Subjects were 45 infants who had birth weight of less than 1,501 grams, were appropriate for gestational age, and were free of major complications. A total of 21 infants were studied during a preintervention (control period), and 24 were studied in a posttraining…

  11. Baseline Cognition, Behavior, and Motor Skills in Children with New-Onset, Idiopathic Epilepsy

    ERIC Educational Resources Information Center

    Bhise, Vikram V.; Burack, Gail D.; Mandelbaum, David E.

    2010-01-01

    Aim: Epilepsy is associated with difficulties in cognition and behavior in children. These problems have been attributed to genetics, ongoing seizures, psychosocial issues, underlying abnormality of the brain, and/or antiepileptic drugs. In a previous study, we found baseline cognitive differences between children with partial versus generalized…

  12. Pre-reproductive maternal enrichment influences offspring developmental trajectories: motor behavior and neurotrophin expression

    PubMed Central

    Caporali, Paola; Cutuli, Debora; Gelfo, Francesca; Laricchiuta, Daniela; Foti, Francesca; De Bartolo, Paola; Mancini, Laura; Angelucci, Francesco; Petrosini, Laura

    2014-01-01

    Environmental enrichment is usually applied immediately after weaning or in adulthood, with strong effects on CNS anatomy and behavior. To examine the hypothesis that a pre-reproductive environmental enrichment of females could affect the motor development of their offspring, female rats were reared in an enriched environment from weaning to sexual maturity, while other female rats used as controls were reared under standard conditions. Following mating with standard-reared males, all females were housed individually. To evaluate the eventual transgenerational influence of positive pre-reproductive maternal experiences, postural and motor development of male pups was analyzed from birth to weaning. Moreover, expression of Brain Derived Neurotrophic Factor and Nerve Growth Factor in different brain regions was evaluated at birth and weaning. Pre-reproductive environmental enrichment of females affected the offspring motor development, as indicated by the earlier acquisition of complex motor abilities displayed by the pups of enriched females. The earlier acquisition of motor abilities was associated with enhanced neurotrophin levels in striatum and cerebellum. In conclusion, maternal positive experiences were transgenerationally transmitted, and influenced offspring phenotype at both behavioral and biochemical levels. PMID:24910599

  13. Analysis of Cooperative Behavior in Multiple Kinesins Motor Protein Transport by Varying Structural and Chemical Properties

    PubMed Central

    Uppulury, Karthik; Efremov, Artem K.; Driver, Jonathan W.; Jamison, D. Kenneth

    2012-01-01

    Intracellular transport is a fundamental biological process during which cellular materials are driven by enzymatic molecules called motor proteins. Recent optical trapping experiments and theoretical analysis have uncovered many features of cargo transport by multiple kinesin motor protein molecules under applied loads. These studies suggest that kinesins cooperate negatively under typical transport conditions, although some productive cooperation could be achieved under higher applied loads. However, the microscopic origins of this complex behavior are still not well understood. Using a discrete-state stochastic approach we analyze factors that affect the cooperativity among kinesin motors during cargo transport. Kinesin cooperation is shown to be largely unaffected by the structural and mechanical parameters of a multiple motor complex connected to a cargo, but much more sensitive to biochemical parameters affecting motor-filament affinities. While such behavior suggests the net negative cooperative responses of kinesins will persist across a relatively wide range of cargo types, it is also shown that the rates with which cargo velocities relax in time upon force perturbations are influenced by structural factors that affect the free energies of and load distributions within a multiple kinesin complex. The implications of these later results on transport phenomena where loads change temporally, as in the case of bidirectional transport, are discussed. PMID:24489614

  14. Motor behaviors in the sheep evoked by electrical stimulation of the subthalamic nucleus.

    PubMed

    Lentz, Linnea; Zhao, Yan; Kelly, Matthew T; Schindeldecker, William; Goetz, Steven; Nelson, Dwight E; Raike, Robert S

    2015-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to treat movement disorders, including advanced Parkinson's disease (PD). The pathogenesis of PD and the therapeutic mechanisms of DBS are not well understood. Large animal models are essential for investigating the mechanisms of PD and DBS. The purpose of this study was to develop a novel sheep model of STN DBS and quantify the stimulation-evoked motor behaviors. To do so, a large sample of animals was chronically-implanted with commercial DBS systems. Neuroimaging and histology revealed that the DBS leads were implanted accurately relative to the neurosurgical plan and also precisely relative to the STN. It was also possible to repeatedly conduct controlled evaluations of stimulation-evoked motor behavior in the awake-state. The evoked motor responses depended on the neuroanatomical location of the electrode contact selected for stimulation, as contacts proximal to the STN evoked movements at significantly lower voltages. Tissue stimulation modeling demonstrated that selecting any of the contacts stimulated the STN, whereas selecting the relatively distal contacts often also stimulated thalamus but only the distal-most contact stimulated internal capsule. The types of evoked motor behaviors were specific to the stimulation frequency, as low but not high frequencies consistently evoked movements resembling human tremor or dyskinesia. Electromyography confirmed that the muscle activity underlying the tremor-like movements in the sheep was consistent with human tremor. Overall, this work establishes that the sheep is a viable a large-animal platform for controlled testing of STN DBS with objective motor outcomes. Moreover, the results support the hypothesis that exaggerated low-frequency activity within individual nodes of the motor network can drive symptoms of human movement disorders, including tremor and dyskinesia. PMID:26231574

  15. Low molecular weight species of TDP-43 generated by abnormal splicing form inclusions in amyotrophic lateral sclerosis and result in motor neuron death.

    PubMed

    Xiao, Shangxi; Sanelli, Teresa; Chiang, Helen; Sun, Yulong; Chakrabartty, Avijit; Keith, Julia; Rogaeva, Ekaterina; Zinman, Lorne; Robertson, Janice

    2015-07-01

    The presence of lower molecular weight species comprising the C-terminal region of TAR DNA-binding protein 43 (TDP-43) is a characteristic of TDP-43 proteinopathy in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here, we have identified a novel splice variant of TDP-43 that is upregulated in ALS and generates a 35-kDa N-terminally truncated species through use of an alternate translation initiation codon (ATG(Met85)), denoted here as Met(85)-TDP-35. Met(85)-TDP-35 expressed ectopically in human neuroblastoma cells exhibited reduced solubility, cytoplasmic distribution, and aggregation. Furthermore, Met(85)-TDP-35 sequestered full-length TDP-43 from the nucleus to form cytoplasmic aggregates. Expression of Met(85)-TDP-35 in primary motor neurons resulted in the formation of Met(85)-TDP-35-positive cytoplasmic aggregates and motor neuron death. A neo-epitope antibody specific for Met(85)-TDP-35 labeled the 35-kDa lower molecular weight species on immunoblots of urea-soluble extracts from ALS-FTLD disease-affected tissues and co-labeled TDP-43-positive inclusions in ALS spinal cord sections, confirming the physiological relevance of this species. These results show that the 35-kDa low molecular weight species in ALS-FTLD can be generated from an abnormal splicing event and use of a downstream initiation codon and may represent a mechanism by which TDP-43 elicits its pathogenicity. PMID:25788357

  16. Early white matter abnormalities, progressive brain pathology and motor deficits in a novel knock-in mouse model of Huntington's disease

    PubMed Central

    Jin, Jing; Peng, Qi; Hou, Zhipeng; Jiang, Mali; Wang, Xin; Langseth, Abraham J.; Tao, Michael; Barker, Peter B.; Mori, Susumu; Bergles, Dwight E.; Ross, Christopher A.; Detloff, Peter J.; Zhang, Jiangyang; Duan, Wenzhen

    2015-01-01

    White matter abnormalities have been reported in premanifest Huntington's disease (HD) subjects before overt striatal neuronal loss, but whether the white matter changes represent a necessary step towards further pathology and the underlying mechanism of these changes remains unknown. Here, we characterized a novel knock-in mouse model that expresses mouse HD gene homolog (Hdh) with extended CAG repeat- HdhQ250, which was derived from the selective breeding of HdhQ150 mice. HdhQ250 mice manifest an accelerated and robust phenotype compared with its parent line. HdhQ250 mice exhibit progressive motor deficits, reduction in striatal and cortical volume, accumulation of mutant huntingtin aggregation, decreased levels of DARPP32 and BDNF and altered striatal metabolites. The abnormalities detected in this mouse model are reminiscent of several aspects of human HD. In addition, disturbed myelination was evident in postnatal Day 14 HdhQ250 mouse brain, including reduced levels of myelin regulatory factor and myelin basic protein, and decreased numbers of myelinated axons in the corpus callosum. Thinner myelin sheaths, indicated by increased G-ratio of myelin, were also detected in the corpus callosum of adult HdhQ250 mice. Moreover, proliferation of oligodendrocyte precursor cells is altered by mutant huntingtin both in vitro and in vivo. Our data indicate that this model is suitable for understanding comprehensive pathogenesis of HD in white matter and gray matter as well as developing therapeutics for HD. PMID:25609071

  17. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life. PMID:26836141

  18. A structured assessment of motor function and behavior in patients with Kleefstra syndrome.

    PubMed

    Schmidt, Susanne; Nag, Heidi E; Hunn, Bente S; Houge, Gunnar; Hoxmark, Lise B

    2016-04-01

    The present study aimed to further our understanding of Kleefstra syndrome, especially regarding motor function and behavioral characteristics. In total, four males and four females between two and 27 years of age with a genetically confirmed diagnosis of Kleefstra syndrome and their parents participated in this study. Four patients had 9q34.3 deletions that caused Euchromatin Histone Methyl Transferase 1 (EHMT1) haplo-insufficiency, and four patients harbored EHMT1 mutations. The motor function was evaluated via systematic observation. Standardized assessments such as the Vineland Adapted Behavior Scales II (VABS II), the Social Communication Questionnaire (SCQ) and the Child or Adult Behavior Checklist (CBCL, ABCL) were used for the behavioral assessment. All patients showed a delayed developmental status. Muscular hypotonia and its manifestations were present in all patients, regardless of their age. The mean values for all VABS II domains (communication, socialization, daily living skills, and motor skills) were significantly lower than the mean of the reference population (p < 0.001), but similar to other rare intellectual disabilities such as Smith-Magenis syndrome and Angelman syndrome. The results from the SCQ indicated that all patient values exceeded the cut-off value, suggesting the possibility of autism spectrum disorder. The behavioral and emotional problems assessed by CBCL and ABCL were less frequent. In conclusion, patients with Kleefstra syndrome present with a broad range of clinical problems in all age groups and are therefore in need of a multidisciplinary follow-up also after their transition into adulthood. PMID:26808425

  19. Harmony from Chaos? Perceptual-Motor Delays Enhance Behavioral Anticipation in Social Interaction

    PubMed Central

    Washburn, Auriel; Kallen, Rachel W.; Coey, Charles A.; Shockley, Kevin; Richardson, Michael J.

    2015-01-01

    Effective interpersonal coordination is fundamental to robust social interaction, and the ability to anticipate a co-actor's behavior is essential for achieving this coordination. However, coordination research has focused on the behavioral synchrony that occurs between the simple periodic movements of co-actors and, thus, little is known about the anticipation that occurs during complex, everyday interaction. Research on the dynamics of coupled neurons, human motor control, electrical circuits, and laser semiconductors universally demonstrates that small temporal feedback delays are necessary for the anticipation of chaotic events. We therefore investigated whether similar feedback delays would promote anticipatory behavior during social interaction. Results revealed that co-actors were not only able to anticipate others' chaotic movements when experiencing small perceptual-motor delays, but also exhibited movement patterns of equivalent complexity. This suggests that such delays, including those within the human nervous system, may enhance, rather than hinder, the anticipatory processes that underlie successful social interaction. PMID:26030437

  20. Developmental delay in motor skill acquisition in Niemann-Pick C1 mice reveals abnormal cerebellar morphogenesis.

    PubMed

    Caporali, Paola; Bruno, Francesco; Palladino, Giampiero; Dragotto, Jessica; Petrosini, Laura; Mangia, Franco; Erickson, Robert P; Canterini, Sonia; Fiorenza, Maria Teresa

    2016-01-01

    Niemann-Pick type C1 (NPC1) disease is a lysosomal storage disorder caused by defective intracellular trafficking of exogenous cholesterol. Purkinje cell (PC) degeneration is the main sign of cerebellar dysfunction in both NPC1 patients and animal models. It has been recently shown that a significant decrease in Sonic hedgehog (Shh) expression reduces the proliferative potential of granule neuron precursors in the developing cerebellum of Npc1 (-/-) mice. Pursuing the hypothesis that this developmental defect translates into functional impairments, we have assayed Npc1-deficient pups belonging to the milder mutant mouse strain Npc1 (nmf164) for sensorimotor development from postnatal day (PN) 3 to PN21. Npc1 (nmf164) / Npc1 (nmf164) pups displayed a 2.5-day delay in the acquisition of complex motor abilities compared to wild-type (wt) littermates, in agreement with the significant disorganization of cerebellar cortex cytoarchitecture observed between PN11 and PN15. Compared to wt, Npc1 (nmf164) homozygous mice exhibited a poorer morphological differentiation of Bergmann glia (BG), as indicated by thicker radial shafts and less elaborate reticular pattern of lateral processes. Also BG functional development was defective, as indicated by the significant reduction in GLAST and Glutamine synthetase expression. A reduced VGluT2 and GAD65 expression also indicated an overall derangement of the glutamatergic/GABAergic stimulation that PCs receive by climbing/parallel fibers and basket/stellate cells, respectively. Lastly, Npc1-deficiency also affected oligodendrocyte differentiation as indicated by the strong reduction of myelin basic protein. Two sequential 2-hydroxypropyl-β-cyclodextrin administrations at PN4 and PN7 counteract these defects, partially preventing functional impairment of BG and fully restoring the normal patterns of glutamatergic/GABAergic stimulation to PCs.These findings indicate that in Npc1 (nmf164) homozygous mice the derangement of synaptic

  1. Natural descriptions of motor behavior: examples from E. coli and C. elegans.

    NASA Astrophysics Data System (ADS)

    Ryu, William

    2007-03-01

    E. coli has a natural behavioral variable - the direction of rotation of its flagellar rotorary motor. Monitoring this one-dimensional behavioral response in reaction to chemical perturbation has been instrumental in the understanding of how E. coli performs chemotaxis at the genetic, physiological, and computational level. Here we apply this experimental strategy to the study of bacterial thermotaxis - a sensory mode that is less well understood. We investigate bacterial thermosensation by studying the motor response of single cells subjected to impulses of heat produced by an IR laser. A simple temperature dependent modification to an existing chemotaxis model can explain the observed temperature response. Higher organisms may have a more complicated behavioral response due to the simple fact that their motions have more degrees of freedom. Here we provide a principled analysis of motor behavior of such an organism -- the roundworm C. elegans. Using tracking video-microscopy we capture a worm's image and extract the skeleton of the shape as a head-to-tail ordered collection of tangent angles sampled along the curve. Applying principal components analysis we show that the space of shapes is remarkably low dimensional, with four dimensions accounting for > 95% of the shape variance. We also show that these dimensions align with behaviorally relevant states. As an application of this analysis we study the thermal response of worms stimulated by laser heating. Our quantitative description of C. elegans movement should prove useful in a wide variety of contexts, from the linking of motor output with neural circuitry to the genetic basis of adaptive behavior.

  2. Comparison of motor, cognitive, and behavioral features in progressive supranuclear palsy and Parkinson's disease.

    PubMed

    Cordato, Nicholas J; Halliday, Glenda M; Caine, Diana; Morris, John G L

    2006-05-01

    Major clinical features and global measures were systematically evaluated and compared in progressive supranuclear palsy (PSP) and Parkinson's disease (PD). In addition to gaze palsy and early postural instability in PSP, absence of levodopa-induced dyskinesia, frontalis muscle overactivity, primitive reflexes, visuospatial impairment, and substantial frontal behavioral disturbances differentiated almost all patients with this disorder from PD. For PSP, behavioral changes related to severity of general disability, thereby challenging previous models of relationships between behavior, motor, and cognitive disturbance for this disorder. PMID:16353177

  3. [Formation of probabilistic structure of motor behavior in bottlenose dolphins in captivity].

    PubMed

    Chechina, O N; Kondrat'eva, N L

    2009-01-01

    A probabilistic structure of the motor behavior was analyzed in dolphin calves Tursiops truncatus in the prenatal period and adult dolphins in an oceanarium. Ethograms were recorded and subjected to a computer analysis. Ranking probabilities of transitions between behavioral acts revealed a highly determined sequence of operations underlying the newborn dolphins' behavior. The principle of formation of the variation ethologic structures providing a contact between a developing organism and the environment was determined. The results are discussed in terms of the concept of the informational brain-environment interaction. PMID:19947534

  4. The Association of Intelligence, Visual-Motor Functioning, and Personality Characteristics With Adaptive Behavior in Individuals With Williams Syndrome.

    PubMed

    Fu, Trista J; Lincoln, Alan J; Bellugi, Ursula; Searcy, Yvonne M

    2015-07-01

    Williams syndrome (WS) is associated with deficits in adaptive behavior and an uneven adaptive profile. This study investigated the association of intelligence, visual-motor functioning, and personality characteristics with the adaptive behavior in individuals with WS. One hundred individuals with WS and 25 individuals with developmental disabilities of other etiologies were included in this study. This study found that IQ and visual-motor functioning significantly predicted adaptive behavior in individuals of WS. Visual-motor functioning especially predicted the most amount of unique variance in overall adaptive behavior and contributed to the variance above and beyond that of IQ. Present study highlights the need for interventions that address visual-motor and motor functioning in individuals with WS. PMID:26161466

  5. Fish Chromatophores--From Molecular Motors to Animal Behavior.

    PubMed

    Sköld, Helen Nilsson; Aspengren, Sara; Cheney, Karen L; Wallin, Margareta

    2016-01-01

    Chromatophores are pigment-bearing cells of lower vertebrates, including fish that cater for the ability of individual animals to shift body coloration and pattern. Color change provides dynamic camouflage and various kinds of communication. It is also a spectacular example of phenotypic plasticity, and of significant importance for adaptation and survival in novel environments. Through different cellular mechanisms, color change can occur within minutes or more slowly over weeks. Chromatophores have different pigment types and are located not only in the skin, but also in the eyes and internally. While morphological color change, including seasonal color change, has received a lot of interest from evolutionary biologists and behavioral ecologists, the more rapid physiological color change has been largely a research subject for cell physiologists. In this cross-disciplinary review, we have highlighted emerging trends in pigment cell research and identified unsolved problems for future research. PMID:26811288

  6. Unipolar resistance switching and abnormal reset behaviors in Pt/CuO/Pt and Cu/CuO/Pt structures

    NASA Astrophysics Data System (ADS)

    Wu, Liang; Li, Xiaomin; Gao, Xiangdong; Zheng, Renkui; Zhang, Feng; Liu, Xinjun; Wang, Qun

    2012-07-01

    The effects of Pt and Cu top electrodes on resistance switching properties were investigated for CuO thin films with Pt/CuO/Pt and Cu/CuO/Pt sandwich structures. Typical unipolar resistance switching (URS) behaviors and two different kinds of resistance changes in the reset process were observed in both structures. When voltages were applied to the film, the low-resistance state (LRS) with relatively low resistance value (<30 Ω) was switched to the high-resistance state (HRS), exhibiting normal reset behavior. For LRS with relatively high resistance value (>50 Ω), the resistance first decreased then increased to HRS, showing abnormal reset behavior. The former variation of LRS could be ascribed to the decrease in filament size induced by Joule heating, while the latter one could be ascribed to the growth of disconnected filaments induced by high electric fields. This study indicates that the switching modes and the abnormal reset behaviors in CuO thin films are not due to Pt and Cu top electrodes, but the intrinsic properties of CuO film.

  7. REM Sleep Behavior and Motor Findings in Parkinson's Disease: A Cross-sectional Analysis

    PubMed Central

    Mahajan, Abhimanyu; Rosenthal, Liana S.; Gamaldo, Charlene; Salas, Rachel E.; Pontone, Gregory M.; McCoy, Arita; Umeh, Chizoba; Mari, Zoltan

    2014-01-01

    Background Parkinson's disease (PD) represents a major public health challenge that will only grow in our aging population. Understanding the connection between PD and associated prodromal conditions, such as rapid eye movement sleep behavioral disorder (RBD), is critical to identifying prevention strategies. However, the relationship between RBD and severity of motor findings in early PD is unknown. This study aims to examine this relationship. Methods The study population consisted of 418 PD patients who completed the Movement Disorders Society-United Parkinson's Disease Rating Scale (MDS-UPDRS) and rapid eye movement sleep (REM) disorder questionnaires at the baseline visit of the Michael J. Fox's Parkinson's Progression Markers Initiative (PPMI). Cross-sectional analysis was carried out to assess the association between REM Sleep Behavior Screening Questionnaire score and MDS UPDRS-3 (motor) score categories. Correlation with a higher score category was described as “worse motor findings”. A score of 5 on the REM disorder questionnaire was defined as predictive of RBD. Results Out of the 418 PD patients, 113 (27.0%) had RBD. With univariate logistic regression analysis, individuals with scores predictive of RBD were 1.66 times more likely to have worse motor findings (p = 0.028). Even with age, gender, and Geriatric Depression Scale scores taken into account, individuals with scores predictive of RBD were 1.69 times more likely to have worse motor findings (p = 0.025). Discussion PD patients with RBD symptoms had worse motor findings than those unlikely to have RBD. This association provides further evidence for the relationship between RBD and PD. PMID:25009765

  8. The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors.

    PubMed

    Cussen, Victoria A; Mench, Joy A

    2015-01-01

    Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long

  9. The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors

    PubMed Central

    Cussen, Victoria A.; Mench, Joy A.

    2015-01-01

    Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long

  10. Distributed Effects of Biological Sex Define Sex-Typical Motor Behavior in Caenorhabditis elegans

    PubMed Central

    Mowrey, William R.; Bennett, Jessica R.

    2014-01-01

    Sex differences in shared behaviors (for example, locomotion and feeding) are a nearly universal feature of animal biology. Though these behaviors may share underlying neural programs, their kinematics can exhibit robust differences between males and females. The neural underpinnings of these differences are poorly understood because of the often-untested assumption that they are determined by sex-specific body morphology. Here, we address this issue in the nematode Caenorhabditis elegans, which features two sexes with distinct body morphologies but similar locomotor circuitry and body muscle. Quantitative behavioral analysis shows that C. elegans and related nematodes exhibit significant sex differences in the dynamics and geometry of locomotor body waves, such that the male is generally faster. Using a recently proposed model of locomotor wave propagation, we show that sex differences in both body mechanics and the intrinsic dynamics of the motor system can contribute to kinematic differences in distinct mechanical contexts. By genetically sex-reversing the properties of specific tissues and cells, however, we find that sex-specific locomotor frequency in C. elegans is determined primarily by the functional modification of shared sensory neurons. Further, we find that sexual modification of body wall muscle together with the nervous system is required to alter body wave speed. Thus, rather than relying on a single focus of modification, sex differences in motor dynamics require independent modifications to multiple tissue types. Our results suggest shared motor behaviors may be sex-specifically optimized though distributed modifications to several aspects of morphology and physiology. PMID:24478342

  11. Biographic and behavioral factors are associated with music-related motor skills in children pianists.

    PubMed

    Spector, June T; Yong, Raymond; Altenmüller, Eckart; Jabusch, Hans-Christian

    2014-10-01

    This study aimed to identify biographical and behavioral factors associated with children pianists' motor skills using an objective assessment of a music-relevant motor task. Motor skills at the piano were assessed in 30 children pianists by measuring temporal unevenness in standardized scale playing using musical instrument digital interface (MIDI)-based scale analysis. Questionnaires were used to collect detailed information about the amount of time playing the piano, practice characteristics, attitudes toward music and practice, and the environment of music and practice. Associations between performance values and variables from the questionnaire were investigated using multivariable linear regression. A higher number of years playing the piano, more frequent parental involvement in the child's practice, more frequent practice of technical exercises, and greater enjoyment of practice and of the visual arts were associated with better motor performance. In addition to cumulative experience and aspects of practice, extrinsic motivational factors (e.g., parental interest) and intrinsic motivational factors (e.g., an artistic disposition) were associated with better performance on a musically-relevant motor task in children pianists. PMID:25215624

  12. Abnormalities of physics and mechanical properties, behavior of helium and hydrogen in the V-Ti alloys (Overview)

    NASA Astrophysics Data System (ADS)

    Staltsov, M. S.; Chernov, I. I.; Kalin, B. A.; Korchagin, O. N.; Anan'in, V. M.

    2016-04-01

    The paper presents the results of studies of physical and mechanical properties, helium and hydrogen behavior in vanadium-titanium alloys depending on titanium content. In particular, the results of helium swelling research, thermal desorption studies of helium and hydrogen behavior, results of internal friction measurements, measuring amount of hydrogen retained introduced by various methods. It was shown that the addition of titanium to vanadium have nonmonotonic influence on the behavior of implanted helium and hydrogen, as well as on the physical and mechanical and radiation properties known in literature. It is expected that such an abnormal influence of titanium on various properties of vanadium-titanium alloys occurs because of the interaction of vanadium and titanium atoms with atoms of interstitial impurities.

  13. Abnormal bipolar resistive switching behavior in a Pt/GaO{sub 1.3}/Pt structure

    SciTech Connect

    Guo, D. Y.; Wu, Z. P.; Zhang, L. J.; Yang, T.; Hu, Q. R.; Lei, M.; Tang, W. H. E-mail: pgli@zstu.edu.cn; Li, P. G. E-mail: pgli@zstu.edu.cn; Li, L. H.

    2015-07-20

    A stable and repeatable abnormal bipolar resistive switching behavior was observed in a Pt/GaO{sub 1.3}/Pt sandwich structure without an electroforming process. The low resistance state (LRS) and the high resistance state (HRS) of the device can be distinguished clearly and be switched reversibly under a train of the voltage pulses. The LRS exhibits a conduction of electron tunneling, while the HRS shows a conduction of Schottky-type. The observed phenomena are considered to be related to the migration of oxygen vacancies which changes the space charge region width of the metal/semiconductor interface and results in a different electron transport mechanism.

  14. Deprivation and Recovery of Sleep in Succession Enhances Reflexive Motor Behavior

    PubMed Central

    Sprenger, Andreas; Weber, Frederik D.; Machner, Bjoern; Talamo, Silke; Scheffelmeier, Sabine; Bethke, Judith; Helmchen, Christoph; Gais, Steffen; Kimmig, Hubert; Born, Jan

    2015-01-01

    Sleep deprivation impairs inhibitory control over reflexive behavior, and this impairment is commonly assumed to dissipate after recovery sleep. Contrary to this belief, here we show that fast reflexive behaviors, when practiced during sleep deprivation, is consolidated across recovery sleep and, thereby, becomes preserved. As a model for the study of sleep effects on prefrontal cortex-mediated inhibitory control in humans, we examined reflexive saccadic eye movements (express saccades), as well as speeded 2-choice finger motor responses. Different groups of subjects were trained on a standard prosaccade gap paradigm before periods of nocturnal sleep and sleep deprivation. Saccade performance was retested in the next morning and again 24 h later. The rate of express saccades was not affected by sleep after training, but slightly increased after sleep deprivation. Surprisingly, this increase augmented even further after recovery sleep and was still present 4 weeks later. Additional experiments revealed that the short testing after sleep deprivation was sufficient to increase express saccades across recovery sleep. An increase in speeded responses across recovery sleep was likewise found for finger motor responses. Our findings indicate that recovery sleep can consolidate motor disinhibition for behaviors practiced during prior sleep deprivation, thereby persistently enhancing response automatization. PMID:26048955

  15. Cellular Mechanisms Underlying Behavioral State-Dependent Bidirectional Modulation of Motor Cortex Output

    PubMed Central

    Schiemann, Julia; Puggioni, Paolo; Dacre, Joshua; Pelko, Miha; Domanski, Aleksander; van Rossum, Mark C.W.; Duguid, Ian

    2015-01-01

    Summary Neuronal activity in primary motor cortex (M1) correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B) pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed) firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1) a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons), and (2) a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons) that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior. PMID:25981037

  16. Tau deposition drives neuropathological, inflammatory and behavioral abnormalities independently of neuronal loss in a novel mouse model

    PubMed Central

    Cook, Casey; Kang, Silvia S.; Carlomagno, Yari; Lin, Wen-Lang; Yue, Mei; Kurti, Aishe; Shinohara, Mitsuru; Jansen-West, Karen; Perkerson, Emilie; Castanedes-Casey, Monica; Rousseau, Linda; Phillips, Virginia; Bu, Guojun; Dickson, Dennis W.; Petrucelli, Leonard; Fryer, John D.

    2015-01-01

    Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints of existing models of tauopathy. In order to generate a more versatile mouse model of tauopathy, somatic brain transgenesis was utilized to deliver adeno-associated virus serotype 1 (AAV1) encoding human mutant P301L-tau compared with GFP control. At 6 months of age, we observed widespread human tau expression with concomitant accumulation of hyperphosphorylated and abnormally folded proteinase K resistant tau. However, no overt neuronal loss was observed, though significant abnormalities were noted in the postsynaptic scaffolding protein PSD95. Neurofibrillary pathology was also detected with Gallyas silver stain and Thioflavin-S, and electron microscopy revealed the deposition of closely packed filaments. In addition to classic markers of tauopathy, significant neuroinflammation and extensive gliosis were detected in AAV1-TauP301L mice. This model also recapitulates the behavioral phenotype characteristic of mouse models of tauopathy, including abnormalities in exploration, anxiety, and learning and memory. These findings indicate that biochemical and neuropathological hallmarks of tauopathies are accurately conserved and are independent of cell death in this novel AAV-based model of tauopathy, which offers exceptional versatility and speed in comparison with existing transgenic models. Therefore, we anticipate this approach will facilitate the identification and validation of genetic modifiers of disease, as well as accelerate preclinical assessment of potential therapeutic targets. PMID:26276810

  17. Proficient Motor Impulse Control in Parkinson Disease patients with Impulsive and Compulsive Behaviors

    PubMed Central

    Claassen, Daniel O.; van den Wildenberg, Wery P. M.; Harrison, Madaline; van Wouwe, Nelleke C.; Kanoff, Kristen; Neimat, Joseph; Wylie, Scott A.

    2014-01-01

    Background Parkinson Disease (PD) patients treated with Dopamine Agonist therapy can develop maladaptive reward-driven behaviors, known as Impulse Control Disorder (ICD). In this study, we assessed if ICD patients have evidence of motor-impulsivity. Methods We used the stop-signal task in a cohort of patients with and without active symptoms of ICD to evaluate motor-impulsivity. Of those with PD, 12 were diagnosed with ICD symptoms (PD-ICD) and were assessed before clinical reduction of Dopamine Agonist medication; 12 were without symptoms of ICD [PD-control] and taking equivalent dosages of Dopamine Agonist. Levodopa, if present, was maintained in both settings. Groups were similar in age, duration, and severity of motor symptoms, levodopa co-therapy, and total levodopa daily dose. All were tested in the Dopamine Agonist medicated and acutely withdrawn (24 hours) state, in a counterbalanced manner. Primary outcome measures were mean reaction time to correct go trials (Go Reaction Time), and mean stop-signal reaction time (SSRT). Results ICD patients produce faster SSRT than both Healthy Controls, and PD Controls. Faster SSRT in ICD patients is apparent in both Dopamine Agonist medication states. Also, we show unique dopamine medication effects on GoRT. In Dopamine Agonist monotherapy patients, Dopamine Agonist administration speeds Go Reaction Time. Conversely, in those with levodopa co-therapy, Dopamine Agonist administration slows Go Reaction Time. Discussion PD patients with active ICD symptoms are significantly faster at stopping initiated motor actions, and this is not altered by acute Dopamine Agonist withdrawal. In addition, the effect of Dopamine Agonist on Go Reaction Time is strongly influenced by the presence or absence of levodopa, even though levodopa co-therapy does not appear to influence SSRT. We discuss these findings as they pertain to the multifaceted definition of ‘impulsivity,’ the lack of evidence for motor-impulsivity in PD-ICD, and

  18. Noninvasive, accurate assessment of the behavior of representative populations of motor units in targeted reinnervated muscles.

    PubMed

    Farina, Dario; Rehbaum, Hubertus; Holobar, Aleš; Vujaklija, Ivan; Jiang, Ning; Hofer, Christian; Salminger, Stefan; van Vliet, Hans-Willem; Aszmann, Oskar C

    2014-07-01

    Targeted muscle reinnervation (TMR) redirects nerves that have lost their target, due to amputation, to remaining muscles in the region of the stump with the intent of establishing intuitive myosignals to control a complex prosthetic device. In order to directly recover the neural code underlying an attempted limb movement, in this paper, we present the decomposition of high-density surface electromyographic (EMG) signals detected from three TMR patients into the individual motor unit spike trains. The aim was to prove, for the first time, the feasibility of decoding the neural drive that would reach muscles of the missing limb in TMR patients, to show the accuracy of the decoding, and to demonstrate the representativeness of the pool of extracted motor units. Six to seven flexible EMG electrode grids of 64 electrodes each were mounted over the reinnervated muscles of each patient, resulting in up to 448 EMG signals. The subjects were asked to attempt elbow extension and flexion, hand open and close, wrist extension and flexion, wrist pronation and supination, of their missing limb. The EMG signals were decomposed using the Convolution Kernel Compensation technique and the decomposition accuracy was evaluated with a signal-based index of accuracy, called pulse-to-noise ratio (PNR). The results showed that the spike trains of 3 to 27 motor units could be identified for each task, with a sensitivity of the decomposition > 90%, as revealed by PNR. The motor unit discharge rates were within physiological values of normally innervated muscles. Moreover, the detected motor units showed a high degree of common drive so that the set of extracted units per task was representative of the behavior of the population of active units. The results open a path for a new generation of human-machine interfaces in which the control signals are extracted from noninvasive recordings and the obtained neural information is based directly on the spike trains of motor neurons. PMID

  19. Structural and functional connectivity in healthy aging: Associations for cognition and motor behavior.

    PubMed

    Hirsiger, Sarah; Koppelmans, Vincent; Mérillat, Susan; Liem, Franziskus; Erdeniz, Burak; Seidler, Rachael D; Jäncke, Lutz

    2016-03-01

    Age-related behavioral declines may be the result of deterioration of white matter tracts, affecting brain structural (SC) and functional connectivity (FC) during resting state. To date, it is not clear if the combination of SC and FC data could better predict cognitive/motor performance than each measure separately. We probed these relationships in the cingulum bundle, a major white matter pathway of the default mode network. We aimed to attain deeper knowledge about: (a) the relationship between age and the cingulum's SC and FC strength, (b) the association between SC and FC, and particularly (c) how the cingulum's SC and FC are related to cognitive/motor performance separately and combined. We examined these associations in a healthy and well-educated sample of 165 older participants (aged 64-85). SC and FC were acquired using probabilistic tractography to derive measures to capture white matter integrity within the cingulum bundle (fractional anisotropy, mean, axial and radial diffusivity) and a seed-based resting-state functional MRI correlation approach, respectively. Participants performed cognitive tests measuring processing speed, memory and executive functions, and motor tests measuring motor speed and grip force. Our data revealed that only SC but not resting state FC was significantly associated with age. Further, the cingulum's SC and FC showed no relation. Different relationships between cognitive/motor performance and SC/FC separately were found, but no additive effect of the combined analysis of cingulum's SC and FC for predicting cognitive/motor performance was apparent. Hum Brain Mapp 37:855-867, 2016. © 2015 Wiley Periodicals, Inc. PMID:26663386

  20. Adolescent Balloon Analog Risk Task and Behaviors that Influence Risk of Motor Vehicle Crash Injury

    PubMed Central

    Vaca, Federico E.; Walthall, Jessica M.; Ryan, Sheryl; Moriarty-Daley, Alison; Riera, Antonio; Crowley, Michael J.; Mayes, Linda C.

    2013-01-01

    Risk-taking propensity is a pivotal facet of motor vehicle crash involvement and subsequent traumatic injury in adolescents. Clinical encounters are important opportunities to identify teens with high risk-taking propensity who may later experience serious injury. Our objective was to compare self-reports of health risk behavior with performance on the Balloon Analog Risk Task (BART), a validated metric of risk-taking propensity, in adolescents during a clinical encounter. 100 adolescent patients from a hospital emergency department and adolescent health clinic completed a computer-based survey of self-reported risk behaviors including substance use behaviors and behaviors that influence crash involvement. They then completed the BART, a validated laboratory-based risk task in which participants earn points by pumping up a computer-generated balloon with greater pumps leading to increased chance of balloon explosion. 20 trials were undertaken. Mean number of pumps on the BART showed a correlation of .243 (p=.015) with self-reported driver/passenger behaviors and attitudes towards driving that influence risk of crash injury. Regression analyses showed that self-reports of substance use and mean number of pumps on the BART uniquely predict self-reports of behaviors influencing the risk of crash injury. The BART is a promising correlate of real-world risk-taking behavior related to traffic safety. It remains a valid predictor of behaviors influencing risk of crash injury when using just 10 trials, suggesting its utility as a quick and effective screening measure for use in busy clinical environments. This tool may be an important link to prevention interventions for those most at-risk for future motor vehicle crash involvement and injury. PMID:24406948

  1. Transition to superdiffusive behavior in intracellular actin-based transport mediated by molecular motors

    NASA Astrophysics Data System (ADS)

    Bruno, L.; Levi, V.; Brunstein, M.; Despósito, M. A.

    2009-07-01

    Intracellular transport of large cargoes, such as organelles, vesicles, or large proteins, is a complex dynamical process that involves the interplay of adenosine triphosphate-consuming molecular motors, cytoskeleton filaments, and the viscoelastic cytoplasm. In this work we investigate the motion of pigment organelles (melanosomes) driven by myosin-V motors in Xenopus laevis melanocytes using a high-spatio-temporal resolution tracking technique. By analyzing the obtained trajectories, we show that the melanosomes mean-square displacement undergoes a transition from a subdiffusive to a superdiffusive behavior. A stochastic theoretical model, which explicitly considers the collective action of the molecular motors, is introduced to generalize the interpretation of our data. Starting from a generalized Langevin equation, we derive an analytical expression for the mean square displacement, which also takes into account the experimental noise. By fitting theoretical expressions to experimental data we were able to discriminate the exponents that characterize the passive and active contributions to the dynamics and to estimate the “global” motor forces correctly. Then, our model gives a quantitative description of active transport in living cells with a reduced number of parameters.

  2. Circuits for grasping: spinal dI3 interneurons mediate cutaneous control of motor behavior.

    PubMed

    Bui, Tuan V; Akay, Turgay; Loubani, Osama; Hnasko, Thomas S; Jessell, Thomas M; Brownstone, Robert M

    2013-04-10

    Accurate motor performance depends on the integration in spinal microcircuits of sensory feedback information. Hand grasp is a skilled motor behavior known to require cutaneous sensory feedback, but spinal microcircuits that process and relay this feedback to the motor system have not been defined. We sought to define classes of spinal interneurons involved in the cutaneous control of hand grasp in mice and to show that dI3 interneurons, a class of dorsal spinal interneurons marked by the expression of Isl1, convey input from low threshold cutaneous afferents to motoneurons. Mice in which the output of dI3 interneurons has been inactivated exhibit deficits in motor tasks that rely on cutaneous afferent input. Most strikingly, the ability to maintain grip strength in response to increasing load is lost following genetic silencing of dI3 interneuron output. Thus, spinal microcircuits that integrate cutaneous feedback crucial for paw grip rely on the intermediary role of dI3 interneurons. PMID:23583114

  3. Regression rate behaviors of HTPB-based propellant combinations for hybrid rocket motor

    NASA Astrophysics Data System (ADS)

    Sun, Xingliang; Tian, Hui; Li, Yuelong; Yu, Nanjia; Cai, Guobiao

    2016-02-01

    The purpose of this paper is to characterize the regression rate behavior of hybrid rocket motor propellant combinations, using hydrogen peroxide (HP), gaseous oxygen (GOX), nitrous oxide (N2O) as the oxidizer and hydroxyl-terminated poly-butadiene (HTPB) as the based fuel. In order to complete this research by experiment and simulation, a hybrid rocket motor test system and a numerical simulation model are established. Series of hybrid rocket motor firing tests are conducted burning different propellant combinations, and several of those are used as references for numerical simulations. The numerical simulation model is developed by combining the Navies-Stokes equations with the turbulence model, one-step global reaction model, and solid-gas coupling model. The distribution of regression rate along the axis is determined by applying simulation mode to predict the combustion process and heat transfer inside the hybrid rocket motor. The time-space averaged regression rate has a good agreement between the numerical value and experimental data. The results indicate that the N2O/HTPB and GOX/HTPB propellant combinations have a higher regression rate, since the enhancement effect of latter is significant due to its higher flame temperature. Furthermore, the containing of aluminum (Al) and/or ammonium perchlorate(AP) in the grain does enhance the regression rate, mainly due to the more energy released inside the chamber and heat feedback to the grain surface by the aluminum combustion.

  4. Heterozygous deletion of a 2-Mb region including the dystroglycan gene in a patient with mild myopathy, facial hypotonia, oral-motor dyspraxia and white matter abnormalities.

    PubMed

    Frost, Amy R; Böhm, Sabrina V; Sewduth, Raj N; Josifova, Dragana; Ogilvie, Caroline Mackie; Izatt, Louise; Roberts, Roland G

    2010-07-01

    Dystroglycan is a protein which binds directly to two proteins defective in muscular dystrophies (dystrophin and laminin alpha2) and whose own aberrant post-translational modification is the common aetiological route of neuromuscular diseases associated with mutations in genes encoding at least six other proteins (POMT1, POMT2, POMGnT1, LARGE, FKTN and FKRP). It is surprising, therefore, that to our knowledge no mutations of the human dystroglycan gene itself have yet been reported. In this study, we describe a patient with a heterozygous de novo deletion of a approximately 2-Mb region of chromosome 3, which includes the dystroglycan gene (DAG1). The patient is a 16-year-old female with learning difficulties, white matter abnormalities, elevated serum creatine kinase, oral-motor dyspraxia and facial hypotonia but minimal clinically significant involvement of other muscles. As these symptoms are a subset of those observed in disorders of dystroglycan glycosylation (muscle-eye-brain disease and Warker-Warburg syndrome), we assess the likely contribution to her phenotype of her heterogosity for a null mutation of DAG1. We also show that the transcriptional compensation observed in the Dag1(+/-) mouse is not observed in the patient. Although we cannot show that haploinsufficiency of DAG1 is the sole cause of this patient's myopathy and white matter changes, this case serves to constrain our ideas of the severity of the phenotypic consequences of heterozygosity for null DAG1 mutations. PMID:20234391

  5. Heterozygous deletion of a 2-Mb region including the dystroglycan gene in a patient with mild myopathy, facial hypotonia, oral-motor dyspraxia and white matter abnormalities

    PubMed Central

    Frost, Amy R; Böhm, Sabrina V; Sewduth, Raj N; Josifova, Dragana; Ogilvie, Caroline Mackie; Izatt, Louise; Roberts, Roland G

    2010-01-01

    Dystroglycan is a protein which binds directly to two proteins defective in muscular dystrophies (dystrophin and laminin α2) and whose own aberrant post-translational modification is the common aetiological route of neuromuscular diseases associated with mutations in genes encoding at least six other proteins (POMT1, POMT2, POMGnT1, LARGE, FKTN and FKRP). It is surprising, therefore, that to our knowledge no mutations of the human dystroglycan gene itself have yet been reported. In this study, we describe a patient with a heterozygous de novo deletion of a ∼2-Mb region of chromosome 3, which includes the dystroglycan gene (DAG1). The patient is a 16-year-old female with learning difficulties, white matter abnormalities, elevated serum creatine kinase, oral-motor dyspraxia and facial hypotonia but minimal clinically significant involvement of other muscles. As these symptoms are a subset of those observed in disorders of dystroglycan glycosylation (muscle–eye–brain disease and Warker–Warburg syndrome), we assess the likely contribution to her phenotype of her heterogosity for a null mutation of DAG1. We also show that the transcriptional compensation observed in the Dag1+/− mouse is not observed in the patient. Although we cannot show that haploinsufficiency of DAG1 is the sole cause of this patient's myopathy and white matter changes, this case serves to constrain our ideas of the severity of the phenotypic consequences of heterozygosity for null DAG1 mutations. PMID:20234391

  6. Abnormal behavioral responses to fenfluramine in patients with affective and personality disorders. Correlation with increased serotonergic responsivity.

    PubMed

    Myers, J E; Mieczkowski, T; Perel, J; Abbondanza, D; Cooper, T B; Mann, J J

    1994-01-15

    Serotonergic responsivity was assessed in 20 psychiatric patients by the prolactin response to a fenfluramine challenge test. During the fenfluramine challenge 6 of 20 patients (30%) spontaneously reported psychopathologic reactions that included: increased anxiety/agitation, psychotic symptoms, illusions, mood elevation, and anergia. The time of peak behavioral symptoms (2.5 +/- 0.8 hrs) corresponded closely to the time of peak increase in prolactin levels (3.0 +/- 1.1 hr). Abnormal behavioral responders had statistically significant greater increases in prolactin 1 to 4 hr after fenfluramine when compared to normal responders. Patients who developed an abnormal psychopathologic response to fenfluramine were characterized by higher levels of anxiety and agitation at the time of admission to the hospital but otherwise were not distinguishable on the basis of severity of other psychiatric symptoms. This study suggests that increased serotonergic transmission may trigger anxiety, psychosis, and mood elevation in specific vulnerable individuals, whereas other patients with similar psychiatric illnesses are not affected. PMID:8167207

  7. Abnormal vibrissa-related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics

    PubMed Central

    Flanigan, Timothy J.; Xue, Yi; Rao, Shailaja Kishan; Anandh, Dhanushkodi; McDonald, Michael P.

    2014-01-01

    A recent study reported lower anxiety in the 5xFAD transgenic mouse model of Alzheimer's disease, as measured by reduced time on the open arms of an elevated plus maze. This is important because all behaviors in experimental animals must be interpreted in light of basal anxiety and response to novel environments. We conducted a comprehensive anxiety battery in the 5xFAD transgenics and replicated the plus-maze phenotype. However, we found that it did not reflect reduced anxiety, but rather abnormal avoidance of the closed arms on the part of transgenics and within-session habituation to the closed arms on the part of wild-type controls. We noticed that the 5xFAD transgenics did not engage in the whisker-barbering behavior typical of mice of this background strain. This is suggestive of abnormal social behavior, and we suspected it might be related to their avoidance of the closed arms on the plus maze. Indeed, transgenic mice exhibited excessive home-cage social behavior and impaired social recognition, and did not permit barbering by wild-type mice when pair-housed. When their whiskers were snipped the 5xFAD transgenics no longer avoided the closed arms on the plus maze. Examination of parvalbumin (PV) staining showed a 28.9% reduction in PV+ inhibitory interneurons in the in barrel fields of 5xFAD mice, and loss of PV+ fibers in layers IV and V. This loss of vibrissal inhibition suggests a putatively aversive overstimulation that may be responsible for the transgenics’ avoidance of the closed arms in the plus maze. PMID:24655396

  8. Effects of moderate prenatal ethanol exposure and age on social behavior, spatial response perseveration errors and motor behavior.

    PubMed

    Hamilton, Derek A; Barto, Daniel; Rodriguez, Carlos I; Magcalas, Christy M; Fink, Brandi C; Rice, James P; Bird, Clark W; Davies, Suzy; Savage, Daniel D

    2014-08-01

    Persistent deficits in social behavior are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked deficits in social behavior following moderate prenatal alcohol exposure (PAE) in the rat to functional alterations in the ventrolateral frontal cortex [21]. In addition to social behaviors, the regions comprising the ventrolateral frontal cortex are critical for diverse processes ranging from orofacial motor movements to flexible alteration of behavior in the face of changing consequences. The broader behavioral implications of altered ventrolateral frontal cortex function following moderate PAE have, however, not been examined. In the present study we evaluated the consequences of moderate PAE on social behavior, tongue protrusion, and flexibility in a variant of the Morris water task that required modification of a well-established spatial response. PAE rats displayed deficits in tongue protrusion, reduced flexibility in the spatial domain, increased wrestling, and decreased investigation, indicating that several behaviors associated with ventrolateral frontal cortex function are impaired following moderate PAE. A linear discriminant analysis revealed that measures of wrestling and tongue protrusion provided the best discrimination of PAE rats from saccharin-exposed control rats. We also evaluated all behaviors in young adult (4-5 months) or older (10-11 months) rats to address the persistence of behavioral deficits in adulthood and possible interactions between early ethanol exposure and advancing age. Behavioral deficits in each domain persisted well into adulthood (10-11 months), however, there was no evidence that aging enhances the effects of moderate PAE within the age ranges that were studied. PMID:24769174

  9. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model

    PubMed Central

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-01-01

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer’s disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency. PMID:27438830

  10. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model.

    PubMed

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-01-01

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer's disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency. PMID:27438830

  11. Odor-identity dependent motor programs underlie behavioral responses to odors

    PubMed Central

    Jung, Seung-Hye; Hueston, Catherine; Bhandawat, Vikas

    2015-01-01

    All animals use olfactory information to perform tasks essential to their survival. Odors typically activate multiple olfactory receptor neuron (ORN) classes and are therefore represented by the patterns of active ORNs. How the patterns of active ORN classes are decoded to drive behavior is under intense investigation. In this study, using Drosophila as a model system, we investigate the logic by which odors modulate locomotion. We designed a novel behavioral arena in which we could examine a fly’s locomotion under precisely controlled stimulus condition. In this arena, in response to similarly attractive odors, flies modulate their locomotion differently implying that odors have a more diverse effect on locomotion than was anticipated. Three features underlie odor-guided locomotion: First, in response to odors, flies modulate a surprisingly large number of motor parameters. Second, similarly attractive odors elicit changes in different motor programs. Third, different ORN classes modulate different subset of motor parameters. DOI: http://dx.doi.org/10.7554/eLife.11092.001 PMID:26439011

  12. The effects of yoga practice in school physical education on children's motor abilities and social behavior

    PubMed Central

    Folleto, Júlia C; Pereira, Keila RG; Valentini, Nadia Cristina

    2016-01-01

    Background: In recent years, yoga programs in childhood have been implemented in schools, to promote the development for children. Aim: To investigate the effects of yoga program in physical education classes on the motor abilities and social behavior parameters of 6–8-year-old children. Methods: The study included 16 children from the 1st grade of a public elementary school in the South of Brazil. The children participated in a 12-week intervention, twice weekly, with 45 min each session. To assess children's performance, we used the Bruininks-Oseretsky Test of Motor Proficiency - Second Edition, the flexibility test (sit and reach – Eurofit, 1988), the Pictorial Scale of Perceived Competence and Social Acceptance for Young Children and semi-structured interviews with children, parents, and classroom’ teacher. Data were analyzed with Wilcoxon test and level of significance was 5%. Results: The yoga program was well accepted by children, children also demonstrated significant and positive changes in overall motor abilities scores (balance, strength, and flexibility). In addition, the interviews reported changing in social behavior and the use of the knowledge learned in the program in contexts outside of school. Conclusion: These findings suggest that the implementation of yoga practice in physical education lessons contributed to children's development. PMID:27512323

  13. Abnormal relationship between GABA, neurophysiology and impulsive behavior in neurofibromatosis type 1

    PubMed Central

    Ribeiro, Maria J.; Violante, Inês R.; Bernardino, Inês; Edden, Richard A.E.; Castelo-Branco, Miguel

    2016-01-01

    Neurofibromatosis type 1 (NF1) is a neurodevelopmental disorder characterized by a broad spectrum of cognitive deficits. In particular, executive dysfunction is recognized as a core deficit of NF1, including impairments in executive attention and inhibitory control. Yet, the neural mechanisms behind these important deficits are still unknown. Here, we studied inhibitory control in a visual go/no-go task in children and adolescents with NF1 and age- and gender-matched controls (n = 16 per group). We applied a multimodal approach using high-density electroencephalography (EEG), to study the evoked brain responses, and magnetic resonance spectroscopy (MRS) to measure the levels of GABA and glutamate + glutamine in the medial frontal cortex, a brain region that plays a pivotal role in inhibitory control, and also in a control region, the occipital cortex. Finally, we run correlation analyses to identify the relationship between inhibitory control, levels of neurotransmitters, and EEG markers of neural function. Individuals with NF1 showed impaired impulse control and reduced EEG correlates of early visual processing (parieto-occipital P1) and inhibitory control (frontal P3). MRS data revealed a reduction in medial frontal GABA+/tCr (total Creatine) levels in the NF1 group, in parallel with the already reported reduced occipital GABA levels. In contrast, glutamate + glutamine/tCr levels were normal, suggesting the existence of abnormal inhibition/excitation balance in this disorder. Notably, medial frontal but not occipital GABA levels correlated with general intellectual abilities (IQ) in NF1, and inhibitory control in both groups. Surprisingly, the relationship between inhibitory control and medial frontal GABA was reversed in NF1: higher GABA was associated with a faster response style whereas in controls it was related to a cautious strategy. Abnormal GABAergic physiology appears, thus, as an important factor underlying impaired cognition in NF1, in a level and

  14. Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra.

    PubMed

    Heng, Yang; Zhang, Qiu-Shuang; Mu, Zheng; Hu, Jin-Feng; Yuan, Yu-He; Chen, Nai-Hong

    2016-01-22

    Parkinson's disease (PD) is pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of aggregated α-synuclein in specific central nervous system (CNS) regions. Disease development is attributed to α-synuclein abnormalities, particularly aggregation and phosphorylation. The ginsenoside Rg1, an active component of ginseng, possesses neuroprotective and anti-inflammatory effects. The purpose of the present study was to evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid (MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms. Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality, behavior defects, loss of dopamine neurons and abnormal ultrastructure changes in the SNpc. Other assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory properties. Rg1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the SNpc. Rg1 also alleviated the unusual MPTP-induced increase in oligomeric, phosphorylated and disease-related α-synuclein in the SNpc. In conclusion, Rg1 protects dopaminergic neurons, most likely by reducing aberrant α-synuclein-mediated neuroinflammation, and holds promise for PD therapeutics. PMID:26723869

  15. The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake.

    PubMed

    Godar, Sean C; Bortolato, Marco; Castelli, M Paola; Casti, Alberto; Casu, Angelo; Chen, Kevin; Ennas, M Grazia; Tambaro, Simone; Shih, Jean C

    2014-09-01

    The termination of serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is regulated by its uptake by the 5-HT transporter (5-HTT), as well as its degradation by monoamine oxidase (MAO)-A. MAO-A deficiency results in a wide set of behavioral alterations, including perseverative behaviors and social deficits. These anomalies are likely related to 5-HTergic homeostatic imbalances; however, the role of 5-HTT in these abnormalities remains unclear. To ascertain the role of 5-HTT in the behavioral anomalies associated to MAO-A deficiency, we tested the behavioral effects of its blocker fluoxetine on perseverative, social and aggressive behaviors in transgenic animals with hypomorphic or null-allele MAO-A mutations. Acute treatment with the 5-HTT blocker fluoxetine (10 mg/kg, i.p.) reduced aggressive behavior in MAO-A knockout (KO) mice and social deficits in hypomorphic MAO-A(Neo) mice. Furthermore, this treatment also reduced perseverative responses (including marble burying and water mist-induced grooming) in both MAO-A mutant genotypes. Both MAO-A mutant lines displayed significant reductions in 5-HTT expression across the prefrontal cortex, amygdala and striatum, as quantified by immunohistochemical detection; however, the down-regulation of 5-HTT in MAO-A(Neo) mice was more pervasive and widespread than in their KO counterparts, possibly indicating a greater ability of the hypomorphic line to enact compensatory mechanisms with respect to 5-HT homeostasis. Collectively, these findings suggest that the behavioral deficits associated with low MAO-A activity may reflect developmental alterations of 5-HTT within 5-HTergic neurons. Furthermore, the translational implications of our results highlight 5-HT reuptake inhibition as an interesting approach for the control of aggressive outbursts in MAO-A deficient individuals. PMID:24882701

  16. Multiplexing of Motor Information in the Discharge of a Collision Detecting Neuron during Escape Behaviors

    PubMed Central

    Fotowat, Haleh; Harrison, Reid R; Gabbiani, Fabrizio

    2010-01-01

    Locusts possess an identified neuron, the descending contralateral movement detector (DCMD), conveying visual information about impending collision from the brain to thoracic motor centers. We built a telemetry system to simultaneously record, in freely behaving animals, the activity of the DCMD and of motoneurons involved in jump execution. Co-contraction of antagonistic leg muscles, a required preparatory phase, was triggered after the DCMD firing rate crossed a threshold. Thereafter, the number of DCMD spikes predicted precisely motoneuron activity and jump occurrence. Additionally, the time of DCMD peak firing rate predicted that of jump. Ablation experiments suggest that the DCMD, together with a nearly identical ipsilateral descending neuron, is responsible for the timely execution of the escape. Thus, three distinct features that are multiplexed in a single neuron’s sensory response to impending collision – firing rate threshold, peak firing time, and spike count – likely control three distinct motor aspects of escape behaviors. PMID:21220105

  17. Multiplexing of motor information in the discharge of a collision detecting neuron during escape behaviors.

    PubMed

    Fotowat, Haleh; Harrison, Reid R; Gabbiani, Fabrizio

    2011-01-13

    Locusts possess an identified neuron, the descending contralateral movement detector (DCMD), conveying visual information about impending collision from the brain to thoracic motor centers. We built a telemetry system to simultaneously record, in freely behaving animals, the activity of the DCMD and of motoneurons involved in jump execution. Cocontraction of antagonistic leg muscles, a required preparatory phase, was triggered after the DCMD firing rate crossed a threshold. Thereafter, the number of DCMD spikes predicted precisely motoneuron activity and jump occurrence. Additionally, the time of DCMD peak firing rate predicted that of jump. Ablation experiments suggest that the DCMD, together with a nearly identical ipsilateral descending neuron, is responsible for the timely execution of the escape. Thus, three distinct features that are multiplexed in a single neuron's sensory response to impending collision-firing rate threshold, peak firing time, and spike count-probably control three distinct motor aspects of escape behaviors. PMID:21220105

  18. Oral supplements of aqueous extract of tomato seeds alleviate motor abnormality, oxidative impairments and neurotoxicity induced by rotenone in mice: relevance to Parkinson's disease.

    PubMed

    Gokul, Krishna; Muralidhara

    2014-07-01

    Although tomato seeds (an industrial by-product) are known to contain several bioactive compounds, studies describing their health effects are limited. Previously, we evidenced that aqueous extract of tomato seeds (TSE) markedly attenuated rotenone (ROT)-induced oxidative stress and neurotoxicity in Drosophila system. This study investigated the neuroprotective effect of TSE in a chronic ROT model of neurotoxicity in mice. Initially, we assessed the potential of oral supplements of TSE to modulate the levels of endogenous markers of oxidative stress in brain regions of mice. Subsequently, employing a co-exposure paradigm, the propensity of TSE (100 mg/kg bw, 3 weeks) to attenuate ROT-induced behavioral phenotype (gait abnormalities, anxiety-like state), oxidative dysfunctions and neurotoxicity was examined. We found that mice provided with TSE supplements exhibited progressive improvement in gait pattern and exploratory behavior. TSE markedly offset ROT-induced oxidative impairments, restored reduced glutathione levels, antioxidant defenses (superoxide dismutase, glutathione peroxidase) and protein carbonyls content in brain regions. Specifically, TSE effectively diminished ROT induced elevation in the activity levels of acetylcholinesterase and restored the dopamine levels in striatum. Interestingly, in mitochondria, TSE was able to restore the activity of mitochondrial complexes and redox state. Collectively, our findings in the chronic ROT model demonstrate the ability of TSE to alleviate behavioral phenotype, oxidative stress, mitochondrial dysfunction and neurotoxicity. Further studies in dopaminergic cell models are necessary to understand the precise molecular mechanism/s by which tomato seed bioactives offer significant neuroprotection. PMID:24831121

  19. LIN-41 inactivation leads to delayed centrosome elimination and abnormal chromosome behavior during female meiosis in Caenorhabditis elegans

    PubMed Central

    Matsuura, Rieko; Ashikawa, Tomoko; Nozaki, Yuka; Kitagawa, Daiju

    2016-01-01

    During oogenesis, two successive meiotic cell divisions occur without functional centrosomes because of the inactivation and subsequent elimination of maternal centrosomes during the diplotene stage of meiosis I. Despite being a conserved phenomenon in most metazoans, the means by which this centrosome behavior is controlled during female meiosis remain elusive. Here, we conducted a targeted RNAi screening in the Caenorhabditis elegans gonad to identify novel regulators of centrosome behavior during oogenesis. We screened 513 genes known to be essential for embryo production and directly visualized GFP–γ-tubulin to monitor centrosome behavior at all stages of oogenesis. In the screening, we found that RNAi-mediated inactivation of 33 genes delayed the elimination of GFP–γ-tubulin at centrosomes during oogenesis, whereas inactivation of nine genes accelerated the process. Depletion of the TRIM-NHL protein LIN-41 led to a significant delay in centrosome elimination and to the separation and reactivation of centrosomes during oogenesis. Upon LIN-41 depletion, meiotic chromosomes were abnormally condensed and pulled toward one of the two spindle poles around late pachytene even though the spindle microtubules emanated from both centrosomes. Overall, our work provides new insights into the regulation of centrosome behavior to ensure critical meiotic events and the generation of intact oocytes. PMID:26764090

  20. Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Monterosso, John R; Simon, Tony J; Glahn, David C; Saleh, Peter A; Hill, Nicole M; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Cannon, Tyrone D

    2004-06-01

    Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships. PMID:15788257

  1. Behavioral, neurochemical and neuroendocrine effects of abnormal savda munziq in the chronic stress mice.

    PubMed

    Amat, Nurmuhammat; Hoxur, Parida; Ming, Dang; Matsidik, Aynur; Kijjoa, Anake; Upur, Halmurat

    2012-01-01

    Oral administration of Abnormal Savda Munsiq (ASMq), a herbal preparation used in Traditional Uighur Medicine, was found to exert a memory-enhancing effect in the chronic stressed mice, induced by electric foot-shock. The memory improvement of the stressed mice was shown by an increase of the latency time in the step-through test and the decrease of the latency time in the Y-maze test. Treatment with ASMq was found to significantly decrease the serum levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT) and β-endorphin (β-EP) as well as the brain and serum level of norepinephrine (NE). Furthermore, ASMq was able to significantly reverse the chronic stress by decreasing the brain and serum levels of the monoamine neurotransmitters dopamine (DA), 5-hydroxytryptamine (5-HT) and 3,4-dihydroxyphenylalanine (DOPAC). The results obtained from this study suggested that the memory-enhancing effect of ASMq was mediated through regulations of neurochemical and neuroendocrine systems. PMID:22919413

  2. Descending influences on escape behavior and motor pattern in the cockroach.

    PubMed

    Schaefer, P L; Ritzmann, R E

    2001-10-01

    The escape behavior of the cockroach is a ballistic behavior with well characterized kinematics. The circuitry known to control the behavior lies in the thoracic ganglia, abdominal ganglia, and abdominal nerve cord. Some evidence suggests inputs may occur from the brain or suboesophageal ganglion. We tested this notion by decapitating cockroaches, removing all descending inputs, and evoking escape responses. The decapitated cockroaches exhibited directionally appropriate escape turns. However, there was a front-to-back gradient of change: the front legs moved little if at all, the middle legs moved in the proper direction but with reduced excursion, and the rear legs moved normally. The same pattern was seen when only inputs from the brain were removed, the suboesophageal ganglion remaining intact and connected to the thoracic ganglia. Electromyogram (EMG) analysis showed that the loss of or reduction in excursion was accompanied by a loss of or reduction in fast motor neuron activity. The loss of fast motor neuron activity was also observed in a reduced preparation in which descending neural signals were reversibly blocked via an isotonic sucrose solution superfusing the neck connectives, indicating that the changes seen were not due to trauma. Our data demonstrate that while the thoracic circuitry is sufficient to produce directional escape, lesion or blockage of the connective affects the excitability of components of the escape circuitry. Because of the rapidity of the escape response, such effects are likely due to the elimination of tonic descending inputs. PMID:11536194

  3. Modulation of Serotonin Transporter Function during Fetal Development Causes Dilated Heart Cardiomyopathy and Lifelong Behavioral Abnormalities

    PubMed Central

    Noorlander, Cornelle W.; Ververs, Frederique F. T.; Nikkels, Peter G. J.; van Echteld, Cees J. A.; Visser, Gerard H. A.; Smidt, Marten P.

    2008-01-01

    Background Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. Methodology/Principal Findings In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. Conclusions These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher

  4. Early life seizures in female rats lead to anxiety-related behavior and abnormal social behavior characterized by reduced motivation to novelty and deficit in social discrimination.

    PubMed

    Castelhano, Adelisandra Silva Santos; Ramos, Fabiane Ochai; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

    2015-03-01

    Previously, we demonstrated that male Wistar rats submitted to neonatal status epilepticus showed abnormal social behavior characterized by deficit in social discrimination and enhanced emotionality. Taking into account that early insult can produce different biological manifestations in a gender-dependent manner, we aimed to investigate the social behavior and anxiety-like behavior in female Wistar rats following early life seizures. Neonate female Wistar rats at 9 days postnatal were subject to pilocarpine-induced status epilepticus and the control received saline. Behavioral tests started from 60 days postnatal and were carried out only during the diestrus phase of the reproductive cycle. In sociability test experimental animals exhibited reduced motivation for social encounter and deficit in social discrimination. In open field and the elevated plus maze, experimental animals showed enhanced emotionality with no changes in basal locomotor activity. The results showed that female rats submitted to neonatal status epipepticus showed impaired social behavior, characterized by reduced motivation to novelty and deficit in social discrimination in addition to enhanced emotionality. PMID:25139483

  5. Increased apoptosis and abnormal visual behavior by histone modifications with exposure to para-xylene in developing Xenopus.

    PubMed

    Gao, Juanmei; Ruan, Hangze; Qi, Xianjie; Guo, Xia; Zheng, Jingna; Liu, Cong; Fang, Yanxiao; Huang, Minjiao; Xu, Miao; Shen, Wanhua

    2016-09-01

    Xylene and its derivatives are raw materials widely used in industry and known to be toxic to animals. However, the mechanism underlying the neurotoxicity of para-xylene (PX) to the central nervous system (CNS) in vivo is less clear. Here, we exposed Xenopus laevis tadpoles to sub-lethal concentrations of PX during the critical period of brain development to determine the effects of PX on Xenopus development and visual behavior. We found that the abnormality rate was significantly increased with exposure to increasing concentrations of PX. In particular, the number of apoptotic cells in the optic tectum was dramatically increased with exposure to PX at 2mM. Long-term PX exposure also resulted in significant deficits in visually guided avoidance behavior. Strikingly, co-incubation with PX and d-glucuronolactone (GA) decreased the number of apoptotic cells and rescued the avoidance behavior. Furthermore, we found that the acetylation of H4K12 (H4K12ac) and the dimethylation of H3K9 (H3K9me2) in the optic tectum were significantly increased in PX-treated animals, and these effects were suppressed by GA treatment. In particular, the increase in apoptotic cells in PX-treated brains was also inhibited by GA treatment. These effects indicate that epigenetic regulation plays a key role in PX-induced apoptosis and animal behavior. In an effort to characterize the neurotoxic effects of PX on brain development and behavior, these results suggest that the neurotoxicity of PX requires further evaluation regarding the safety of commercial and industrial uses. PMID:27343828

  6. Abnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairments

    PubMed Central

    Zumbrennen-Bullough, Kimberly B.; Becker, Lore; Garrett, Lillian; Hölter, Sabine M.; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J.; Leibold, Elizabeth A.

    2014-01-01

    Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments. PMID:24896637

  7. Dissociation of Structural and Functional Integrities of the Motor System in Amyotrophic Lateral Sclerosis and Behavioral-Variant Frontotemporal Dementia

    PubMed Central

    Bae, Jong Seok; Ferguson, Michele; Tan, Rachel; Mioshi, Eneida; Simon, Neil; Burrell, James; Vucic, Steve; Hodges, John R.; Kiernan, Matthew C

    2016-01-01

    Background and Purpose This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37). Methods Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. Results The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. Conclusions Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders. PMID:26932257

  8. Behavioral Problems in Children with Motor and Intellectual Disabilities: Prevalence and Associations with Maladaptive Personality and Marital Relationship

    ERIC Educational Resources Information Center

    Vrijmoeth, Cis; Monbaliu, Elegast; Lagast, Emmy; Prinzie, Peter

    2012-01-01

    Prevalence rates of behavioral problems in children with motor disabilities are commonly based on questionnaires developed for a general population (e.g., Child Behavior CheckList). These questionnaires do not take into account lower levels of intellectual functioning. The first aim of this study was to examine the prevalence of parent-reported…

  9. The Cinderella of Psychology: The Neglect of Motor Control in the Science of Mental Life and Behavior

    ERIC Educational Resources Information Center

    Rosenbaum, David A.

    2005-01-01

    One would expect psychology--the science of mental life and behavior--to place great emphasis on the means by which mental life is behaviorally expressed. Surprisingly, however, the study of how decisions are enacted--the focus of motor control research--has received little attention in psychology. This article documents the neglect and considers…

  10. Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice.

    PubMed

    Li, Qi; Chan, Siu Yuen; Wong, Kwun K; Wei, Ran; Leung, Yu On; Ding, Abby Y; Hui, Tomy C K; Cheung, Charlton; Chua, Siew E; Sham, Pak C; Wu, Ed X; McAlonan, Grainne M

    2016-07-01

    Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more 'sensitive' to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits. PMID:26826030

  11. Loss of GSK-3 Causes Abnormal Astrogenesis and Behavior in Mice.

    PubMed

    Jung, Eui-Man; Ka, Minhan; Kim, Woo-Yang

    2016-08-01

    Altered activity of glycogen synthase kinase-3 (GSK-3) is associated with psychiatric diseases and neurodegenerative diseases. GSK-3 is a key regulator in multiple aspects of neuronal differentiation in the brain. However, little is known about the role of GSK-3 in astrocyte development. To examine the role of GSK-3 in astrocytes, we generated a conditional knockout mouse using a glial fibrillary acidic protein (GFAP)-cre driver, in which the GSK-3 alpha and beta genes are deleted in astrocytes. We found that GFAP-cre-mediated GSK-3 deletion led to a larger brain. The number and size of astrocytes were increased in GSK-3 mutant brains. The levels of GFAP and phospho-STAT3, indicators of astrogenesis, were elevated in GSK-3 mutants. Furthermore, we found upregulation of astrocyte regulatory molecules such as phospho-AKT, phospho-S6, and cyclin D in GSK-3 mutant brains. Finally, GSK-3 mutant mice exhibited aberrant anxiety and social behavior. Our results suggest that GSK-3 plays a significant role in astrocyte development and behavioral control in mice. PMID:26179612

  12. Abnormal behavior of midgap electron trap in HB-GaAs during thermal annealing

    NASA Astrophysics Data System (ADS)

    Min, Suk-Ki; Kim, Eun Kyu; Cho, Hoon Young

    1988-05-01

    The behavior of the EL2 family in horizontal Bridgman-(HB) grown GaAs by two thermal annealing methods, furnace annealing and rapid thermal annealing, was studied through deep level transient spectroscopy (DLTS) measurements, and a similar behavior of another group of electron traps was observed. As the annealing time is increased, the EL2 trap (Ec-0.81 eV) is transformed to the new trap, EX2 (Ec-0.73 eV), and finally to the other new trap, EX1 (Ec-0.86 eV). Also the EL6 group (Ec-0.18, 0.22, 0.27, and 0.35 eV) varied similarly to the EL2 family as a trap (Ec-0.27 eV) is transformed to the first trap (Ec-0.18 eV) and then the second trap (Ec-0.22 eV). This result revealed that the EL2 family is related to the EL6 group. From the study of photocapacitance quenching, the existence of metastable states of the EL2 family is identified. These results suggest that the atomic structure of the EL2 trap may be an arsenic antisite with an interstitial arsenic and a double vacancy, such as VAsAsIVGaAsGa or its complex.

  13. Motor Circuit-Specific Burst Patterns Drive Different Muscle and Behavior Patterns

    PubMed Central

    Diehl, Florian; White, Rachel S.; Stein, Wolfgang

    2013-01-01

    In the isolated CNS, different modulatory inputs can enable one motor network to generate multiple output patterns. Thus far, however, few studies have established whether different modulatory inputs also enable a defined network to drive distinct muscle and movement patterns in vivo, much as they enable these distinctions in behavioral studies. This possibility is not a foregone conclusion, because additional influences present in vivo (e.g., sensory feedback, hormonal modulation) could alter the motor patterns. Additionally, rhythmic neuronal activity can be transformed into sustained muscle contractions, particularly in systems with slow muscle dynamics, as in the crab (Cancer borealis) stomatogastric system used here. We assessed whether two different versions of the biphasic (protraction, retraction) gastric mill (chewing) rhythm, triggered in the isolated stomatogastric system by the modulatory ventral cardiac neurons (VCNs) and postoesophageal commissure (POC) neurons, drive different muscle and movement patterns. One distinction between these rhythms is that the lateral gastric (LG) protractor motor neuron generates tonic bursts during the VCN rhythm, whereas its POC-rhythm bursts are divided into fast, rhythmic burstlets. Intracellular muscle fiber recordings and tension measurements show that the LG-innervated muscles retain the distinct VCN-LG and POC-LG neuron burst structures. Moreover, endoscope video recordings in vivo, during VCN-triggered and POC-triggered chewing, show that the lateral teeth protraction movements exhibit the same, distinct protraction patterns generated by LG in the isolated nervous system. Thus, the multifunctional nature of an identified motor network in the isolated CNS can be preserved in vivo, where it drives different muscle activity and movement patterns. PMID:23864688

  14. Cocaine Self-Administration Experience Induces Pathological Phasic Accumbens Dopamine Signals and Abnormal Incentive Behaviors in Drug-Abstinent Rats

    PubMed Central

    Wang, Xuefei; Sugam, Jonathan A.; Carelli, Regina M.

    2016-01-01

    Chronic exposure to drugs of abuse is linked to long-lasting alterations in the function of limbic system structures, including the nucleus accumbens (NAc). Although cocaine acts via dopaminergic mechanisms within the NAc, less is known about whether phasic dopamine (DA) signaling in the NAc is altered in animals with cocaine self-administration experience or if these animals learn and interact normally with stimuli in their environment. Here, separate groups of rats self-administered either intravenous cocaine or water to a receptacle (controls), followed by 30 d of enforced abstinence. Next, all rats learned an appetitive Pavlovian discrimination and voltammetric recordings of real-time DA release were taken in either the NAc core or shell of cocaine and control subjects. Cocaine experience differentially impaired DA signaling in the core and shell relative to controls. Although phasic DA signals in the shell were essentially abolished for all stimuli, in the core, DA did not distinguish between cues and was abnormally biased toward reward delivery. Further, cocaine rats were unable to learn higher-order associations and even altered simple conditioned approach behaviors, displaying enhanced preoccupation with cue-associated stimuli (sign-tracking; ST) but diminished time at the food cup awaiting reward delivery (goal-tracking). Critically, whereas control DA signaling correlated with ST behaviors, cocaine experience abolished this relationship. These findings show that cocaine has persistent, differential, and pathological effects on both DA signaling and DA-dependent behaviors and suggest that psychostimulant experience may remodel the very circuits that bias organisms toward repeated relapse. SIGNIFICANCE STATEMENT Relapsing to drug abuse despite periods of abstinence and sincere attempts to quit is one of the most pernicious facets of addiction. Unfortunately, little is known about how the dopamine (DA) system functions after periods of drug abstinence

  15. Dietary glycemic index modulates the behavioral and biochemical abnormalities associated with autism spectrum disorder.

    PubMed

    Currais, A; Farrokhi, C; Dargusch, R; Goujon-Svrzic, M; Maher, P

    2016-03-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder of unknown etiology, but very likely resulting from both genetic and environmental factors. There is good evidence for immune system dysregulation in individuals with ASD. However, the contribution of insults such as dietary factors that can also activate the immune system have not been explored in the context of ASD. In this paper, we show that the dietary glycemic index has a significant impact on the ASD phenotype. By using BTBR mice, an inbred strain that displays behavioral traits that reflect the diagnostic symptoms of human ASD, we found that the diet modulates plasma metabolites, neuroinflammation and brain markers of neurogenesis in a manner that is highly reflective of ASD in humans. Overall, the manuscript supports the idea that ASD results from gene-environment interactions and that in the presence of a genetic predisposition to ASD, diet can make a large difference in the expression of the condition. PMID:26055422

  16. Pomegranate supplementation improves affective and motor behavior in mice after radiation exposure.

    PubMed

    Dulcich, Melissa S; Hartman, Richard E

    2013-01-01

    Currently, NASA has plans for extended space travel, and previous research indicates that space radiation can have negative effects on cognitive skills as well as physical and mental health. With long-term space travel, astronauts will be exposed to greater radiation levels. Research shows that an antioxidant-enriched diet may offer some protection against the cellular effects of radiation and may provide significant neuroprotection from the effects of radiation-induced cognitive and behavioral skill deficits. Ninety-six C57BL/6 mice (48 pomegranate fed and 48 control) were irradiated with proton radiation (2 Gy), and two-month postradiation behaviors were assessed using a battery of behavioral tests to measure cognitive and motor functions. Proton irradiation was associated with depression-like behaviors in the tail suspension test, but this effect was ameliorated by the pomegranate diet. Males, in general, displayed worse coordination and balance than females on the rotarod task, and the pomegranate diet ameliorated this effect. Overall, it appears that proton irradiation, which may be encountered in space, may induce a different pattern of behavioral deficits in males than females and that a pomegranate diet may confer protection against some of those effects. PMID:23662154

  17. Functional architectures and structured flows on manifolds: a dynamical framework for motor behavior.

    PubMed

    Huys, Raoul; Perdikis, Dionysios; Jirsa, Viktor K

    2014-07-01

    We outline a dynamical framework for sequential sensorimotor behavior based on the sequential composition of basic behavioral units. Basic units are conceptualized as temporarily existing low-dimensional dynamical objects, or structured flows, emerging from a high-dimensional system, referred to as structured flows on manifolds. Theorems from dynamical system theory allow for the unambiguous classification of behaviors as represented by structured flows, and thus provide a means to define and identify basic units. The ensemble of structured flows available to an individual defines his or her dynamical repertoire. We briefly review experimental evidence that has identified a few basic elements likely to contribute to each individual's repertoire. Complex behavior requires the involvement of a (typically high-dimensional) dynamics operating at a time scale slower than that of the elements in the dynamical repertoire. At any given time, in the competition between units of the repertoire, the slow dynamics temporarily favor the dominance of one element over others in a sequential fashion, binding together the units and generating complex behavior. The time scale separation between the elements of the repertoire and the slow dynamics define a time scale hierarchy, and their ensemble defines a functional architecture. We illustrate the approach with a functional architecture for handwriting as proof of concept and discuss the implications of the framework for motor control. PMID:25090422

  18. A Perceptual Motor Intervention Improves Play Behavior in Children with Moderate to Severe Cerebral Palsy

    PubMed Central

    Ryalls, Brigette O.; Harbourne, Regina; Kelly-Vance, Lisa; Wickstrom, Jordan; Stergiou, Nick; Kyvelidou, Anastasia

    2016-01-01

    For children with moderate or severe cerebral palsy (CP), a foundational early goal is independent sitting. Sitting offers additional opportunities for object exploration, play and social engagement. The achievement of sitting coincides with important milestones in other developmental areas, such as social engagement with others, understanding of spatial relationships, and the use of both hands to explore objects. These milestones are essential skills necessary for play behavior. However, little is known about how sitting and play behavior might be affected by a physical therapy intervention in children with moderate or severe CP. Therefore, our overall purpose in this study was to determine if sitting skill could be advanced in children with moderate to severe CP using a perceptual motor intervention, and if play skills would change significantly as sitting advanced. Thirty children between the ages of 18 months and 6 years who were able to hold prop sitting for at least 10 s were recruited for this study. Outcome measures were the sitting subsection of the Gross Motor Function Measure (GMFM), and the Play Assessment of Children with Motor Impairment play assessment scale, which is a modified version of the Play in Early Childhood Evaluation System. Significant improvements in GMFM sitting scores (p < 0.001) and marginally significant improvement in play assessment scores (p = 0.067) were found from pre- to post-intervention. Sitting change explained a significant portion of the variance in play change for children over the age of 3 years, who were more severely affected by CP. The results of this study indicate that advances in sitting skill may be a factor in supporting improvements in functional play, along with age and severity of physical impairment. PMID:27199868

  19. Effects of brain-derived neurotrophic factor on dopaminergic function and motor behavior during aging

    PubMed Central

    Boger, Heather A.; Mannangatti, Padmanabhan; Samuvel, Devadoss J.; Saylor, Alicia J.; Bender, Tara S.; McGinty, Jacqueline F.; Fortress, Ashley M.; Zaman, Vandana; Huang, Peng; Middaugh, Lawrence D.; Randall, Patrick K.; Jayanthi, Lankupalle D.; Rohrer, Baerbel; Helke, Kristi L.; Granholm, Ann-Charlotte; Ramamoorthy, Sammanda

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) is critical in synaptic plasticity and in the survival and function of midbrain dopamine neurons. In the present study, we assessed the effects of a partial genetic deletion of BDNF on motor function and dopamine (DA) neurotransmitter measures by comparing (Bdnf+/−) with wildtype mice (WT) at different ages. Bdnf+/ and WT mice had similar body weights until 12 months of age; however, at 21 months, Bdnf+/− mice were significantly heavier than WT mice. Horizontal and vertical motor activity was reduced for Bdnf+/− compared to WT mice; but was not influenced by Age. Performance on an accelerating rotarod declined with age for both genotypes and was exacerbated for Bdnf+/− mice. Body weight did not correlate with any of the three behavioral measures studied. DA neurotransmitter markers indicated no genotypic difference in striatal tyrosine hydroxylase (TH), dopamine transporter (DAT), or vesicular monoamine transporter 2 (VMAT2) immunoreactivity at any age. However, DA transport via DAT (starting at 12 months) and VMAT2 (starting at 3 months) as well as KCl-stimulated DA release were reduced in Bdnf+/− mice and declined with age suggesting an increasingly important role for BDNF in the release and uptake of DA with the aging process. These findings suggest that a BDNF expression deficit becomes more critical to dopaminergic dynamics and related behavioral activities with increasing age. PMID:20860702

  20. Chronic behavioral stress exaggerates motor deficit and neuroinflammation in the MPTP mouse model of Parkinson's disease

    PubMed Central

    Lauretti, E; Di Meco, A; Merali, S; Praticò, D

    2016-01-01

    Environmental stressor exposure is associated with a variety of age-related diseases including neurodegeneration. Although the initial events of sporadic Parkinson's disease (PD) are not known, consistent evidence supports the hypothesis that the disease results from the combined effect of genetic and environmental risk factors. Among them, behavioral stress has been shown to cause damage and neuronal loss in different areas of the brain, however, its effect on the dopaminergic system and PD pathogenesis remains to be characterized. The C57BL/6 mice underwent chronic restraint/isolation (RI) stress and were then treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), whereas the control mice were treated only with MPTP and the effect on the PD-like phenotype was evaluated. The mice that underwent RI before the administration of MPTP manifested an exaggerated motor deficit and impairment in the acquisition of motor skills, which were associated with a greater loss of neuronal tyrosine hydroxylase and astrocytes activation. By showing that RI influences the onset and progression of the PD-like phenotype, our study underlines the novel pathogenetic role that chronic behavioral stressor has in the disease process by triggering neuroinflammation and degeneration of the nigral dopaminergic system. PMID:26859816

  1. Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish

    PubMed Central

    Grone, Brian P.; Marchese, Maria; Hamling, Kyla R.; Kumar, Maneesh G.; Krasniak, Christopher S.; Sicca, Federico; Santorelli, Filippo M.; Patel, Manisha; Baraban, Scott C.

    2016-01-01

    Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1), are linked to childhood epilepsies and other neurodevelopmental disorders. Zebrafish STXBP1 homologs (stxbp1a and stxbp1b) have highly conserved sequence and are prominently expressed in the larval zebrafish brain. To understand the functions of stxbp1a and stxbp1b, we generated loss-of-function mutations using CRISPR/Cas9 gene editing and studied brain electrical activity, behavior, development, heart physiology, metabolism, and survival in larval zebrafish. Homozygous stxbp1a mutants exhibited a profound lack of movement, low electrical brain activity, low heart rate, decreased glucose and mitochondrial metabolism, and early fatality compared to controls. On the other hand, homozygous stxbp1b mutants had spontaneous electrographic seizures, and reduced locomotor activity response to a movement-inducing “dark-flash” visual stimulus, despite showing normal metabolism, heart rate, survival, and baseline locomotor activity. Our findings in these newly generated mutant lines of zebrafish suggest that zebrafish recapitulate clinical phenotypes associated with human syntaxin-binding protein 1 mutations. PMID:26963117

  2. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  3. Behavioral abnormalities and Parkinson’s-like histological changes resulting from Id2 inactivation in mice

    PubMed Central

    Havrda, Matthew C.; Paolella, Brenton R.; Ward, Nora M.; Holroyd, Kathryn B.

    2013-01-01

    SUMMARY Characterizing dopaminergic neuronal development and function in novel genetic animal models might uncover strategies for researchers to develop disease-modifying treatments for neurologic disorders. Id2 is a transcription factor expressed in the developing central nervous system. Id2−/− mice have fewer dopaminergic neurons in the olfactory bulb and reduced olfactory discrimination, a pre-clinical marker of Parkinson’s disease. Here, we summarize behavioral, histological and in vitro molecular biological analyses to determine whether midbrain dopaminergic neurons are affected by Id2 loss. Id2−/− mice were hyperactive at 1 and 3 months of age, but by 6 months showed reduced activity. Id2−/− mice showed age-dependent histological alterations in dopaminergic neurons of the substantia nigra pars compacta (SNpC) associated with changes in locomotor activity. Reduced dopamine transporter (DAT) expression was observed at early ages in Id2−/− mice and DAT expression was dependent on Id2 expression in an in vitro dopaminergic differentiation model. Evidence of neurodegeneration, including activated caspase-3 and glial infiltration, were noted in the SNpC of older Id2−/− mice. These findings document a novel role for Id2 in the maintenance of midbrain dopamine neurons. The Id2−/− mouse should provide unique opportunities to study the progression of neurodegenerative disorders involving the dopamine system. PMID:23264561

  4. Surface Structure Evolution and Abnormal Wear Behavior of the TiNiNb Alloy under Impact Load

    NASA Astrophysics Data System (ADS)

    Zhang, Jianjun; Zhu, Jinhua

    2009-05-01

    The TiNiNb alloy exhibits a linear increase in wear with a number of impacts at the low impact energy density E im of 1.6 J/cm2. However, a change in the volume wear occurs on the wear curve when E im is increased to 2.42 J/cm2. In this case, when the number of impacts N is more than 3 × 105 cycles, the wear rate decreases from 5.8 × 10-6 to 1.9 × 10-6 mm3/cycle, which is only one-half of that under low E im (1.6 J/cm2). It is significant for practical applications because impact energy increases while the wear rate decreases. X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses show that a large number of amorphous structures are produced on the sample surface at high E im , while no new crystalline phases appear. The abnormal wear behavior of the TiNiNb alloy can be attributed to the excellent wear behavior of amorphous structure and the consumption of impact energy during amorphous structure production.

  5. Aberrant IgG isotype generation in mice with abnormal behaviors.

    PubMed

    Kim, So-Nam; Jo, Gwang-Ho; Kim, Hyoung-Ah; Heo, Yong

    2016-01-01

    BTBR T+tf/J (BTBR) mice were recently cited as a suitable animal model for the study of autism because of their behavioral characteristics and immunological changes similar to those reported from autistic subjects. The BTBR mouse was reported to have significantly higher levels of serum IgG, brain IgG deposits and anti-brain IgG than highly social C57BL/6 mice, suggesting involvement of aberrant immune responses in the occurrence of autism. Up-regulation of IgG production was investigated here, with a focus on the pattern of IgG isotype distribution compared with that in FVB/NJ (FVB) mice, another highly social control strain. The results indicated that levels of serum IgG1, IgG2b and IgG3 in post-natal day 21 BTBR mice was significantly higher than FVB mice, regardless of sex, resulting in higher IgG1:IgG2a ratios in BTBR mice than in FVB mice (statistical significance in males). A similar outcome regarding the IgG1:IgG2a ratio was observed in culture supernatants of bone marrow cells from these hosts. A presence of brain-reactive IgG in the sera of BTBR was higher than in FVB mice; levels of brain-reactive IgG against whole brain homogenates were higher in BTBR than in FVB mice, with significant differences seen in the striatum and substantia nigra regions. Levels of IgG1 deposited in the cerebellum, cortex, hippocampus or striatum of both BTBR male and female mice were significantly higher than in FVB counterparts. Overall, these results suggest that alterations in IgG isotype production or deposition in the brain could be implicated in the aberrant immune reactivities of BTBR mice. PMID:25691089

  6. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

    SciTech Connect

    Dannhausen, Katharina; Karlstetter, Marcus; Caramoy, Albert; Volz, Cornelia; Jägle, Herbert; Liebisch, Gerhard; Utermöhlen, Olaf; Langmann, Thomas

    2015-08-21

    Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice. • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.

  7. Neuropsychological evaluation and parental assessment of behavioral and motor difficulties in children with neurofibromatosis type 1.

    PubMed

    Coutinho, V; Kemlin, I; Dorison, N; Billette de Villemeur, T; Rodriguez, D; Dellatolas, G

    2016-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystem disorder, with large inter and intrafamilial clinical variability and uncertain prognosis. In children with NF1 cognitive disorders, learning difficulties and behavioral problems are common. The present study aims to establish the neuropsychological and behavioral profiles of 78 patients with NF1, aged between 5 and 18 years, and to examine the relationship between these profiles and the transmission of NF1 (sporadic vs. familial), clinical manifestations, and environmental factors. We used several questionnaires completed by parents and neuropsychological tests. The results confirmed specific neuropsychological disabilities in children with NF1, especially involving visuospatial and fine motor skills, learning difficulties and behavioral problems. Cognitive difficulties were significantly more frequent in patients with familial than in those with sporadic NF1. All parental questionnaires were correlated with each other, but parental reports were not associated with FSIQ, SES, school status, and clinical manifestations of the disease. Neuropsychological tests were poorly related to parental reports of cognitive and behavioral difficulties. PMID:26625207

  8. Changes in Sensitivity of Reward and Motor Behavior to Dopaminergic, Glutamatergic, and Cholinergic Drugs in a Mouse Model of Fragile X Syndrome

    PubMed Central

    Fish, Eric W.; Krouse, Michael C.; Stringfield, Sierra J.; DiBerto, Jeffrey F.; Robinson, J. Elliott; Malanga, C. J.

    2013-01-01

    Fragile X syndrome (FXS) is a leading cause of intellectual disability. FXS is caused by loss of function of the FMR1 gene, and mice in which Fmr1 has been inactivated have been used extensively as a preclinical model for FXS. We investigated the behavioral pharmacology of drugs acting through dopaminergic, glutamatergic, and cholinergic systems in fragile X (Fmr1-/Y) mice with intracranial self-stimulation (ICSS) and locomotor activity measurements. We also measured brain expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis. Fmr1-/Y mice were more sensitive than wild type mice to the rewarding effects of cocaine, but less sensitive to its locomotor stimulating effects. Anhedonic but not motor depressant effects of the atypical neuroleptic, aripiprazole, were reduced in Fmr1-/Y mice. The mGluR5-selective antagonist, 6-methyl-2-(phenylethynyl)pyridine (MPEP), was more rewarding and the preferential M1 antagonist, trihexyphenidyl, was less rewarding in Fmr1-/Y than wild type mice. Motor stimulation by MPEP was unchanged, but stimulation by trihexyphenidyl was markedly increased, in Fmr1-/Y mice. Numbers of midbrain TH+ neurons in the ventral tegmental area were unchanged, but were lower in the substantia nigra of Fmr1-/Y mice, although no changes in TH levels were found in their forebrain targets. The data are discussed in the context of known changes in the synaptic physiology and pharmacology of limbic motor systems in the Fmr1-/Y mouse model. Preclinical findings suggest that drugs acting through multiple neurotransmitter systems may be necessary to fully address abnormal behaviors in individuals with FXS. PMID:24205018

  9. A high performance sensorimotor beta rhythm-based brain computer interface associated with human natural motor behavior

    NASA Astrophysics Data System (ADS)

    Bai, Ou; Lin, Peter; Vorbach, Sherry; Floeter, Mary Kay; Hattori, Noriaki; Hallett, Mark

    2008-03-01

    To explore the reliability of a high performance brain-computer interface (BCI) using non-invasive EEG signals associated with human natural motor behavior does not require extensive training. We propose a new BCI method, where users perform either sustaining or stopping a motor task with time locking to a predefined time window. Nine healthy volunteers, one stroke survivor with right-sided hemiparesis and one patient with amyotrophic lateral sclerosis (ALS) participated in this study. Subjects did not receive BCI training before participating in this study. We investigated tasks of both physical movement and motor imagery. The surface Laplacian derivation was used for enhancing EEG spatial resolution. A model-free threshold setting method was used for the classification of motor intentions. The performance of the proposed BCI was validated by an online sequential binary-cursor-control game for two-dimensional cursor movement. Event-related desynchronization and synchronization were observed when subjects sustained or stopped either motor execution or motor imagery. Feature analysis showed that EEG beta band activity over sensorimotor area provided the largest discrimination. With simple model-free classification of beta band EEG activity from a single electrode (with surface Laplacian derivation), the online classifications of the EEG activity with motor execution/motor imagery were: >90%/~80% for six healthy volunteers, >80%/~80% for the stroke patient and ~90%/~80% for the ALS patient. The EEG activities of the other three healthy volunteers were not classifiable. The sensorimotor beta rhythm of EEG associated with human natural motor behavior can be used for a reliable and high performance BCI for both healthy subjects and patients with neurological disorders. Significance: The proposed new non-invasive BCI method highlights a practical BCI for clinical applications, where the user does not require extensive training.

  10. C9ORF72 hexanucleotide repeats in behavioral and motor neuron disease: clinical heterogeneity and pathological diversity

    PubMed Central

    Yokoyama, Jennifer S; Sirkis, Daniel W; Miller, Bruce L

    2014-01-01

    Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of frontotemporal dementia (FTD), a predominantly behavioral disease, and amyotrophic lateral sclerosis (ALS), a disease of motor neurons. The primary objectives of this review are to highlight the clinical heterogeneity associated with C9ORF72 pathogenic expansion and identify potential molecular mechanisms underlying selective vulnerability of distinct neural populations. The proposed mechanisms by which C9ORF72 expansion causes behavioral and motor neuron disease highlight the emerging role of impaired RNA and protein homeostasis in a spectrum of neurodegeneration and strengthen the biological connection between FTD and ALS. PMID:24753999

  11. The Sensorimotor System Can Sculpt Behaviorally Relevant Representations for Motor Learning.

    PubMed

    Franklin, David W; Batchelor, Alexandra V; Wolpert, Daniel M

    2016-01-01

    The coordinate system in which humans learn novel motor skills is controversial. The representation of sensorimotor skills has been extensively studied by examining generalization after learning perturbations specifically designed to be ambiguous as to their coordinate system. Recent studies have found that learning is not represented in any simple coordinate system and can potentially be accounted for by a mixed representation. Here, instead of probing generalization, which has led to conflicting results, we examine whether novel dynamics can be learned when explicitly and unambiguously presented in particular coordinate systems. Subjects performed center-out reaches to targets in the presence of a force field, while varying the orientation of their hand (i.e., the wrist angle) across trials. Different groups of subjects experienced force fields that were explicitly presented either in Cartesian coordinates (field independent of hand orientation), in object coordinates (field rotated with hand orientation), or in anti-object coordinates (field rotated counter to hand orientation). Subjects learned to represent the dynamics when presented in either Cartesian or object coordinates, learning these as well as an ambiguous force field. However, learning was slower for the object-based dynamics and substantially impaired for the anti-object presentation. Our results show that the motor system is able to tune its representation to at least two natural coordinate systems but is impaired when the representation of the task does not correspond to a behaviorally relevant coordinate system. Our results show that the motor system can sculpt its representation through experience to match those of natural tasks. PMID:27588304

  12. The Sensorimotor System Can Sculpt Behaviorally Relevant Representations for Motor Learning

    PubMed Central

    2016-01-01

    Abstract The coordinate system in which humans learn novel motor skills is controversial. The representation of sensorimotor skills has been extensively studied by examining generalization after learning perturbations specifically designed to be ambiguous as to their coordinate system. Recent studies have found that learning is not represented in any simple coordinate system and can potentially be accounted for by a mixed representation. Here, instead of probing generalization, which has led to conflicting results, we examine whether novel dynamics can be learned when explicitly and unambiguously presented in particular coordinate systems. Subjects performed center–out reaches to targets in the presence of a force field, while varying the orientation of their hand (i.e., the wrist angle) across trials. Different groups of subjects experienced force fields that were explicitly presented either in Cartesian coordinates (field independent of hand orientation), in object coordinates (field rotated with hand orientation), or in anti-object coordinates (field rotated counter to hand orientation). Subjects learned to represent the dynamics when presented in either Cartesian or object coordinates, learning these as well as an ambiguous force field. However, learning was slower for the object-based dynamics and substantially impaired for the anti-object presentation. Our results show that the motor system is able to tune its representation to at least two natural coordinate systems but is impaired when the representation of the task does not correspond to a behaviorally relevant coordinate system. Our results show that the motor system can sculpt its representation through experience to match those of natural tasks. PMID:27588304

  13. The first mecp2-null zebrafish model shows altered motor behaviors

    PubMed Central

    Pietri, Thomas; Roman, Angel-Carlos; Guyon, Nicolas; Romano, Sebastián A.; Washbourne, Philip; Moens, Cecilia B.; de Polavieja, Gonzalo G.; Sumbre, Germán

    2013-01-01

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder and one of the most common causes of mental retardation in affected girls. Other symptoms include a rapid regression of motor and cognitive skills after an apparently early normal development. Sporadic mutations in the transcription factor MECP2 has been shown to be present in more than 90% of the patients and several models of MeCP2-deficient mice have been created to understand the role of this gene. These models have pointed toward alterations in the maintenance of the central nervous system rather than its development, in line with the late onset of the disease in humans. However, the exact functions of MeCP2 remain difficult to delineate and the animal models have yielded contradictory results. Here, we present the first mecp2-null allele mutation zebrafish model. Surprisingly and in contrast to MeCP2-null mouse models, mecp2-null zebrafish are viable and fertile. They present nonetheless clear behavioral alterations during their early development, including spontaneous and sensory-evoked motor anomalies, as well as defective thigmotaxis. PMID:23874272

  14. Are There Gender-Specific Pathways from Early Adolescence Psychological Distress Symptoms toward the Development of Substance Use and Abnormal Eating Behavior?

    ERIC Educational Resources Information Center

    Beato-Fernandez, Luis; Rodriguez-Cano, Teresa; Pelayo-Delgado, Esther; Calaf, Myralys

    2007-01-01

    The aim of the present longitudinal community study was to test whether psychological distress at 13 years of age predicted reported substance use problems in boys and abnormal eating behavior in girls 2 years later. The sample consisted of 500 male and 576 female students. The use of substances was evaluated using a semi-structured interview,…

  15. Group Cognitive Behavioral Treatment for PTSD: Treatment of Motor Vehicle Accident Survivors

    PubMed Central

    Beck, J. Gayle; Coffey, Scott F.

    2006-01-01

    Individual cognitive behavioral therapies (CBT) are now considered the first-line treatment for posttraumatic stress disorder (PTSD; Foa, Keane, & Friedman, 2000). As mental health reimbursement becomes more restricted, it is imperative that we adapt individual-format therapies for use in a small group format. Group therapies have a number of advantages, including provision of a natural support group, the ability to reach more patients, and greater cost efficiency. In this article, we describe the development of a group CBT for PTSD in the aftermath of a serious motor vehicle accident (MVA). Issues unique to the group treatment format are discussed, along with special considerations such as strategies to reduce the potential for triggering reexperiencing symptoms during group sessions. A case example is presented, along with discussion of group process issues. Although still in the early stages, this group CBT may offer promise as an effective treatment of MVA-related PTSD. PMID:16525513

  16. Early Social Enrichment Rescues Adult Behavioral and Brain Abnormalities in a Mouse Model of Fragile X Syndrome

    PubMed Central

    Oddi, Diego; Subashi, Enejda; Middei, Silvia; Bellocchio, Luigi; Lemaire-Mayo, Valerie; Guzmán, Manuel; Crusio, Wim E; D'Amato, Francesca R; Pietropaolo, Susanna

    2015-01-01

    Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases. PMID:25348604

  17. Regression rate and pyrolysis behavior of HTPB-based solid fuels in a hybrid rocket motor

    NASA Astrophysics Data System (ADS)

    Chiaverini, Martin John

    An experimental investigation on the regression rate and pyrolysis behavior of hydroxyl-terminated polybutadiene-based solid fuels has been conducted. The overall objective was to obtain a better understanding of the physical processes governing solid-fuel regression and pyrolysis under different operating regimes. Experiments were conducted using a windowed, slab geometry hybrid motor and a conductive-heating induced thermal pyrolysis test rig. Gaseous oxygen was employed as the oxidizer in the 1-m long, lab-scale hybrid motor, which had realistic operating conditions. A real-time X-ray radiography system and an ultrasonic pulse-echo system were both used to obtain the local, instantaneous solid fuel regression rates. A semi-empirical approach was developed to analyze the experimental results and to correlate the regression rates with physically descriptive, dimensionless parameters. For relatively high surface temperatures above 722 K, the activation energy of pure HTPB was 4.91 kcal/mole, indicating that the pyrolysis process was governed by formation and desorption of high molecular weight fragments from the fuel surface. The conductive-heating induced pyrolysis rates of HTPB, conducted at atmospheric pressure, were very similar to those measured in the hybrid motor tests at much higher pressures. This result implies that the regression rate of HTPB was governed primarily by thermal decomposition processes and not influenced by heterogeneous surface reactions. Radiant heat transfer had a significant effect on the overall regression rate behavior of HTPB. Radiation from soot generally accounted for about 80 to 90% of the total radiant heat flux. Two separate expressions, one for the developing flow regime and one for fully-developed flow, were used to correlate the regression rate data. Both correlations show that standard hybrid boundary layer correlations must be modified to account for the effects of variable fluid properties across the boundary layer and

  18. Long-Term Post-Stroke Changes Include Myelin Loss, Specific Deficits in Sensory and Motor Behaviors and Complex Cognitive Impairment Detected Using Active Place Avoidance

    PubMed Central

    Li, Jie; Ooi, Evelyn; Bloom, Jonathan; Poon, Carrie; Lax, Daniel; Rosenbaum, Daniel M.; Barone, Frank C.

    2013-01-01

    Persistent neurobehavioral deficits and brain changes need validation for brain restoration. Two hours middle cerebral artery occlusion (tMCAO) or sham surgery was performed in male Sprague-Dawley rats. Neurobehavioral and cognitive deficits were measured over 10 weeks included: (1) sensory, motor, beam balance, reflex/abnormal responses, hindlimb placement, forepaw foot fault and cylinder placement tests, and (2) complex active place avoidance learning (APA) and simple passive avoidance retention (PA). Electroretinogram (ERG), hemispheric loss (infarction), hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue) staining in several fiber tracts were also measured. In comparison to Sham surgery, tMCAO surgery produced significant deficits in all behavioral tests except reflex/abnormal responses. Acute, short lived deficits following tMCAO were observed for forelimb foot fault and forelimb cylinder placement. Persistent, sustained deficits for the whole 10 weeks were exhibited for motor (p<0.001), sensory (p<0.001), beam balance performance (p<0.01) and hindlimb placement behavior (p<0.01). tMCAO produced much greater and prolonged cognitive deficits in APA learning (maximum on last trial of 604±83% change, p<0.05) but only a small, comparative effect on PA retention. Hemispheric loss/atrophy was measured 10 weeks after tMCAO and cross-validated by two methods (e.g., almost identical % ischemic hemispheric loss of 33.4±3.5% for H&E and of 34.2±3.5% for TTC staining). No visual dysfunction by ERG and no hippocampus neuronal loss were detected after tMCAO. Fiber tract damage measured by Luxol Fast Blue myelin staining intensity was significant (p<0.01) in the external capsule and striatum but not in corpus callosum and anterior commissure. In summary, persistent neurobehavioral deficits were validated as important endpoints for stroke restorative research in the future. Fiber myelin loss appears to contribute to these long term behavioral dysfunctions and can be

  19. Long-term post-stroke changes include myelin loss, specific deficits in sensory and motor behaviors and complex cognitive impairment detected using active place avoidance.

    PubMed

    Zhou, Jin; Zhuang, Jian; Li, Jie; Ooi, Evelyn; Bloom, Jonathan; Poon, Carrie; Lax, Daniel; Rosenbaum, Daniel M; Barone, Frank C

    2013-01-01

    Persistent neurobehavioral deficits and brain changes need validation for brain restoration. Two hours middle cerebral artery occlusion (tMCAO) or sham surgery was performed in male Sprague-Dawley rats. Neurobehavioral and cognitive deficits were measured over 10 weeks included: (1) sensory, motor, beam balance, reflex/abnormal responses, hindlimb placement, forepaw foot fault and cylinder placement tests, and (2) complex active place avoidance learning (APA) and simple passive avoidance retention (PA). Electroretinogram (ERG), hemispheric loss (infarction), hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue) staining in several fiber tracts were also measured. In comparison to Sham surgery, tMCAO surgery produced significant deficits in all behavioral tests except reflex/abnormal responses. Acute, short lived deficits following tMCAO were observed for forelimb foot fault and forelimb cylinder placement. Persistent, sustained deficits for the whole 10 weeks were exhibited for motor (p<0.001), sensory (p<0.001), beam balance performance (p<0.01) and hindlimb placement behavior (p<0.01). tMCAO produced much greater and prolonged cognitive deficits in APA learning (maximum on last trial of 604±83% change, p<0.05) but only a small, comparative effect on PA retention. Hemispheric loss/atrophy was measured 10 weeks after tMCAO and cross-validated by two methods (e.g., almost identical % ischemic hemispheric loss of 33.4±3.5% for H&E and of 34.2±3.5% for TTC staining). No visual dysfunction by ERG and no hippocampus neuronal loss were detected after tMCAO. Fiber tract damage measured by Luxol Fast Blue myelin staining intensity was significant (p<0.01) in the external capsule and striatum but not in corpus callosum and anterior commissure. In summary, persistent neurobehavioral deficits were validated as important endpoints for stroke restorative research in the future. Fiber myelin loss appears to contribute to these long term behavioral dysfunctions and can be

  20. Children with Multiple Disabilities and Minimal Motor Behavior Using Chin Movements to Operate Microswitches to Obtain Environmental Stimulation

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; O'Reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Tota, Alessia; Antonucci, Massimo; Oliva, Doretta

    2006-01-01

    In these two studies, two children with multiple disabilities and minimal motor behavior were assessed to see if they could use chin movements to operate microswitches to obtain environmental stimulation. In Study I, we applied an adapted version of a recently introduced electronic microswitch [Lancioni, G. E., O'Reilly, M. F., Singh, N. N.,…

  1. Assisting People with Multiple Disabilities and Minimal Motor Behavior to Control Environmental Stimulation through a Mouse Wheel

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang; Shih, Ching-Tien; Lin, Kun-Tsan; Chiang, Ming-Shan

    2009-01-01

    This study assessed whether two people with profound multiple disabilities and minimal motor behavior would be able to control environmental stimulation using thumb poke ability with a mouse wheel and a newly developed mouse driver (i.e., a new mouse driver replacing standard mouse driver, and turning a mouse into a precise thumb poke detector).…

  2. Assisting People with Multiple Disabilities and Minimal Motor Behavior to Improve Computer Pointing Efficiency through a Mouse Wheel

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang; Chang, Man-Ling; Shih, Ching-Tien

    2009-01-01

    This study evaluated whether two people with multiple disabilities and minimal motor behavior would be able to improve their pointing performance using finger poke ability with a mouse wheel through a Dynamic Pointing Assistive Program (DPAP) and a newly developed mouse driver (i.e., a new mouse driver replaces standard mouse driver, changes a…

  3. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  4. Fundamental motor skill, physical activity, and sedentary behavior in socioeconomically disadvantaged kindergarteners.

    PubMed

    Gu, Xiangli

    2016-10-01

    Guided by Stodden et al's conceptual model, the main purpose of the study was to examine the relation between fundamental motor skills (FMS; locomotor and objective control skills), different intensity levels of physical activity (light PA [LPA], moderate-to-vigorous PA [MVPA], and vigorous PA[VPA]), and sedentary behavior (SB) in socioeconomically disadvantaged kindergarteners. A prospective design was used in this study and the data were collected across the 2013-2014 academic school year. Participants were 256 (129 boys; 127 girls; Mage = 5.37, SD = 0.48) kindergarteners recruited from three public schools in the southern United States. Results found that FMS were significantly related to LPA, MVPA, VPA, and SB. Regression analyses indicate that locomotor skills explained significant variance for LPA (6.4%; p < .01), MVPA (7.9%; p < .001), and VPA (5.3%; p < .01) after controlling for weight status. Mediational analysis supports the significant indirect effect of MVPA on the relation between FMS and SB (95% CI: [-0.019, -0.006]). Adequate FMS development during early childhood may result in participating in more varied physical activities, thus leading to lower risk of obesity-related behaviors. PMID:26691744

  5. Nonlinear dynamic behaviors of permanent magnet synchronous motors in electric vehicles caused by unbalanced magnetic pull

    NASA Astrophysics Data System (ADS)

    Xiang, Changle; Liu, Feng; Liu, Hui; Han, Lijin; Zhang, Xun

    2016-06-01

    Unbalanced magnetic pull (UMP) plays a key role in nonlinear dynamic behaviors of permanent magnet synchronous motors (PMSM) in electric vehicles. Based on Jeffcott rotor model, the stiffness characteristics of the rotor system of the PMSM are analyzed and the nonlinear dynamic behaviors influenced by UMP are investigated. In free vibration study, eigenvalue-based stability analysis for multiple equilibrium points is performed which offers an insight in system stiffness. Amplitude modulation effects are discovered of which the mechanism is explained and the period of modulating signal is carried out by phase analysis and averaging method. The analysis indicates that the effects are caused by the interaction of the initial phases of forward and backward whirling motions. In forced vibration study, considering dynamic eccentricity, frequency characteristics revealing softening type are obtained by harmonic balance method, and the stability of periodic solution is investigated by Routh-Hurwitz criterion. The frequency characteristics analysis indicates that the response amplitude is limited in the range between the amplitudes of the two kinds of equilibrium points. In the vicinity of the continuum of equilibrium points, the system hardly provides resistance to bending, and hence external disturbances easily cause loss of stability. It is useful for the design of the PMSM with high stability and low vibration and acoustic noise.

  6. X-linked Christianson syndrome: heterozygous female Slc9a6 knockout mice develop mosaic neuropathological changes and related behavioral abnormalities.

    PubMed

    Sikora, Jakub; Leddy, Jennifer; Gulinello, Maria; Walkley, Steven U

    2016-01-01

    Christianson syndrome (CS) is an X-linked neurodevelopmental and neurological disorder characterized in males by core symptoms that include non-verbal status, intellectual disability, epilepsy, truncal ataxia, postnatal microcephaly and hyperkinesis. CS is caused by mutations in the SLC9A6 gene, which encodes a multipass transmembrane sodium (potassium)-hydrogen exchanger 6 (NHE6) protein, functional in early recycling endosomes. The extent and variability of the CS phenotype in female heterozygotes, who presumably express the wild-type and mutant SLC9A6 alleles mosaically as a result of X-chromosome inactivation (XCI), have not yet been systematically characterized. Slc9a6 knockout mice (Slc9a6 KO) were generated by insertion of the bacterial lacZ/β-galactosidase (β-Gal) reporter into exon 6 of the X-linked gene. Mutant Slc9a6 KO male mice have been shown to develop late endosomal/lysosomal dysfunction associated with glycolipid accumulation in selected neuronal populations and patterned degeneration of Purkinje cells (PCs). In heterozygous female Slc9a6 KO mice, β-Gal serves as a transcriptional/XCI reporter and thus facilitates testing of effects of mosaic expression of the mutant allele on penetrance of the abnormal phenotype. Using β-Gal, we demonstrated mosaic expression of the mutant Slc9a6 allele and mosaically distributed lysosomal glycolipid accumulation and PC pathology in the brains of heterozygous Slc9a6 KO female mice. At the behavioral level, we showed that heterozygous female mice suffer from visuospatial memory and motor coordination deficits similar to but less severe than those observed in X-chromosome hemizygous mutant males. Our studies in heterozygous Slc9a6 KO female mice provide important clues for understanding the likely phenotypic range of Christianson syndrome among females heterozygous for SLC9A6 mutations and might improve diagnostic practice and genetic counseling by helping to characterize this presumably underappreciated patient

  7. X-linked Christianson syndrome: heterozygous female Slc9a6 knockout mice develop mosaic neuropathological changes and related behavioral abnormalities

    PubMed Central

    Sikora, Jakub; Leddy, Jennifer; Gulinello, Maria; Walkley, Steven U.

    2016-01-01

    ABSTRACT Christianson syndrome (CS) is an X-linked neurodevelopmental and neurological disorder characterized in males by core symptoms that include non-verbal status, intellectual disability, epilepsy, truncal ataxia, postnatal microcephaly and hyperkinesis. CS is caused by mutations in the SLC9A6 gene, which encodes a multipass transmembrane sodium (potassium)-hydrogen exchanger 6 (NHE6) protein, functional in early recycling endosomes. The extent and variability of the CS phenotype in female heterozygotes, who presumably express the wild-type and mutant SLC9A6 alleles mosaically as a result of X-chromosome inactivation (XCI), have not yet been systematically characterized. Slc9a6 knockout mice (Slc9a6 KO) were generated by insertion of the bacterial lacZ/β-galactosidase (β-Gal) reporter into exon 6 of the X-linked gene. Mutant Slc9a6 KO male mice have been shown to develop late endosomal/lysosomal dysfunction associated with glycolipid accumulation in selected neuronal populations and patterned degeneration of Purkinje cells (PCs). In heterozygous female Slc9a6 KO mice, β-Gal serves as a transcriptional/XCI reporter and thus facilitates testing of effects of mosaic expression of the mutant allele on penetrance of the abnormal phenotype. Using β-Gal, we demonstrated mosaic expression of the mutant Slc9a6 allele and mosaically distributed lysosomal glycolipid accumulation and PC pathology in the brains of heterozygous Slc9a6 KO female mice. At the behavioral level, we showed that heterozygous female mice suffer from visuospatial memory and motor coordination deficits similar to but less severe than those observed in X-chromosome hemizygous mutant males. Our studies in heterozygous Slc9a6 KO female mice provide important clues for understanding the likely phenotypic range of Christianson syndrome among females heterozygous for SLC9A6 mutations and might improve diagnostic practice and genetic counseling by helping to characterize this presumably

  8. Longitudinal Motor and Behavioral Assessment of Blood-Brain Barrier Opening with Transcranial Focused Ultrasound.

    PubMed

    Olumolade, Oluyemi O; Wang, Shutao; Samiotaki, Gesthimani; Konofagou, Elisa E

    2016-09-01

    Focused ultrasound (FUS), in combination with microbubbles, has been found to open the blood-brain barrier (BBB) non-invasively. When this technique is used for drug delivery, repeated drug administration and BBB opening are likely required. Therefore, it is worth investigating the long-term effects of FUS-induced BBB opening. In this study, we focused on the assessment of potential behavior changes in mice that could be attributed to repeated BBB opening for up to 6 months. The striatum of animals was unilaterally sonicated either monthly or biweekly throughout the monitoring period. Behavioral assessments were conducted using open-field and rotarod performance tests. Upon completion of each sonication, mice underwent magnetic resonance imaging (MRI) to confirm and assess the volume of the BBB opening. No differences in locomotor activity between BBB-opened and control groups in both biweekly and monthly treated mice were evident up to 6 months. Similarly, there was no affinity for a particular turn angle in the sonicated mice compared with the control animals. However, the positive control group exhibited a significant decrease in locomotor activity, as well as rotation ipsilateral to the sonicated hemisphere. Our results based on the assessment using open-field and rotarod tests indicated that repeated opening of the BBB in the striatum using FUS in conjunction with microbubbles over a period of 6 mo and under the parameters used here did not cause motor impairment, behavioral changes or morphologic alterations. This reinforces the tolerability of repeated and long-term drug delivery using FUS-induced BBB opening. PMID:27339763

  9. PKA Controls Calcium Influx into Motor Neurons during a Rhythmic Behavior

    PubMed Central

    Wang, Han; Sieburth, Derek

    2013-01-01

    Cyclic adenosine monophosphate (cAMP) has been implicated in the execution of diverse rhythmic behaviors, but how cAMP functions in neurons to generate behavioral outputs remains unclear. During the defecation motor program in C. elegans, a peptide released from the pacemaker (the intestine) rhythmically excites the GABAergic neurons that control enteric muscle contractions by activating a G protein-coupled receptor (GPCR) signaling pathway that is dependent on cAMP. Here, we show that the C. elegans PKA catalytic subunit, KIN-1, is the sole cAMP target in this pathway and that PKA is essential for enteric muscle contractions. Genetic analysis using cell-specific expression of dominant negative or constitutively active PKA transgenes reveals that knockdown of PKA activity in the GABAergic neurons blocks enteric muscle contractions, whereas constitutive PKA activation restores enteric muscle contractions to mutants defective in the peptidergic signaling pathway. Using real-time, in vivo calcium imaging, we find that PKA activity in the GABAergic neurons is essential for the generation of synaptic calcium transients that drive GABA release. In addition, constitutively active PKA increases the duration of calcium transients and causes ectopic calcium transients that can trigger out-of-phase enteric muscle contractions. Finally, we show that the voltage-gated calcium channels UNC-2 and EGL-19, but not CCA-1 function downstream of PKA to promote enteric muscle contractions and rhythmic calcium influx in the GABAergic neurons. Thus, our results suggest that PKA activates neurons during a rhythmic behavior by promoting presynaptic calcium influx through specific voltage-gated calcium channels. PMID:24086161

  10. Inducible Nitric Oxide Inhibitors Block NMDA Antagonist-Stimulated Motoric Behaviors and Medial Prefrontal Cortical Glutamate Efflux

    PubMed Central

    Bergstrom, Hadley C.; Darvesh, Altaf S.; Berger, S. P.

    2015-01-01

    Nitric oxide (NO) plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA)-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS) for studying the neurobehavioral effects of non-competitive NMDA-antagonist stimulants such as dizocilpine (MK-801) and phencyclidine (PCP). This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS) aminoguanidine (AG) and (-)-epigallocatechin-3-gallate (EGCG) in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG, or vehicle prior to receiving NMDA antagonists MK-801, PCP, or a conventional psychostimulant (cocaine) and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex (mPFC) was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated mPFC glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in “green tea” and chocolate) may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia. PMID:26696891

  11. 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. PMID:26562314

  12. Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in Knock-in Huntington’s disease mice

    PubMed Central

    Hickey, Miriam A.; Kosmalska, Agata; Enayati, Joseph; Cohen, Rachel; Zeitlin, Scott; Levine, Michael S.; Chesselet, Marie-Françoise

    2008-01-01

    Huntington’s disease is a neurodegenerative disorder, caused by an elongation of CAG repeats in the huntingtin gene. Mice with an insertion of an expanded polyglutamine repeat in the mouse huntingtin gene (knock-in mice) most closely model the disease because the mutation is expressed in the proper genomic and protein context. However, few knock-in mouse lines have been extensively characterized and available data suggest marked differences in the extent and time course of their behavioral and pathological phenotype. We have previously described behavioral anomalies in the open field as early as 1 month of age, followed by the appearance at 2 months of progressive huntingtin neuropathology, in a mouse carrying a portion of human exon 1 with approximately 140 CAG repeats inserted into the mouse huntingtin gene. Here we extend these observations by showing that early behavioral anomalies exist in a wide range of motor (climbing, vertical pole, rotarod, and running wheel performance) and non-motor functions (fear conditioning and anxiety) starting at 1–4 months of age, and are followed by progressive gliosis and decrease in DARPP32 (12 months) and a loss of striatal neurons at 2 years. At this age, mice also present striking spontaneous behavioral deficits in their home cage. The data show that this line of knock-in mice reproduces canonical characteristics of Huntington’s disease, preceded by deficits which may correspond to the protracted pre-manifest phase of the disease in humans. Accordingly, they provide a useful model to elucidate early mechanisms of pathophysiology and the progression to overt neurodegeneration. PMID:18805465

  13. Rotating bouncing disks, tossing pizza dough, and the behavior of ultrasonic motors

    NASA Astrophysics Data System (ADS)

    Liu, Kuang-Chen; Friend, James; Yeo, Leslie

    2009-10-01

    Pizza tossing and certain forms of standing-wave ultrasonic motors (SWUMs) share a similar process for converting reciprocating input into continuous rotary motion. We show that the key features of this motion conversion process such as collision, separation and friction coupling are captured by the dynamics of a disk bouncing on a vibrating platform. The model shows that the linear or helical hand motions commonly used by pizza chefs and dough-toss performers for single tosses maximize energy efficiency and the dough’s airborne rotational speed; on the other hand, the semielliptical hand motions used for multiple tosses make it easier to maintain dough rotation at the maximum speed. The system’s bifurcation diagram and basins of attraction also provide a physical basis for understanding the peculiar behavior of SWUMs and provide a means to design them. The model is able to explain the apparently chaotic oscillations that occur in SWUMs and predict the observed trends in steady-state speed and stall torque as preload is increased.

  14. Binocular Perception of 2D Lateral Motion and Guidance of Coordinated Motor Behavior.

    PubMed

    Fath, Aaron J; Snapp-Childs, Winona; Kountouriotis, Georgios K; Bingham, Geoffrey P

    2016-04-01

    Zannoli, Cass, Alais, and Mamassian (2012) found greater audiovisual lag between a tone and disparity-defined stimuli moving laterally (90-170 ms) than for disparity-defined stimuli moving in depth or luminance-defined stimuli moving laterally or in depth (50-60 ms). We tested if this increased lag presents an impediment to visually guided coordination with laterally moving objects. Participants used a joystick to move a virtual object in several constant relative phases with a laterally oscillating stimulus. Both the participant-controlled object and the target object were presented using a disparity-defined display that yielded information through changes in disparity over time (CDOT) or using a luminance-defined display that additionally provided information through monocular motion and interocular velocity differences (IOVD). Performance was comparable for both disparity-defined and luminance-defined displays in all relative phases. This suggests that, despite lag, perception of lateral motion through CDOT is generally sufficient to guide coordinated motor behavior. PMID:26614099

  15. Premixed ignition behavior of C{sub 9} fatty acid esters: A motored engine study

    SciTech Connect

    Zhang, Yu.; Yang, Yi; Boehman, Andre L.

    2009-06-15

    An experimental study on the premixed ignition behavior of C{sub 9} fatty acid esters has been conducted in a motored CFR engine. For each test fuel, the engine compression ratio was gradually increased from the lowest point (4.43) to the point where significant high temperature heat release (HTHR) was observed. The engine exhaust was sampled and analyzed through GC-FID/TCD and GC-MS. Combustion analysis showed that the four C{sub 9} fatty acid esters tested in this study exhibited evidently different ignition behavior. The magnitude of low temperature heat release (LTHR) follows the order, ethyl nonanoate > methyl nonanoate >> methyl 2-nonenoate > methyl 3-nonenoate. The lower oxidation reactivity for the unsaturated fatty acid esters in the low temperature regime can be explained by the reduced amount of six- or seven-membered transition state rings formed during the oxidation of the unsaturated esters due to the presence of a double bond in the aliphatic chain of the esters. The inhibition effect of the double bond on the low temperature oxidation reactivity of fatty acid esters becomes more pronounced as the double bond moves toward the central position of the aliphatic chain. GC-MS analysis of exhaust condensate collected under the engine conditions where only LTHR occurred showed that the alkyl chain of the saturated fatty acid esters participated in typical paraffin-like low temperature oxidation sequences. In contrast, for unsaturated fatty acid esters, the autoignition can undergo olefin ignition pathways. For all test compounds, the ester functional group remains largely intact during the early stage of oxidation. (author)

  16. Influence of flow velocity on motor behavior of sea cucumber Apostichopus japonicus.

    PubMed

    Pan, Yang; Zhang, Libin; Lin, Chenggang; Sun, Jiamin; Kan, Rentao; Yang, Hongsheng

    2015-05-15

    The influence of flow velocity on the motor behavior of the sea cucumber, Apostichopus japonicus was investigated in the laboratory. Cameras were used to record sea cucumber movements and behavior analysis software was used to measure the distance traveled, time spent, upstream or downstream of the start position and the speed of movements. In general, the mean velocity of A. japonicus was below 0.7mms(-1). The maximum velocity recorded for all the sea cucumbers tested was for a large individual (89.25±17.11g), at a flow rate of 4.6±0.5cms(-1). Medium sized (19.68±5.53g) and large individuals moved significantly faster than small individuals (2.65±1.24g) at the same flow rate. A. japonicus moved significantly faster when there was a moderate current (4.6±0.5cms(-1) and 14.7±0.3cms(-1)), compared with the fast flow rate (29.3±3.7cms(-1)) and when there was no flow (0cms(-1)). Sea cucumbers did not show positive rheotaxis in general, but did move in a downstream direction at faster current speeds. Large, medium and small sized individuals moved downstream at the fastest current speed tested, 29.3±3.7cms(-1). When there was no water flow, sea cucumbers tended to move in an irregular pattern. The movement patterns show that the sea cucumber, A. japonicus can move across the direction of flow, and can move both upstream and downstream along the direction of flow. PMID:25727024

  17. Interhemispheric claustral circuits coordinate sensory and motor cortical areas that regulate exploratory behaviors

    PubMed Central

    Smith, Jared B.; Alloway, Kevin D.

    2014-01-01

    The claustrum has a role in the interhemispheric transfer of certain types of sensorimotor information. Whereas the whisker region in rat motor (M1) cortex sends dense projections to the contralateral claustrum, the M1 forelimb representation does not. The claustrum sends strong ipsilateral projections to the whisker regions in M1 and somatosensory (S1) cortex, but its projections to the forelimb cortical areas are weak. These distinctions suggest that one function of the M1 projections to the contralateral claustrum is to coordinate the cortical areas that regulate peripheral sensor movements during behaviors that depend on bilateral sensory acquisition. If this hypothesis is true, then similar interhemispheric circuits should interconnect the frontal eye fields (FEF) with the contralateral claustrum and its network of projections to vision-related cortical areas. To test this hypothesis, anterograde and retrograde tracers were placed in physiologically-defined parts of the FEF and primary visual cortex (V1) in rats. We observed dense FEF projections to the contralateral claustrum that terminated in the midst of claustral neurons that project to both FEF and V1. While the FEF inputs to the claustrum come predominantly from the contralateral hemisphere, the claustral projections to FEF and V1 are primarily ipsilateral. Detailed comparison of the present results with our previous studies on somatomotor claustral circuitry revealed a well-defined functional topography in which the ventral claustrum is connected with visuomotor cortical areas and the dorsal regions are connected with somatomotor areas. These results suggest that subregions within the claustrum play a critical role in coordinating the cortical areas that regulate the acquisition of modality-specific sensory information during exploration and other behaviors that require sensory attention. PMID:24904315

  18. Intercostal muscle motor behavior during tracheal occlusion conditioning in conscious rats.

    PubMed

    Jaiswal, Poonam B; Davenport, Paul W

    2016-04-01

    A respiratory load compensation response is characterized by increases in activation of primary respiratory muscles and/or recruitment of accessory respiratory muscles. The contribution of the external intercostal (EI) muscles, which are a primary respiratory muscle group, during normal and loaded breathing remains poorly understood in conscious animals. Consciousness has a significant role on modulation of respiratory activity, as it is required for the integration of behavioral respiratory responses and voluntary control of breathing. Studies of respiratory load compensation have been predominantly focused in anesthetized animals, which make their comparison to conscious load compensation responses challenging. Using our established model of intrinsic transient tracheal occlusions (ITTO), our aim was to evaluate the motor behavior of EI muscles during normal and loaded breathing in conscious rats. We hypothesized that1) conscious rats exposed to ITTO will recruit the EI muscles with an increased electromyogram (EMG) activation and2) repeated ITTO for 10 days would potentiate the baseline EMG activity of this muscle in conscious rats. Our results demonstrate that conscious rats exposed to ITTO respond by recruiting the EI muscle with a significantly increased EMG activation. This response to occlusion remained consistent over the 10-day experimental period with little or no effect of repeated ITTO exposure on the baseline ∫EI EMG amplitude activity. The pattern of activation of the EI muscle in response to an ITTO is discussed in detail. The results from the present study demonstrate the importance of EI muscles during unloaded breathing and respiratory load compensation in conscious rats. PMID:26823339

  19. 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…

  20. Motor neuron pathology and behavioral alterations at late stages in a SMA mouse model.

    PubMed

    Fulceri, Federica; Bartalucci, Alessia; Paparelli, Silvio; Pasquali, Livia; Biagioni, Francesca; Ferrucci, Michela; Ruffoli, Riccardo; Fornai, Francesco

    2012-03-01

    Spinal muscular atrophy (SMA) is a neurogenetic autosomal recessive disorder characterized by degeneration of lower motor neurons. The validation of appropriate animal models is key in fostering SMA research. Recent studies set up an animal model showing long survival and slow disease progression. This model is knocked out for mouse SMN (Smn(-/-)) gene and carries a human mutation of the SMN1 gene (SMN1A2G), along with human SMN2 gene. In the present study we used this knock out double transgenic mouse model (SMN2(+/+); Smn(-/-); SMN1A2G(+/-)) to characterize the spinal cord pathology along with motor deficit at prolonged survival times. In particular, motor neuron loss was established stereologically (44.77%) after motor deficit reached a steady state. At this stage, spared motor neurons showed significant cell body enlargement. Moreover, similar to what was described in patients affected by SMA we found neuronal heterotopy (almost 4% of total motor neurons) in the anterior white matter. The delayed disease progression was likely to maintain fair motor activity despite a dramatic loss of large motor neurons. This provides a wonderful tool to probe novel drugs finely tuning the survival of motor neurons. In fact, small therapeutic effects protracted over considerable time intervals (even more than a year) are expected to be magnified. PMID:22306031

  1. Effect of Implicit Perceptual-Motor Training on Decision-Making Skills and Underpinning Gaze Behavior in Combat Athletes.

    PubMed

    Milazzo, Nicolas; Farrow, Damian; Fournier, Jean F

    2016-08-01

    This study investigated the effect of a 12-session, implicit perceptual-motor training program on decision-making skills and visual search behavior of highly skilled junior female karate fighters (M age = 15.7 years, SD = 1.2). Eighteen participants were required to make (physical or verbal) reaction decisions to various attacks within different fighting scenarios. Fighters' performance and eye movements were assessed before and after the intervention, and during acquisition through the use of video-based and on-mat decision-making tests. The video-based test revealed that following training, only the implicit perceptual-motor group (n = 6) improved their decision-making accuracy significantly compared to a matched motor training (placebo, n = 6) group and a control group (n = 6). Further, the implicit training group significantly changed their visual search behavior by focusing on fewer locations for longer durations. In addition, the session-by-session analysis showed no significant improvement in decision accuracy between training session 1 and all the other sessions, except the last one. Coaches should devote more practice time to implicit learning approaches during perceptual-motor training program to achieve significant decision-making improvements and more efficient visual search strategy with elite athletes. PMID:27371637

  2. Abnormal Eu behavior at formation of H2O- and Cl-bearing fluids during degassing of granite magmas

    NASA Astrophysics Data System (ADS)

    Lukanin, Oleg

    2010-05-01

    melt. The abnormal behavior of Eu shows itself the stronger, the lower fO2and, accordingly, the more fraction of Eu2+is present in melt. The work is supported of the Geosciences Department of the Russian Academy of Science (the program 2- 2010) and RFBR (grant 08-05-00022). References [1] Reed M.J., Candela Ph.A., Piccoli Ph.M. Contrib. Mineral. Petrol. 2000. V. 140. P. 251-262. [2] Lukanin O.A., Dernov-Pegarev V.F. Vestnik Otd. Nauk Zemle RAN, No 1(25)'2007 URL: http://www.scgis.ru/russian/cp1251/h_dgggms/1-2007/informbul-1_2007/term-30e.pdf [3] Drake M.J. Geochim. Cosmochim. Acta. 1975. V. 39. P. 55-64. [4] Wilke M. Behrens H. Contrib. Mineral. Petrol. 1999. V. 137. P. 102-114. [5] Lukanin O.A. Vestnik Otd. Nauk o Zemle RAN, No 1(26)'2008. URL: http://www.scgis.ru/russian/cp1251/h_dgggms/1-2008/informbul-1_2008/magm-20e.pdf [6] Lukanin O.A., Dernov-Pegarev V.F. Geochemistry International, 2010 (in press)

  3. Effects of Vestibular Stimulation on Motor Development and Stereotyped Behavior of Developmentally Delayed Children.

    ERIC Educational Resources Information Center

    MacLean, William E., Jr.; Baumeister, Alfred A.

    1982-01-01

    Four developmentally delayed babies were given semicircular canal stimulation in an effort to facilitate their motor and reflex development. All of the children showed motor and/or reflex changes that were attributable to the vestibular stimulation. In addition, some evidence was obtained linking changes in stereotypic responding to the vestibular…

  4. Generalized Motor Abilities and Timing Behavior in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Zelaznik, Howard N.; Goffman, Lisa

    2010-01-01

    Purpose: To examine whether children with specific language impairment (SLI) differ from normally developing peers in motor skills, especially those skills related to timing. Method: Standard measures of gross and fine motor development were obtained. Furthermore, finger and hand movements were recorded while children engaged in 4 different timing…

  5. Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice

    PubMed Central

    Tanda, Koichi; Nishi, Akinori; Matsuo, Naoki; Nakanishi, Kazuo; Yamasaki, Nobuyuki; Sugimoto, Tohru; Toyama, Keiko; Takao, Keizo; Miyakawa, Tsuyoshi

    2009-01-01

    Background Neuronal nitric oxide synthase (nNOS) is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO) mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice. Results nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice. Conclusion These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders. PMID:19538708

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

    PubMed

    Lamont, Matthew G; Weber, John T

    2015-06-01

    The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication. PMID:25721739

  7. Behavioral and Neural Plasticity of Ocular Motor Control: Changes in Performance and fMRI Activity Following Antisaccade Training

    PubMed Central

    Jamadar, Sharna D.; Johnson, Beth P.; Clough, Meaghan; Egan, Gary F.; Fielding, Joanne

    2015-01-01

    The antisaccade task provides a model paradigm that sets the inhibition of a reflexively driven behavior against the volitional control of a goal-directed behavior. The stability and adaptability of antisaccade performance was investigated in 23 neurologically healthy individuals. Behavior and brain function were measured using functional magnetic resonance imaging (fMRI) prior to and immediately following 2 weeks of daily antisaccade training. Participants performed antisaccade trials faster with no change in directional error rate following 2 weeks of training; however this increased speed came at the cost of the spatial accuracy of the saccade (gain) which became more hypometric following training. Training on the antisaccade task resulted in increases in fMRI activity in the fronto-basal ganglia-parietal-cerebellar ocular motor network. Following training, antisaccade latency was positively associated with fMRI activity in the frontal and supplementary eye fields, anterior cingulate and intraparietal sulcus; antisaccade gain was negatively associated with fMRI activity in supplementary eye fields, anterior cingulate, intraparietal sulcus, and cerebellar vermis. In sum, the results suggest that following training, larger antisaccade latency is associated with larger activity in fronto-parietal-cerebellar ocular motor regions, and smaller antisaccade gain is associated with larger activity in fronto-parietal ocular motor regions. PMID:26733841

  8. The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior

    NASA Astrophysics Data System (ADS)

    Rajan, Alexander T.; Boback, Jessica L.; Dammann, John F.; Tenore, Francesco V.; Wester, Brock A.; Otto, Kevin J.; Gaunt, Robert A.; Bensmaia, Sliman J.

    2015-12-01

    Objective. One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal’s ability to use their hand—the cortical representation of which is targeted by the ICMS—as a further assay of possible neuronal damage. Approach. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. Main results. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Significance. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

  9. Sensory gating of an embryonic zebrafish interneuron during spontaneous motor behaviors

    PubMed Central

    Knogler, Laura D.; Drapeau, Pierre

    2014-01-01

    In all but the simplest monosynaptic reflex arcs, sensory stimuli are encoded by sensory neurons that transmit a signal via sensory interneurons to downstream partners in order to elicit a response. In the embryonic zebrafish (Danio rerio), cutaneous Rohon-Beard (RB) sensory neurons fire in response to mechanical stimuli and excite downstream glutamatergic commissural primary ascending (CoPA) interneurons to produce a flexion response contralateral to the site of stimulus. In the absence of sensory stimuli, zebrafish spinal locomotor circuits are spontaneously active during development due to pacemaker activity resulting in repetitive coiling of the trunk. Self-generated movement must therefore be distinguishable from external stimuli in order to ensure the appropriate activation of touch reflexes. Here, we recorded from CoPAs during spontaneous and evoked fictive motor behaviors in order to examine how responses to self-movement are gated in sensory interneurons. During spontaneous coiling, CoPAs received glycinergic inputs coincident with contralateral flexions that shunted firing for the duration of the coiling event. Shunting inactivation of CoPAs was caused by a slowly deactivating chloride conductance that resulted in lowered membrane resistance and increased action potential threshold. During spontaneous burst swimming, which develops later, CoPAs received glycinergic inputs that arrived in phase with excitation to ipsilateral motoneurons and provided persistent shunting. During a touch stimulus, short latency glutamatergic inputs produced cationic currents through AMPA receptors that drove a single, large amplitude action potential in the CoPA before shunting inhibition began, providing a brief window for the activation of downstream neurons. We compared the properties of CoPAs to those of other spinal neurons and propose that glycinergic signaling onto CoPAs acts as a corollary discharge signal for reflex inhibition during movement. PMID:25324729

  10. ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

    PubMed Central

    2013-01-01

    Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious

  11. Rapid Amygdala Kindling Causes Motor Seizure and Comorbidity of Anxiety- and Depression-Like Behaviors in Rats

    PubMed Central

    Chen, Shang-Der; Wang, Yu-Lin; Liang, Sheng-Fu; Shaw, Fu-Zen

    2016-01-01

    Amygdala kindling is a model of temporal lobe epilepsy (TLE) with convulsion. The rapid amygdala kindling has an advantage on quick development of motor seizures and for antiepileptic drugs screening. The rapid amygdala kindling causes epileptogenesis accompanied by an anxiolytic response in early isolation of rat pups or depressive behavior in immature rats. However, the effect of rapid amygdala kindling on comorbidity of anxiety- and depression-like behaviors is unexplored in adult rats with normal breeding. In the present study, 40 amygdala stimulations given within 2 days were applied in adult Wistar rats. Afterdischarge (AD) and seizure stage were recorded throughout the amygdala kindling. Anxiety-like behaviors were evaluated by the elevated plus maze (EPM) test and open field (OF) test, whereas depression-like behaviors were assessed by the forced swim (FS) and sucrose consumption (SC) tests. A tonic-clonic convulsion was provoked in the kindle group. Rapid amygdala kindling resulted in a significantly lower frequency entering an open area of either open arms of the EPM or the central zone of an OF, lower sucrose intake, and longer immobility of the FS test in the kindle group. Our results suggest that rapid amygdala kindling elicited severe motor seizures comorbid with anxiety- and depression-like behaviors. PMID:27445726

  12. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  13. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

  14. Stepper motor

    NASA Technical Reports Server (NTRS)

    Dekramer, Cornelis

    1994-01-01

    The purpose of this document is to describe the more commonly used permanent magnet stepper motors for spaceflight. It will discuss the mechanical and electrical aspects of the devices, their torque behavior, those parameters which need to be controlled and measured, and test methods to be employed. It will also discuss torque margins, compare these to the existing margin requirements, and determine the applicability of these requirements. Finally it will attempt to generate a set of requirements which will be used in any stepper motor procurement and will fully characterize the stepper motor behavior in a consistent and repeatable fashion.

  15. How does environmental enrichment reduce repetitive motor behaviors? Neuronal activation and dendritic morphology in the indirect basal ganglia pathway of a mouse model.

    PubMed

    Bechard, Allison R; Cacodcar, Nadia; King, Michael A; Lewis, Mark H

    2016-02-15

    Repetitive motor behaviors are observed in many neurodevelopmental and neurological disorders (e.g., autism spectrum disorders, Tourette syndrome, fronto-temporal dementia). Despite their clinical importance, the neurobiology underlying these highly stereotyped, apparently functionless behaviors is poorly understood. Identification of mechanisms that mediate the development of repetitive behaviors will aid in the discovery of new therapeutic targets and treatment development. Using a deer mouse model, we have shown that decreased indirect basal ganglia pathway activity is associated with high levels of repetitive behavior. Environmental enrichment (EE) markedly attenuates the development of such aberrant behaviors in mice, although mechanisms driving this effect are unknown. We hypothesized that EE would reduce repetitive motor behaviors by increasing indirect basal ganglia pathway function. We assessed neuronal activation and dendritic spine density in basal ganglia of adult deer mice reared in EE and standard housing. Significant increases in neuronal activation and dendritic spine densities were observed only in the subthalamic nucleus (STN) and globus pallidus (GP), and only for those mice that exhibited an EE-induced decrease in repetitive motor behavior. As the STN and GP lie within the indirect pathway, these data suggest that EE-induced attenuation of repetitive motor behaviors is associated with increased functional activation of the indirect basal ganglia pathway. These results are consistent with our other findings highlighting the importance of the indirect pathway in mediating repetitive motor behaviors. PMID:26620495

  16. Behavioral and neurophysiological effects of delayed training following a small ischemic infarct in primary motor cortex of squirrel monkeys

    PubMed Central

    Plautz, Erik J.; Friel, Kathleen M.; Frost, Shawn B.; Dancause, Numa; Stowe, Ann M.; Nudo, Randolph J.

    2009-01-01

    A focal injury within the cerebral cortex results in functional reorganization within the spared cortex through time-dependent metabolic and physiological reactions. Physiological changes are also associated with specific post-injury behavioral experiences. Knowing how these factors interact can be beneficial in planning rehabilitative intervention after a stroke. The purpose of this study was to assess the functional impact of delaying the rehabilitative behavioral experience upon movement representations within the primary motor cortex (M1) in an established nonhuman primate, ischemic infarct model. Five adult squirrel monkeys were trained on a motor-skill task prior to and 1 month after an experimental ischemic infarct was induced in M1. Movement representations of the hand were derived within M1 using standard electrophysiological procedures prior to the infarct and again one and two months after the infarct. The results of this study show that even though recovery of motor skills was similar to that of a previous study in squirrel monkeys after early training, unlike early training, delayed training did not result in maintenance of the spared hand representation within the M1 peri-infarct hand area. Instead, delaying training resulted in a large decrease in spared hand representation during the spontaneous recovery period that persisted following the delayed training. In addition, delayed training resulted in an increase of simultaneously evoked movements that are typically independent. These results indicate that post-injury behavioral experience, such as motor skill training, may modulate peri-infarct cortical plasticity in different ways in the acute versus chronic stages following stroke. PMID:16273404

  17. A temporal predictive code for voice motor control: Evidence from ERP and behavioral responses to pitch-shifted auditory feedback.

    PubMed

    Behroozmand, Roozbeh; Sangtian, Stacey; Korzyukov, Oleg; Larson, Charles R

    2016-04-01

    The predictive coding model suggests that voice motor control is regulated by a process in which the mismatch (error) between feedforward predictions and sensory feedback is detected and used to correct vocal motor behavior. In this study, we investigated how predictions about timing of pitch perturbations in voice auditory feedback would modulate ERP and behavioral responses during vocal production. We designed six counterbalanced blocks in which a +100cents pitch-shift stimulus perturbed voice auditory feedback during vowel sound vocalizations. In three blocks, there was a fixed delay (500, 750 or 1000ms) between voice and pitch-shift stimulus onset (predictable), whereas in the other three blocks, stimulus onset delay was randomized between 500, 750 and 1000ms (unpredictable). We found that subjects produced compensatory (opposing) vocal responses that started at 80ms after the onset of the unpredictable stimuli. However, for predictable stimuli, subjects initiated vocal responses at 20ms before and followed the direction of pitch shifts in voice feedback. Analysis of ERPs showed that the amplitudes of the N1 and P2 components were significantly reduced in response to predictable compared with unpredictable stimuli. These findings indicate that predictions about temporal features of sensory feedback can modulate vocal motor behavior. In the context of the predictive coding model, temporally-predictable stimuli are learned and reinforced by the internal feedforward system, and as indexed by the ERP suppression, the sensory feedback contribution is reduced for their processing. These findings provide new insights into the neural mechanisms of vocal production and motor control. PMID:26835556

  18. Development and Validation of a Computational Model for Predicting the Behavior of Plumes from Large Solid Rocket Motors

    NASA Technical Reports Server (NTRS)

    Wells, Jason E.; Black, David L.; Taylor, Casey L.

    2013-01-01

    Exhaust plumes from large solid rocket motors fired at ATK's Promontory test site carry particulates to high altitudes and typically produce deposits that fall on regions downwind of the test area. As populations and communities near the test facility grow, ATK has become increasingly concerned about the impact of motor testing on those surrounding communities. To assess the potential impact of motor testing on the community and to identify feasible mitigation strategies, it is essential to have a tool capable of predicting plume behavior downrange of the test stand. A software package, called PlumeTracker, has been developed and validated at ATK for this purpose. The code is a point model that offers a time-dependent, physics-based description of plume transport and precipitation. The code can utilize either measured or forecasted weather data to generate plume predictions. Next-Generation Radar (NEXRAD) data and field observations from twenty-three historical motor test fires at Promontory were collected to test the predictive capability of PlumeTracker. Model predictions for plume trajectories and deposition fields were found to correlate well with the collected dataset.

  19. Cause and Consequence: Mitochondrial Dysfunction Initiates and Propagates Neuronal Dysfunction, Neuronal Death and Behavioral Abnormalities in Age Associated Neurodegenerative Diseases

    PubMed Central

    Gibson, Gary E.; Starkov, Anatoly; Blass, John P.; Ratan, Rajiv R.; Beal, M. Flint

    2009-01-01

    SUMMARY Age-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ordinarily sub lethal metabolic insults. Mild impairment of metabolism accrue from and lead to increased reactive oxygen species (ROS). Increased ROS change cell signaling via post transcriptional and transcriptional changes. The cause and consequences of mild impairment of mitochondrial metabolism is one focus of this review. Many experiments in tissues from humans support the notion that oxidative modification of the α-ketoglutarate dehydrogenase complex (KGDHC) compromises neuronal energy metabolism and enhance ROS production in Alzheimer’s Disease (AD). These data suggest that cognitive decline in AD derives from the selective tricarboxylic acid (TCA) cycle abnormalities. By contrast in Huntington’s Disease (HD), a movement disorder with cognitive features distinct form AD, complex II + III abnormalities may dominate. These distinct mitochondrial abnormalities culminate in oxidative stress, energy dysfunction, and aberrant homeostasis of cytosolic calcium. Cytosolic calcium, elevations even only transiently, leads to hyperactivity of a number of enzymes. One calcium activated enzyme with demonstrated pathophysiological import in HD and AD is transglutaminase (TGase). TGase is a cross linking enzymes that can modulate transcrption, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TGase can silence expression of genes involved in compensating for metabolic stress. Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic

  20. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities.

    PubMed

    Brunetti-Pierri, Nicola; Berg, Jonathan S; Scaglia, Fernando; Belmont, John; Bacino, Carlos A; Sahoo, Trilochan; Lalani, Seema R; Graham, Brett; Lee, Brendan; Shinawi, Marwan; Shen, Joseph; Kang, Sung-Hae L; Pursley, Amber; Lotze, Timothy; Kennedy, Gail; Lansky-Shafer, Susan; Weaver, Christine; Roeder, Elizabeth R; Grebe, Theresa A; Arnold, Georgianne L; Hutchison, Terry; Reimschisel, Tyler; Amato, Stephen; Geragthy, Michael T; Innis, Jeffrey W; Obersztyn, Ewa; Nowakowska, Beata; Rosengren, Sally S; Bader, Patricia I; Grange, Dorothy K; Naqvi, Sayed; Garnica, Adolfo D; Bernes, Saunder M; Fong, Chin-To; Summers, Anne; Walters, W David; Lupski, James R; Stankiewicz, Pawel; Cheung, Sau Wai; Patel, Ankita

    2008-12-01

    Chromosome region 1q21.1 contains extensive and complex low-copy repeats, and copy number variants (CNVs) in this region have recently been reported in association with congenital heart defects, developmental delay, schizophrenia and related psychoses. We describe 21 probands with the 1q21.1 microdeletion and 15 probands with the 1q21.1 microduplication. These CNVs were inherited in most of the cases in which parental studies were available. Consistent and statistically significant features of microcephaly and macrocephaly were found in individuals with microdeletion and microduplication, respectively. Notably, a paralog of the HYDIN gene located on 16q22.2 and implicated in autosomal recessive hydrocephalus was inserted into the 1q21.1 region during the evolution of Homo sapiens; we found this locus to be deleted or duplicated in the individuals we studied, making it a probable candidate for the head size abnormalities observed. We propose that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies. These phenotypes are subject to incomplete penetrance and variable expressivity. PMID:19029900

  1. Fish Oil Diet Associated with Acute Reperfusion Related Hemorrhage, and with Reduced Stroke-Related Sickness Behaviors and Motor Impairment

    PubMed Central

    Pascoe, Michaela C.; Howells, David W.; Crewther, David P.; Constantinou, Nicki; Carey, Leeanne M.; Rewell, Sarah S.; Turchini, Giovanni M.; Kaur, Gunveen; Crewther, Sheila G.

    2014-01-01

    Ischemic stroke is associated with motor impairment and increased incidence of affective disorders such as anxiety/clinical depression. In non-stroke populations, successful management of such disorders and symptoms has been reported following diet supplementation with long chain omega-3-polyunsaturated-fatty-acids (PUFAs). However, the potential protective effects of PUFA supplementation on affective behaviors after experimentally induced stroke and sham surgery have not been examined previously. This study investigated the behavioral effects of PUFA supplementation over a 6-week period following either middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The PUFA diet supplied during the acclimation period prior to surgery was found to be associated with an increased risk of acute hemorrhage following the reperfusion component of the surgery. In surviving animals, PUFA supplementation did not influence infarct size as determined 6 weeks after surgery, but did decrease omega-6-fatty-acid levels, moderate sickness behaviors, acute motor impairment, and longer-term locomotor hyperactivity and depression/anxiety-like behavior. PMID:24567728

  2. Fish oil diet associated with acute reperfusion related hemorrhage, and with reduced stroke-related sickness behaviors and motor impairment.

    PubMed

    Pascoe, Michaela C; Howells, David W; Crewther, David P; Constantinou, Nicki; Carey, Leeanne M; Rewell, Sarah S; Turchini, Giovanni M; Kaur, Gunveen; Crewther, Sheila G

    2014-01-01

    Ischemic stroke is associated with motor impairment and increased incidence of affective disorders such as anxiety/clinical depression. In non-stroke populations, successful management of such disorders and symptoms has been reported following diet supplementation with long chain omega-3-polyunsaturated-fatty-acids (PUFAs). However, the potential protective effects of PUFA supplementation on affective behaviors after experimentally induced stroke and sham surgery have not been examined previously. This study investigated the behavioral effects of PUFA supplementation over a 6-week period following either middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The PUFA diet supplied during the acclimation period prior to surgery was found to be associated with an increased risk of acute hemorrhage following the reperfusion component of the surgery. In surviving animals, PUFA supplementation did not influence infarct size as determined 6 weeks after surgery, but did decrease omega-6-fatty-acid levels, moderate sickness behaviors, acute motor impairment, and longer-term locomotor hyperactivity and depression/anxiety-like behavior. PMID:24567728

  3. Abnormal chromosome behavior during meiosis in the allotetraploid of Carassius auratus red var. (♀) × Megalobrama amblycephala (♂)

    PubMed Central

    2014-01-01

    Background Allopolyploids generally undergo bivalent pairing at meiosis because only homologous chromosomes pair up. On the other hand, several studies have documented abnormal chromosome behavior during mitosis and meiosis in allopolyploids plants leading to the production of gametes with complete paternal or maternal chromosomes. Polyploidy is relatively rare in animals compared with plants; thus, chromosome behavior at meiosis in the allopolyploid animals is poorly understood. Results Tetraploid hybrids (abbreviated as 4nRB) (4n = 148, RRBB) of Carassius auratus red var. (abbreviated as RCC) (2n = 100, RR) (♀) × Megalobrama amblycephala (abbreviated as BSB) (2n = 48, BB) (♂) generated gametes of different size. To test the genetic composition of these gametes, the gynogenetic offspring and backcross progenies of 4nRB were produced, and their genetic composition were examined by chromosome analysis and FISH. Our results suggest that 4nRB can produce several types of gametes with different genetic compositions, including allotetraploid (RRBB), autotriploid (RRR), autodiploid (RR), and haploid (R) gametes. Conclusions This study provides direct evidence of abnormal chromosome behavior during meiosis in an allotetraploid fish. PMID:25178799

  4. Congenital Abnormalities

    MedlinePlus

    ... serious health problems (e.g. Down syndrome ). Single-Gene Abnormalities Sometimes the chromosomes are normal in number, ... blood flow to the fetus impair fetal growth. Alcohol consumption and certain drugs during pregnancy significantly increase ...

  5. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  6. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  7. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  8. Nail abnormalities

    MedlinePlus

    Nail abnormalities are problems with the color, shape, texture, or thickness of the fingernails or toenails. ... Fungus or yeast cause changes in the color, texture, and shape of the nails. Bacterial infection may ...

  9. Effects of short-term training on behavioral learning and skill acquisition during intraoral fine motor task.

    PubMed

    Kumar, A; Grigoriadis, J; Trulsson, M; Svensson, P; Svensson, K G

    2015-10-15

    Sensory information from the orofacial mechanoreceptors are used by the nervous system to optimize the positioning of food, determine the force levels, and force vectors involved in biting of food morsels. Moreover, practice resulting from repetition could be a key to learning and acquiring a motor skill. Hence, the aim of the experiment was to test the hypothesis that repeated splitting of a food morsel during a short-term training with an oral fine motor task would result in increased performance and optimization of jaw movements, in terms of reduction in duration of various phases of the jaw movements. Thirty healthy volunteers were asked to intraorally manipulate and split a chocolate candy, into two equal halves. The participants performed three series (with 10 trials) of the task before and after a short-term (approximately 30 min) training. The accuracy of the split and vertical jaw movement during the task were recorded. The precision of task performance improved significantly after training (22% mean deviation from ideal split after vs. 31% before; P<0.001). There was a significant decrease in the total duration of jaw movements during the task after the training (1.21 s total duration after vs. 1.56 s before; P<0.001). Further, when the jaw movements were divided into different phases, the jaw opening phase and contact phase were significantly shorter after training than before training (P=0.001, P=0.002). The results indicate that short-term training of an oral fine motor task induces behavior learning, skill acquisition and optimization of jaw movements in terms of better performance and reduction in the duration of jaw movements, during the task. The finding of the present study provides insights into how humans learn oral motor behaviors or the kind of adaptation that takes place after a successful prosthetic rehabilitation. PMID:26162238

  10. Properties of the Driving Behavior Survey Among Individuals with Motor Vehicle Accident-Related Posttraumatic Stress Disorder

    PubMed Central

    Clapp, Joshua D.; Baker, Aaron S.; Litwack, Scott D.; Sloan, Denise M.; Beck, J. Gayle

    2014-01-01

    Data suggest anxious drivers may engage in problematic behaviors that place themselves and others at increased risk of negative traffic events. Three domains of problematic behavior – exaggerated safety/caution, performance deficits, and hostile/aggressive behaviors – previously were identified during development of the Driving Behavior Survey (DBS), a novel measure of anxiety-related behavior. Extending this research, the current study examined the psychometric properties of DBS scores among individuals with posttraumatic stress disorder (PTSD) subsequent to motor vehicle trauma (N = 40). Internal consistencies and 12-week test-retest reliabilities for DBS scales ranged from good to excellent. Comparison of scores to normative student data indicated dose-response relationships for safety/caution and performance deficit subscales, with increased frequency of anxious behavior occurring within the PTSD sample. Associations with standard clinical measures provide additional evidence for anxiety-related driving behavior as a unique marker of functional impairment, distinct from both avoidance and disorder-specific symptoms. PMID:24325891

  11. Properties of the Driving Behavior Survey among individuals with motor vehicle accident-related posttraumatic stress disorder.

    PubMed

    Clapp, Joshua D; Baker, Aaron S; Litwack, Scott D; Sloan, Denise M; Beck, J Gayle

    2014-01-01

    Data suggest anxious drivers may engage in problematic behaviors that place themselves and others at increased risk of negative traffic events. Three domains of problematic behavior--exaggerated safety/caution, performance deficits, and hostile/aggressive behaviors--previously were identified during development of the Driving Behavior Survey (DBS), a novel measure of anxiety-related behavior. Extending this research, the current study examined the psychometric properties of DBS scores among individuals with posttraumatic stress disorder (PTSD) subsequent to motor vehicle trauma (N=40). Internal consistencies and 12-week test-retest reliabilities for DBS scales ranged from good to excellent. Comparison of scores to normative student data indicated dose-response relationships for safety/caution and performance deficit subscales, with increased frequency of anxious behavior occurring within the PTSD sample. Associations with standard clinical measures provide additional evidence for anxiety-related driving behavior as a unique marker of functional impairment, distinct from both avoidance and disorder-specific symptoms. PMID:24325891

  12. Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic acid in mice.

    PubMed

    Farfán-García, E D; Pérez-Rodríguez, M; Espinosa-García, C; Castillo-Mendieta, N T; Maldonado-Castro, M; Querejeta, E; Trujillo-Ferrara, J G; Soriano-Ursúa, M A

    2016-09-15

    The scarcity of studies on boron containing compounds (BCC) in the medicinal field is gradually being remedied. Efforts have been made to explore the effects of BCCs due to the properties that boron confers to molecules. Research has shown that the safety of some BCCs is similar to that found for boron-free compounds (judging from the acute toxicological evaluation). However, it has been observed that the administration of 3-thienylboronic acid (3TB) induced motor disruption in CD1 mice. In the current contribution we studied in deeper form the disruption of motor performance produced by the intraperitoneal administration of 3TB in mice from two strains (CD1 and C57BL6). Disruption of motor activity was dependent not only on the dose of 3TB administered, but also on the DMSO concentration in the vehicle. The ability of 3TB to enter the Central Nervous System (CNS) was evidenced by Raman spectroscopy as well as morphological effects on the CNS, such as loss of neurons yielding biased injury to the substantia nigra and striatum at doses ≥200mg/kg, and involving granular cell damage at doses of 400mg/kg but less injury in the motor cortex. Our work acquaints about the use of this compound in drug design, but the interesting profile as neurotoxic agent invite us to study it regarding the damage on the motor system. PMID:27495897

  13. The effects of oral motor stimulation on feeding behaviors of infants born with univentricle anatomy.

    PubMed

    Coker-Bolt, Patty; Jarrard, Courtney; Woodard, Francis; Merrill, Paige

    2013-01-01

    The purpose of this pilot study was to determine the effects of oral motor stimulation on infants born with complex univentricle anatomy who required surgery shortly after birth. A quasi-experimental group design was used to compare 18 infants receiving an oral motor stimulation program with 10 infants who did not receive any oral motor intervention. Infants in the treatment group received the oral motor treatment prior to cardiac surgery and immediately following surgery, one time a day, 6 days a week. Outcomes data were collected for length of time to reach full bottle-feeds and length of hospital stay. A statistically significant difference was seen in the overall length of hospital stay between the two groups (p = .04). Infants in the experimental group were hospitalized for a mean of 28.6 days and infants in the comparison group for a mean of 35.3 days. Infants in the treatment group achieved full bottle-feeds 2 days earlier than infants in the comparison group, although this was not statistically significant. There is positive support for the use of oral motor stimulation for infants born with univentricle anatomy, but further study is needed to determine the long-lasting effects of this intervention. PMID:22497742

  14. Collective behavior of minus-ended motors in mitotic microtubule asters gliding toward DNA

    NASA Astrophysics Data System (ADS)

    Athale, Chaitanya A.; Dinarina, Ana; Nedelec, Francois; Karsenti, Eric

    2014-02-01

    Microtubules (MTs) nucleated by centrosomes form star-shaped structures referred to as asters. Aster motility and dynamics is vital for genome stability, cell division, polarization and differentiation. Asters move either toward the cell center or away from it. Here, we focus on the centering mechanism in a membrane independent system of Xenopus cytoplasmic egg extracts. Using live microscopy and single particle tracking, we find that asters move toward chromatinized DNA structures. The velocity and directionality profiles suggest a random-walk with drift directed toward DNA. We have developed a theoretical model that can explain this movement as a result of a gradient of MT length dynamics and MT gliding on immobilized dynein motors. In simulations, the antagonistic action of the motor species on the radial array of MTs leads to a tug-of-war purely due to geometric considerations and aster motility resembles a directed random-walk. Additionally, our model predicts that aster velocities do not change greatly with varying initial distance from DNA. The movement of asymmetric asters becomes increasingly super-diffusive with increasing motor density, but for symmetric asters it becomes less super-diffusive. The transition of symmetric asters from superdiffusive to diffusive mobility is the result of number fluctuations in bound motors in the tug-of-war. Overall, our model is in good agreement with experimental data in Xenopus cytoplasmic extracts and predicts novel features of the collective effects of motor-MT interactions.

  15. Collective behavior of minus-ended motors in mitotic microtubule asters gliding toward DNA.

    PubMed

    Athale, Chaitanya A; Dinarina, Ana; Nedelec, Francois; Karsenti, Eric

    2014-02-01

    Microtubules (MTs) nucleated by centrosomes form star-shaped structures referred to as asters. Aster motility and dynamics is vital for genome stability, cell division, polarization and differentiation. Asters move either toward the cell center or away from it. Here, we focus on the centering mechanism in a membrane independent system of Xenopus cytoplasmic egg extracts. Using live microscopy and single particle tracking, we find that asters move toward chromatinized DNA structures. The velocity and directionality profiles suggest a random-walk with drift directed toward DNA. We have developed a theoretical model that can explain this movement as a result of a gradient of MT length dynamics and MT gliding on immobilized dynein motors. In simulations, the antagonistic action of the motor species on the radial array of MTs leads to a tug-of-war purely due to geometric considerations and aster motility resembles a directed random-walk. Additionally, our model predicts that aster velocities do not change greatly with varying initial distance from DNA. The movement of asymmetric asters becomes increasingly super-diffusive with increasing motor density, but for symmetric asters it becomes less super-diffusive. The transition of symmetric asters from superdiffusive to diffusive mobility is the result of number fluctuations in bound motors in the tug-of-war. Overall, our model is in good agreement with experimental data in Xenopus cytoplasmic extracts and predicts novel features of the collective effects of motor-MT interactions. PMID:24476749

  16. Delta-9-tetrahydrocannabinol (THC) affects forelimb motor map expression but has little effect on skilled and unskilled behavior.

    PubMed

    Scullion, K; Guy, A R; Singleton, A; Spanswick, S C; Hill, M N; Teskey, G C

    2016-04-01

    It has previously been shown in rats that acute administration of delta-9-tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naïve rats resulted in dose-dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior. PMID:26826333

  17. Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism.

    PubMed

    Maurice, Nicolas; Liberge, Martine; Jaouen, Florence; Ztaou, Samira; Hanini, Marwa; Camon, Jeremy; Deisseroth, Karl; Amalric, Marianne; Kerkerian-Le Goff, Lydia; Beurrier, Corinne

    2015-10-27

    Despite evidence showing that anticholinergic drugs are of clinical relevance in Parkinson's disease (PD), the causal role of striatal cholinergic interneurons (CINs) in PD pathophysiology remains elusive. Here, we show that optogenetic inhibition of CINs alleviates motor deficits in PD mouse models, providing direct demonstration for their implication in parkinsonian motor dysfunctions. As neural correlates, CIN inhibition in parkinsonian mice differentially impacts the excitability of striatal D1 and D2 medium spiny neurons, normalizes pathological bursting activity in the main basal ganglia output structure, and increases the functional weight of the direct striatonigral pathway in cortical information processing. By contrast, CIN inhibition in non-lesioned mice does not affect locomotor activity, equally modulates medium spiny neuron excitability, and does not modify spontaneous or cortically driven activity in the basal ganglia output, suggesting that the role of these interneurons in motor function is highly dependent on dopamine tone. PMID:26489458

  18. Thalamocortical Projections onto Behaviorally Relevant Neurons Exhibit Plasticity during Adult Motor Learning.

    PubMed

    Biane, Jeremy S; Takashima, Yoshio; Scanziani, Massimo; Conner, James M; Tuszynski, Mark H

    2016-03-16

    Layer 5 neurons of the neocortex receive direct and relatively strong input from the thalamus. However, the intralaminar distribution of these inputs and their capacity for plasticity in adult animals are largely unknown. In slices of the primary motor cortex (M1), we simultaneously recorded from pairs of corticospinal neurons associated with control of distinct motor outputs: distal forelimb versus proximal forelimb. Activation of ChR2-expressing thalamocortical afferents in M1 before motor learning produced equivalent responses in monosynaptic excitation of neurons controlling the distal and proximal forelimb, suggesting balanced thalamic input at baseline. Following skilled grasp training, however, thalamocortical input shifted to bias activation of corticospinal neurons associated with control of the distal forelimb. This increase was associated with a cell-specific increase in mEPSC amplitude but not presynaptic release probability. These findings demonstrate distinct and highly segregated plasticity of thalamocortical projections during adult learning. PMID:26948893

  19. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

    PubMed Central

    Kron, Miriam; Lang, Min; Adams, Ian T.; Sceniak, Michael; Longo, Frank; Katz, David M.

    2014-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to contribute to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). In Mecp2 mutant mice, BDNF deficits have been associated with breathing abnormalities, a core feature of RTT, as well as with synaptic hyperexcitability within the brainstem respiratory network. Application of BDNF can reverse hyperexcitability in acute brainstem slices from Mecp2-null mice, suggesting that therapies targeting BDNF or its receptor, TrkB, could be effective at acute reversal of respiratory abnormalities in RTT. Therefore, we examined the ability of LM22A-4, a small-molecule BDNF loop-domain mimetic and TrkB partial agonist, to modulate synaptic excitability within respiratory cell groups in the brainstem nucleus tractus solitarius (nTS) and to acutely reverse abnormalities in breathing at rest and during behavioral arousal in Mecp2 mutants. Patch-clamp recordings in Mecp2-null brainstem slices demonstrated that LM22A-4 decreases excitability at primary afferent synapses in the nTS by reducing the amplitude of evoked excitatory postsynaptic currents and the frequency of spontaneous and miniature excitatory postsynaptic currents. In vivo, acute treatment of Mecp2-null and -heterozygous mutants with LM22A-4 completely eliminated spontaneous apneas in resting animals, without sedation. Moreover, we demonstrate that respiratory dysregulation during behavioral arousal, a feature of human RTT, is also reversed in Mecp2 mutants by acute treatment with LM22A-4. Together, these data support the hypothesis that reduced BDNF signaling and respiratory dysfunction in RTT are linked, and establish the proof-of-concept that treatment with a small-molecule structural mimetic of a BDNF loop domain and a TrkB partial agonist can acutely reverse abnormal breathing at rest and in response to behavioral arousal

  20. Molecular motors

    NASA Astrophysics Data System (ADS)

    Allemand, Jean François Desbiolles, Pierre

    2015-10-01

    How do we move? More precisely, what are the molecular mechanisms that can explain that our muscles, made of very small components can move at a osopic scale? To answer these questions we must introduce molecular motors. Those motors are proteins, or small protein assemblies that, in our cells, transform chemical energy into mechanical work. Then, like we could do for a oscopic motor, used in a car or in a fan, we are going to study the basic behavior of these molecular machines, present what are their energy sources, calculate their power, their yield. If molecular motors are crucial for our oscopic movements, we are going to see that they are also essential to cellular transport and that considering the activity of some enzymes as molecular motors bring some interesting new insights on their activity.

  1. Immunoglobulins from Animal Models of Motor Neuron Disease and from Human Amyotrophic Lateral Sclerosis Patients Passively Transfer Physiological Abnormalities to the Neuromuscular Junction

    NASA Astrophysics Data System (ADS)

    Apel, Stanley H.; Engelhardt, Jozsef I.; Garcia, Jesus; Stefani, Enrico

    1991-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating human disease of upper and lower motoneurons of unknown etiology. In support of the potential role of autoimmunity in ALS, two immune-mediated animal models of motoneuron disease have been developed that resemble ALS with respect to the loss of motoneurons, the presence of IgG within motoneurons and at the neuromuscular junction, and with respect to altered physiology of the motor nerve terminal. To provide direct evidence for the primary role of humoral immunity, passive transfer with immunoglobulins from the two animal models and human ALS was carried out. Mice injected with serum or immunoglobulins from the animal disease models and human ALS but not controls demonstrated IgG in motoneurons and at the neuromuscular junction. The mice also demonstrated an increase in miniature end-plate potential (mepp) frequency, with normal amplitude and time course and normal resting membrane potential, indicating an increased resting quantal release of acetylcholine from the nerve terminal. The ability to transfer motoneuron dysfunction with serum immunoglobulins provides evidence for autoimmune mechanisms in the pathogenesis of both the animal models and human ALS.

  2. The beneficial effects of berries on cognition, motor behavior, and neuronal function in aging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously, it has been shown that strawberry or blueberry supplementations, when fed to rats from 19-21 months of age, reverse age-related decrements in motor and cognitive performance. We have postulated that these effects may be the result of a number of positive benefits of the berry polyphenol...

  3. A Neurobehavioral Investigation into Judgmental Processes: Effect of Bilateral Motor Behaviors

    ERIC Educational Resources Information Center

    Cretenet, Joel; Dru, Vincent

    2008-01-01

    Two experiments were conducted in order to examine how different bilateral motor activations of the approach and avoidance motivational systems influenced participants' evaluations of valenced stimuli (figurative expressions and pictures of everyday situations). The first Study (Study 1) showed that participants judged valenced expressions…

  4. Muscle fiber and motor unit behavior in the longest human skeletal muscle.

    PubMed

    Harris, A John; Duxson, Marilyn J; Butler, Jane E; Hodges, Paul W; Taylor, Janet L; Gandevia, Simon C

    2005-09-14

    The sartorius muscle is the longest muscle in the human body. It is strap-like, up to 600 mm in length, and contains five to seven neurovascular compartments, each with a neuromuscular endplate zone. Some of its fibers terminate intrafascicularly, whereas others may run the full length of the muscle. To assess the location and timing of activation within motor units of this long muscle, we recorded electromyographic potentials from multiple intramuscular electrodes along sartorius muscle during steady voluntary contraction and analyzed their activity with spike-triggered averaging from a needle electrode inserted near the proximal end of the muscle. Approximately 30% of sartorius motor units included muscle fibers that ran the full length of the muscle, conducting action potentials at 3.9 +/- 0.1 m/s. Most motor units were innervated within a single muscle endplate zone that was not necessarily near the midpoint of the fiber. As a consequence, action potentials reached the distal end of a unit as late as 100 ms after initiation at an endplate zone. Thus, contractile activity is not synchronized along the length of single sartorius fibers. We postulate that lateral transmission of force from fiber to endomysium and a wide distribution of motor unit endplates along the muscle are critical for the efficient transmission of force from sarcomere to tendon and for the prevention of muscle injury caused by overextension of inactive regions of muscle fibers. PMID:16162934

  5. Mandibular Motor Control during the Early Development of Speech and Nonspeech Behaviors

    ERIC Educational Resources Information Center

    Steeve, Roger W.; Moore, Christopher A.

    2009-01-01

    Purpose: The mandible is often portrayed as a primary structure of early babble production, but empiricists still need to specify (a) how mandibular motor control and kinematics vary among different types of multisyllabic babble, (b) whether chewing or jaw oscillation relies on a coordinative infrastructure that can be exploited for early types of…

  6. Beneficial effects of gfap/vimentin reactive astrocytes for axonal remodeling and motor behavioral recovery in mice after stroke.

    PubMed

    Liu, Zhongwu; Li, Yi; Cui, Yisheng; Roberts, Cynthia; Lu, Mei; Wilhelmsson, Ulrika; Pekny, Milos; Chopp, Michael

    2014-12-01

    The functional role of reactive astrocytes after stroke is controversial. To elucidate whether reactive astrocytes contribute to neurological recovery, we compared behavioral outcome, axonal remodeling of the corticospinal tract (CST), and the spatio-temporal change of chondroitin sulfate proteoglycan (CSPG) expression between wild-type (WT) and glial fibrillary acidic protein/vimentin double knockout (GFAP(-/-) Vim(-/-) ) mice subjected to Rose Bengal induced cerebral cortical photothrombotic stroke in the right forelimb motor area. A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA) was injected into the left motor cortex to anterogradely label the CST axons. Compared with WT mice, the motor functional recovery and BDA-positive CST axonal length in the denervated side of the cervical gray matter were significantly reduced in GFAP(-/-) Vim(-/-) mice (n = 10/group, P < 0.01). Immunohistological data showed that in GFAP(-/-) Vim(-/-) mice, in which astrocytic reactivity is attenuated, CSPG expression was significantly increased in the lesion remote areas in both hemispheres, but decreased in the ischemic lesion boundary zone, compared with WT mice (n = 12/group, P < 0.001). Our data suggest that attenuated astrocytic reactivity impairs or delays neurological recovery by reducing CST axonal remodeling in the denervated spinal cord. Thus, manipulation of astrocytic reactivity post stroke may represent a therapeutic target for neurorestorative strategies. PMID:25043249

  7. Adaptive intermittent control: A computational model explaining motor intermittency observed in human behavior.

    PubMed

    Sakaguchi, Yutaka; Tanaka, Masato; Inoue, Yasuyuki

    2015-07-01

    It is a fundamental question how our brain performs a given motor task in a real-time fashion with the slow sensorimotor system. Computational theory proposed an influential idea of feed-forward control, but it has mainly treated the case that the movement is ballistic (such as reaching) because the motor commands should be calculated in advance of movement execution. As a possible mechanism for operating feed-forward control in continuous motor tasks (such as target tracking), we propose a control model called "adaptive intermittent control" or "segmented control," that brain adaptively divides the continuous time axis into discrete segments and executes feed-forward control in each segment. The idea of intermittent control has been proposed in the fields of control theory, biological modeling and nonlinear dynamical system. Compared with these previous models, the key of the proposed model is that the system speculatively determines the segmentation based on the future prediction and its uncertainty. The result of computer simulation showed that the proposed model realized faithful visuo-manual tracking with realistic sensorimotor delays and with less computational costs (i.e., with fewer number of segments). Furthermore, it replicated "motor intermittency", that is, intermittent discontinuities commonly observed in human movement trajectories. We discuss that the temporally segmented control is an inevitable strategy for brain which has to achieve a given task with small computational (or cognitive) cost, using a slow control system in an uncertain variable environment, and the motor intermittency is the side-effect of this strategy. PMID:25897510

  8. The Effect of a Developmental Play Program on the Self Concept, Risk-Taking Behaviors, and Motoric Proficiency of Mildly Handicapped Children.

    ERIC Educational Resources Information Center

    Roswal, Glenn; And Others

    1984-01-01

    The results of an investigation to determine the effect of the Children's Developmental Play Program on behavioral and neuromotor functioning of developmentally disabled children indicates that it serves as a valuable resource to the child, community, and inservice teachers. This study observed risk-taking behaviors, self-concept, and motor skills…

  9. Chronic exposure to environmentally-relevant concentrations of fluoxetine (Prozac) decreases survival, increases abnormal behaviors, and delays predator escape responses in guppies.

    PubMed

    Pelli, Marco; Connaughton, Victoria P

    2015-11-01

    This study evaluates the impact of fluoxetine, an antidepressant drug and common pollutant in aquatic environments, on growth, survival, and behavior in juvenile guppies and on predator escape responses in adult guppies (Poecilia reticulata). In juveniles, the effects of acute (4d) and chronic (35d) exposure on growth and survival were examined, and behavioral changes were noted throughout the chronic experiment. In adults, escape responses to a mock predator during chronic (28d) fluoxetine exposure were videotaped to determine the overall speed of response in treated vs. control fish. The effects of fish gender and the presence of a group/school on escape responses were also determined. Our results show that acute exposure to nominal concentrations of 0.03 and 0.5μg/L, levels within the environment, did not adversely impact juvenile guppy survival. However, chronic exposure significantly reduced weight, length, and belly width/girth measurements compared to controls. Chronic exposure also resulted in abnormal swimming behavior and reduced survival in juveniles. In adults, fluoxetine exposure significantly delayed predator escape responses in both males and females. Escape responses were also reduced when adults were tested either individually or in a group, with significantly more delayed responses seen in individually tested fish. Taken together, these findings suggest that fluoxetine can impact guppy populations, during both juvenile and adult stages, with chronic exposure resulting in decreased survival and growth and altered behavioral responses. PMID:26126230

  10. Alzheimer Disease in a Mouse Model: MR Imaging–guided Focused Ultrasound Targeted to the Hippocampus Opens the Blood-Brain Barrier and Improves Pathologic Abnormalities and Behavior

    PubMed Central

    Dubey, Sonam; Yeung, Sharon; Hough, Olivia; Eterman, Naomi; Aubert, Isabelle; Hynynen, Kullervo

    2014-01-01

    Purpose To validate whether repeated magnetic resonance (MR) imaging–guided focused ultrasound treatments targeted to the hippocampus, a brain structure relevant for Alzheimer disease (ADAlzheimer disease), could modulate pathologic abnormalities, plasticity, and behavior in a mouse model. Materials and Methods All animal procedures were approved by the Animal Care Committee and are in accordance with the Canadian Council on Animal Care. Seven-month-old transgenic (TgCRND8) (Tg) mice and their nontransgenic (non-Tg) littermates were entered in the study. Mice were treated weekly with MR imaging–guided focused ultrasound in the bilateral hippocampus (1.68 MHz, 10-msec bursts, 1-Hz burst repetition frequency, 120-second total duration). After 1 month, spatial memory was tested in the Y maze with the novel arm prior to sacrifice and immunohistochemical analysis. The data were compared by using unpaired t tests and analysis of variance with Tukey post hoc analysis. Results Untreated Tg mice spent 61% less time than untreated non-Tg mice exploring the novel arm of the Y maze because of spatial memory impairments (P < .05). Following MR imaging–guided focused ultrasound, Tg mice spent 99% more time exploring the novel arm, performing as well as their non-Tg littermates. Changes in behavior were correlated with a reduction of the number and size of amyloid plaques in the MR imaging–guided focused ultrasound–treated animals (P < .01). Further, after MR imaging–guided focused ultrasound treatment, there was a 250% increase in the number of newborn neurons in the hippocampus (P < .01). The newborn neurons had longer dendrites and more arborization after MR imaging–guided focused ultrasound, as well (P < .01). Conclusion Repeated MR imaging–guided focused ultrasound treatments led to spatial memory improvement in a Tg mouse model of ADAlzheimer disease. The behavior changes may be mediated by decreased amyloid pathologic abnormalities and increased neuronal

  11. Variability in Post-Error Behavioral Adjustment Is Associated with Functional Abnormalities in the Temporal Cortex in Children with ADHD

    ERIC Educational Resources Information Center

    Spinelli, Simona; Vasa, Roma A.; Joel, Suresh; Nelson, Tess E.; Pekar, James J.; Mostofsky, Stewart H.

    2011-01-01

    Background: Error processing is reflected, behaviorally, by slower reaction times (RT) on trials immediately following an error (post-error). Children with attention-deficit hyperactivity disorder (ADHD) fail to show RT slowing and demonstrate increased intra-subject variability (ISV) on post-error trials. The neural correlates of these behavioral…

  12. Comments on "the Feldenkrais Method: a dynamic approach to changing motor behavior".

    PubMed

    Ives, Jeffrey C

    2003-06-01

    The Feldenkrais Method has recently been discussed to fit within a dynamic systems model of human movement. One basis for this discussion is that small changes in one system--for example, enhanced body awareness--has far reaching implications across the whole of human performance. An alternative view on the Feldenkrais Method is argued here. It is argued that the clinical data do not support the Feldenkrais Method as being an effective way to improve motor performance. Further, it is argued that positive outcomes in pain and other wellness measures following Feldenkrais interventions can be ascribed to self-regulation. As part of this discussion, the role of body awareness, attentional focus, and kinesthesia in motor leaning and control are explored. PMID:12848224

  13. Chromosomal Abnormalities and Schizophrenia

    PubMed Central

    BASSETT, ANNE S.; CHOW, EVA W.C.; WEKSBERG, ROSANNA

    2011-01-01

    Schizophrenia is a common and serious psychiatric illness with strong evidence for genetic causation, but no specific loci yet identified. Chromosomal abnormalities associated with schizophrenia may help to understand the genetic complexity of the illness. This paper reviews the evidence for associations between chromosomal abnormalities and schizophrenia and related disorders. The results indicate that 22q11.2 microdeletions detected by fluorescence in-situ hybridization (FISH) are significantly associated with schizophrenia. Sex chromosome abnormalities seem to be increased in schizophrenia but insufficient data are available to indicate whether schizophrenia or related disorders are increased in patients with sex chromosome aneuploidies. Other reports of chromosomal abnormalities associated with schizophrenia have the potential to be important adjuncts to linkage studies in gene localization. Advances in molecular cytogenetic techniques (i.e., FISH) have produced significant increases in rates of identified abnormalities in schizophrenia, particularly in patients with very early age at onset, learning difficulties or mental retardation, or dysmorphic features. The results emphasize the importance of considering behavioral phenotypes, including adult onset psychiatric illnesses, in genetic syndromes and the need for clinicians to actively consider identifying chromosomal abnormalities and genetic syndromes in selected psychiatric patients. PMID:10813803

  14. Prediction of propellant behavior in spinning flow of a space motor

    NASA Technical Reports Server (NTRS)

    Gany, A.; Levy, Y.; Timnat, Y. M.

    1992-01-01

    A model for 2-phase flow dynamics in a spinning spherical rocket motor, developed for the Ofeq satellite program, is based on the sectional approach to solution of the flow equations. An experimental model was built, to enable the motion of the aluminum/aluminum-oxide particles resulting from combustion within a solid-fuel motor to be simulated by injected paraffin droplets. The injected droplets included under-5 micrometer droplets which move with the gas stream and larger droplets, averaging 20 micrometer diameter, which simulate the motion of aluminum particles. The test chamber comprised a pair of cylindrical pyrex tubes with a sharp contraction in diameter, rotated at various speeds by a frequency-controllable motor. An optical system, based on a 5 W argon ion laser with a beam splitter and frequency shifter, mounted on a movable table, facilitated sectional measurements of the three velocity components and determination of size-velocity relationships. Preliminary results indicate that the effect of rotation on axial velocity is negligible, while its effect on tangential velocity approximates to solid-body rotation.

  15. Absence of glia maturation factor protects dopaminergic neurons and improves motor behavior in mouse model of Parkinsonism

    PubMed Central

    Khan, Mohammad Moshahid; Zaheer, Smita; Ramasamy, Thangavel; Patel, Margi; Kempuraj, Duraisamy; Zaheer, Asgar

    2015-01-01

    Previously, we have shown that aberrant expression of glia maturation factor (GMF), a proinflammatory protein, is associated with the neuropathological conditions underlying diseases suggesting an important role for GMF in neurodegeneration. In the present study, we demonstrate that absence of GMF suppresses dopaminergic (DA) neuron loss, glial activation, and expression of proinflammatory mediators in the substantia nigra pars compacta (SN) and striatum (STR) of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) treated mice. Dopaminergic neuron numbers in the SN and fiber densities in the STR were reduced in wild type (Wt) mice when compared with GMF-deficient (GMF-KO) mice after MPTP treatment. We compared the motor abnormalities caused by MPTP treatment in Wt and GMF-KO mice as measured by Rota rod and grip strength test. Results show that the deficits in motor coordination and decrease in dopamine and its metabolite content were protected significantly in GMF-KO mice after MPTP treatment when compared with control Wt mice under identical experimental conditions. These findings were further supported by the immunohistochemical analysis that showed reduced glial activation in the SN of MPTP-treated GMF-KO mice. Similarly, in MPTP-treated GMF-KO mice, production of inflammatory tumor necrosis factor alpha (TNF-α), interleukine-1 beta (IL-1β), granulocyte macrophage-colony stimulating factor (GM-CSF), and the chemokine (C-C motif) ligand 2 (CCL2) MCP-1 was suppressed, findings consistent with a role for GMF in MPTP neurotoxicity. In conclusion, present investigation provides the first evidence that deficiency of GMF protects the DA neuron loss and reduces the inflammatory load following MPTP administration in mice. Thus depletion of endogenous GMF represents an effective and selective strategy to slow down the MPTP-induced neurodegeneration. PMID:25754447

  16. Abnormal Pre-Attentive Arousal in Young Children with Autism Spectrum Disorder Contributes to Their Atypical Auditory Behavior: An ERP Study

    PubMed Central

    Stroganova, Tatiana A.; Kozunov, Vladimir V.; Posikera, Irina N.; Galuta, Ilia A.; Gratchev, Vitaliy V.; Orekhova, Elena V.

    2013-01-01

    Auditory sensory modulation difficulties and problems with automatic re-orienting to sound are well documented in autism spectrum disorders (ASD). Abnormal preattentive arousal processes may contribute to these deficits. In this study, we investigated components of the cortical auditory evoked potential (CAEP) reflecting preattentive arousal in children with ASD and typically developing (TD) children aged 3-8 years. Pairs of clicks (‘S1’ and ‘S2’) separated by a 1 sec S1-S2 interstimulus interval (ISI) and much longer (8-10 sec) S1-S1 ISIs were presented monaurally to either the left or right ear. In TD children, the P50, P100 and N1c CAEP components were strongly influenced by temporal novelty of clicks and were much greater in response to the S1 than the S2 click. Irrespective of the stimulation side, the ‘tangential’ P100 component was rightward lateralized in TD children, whereas the ‘radial’ N1c component had higher amplitude contralaterally to the stimulated ear. Compared to the TD children, children with ASD demonstrated 1) reduced amplitude of the P100 component under the condition of temporal novelty (S1) and 2) an attenuated P100 repetition suppression effect. The abnormalities were lateralized and depended on the presentation side. They were evident in the case of the left but not the right ear stimulation. The P100 abnormalities in ASD correlated with the degree of developmental delay and with the severity of auditory sensory modulation difficulties observed in early life. The results suggest that some rightward-lateralized brain networks that are crucially important for arousal and attention re-orienting are compromised in children with ASD and that this deficit contributes to sensory modulation difficulties and possibly even other behavioral deficits in ASD. PMID:23935931

  17. Abnormal pre-attentive arousal in young children with autism spectrum disorder contributes to their atypical auditory behavior: an ERP study.

    PubMed

    Stroganova, Tatiana A; Kozunov, Vladimir V; Posikera, Irina N; Galuta, Ilia A; Gratchev, Vitaliy V; Orekhova, Elena V

    2013-01-01

    Auditory sensory modulation difficulties and problems with automatic re-orienting to sound are well documented in autism spectrum disorders (ASD). Abnormal preattentive arousal processes may contribute to these deficits. In this study, we investigated components of the cortical auditory evoked potential (CAEP) reflecting preattentive arousal in children with ASD and typically developing (TD) children aged 3-8 years. Pairs of clicks ('S1' and 'S2') separated by a 1 sec S1-S2 interstimulus interval (ISI) and much longer (8-10 sec) S1-S1 ISIs were presented monaurally to either the left or right ear. In TD children, the P50, P100 and N1c CAEP components were strongly influenced by temporal novelty of clicks and were much greater in response to the S1 than the S2 click. Irrespective of the stimulation side, the 'tangential' P100 component was rightward lateralized in TD children, whereas the 'radial' N1c component had higher amplitude contralaterally to the stimulated ear. Compared to the TD children, children with ASD demonstrated 1) reduced amplitude of the P100 component under the condition of temporal novelty (S1) and 2) an attenuated P100 repetition suppression effect. The abnormalities were lateralized and depended on the presentation side. They were evident in the case of the left but not the right ear stimulation. The P100 abnormalities in ASD correlated with the degree of developmental delay and with the severity of auditory sensory modulation difficulties observed in early life. The results suggest that some rightward-lateralized brain networks that are crucially important for arousal and attention re-orienting are compromised in children with ASD and that this deficit contributes to sensory modulation difficulties and possibly even other behavioral deficits in ASD. PMID:23935931

  18. An Item Response Analysis of the Motor and Behavioral Subscales of the Unified Huntington's Disease Rating Scale in Huntington Disease Gene Expansion Carriers

    PubMed Central

    Vaccarino, Anthony L.; Anderson, Karen; Borowsky, Beth; Duff, Kevin; Giuliano, Joseph; Guttman, Mark; Ho, Aileen K.; Orth, Michael; Paulsen, Jane S.; Sills, Terrence; van Kammen, Daniel P.; Evans, Kenneth R.

    2011-01-01

    Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (i.e., prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a non-parametric item response analysis was performed on retrospective data from two multicentre, longitudinal studies. Motor and Behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent saccade velocity, dysarthia, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features. PMID:21370269

  19. Parallel evolution of serotonergic neuromodulation underlies independent evolution of rhythmic motor behavior.

    PubMed

    Lillvis, Joshua L; Katz, Paul S

    2013-02-01

    Neuromodulation can dynamically alter neuronal and synaptic properties, thereby changing the behavioral output of a neural circuit. It is therefore conceivable that natural selection might act upon neuromodulation as a mechanism for sculpting the behavioral repertoire of a species. Here we report that the presence of neuromodulation is correlated with the production of a behavior that most likely evolved independently in two species: Tritonia diomedea and Pleurobranchaea californica (Mollusca, Gastropoda, Opisthobranchia, Nudipleura). Individuals of both species exhibit escape swimming behaviors consisting of repeated dorsal-ventral whole-body flexions. The central pattern generator (CPG) circuits underlying these behaviors contain homologous identified neurons: DSI and C2 in Tritonia and As and A1 in Pleurobranchaea. Homologs of these neurons also can be found in Hermissenda crassicornis where they are named CPT and C2, respectively. However, members of this species do not exhibit an analogous swimming behavior. In Tritonia and Pleurobranchaea, but not in Hermissenda, the serotonergic DSI homologs modulated the strength of synapses made by C2 homologs. Furthermore, the serotonin receptor antagonist methysergide blocked this neuromodulation and the swimming behavior. Additionally, in Pleurobranchaea, the robustness of swimming correlated with the extent of the synaptic modulation. Finally, injection of serotonin induced the swimming behavior in Tritonia and Pleurobranchaea, but not in Hermissenda. This suggests that the analogous swimming behaviors of Tritonia and Pleurobranchaea share a common dependence on serotonergic neuromodulation. Thus, neuromodulation may provide a mechanism that enables species to acquire analogous behaviors independently using homologous neural circuit components. PMID:23392697

  20. Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders

    PubMed Central

    Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

    2016-01-01

    The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

  1. Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders.

    PubMed

    Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

    2016-01-01

    The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

  2. Are there gender-specific pathways from early adolescence psychological distress symptoms toward the development of substance use and abnormal eating behavior?

    PubMed

    Beato-Fernández, Luis; Rodríguez-Cano, Teresa; Pelayo-Delgado, Esther; Calaf, Myralys

    2007-02-01

    The aim of the present longitudinal community study was to test whether psychological distress at 13 years of age predicted reported substance use problems in boys and abnormal eating behavior in girls 2 years later. The sample consisted of 500 male and 576 female students. The use of substances was evaluated using a semi-structured interview, psychological distress with the General Health Questionnaire (GHQ) and eating psychopathology with the Eating Attitudes Test (EAT-40), and the Bulimic Investigatory Test Edinburgh (BITE). Controlling the effect of initial substance use problems, psychological distress predicted later reported substance use problems in males. Girls with an initial score above the cut-off point on the GHQ were two times more likely to be at risk of having an eating disorder 2 years later. Therefore, psychological distress might take different developmental pathways in males and females, leading toward eating problems in the latter versus substance use in the former. PMID:17001526

  3. Splitting of the cerebellar vermis in juvenile rats--effects on social behavior, vocalization and motor activity.

    PubMed

    Al-Afif, Shadi; Staden, Mareike; Krauss, Joachim K; Schwabe, Kerstin; Hermann, Elvis J

    2013-08-01

    Radical resection of malignant midline tumors of the posterior fossa in childhood followed by adjuvant therapies like chemotherapy or radiotherapy often leads to longterm survival and even healing of such patients. Therefore, quality of life becomes particular important. Postoperative neurological deficits, such as cerebellar mutism and ataxia have been attributed to splitting of the cerebellar vermis to remove these tumors. Here, we tested the effect of vermian splitting in juvenile rats on social behavior, vocalization and motor activity. Juvenile male Sprague Dawley rats, aged 23 days, underwent vermian splitting under general anesthesia after medial suboccipital craniotomy (lesioned group, n=16). In sham-lesioned rats, only craniotomy was performed and the dura was opened with release of cerebrospinal fluid (n=16). Naïve rats served as controls (n=14). All groups were tested on day 0 (before surgery), and on days 1-4 and 7 after surgery for locomotor activity, motor coordination, social behavior, and ultrasound vocalization during social interaction. Finally, splitting of the vermis was histologically verified. Social interaction was reduced for two days after surgery in lesioned rats compared to sham-lesioned rats and controls. Vocalization was decreased for one day compared to controls. Locomotor activity was disturbed for several days after surgery in both lesioned and sham-lesioned rats as compared to controls. Deficient social behavior and vocalization after surgery are related to vermian splitting in juvenile rats. These results indicate that similar to the human context vermian splitting can reduce communicative drive in the early postsurgical phase. PMID:23685319

  4. Behavioral and neurochemical effects of chronic L-DOPA treatment on non-motor sequelae in the hemiparkinsonian rat

    PubMed Central

    Eskow Jaunarajs, Karen L.; Dupre, Kristin B.; Ostock, Corinne Y.; Button, Thomas; Deak, Terrence; Bishop, Christopher

    2010-01-01

    Depression and anxiety are prevalent non-motor symptoms that worsen quality of life for Parkinson’s disease (PD) patients. While dopamine (DA) cell loss is a commonly proposed mechanism, the reported efficacy of DA replacement therapy with L-DOPA on affective symptoms is inconsistent. In order to delineate the effects of DA denervation and chronic L-DOPA treatment on affective behaviors, male Sprague-Dawley rats received unilateral 6-OHDA or sham lesions and were treated daily with L-DOPA (12 mg/kg + benserazide, 15 mg/kg, sc) or vehicle (0.9% NaCl, 0.1% ascorbic acid) for 28 days before commencing investigations into anxiety (locomotor chambers, social interaction) and depression-like behaviors (forced swim test) during the OFF phase of L-DOPA. One h after final treatments, rats were killed and striatum, prefrontal cortex, hippocampus, and amygdala were analyzed via high performance liquid chromatography for monoamine levels. In locomotor chambers and social interaction, DA lesions exerted mild anxiogenic effects. Surprisingly, chronic L-DOPA treatment did not improve these effects. While DA lesion reduced climbing behaviors on day 2 of exposure to the forced swim test, chronic L-DOPA treatment did not reverse these effects. Neurochemically, L-DOPA treatment in hemiparkinsonian rats reduced NE levels in the prefrontal cortex, striatum, and hippocampus. Collectively, the present data suggest that chronic L-DOPA therapy in severely DA-lesioned rats does not improve non-motor symptoms and may impair non-dopaminergic processes, indicating that long-term L-DOPA therapy does not exert necessary cause neuroplastic changes for improving affect. PMID:20838211

  5. Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

    PubMed Central

    Xiao, Lan; Kish, Vincent L.; Benders, Katherine M.

    2016-01-01

    Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life. PMID:26503133

  6. Behavioral Abnormalities in a Mouse Model of Chronic Toxoplasmosis Are Associated with MAG1 Antibody Levels and Cyst Burden.

    PubMed

    Xiao, Jianchun; Li, Ye; Prandovszky, Emese; Kannan, Geetha; Viscidi, Raphael P; Pletnikov, Mikhail V; Yolken, Robert H

    2016-04-01

    There is marked variation in the human response to Toxoplasma gondii infection. Epidemiological studies indicate associations between strain virulence and severity of toxoplasmosis. Animal studies on the pathogenic effect of chronic infection focused on relatively avirulent strains (e.g. type II) because they can easily establish latent infections in mice, defined by the presence of bradyzoite-containing cysts. To provide insight into virulent strain-related severity of human toxoplasmosis, we established a chronic model of the virulent type I strain using outbred mice. We found that type I-exposed mice displayed variable outcomes ranging from aborted to severe infections. According to antibody profiles, we found that most of mice generated antibodies against T. gondii organism but varied greatly in the production of antibodies against matrix antigen MAG1. There was a strong correlation between MAG1 antibody level and brain cyst burden in chronically infected mice (r = 0.82, p = 0.0021). We found that mice with high MAG1 antibody level displayed lower weight, behavioral changes, altered levels of gene expression and immune activation. The most striking change in behavior we discovered was a blunted response to amphetamine-trigged locomotor activity. The extent of most changes was directly correlated with levels of MAG1 antibody. These changes were not found in mice with less cyst burden or mice that were acutely but not chronically infected. Our finding highlights the critical role of cyst burden in a range of disease severity during chronic infection, the predictive value of MAG1 antibody level to brain cyst burden and to changes in behavior or other pathology in chronically infected mice. Our finding may have important implications for understanding the heterogeneous effects of T. gondii infections in human. PMID:27124472

  7. Behavioral Abnormalities in a Mouse Model of Chronic Toxoplasmosis Are Associated with MAG1 Antibody Levels and Cyst Burden

    PubMed Central

    Xiao, Jianchun; Li, Ye; Prandovszky, Emese; Kannan, Geetha; Viscidi, Raphael P.; Pletnikov, Mikhail V.; Yolken, Robert H.

    2016-01-01

    There is marked variation in the human response to Toxoplasma gondii infection. Epidemiological studies indicate associations between strain virulence and severity of toxoplasmosis. Animal studies on the pathogenic effect of chronic infection focused on relatively avirulent strains (e.g. type II) because they can easily establish latent infections in mice, defined by the presence of bradyzoite-containing cysts. To provide insight into virulent strain-related severity of human toxoplasmosis, we established a chronic model of the virulent type I strain using outbred mice. We found that type I-exposed mice displayed variable outcomes ranging from aborted to severe infections. According to antibody profiles, we found that most of mice generated antibodies against T. gondii organism but varied greatly in the production of antibodies against matrix antigen MAG1. There was a strong correlation between MAG1 antibody level and brain cyst burden in chronically infected mice (r = 0.82, p = 0.0021). We found that mice with high MAG1 antibody level displayed lower weight, behavioral changes, altered levels of gene expression and immune activation. The most striking change in behavior we discovered was a blunted response to amphetamine-trigged locomotor activity. The extent of most changes was directly correlated with levels of MAG1 antibody. These changes were not found in mice with less cyst burden or mice that were acutely but not chronically infected. Our finding highlights the critical role of cyst burden in a range of disease severity during chronic infection, the predictive value of MAG1 antibody level to brain cyst burden and to changes in behavior or other pathology in chronically infected mice. Our finding may have important implications for understanding the heterogeneous effects of T. gondii infections in human. PMID:27124472

  8. Hierarchical representation and machine learning from faulty jet engine behavioral examples to detect real time abnormal conditions

    NASA Technical Reports Server (NTRS)

    Gupta, U. K.; Ali, M.

    1988-01-01

    The theoretical basis and operation of LEBEX, a machine-learning system for jet-engine performance monitoring, are described. The behavior of the engine is modeled in terms of four parameters (the rotational speeds of the high- and low-speed sections and the exhaust and combustion temperatures), and parameter variations indicating malfunction are transformed into structural representations involving instances and events. LEBEX extracts descriptors from a set of training data on normal and faulty engines, represents them hierarchically in a knowledge base, and uses them to diagnose and predict faults on a real-time basis. Diagrams of the system architecture and printouts of typical results are shown.

  9. Deletion in the N-terminal Half of Olfactomedin 1 Modifies Its Interaction with Synaptic Proteins and Causes Brain Dystrophy and Abnormal Behavior in Mice

    PubMed Central

    Nakaya, Naoki; Sultana, Afia; Munasinghe, Jeeva; Cheng, Aiwu; Mattson, Mark P.; Tomarev, Stanislav I.

    2013-01-01

    Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part of the protein, increased neonatal death and reduced body weight of surviving homozygous mice. Magnetic resonance imaging analyses revealed reduced brain volume and attenuated size of white matter tracts such as the anterior commissure, corpus callosum, and optic nerve. Adult Olfm1 mutant mice demonstrated abnormal behavior in several tests including reduced marble digging, elevated plus maze test, nesting activity and latency on balance beam tests as compared with their wild-type littermates. The olfactory system was both structurally and functionally disturbed by the mutation in the Olfm1 gene as shown by functional magnetic resonance imaging analysis and a smell test. Deficiencies of the olfactory system may contribute to the neonatal death and loss of body weight of Olfm1 mutant. Shotgun proteomics revealed 59 candidate proteins that co-precipitated with wild-type or mutant Olfm1 proteins in postnatal day 1 brain. Olfm1-binding targets included GluR2, Cav2.1, Teneurin-4 and Kidins220. Modified interaction of Olfm1 with binding targets led to an increase in intracellular Ca2+ concentration and activation of ERK1/2, MEK1 and CaMKII in the hippocampus and olfactory bulb of Olfm1 mutant mice compared with their wild-type littermates. Excessive activation of the CaMKII and Ras-ERK pathways in the Olfm1 mutant olfactory bulb and hippocampus by elevated intracellular calcium may contribute to the abnormal behavior and olfactory activity of Olfm1 mutant mice. PMID:24095980

  10. Deletion in the N-terminal half of olfactomedin 1 modifies its interaction with synaptic proteins and causes brain dystrophy and abnormal behavior in mice.

    PubMed

    Nakaya, Naoki; Sultana, Afia; Munasinghe, Jeeva; Cheng, Aiwu; Mattson, Mark P; Tomarev, Stanislav I

    2013-12-01

    Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part of the protein, increased neonatal death and reduced body weight of surviving homozygous mice. Magnetic resonance imaging analyses revealed reduced brain volume and attenuated size of white matter tracts such as the anterior commissure, corpus callosum, and optic nerve. Adult Olfm1 mutant mice demonstrated abnormal behavior in several tests including reduced marble digging, elevated plus maze test, nesting activity and latency on balance beam tests as compared with their wild-type littermates. The olfactory system was both structurally and functionally disturbed by the mutation in the Olfm1 gene as shown by functional magnetic resonance imaging analysis and a smell test. Deficiencies of the olfactory system may contribute to the neonatal death and loss of body weight of Olfm1 mutant. Shotgun proteomics revealed 59 candidate proteins that co-precipitated with wild-type or mutant Olfm1 proteins in postnatal day 1 brain. Olfm1-binding targets included GluR2, Cav2.1, teneurin-4 and Kidins220. Modified interaction of Olfm1 with binding targets led to an increase in intracellular Ca(2+) concentration and activation of ERK1/2, MEK1 and CaMKII in the hippocampus and olfactory bulb of Olfm1 mutant mice compared with their wild-type littermates. Excessive activation of the CaMKII and Ras-ERK pathways in the Olfm1 mutant olfactory bulb and hippocampus by elevated intracellular calcium may contribute to the abnormal behavior and olfactory activity of Olfm1 mutant mice. PMID:24095980

  11. Sleep and Sex: What Can Go Wrong? A Review of the Literature on Sleep Related Disorders and Abnormal Sexual Behaviors and Experiences

    PubMed Central

    Schenck, Carlos H.; Arnulf, Isabelle; Mahowald, Mark W.

    2007-01-01

    Study Objectives: To formulate the first classification of sleep related disorders and abnormal sexual behaviors and experiences. Design: A computerized literature search was conducted, and other sources, such as textbooks, were searched. Results: Many categories of sleep related disorders were represented in the classification: parasomnias (confusional arousals/sleepwalking, with or without obstructive sleep apnea; REM sleep behavior disorder); sleep related seizures; Kleine-Levin syndrome (KLS); severe chronic insomnia; restless legs syndrome; narcolepsy; sleep exacerbation of persistent sexual arousal syndrome; sleep related painful erections; sleep related dissociative disorders; nocturnal psychotic disorders; miscellaneous states. Kleine-Levin syndrome (78 cases) and parasomnias (31 cases) were most frequently reported. Parasomnias and sleep related seizures had overlapping and divergent clinical features. Thirty-one cases of parasomnias (25 males; mean age, 32 years) and 7 cases of sleep related seizures (4 males; mean age, 38 years) were identified. A full range of sleep related sexual behaviors with self and/or bed partners or others were reported, including masturbation, sexual vocalizations, fondling, sexual intercourse with climax, sexual assault/rape, ictal sexual hyperarousal, ictal orgasm, and ictal automatism. Adverse physical and/or psychosocial effects from the sleepsex were present in all parasomnia and sleep related seizure cases, but pleasurable effects were reported by 5 bed partners and by 3 patients with sleep related seizures. Forensic consequences were common, occurring in 35.5% (11/31) of parasomnia cases, with most (9/11) involving minors. All parasomnias cases reported amnesia for the sleepsex, in contrast to 28.6% (2/7) of sleep related seizure cases. Polysomnography (without penile tumescence monitoring), performed in 26 of 31 parasomnia cases, documented sexual moaning from slow wave sleep in 3 cases and sexual intercourse during

  12. Chaotic motors

    NASA Astrophysics Data System (ADS)

    Laroche, C.; Labbé, R.; Pétrélis, F.; Fauve, S.

    2012-02-01

    We show that electric motors and dynamos can be used to illustrate most elementary instabilities or bifurcations discussed in courses on nonlinear oscillators and dynamical systems. These examples are easier to understand and display a richer behavior than the ones commonly used from mechanics, electronics, hydrodynamics, lasers, chemical reactions, and population dynamics. In particular, an electric motor driven by a dynamo can display stationary, Hopf, and codimension-two bifurcations by tuning the driving speed of the dynamo and the electric current in the stator of the electric motor. When the dynamo is driven at constant torque instead of constant rotation rate, chaotic reversals of the generated current and of the angular rotation of the motor are observed. Simple deterministic models are presented which capture the observed dynamical regimes.

  13. Abnormal Osmotic Avoidance Behavior in C. elegans Is Associated with Increased Hypertonic Stress Resistance and Improved Proteostasis

    PubMed Central

    Lee, Elaine C.; Kim, Heejung; Ditano, Jennifer; Manion, Dacie; King, Benjamin L.; Strange, Kevin

    2016-01-01

    Protein function is controlled by the cellular proteostasis network. Proteostasis is energetically costly and those costs must be balanced with the energy needs of other physiological functions. Hypertonic stress causes widespread protein damage in C. elegans. Suppression and management of protein damage is essential for optimal survival under hypertonic conditions. ASH chemosensory neurons allow C. elegans to detect and avoid strongly hypertonic environments. We demonstrate that mutations in osm-9 and osm-12 that disrupt ASH mediated hypertonic avoidance behavior or genetic ablation of ASH neurons are associated with enhanced survival during hypertonic stress. Improved survival is not due to altered systemic volume homeostasis or organic osmolyte accumulation. Instead, we find that osm-9(ok1677) mutant and osm-9(RNAi) worms exhibit reductions in hypertonicity induced protein damage in non-neuronal cells suggesting that enhanced proteostasis capacity may account for improved hypertonic stress resistance in worms with defects in osmotic avoidance behavior. RNA-seq analysis revealed that genes that play roles in managing protein damage are upregulated in osm-9(ok1677) worms. Our findings are consistent with a growing body of work demonstrating that intercellular communication between neuronal and non-neuronal cells plays a critical role in integrating cellular stress resistance with other organismal physiological demands and associated energy costs. PMID:27111894

  14. Frontocentral DC-potential shifts predicting behavior with or without a motor task.

    PubMed

    Morgan, J M; Wenzl, M; Lang, W; Lindinger, G; Deecke, L

    1992-12-01

    This study was designed to investigate the predictive value of the event-related potentials (ERPs) preceding the initiation of a difficult perceptual-memory task and to investigate whether these ERPs require a motor movement on the part of the subject for their occurrence. Across 4 conditions the DC-potential shifts were recorded from 23 right-handed subjects using DC amplifiers. Although the start of each trial began with a ready signal, the conditions differed in that the subjects initiated the task by a button press in 2 conditions and the computer initiated it in 2 others without a press. The results showed that, especially in the frontocentral electrode sites, the DC-potential shifts which began those trials ending in correct performance were more negative relative to those trials ending in an incorrect response. Those conditions which required the subjects to self-initiate the trial and those which were initiated by the computer showed similar results indicating that the negative DC-potential shifts preceding correct performance are neither produced by nor depend on a task initiating motor movement. The onset of the DC-potential shifts preceded task initiation by up to 4.1 sec indicating that they were more than the Bereitschaftspotential. PMID:1281084

  15. A Large-Scale Behavioral Screen to Identify Neurons Controlling Motor Programs in the Drosophila Brain

    PubMed Central

    Flood, Thomas F.; Gorczyca, Michael; White, Benjamin H.; Ito, Kei; Yoshihara, Motojiro

    2013-01-01

    Drosophila is increasingly used for understanding the neural basis of behavior through genetically targeted manipulation of specific neurons. The primary approach in this regard has relied on the suppression of neuronal activity. Here, we report the results of a novel approach to find and characterize neural circuits by expressing neuronal activators to stimulate subsets of neurons to induce behavior. Classical electrophysiological studies demonstrated that stimulation of command neurons could activate neural circuits to trigger fixed action patterns. Our method was designed to find such command neurons for diverse behaviors by screening flies in which random subsets of brain cells were activated. We took advantage of the large collection of Gal4 lines from the NP project and crossed 835 Gal4 strains with relatively limited Gal4 expression in the brain to flies carrying a UAS transgene encoding TRPM8, a cold-sensitive ion channel. Low temperatures opened the TRPM8 channel in Gal4-expressing cells, leading to their excitation, and in many cases induced overt behavioral changes in adult flies. Paralysis was reproducibly observed in the progeny of crosses with 84 lines, whereas more specific behaviors were induced with 24 other lines. Stimulation performed using the heat-activated channel, TrpA1, resulted in clearer and more robust behaviors, including flight, feeding, and egg-laying. Through follow-up studies starting from this screen, we expect to find key components of the neural circuits underlying specific behaviors, thus providing a new avenue for their functional analysis. PMID:23934998

  16. The effects of load-sensitive behavior on the operability margins of motor-operated gate valves

    SciTech Connect

    Steele, R. Jr.; Russell, M.J.; DeWall, K.G.; Watkins, J.C.

    1993-01-01

    Testing of motor-operated gate valves at various loads has produced a phenomenon we call load-sensitive behavior. This phenomenon has a significant effect on the accuracy of the methods used (and proposed) in the nuclear industry for determining that these valves can perform their design basis function. A valve subjected to tests with low flow and pressure loadings may achieve a stem thrust (at seating) analytically determined to be adequate for design basis flows and pressures, but this is no guarantee that the valve will achieve the same stem thrust when actually subjected to those design basis loads. This is because the friction at the interface between the stem and the stem nut is higher in tests with higher flow and pressure loadings, and this loss to friction is outside the control of the motor-operator's torque switch. This paper identifies a tentative method for determining, a stable, useful value for the stem/stem-nut coefficient of friction, one that can possibly be extrapolated and used in calculations to accurately estimate the design basis thrust requirements of these valves.

  17. The effects of load-sensitive behavior on the operability margins of motor-operated gate valves

    SciTech Connect

    Steele, R. Jr.; Russell, M.J.; DeWall, K.G.; Watkins, J.C.

    1993-05-01

    Testing of motor-operated gate valves at various loads has produced a phenomenon we call load-sensitive behavior. This phenomenon has a significant effect on the accuracy of the methods used (and proposed) in the nuclear industry for determining that these valves can perform their design basis function. A valve subjected to tests with low flow and pressure loadings may achieve a stem thrust (at seating) analytically determined to be adequate for design basis flows and pressures, but this is no guarantee that the valve will achieve the same stem thrust when actually subjected to those design basis loads. This is because the friction at the interface between the stem and the stem nut is higher in tests with higher flow and pressure loadings, and this loss to friction is outside the control of the motor-operator`s torque switch. This paper identifies a tentative method for determining, a stable, useful value for the stem/stem-nut coefficient of friction, one that can possibly be extrapolated and used in calculations to accurately estimate the design basis thrust requirements of these valves.

  18. Long-term recovery from hippocampal-related behavioral and biochemical abnormalities induced by noise exposure during brain development. Evaluation of auditory pathway integrity.

    PubMed

    Uran, S L; Gómez-Casati, M E; Guelman, L R

    2014-10-01

    Sound is an important part of man's contact with the environment and has served as critical means for survival throughout his evolution. As a result of exposure to noise, physiological functions such as those involving structures of the auditory and non-auditory systems might be damaged. We have previously reported that noise-exposed developing rats elicited hippocampal-related histological, biochemical and behavioral changes. However, no data about the time lapse of these changes were reported. Moreover, measurements of auditory pathway function were not performed in exposed animals. Therefore, with the present work, we aim to test the onset and the persistence of the different extra-auditory abnormalities observed in noise-exposed rats and to evaluate auditory pathway integrity. Male Wistar rats of 15 days were exposed to moderate noise levels (95-97 dB SPL, 2 h a day) during one day (acute noise exposure, ANE) or during 15 days (sub-acute noise exposure, SANE). Hippocampal biochemical determinations as well as short (ST) and long term (LT) behavioral assessments were performed. In addition, histological and functional evaluations of the auditory pathway were carried out in exposed animals. Our results show that hippocampal-related behavioral and biochemical changes (impairments in habituation, recognition and associative memories as well as distortion of anxiety-related behavior, decreases in reactive oxygen species (ROS) levels and increases in antioxidant enzymes activities) induced by noise exposure were almost completely restored by PND 90. In addition, auditory evaluation shows that increased cochlear thresholds observed in exposed rats were re-established at PND 90, although with a remarkable supra-threshold amplitude reduction. These data suggest that noise-induced hippocampal and auditory-related alterations are mostly transient and that the effects of noise on the hippocampus might be, at least in part, mediated by the damage on the auditory pathway

  19. Caenorhabditis elegans male sensory-motor neurons and dopaminergic support cells couple ejaculation and post-ejaculatory behaviors.

    PubMed

    LeBoeuf, Brigitte; Correa, Paola; Jee, Changhoon; García, L René

    2014-01-01

    The circuit structure and function underlying post-coital male behaviors remain poorly understood. Using mutant analysis, laser ablation, optogenetics, and Ca2+ imaging, we observed that following C. elegans male copulation, the duration of post-coital lethargy is coupled to cellular events involved in ejaculation. We show that the SPV and SPD spicule-associated sensory neurons and the spicule socket neuronal support cells function with intromission circuit components, including the cholinergic SPC and PCB and the glutamatergic PCA sensory-motor neurons, to coordinate sex muscle contractions with initiation and continuation of sperm movement. Our observations suggest that the SPV and SPD and their associated dopamine-containing socket cells sense the intrauterine environment through cellular endings exposed at the spicule tips and regulate both sperm release into the hermaphrodite and the recovery from post-coital lethargy. PMID:24915976

  20. Walking in School-Aged Children in a Dual-Task Paradigm Is Related to Age But Not to Cognition, Motor Behavior, Injuries, or Psychosocial Functioning

    PubMed Central

    Hagmann-von Arx, Priska; Manicolo, Olivia; Lemola, Sakari; Grob, Alexander

    2016-01-01

    Age-dependent gait characteristics and associations with cognition, motor behavior, injuries, and psychosocial functioning were investigated in 138 typically developing children aged 6.7–13.2 years (M = 10.0 years). Gait velocity, normalized velocity, and variability were measured using the walkway system GAITRite without an additional task (single task) and while performing a motor or cognitive task (dual task). Assessment of children’s cognition included tests for intelligence and executive functions; parents reported on their child’s motor behavior, injuries, and psychosocial functioning. Gait variability (an index of gait regularity) decreased with increasing age in both single- and dual-task walking. Dual-task gait decrements were stronger when children walked in the motor compared to the cognitive dual-task condition and decreased with increasing age in both dual-task conditions. Gait alterations from single- to dual-task conditions were not related to children’s cognition, motor behavior, injuries, or psychosocial functioning. PMID:27014158

  1. Transplantation of melanocytes obtained from the skin ameliorates apomorphine-induced abnormal behavior in rodent hemi-parkinsonian models.

    PubMed

    Asanuma, Masato; Miyazaki, Ikuko; Diaz-Corrales, Francisco J; Higashi, Youichirou; Namba, Masayoshi; Ogawa, Norio

    2013-01-01

    Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-parkinsonian model rats or mice lesioned with 6-hydroxydopamine. Marked improvement in apomorphine-induced rotation was noted at day 40 after intrastriatal melanoma cell transplantation. Transplantation of tyrosinase cDNA-transfected hepatoma cells, which constitutively produce L-DOPA, resulted in marked amelioration of the asymmetric apomorphine-induced rotation in hemi-parkinsonian mice and the effect was present up to 2 months. Moreover, parkinsonian mice transplanted with melanocytes from the back skin of black newborn mice, but not from albino mice, showed marked improvement in the apomorphine-induced rotation behavior up to 3 months after the transplantation. Dopamine-positive signals were seen around the surviving transplants in these experiments. Taken together with previous studies showing dopamine synthesis and metabolism by tyrosinase, these results highlight therapeutic potential of intrastriatal autograft cell transplantation of melanocytes in patients with Parkinson's disease. PMID:23776585

  2. Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice

    PubMed Central

    Yang, Eun-Jeong; Ahn, Sangzin; Lee, Kihwan; Mahmood, Usman; Kim, Hye-Sun

    2016-01-01

    Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model. We examined the early behavioral and anatomical changes as well as molecular changes in mice prenatally exposed to VPA (VPA mice). In this study, we first showed that VPA mice showed developmental delays as assessed with self-righting, eye opening tests and impaired social recognition. In addition, we provide the first evidence that primary cultured neurons from VPA-treated embryos present an increase in dendritic spines, compared with those from control mice. Mutations in phosphatase and tensin homolog (PTEN) gene are also known to be associated with autism, and mice with PTEN knockout show autistic characteristics. Protein expression of PTEN was decreased and the ratio of p-AKT/AKT was increased in the cerebral cortex and the hippocampus, and a distinctive anatomical change in the CA1 region of the hippocampus was observed. Taken together, our study suggests that prenatal exposure to VPA induces developmental delays and neuroanatomical changes via the reduction of PTEN level and these changes were detectable in the early days of life. PMID:27071011

  3. Endogenous attention modulates attentional and motor interference from distractors: evidence from behavioral and electrophysiological results

    PubMed Central

    Martín-Arévalo, Elisa; Lupiáñez, Juan; Botta, Fabiano; Chica, Ana B.

    2015-01-01

    Selective visual attention enhances the processing of relevant stimuli and filters out irrelevant stimuli and/or distractors. However, irrelevant information is sometimes processed, as demonstrated by the Simon effect (Simon and Rudell, 1967). We examined whether fully irrelevant distractors (task and target-irrelevant) produce interference (measured as the Simon effect), and whether endogenous orienting modulated this interference. Despite being fully irrelevant, distractors were attentionally coded (as reflected by the distractor-related N2pc component), and interfered with the processing of the target response (as reflected by the target-related lateralized readiness potential component). Distractors’ attentional capture depended on endogenous attention, and their interference with target responses was modulated by both endogenous attention and distractor location repetition. These results demonstrate both endogenous attentional and motor modulations over the Simon effect produced by fully irrelevant distractors. PMID:25750629

  4. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    PubMed Central

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David JP; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-01-01

    Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus

  5. Surface IgM expression and function are associated with clinical behavior, genetic abnormalities, and DNA methylation in CLL.

    PubMed

    D'Avola, Annalisa; Drennan, Samantha; Tracy, Ian; Henderson, Isla; Chiecchio, Laura; Larrayoz, Marta; Rose-Zerilli, Matthew; Strefford, Jonathan; Plass, Christoph; Johnson, Peter W; Steele, Andrew J; Packham, Graham; Stevenson, Freda K; Oakes, Christopher C; Forconi, Francesco

    2016-08-11

    Chronic lymphocytic leukemia (CLL) with unmutated (U-CLL) or mutated (M-CLL) immunoglobulin gene heavy-chain variable region (IGHV) displays different states of anergy, indicated by reduced surface immunoglobulin M (sIgM) levels and signaling, consequent to chronic (super)antigen exposure. The subsets also differ in the incidence of high-risk genetic aberrations and in DNA methylation profile, preserved from the maturational status of the original cell. We focused on sIgM expression and function, measured as intracellular Ca(2+) mobilization following stimulation, and probed correlations with clinical outcome. The relationship with genetic features and maturation status defined by DNA methylation of an 18-gene panel signature was then investigated. sIgM levels/signaling were higher and less variable in U-CLL than in M-CLL and correlated with disease progression between and within U-CLL and M-CLL. In U-CLL, increased levels/signaling associated with +12, del(17p) or NOTCH1 mutations. In M-CLL, there were fewer genetic lesions, although the methylation maturation status, generally higher than in U-CLL, varied and was increased in cases with lower sIgM levels/signaling. These features revealed heterogeneity in M-CLL and U-CLL with clear clinical correlations. Multivariate analyses with phenotype, genetic lesions, or DNA methylation maturation status identified high sIgM levels as a new potential independent factor for disease progression. Multiple influences on sIgM include the cell of origin, the clonal history of antigen encounter in vivo, and genetic damage. This simple marker compiles these different factors into an indicator worthy of further investigations for prediction of clinical behavior, particularly within the heterogeneous M-CLL subset. PMID:27301861

  6. The duplication 17p13.3 phenotype: analysis of 21 families delineates developmental, behavioral and brain abnormalities, and rare variant phenotypes.

    PubMed

    Curry, Cynthia J; Rosenfeld, Jill A; Grant, Erica; Gripp, Karen W; Anderson, Carol; Aylsworth, Arthur S; Saad, Taha Ben; Chizhikov, Victor V; Dybose, Giedre; Fagerberg, Christina; Falco, Michelle; Fels, Christina; Fichera, Marco; Graakjaer, Jesper; Greco, Donatella; Hair, Jennifer; Hopkins, Elizabeth; Huggins, Marlene; Ladda, Roger; Li, Chumei; Moeschler, John; Nowaczyk, Malgorzata J M; Ozmore, Jillian R; Reitano, Santina; Romano, Corrado; Roos, Laura; Schnur, Rhonda E; Sell, Susan; Suwannarat, Pim; Svaneby, Dea; Szybowska, Marta; Tarnopolsky, Mark; Tervo, Raymond; Tsai, Anne Chun-Hui; Tucker, Megan; Vallee, Stephanie; Wheeler, Ferrin C; Zand, Dina J; Barkovich, A James; Aradhya, Swaroop; Shaffer, Lisa G; Dobyns, William B

    2013-08-01

    Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34 additional patients from 21 families to further delineate the clinical, neurological, behavioral, and brain imaging findings. We found a highly diverse phenotype with inter- and intrafamilial variability, especially in cognitive development. The most specific phenotype occurred in individuals with large duplications that include both the YWHAE and LIS1 genes. These patients had a relatively distinct facial phenotype and frequent structural brain abnormalities involving the corpus callosum, cerebellar vermis, and cranial base. Autism spectrum disorders were seen in a third of duplication probands, most commonly in those with duplications of YWHAE and flanking genes such as CRK. The typical neurobehavioral phenotype was usually seen in those with the larger duplications. We did not confirm the association of early overgrowth with involvement of YWHAE and CRK, or growth failure with duplications of LIS1. Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome. PMID:23813913

  7. Does listening to action-related sentences modulate the activity of the motor system? Replication of a combined TMS and behavioral study

    PubMed Central

    Gianelli, Claudia; Dalla Volta, Riccardo

    2015-01-01

    The neurophysiological and behavioral correlates of action-related language processing have been debated for long time. A precursor in this field was the study by Buccino et al. (2005) combining transcranial magnetic stimulation (TMS) and behavioral measures (reaction times, RTs) to study the effect of listening to hand- and foot-related sentences. In the TMS experiment, the authors showed a decrease of motor evoked potentials (MEPs) recorded from hand muscles when processing hand-related verbs as compared to foot-related verbs. Similarly, MEPs recorded from leg muscles decreased when participants processed foot-related as compared to hand-related verbs. In the behavioral experiment, using the same stimuli and a semantic decision task the authors found slower RTs when the participants used the body effector (hand or foot) involved in the actual execution of the action expressed by the presented verb to give their motor responses. These findings were interpreted as an interference effect due to a simultaneous involvement of the motor system in both a language and a motor task. Our replication aimed to enlarge the sample size and replicate the findings with higher statistical power. The TMS experiment showed a significant modulation of hand MEPs, but in the sense of a motor facilitation when processing hand-related verbs. On the contrary, the behavioral experiment did not show significant results. The results are discussed within the general debate on the time-course of the modulation of motor cortex during implicit and explicit language processing and in relation to the studies on action observation/understanding. PMID:25601845

  8. Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morphofunctional abnormalities.

    PubMed

    Wöhr, M; Orduz, D; Gregory, P; Moreno, H; Khan, U; Vörckel, K J; Wolfer, D P; Welzl, H; Gall, D; Schiffmann, S N; Schwaller, B

    2015-01-01

    Gene mutations and gene copy number variants are associated with autism spectrum disorders (ASDs). Affected gene products are often part of signaling networks implicated in synapse formation and/or function leading to alterations in the excitation/inhibition (E/I) balance. Although the network of parvalbumin (PV)-expressing interneurons has gained particular attention in ASD, little is known on PV's putative role with respect to ASD. Genetic mouse models represent powerful translational tools for studying the role of genetic and neurobiological factors underlying ASD. Here, we report that PV knockout mice (PV(-/-)) display behavioral phenotypes with relevance to all three core symptoms present in human ASD patients: abnormal reciprocal social interactions, impairments in communication and repetitive and stereotyped patterns of behavior. PV-depleted mice also showed several signs of ASD-associated comorbidities, such as reduced pain sensitivity and startle responses yet increased seizure susceptibility, whereas no evidence for behavioral phenotypes with relevance to anxiety, depression and schizophrenia was obtained. Reduced social interactions and communication were also observed in heterozygous (PV(+/-)) mice characterized by lower PV expression levels, indicating that merely a decrease in PV levels might be sufficient to elicit core ASD-like deficits. Structural magnetic resonance imaging measurements in PV(-/-) and PV(+/-) mice further revealed ASD-associated developmental neuroanatomical changes, including transient cortical hypertrophy and cerebellar hypoplasia. Electrophysiological experiments finally demonstrated that the E/I balance in these mice is altered by modification of both inhibitory and excitatory synaptic transmission. On the basis of the reported changes in PV expression patterns in several, mostly genetic rodent models of ASD, we propose that in these models downregulation of PV might represent one of the points of convergence, thus providing a

  9. Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morphofunctional abnormalities

    PubMed Central

    Wöhr, M; Orduz, D; Gregory, P; Moreno, H; Khan, U; Vörckel, K J; Wolfer, D P; Welzl, H; Gall, D; Schiffmann, S N; Schwaller, B

    2015-01-01

    Gene mutations and gene copy number variants are associated with autism spectrum disorders (ASDs). Affected gene products are often part of signaling networks implicated in synapse formation and/or function leading to alterations in the excitation/inhibition (E/I) balance. Although the network of parvalbumin (PV)-expressing interneurons has gained particular attention in ASD, little is known on PV's putative role with respect to ASD. Genetic mouse models represent powerful translational tools for studying the role of genetic and neurobiological factors underlying ASD. Here, we report that PV knockout mice (PV−/−) display behavioral phenotypes with relevance to all three core symptoms present in human ASD patients: abnormal reciprocal social interactions, impairments in communication and repetitive and stereotyped patterns of behavior. PV-depleted mice also showed several signs of ASD-associated comorbidities, such as reduced pain sensitivity and startle responses yet increased seizure susceptibility, whereas no evidence for behavioral phenotypes with relevance to anxiety, depression and schizophrenia was obtained. Reduced social interactions and communication were also observed in heterozygous (PV+/−) mice characterized by lower PV expression levels, indicating that merely a decrease in PV levels might be sufficient to elicit core ASD-like deficits. Structural magnetic resonance imaging measurements in PV−/− and PV+/− mice further revealed ASD-associated developmental neuroanatomical changes, including transient cortical hypertrophy and cerebellar hypoplasia. Electrophysiological experiments finally demonstrated that the E/I balance in these mice is altered by modification of both inhibitory and excitatory synaptic transmission. On the basis of the reported changes in PV expression patterns in several, mostly genetic rodent models of ASD, we propose that in these models downregulation of PV might represent one of the points of convergence, thus

  10. The Use of Music to Increase Task-Oriented Behaviors in Preschool Children with Autism Spectrum Disorders in a Gross Motor Setting

    ERIC Educational Resources Information Center

    Dieringer, Shannon M.

    2012-01-01

    The purpose of this study is to determine the effect of music and music + instruction on task-oriented behaviors in preschool children with ASD within individual gross motor movement settings. Five preschool children (four boys; one girl) diagnosed with ASD attending a Midwestern private preschool for children with ASD served as participants. The…

  11. Children's Search Strategies and Accompanying Verbal and Motor Strategic Behavior: Developmental Trends and Relations with Task Performance among Children Age 5 to 17

    ERIC Educational Resources Information Center

    Winsler, Adam; Naglieri, Jack; Manfra, Louis

    2006-01-01

    Children's reported use of single and multiple search strategies during a matching numbers task, along with accompanying verbal (private speech, self-talk) and motoric (finger pointing, place-holding) strategic behaviors were examined with a large, nationally representative cross-sectional sample ("n"=1,979) of children between the ages of 5 and…

  12. The Effect of Voice Ambulatory Biofeedback on the Daily Performance and Retention of a Modified Vocal Motor Behavior in Participants with Normal Voices

    ERIC Educational Resources Information Center

    Van Stan, Jarrad H.; Mehta, Daryush D.; Hillman, Robert E.

    2015-01-01

    Purpose: Ambulatory biofeedback has potential to improve carryover of newly established vocal motor behaviors into daily life outside of the clinic and warrants systematic research that is lacking in the literature. This proof-of-concept study was designed to establish an empirical basis for future work in this area by formally assessing whether…

  13. The effect of voice ambulatory biofeedback on the daily performance and retention of a modified vocal motor behavior in participants with normal voices

    PubMed Central

    Van Stan, Jarrad H.; Mehta, Daryush D.; Hillman, Robert E.

    2015-01-01

    Purpose Ambulatory biofeedback has potential to improve carryover of newly-established vocal motor behaviors into daily life outside of the clinic and warrants systematic research that is lacking in the literature. This proof-of-concept study was designed to establish an empirical basis for future work in this area by formally assessing whether ambulatory biofeedback reduces daily vocal intensity (performance) and the extent to which this change remains after biofeedback removal (retention). Method Six participants with normal voices wore the KayPENTAX Ambulatory Phonation Monitor for three baseline days followed by four days with biofeedback provided on odd days. Results Compared to baseline days, participants exhibited a statistically significant decrease in mean vocal intensity (4.4 dB) and an increase in compliance (16.8 percentage points) when biofeedback was provided above a participant-specific intensity threshold. After biofeedback removal, mean vocal intensity and compliance reverted back to baseline levels. Conclusions These findings suggest that although current ambulatory biofeedback approaches have potential to modify a vocal motor behavior, the modified behavior may not be retained after biofeedback removal. Future work calls for the testing of more innovative ambulatory biofeedback approaches based on motor control and learning theories to improve retention of a desired vocal motor behavior. PMID:25765862

  14. Assisting People with Multiple Disabilities and Minimal Motor Behavior to Improve Computer Drag-and-Drop Efficiency through a Mouse Wheel

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang

    2011-01-01

    This study evaluated whether two people with multiple disabilities and minimal motor behavior would be able to improve their Drag-and-Drop (DnD) performance using their finger/thumb poke ability with a mouse scroll wheel through a Dynamic Drag-and-Drop Assistive Program (DDnDAP). A multiple probe design across participants was used in this study…

  15. Neural Basis of Stimulus-Angle-Dependent Motor Control of Wind-Elicited Walking Behavior in the Cricket Gryllus bimaculatus

    PubMed Central

    Oe, Momoko; Ogawa, Hiroto

    2013-01-01

    Crickets exhibit oriented walking behavior in response to air-current stimuli. Because crickets move in the opposite direction from the stimulus source, this behavior is considered to represent ‘escape behavior’ from an approaching predator. However, details of the stimulus-angle-dependent control of locomotion during the immediate phase, and the neural basis underlying the directional motor control of this behavior remain unclear. In this study, we used a spherical-treadmill system to measure locomotory parameters including trajectory, turn angle and velocity during the immediate phase of responses to air-puff stimuli applied from various angles. Both walking direction and turn angle were correlated with stimulus angle, but their relationships followed different rules. A shorter stimulus also induced directionally-controlled walking, but reduced the yaw rotation in stimulus-angle-dependent turning. These results suggest that neural control of the turn angle requires different sensory information than that required for oriented walking. Hemi-severance of the ventral nerve cords containing descending axons from the cephalic to the prothoracic ganglion abolished stimulus-angle-dependent control, indicating that this control required descending signals from the brain. Furthermore, we selectively ablated identified ascending giant interneurons (GIs) in vivo to examine their functional roles in wind-elicited walking. Ablation of GI8-1 diminished control of the turn angle and decreased walking distance in the initial response. Meanwhile, GI9-1b ablation had no discernible effect on stimulus-angle-dependent control or walking distance, but delayed the reaction time. These results suggest that the ascending signals conveyed by GI8-1 are required for turn-angle control and maintenance of walking behavior, and that GI9-1b is responsible for rapid initiation of walking. It is possible that individual types of GIs separately supply the sensory signals required to control

  16. Group Cognitive Behavioral Treatment for PTSD: Treatment of Motor Vehicle Accident Survivors

    ERIC Educational Resources Information Center

    Beck, J. Gayle; Coffey, Scott F.

    2005-01-01

    Individual cognitive behavioral therapies (CBT) are now considered the first-line treatment for posttraumatic stress disorder (PTSD; Foa, Keane, & Friedman, 2000). As mental health reimbursement becomes more restricted, it is imperative that we adapt individual-format therapies for use in a small group format. Group therapies have a number of…

  17. The Effect of Geography and Citizen Behavior on Motor Vehicle Deaths in the United States

    PubMed Central

    Abaid, Nicole; Macinko, James; Silver, Diana; Porfiri, Maurizio

    2015-01-01

    Death due to motor vehicle collisions (MVCs) remains a leading cause of death in the US and alcohol plays a prominent role in a large proportion of these fatalities nationwide. Rates for these incidents vary widely among states and over time. Here, we explore the extent to which driving volume, alcohol consumption, legislation, political ideology, and geographical factors influence MVC deaths across states and time. We specify structural equation models for extracting associations between the factors and outcomes for MVC deaths and compute correlation functions of states’ relative geographic and political positions to elucidate the relative contribution of these factors. We find evidence that state-level variation in MVC deaths is associated with time-varying driving volume, alcohol consumption, and legislation. These relationships are modulated by state spatial proximity, whereby neighboring states are found to share similar MVC death rates over the thirty-year observation period. These results support the hypothesis that neighboring states exhibit similar risk and protective characteristics, despite differences in political ideology. PMID:25850105

  18. From one to many: dynamic assembly and collective behavior of self-propelled colloidal motors.

    PubMed

    Wang, Wei; Duan, Wentao; Ahmed, Suzanne; Sen, Ayusman; Mallouk, Thomas E

    2015-07-21

    The assembly of complex structures from simpler, individual units is a hallmark of biology. Examples include the pairing of DNA strands, the assembly of protein chains into quaternary structures, the formation of tissues and organs from cells, and the self-organization of bacterial colonies, flocks of birds, and human beings in cities. While the individual behaviors of biomolecules, bacteria, birds, and humans are governed by relatively simple rules, groups assembled from many individuals exhibit complex collective behaviors and functions that do not exist in the absence of the hierarchically organized structure. Self-assembly is a familiar concept to chemists who study the formation and properties of monolayers, crystals, and supramolecular structures. In chemical self-assembly, disorder evolves to order as the system approaches equilibrium. In contrast, living assemblies are typically characterized by two additional features: (1) the system constantly dissipates energy and is not at thermodynamic equilibrium; (2) the structure is dynamic and can transform or disassemble in response to stimuli or changing conditions. To distinguish them from equilibrium self-assembled structures, living (or nonliving) assemblies of objects with these characteristics are referred to as active matter. In this Account, we focus on the powered assembly and collective behavior of self-propelled colloids. These nano- and microparticles, also called nano- and micromotors or microswimmers, autonomously convert energy available in the environment (in the form of chemical, electromagnetic, acoustic, or thermal energy) into mechanical motion. Collections of these colloids are a form of synthetic active matter. Because of the analogy to living swimmers of similar size such as bacteria, the dynamic interactions and collective behavior of self-propelled colloids are interesting in the context of understanding biological active matter and in the development of new applications. The progression

  19. Emergent behaviors of a fuzzy sensory-motor controller evolved by genetic algorithm.

    PubMed

    Lee, S I; Cho, S B

    2001-01-01

    Recently, there has been extensive work on the construction of fuzzy controllers for mobile robots by a genetic algorithm (GA); therefore, we can realize evolutionary optimization as a promising method for developing fuzzy controllers. However, much investigation on the evolutionary fuzzy controller remains because most of the previous works have not seriously attempted to analyze the fuzzy controller obtained by evolution. This paper develops a fuzzy logic controller for a mobile robot with a GA in simulation environments and analyzes the behaviors of the controller with a state transition diagram of the internal model. Experimental results show that appropriate control mechanisms of the fuzzy controller are obtained by evolution. The controller has evolved wen enough to smoothly drive the robot in different environments. The robot produces emergent behaviors by the interaction of several fuzzy rules obtained. PMID:18244857

  20. Influences of early thyroid hormone manipulations: delays in pup motor and exploratory behavior are evident in adult operant performance.

    PubMed

    Brosvic, Gary M; Taylor, Jodi N; Dihoff, Roberta E

    2002-04-15

    The effects of thyroid hormone depletion and enhancement on litter size, survival, body mass, ambulation, quadrant crossing, home orientation, day of eye opening, and free serum T3 and T4 levels were examined in Study 1. In Study 2, the effects of the timing of prenatal insult and the level of thyroid hormone depletion on litter size, survival, body mass, and free serum T3 and T4 levels were examined. Upon the completion of Study 1, randomly selected pups were maintained on ad-libitum water and food for 2 years, and performance was evaluated on fixed and variable ratio schedules, fixed and variable interval schedules, and probability and reversal learning tasks (Study 3). In Study 4, human subjects diagnosed with and treated for either congenital hypothyroidism or congenital hyperthyroidism were tested on the operant procedures used in Study 3, as well as on a series of simple reaction time, serial timing, and conjunctive and disjunctive search tasks. Dose-dependent decreases in survival and delays in the presentation of early motor and exploratory skills were observed following thyroid hormone depletion; dose-dependent accelerations in the presentation of early motor and exploratory skills were observed following thyroid hormone enhancement. Pups that had been prenatally exposed to propylthiouracil (PTU) 1-2 years after the return of thyroid hormones to baseline levels were significantly less accurate at timing on fixed and variable interval schedules, demonstrated an inability to allocate responding on probability tasks, and committed more errors during original learning (OL) and on each reversal problem. Similar deficits were observed in follow-up tests with humans diagnosed with congenital hypothyroidism, as were deficits in serial timing and visual searching. Collectively, the present results demonstrate that the pervasive and negative effects of prenatal thyroid deficiency on early behavior are also expressed during adult operant performance. PMID:12020735

  1. Attentive, Affective, and Adaptive Behavior in the Cat: Sensory deprivation of the forebrain by lesions in the brain stem results in striking behavioral abnormalities.

    PubMed

    Sprague, J M; Chambers, W W; Stellar, E

    1961-01-20

    Lesions of the lateral portion of the upper midbrain, involving medial, lateral, spinal, and trigeminal lemnisci primarily, result in a consistent syndrome of symptoms in the cat. (i) There is a marked sensory deficit, characterized mainly by sensory inattention and poor localization in the tactile, proprioceptive, auditory, gustatory, and nociceptive modalities, where direct pathways are interrupted. Similar defectsappear in vision and olfaction where no known direct or primary paths are interrupted. (ii) These cats are characterized by a lack of affect, showing little or no defensive and aggressive reaction to noxious and aversive situations and no response to pleasurable stimulation or solicitation of affection or petting. The animals are mute, lack facial expression, and show minimal autonomic responses. (iii) They show a hyperexploratory activity characterized by incessant, stereotyped wandering, sniffing, and visual searching, as though hallucinating. This behavior appears to be centrally directed and is very difficult to interrupt with environmental stimuli. (iv) They also demonstrate exaggerated oral activities: they snap in response to tactile stimulation of the lips, seizing and swallowing small objects even if inedible; they overeat; they hold objects too large to swallow (a mouse, a catnip ball) firmly clamped in the mouth for long periods of time; they mount and seize other animals (rat, cat, dog, monkey) by the back or the neck; they lick and chew the hair and skin of the back or tail incessantly when confined in a cage. In interpreting these results we emphasize the view that the syndrome is due chiefly to the extensive, specific, sensory deprivation produced by interruption of the lemnisci at the rostral midbrain. The relation of these findings to the effects of sensory isolation in man and animals, to the effects of midbrain lesions and neodecortication, to parietal lobe syndrome in primates, and to the behavior of autistic children is discussed

  2. Effects of sex and housing on social, spatial, and motor behavior in adult rats exposed to moderate levels of alcohol during prenatal development.

    PubMed

    Rodriguez, Carlos I; Magcalas, Christy M; Barto, Daniel; Fink, Brandi C; Rice, James P; Bird, Clark W; Davies, Suzy; Pentkowski, Nathan S; Savage, Daniel D; Hamilton, Derek A

    2016-10-15

    Persistent deficits in social behavior, motor behavior, and behavioral flexibility are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked moderate prenatal alcohol exposure (PAE) in the rat to deficits in these behavioral domains, which depend upon the ventrolateral frontal cortex (Hamilton et al., 2014) [20]. Manipulations of the social environment cause modifications of dendritic morphology and experience-dependent immediate early gene expression in ventrolateral frontal cortex (Hamilton et al., 2010) [19], and may yield positive behavioral outcomes following PAE. In the present study we evaluated the effects of housing PAE rats with non-exposed control rats on adult behavior. Rats of both sexes were either paired with a partner from the same prenatal treatment condition (ethanol or saccharin) or from the opposite condition (mixed housing condition). At four months of age (∼3 months after the housing manipulation commenced), social behavior, tongue protrusion, and behavioral flexibility in the Morris water task were measured as in (Hamilton et al., 2014) [20]. The behavioral effects of moderate PAE were primarily limited to males and were not ameliorated by housing with a non-ethanol exposed partner. Unexpectedly, social behavior, motor behavior, and spatial flexibility were adversely affected in control rats housed with a PAE rat (i.e., in mixed housing), indicating that housing with a PAE rat has broad behavioral consequences beyond the social domain. These observations provide further evidence that moderate PAE negatively affects social behavior, and underscore the importance of considering potential negative effects of housing with PAE animals on the behavior of critical comparison groups. PMID:27424779

  3. Evidence for distinct brain networks in the control of rule-based motor behavior

    PubMed Central

    Granek, Joshua A.

    2015-01-01

    Reach guidance when the spatial location of the viewed target and hand movement are incongruent (i.e., decoupled) necessitates use of explicit cognitive rules (strategic control) or implicit recalibration of gaze and limb position (sensorimotor recalibration). In a patient with optic ataxia (OA) and bilateral superior parietal lobule damage, we recently demonstrated an increased reliance on strategic control when the patient performed a decoupled reach (Granek JA, Pisella L, Stemberger J, Vighetto A, Rossetti Y, Sergio LE. PLoS One 8: e86138, 2013). To more generally understand the fundamental mechanisms of decoupled visuomotor control and to more specifically test whether we could distinguish these two modes of movement control, we tested healthy participants in a cognitively demanding dual task. Participants continuously counted backward while simultaneously reaching toward horizontal (left or right) or diagonal (equivalent to top-left or top-right) targets with either veridical or rotated (90°) cursor feedback. By increasing the overall neural load and selectively compromising potentially overlapping neural circuits responsible for strategic control, the complex dual task served as a noninvasive means to disrupt the integration of a cognitive rule into a motor action. Complementary to our previous results observed in patients with optic ataxia, here our dual task led to greater performance deficits during movements that required an explicit rule, implying a selective disruption of strategic control in decoupled reaching. Our results suggest that distinct neural processing is required to control these different types of reaching because in considering the current results and previous patient results together, the two classes of movement could be differentiated depending on the type of interference. PMID:26133796

  4. Evidence for distinct brain networks in the control of rule-based motor behavior.

    PubMed

    Granek, Joshua A; Sergio, Lauren E

    2015-08-01

    Reach guidance when the spatial location of the viewed target and hand movement are incongruent (i.e., decoupled) necessitates use of explicit cognitive rules (strategic control) or implicit recalibration of gaze and limb position (sensorimotor recalibration). In a patient with optic ataxia (OA) and bilateral superior parietal lobule damage, we recently demonstrated an increased reliance on strategic control when the patient performed a decoupled reach (Granek JA, Pisella L, Stemberger J, Vighetto A, Rossetti Y, Sergio LE. PLoS One 8: e86138, 2013). To more generally understand the fundamental mechanisms of decoupled visuomotor control and to more specifically test whether we could distinguish these two modes of movement control, we tested healthy participants in a cognitively demanding dual task. Participants continuously counted backward while simultaneously reaching toward horizontal (left or right) or diagonal (equivalent to top-left or top-right) targets with either veridical or rotated (90°) cursor feedback. By increasing the overall neural load and selectively compromising potentially overlapping neural circuits responsible for strategic control, the complex dual task served as a noninvasive means to disrupt the integration of a cognitive rule into a motor action. Complementary to our previous results observed in patients with optic ataxia, here our dual task led to greater performance deficits during movements that required an explicit rule, implying a selective disruption of strategic control in decoupled reaching. Our results suggest that distinct neural processing is required to control these different types of reaching because in considering the current results and previous patient results together, the two classes of movement could be differentiated depending on the type of interference. PMID:26133796

  5. A Cholinergic-Regulated Circuit Coordinates the Maintenance and Bi-Stable States of a Sensory-Motor Behavior during Caenorhabditis elegans Male Copulation

    PubMed Central

    Liu, Yishi; LeBeouf, Brigitte; Guo, Xiaoyan; Correa, Paola A.; Gualberto, Daisy G.; Lints, Robyn; Garcia, L. Rene

    2011-01-01

    Penetration of a male copulatory organ into a suitable mate is a conserved and necessary behavioral step for most terrestrial matings; however, the detailed molecular and cellular mechanisms for this distinct social interaction have not been elucidated in any animal. During mating, the Caenorhabditis elegans male cloaca is maintained over the hermaphrodite's vulva as he attempts to insert his copulatory spicules. Rhythmic spicule thrusts cease when insertion is sensed. Circuit components consisting of sensory/motor neurons and sex muscles for these steps have been previously identified, but it was unclear how their outputs are integrated to generate a coordinated behavior pattern. Here, we show that cholinergic signaling between the cloacal sensory/motor neurons and the posterior sex muscles sustains genital contact between the sexes. Simultaneously, via gap junctions, signaling from these muscles is transmitted to the spicule muscles, thus coupling repeated spicule thrusts with vulval contact. To transit from rhythmic to sustained muscle contraction during penetration, the SPC sensory-motor neurons integrate the signal of spicule's position in the vulva with inputs from the hook and cloacal sensilla. The UNC-103 K+ channel maintains a high excitability threshold in the circuit, so that sustained spicule muscle contraction is not stimulated by fewer inputs. We demonstrate that coordination of sensory inputs and motor outputs used to initiate, maintain, self-monitor, and complete an innate behavior is accomplished via the coupling of a few circuit components. PMID:21423722

  6. A Low Concentration of Ethanol Impairs Learning but Not Motor and Sensory Behavior in Drosophila Larvae

    PubMed Central

    Ghezzi, Alfredo; Cady, Amanda M.; Najjar, Kristina; Hatch, Michael M.; Shah, Ruchita R.; Bhat, Amar; Hariri, Omar; Haroun, Kareem B.; Young, Melvin C.; Fife, Kathryn; Hooten, Jeff; Tran, Tuan; Goan, Daniel; Desai, Foram; Husain, Farhan; Godinez, Ryan M.; Sun, Jeffrey C.; Corpuz, Jonathan; Moran, Jacxelyn; Zhong, Allen C.; Chen, William Y.; Atkinson, Nigel S.

    2012-01-01

    Drosophila melanogaster has proven to be a useful model system for the genetic analysis of ethanol-associated behaviors. However, past studies have focused on the response of the adult fly to large, and often sedating, doses of ethanol. The pharmacological effects of low and moderate quantities of ethanol have remained understudied. In this study, we tested the acute effects of low doses of ethanol (∼7 mM internal concentration) on Drosophila larvae. While ethanol did not affect locomotion or the response to an odorant, we observed that ethanol impaired associative olfactory learning when the heat shock unconditioned stimulus (US) intensity was low but not when the heat shock US intensity was high. We determined that the reduction in learning at low US intensity was not a result of ethanol anesthesia since ethanol-treated larvae responded to the heat shock in the same manner as untreated animals. Instead, low doses of ethanol likely impair the neuronal plasticity that underlies olfactory associative learning. This impairment in learning was reversible indicating that exposure to low doses of ethanol does not leave any long lasting behavioral or physiological effects. PMID:22624024

  7. Motor Planning.

    PubMed

    Wong, Aaron L; Haith, Adrian M; Krakauer, John W

    2015-08-01

    Motor planning colloquially refers to any process related to the preparation of a movement that occurs during the reaction time prior to movement onset. However, this broad definition encompasses processes that are not strictly motor-related, such as decision-making about the identity of task-relevant stimuli in the environment. Furthermore, the assumption that all motor-planning processes require processing time, and can therefore be studied behaviorally by measuring changes in the reaction time, needs to be reexamined. In this review, we take a critical look at the processes leading from perception to action and suggest a definition of motor planning that encompasses only those processes necessary for a movement to be executed-that is, processes that are strictly movement related. These processes resolve the ambiguity inherent in an abstract goal by defining a specific movement to achieve it. We propose that the majority of processes that meet this definition can be completed nearly instantaneously, which means that motor planning itself in fact consumes only a small fraction of the reaction time. PMID:24981338

  8. From neuron to behavior: dynamic equation-based prediction of biological processes in motor control.

    PubMed

    Daun-Gruhn, Silvia; Büschges, Ansgar

    2011-07-01

    This article presents the use of continuous dynamic models in the form of differential equations to describe and predict temporal changes in biological processes and discusses several of its important advantages over discontinuous bistable ones, exemplified on the stick insect walking system. In this system, coordinated locomotion is produced by concerted joint dynamics and interactions on different dynamical scales, which is therefore difficult to understand. Modeling using differential equations possesses, in general, the potential for the inclusion of biological detail, the suitability for simulation, and most importantly, parameter manipulation to make predictions about the system behavior. We will show in this review article how, in case of the stick insect walking system, continuous dynamical system models can help to understand coordinated locomotion. PMID:21769740

  9. [Reaching behavior of rats during realization of a lateralized motor food skill].

    PubMed

    Stashkevich, I S; Kulikov, M A

    2004-01-01

    Adult Wistar rats were trained to obtain food pellets from a narrow horizontal tube with a preferred forepaw. The feeder was equipped with five photoelectric sensors with 5-mm spacing. The following parameters were recorded: total number of movements performed for a given task, amplitude (depth) of each movement, number of anticipatory movements performed with different amplitudes, and amplitude of a successful movement. It was shown that in rats with good skill acquisition, a successful food extraction was preceded by a series of differently organized sequence of preliminary movements. In some rats, such a series consisted of initial non-deep attempts followed by movements with high amplitude, whereas in other animals, it was represented, mainly, by deep attempts. Both groups of animals terminated the series by grasping and extracting food from a long distance. It is suggested that the observed organizations of the lateralized food-getting behavior of rats under the given experimental conditions represent fixed (stereotyped) action patterns. PMID:15326954

  10. Exercise Effects on Motor and Affective Behavior and Catecholamine Neurochemistry in the MPTP-Lesioned Mouse

    PubMed Central

    Gorton, Lori M.; Vuckovic, Marta G.; Vertelkina, Nina; Petzinger, Giselle M.; Jakowec, Michael W.; Wood, Ruth I.

    2010-01-01

    This study used 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) in mice to determine if exercise improves behavior and dopamine (DA) and serotonin (5HT) content. Male C57BL/6 mice received MPTP (4×20 mg/kg) or saline. They remained sedentary or exercised by treadmill or voluntary running wheel for 6 weeks (n=8/group). Saline-treated mice ran significantly faster on running wheels (22.8±1.0 m/min) than on treadmill (8.5±0.5 m/min), and MPTP lesion did not reduce voluntary exercise (19.3±1.5 m/min, p>0.05). There was a significant effect of both lesion and exercise on overall Rotarod performance (ORP): MPTP lesion reduced ORP, while treadmill exercise increased ORP vs sedentary mice (p<0.05). MPTP increased anxiety in the marble-burying test: sedentary lesioned mice buried more marbles (74.0±5.2%) than sedentary controls (34.8±11.8%, p<0.05). Conversely, exercise reduced anxiety on the elevated plus maze. Among saline-treated mice, those exposed to voluntary wheel-running showed an increased percent of open arm entries (49.8±3.5%, p<0.05) relative to relative to sedentary controls (36.2±4.0%, p<0.05). Neither MPTP nor exercise altered symptoms of depression measured by sucrose preference or tail suspension. MPTP significantly reduced DA in striatum (in sedentary lesioned mice to 42.1±3.0% of saline controls), and lowered 5HT in amygdala and striatum (in sedentary lesioned mice to 86.1±4.1% and 66.5±8.2% of saline controls, respectively); exercise had no effect. Thus, exercise improves behavior in a model of DA depletion, without changes in DA or 5HT. PMID:20472000

  11. Focal dystonia and the Sensory-Motor Integrative Loop for Enacting (SMILE)

    PubMed Central

    Perruchoud, David; Murray, Micah M.; Lefebvre, Jeremie; Ionta, Silvio

    2014-01-01

    Performing accurate movements requires preparation, execution, and monitoring mechanisms. The first two are coded by the motor system, the latter by the sensory system. To provide an adaptive neural basis to overt behaviors, motor and sensory information has to be properly integrated in a reciprocal feedback loop. Abnormalities in this sensory-motor loop are involved in movement disorders such as focal dystonia, a hyperkinetic alteration affecting only a specific body part and characterized by sensory and motor deficits in the absence of basic motor impairments. Despite the fundamental impact of sensory-motor integration mechanisms on daily life, the general principles of healthy and pathological anatomic–functional organization of sensory-motor integration remain to be clarified. Based on the available data from experimental psychology, neurophysiology, and neuroimaging, we propose a bio-computational model of sensory-motor integration: the Sensory-Motor Integrative Loop for Enacting (SMILE). Aiming at direct therapeutic implementations and with the final target of implementing novel intervention protocols for motor rehabilitation, our main goal is to provide the information necessary for further validating the SMILE model. By translating neuroscientific hypotheses into empirical investigations and clinically relevant questions, the prediction based on the SMILE model can be further extended to other pathological conditions characterized by impaired sensory-motor integration. PMID:24999327

  12. LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors

    PubMed Central

    2012-01-01

    Mutations in the LRRK2 gene are the most common cause of genetic Parkinson’s disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations are still not clear, data emerging from in vitro and in vivo models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation. We created mice lacking exon 41 that encodes the activation hinge of the kinase domain of LRRK2. We have performed a comprehensive analysis of these mice up to 20 months of age, including evaluation of dopamine storage, release, uptake and synthesis, behavioral testing, dendritic spine and proliferation/neurogenesis analysis. Our results show that the dopaminergic system was not functionally comprised in LRRK2 knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than their wild type littermates on the accelerated rod during rotarod testing. Finally, we confirm that loss of LRRK2 caused degeneration in the kidney, accompanied by a progressive enhancement of autophagic activity and accumulation of autofluorescent material, but without evidence of biphasic changes. PMID:22647713

  13. Curcumin Treatment Improves Motor Behavior in α-Synuclein Transgenic Mice

    PubMed Central

    Spinelli, Kateri J.; Osterberg, Valerie R.; Meshul, Charles K.; Soumyanath, Amala; Unni, Vivek K.

    2015-01-01

    The curry spice curcumin plays a protective role in mouse models of neurodegenerative diseases, and can also directly modulate aggregation of α-synuclein protein in vitro, yet no studies have described the interaction of curcumin and α-synuclein in genetic synucleinopathy mouse models. Here we examined the effect of chronic and acute curcumin treatment in the Syn-GFP mouse line, which overexpresses wild-type human α-synuclein protein. We discovered that curcumin diet intervention significantly improved gait impairments and resulted in an increase in phosphorylated forms of α-synuclein at cortical presynaptic terminals. Acute curcumin treatment also caused an increase in phosphorylated α-synuclein in terminals, but had no direct effect on α-synuclein aggregation, as measured by in vivo multiphoton imaging and Proteinase-K digestion. Using LC-MS/MS, we detected ~5 ng/mL and ~12 ng/mL free curcumin in the plasma of chronic or acutely treated mice, with a glucuronidation rate of 94% and 97%, respectively. Despite the low plasma levels and extensive metabolism of curcumin, these results show that dietary curcumin intervention correlates with significant behavioral and molecular changes in a genetic synucleinopathy mouse model that mimics human disease. PMID:26035833

  14. Long-term treatment with L-DOPA or pramipexole affects adult neurogenesis and corresponding non-motor behavior in a mouse model of Parkinson's disease.

    PubMed

    Chiu, W-H; Depboylu, C; Hermanns, G; Maurer, L; Windolph, A; Oertel, W H; Ries, V; Höglinger, G U

    2015-08-01

    Non-motor symptoms such as hyposmia and depression are often observed in Parkinson's disease (PD) and can precede the onset of motor symptoms for years. The underlying pathological alterations in the brain are not fully understood so far. Dysregulation of adult neurogenesis in the dentate gyrus of the hippocampus and the olfactory bulb has been recently suggested to be implicated in non-motor symptoms of PD. However, there is so far no direct evidence to support the relationship of non-motor symptoms and the modulation of adult neurogenesis following dopamine depletion and/or dopamine replacement. In this study, we investigated the long-term effects of l-DOPA and pramipexole, a dopamine agonist, in a mouse model of bilateral intranigral 6-OHDA lesion, in order to assess the impact of adult neurogenesis on non-motor behavior. We found that l-DOPA and pramipexole can normalize decreased neurogenesis in the hippocampal dentate gyrus and the periglomerular layer of the olfactory bulb caused by a 6-OHDA lesion. Interestingly, pramipexole showed an antidepressant and anxiolytic effect in the forced swim test and social interaction test. However, there was no significant change in learning and memory function after dopamine depletion and dopamine replacement, respectively. PMID:25839898

  15. Exendin-4 reverses biochemical and behavioral deficits in a pre-motor rodent model of Parkinson's disease with combined noradrenergic and serotonergic lesions.

    PubMed

    Rampersaud, N; Harkavyi, A; Giordano, G; Lever, R; Whitton, J; Whitton, P S

    2012-10-01

    Research on Parkinson's disease (PD) has mainly focused on the degeneration of the dopaminergic neurons of nigro-striatal pathway; however, post-mortem studies have demonstrated that other brain regions such as the locus coeruleus (LC) and raphe nuclei (RN) are significantly affected as well. Degeneration of these crucial neuronal cell bodies may be responsible for depressive behavior and cognitive decline present in the pre-motor stage of PD. We have thus set out to create a pre-motor rodent model of PD which mimics the early stages of the condition. N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a selective noradrenergic neurotoxin, and parachloroampetamine (pCA), a selective serotonergic neurotoxin, were utilized concomitantly with bilateral 6-hydroxydopamine (6-OHDA) injections into the striatum to produce a pre-motor rodent model of PD with partial deficits in the dopaminergic, noradrenergic, and serotonergic systems. Our model exhibited a depressive/anhedonic condition as assessed using sucrose preference testing and the forced swim test. Our model also demonstrated deficits in object memory. These behavioral impairments were accompanied by a decline in both tissue and extracellular levels of all three neurotransmitters in both the frontal cortex and striatum. Immunohistochemistry also revealed a decrease in TH+ cells in the LC and substantia nigra. Exendin-4 (EX-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, promoted recovery of both the biochemical and behavioral dysfunction exhibited by our model. EX-4 was able to preserve the functional integrity of the dopaminergic, noradrenergic, and serotonergic systems. In conclusion, we have generated a novel animal model of PD that recapitulates certain pre-motor symptomology. These symptoms and causative physiology are ameliorated upon treatment with EX-4 and thus it could be used as a possible therapy for the non-motor symptoms prominent in the early stages of PD. PMID:22921965

  16. Deficits in coordinated motor behavior and in nigrostriatal dopaminergic system ameliorated and VMAT2 expression up-regulated in aged male rats by administration of testosterone propionate.

    PubMed

    Wang, Li; Kang, Yunxiao; Zhang, Guoliang; Zhang, Yingbo; Cui, Rui; Yan, Wensheng; Tan, Huibing; Li, Shuangcheng; Wu, Baiyila; Cui, Huixian; Shi, Geming

    2016-06-01

    The effects of testosterone propionate (TP) supplements on the coordinated motor behavior and nigrostriatal dopaminergic (NSDA) system were analyzed in aged male rats. The present study showed the coordinated motor behavioral deficits, the reduced activity of NSDA system and the decreased expression of vesicular monoamine transporter 2 (VMAT2) in 24month-old male rats. Long term TP treatment improved the motor coordination dysfunction with aging. Increased tyrosine hydroxylase and dopamine transporter, as well as dopamine and its metabolites were found in the NSDA system of TP-treated 24month-old male rats, indicative of the amelioratory effects of TP supplements on NSDA system of aged male rats. The enhancement of dopaminergic (DAergic) activity of NSDA system by TP supplements might underlie the amelioration of the coordinated motor dysfunction in aged male rats. TP supplements up-regulated VMAT2 expression in NSDA system of aged male rats. Up-regulation of VMAT2 expression in aged male rats following chronic TP treatment might be involved in the maintenance of DAergic function of NSDA system in aged male rats. PMID:26956479

  17. Detection of Structural Abnormalities Using Neural Nets

    NASA Technical Reports Server (NTRS)

    Zak, M.; Maccalla, A.; Daggumati, V.; Gulati, S.; Toomarian, N.

    1996-01-01

    This paper describes a feed-forward neural net approach for detection of abnormal system behavior based upon sensor data analyses. A new dynamical invariant representing structural parameters of the system is introduced in such a way that any structural abnormalities in the system behavior are detected from the corresponding changes to the invariant.

  18. Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice.

    PubMed

    Stroh, Matthew A; Winter, Michelle K; Swerdlow, Russell H; McCarson, Kenneth E; Zhu, Hao

    2016-08-01

    Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain. Assessment of molecular markers in the cerebellum of CKO mice revealed changes in pathways associated with cellular and mitochondrial iron homeostasis. (59)Fe pulse-feeding experiments revealed cerebellum-specific increased or decreased uptake of iron by 7 and 16 weeks of age, respectively. Additionally, we characterized behavioral changes associated with loss of NCB5OR in the cerebellum and midbrain in the context of dietary iron deprivation-evoked generalized iron deficiency. Locomotor activity was reduced and complex motor task execution was altered in CKO mice treated with an iron deficient diet. A sucrose preference test revealed that the reward response was intact in CKO mice, but that iron deficient diet consumption altered sucrose preference in all mice. Detailed gait analysis revealed locomotor changes in CKO mice associated with dysfunctional proprioception and locomotor activation independent of dietary iron deficiency. Finally, we demonstrate that loss of NCB5OR in the cerebellum and midbrain exacerbated harmaline-induced tremor activity. Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain. PMID:27188291

  19. Socio-behavioral characteristics of children with Rubinstein-Taybi syndrome.

    PubMed

    Galéra, Cédric; Taupiac, Emmanuelle; Fraisse, Sonia; Naudion, Sophie; Toussaint, Eva; Rooryck-Thambo, Caroline; Delrue, Marie-Ange; Arveiler, Benoit; Lacombe, Didier; Bouvard, Manuel-Pierre

    2009-09-01

    Research regarding the behavioral aspects of children with Rubinstein-Taybi syndrome (RTS) has suggested some possible behavioral patterns including autistic features. Caregivers of 39 children (mean age = 8.4 years) with RTS (49% showing abnormality in CREBBP gene) and 39 children (mean age = 8.6 years) matched on developmental level, age and gender were administered the Child Behavior Checklist and the Children's Social Behavior Questionnaire. Children with RTS did not exhibit higher internalizing (affective and anxiety symptoms) or externalizing (disruptive symptoms) behavioral problems than expected for their age/developmental range. However, they displayed some specific behaviors: short attention span, motor stereotypies, poor coordination, and overweight. The presence of an identified CREBBP gene abnormality was possibly related to the motor difficulties through impaired motor skills learning. PMID:19350377

  20. Alterations in local thyroid hormone signaling in the hippocampus of the SAMP8 mouse at younger ages: association with delayed myelination and behavioral abnormalities.

    PubMed

    Sawano, Erika; Negishi, Takayuki; Aoki, Tomoyuki; Murakami, Masami; Tashiro, Tomoko

    2013-03-01

    The senescence-accelerated mouse (SAM) strains were established through selective inbreeding of the AKR/J strain based on phenotypic variations of aging and consist of senescence-prone (SAMP) and senescence-resistant (SAMR) strains. Among them, SAMP8 is considered as a model of neurodegeneration displaying age-associated learning and memory impairment and altered emotional status. Because adult hypothyroidism is one of the common causes of cognitive impairment and various psychiatric disorders, we examined the possible involvement of thyroid hormone (TH) signaling in the pathological aging of SAMP8 using the senescence-resistant SAMR1 as control. Although plasma TH levels were similar in both strains, a significant decrease in type 2 deiodinase (D2) gene expression was observed in the SAMP8 hippocampus from 1 to 8 months of age, which led to a 35-50% reductions at the protein level and 20% reduction of its enzyme activity at 1, 3, and 5 months. D2 is responsible for local conversion of thyroxine into transcriptionally active 3,5,3'-triiodothyronine (T3), so the results suggest a reduction in T3 level in the SAMP8 hippocampus. Attenuation of local TH signaling was confirmed by downregulation of TH-dependent genes and by immunohistochemical demonstration of delayed and reduced accumulation of myelin basic protein, the expression of which is highly dependent on TH. Furthermore, we found that hyperactivity and reduced anxiety were not age-associated but were characteristic of young SAMP8 before they start showing impairments in learning and memory. Early alterations in local TH signaling may thus underlie behavioral abnormalities as well as the pathological aging of SAMP8. PMID:23224839

  1. Language and Motor Abilities of Preschool Children Who Stutter: Evidence from Behavioral and Kinematic Indices of Nonword Repetition Performance

    ERIC Educational Resources Information Center

    Smith, Anne; Goffman, Lisa; Sasisekaran, Jayanthi; Weber-Fox, Christine

    2012-01-01

    Stuttering is a disorder of speech production that typically arises in the preschool years, and many accounts of its onset and development implicate language and motor processes as critical underlying factors. There have, however, been very few studies of speech motor control processes in preschool children who stutter. Hearing novel nonwords and…

  2. Online and Offline Performance Gains Following Motor Imagery Practice: A Comprehensive Review of Behavioral and Neuroimaging Studies.

    PubMed

    Di Rienzo, Franck; Debarnot, Ursula; Daligault, Sébastien; Saruco, Elodie; Delpuech, Claude; Doyon, Julien; Collet, Christian; Guillot, Aymeric

    2016-01-01

    There is now compelling evidence that motor imagery (MI) promotes motor learning. While MI has been shown to influence the early stages of the learning process, recent data revealed that sleep also contributes to the consolidation of the memory trace. How such "online" and "offline" processes take place and how they interact to impact the neural underpinnings of movements has received little attention. The aim of the present review is twofold: (i) providing an overview of recent applied and fundamental studies investigating the effects of MI practice (MIP) on motor learning; and (ii) detangling applied and fundamental findings in support of a sleep contribution to motor consolidation after MIP. We conclude with an integrative approach of online and offline learning resulting from intense MIP in healthy participants, and underline research avenues in the motor learning/clinical domains. PMID:27445755

  3. Online and Offline Performance Gains Following Motor Imagery Practice: A Comprehensive Review of Behavioral and Neuroimaging Studies

    PubMed Central

    Di Rienzo, Franck; Debarnot, Ursula; Daligault, Sébastien; Saruco, Elodie; Delpuech, Claude; Doyon, Julien; Collet, Christian; Guillot, Aymeric

    2016-01-01

    There is now compelling evidence that motor imagery (MI) promotes motor learning. While MI has been shown to influence the early stages of the learning process, recent data revealed that sleep also contributes to the consolidation of the memory trace. How such “online” and “offline” processes take place and how they interact to impact the neural underpinnings of movements has received little attention. The aim of the present review is twofold: (i) providing an overview of recent applied and fundamental studies investigating the effects of MI practice (MIP) on motor learning; and (ii) detangling applied and fundamental findings in support of a sleep contribution to motor consolidation after MIP. We conclude with an integrative approach of online and offline learning resulting from intense MIP in healthy participants, and underline research avenues in the motor learning/clinical domains. PMID:27445755

  4. 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.

  5. [Motor neuron disease: metabolic evaluation].

    PubMed

    Godoy, J M; Skacel, M; Balassiano, S L; Neves, J R

    1992-03-01

    The authors studied serum and urinary calcium and phosphorus levels, as well as abnormalities on the spine of 30 patients with motor neuron disease. The authors believe in multifactorial aspects in the pathogenesis of motor neuron disease, calling special attention to toxic and metabolic factors. PMID:1307483

  6. Visual Behaviors and Adaptations Associated with Cortical and Ocular Impairment in Children.

    ERIC Educational Resources Information Center

    Jan, J. E.; Groenveld, M.

    1993-01-01

    This article shows the usefulness of understanding visual behaviors in the diagnosis of various types of visual impairments that are due to ocular and cortical disorders. Behaviors discussed include nystagmus, ocular motor dyspraxia, head position, close viewing, field loss adaptations, mannerisms, photophobia, and abnormal color perception. (JDD)

  7. Mental and Behavioral Symptoms of Person's with Asperger's Syndrome: Relationships with Social Isolation and Handicaps

    ERIC Educational Resources Information Center

    Tani, Masayuki; Kanai, Chieko; Ota, Haruhisa; Yamada, Takashi; Watanabe, Hiromi; Yokoi, Hideki; Takayama, Yuko; Ono, Taisei; Hashimoto, Ryuichiro; Kato, Nobumasa; Iwanami, Akira

    2012-01-01

    People with Asperger's syndrome (AS) experience mental comorbidities, and behavioral symptoms that can deepen social isolation and handicaps. We compared the frequency of mental and behavioral symptoms, motor abnormality, and life history between adults with AS and those with no mental disorders but with disturbance of social functions and…

  8. Sensory signals and neuronal groups involved in guiding the sea-ward motor behavior in turtle hatchlings of Chelonia agassizi

    NASA Astrophysics Data System (ADS)

    Fuentes, A. L.; Camarena, V.; Ochoa, G.; Urrutia, J.; Gutierrez, G.

    2007-05-01

    Turtle hatchlings orient display sea-ward oriented movements as soon as they emerge from the nest. Although most studies have emphasized the role of the visual information in this process, less attention has been paid to other sensory modalities. Here, we evaluated the nature of sensory cues used by turtle hatchlings of Chelonia agassizi to orient their movements towards the ocean. We recorded the time they took to crawl from the nest to the beach front (120m long) in control conditions and in visually, olfactory and magnetically deprived circumstances. Visually-deprived hatchlings displayed a high degree of disorientation. Olfactory deprivation and magnetic field distortion impaired, but not abolished, sea-ward oriented movements. With regard to the neuronal mapping experiments, visual deprivation reduced dramatically c-fos expression in the whole brain. Hatchlings with their nares blocked revealed neurons with c-fos expression above control levels principally in the c and d areas, while those subjected to magnetic field distortion had a wide spread activation of neurons throughout the brain predominantly in the dorsal ventricular ridge The present results support that Chelonia agassizi hatchlings use predominantly visual cues to orient their movements towards the sea. Olfactory and magnetic cues may also be use but their influence on hatchlings oriented motor behavior is not as clear as it is for vision. This conclusion is supported by the fact that in the absence of olfactory and magnetic cues, the brain turns on the expression of c- fos in neuronal groups that, in the intact hatchling, are not normally involved in accomplishing the task.

  9. Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Δ-9-tetrahydrocannabinol in humans

    PubMed Central

    Braley, Gabriel; Blaise, Rebecca; Vendetti, Michael; Oliver, Stephen; Pittman, Brian; Ranganathan, Mohini; Bhakta, Savita; Zimolo, Zoran; Cooper, Thomas; Perry, Edward

    2010-01-01

    Introduction Cannabinoids produce a spectrum of effects in humans including euphoria, cognitive impairments, psychotomimetic effects, and perceptual alterations. The extent to which dopaminergic systems contribute to the effects of Δ-9-tetrahydrocannabinol (Δ-9-THC) remains unclear. This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Δ-9-THC in humans. Materials and methods In a 2-test-day double-blind study, 28 subjects including healthy subjects (n=17) and frequent users of cannabis (n=11) were administered active (0.057 mg/kg) or placebo oral haloperidol in random order followed 90 and 215 min later by fixed order intravenous administration of placebo (vehicle) and active (0.0286 mg/kg) Δ-9-THC, respectively. Results Consistent with previous reports, intravenous Δ-9-THC produced psychotomimetic effects, perceptual alterations, and subjective effects including “high.” Δ-9-THC also impaired verbal recall and attention. Haloperidol pretreatment did not reduce any of the behavioral effects of Δ-9-THC. Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Δ-9-THC. Haloperidol and Δ-9-THC worsened distractibility and vigilance. Neither drug impaired performance on a motor screening task, the Stockings of Cambridge task, or the delayed match to sample task. Frequent users had lower baseline plasma prolactin levels and blunted Δ-9-THC induced memory impairments. Conclusions The deleterious effects of haloperidol pretreatment on the cognitive effects of Δ-9-THC are consistent with the preclinical literature in suggesting crosstalk between DAergic and CBergic systems. However, it is unlikely that DA D2 receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Δ-9-THC. Further investigation is warranted to understand the basis of the psychotomimetic effects of Δ-9-THC and to better understand the crosstalk between DAergic

  10. Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions

    PubMed Central

    Manto, Mario; Honnorat, Jérôme; Hampe, Christiane S.; Guerra-Narbona, Rafael; López-Ramos, Juan Carlos; Delgado-García, José María; Saitow, Fumihito; Suzuki, Hidenori; Yanagawa, Yuchio; Mizusawa, Hidehiro; Mitoma, Hiroshi

    2015-01-01

    Autoantibodies to the smaller isoform of glutamate decarboxylase (GAD) can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct GAD autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal GAD antibodies. We found that GAD autoantibodies present in patients with stiff person syndrome (n = 7) and cerebellar ataxia (n = 15) recognized an epitope distinct from that recognized by GAD autoantibodies present in patients with type 1 diabetes mellitus (n = 10) or limbic encephalitis (n = 4). We demonstrated that the administration of a monoclonal GAD antibody representing this epitope specificity; (1) disrupted in vitro the association of GAD with γ-Aminobutyric acid containing synaptic vesicles; (2) depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect; (3) significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task; (4) markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm; and (5) induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of GAD by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such GAD antibodies could be envisioned. PMID:25870548

  11. 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

  12. Daily oral intake of theanine prevents the decline of 5-bromo-2'-deoxyuridine incorporation in hippocampal dentate gyrus with concomitant alleviation of behavioral abnormalities in adult mice with severe traumatic stress.

    PubMed

    Takarada, Takeshi; Nakamichi, Noritaka; Kakuda, Takami; Nakazato, Ryota; Kokubo, Hiroshi; Ikeno, Shinsuke; Nakamura, Saki; Hinoi, Eiichi; Yoneda, Yukio

    2015-03-01

    Posttraumatic stress disorder is a long-lasting psychiatric disease with the consequence of hippocampal atrophy in humans exposed to severe fatal stress. We demonstrated a positive correlation between the transient decline of 5-bromo-2'-deoxyuridine (BrdU) incorporation in the hippocampal dentate gyrus (DG) and long-lasting behavioral abnormalities in mice with traumatic stress. Here, we investigated pharmacological properties of theanine on the declined BrdU incorporation and abnormal behaviors in mice with traumatic stress. Prior daily oral administration of theanine at 50-500 mg/kg for 5 days significantly prevented the decline of BrdU incorporation, while theanine significantly prevented the decline in the DG even when administered for 5 days after stress. Consecutive daily administration of theanine significantly inhibited the prolonged immobility in mice with stress in forced swimming test seen 14 days later. Although traumatic stress significantly increased spontaneous locomotor activity over 30 min even when determined 14 days later, the increased total locomotion was significantly ameliorated following the administration of theanine at 50 mg/kg for 14 days after stress. These results suggest that theanine alleviates behavioral abnormalities together with prevention of the transient decline of BrdU incorporation in the hippocampal DG in adult mice with severe traumatic stress. PMID:25837925

  13. Neurophysiology of spontaneous facial expressions: I. Motor control of the upper and lower face is behaviorally independent in adults.

    PubMed

    Ross, Elliott D; Gupta, Smita S; Adnan, Asif M; Holden, Thomas L; Havlicek, Joseph; Radhakrishnan, Sridhar

    2016-03-01

    Facial expressions are described traditionally as monolithic entities. However, humans have the capacity to produce facial blends, in which the upper and lower face simultaneously display different emotional expressions. This, in turn, has led to the Component Theory of facial expressions. Recent neuroanatomical studies in monkeys have demonstrated that there are separate cortical motor areas for controlling the upper and lower face that, presumably, also occur in humans. The lower face is represented on the posterior ventrolateral surface of the frontal lobes in the primary motor and premotor cortices and the upper face is represented on the medial surface of the posterior frontal lobes in the supplementary motor and anterior cingulate cortices. Our laboratory has been engaged in a series of studies exploring the perception and production of facial blends. Using high-speed videography, we began measuring the temporal aspects of facial expressions to develop a more complete understanding of the neurophysiology underlying facial expressions and facial blends. The goal of the research presented here was to determine if spontaneous facial expressions in adults are predominantly monolithic or exhibit independent motor control of the upper and lower face. We found that spontaneous facial expressions are very complex and that the motor control of the upper and lower face is overwhelmingly independent, thus robustly supporting the Component Theory of facial expressions. Seemingly monolithic expressions, be they full facial or facial blends, are most likely the result of a timing coincident rather than a synchronous coordination between the ventrolateral and medial cortical motor areas responsible for controlling the lower and upper face, respectively. In addition, we found evidence that the right and left face may also exhibit independent motor control, thus supporting the concept that spontaneous facial expressions are organized predominantly across the horizontal facial

  14. Abnormal Pressure Pain, Touch Sensitivity, Proprioception, and Manual Dexterity in Children with Autism Spectrum Disorders

    PubMed Central

    Riquelme, Inmaculada; Hatem, Samar M.

    2016-01-01

    Children with autism spectrum disorders (ASD) often display an abnormal reactivity to tactile stimuli, altered pain perception, and lower motor skills than healthy children. Nevertheless, these motor and sensory deficits have been mostly assessed by using clinical observation and self-report questionnaires. The present study aims to explore somatosensory and motor function in children with ASD by using standardized and objective testing procedures. Methods. Tactile and pressure pain thresholds in hands and lips, stereognosis, proprioception, and fine motor performance of the upper limbs were assessed in high-functioning children with ASD (n = 27) and compared with typically developing peers (n = 30).  Results. Children with ASD showed increased pain sensitivity, increased touch sensitivity in C-tactile afferents innervated areas, and diminished fine motor performance and proprioception compared to healthy children. No group differences were observed for stereognosis. Conclusion. Increased pain sensitivity and increased touch sensitivity in areas classically related to affective touch (C-tactile afferents innervated areas) may explain typical avoiding behaviors associated with hypersensitivity. Both sensory and motor impairments should be assessed and treated in children with ASD. PMID:26881091

  15. Modulation of motor behavior by dopamine and the D1-like dopamine receptor AmDOP2 in the honey bee

    PubMed Central

    Mustard, Julie A.; Pham, Priscilla M.; Smith, Brian H.

    2009-01-01

    Determining the specific molecular pathways through which dopamine affects behavior has been complicated by the presence of multiple dopamine receptor subtypes that couple to different second messenger pathways. The observation of freely moving adult bees in an arena was used to investigate the role of dopamine signaling in regulating the behavior of the honey bee. Dopamine or the dopamine receptor antagonist flupenthixol was injected into the hemolymph of worker honey bees. Significant differences between treated and control bees were seen for all behaviors (walking, stopped, upside down, grooming, flying and fanning), and behavioral shifts were dependent on drug dosage and time after injection. To examine the role of dopamine signaling through a specific dopamine receptor in the brain, RNA interference was used to reduce expression levels of a D1-like receptor, AmDOP2. Injection of Amdop2 dsRNA into the mushroom bodies reduced the levels of Amdop2 mRNA and produced significant changes in the amount of time honey bees spent performing specific behaviors with reductions in time spent walking offset by increases in grooming or time spent stopped. Taken together these results establish that dopamine plays an important role in regulating motor behavior of the honey bee. PMID:19945462

  16. Differences in the Transmission of Sensory Input into Motor Output between Introverts and Extraverts: Behavioral and Psychophysiological Analyses

    ERIC Educational Resources Information Center

    Stahl, J.; Rammsayer, T.

    2004-01-01

    The present study was designed to investigate extraversion-related individual differences in the speed of transmission of sensory input into motor output. In a sample of 16 introverted and 16 extraverted female volunteers, event-related potentials, lateralized readiness potentials (LRPs), and electromyogram (EMG) were recorded as participants…

  17. Language and motor abilities of preschool children who stutter: Evidence from behavioral and kinematic indices of nonword repetition performance

    PubMed Central

    Smith, Anne; Goffman, Lisa; Sasisekaran, Jayanthi; Weber-Fox, Christine

    2012-01-01

    Stuttering is a disorder of speech production that typically arises in the preschool years, and many accounts of its onset and development implicate language and motor processes as critical underlying factors. There have, however, been very few studies of speech motor control processes in preschool children who stutter. Hearing novel nonwords and reproducing them engages multiple neural networks, including those involved in phonological analysis and storage and speech motor programming and execution. We used this task to explore speech motor and language abilities of 31 children aged 4–5 years who were diagnosed as stuttering. We also used sensitive and specific standardized tests of speech and language abilities to determine which of the children who stutter had concomitant language and/or phonological disorders. Approximately half of our sample of stuttering children had language and/or phonological disorders. As previous investigations would suggest, the stuttering children with concomitant language or speech sound disorders produced significantly more errors on the nonword repetition task compared to typically developing children. In contrast, the children who were diagnosed as stuttering, but who had normal speech sound and language abilities, performed the nonword repetition task with equal accuracy compared to their normally fluent peers. Analyses of interarticulator motions during accurate and fluent productions of the nonwords revealed that the children who stutter (without concomitant disorders) showed higher variability in oral motor coordination indices. These results provide new evidence that preschool children diagnosed as stuttering lag their typically developing peers in maturation of speech motor control processes. Educational objectives The reader will be able to: (a) discuss why performance on nonword repetition tasks has been investigated in children who stutter; (b) discuss why children who stutter in the current study had a higher incidence

  18. Abnormal Head Position

    MedlinePlus

    ... cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal head posture could cause permanent ... occipitocervical synostosis and unilateral hearing loss. Are there any ... postures? Yes. Abnormal head postures can usually be improved depending ...

  19. Urine - abnormal color

    MedlinePlus

    ... straw-yellow. Abnormally colored urine may be cloudy, dark, or blood-colored. Causes Abnormal urine color may ... red blood cells, or mucus in the urine. Dark brown but clear urine is a sign of ...

  20. Perceptual-Cognitive Changes During Motor Learning: The Influence of Mental and Physical Practice on Mental Representation, Gaze Behavior, and Performance of a Complex Action

    PubMed Central

    Frank, Cornelia; Land, William M.; Schack, Thomas

    2016-01-01

    Despite the wealth of research on differences between experts and novices with respect to their perceptual-cognitive background (e.g., mental representations, gaze behavior), little is known about the change of these perceptual-cognitive components over the course of motor learning. In the present study, changes in one’s mental representation, quiet eye behavior, and outcome performance were examined over the course of skill acquisition as it related to physical and mental practice. Novices (N = 45) were assigned to one of three conditions: physical practice, combined physical plus mental practice, and no practice. Participants in the practice groups trained on a golf putting task over the course of 3 days, either by repeatedly executing the putt, or by both executing and imaging the putt. Findings revealed improvements in putting performance across both practice conditions. Regarding the perceptual-cognitive changes, participants practicing mentally and physically revealed longer quiet eye durations as well as more elaborate representation structures in comparison to the control group, while this was not the case for participants who underwent physical practice only. Thus, in the present study, combined mental and physical practice led to both formation of mental representations in long-term memory and longer quiet eye durations. Interestingly, the length of the quiet eye directly related to the degree of elaborateness of the underlying mental representation, supporting the notion that the quiet eye reflects cognitive processing. This study is the first to show that the quiet eye becomes longer in novices practicing a motor action. Moreover, the findings of the present study suggest that perceptual and cognitive adaptations co-occur over the course of motor learning. PMID:26779089

  1. Perceptual-Cognitive Changes During Motor Learning: The Influence of Mental and Physical Practice on Mental Representation, Gaze Behavior, and Performance of a Complex Action.

    PubMed

    Frank, Cornelia; Land, William M; Schack, Thomas

    2015-01-01

    Despite the wealth of research on differences between experts and novices with respect to their perceptual-cognitive background (e.g., mental representations, gaze behavior), little is known about the change of these perceptual-cognitive components over the course of motor learning. In the present study, changes in one's mental representation, quiet eye behavior, and outcome performance were examined over the course of skill acquisition as it related to physical and mental practice. Novices (N = 45) were assigned to one of three conditions: physical practice, combined physical plus mental practice, and no practice. Participants in the practice groups trained on a golf putting task over the course of 3 days, either by repeatedly executing the putt, or by both executing and imaging the putt. Findings revealed improvements in putting performance across both practice conditions. Regarding the perceptual-cognitive changes, participants practicing mentally and physically revealed longer quiet eye durations as well as more elaborate representation structures in comparison to the control group, while this was not the case for participants who underwent physical practice only. Thus, in the present study, combined mental and physical practice led to both formation of mental representations in long-term memory and longer quiet eye durations. Interestingly, the length of the quiet eye directly related to the degree of elaborateness of the underlying mental representation, supporting the notion that the quiet eye reflects cognitive processing. This study is the first to show that the quiet eye becomes longer in novices practicing a motor action. Moreover, the findings of the present study suggest that perceptual and cognitive adaptations co-occur over the course of motor learning. PMID:26779089

  2. A New Type of Motor: Pneumatic Step Motor

    PubMed Central

    Stoianovici, Dan; Patriciu, Alexandru; Petrisor, Doru; Mazilu, Dumitru; Kavoussi, Louis

    2011-01-01

    This paper presents a new type of pneumatic motor, a pneumatic step motor (PneuStep). Directional rotary motion of discrete displacement is achieved by sequentially pressurizing the three ports of the motor. Pulsed pressure waves are generated by a remote pneumatic distributor. The motor assembly includes a motor, gearhead, and incremental position encoder in a compact, central bore construction. A special electronic driver is used to control the new motor with electric stepper indexers and standard motion control cards. The motor accepts open-loop step operation as well as closed-loop control with position feedback from the enclosed sensor. A special control feature is implemented to adapt classic control algorithms to the new motor, and is experimentally validated. The speed performance of the motor degrades with the length of the pneumatic hoses between the distributor and motor. Experimental results are presented to reveal this behavior and set the expectation level. Nevertheless, the stepper achieves easily controllable precise motion unlike other pneumatic motors. The motor was designed to be compatible with magnetic resonance medical imaging equipment, for actuating an image-guided intervention robot, for medical applications. For this reason, the motors were entirely made of nonmagnetic and dielectric materials such as plastics, ceramics, and rubbers. Encoding was performed with fiber optics, so that the motors are electricity free, exclusively using pressure and light. PneuStep is readily applicable to other pneumatic or hydraulic precision-motion applications. PMID:21528106

  3. A New Type of Motor: Pneumatic Step Motor.

    PubMed

    Stoianovici, Dan; Patriciu, Alexandru; Petrisor, Doru; Mazilu, Dumitru; Kavoussi, Louis

    2007-02-01

    This paper presents a new type of pneumatic motor, a pneumatic step motor (PneuStep). Directional rotary motion of discrete displacement is achieved by sequentially pressurizing the three ports of the motor. Pulsed pressure waves are generated by a remote pneumatic distributor. The motor assembly includes a motor, gearhead, and incremental position encoder in a compact, central bore construction. A special electronic driver is used to control the new motor with electric stepper indexers and standard motion control cards. The motor accepts open-loop step operation as well as closed-loop control with position feedback from the enclosed sensor. A special control feature is implemented to adapt classic control algorithms to the new motor, and is experimentally validated. The speed performance of the motor degrades with the length of the pneumatic hoses between the distributor and motor. Experimental results are presented to reveal this behavior and set the expectation level. Nevertheless, the stepper achieves easily controllable precise motion unlike other pneumatic motors. The motor was designed to be compatible with magnetic resonance medical imaging equipment, for actuating an image-guided intervention robot, for medical applications. For this reason, the motors were entirely made of nonmagnetic and dielectric materials such as plastics, ceramics, and rubbers. Encoding was performed with fiber optics, so that the motors are electricity free, exclusively using pressure and light. PneuStep is readily applicable to other pneumatic or hydraulic precision-motion applications. PMID:21528106

  4. Is There a Relationship between Restricted, Repetitive, Stereotyped Behaviors and Interests and Abnormal Sensory Response in Children with Autism Spectrum Disorders?

    ERIC Educational Resources Information Center

    Gabriels, Robin L.; Agnew, John A.; Miller, Lucy Jane; Gralla, Jane; Pan, Zhaoxing; Goldson, Edward; Ledbetter, James C.; Dinkins, Juliet P.; Hooks, Elizabeth

    2008-01-01

    This study examined the relation between restricted, repetitive, and stereotyped behaviors and interests (RBs) and sensory responses in a group of 70 children and adolescents diagnosed with an autism spectrum disorder (ASD). Caregivers completed the Repetitive Behavior Scale-Revised (RBS-R) and the Sensory Profile. Controlling for IQ and age,…

  5. Computational approaches to motor control

    PubMed Central

    Flash, Tamar; Sejnowski, Terrence J

    2010-01-01

    New concepts and computational models that integrate behavioral and neurophysiological observations have addressed several of the most fundamental long-standing problems in motor control. These problems include the selection of particular trajectories among the large number of possibilities, the solution of inverse kinematics and dynamics problems, motor adaptation and the learning of sequential behaviors. PMID:11741014

  6. Translating working memory into action: behavioral and neural evidence for using motor representations in encoding visuo-spatial sequences.

    PubMed

    Langner, Robert; Sternkopf, Melanie A; Kellermann, Tanja S; Grefkes, Christian; Kurth, Florian; Schneider, Frank; Zilles, Karl; Eickhoff, Simon B

    2014-07-01

    The neurobiological organization of action-oriented working memory is not well understood. To elucidate the neural correlates of translating visuo-spatial stimulus sequences into delayed (memory-guided) sequential actions, we measured brain activity using functional magnetic resonance imaging while participants encoded sequences of four to seven dots appearing on fingers of a left or right schematic hand. After variable delays, sequences were to be reproduced with the corresponding fingers. Recall became less accurate with longer sequences and was initiated faster after long delays. Across both hands, encoding and recall activated bilateral prefrontal, premotor, superior and inferior parietal regions as well as the basal ganglia, whereas hand-specific activity was found (albeit to a lesser degree during encoding) in contralateral premotor, sensorimotor, and superior parietal cortex. Activation differences after long versus short delays were restricted to motor-related regions, indicating that rehearsal during long delays might have facilitated the conversion of the memorandum into concrete motor programs at recall. Furthermore, basal ganglia activity during encoding selectively predicted correct recall. Taken together, the results suggest that to-be-reproduced visuo-spatial sequences are encoded as prospective action representations (motor intentions), possibly in addition to retrospective sensory codes. Overall, our study supports and extends multi-component models of working memory, highlighting the notion that sensory input can be coded in multiple ways depending on what the memorandum is to be used for. PMID:24222405

  7. Motor dysfunction within the schizophrenia-spectrum: A dimensional step towards an underappreciated domain.

    PubMed

    Hirjak, Dusan; Thomann, Philipp A; Kubera, Katharina M; Wolf, Nadine D; Sambataro, Fabio; Wolf, Robert C

    2015-12-01

    At the beginning of the 20th century, genuine motor abnormalities (GMA) were considered to be intricately linked to schizophrenia. Subsequently, however, GMA have been increasingly regarded as unspecific transdiagnostic phenomena or related to side effects of antipsychotic treatment. Despite possible medication confounds, within the schizophrenia spectrum GMA have been categorized into three broad categories, i.e. neurological soft signs, abnormal involuntary movements and catatonia. Schizophrenia patients show a substantial overlap across a broad range of distinct motor signs and symptoms suggesting a prominent involvement of the motor system in disease pathophysiology. There have been several attempts to increase reliability and validity in diagnosing schizophrenia based on behavior and neurobiology, yet relatively little attention has been paid to the motor domain in the past. Nevertheless, accumulating neuroscientific evidence suggests the possibility of a motor endophenotype in schizophrenia, and that GMA could represent a specific dimension within the schizophrenia-spectrum. Here, we review current neuroimaging research on GMA in schizophrenia with an emphasis on distinct and common mechanisms of brain dysfunction. Based on a dimensional approach we show that multimodal neuroimaging combined with fine-grained clinical examination can result in a comprehensive characterization of structural and functional brain changes that are presumed to underlie core GMA in schizophrenia. We discuss the possibility of a distinct motor domain, together with its implications for future research. Investigating GMA by means of multimodal neuroimaging can essentially contribute at identifying novel and biologically reliable phenotypes in psychiatry. PMID:26547881

  8. The importance of measurement precision and behavioral homologies in evaluating the behavioral consequences of fetal-ethanol exposure: commentary on Williams and colleagues ("Sensory-motor deficits in children with fetal alcohol spectrum disorder assessed using a robotic virtual reality platform").

    PubMed

    Hamilton, Derek A

    2014-01-01

    The recent study by Willams and colleagues utilized a novel robotic virtual reality measurement system to measure sensory-motor processing deficits in children with fetal alcohol spectrum disorders (FASDs). This system and the precise quantitation of distinct constituent behavioral processes may hold considerable utility and importance for the study of FASD-related motor deficits, their neural bases, and translational research efforts using homologous behavioral approaches in animal and human studies.. PMID:24299062

  9. In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice

    PubMed Central

    Sano, Kazuhiro; Isobe, Tomohiko; Yang, Jiaxin; Win-Shwe, Tin-Tin; Yoshikane, Mitsuha; Nakayama, Shoji F.; Kawashima, Takaharu; Suzuki, Go; Hashimoto, Shunji; Nohara, Keiko; Tohyama, Chiharu; Maekawa, Fumihiko

    2016-01-01

    Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID:27375407

  10. In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice.

    PubMed

    Sano, Kazuhiro; Isobe, Tomohiko; Yang, Jiaxin; Win-Shwe, Tin-Tin; Yoshikane, Mitsuha; Nakayama, Shoji F; Kawashima, Takaharu; Suzuki, Go; Hashimoto, Shunji; Nohara, Keiko; Tohyama, Chiharu; Maekawa, Fumihiko

    2016-01-01

    Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID:27375407

  11. Continuous exposure to glial cell line-derived neurotrophic factor to mature dopaminergic transplants impairs the graft's ability to improve spontaneous motor behavior in parkinsonian rats.

    PubMed

    Winkler, C; Georgievska, B; Carlsson, T; Lacar, B; Kirik, D

    2006-08-11

    Functional recovery following intrastriatal transplantation of fetal dopaminergic neurons in animal models of Parkinson's disease is, at least in part, dependent on the number of surviving dopaminergic neurons and the degree of graft-derived dopaminergic reinnervation of the host striatum. In the present study, we analyzed whether continuous exposure of glial cell line-derived neurotrophic factor (GDNF) to mature dopaminergic grafts could further boost the functional outcome of widespread intrastriatal dopaminergic grafts. Rats with dopamine-denervating lesions received multiple intrastriatal transplants of fetal dopaminergic cells and graft-induced behavioral effects were analyzed in drug-induced and spontaneous motor behaviors. At three months after grafting, animals received intrastriatal injections of recombinant lentiviral vectors encoding for either human GDNF or the green fluorescent protein. Continuous exposure of GDNF to the grafts did not boost the functional recovery beyond what was observed in the control animals. Rather, in some of the spontaneous motor behaviors, animals in the GDNF-group showed deterioration as compared with control animals, and this negative effect of GDNF was associated with a down-regulation of the tyrosine hydroxylase enzyme. Based on these and our earlier results, we propose that intrastriatal administration of GDNF at the time of or shortly after grafting is highly effective in initially promoting the cell survival and fiber outgrowth from the grafts. However, once the grafts are mature, GDNF's ability to boost dopaminergic neurotransmission follows the same dynamics as for the native nigral dopaminergic neurons, which appears to be dependent on the concentration of GDNF. Since rather low doses of glial cell line-derived neurotrophic factor at nanogram levels appear to saturate these effects, it may be critical to adjust GDNF levels using tightly regulated gene expression systems. PMID:16697115

  12. Neurobehavioral phenotyping of Gαq knockout mice reveals impairments in motor functions and spatial working memory without changes in anxiety or behavioral despair

    PubMed Central

    Frederick, Aliya L.; Saborido, Tommy P.; Stanwood, Gregg D.

    2012-01-01

    Many neurotransmitters, hormones, and sensory stimuli elicit their cellular responses through the targeted activation of receptors coupled to the Gαq family of heterotrimeric G proteins. Nevertheless, we still understand little about the consequences of loss of this signaling activity on brain function. We therefore examined the effects of genetic inactivation of Gnaq, the gene that encode for Gαq, on responsiveness in a battery of behavioral tests in order to assess the contribution of Gαq signaling capacity in the brain circuits mediating expression of affective behaviors (anxiety and behavioral despair), spatial working memory, and locomotor output (coordination, strength, spontaneous activity, and drug-induced responses). First, we replicated and extended findings showing clear motor deficits in Gαq knockout mice as assessed on an accelerating rotarod and the inverted screen test. We then assessed the contribution of the basal ganglia motor loops to these impairments, using open field testing and analysis of drug-induced locomotor responses to the psychostimulant cocaine, the benzazepine D1 receptor agonists SKF83822 and SKF83959, and the NMDA receptor antagonist MK-801. We observed significant increases in drug-induced locomotor activity in Gαq knockout mice from the dopaminergic agonists but not MK-801, indicating that basal ganglia locomotor circuitry is largely intact in the absence of Gαq. Additionally, we observed normal phenotypes in both the elevated zero maze and the forced swim test indicating that anxiety and depression-related circuitry appears to be largely intact after loss of Gnaq expression. Lastly, use of the Y-maze revealed spatial memory deficits in Gαq knockout mice, indicating that receptors signaling through Gαq are necessary in these circuits for proficiency in this task. PMID:22723772

  13. Gangliosides attenuate stress-induced changes on body weight, motor activity and on the behavioral response to 5-methoxy-N,N-dimethyltryptamine.

    PubMed

    Cancela, L M; Volosin, M; Molina, V A

    1996-01-01

    The major goal of this study was to evaluate the influence of gangliosides (GANG) treatment on the onset of adaptive changes and the sequelae induced by stress exposure. With this purpose, the behavioral response to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 5 mg/kg, IP) and motor activity were evaluated in rats previously submitted either to a single restraint session (2 h) or to a daily restraint event for 3 consecutive days, combined or not to GANG administration (30 mg/kg IP). GANG was always injected 2 h before stress exposure. In addition, differences in body weights were recorded throughout the experiments. A similar behavioral response after 5-MeODMT was observed between saline (SAL) and GANG unstressed rats. Exposure to one or three restraint sessions did not modify the behavioral response to 5-MeODMT, whereas the association of GANG and stress during 3 consecutive days enhanced forepaw treading and hindlimb abduction. SAL-treated animals submitted to a single or to three stressful stimuli showed reduced locomotion and rearing. The combination of GANG and stress for 3 days, but not after a unique association, reversed the decrease on motor activity induced by the aversive experience. The decrease of body weights produced by one or three stress sessions was recovered only in animals treated with GANG and stress for 3 days. These findings suggest that GANG may accelerate the onset of adaptive changes on 5-HT1 sites and attenuate certain sequelae induced by previous stress experience. PMID:8724427

  14. Dyspraxia in autism: association with motor, social, and communicative deficits.

    PubMed

    Dziuk, M A; Gidley Larson, J C; Apostu, A; Mahone, E M; Denckla, M B; Mostofsky, S H

    2007-10-01

    Impaired performance of skilled gestures, referred to as dyspraxia, is consistently reported in children with autism; however, its neurological basis is not well understood. Basic motor skill deficits are also observed in children with autism and it is unclear whether dyspraxia observed in children with autism can be accounted for by problems with motor skills. Forty-seven high-functioning children with an autism spectrum disorder (ASD), autism, or Asperger syndrome (43 males, four females; mean age 10y 7m [SD 1y 10m], mean Full-scale IQ (FSIQ) 99.4 [SD 15.9]), and 47 typically developing (TD) controls (41 males, six females; mean age 10y 6m [SD 1y 5m], mean FSIQ 113.8 [SD 12.3], age range 8-4y) completed: (1) the Physical and Neurological Assessment of Subtle Signs, an examination of basic motor skills standardized for children, and (2) a praxis examination that included gestures to command, to imitation, and with tool-use. Hierarchical regression was used to examine the association between basic motor skill performance (i.e. times to complete repetitive limb movements) and praxis performance (total praxis errors). After controlling for age and IQ, basic motor skill was a significant predictor of performance on praxis examination. Nevertheless, the ASD group continued to show significantly poorer praxis than controls after accounting for basic motor skill. Furthermore, praxis performance was a strong predictor of the defining features of autism, measured using the Autism Diagnostic Observation Schedule, and this correlation remained significant after accounting for basic motor skill. Results indicate that dyspraxia in autism cannot be entirely accounted for by impairments in basic motor skills, suggesting the presence of additional contributory factors. Furthermore, praxis in children with autism is strongly correlated with the social, communicative, and behavioral impairments that define the disorder, suggesting that dyspraxia may be a core feature of autism or a

  15. Motor mapping in cerebral palsy.

    PubMed

    Wittenberg, George F

    2009-10-01

    The measurement of motor deficits in individuals with cerebral palsy (CP) has been largely based on clinical criteria. Yet functional imaging and non-invasive stimulation methods provide a means to measure directly abnormalities of the motor system. The size and location of muscles and movement representations can be determined with transcranial magnetic stimulation (TMS) and functional magnetics resonance imaging. Thus the homunculus can be individually mapped in children with CP. Because size of representation within the homunculus relates to quality of motor control, measurement of the distance between body parts provides a metric that may be useful in classifying deficits. Bilateral motor control in one hemisphere, while normal in neonates, persists variably in CP, providing another physiological metric. In this study, we used TMS to measure hand and ankle representations in a convenience sample of children with spastic CP. Overlapping thumb and ankle maps were found in children with both hemiplegia and diplegia, and these maps may be from either side of the body. While more participants are required to make conclusions about disability and compression/bilaterality of the homunculus, it appears as if TMS-derived metrics relate to motor abnormalities. These abnormal motor maps also are a therapeutic target, as stimulation methods are being developed as adjuncts to physical means of rehabilitation. PMID:19740221

  16. Influence of chronic dopamine transporter inhibition by RTI-336 on motor behavior, sleep, and hormone levels in rhesus monkeys.

    PubMed

    Andersen, Monica L; Sawyer, Eileen K; Carroll, F Ivy; Howell, Leonard L

    2012-04-01

    Dopamine transporter (DAT) inhibitors have been developed as a promising treatment approach for cocaine dependence. However, the stimulant effects of DAT inhibitors have the potential to disrupt sleep patterns, and the influence of long-term treatment on dopamine neurochemistry is still unknown. The objectives of this study were to (1) explore the stimulant-related effects of chronic DAT inhibitor (RTI-336) treatment on motor activity and sleep-like measures in male rhesus monkeys (Macaca mulatta; n = 4) and (2) to determine the effect of drug treatment on prolactin and cortisol levels. Subjects were fitted with a collar-mounted activity monitor to evaluate their motor activity, with 4 days of baseline recording preceding 21 days of daily saline or RTI-336 (1 mg/kg/day; intramuscular) injections. Blood samples were collected immediately prior to and following chronic treatment to assess hormone levels. RTI-336 produced a significant increase in locomotor activity at the end of the daytime period compared to saline administration. During the 3-week treatment period, sleep efficiency was decreased and the fragmentation index and latency to sleep onset were significantly increased. Hormone levels were not changed throughout the study. Chronic treatment with RTI-336 has a mild but significant stimulant effect, as evidenced by the significant increase in activity during the evening period which may cause minor disruptions in sleep measures. PMID:22023668

  17. Blockage of vibrissae afferents: I. Motor effects.

    PubMed

    Prchal, A; Albarracín, A L; Décima, E E

    2004-02-01

    In the past, it has been proposed that the rat vibrissae play an important role in other hand, postural abnormalities, muscle tone decreases and hypomotility after sensory organ destructions were proposed as evidence supporting the "level setting" or "tonic" hypothesis. This hypothesis postulates that afferent activity, besides its well know transductive functions, sets the excitability state of the central nervous system. We thought the vibrissal system to be a good model to dissect these two postulated roles because vibrissae trimming would annul the transductive function without affecting the integrity of nerve activity. Thus we compare the effects of trimming the whiskers with blocking the vibrissal afferent nerves on two types of motor behavior: activity in an open field and walking over a rope connecting two elevated platforms. We found that only vibrissal afferent blockage (both nerve section and local anaesthesia) produced severe failures in the motor performances studied. These effects could not be fully explained by the abolition of the vibrissae as a sensory modality because cutting the whiskers did not significantly affect the motor performance. These data are discussed in reference to a tonic or general excitatory function of sensory inputs upon the central nervous system. PMID:15143620

  18. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  19. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... from many different conditions. Specific diseases can affect tooth shape, tooth color, time of appearance, or absence ...

  20. Pilot randomized trial demonstrating reversal of obesity-related abnormalities in reward system responsivity to food cues with a behavioral intervention

    PubMed Central

    Deckersbach, T; Das, S K; Urban, L E; Salinardi, T; Batra, P; Rodman, A M; Arulpragasam, A R; Dougherty, D D; Roberts, S B

    2014-01-01

    Objectives: Obesity is associated with hyperactivation of the reward system for high-calorie (HC) versus low-calorie (LC) food cues, which encourages unhealthy food selection and overeating. However, the extent to which this hyperactivation can be reversed is uncertain, and to date there has been no demonstration of changes by behavioral intervention. Subjects and methods: We used functional magnetic resonance imaging to measure changes in activation of the striatum for food images at baseline and 6 months in a pilot study of 13 overweight or obese adults randomized to a control group or a novel weight-loss intervention. Results: Compared to controls, intervention participants achieved significant weight loss (−6.3±1.0 kg versus +2.1±1.1 kg, P<0.001) and had increased activation for LC food images with a composition consistent with that recommended in the behavioral intervention at 6 months versus baseline in the right ventral putamen (P=0.04), decreased activation for HC images of typically consumed foods in the left dorsal putamen (P=0.01). There was also a large significant shift in relative activation favoring LC versus HC foods in both regions (P<0.04). Conclusions: This study provides the first demonstration of a positive shift in activation of the reward system toward healthy versus unhealthy food cues in a behavioral intervention, suggesting new avenues to enhance behavioral treatments of obesity. PMID:25177910

  1. Abnormal behavior of threshold voltage shift in bias-stressed a-Si:H thin film transistor under extremely high intensity illumination.

    PubMed

    Han, Sang Youn; Park, Kyung Tea; Kim, Cheolkyu; Jeon, Sanghyun; Yang, Sung-Hoon; Kong, Hyang-Shik

    2015-07-22

    We report on the unusual behavior of threshold voltage turnaround in a hydrogenated amorphous silicon (a-Si:H) thin film transistor (TFT) when biased under extremely high intensity illumination. The threshold voltage shift changes from negative to positive gate bias direction after ∼30 min of bias stress even when the negative gate bias stress is applied under high intensity illumination (>400 000 Cd/cm(2)), which has not been observed in low intensity (∼6000 Cd/cm(2)). This behavior is more pronounced in a low work function gate metal structure (Al: 4.1-4.3 eV), compared to the high work function of Cu (4.5-5.1 eV). Also this is mainly observed in shorter wavelength of high photon energy illumination. However, this behavior is effectively prohibited by embedding the high energy band gap (∼8.6 eV) of SiOx in the gate insulator layer. These imply that this behavior could be originated from the injection of electrons from gate electrode, transported and trapped in the electron trap sites of the SiNx/a-Si:H interface, which causes the shift of threshold voltage toward positive gate bias direction. The results reported here can be applicable to the large-sized outdoor displays which are usually exposed to the extremely high intensity illumination. PMID:26132513

  2. Sensory representation abnormalities that parallel focal hand dystonia in a primate model

    PubMed Central

    Blake, David T.; Byl, Nancy N.; Cheung, Steven; Bedenbaugh, Purvis; Nagarajan, Srikantan; Lamb, Michelle; Merzenich, Michael

    2010-01-01

    In our hypothesis of focal dystonia, attended repetitive behaviors generate aberrant sensory representations. Those aberrant representations interfere with motor control. Abnormal motor control strengthens sensory abnormalities. The positive feedback loop reinforces the dystonic condition. Previous studies of primates with focal hand dystonia have demonstrated multi-digit or hairy-glabrous responses at single sites in area 3b, receptive fields that average ten times larger than normal, and high receptive field overlap as a function of horizontal distance. In this study, we strengthen and elaborate these findings. One animal was implanted with an array of micro-electrodes that spanned the border between the face and digits. After the animal developed hand dystonia, responses in the initial hand representation increasingly responded to low threshold stimulation of the face in a columnar substitution. The hand-face border that is normally sharp became patchy and smeared over one millimeter of cortex within six weeks. Two more trained animals developed a focal hand dystonia variable in severity across the hand. Receptive field size, presence of multi-digit or hairy-glabrous receptive fields, and columnar overlap covaried with the animal’s ability to use specific digits. A fourth animal performed the same behaviors without developing dystonia. Many of its physiological measures were similar to the dystonic animals, but receptive field overlap functions were minimally abnormal, and no sites shared response properties that are normally segregated such as hairy-glabrous combined fields, or multi-digit fields. Thalamic mapping demonstrated proportionate levels of abnormality in thalamic representations as was found in cortical representations. PMID:12590836

  3. Pre-Motor Parkinson’s Disease: Concepts and Definitions

    PubMed Central

    Siderowf, Andrew; Lang, Anthony E.

    2012-01-01

    Parkinson’s disease (PD) has a prodromal phase during which non-motor clinical features as well as physiological abnormalities may be present. These pre-motor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta (SNc) involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies, like dopamine transporter imaging, currently offer the highest degree of accuracy for identifying pre-motor PD, but they are expensive as screening tools and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a pre-screening test, such as olfactory testing. This two-step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high-risk populations (e.g. patients with rapid eye movement behavior disorder (RBD) or LRRK2 mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of pre-clinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large-scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease modifying therapy even before the development of evidence for dopamine deficiency. PMID:22508279

  4. Abnormal Ocular Movement With Executive Dysfunction and Personality Change in Subject With Thalamic Infarction: A Case Report

    PubMed Central

    Kim, Ee Jin; Kim, Myeong Ok; Kim, Chang Hwan; Joa, Kyung Lim

    2015-01-01

    The thalamus, located between the cerebrum and midbrain, is a nuclear complex connected to the cerebral cortex that influences motor skills, cognition, and mood. The thalamus is composed of 50-60 nuclei and can be divided into four areas according to vascular supply. In addition, it can be divided into five areas according to function. Many studies have reported on a thalamic infarction causing motor or sensory changes, but few have reported on behavioral and executive aspects of the ophthalmoplegia of the thalamus. This study reports a rare case of a paramedian thalamus infarction affecting the dorsomedial area of the thalamus, manifesting as oculomotor nerve palsy, an abnormal behavioral change, and executive dysfunction. This special case is presented with a review of the anatomical basis and function of the thalamus. PMID:26798620

  5. Abnormal interhemispheric connectivity in male psychopathic offenders

    PubMed Central

    Hoppenbrouwers, Sylco S.; De Jesus, Danilo R.; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J.; Schutter, Dennis J.L.G.

    2014-01-01

    Background Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. Methods We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. Results We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. Limitations The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. Conclusion To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders. PMID:23937798

  6. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  7. Promoting Adaptive Behavior in Persons with Acquired Brain Injury, Extensive Motor and Communication Disabilities, and Consciousness Disorders

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Belardinelli, Marta Olivetti; Buonocunto, Francesca; Sacco, Valentina; Navarro, Jorge; Lanzilotti, Crocifissa; De Tommaso, Marina; Megna, Marisa; Badagliacca, Francesco

    2012-01-01

    These two studies extended the evidence on the use of technology-based intervention packages to promote adaptive behavior in persons with acquired brain injury and multiple disabilities. Study I involved five participants in a minimally conscious state who were provided with intervention packages based on specific arrangements of optic, tilt, or…

  8. Creep behavior of thin laminates of iron-cobalt alloys for use in switched reluctance motors and generators

    NASA Astrophysics Data System (ADS)

    Fingers, Richard Todd

    The United States Air Force is in the process of developing magnetic bearings as well as an aircraft Integrated Power Unit and an Internal Starter/Generator for main propulsion engines. These developments are the driving force behind a new emphasis on high temperature, high strength magnetic materials for power applications. Analytical work, utilizing elasticity theory, in conjunction with design requirements, indicates a need for magnetic materials to have strengths in excess of 80 ksi up to about 1000sp°F. It is this combination of desired material characteristics that is the motivation for this effort to measure, model, and predict the creep behavior of such advanced magnetic materials. Hipercosp°ler Alloy 50HS, manufactured by Carpenter Technology Corporation, is one of the leading candidates for application and is studied in this effort by subjecting mechanical test specimens to a battery of tensile and creep tests. The tensile tests provide stress versus strain behaviors that clearly indicate: a yield point, a heterogeneous deformation described as Luders elongation, the Portevin-LeChatelier effect at elevated temperatures, and, most often, a section of homogeneous deformation that concluded with necking and fracture. Creep testing indicated two distinct types of behavior. The first was a traditional response with primary, secondary and tertiary stages, while the second type could be characterized by an abrupt increase in strain rate that acted as a transition from one steady state behavior to another. This second linear region was then followed by the tertiary stage. The relationship between the tensile response and the creep responses is discussed. Analyses of the mechanical behavior includes double linear regression of empirically modeled data, scanning electron microscopy for microstructural investigations, isochronous stress-strain relations, and constant strain rate testing to relate the tensile and creep test parameters. Also, elastic and creep

  9. Repeated stress-induced expression pattern alterations of the hippocampal chloride transporters KCC2 and NKCC1 associated with behavioral abnormalities in female mice.

    PubMed

    Tsukahara, Takao; Masuhara, Masaaki; Iwai, Haruki; Sonomura, Takahiro; Sato, Tomoaki

    2015-09-11

    The balance of cation-chloride co-transporters, particularly KCC2 and NKCC1, is critical for GABAergic inhibitory signaling. However, KCC2/NKCC1 balance is disrupted in many neurodegenerative diseases. Moreover, correlations between chronic stress, KCC2 and NKCC1 in the hippocampus remain poorly understood. Despite the fact that emotional disorders in humans are far more prevalent in women, there have been relatively few studies about female subjects. Here we investigated behaviors and expression patterns of KCC2 and NKCC1 in the hippocampi of female mice under chronic stress. Repeated stress (RS) was induced in experimental mice by repeated forced water administration. Then, expression patterns of GABAergic signaling molecules were identified by immunohistochemical analysis and performance was assessed using several behavioral tests. The results of semi-quantitative analysis showed that RS decreased KCC2 expression and increased NKCC1 expression in membranes of granular and pyramidal cells in the hippocampus. The novel object recognition (NOR) test and sociability test revealed that RS induced cognitive and sociability deficits, whereas RS increased the time spent in the open arms of the elevated plus maze test and induced attention deficits in other tests. In summary, RS induced alterations in membrane KCC2/NKCC1 balance in the hippocampus of female mice, which may contribute to GABAergic disinhibition associated with cognitional, sociability and attention deficits. PMID:26239662

  10. Motor Priming in Neurorehabilitation

    PubMed Central

    Stoykov, Mary Ellen; Madhavan, Sangeetha

    2014-01-01

    Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few are practical for the current clinical environment, and the optimal priming modalities for specific clinical presentations are not known. Accordingly, developing an understanding of the various types of motor priming paradigms and their underlying neural mechanisms is an important step for therapists in neurorehabilitation. Most importantly, an understanding of the methods and their underlying mechanisms is essential for optimizing rehabilitation outcomes. The future of neurorehabilitation is likely to include these priming methods, which are delivered prior to or in conjunction with primary neurorehabilitation therapies. In this Special Interest article we discuss those priming paradigms that are supported by the greatest amount of evidence including: (i) stimulation-based priming, (ii) motor imagery and action observation, (iii) sensory priming, (iv) movement-based priming, and (v) pharmacological priming. PMID:25415551

  11. Unidirectional startle responses and disrupted left-right coordination of motor behaviors in robo3 mutant zebrafish

    PubMed Central

    Burgess, Harold A.; Johnson, Stephen L.; Granato, Michael

    2009-01-01

    The Roundabout (Robo) family of receptors and their Slit ligands play well-established roles in axonal guidance, including in humans where horizontal gaze palsy with progressive scoliosis (HGPPS) is caused by mutations in the robo3 gene. While significant progress has been made towards understanding the mechanism by which Robo receptors establish commissural projections in the central nervous system, less is known about how these projections contribute to neural circuits mediating behavior. Here we report cloning of the zebrafish behavioral mutant twitch twice and show that twitch twice encodes robo3. We demonstrate that in mutant hindbrains the axons of an identified pair of neurons, the Mauthner cells, fail to cross the midline. The Mauthner neurons are essential for the startle response, and in twitch twice/robo3 mutants misguidance of the Mauthner axons results in a unidirectional startle response. Moreover, we show that twitch twice mutants exhibit normal visual acuity but display defects in horizontal eye movements, suggesting a specific and critical role for twitch twice/robo3 in sensory guided behavior. PMID:19496826

  12. Retention of Motor Skills: Review.

    ERIC Educational Resources Information Center

    Schendel, J. D.; And Others

    A summary of an extensive literature survey deals with the variables known or suspected to affect the retention of learned motor behaviors over lengthy no-practice intervals. Emphasis was given to research conducted by or for the military. The variables that may affect the retention of motor skills were dichotomized into task variables and…

  13. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  14. Abnormal Uterine Bleeding

    MedlinePlus

    ... Abnormal uterine bleeding is any bleeding from the uterus (through your vagina) other than your normal monthly ... or fibroids (small and large growths) in the uterus can also cause bleeding. Rarely, a thyroid problem, ...

  15. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... as cancer of the uterus, cervix, or vagina • Polycystic ovary syndrome How is abnormal bleeding diagnosed? Your health care ... before the fetus can survive outside the uterus. Polycystic Ovary Syndrome: A condition characterized by two of the following ...

  16. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior.

    PubMed

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza; Strandgren, Charlotte; Pernold, Karin; Richard, Thibaud J C; Van Leeuwen, Fred W; Dantuma, Nico P; Damberg, Peter; Hultenby, Kjell; Ulfhake, Brun; Mugnaini, Enrico; Rozell, Björn; Eriksson, Maria

    2015-03-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS mutation in brain, skin, bone and heart to investigate how the mutation affects these organs. Ultrastructural analysis of neuronal nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with multiple lobulations and irregular extensions. Despite severe distortions in the nuclei of hippocampal neurons of HGPS animals, there were only negligible changes in gene expression after 63 weeks of transgenic expression. Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology. Our results suggest that certain tissues are protected from functional deleterious effects of progerin. PMID:25343989

  17. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    PubMed Central

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza; Strandgren, Charlotte; Pernold, Karin; Richard, Thibaud J. C.; Van Leeuwen, Fred W.; Dantuma, Nico P.; Damberg, Peter; Hultenby, Kjell; Ulfhake, Brun; Mugnaini, Enrico; Rozell, Björn; Eriksson, Maria

    2015-01-01

    Hutchinson–Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS mutation in brain, skin, bone and heart to investigate how the mutation affects these organs. Ultrastructural analysis of neuronal nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with multiple lobulations and irregular extensions. Despite severe distortions in the nuclei of hippocampal neurons of HGPS animals, there were only negligible changes in gene expression after 63 weeks of transgenic expression. Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology. Our results suggest that certain tissues are protected from functional deleterious effects of progerin. PMID:25343989

  18. Quantitative Evaluation of 3D Mouse Behaviors and Motor Function in the Open-Field after Spinal Cord Injury Using Markerless Motion Tracking

    PubMed Central

    Sheets, Alison L.; Lai, Po-Lun; Fisher, Lesley C.; Basso, D. Michele

    2013-01-01

    Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI). Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study’s goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches. Three-dimensional movements of eight naïve, five mild, five moderate, and four severe SCI mice were recorded using 10 cameras (100 Hz). Background subtraction was used in each video frame to identify the animal’s silhouette, and the 3D shape at each time was reconstructed using shape-from-silhouette. The reconstructed volume was divided into front and back halves using k-means clustering. The animal’s front Center of Volume (CoV) height and whole-body CoV speed were calculated and used to automatically classify animal behaviors including directed locomotion, exploratory locomotion, meandering, standing, and rearing. More detailed analyses of CoV height, speed, and lateral deviation during directed locomotion revealed behavioral differences and functional impairments in animals with mild, moderate, and severe SCI when compared with naïve animals. Naïve animals displayed the widest variety of behaviors including rearing and crossing the center of the open-field, the fastest speeds, and tallest rear CoV heights. SCI reduced the range of behaviors, and decreased speed (r = .70 p<.005) and rear CoV height (r = .65 p<.01) were significantly correlated with greater lesion size. This markerless tracking approach is a first step toward fundamentally changing how rodent movement studies are conducted. By providing scientists with sensitive, quantitative measurement

  19. Motor Starters

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The power factor controller (PFC) was invented by a NASA engineer. It matches voltage with a motor's actual need by sensing shifts in the relationship between voltage and current flow. With the device, power can be trimmed as much as 65%. Intellinet adopted this technology and designed "soft start" and "load-responsive" control modes to start engines gradually and recycle voltage without reducing motor speed. Other features are lower motor heat and faster fault identification.

  20. Motor syndromes.

    PubMed

    Corea, Francesco; Micheli, Sara

    2012-01-01

    Motor disturbances alone or associated with other focal deficits are the most common symptoms suggesting a neurovascular event. An appropriate clinical assessment of these signs and symptoms may help physicians to better diagnose and to both better treat and predict outcome. In this paper the main clinical features of motor deficit are described together with other motor-related events such as ataxia and movement disturbances. PMID:22377850

  1. Many Faces of Parkinson’s Disease: Non-Motor Symptoms of Parkinson’s Disease

    PubMed Central

    Lee, Hye Mi; Koh, Seong-Beom

    2015-01-01

    Parkinson’s disease (PD) is a multi-systemic disorder that is characterized by a combination of motor and non-motor symptoms (NMS). The dopaminergic neurodegeneration of PD is involved in the genesis of NMS, but other conditions and side effects of levodopa are also associated with NMS. NMS can develop at all stage of PD and rapid eyeball movement sleep behavior disorder (RBD), constipation, depression, and olfactory dysfunction are considered prodromal signs of PD. Many NMS related with motor deficits and cognitive dysfunction. Some NMS including olfactory dysfunction, RBD and abnormal stereopsis are associated with presence of other NMS of PD. In addition, several NMS can be helpful to differentiate between idiopathic PD and other parkinsonian disorders. Early recognition and management of NMS in PD patients is important for preserving quality of life. PMID:26090081

  2. Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease.

    PubMed

    Santana, Maxwell B; Halje, Pär; Simplício, Hougelle; Richter, Ulrike; Freire, Marco Aurelio M; Petersson, Per; Fuentes, Romulo; Nicolelis, Miguel A L

    2014-11-19

    Although deep brain electrical stimulation can alleviate the motor symptoms of Parkinson disease (PD), just a small fraction of patients with PD can take advantage of this procedure due to its invasive nature. A significantly less invasive method--epidural spinal cord stimulation (SCS)--has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through SCS are unknown. Here, we show that SCS reproducibly alleviates motor deficits in a primate model of PD. Simultaneous neuronal recordings from multiple structures of the cortico-basal ganglia-thalamic loop in parkinsonian monkeys revealed abnormal highly synchronized neuronal activity within each of these structures and excessive functional coupling among them. SCS disrupted this pathological circuit behavior in a manner that mimics the effects caused by pharmacological dopamine replacement therapy or deep brain stimulation. These results suggest that SCS should be considered as an additional treatment option for patients with PD. PMID:25447740

  3. Neurobehavioral Abnormalities in the HIV-1 Transgenic Rat Do Not Correspond to Neuronal Hypometabolism on 18F-FDG-PET

    PubMed Central

    Papadakis, Georgios Z.; Muthusamy, Siva; Lee, Dianne E.; Ibrahim, Wael G.; Nair, Anand; Koziol, Deloris; Maric, Dragan; Hammoud, Dima A.

    2016-01-01

    Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era. PMID:27010205

  4. Neurobehavioral Abnormalities in the HIV-1 Transgenic Rat Do Not Correspond to Neuronal Hypometabolism on 18F-FDG-PET.

    PubMed

    Reid, William C; Casas, Rafael; Papadakis, Georgios Z; Muthusamy, Siva; Lee, Dianne E; Ibrahim, Wael G; Nair, Anand; Koziol, Deloris; Maric, Dragan; Hammoud, Dima A

    2016-01-01

    Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era. PMID:27010205

  5. 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

  6. Targeted mutations in the Na,K-ATPase α 2 isoform confer ouabain resistance and result in abnormal behavior in mice.

    PubMed

    Schaefer, Tori L; Lingrel, Jerry B; Moseley, Amy E; Vorhees, Charles V; Williams, Michael T

    2011-06-01

    Sodium and potassium-activated adenosine triphosphatases (Na,K-ATPase) are ubiquitous, participate in osmotic balance and membrane potential, and are composed of α, β, and γ subunits. The α subunit is required for the catalytic and transport properties of the enzyme and contains binding sites for cations, ATP, and digitalis-like compounds including ouabain. There are four known α isoforms; three that are expressed in the CNS in a regional and cell-specific manner. The α2 isoform is most commonly found in astrocytes, pyramidal cells of the hippocampus in adults, and developmentally in several other neuronal types. Ouabain-like compounds are thought to be produced endogenously in mammals, bind the Na,K-ATPase, and function as a stress-related hormone, however, the impact of the Na,K-ATPase ouabain binding site on neurobehavioral function is largely unknown. To determine if the ouabain binding site of the α2 isoform plays a physiological role in CNS function, we examined knock-in mice in which the normally ouabain-sensitive α2 isoform was made resistant (α2(R/R) ) while still retaining basal Na,K-ATPase enzymatic function. Egocentric learning (Cincinnati water maze) was impaired in adult α2(R/R) mice compared to wild type (WT) mice. They also exhibited decreased locomotor activity in a novel environment and increased responsiveness to a challenge with an indirect sympathomimetic agonist (methamphetamine) relative to WT mice. The α2(R/R) mice also demonstrated a blunted acoustic startle reflex and a failure to habituate to repeated acoustic stimuli. The α2(R/R) mice showed no evidence of altered anxiety (elevated zero maze) nor were they impaired in spatial learning or memory in the Morris water maze and neither group could learn in a large Morris maze. These results suggest that the ouabain binding site is involved in specific types of learning and the modulation of dopamine-mediated locomotor behavior. PMID:20936682

  7. Targeted Mutations in the Na,K-ATPase Alpha 2 Isoform Confer Ouabain Resistance and Result in Abnormal Behavior in Mice

    PubMed Central

    Schaefer, Tori L.; Lingrel, Jerry B; Moseley, Amy E.; Vorhees, Charles V.; Williams, Michael T.

    2011-01-01

    Sodium and potassium-activated adenosine triphosphatases (Na,K-ATPase) are ubiquitous, participate in osmotic balance and membrane potential, and are composed of α, β, and γ subunits. The α subunit is required for the catalytic and transport properties of the enzyme and contains binding sites for cations, ATP, and digitalis-like compounds including ouabain. There are four known α isoforms; three that are expressed in the CNS in a regional and cell-specific manner. The α2 isoform is most commonly found in astrocytes, pyramidal cells of the hippocampus in adults, and developmentally in several other neuronal types. Ouabain-like compounds are thought to be produced endogenously in mammals, bind the Na,K-ATPase, and function as a stress-related hormone, however, the impact of the Na,K-ATPase ouabain binding site on neurobehavioral function is largely unknown. To determine if the ouabain binding site of the α2 isoform plays a physiological role in CNS function, we examined knock-in mice in which the normally ouabain-sensitive α2 isoform was made resistant (α2R/R) while still retaining basal Na,K-ATPase enzymatic function. Egocentric learning (Cincinnati water maze) was impaired in adult α2R/R mice compared to wild type (WT) mice. They also exhibited decreased locomotor activity in a novel environment and increased responsiveness to a challenge with an indirect sympathomimetic agonist (methamphetamine) relative to WT mice. The α2R/R mice also demonstrated a blunted acoustic startle reflex and a failure to habituate to repeated acoustic stimuli. The α2R/R mice showed no evidence of altered anxiety (elevated zero maze) nor were they impaired in spatial learning or memory in the Morris water maze and neither group could learn in a large Morris maze. These results suggest that the ouabain binding site is involved in specific types of learning and the modulation of dopamine-mediated locomotor behavior. PMID:20936682

  8. Adults with Chromosome 18 Abnormalities.

    PubMed

    Soileau, Bridgette; Hasi, Minire; Sebold, Courtney; Hill, Annice; O'Donnell, Louise; Hale, Daniel E; Cody, Jannine D

    2015-08-01

    The identification of an underlying chromosome abnormality frequently marks the endpoint of a diagnostic odyssey. However, families are frequently left with more questions than answers as they consider their child's future. In the case of rare chromosome conditions, a lack of longitudinal data often makes it difficult to provide anticipatory guidance to these families. The objective of this study is to describe the lifespan, educational attainment, living situation, and behavioral phenotype of adults with chromosome 18 abnormalities. The Chromosome 18 Clinical Research Center has enrolled 483 individuals with one of the following conditions: 18q-, 18p-, Tetrasomy 18p, and Ring 18. As a part of the ongoing longitudinal study, we collect data on living arrangements, educational level attained, and employment status as well as data on executive functioning and behavioral skills on an annual basis. Within our cohort, 28 of the 483 participants have died, the majority of whom have deletions encompassing the TCF4 gene or who have unbalanced rearrangement involving other chromosomes. Data regarding the cause of and age at death are presented. We also report on the living situation, educational attainment, and behavioral phenotype of the 151 participants over the age of 18. In general, educational level is higher for people with all these conditions than implied by the early literature, including some that received post-high school education. In addition, some individuals are able to live independently, though at this point they represent a minority of patients. Data on executive function and behavioral phenotype are also presented. Taken together, these data provide insight into the long-term outcome for individuals with a chromosome 18 condition. This information is critical in counseling families on the range of potential outcomes for their child. PMID:25403900

  9. Muscle synergy patterns as physiological markers of motor cortical damage

    PubMed Central

    Cheung, Vincent C. K.; Turolla, Andrea; Agostini, Michela; Silvoni, Stefano; Bennis, Caoimhe; Kasi, Patrick; Paganoni, Sabrina; Bonato, Paolo; Bizzi, Emilio

    2012-01-01

    The experimental findings herein reported are aimed at gaining a perspective on the complex neural events that follow lesions of the motor cortical areas. Cortical damage, whether by trauma or stroke, interferes with the flow of descending signals to the modular interneuronal structures of the spinal cord. These spinal modules subserve normal motor behaviors by activating groups of muscles as individual units (muscle synergies). Damage to the motor cortical areas disrupts the orchestration of the modules, resulting in abnormal movements. To gain insights into this complex process, we recorded myoelectric signals from multiple upper-limb muscles in subjects with cortical lesions. We used a factorization algorithm to identify the muscle synergies. Our factorization analysis revealed, in a quantitative way, three distinct patterns of muscle coordination—including preservation, merging, and fractionation of muscle synergies—that reflect the multiple neural responses that occur after cortical damage. These patterns varied as a function of both the severity of functional impairment and the temporal distance from stroke onset. We think these muscle-synergy patterns can be used as physiological markers of the status of any patient with stroke or trauma, thereby guiding the development of different rehabilitation approaches, as well as future physiological experiments for a further understanding of postinjury mechanisms of motor control and recovery. PMID:22908288

  10. Reduced endplate currents underlie motor unit dysfunction in canine motor neuron disease.

    PubMed

    Rich, Mark M; Waldeck, Robert F; Cork, Linda C; Balice-Gordon, Rita J; Fyffe, Robert E W; Wang, Xueyong; Cope, Timothy C; Pinter, Martin J

    2002-12-01

    Hereditary canine spinal muscular atrophy (HCSMA) is an autosomal dominant degenerative disorder of motor neurons. In homozygous animals, motor units produce decreased force output and fail during repetitive activity. Previous studies suggest that decreased efficacy of neuromuscular transmission underlies these abnormalities. To examine this, we recorded muscle fiber endplate currents (EPCs) and found reduced amplitudes and increased failures during nerve stimulation in homozygotes compared with wild-type controls. Comparison of EPC amplitudes with muscle fiber current thresholds indicate that many EPCs from homozygotes fall below threshold for activating muscle fibers but can be raised above threshold following potentiation. To determine whether axonal abnormalities might play a role in causing motor unit dysfunction, we examined the postnatal maturation of axonal conduction velocity in relation to the appearance of tetanic failure. We also examined intracellularly labeled motor neurons for evidence of axonal neurofilament accumulations, which are found in many instances of motor neuron disease including HCSMA. Despite the appearance of tetanic failure between 90 and 120 days, average motor axon conduction velocity increased with age in homozygotes and achieved adult levels. Normal correlations between motor neuron properties (including conduction velocity) and motor unit properties were also observed. Labeled proximal motor axons of several motor neurons that supplied failing motor units exhibited little or no evidence of axonal swellings. We conclude that decreased release of transmitter from motor terminals underlies motor unit dysfunction in HCSMA and that the mechanisms determining the maturation of axonal conduction velocity and the pattern of correlation between motor neuron and motor unit properties do not contribute to the appearance or evolution of motor unit dysfunction. PMID:12466447

  11. Mapping Genetically Controlled Neural Circuits of Social Behavior and Visuo-Motor Integration by a Preliminary Examination of Atypical Deletions with Williams Syndrome

    PubMed Central

    Hoeft, Fumiko; Dai, Li; Haas, Brian W.; Sheau, Kristen; Mimura, Masaru; Mills, Debra; Galaburda, Albert; Bellugi, Ursula

    2014-01-01

    In this study of eight rare atypical deletion cases with Williams-Beuren syndrome (WS; also known as 7q11.23 deletion syndrome) consisting of three different patterns of deletions, compared to typical WS and typically developing (TD) individuals, we show preliminary evidence of dissociable genetic contributions to brain structure and human cognition. Univariate and multivariate pattern classification results of morphometric brain patterns complemented by behavior implicate a possible role for the chromosomal region that includes: 1) GTF2I/GTF2IRD1 in visuo-spatial/motor integration, intraparietal as well as overall gray matter structures, 2) the region spanning ABHD11 through RFC2 including LIMK1, in social cognition, in particular approachability, as well as orbitofrontal, amygdala and fusiform anatomy, and 3) the regions including STX1A, and/or CYLN2 in overall white matter structure. This knowledge contributes to our understanding of the role of genetics on human brain structure, cognition and pathophysiology of altered cognition in WS. The current study builds on ongoing research designed to characterize the impact of multiple genes, gene-gene interactions and changes in gene expression on the human brain. PMID:25105779

  12. The effects of formalized and trained non-reciprocal peer teaching on psychosocial, behavioral, pedagogical, and motor learning outcomes in physical education

    PubMed Central

    Whipp, Peter R.; Jackson, Ben; Dimmock, James A.; Soh, Jenny

    2015-01-01

    Peer teaching is recognized as a powerful instructional method; however, there is a paucity of studies that have evaluated the outcomes experienced by peer-teachers and their student recipients in the context of trained, non-reciprocal, high school physical education (PE). Accordingly, the effectiveness of a formalized and trained non-reciprocal peer teaching (T-PT) program upon psychosocial, behavioral, pedagogical, and student learning outcomes within high school PE classes was investigated. Students from eight intact classes (106 males, 94 females, Mage = 12.46, SD = 0.59) were randomly assigned to either a T-PT intervention group (taught by a volunteer peer-teacher who was trained in line with a tactical games approach) or untrained group (U-PT; where volunteer peer-teachers received no formal training, but did receive guidance on the game concepts to teach). Data were collected over 10 lessons in a 5-week soccer unit. Mixed-model ANOVAs/MANOVAs revealed that, in comparison to U-PT, the T-PT program significantly enhanced in-game performance actions and academic learning time among student recipients. Those in the T-PT also provided greater levels of feedback and structured learning time, as well as reporting more positive feelings about peer teaching and fewer perceived barriers to accessing learning outcomes. These findings show that non-reciprocal peer-teachers who receive formalized support through training and tactical games approach-based teaching resources can enhance behavioral, pedagogical, and motor performance outcomes in PE. PMID:25741309

  13. Subchronic oral administration of Benzo[a]pyrene impairs motor and cognitive behavior and modulates S100B levels and MAPKs in rats.

    PubMed

    Maciel, Erica Santos; Biasibetti, Regina; Costa, Ana Paula; Lunardi, Paula; Schunck, Rebeca Vargas Antunes; Becker, Gabriela Curbeti; Arbo, Marcelo Dutra; Dallegrave, Eliane; Gonçalves, Carlos Alberto; Saldiva, Paulo H Nascimento; Garcia, Solange Cristina; Leal, Rodrigo Bainy; Leal, Mirna Bainy

    2014-04-01

    Benzo[a]pyrene (BaP) is an environmental contaminant produced during incomplete combustion of organic material that is well known as a mutagenic and carcinogenic toxin. There are few studies addressing the molecular and cellular basis of behavioural alterations related to BaP exposure. The aim of this study was to evaluate the effect of subchronic oral administration of BaP on behavioral and neurochemical parameters. Wistar male rats received BaP (2 mg/kg) or corn oil (control), once a day for 28 days (n = 12/group). Spontaneous locomotor activity and short- and long-term memories were evaluated. Glial fibrillary acid protein and S100B content in the hippocampus, serum and CSF were measured using ELISA and total and phosphorylated forms of mitogen activated protein kinases (MAPKs) named extracellular signal-regulated kinases 1 and 2, p38(MAPK) and c-Jun amino-terminal kinases 1 and 2, in the hippocampus, were evaluated by western blotting. BaP induced a significant increase on locomotor activity and a decrease in short-term memory. S100B content was increased significantly in cerebrospinal fluid. BaP induced a decrease on ERK2 phosphorylation in the hippocampus. Thus, BaP subchronic treatment induces an astroglial response and impairs both motor and cognitive behavior, with parallel inhibition of ERK2, a signaling enzyme involved in the hippocampal neuroplasticity. All these effects suggest that BaP neurotoxicity is a concern for environmental pollution. PMID:24584819

  14. Trophic Factor Expression in Phrenic Motor Neurons

    PubMed Central

    Mantilla, Carlos B.; Sieck, Gary C.

    2008-01-01

    The function of a motor neuron and the muscle fibers it innervates (i.e., a motor unit) determines neuromotor output. Unlike other skeletal muscles, respiratory muscles (e.g., the diaphragm, DIAm) must function from birth onwards in sustaining ventilation. DIAm motor units are capable of both ventilatory and non-ventilatory behaviors, including expulsive behaviors important for airway clearance. There is significant diversity in motor unit properties across different types of motor units in the DIAm. The mechanisms underlying the development and maintenance of motor unit diversity in respiratory muscles (including the DIAm) are not well understood. Recent studies suggest that trophic factor influences contribute to this diversity. Remarkably little is known about the expression of trophic factors and their receptors in phrenic motor neurons. This review will focus on the contribution of trophic factors to the establishment and maintenance of motor unit diversity in the DIAm, during development and in response to injury or disease. PMID:18708170

  15. Motor Learning and Control Foundations of Kinesiology: Defining the Academic Core

    ERIC Educational Resources Information Center

    Fischman, Mark G.

    2007-01-01

    This paper outlines the kinesiological foundations of the motor behavior subdisciplines of motor learning and motor control. After defining the components of motor behavior, the paper addresses the undergraduate major and core knowledge by examining several classic textbooks in motor learning and control, as well as a number of contemporary…

  16. Lack of tryptophan hydroxylase-1 in mice results in gait abnormalities.

    PubMed

    Suidan, Georgette L; Duerschmied, Daniel; Dillon, Gregory M; Vanderhorst, Veronique; Hampton, Thomas G; Wong, Siu Ling; Voorhees, Jaymie R; Wagner, Denisa D

    2013-01-01

    The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (-/-) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system. PMID:23516593

  17. The Effects of Peer Social Behavior on the Motor and Social Responses of Preschool Children with Severe Disabilities in Childcare Settings.

    ERIC Educational Resources Information Center

    Martin, Sylvia S.

    This study assessed the effects of social interaction with nondisabled peers on the motor and